Advertisement

Covid-19 and alcohol associated liver disease

  • Sasha Deutsch-Link
    Affiliations
    Division of Gastroenterology & Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, United States
    Search for articles by this author
  • Brenda Curtis
    Affiliations
    National Institute on Drug Abuse, Baltimore, MD, United States
    Search for articles by this author
  • Ashwani K. Singal
    Correspondence
    Corresponding author at: University of South Dakota Sanford School of Medicine, Hepatologist and Chief Clinical Research Avera Transplant Institute, Director Hepatology Elective Sanford SOM, Health Research Scientist, VA Medical Center Sioux Falls, United States.
    Affiliations
    Division of Gastroenterology & Hepatology, University of South Dakota Sanford School of Medicine, Sioux Falls, SD, United States
    Search for articles by this author
Published:August 03, 2022DOI:https://doi.org/10.1016/j.dld.2022.07.007

      Abstract

      The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden.

      Keywords

      1. Introduction

      The COVID-19 pandemic is having substantial impacts on the health status of individuals with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). AUD and ALD have both been impacted throughout the pandemic, with increases in alcohol use during the early stages of the pandemic, reduced access to treatment during the mid-pandemic, and challenges in managing the downstream effects in the post-COVID era. This review will focus on how the COVID-19 pandemic has impacted AUD and ALD epidemiology and access to treatment, and will discuss to address this rising AUD and ALD disease burden (Table 1 and 2).
      Table 1COVID-19 and alcohol-associated liver disease.
      Alcohol Consumption and Alcohol Use Disorder
      Epidemiology
      • -
        AUD prevalence was rising pre-pandemic
        • Grant B.F.
        • Chou S.P.
        • Saha T.D.
        • et al.
        Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      • -
        Alcohol sales increased in the first year of the pandemic
        • Lee B.P.
        • Dodge J.L.
        • Leventhal A.
        • et al.
        Retail alcohol and tobacco sales during COVID-19.
      • -
        Alcohol-related hospitalizations and alcohol-related mortality increased post-pandemic
        • Moon A.M.
        • Yang J.Y.
        • Barritt A.S.
        • et al.
        Rising mortality from alcohol-associated liver disease in the United States in the 21st century.
        ,
        • Sharma R.A.
        • Subedi K.
        • Gbadebo B.M.
        • et al.
        Alcohol withdrawal rates in hospitalized patients during the COVID-19 pandemic.
        ,
        • White A.M.
        • Castle I.-.J.P.
        • Powell P.A.
        • et al.
        Alcohol-related deaths during the COVID-19 pandemic.
      Mechanisms
      • -
        Mass traumatic events associated with short-term increases in alcohol consumption
        • Keyes K.M.
        • Hatzenbuehler M.L.
        • Hasin D.S
        Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors.
      • -
        Financial insecurity and unemployment associated with increased substance use disorders
        • de Goeij M.C.M.
        • Suhrcke M.
        • Toffolutti V.
        • et al.
        How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.
      • -
        Psychological distress and isolation
        • Rodriguez L.M.
        • Litt D.M.
        • Stewart S.H
        Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
        ,
        • Le T.M.
        • Wang W.
        • Zhornitsky S.
        • et al.
        The neural processes interlinking social isolation, social support, and problem alcohol use.
        ,
        • Stewart S.D
        COVID-19, coronavirus-related anxiety, and changes in women's alcohol use.
      Impaction on Substance Use Disorder Treatment
      • -
        Group SUD treatment curtailed
        With meetings banned, millions struggle to stay sober on their own.
        ,
        • Polcin D.L.
        • Mahoney E.
        • Wittman F.
        • et al.
        Understanding challenges for recovery homes during COVID-19.
      • -
        Residential treatment settings impacted by COVID-19
        • Polcin D.L.
        • Mahoney E.
        • Wittman F.
        • et al.
        Understanding challenges for recovery homes during COVID-19.
        ,
        • Aponte-Melendez Y.
        • Mateu-Gelabert P.
        • Fong C.
        • et al.
        The impact of COVID-19 on people who inject drugs in New York City: increased risk and decreased access to services.
      Alcohol-Associated Liver Disease Epidemiology
      Pre-Pandemic
      • -
        ALD prevalence increased prior to the pandemic
        • Mellinger J.L.
        • Shedden K.
        • Winder G.S.
        • et al.
        The high burden of alcoholic cirrhosis in privately insured persons in the United States.
      • -
        Hospitalizations for AC and AH were rising
        • Shirazi F.
        • Singal A.K.
        • Wong R.J
        Alcohol-associated Cirrhosis and Alcoholic Hepatitis Hospitalization Trends in the United States.
        ,
        • Barritt A.S.
        • Jiang Y.
        • Schmidt M.
        • et al.
        Charges for alcoholic cirrhosis exceed all other etiologies of cirrhosis combined: a national and state inpatient survey analysis.
      • -
        ALD became the leading indication for liver transplantation
        • Cholankeril G.
        • Ahmed A
        Alcoholic liver disease replaces hepatitis c virus infection as the leading indication for liver transplantation in the United States.
        ,
        • Wong R.J.
        • Singal A.K
        Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014-2019.
      Post-pandemic
      • -
        AH admissions increased more than 50%
        • Gonzalez H.C.
        • Zhou Y.
        • Nimri F.M.
        • et al.
        Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.
        ,
        • Sohal A.
        • Khalid S.
        • Green V.
        • et al.
        The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
      • -
        ALD mortality accelerated during the covid 19 pandemic, increasing more than 20% in males and females
        • Deutsch-Link S.
        • Jiang Y.
        • Peery A.F.
        • et al.
        Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      • -
        Females and younger adults experienced highest relative increases in ALD
        • Deutsch-Link S.
        • Jiang Y.
        • Peery A.F.
        • et al.
        Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      Impact on Alcohol-Associated Liver Disease Outcomes
      Rising Alcohol Consumption
      • -
        Alcohol use in cirrhosis associated with increased mortality, infection, and gastrointestinal bleeding
        • Pearson M.M.
        • Kim N.J.
        • Berry K.
        • et al.
        Associations between alcohol use and liver-related outcomes in a large national cohort of patients with cirrhosis.
        ,
        • Santos SGR dos
        • Mattos A.A.
        • Guimarães M.M.
        • et al.
        Alcohol consumption influences clinical outcome in patients admitted to a referral center for liver disease.
      • -
        Higher prevalence of ALD in ACLF hospital admissions
        • Görgülü E.
        • Gu W.
        • Trebicka J.
        • et al.
        Acute-on-chronic liver failure (ACLF) precipitated by severe alcoholic hepatitis: another collateral damage of the COVID-19 pandemic?.
      • -
        Alcohol consumption may have a detrimental impact on the immune system
        • Szabo G.
        • Saha B
        Alcohol's effect on host defense.
        ,
        • Huang W.
        • Zhou H.
        • Hodgkinson C.
        • et al.
        Network meta-analysis on the mechanisms underlying alcohol augmentation of COVID-19 pathologies.
      COVID-related outcomes
      Impact on ALD Treatment and Liver Transplantation
      ALD Treatment
      • -
        Early in the pandemic, cirrhosis and ALD-related hospitalizations declined likely reflecting delays in care
        • Mahmud N.
        • Hubbard R.A.
        • Kaplan D.E.
        • et al.
        Declining cirrhosis hospitalizations in the wake of the COVID-19 pandemic: a national cohort study.
      • -
        Access to outpatient hepatology treatments and early alcohol treatment may have been impacted by COVID-19
      Liver Transplantation
      • -
        Transplant candidates have increased risk of severe COVID-19 and death
        • Belli L.S.
        • Duvoux C.
        • Cortesi P.A.
        • et al.
        COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.
      • -
        Transplants for severe AH increased by more than 50% during the COVID era and median MELD-Na at transplant rose
        • Cholankeril G.
        • Goli K.
        • Rana A.
        • et al.
        Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
        ,
        • Bittermann T.
        • Mahmud N.
        • Abt P
        Trends in liver transplantation for acute alcohol-associated hepatitis during the COVID-19 pandemic in the US.
      Post-Transplant Care
      • -
        Concerns regarding immunosuppressed status, however mortality has been similar across LT-recipients and non-LT patients when accounting for other confounders
        • Kulkarni A.V.
        • Tevethia H.V.
        • Premkumar M.
        • et al.
        Impact of COVID-19 on liver transplant recipients–a systematic review and meta-analysis.
      Demographic Trends and Increasing Inequities
      Pre-pandemic
      • -
        AUD and ALD prevalence highest in American Indian/Alaska Native Populations
        • Grant B.F.
        • Chou S.P.
        • Saha T.D.
        • et al.
        Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      • -
        Racial and ethnic minority groups have worse AUD outcomes compared to White individuals
        • Vaeth P.A.C.
        • Wang-Schweig M.
        • Caetano R
        Drinking, alcohol use disorder, and treatment access and utilization among U.S. racial/ethnic groups.
      • -
        Among patients hospitalized with cirrhosis, Black patients have the highest mortality
        • Singal A.
        • Yong-Fang K.
        • Arab J.
        • et al.
        Racial and health disparities among cirrhosis-related hospitalizations in the USA.
      Post-Pandemic
      • -
        Black and Hispanic/Latinx patients with CLD were disproportionately impacted by COVID-19
        • Adeniji N.
        • Carr R.M.
        • Aby E.S.
        • et al.
        Socioeconomic factors contribute to the higher risk of COVID-19 in racial and ethnic minorities with chronic liver diseases.
      • -
        Highest relative increase in alcohol use in women and Black individuals
        • Barbosa C.
        • Cowell A.J.
        • Dowd W.N
        Alcohol consumption in response to the COVID-19 pandemic in the United States.
      • -
        Highest relative increase in AH admissions in women and Black patients
        • Damjanovska S.
        • Karb D.B.
        • Cohen S.M
        Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
      • -
        Highest relative increase in ALD mortality in women and young adults
        • Deutsch-Link S.
        • Jiang Y.
        • Peery A.F.
        • et al.
        Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      *These disparities likely reflect inequitable access to treatment, social and economic exclusion, and other downstream sequelae of structural racism
      Improving AUD and ALD Care During the COVID-19 Pandemic
      Telemedicine
      • -
        Effective for providing specialty hepatology care
        • Serper M.
        • Cubell A.W.
        • Deleener M.E.
        • et al.
        Telemedicine in liver disease and beyond: can the COVID-19 crisis lead to action?.
      • -
        Effective in reducing alcohol use
        • Kruse C.S.
        • Lee K.
        • Watson J.B.
        • et al.
        Measures of effectiveness, efficiency, and quality of telemedicine in the management of alcohol abuse, addiction, and rehabilitation: systematic review.
        ,
        • Kaner E.F.
        • Beyer F.R.
        • Garnett C.
        • et al.
        Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.
      • -
        Virtual and web-based programs during the pandemic were effective at treating AUD in ALD patients
        • Bossi M.M.
        • Tufoni M.
        • Zaccherini G.
        • et al.
        A web-based group treatment for patients with alcoholic liver diseases at the time of the COVID-19 pandemic.
        ,
        • Yau M.T.K.
        • Bromley L.
        • Treuil K.
        • et al.
        The management of alcohol-use disorder during the COVID-19 pandemic: evaluating the efficacy of virtual care in patients with alcohol-related liver disease.
      • -
        May neglect at-risk populations without stable housing or internet options
        • Scott Kruse C.
        • Karem P.
        • Shifflett K.
        • et al.
        Evaluating barriers to adopting telemedicine worldwide: a systematic review.
      Prevention and Treatment of COVID-19
      • -
        Vaccination should be emphasized for those with chronic liver disease
      • -
        Medications for the treatment of COVID-19 need to be understood in the context of liver dysfunction
      Response to Rising AUD and ALD
      Prevention
      • -
        Improve public health messaging
        • Sugarman D.E.
        • Greenfield S.F
        Alcohol and COVID-19: how do we respond to this growing public health crisis?.
      • -
        Higher taxation on alcohol has been associated with reduce alcohol consumption and lower ALD
        • Elder R.W.
        • Lawrence B.
        • Ferguson A.
        • et al.
        The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
        ,
        • Rush B.
        • Steinberg M.
        • Brook R
        The relationships among alcohol availability, alcohol consumption and alcohol-related damage in the Province of Ontario and the State of Michigan 1955-1982.
        ,
        • Ponicki W.R.
        • Gruenewald P.J
        The impact of alcohol taxation on liver cirrhosis mortality.
        ,
        • Aslam S.
        • Buggs J.
        • Melo S.
        • et al.
        The association between alcoholic liver disease and alcohol tax.
      Screening
      • -
        Sensitivity in primary care screening is < 50% and evidence-based tools are underused
        • Mitchell A.J.
        • Meader N.
        • Bird V.
        • et al.
        Clinical recognition and recording of alcohol disorders by clinicians in primary and secondary care: meta-analysis.
        ,
        • McNeely J.
        • Adam A.
        • Rotrosen J.
        • et al.
        Comparison of methods for alcohol and drug screening in primary care clinics.
        ,
        • Friedmann P.D.
        • McCullough D.
        • Chin M.H.
        • et al.
        Screening and intervention for alcohol problems. A national survey of primary care physicians and psychiatrists.
      • -
        AUDIT-C or SASQ as evidence-based screening tools
        • Bush K.
        • Kivlahan D.R.
        • McDonell M.B.
        • et al.
        The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking.
        ,
        • Curry S.J.
        • Krist A.H.
        • et al.
        US Preventive Services Task Force
        Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: us preventive services task force recommendation statement.
      Treatment
      • -
        AUD treatment reduces hepatic decompensations and all-cause mortality in patients with cirrhosis
        • Rogal S.
        • Youk A.
        • Zhang H.
        • et al.
        Impact of alcohol use disorder treatment on clinical outcomes among patients with cirrhosis.
      • -
        Patients with ALD are often undertreated for their AUD
        • Lucey M.R.
        • Singal A.K
        Integrated treatment of alcohol use disorder in patients with alcohol-associated liver disease: an evolving story.
      • -
        Integrated care and team-based approaches should be used
        • DiMartini A.F.
        • Leggio L.
        • Singal A.K
        Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.
      • -
        Profound shortage of addiction providers
        • Cummings J.R.
        • Allen L.
        • Clennon J.
        • et al.
        Geographic access to specialty mental health care across high- and low-income US communities.
        ,
        • Thomas K.C.
        • Ellis A.R.
        • Konrad T.R.
        • et al.
        County-level estimates of mental health professional shortage in the United States.
      • -
        Brief alcohol interventions in primary care
        • O'Donnell A.
        • Anderson P.
        • Newbury-Birch D.
        • et al.
        The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews.
      • -
        Collaborative care models for AUD in primary care
        • Watkins K.
        • Ober A.
        • Lamp K.
        • et al.
        Collaborative care for opioid and alcohol use disorders in primary care: the summit randomized clinical trial.
      ACLF; Acute-on-chronic liver failure. AH; Alcohol-associated hepatitis; ALD; Alcohol-associated liver disease. AUD; Alcohol use disorder. AUDIT-C; Alcohol use disorders identification test – consumption. CLD; Chronic liver disease. SASQ; Single alcohol screening question. SUD; Substance use disorder.
      Table 2Studies exploring the impact of the COVID-19 pandemic on alcohol consumption and alcohol-associated liver disease.
      Author (Year)Ref.Primary outcomeStudy DesignStudy PopulationMain Study Findings
      Alcohol Consumption and Alcohol-Related Complications
      Jackson et al. (2021)
      • Jackson S.E.
      • Garnett C.
      • Shahab L.
      • et al.
      Association of the COVID-19 lockdown with smoking, drinking and attempts to quit in England: an analysis of 2019-20 data.
      High-risk alcohol consumptionCross-sectional surveyAdults ≥ 16 years old living in England

      (N = 20,558)
      High-risk alcohol use increased from 25% in April 2019-February 2020 to 38% in April 2020, and use of evidence-based treatment declined (4.0% to 1.2%).
      Lee et al. (2021)
      • Lee B.P.
      • Dodge J.L.
      • Leventhal A.
      • et al.
      Retail alcohol and tobacco sales during COVID-19.
      Alcohol salesNielsen National Consumer Panel prospective cohort studyHouseholds in the contiguous United States (N = 144,704 households)Alcohol sales from April-June increased from $7.1 billion in 2018 to $9.55 billion in 2020.
      Sharma et al. (2021)
      • Sharma R.A.
      • Subedi K.
      • Gbadebo B.M.
      • et al.
      Alcohol withdrawal rates in hospitalized patients during the COVID-19 pandemic.
      Alcohol-related hospitalizationsRetrospective CohortHospitalizations for alcohol withdrawal at a tertiary hospital in Delaware (N = 847)34% increase in hospitalizations for alcohol withdrawal at the end of stay-at-home orders in 2020 compared to 2019.
      White et al. (2022)
      • White A.M.
      • Castle I.-.J.P.
      • Powell P.A.
      • et al.
      Alcohol-related deaths during the COVID-19 pandemic.
      Alcohol-related deathsCross-sectionalUnited States mortality data from the National Center for Health StatisticsAlcohol-related deaths increased 26% from 2019 to 2020, largest increases in adults aged 35 to 44 years (40%) and 25 to 34 years (27%).
      Alcohol-Associated Liver Disease Burden
      Deutsch-Link et al. (2022)
      • Itoshima H.
      • Shin J.-.H.
      • Takada D.
      • et al.
      The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.
      ALD mortalityCross-sectionalUnited States mortality data from the National Center for Health StatisticsFrom 2019 to 2020, ALD-related mortality increased 21% in males and 27% in females. Highest relative increases observed in those under age 45.
      Gonzalez et al. (2022)
      • Gonzalez H.C.
      • Zhou Y.
      • Nimri F.M.
      • et al.
      Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.
      AH hospitalizationsRetrospective cohortHospitalizations for AH at a tertiary hospital in Michigan (N = 337)AH admissions increased 50% in 2020 from 2016 to 2019.
      Görgülü et al. (2022)
      • Görgülü E.
      • Gu W.
      • Trebicka J.
      • et al.
      Acute-on-chronic liver failure (ACLF) precipitated by severe alcoholic hepatitis: another collateral damage of the COVID-19 pandemic?.
      ICU admissions for ACLFRetrospective cohortICU admissions for ACLF in Germany (N = 237)From 2017–2019, 24–27% of ICU admissions for ACLF were from AH; in 2020, 57% of ACLF admissions were from AH.
      Julien et al. (2021)
      • Julien J.
      • Ayer T.
      • Tapper E.B.
      • et al.
      Effect of increased alcohol consumption during covid-19 pandemic on alcohol-related liver disease: a modeling study.
      ALD BurdenMicrosimulation modeling studyUS adults born between 1920 and 2012Increased alcohol use during the pandemic is projected to result in 8000 additional ALD deaths and 18,7000 additional cases of decompensated cirrhosis between 2020 and 2040.
      Shaheen et al. (2022)
      • Shaheen A.A.
      • Kong K.
      • Ma C.
      • et al.
      Impact of the COVID-19 pandemic on hospitalizations for alcoholic hepatitis or cirrhosis in Alberta, Canada.
      AH and AC hospitalizationsRetrospective cohortAdult hospitalizations for AH or AC in Alberta, Canada. (N = 6642)Average monthly admissions for AH increased from 11.6/10,000 admissions before March 2020 to 22.1/10,000 admissions after. AC hospitalizations were stable.
      Sohal et al. (2022)
      • Sohal A.
      • Khalid S.
      • Green V.
      • et al.
      The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
      AH hospitalizationsRetrospective cohortHospitalizations for AH at 2 community hospitals in California (N = 329)AH admissions increased 51% between 2019 and 2020, 100% increase in patients < 40 years, and 125% increase in female patients.
      COVID-19-related Outcomes
      Belli et al. (2021)
      • Belli L.S.
      • Duvoux C.
      • Cortesi P.A.
      • et al.
      COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.
      COVID-19 outcomes in LT candidates and post transplant outcomesProspective cohort studyAdult patients listed for LT who contracted COVID-19. Multi-center study at 149 transplant centers across Europe. (N = 113)Mortality in LT candidates from COVID-19 was 33% (45% in decompensated cirrhosis). Prior COVID-19 infection did not impact early post-transplant survival.
      Iavarone et al. (2020)
      • Iavarone M.
      • D'Ambrosio R.
      • Soria A.
      • et al.
      High rates of 30-day mortality in patients with cirrhosis and COVID-19.
      Cirrhosis and COVID-19 outcomesMulti-center retrospective cohort studyHospitalized patients with cirrhosis and COVID-19 across 9 hospitals in Northern Italy from March 1st-31st 2020 (N = 50)Out of 50 patients with cirrhosis and COVID-19, 28% of patients developed ACLF and the 30-day mortality was 34%.
      Kulkarni et al. (2021)
      • Kulkarni A.V.
      • Tevethia H.V.
      • Premkumar M.
      • et al.
      Impact of COVID-19 on liver transplant recipients–a systematic review and meta-analysis.
      COVID-19 outcomes in LT recipientsSystematic Review and Meta-AnalysisMeta-analysis of 18 studies with 1522 LT recipients infected with COVID-19 (December 2019-May 2020)Mortality in LT recipients was 17.4%. Mortality in LT recipients was similar to non-LT recipients after adjusting for age and comorbidities.
      Marjot et al. (2021)
      • Marjot T.
      • Moon A.M.
      • Cook J.A.
      • et al.
      Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study.
      CLD and COVID-19 outcomesMulti-center international cohort studyPatients with CLD > 16 years old with COVID-19 (N = 745)Case fatality rate for patients with ALD was 36%, the highest of any CLD etiology. Case fatality rate for CP-A, B, and C cirrhosis was 24%, 35%, and 54%, respectively.
      Wang et al. (2021)
      • Wang Q.Q.
      • Kaelber D.C.
      • Xu R.
      • et al.
      COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
      SUD and risk of COVID-19Retrospective case control studyUS EHR data from IBM Watson Health Explorys (N = 73,099,850)History of AUD in the past year was associated with an increased risk of contracting COVID-19 (AOR=7.75). Patients with any SUD had increased risk of death (9.6% vs 6.6%) and hospitalization (41% vs 30%) compared to general COVID-19 patients.
      ALD Treatment and Liver Transplantation
      Anderson et al. (2021)
      • Anderson M.S.
      • Valbuena V.S.M.
      • Brown C.S.
      • et al.
      Association of COVID-19 with new waiting list registrations and liver transplantation for alcoholic hepatitis in the United States.
      Liver Transplantation for AHRetrospective cohort studyAdults registered in the UNOS databaseFrom June 2020 to January 2021, wait-list registrations for AH increased by 60% and transplants for AH increased by 62%.
      Bittermann et al. (2021)
      • Cholankeril G.
      • Goli K.
      • Rana A.
      • et al.
      Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
      Liver Transplantation for AHRetrospective cohort studyAdults registered in the UNOS databaseFrom March 2020 to February 2021, AH listing increased by 107% and AHD liver transplants increased by 210%.
      Cholankeril et al. (2021)
      • Cholankeril G.
      • Goli K.
      • Rana A.
      • et al.
      Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
      Liver Transplantation for ALDRetrospective cohort studyAdults registered in the UNOS databaseALD listing increased by 7.3% and ALD transplants increased by 10.7% during the pandemic, with ALD accounting for more listings (40.1%) than HCV (12.4%) and NASH (23.4%) combined.
      Mahmud et al. (2020)
      • Mahmud N.
      • Hubbard R.A.
      • Kaplan D.E.
      • et al.
      Declining cirrhosis hospitalizations in the wake of the COVID-19 pandemic: a national cohort study.
      CLD HospitalizationsRetrospective cohort studyVA patients ≥ 18 years of age hospitalized for any reason between January 1st-April 15 in 2019 and 2020 (N = 12,467 hospitalizations)During the first few weeks of the pandemic, cirrhosis-related hospital admissions declined by more than 50%. Hospitalizations had significantly higher MELD-Na.
      Demographic Trends and Disparities
      Adeniji et al. (2021)
      • Adeniji N.
      • Carr R.M.
      • Aby E.S.
      • et al.
      Socioeconomic factors contribute to the higher risk of COVID-19 in racial and ethnic minorities with chronic liver diseases.
      COVID-19 in and socioeconomic factors in patients with CLDRetrospective cohort studyAdults ≥ 18 years old and a diagnosis of CLD diagnosed with COVID-19 across 21 medical centers in the US from March-May 2020. (N = 909)Black and Hispanic patients with CLD were more likely to contract COVID-19 compared to White patients with CLD. Black and Hispanic patients were less likely to have private insurance, and were more likely to experience poverty and overcrowding.
      Barbosa et al. (2021)
      • Barbosa C.
      • Cowell A.J.
      • Dowd W.N
      Alcohol consumption in response to the COVID-19 pandemic in the United States.
      Disparities in alcohol consumptionCross-sectional studyOnline survey of US adults (≥21 years old) (N = 993) in February 2020 and April 2020.Compared to February 2020, in April 2020, average drinks per day was 29% higher, risky drinking was 20% higher, and binge drinking was 21% higher. The increases were larger for women than men, and Black patients.
      Damjanovska et al. (2021)
      • Damjanovska S.
      • Karb D.B.
      • Cohen S.M
      Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
      Disparities in ALDRetrospective cohort studyClaims data from the US (N = 8445,720)Prevalence of AH treatment more than doubled from pre-covid to during the COVID era. Black patients were more likely to be diagnosed with AH (OR 2.63) or alcohol-associated pancreatitis (OR 2.17).
      Deutsch-Link et al. (2022)
      • Itoshima H.
      • Shin J.-.H.
      • Takada D.
      • et al.
      The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.
      ALD mortalityCross-sectional studyUnited States mortality data from the National Center for Health StatisticsFrom 2019–2020, the highest relative increase in ALD mortality was observed in American Indian/Alaska Native and Asian men, and American/Indian Alaska Native and Hispanic/Latina women. Women had a higher relative increase (27%) than men (21%).
      Devoto et al. (2022)
      • Devoto A.
      • Himelein-Wachowiak M.
      • Liu T.
      • et al.
      Women's substance use and mental health during the COVID-19 pandemic.
      Mental health and alcohol consumptionProspective cohort studyUS online survey of adult women as part of a larger longitudinal study (N = 499)30% of women reported worsening intimate partner violence, and 17% of women reported using drugs or alcohol to cope with relationship problems after the onset of the pandemic. Risky alcohol consumption was associated with anxiety and depression.
      Lee et al. (2021)
      • Lee B.P.
      • Dodge J.L.
      • Leventhal A.
      • et al.
      Retail alcohol and tobacco sales during COVID-19.
      Alcohol salesNielsen National Consumer Panel prospective cohort studyHouseholds in the contiguous United States (N = 144,704 households)Asian (55%), Black (42%) and Hispanic/Latinx (40%) individuals had a higher relative increase in alcohol purchases from 2019 to 2020 compare to White people (34%) or Other (25%); the absolute increase was highest in White individuals.
      Rodriguez et al. (2020)
      • Rodriguez L.M.
      • Litt D.M.
      • Stewart S.H
      Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
      Alcohol consumptionCross-sectional surveyAdults living in the United States (N = 754)Psychological distress from COVID-19 was associated with higher alcohol consumption in women, but not men.
      Sohal et al. (2022)
      • Sohal A.
      • Khalid S.
      • Green V.
      • et al.
      The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
      AH hospitalizationsRetrospective cohortHospitalizations for AH at 2 community hospitals in California (N = 329)Between 2019 and 2020, relative AH admissions increased more in female patients (125%) than male patients (35%). Higher increases were seen in those < 40 years (100%), than 40–60 years (28%).
      Improving Care Delivery and the Incorporation of Telemedicine
      Bossi et al. (2020)
      • Bossi M.M.
      • Tufoni M.
      • Zaccherini G.
      • et al.
      A web-based group treatment for patients with alcoholic liver diseases at the time of the COVID-19 pandemic.
      Web-based program for group treatment of ALDIntervention/Case-series. 10 patients enrolled into 3 weeks of web-based group treatment.Ten adult ALD patients included starting in March 2020Adherence was high (7/10 patients attended over 90% of group meetings). 2/10 dropped out, and 2/10 experience a relapse.
      Kaner et al. (2017)
      • Kaner E.F.
      • Beyer F.R.
      • Garnett C.
      • et al.
      Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.
      Digital interventions for AUDCochrane Review57 studies included with 34,390 participantsNo difference in outcomes comparing digital and face-to-face interventions. Majority of studies demonstrated some reduction in binge-drinking (moderate-quality evidence), with an average reduction of 3 standard drinks per week.
      Kruse et al. (2020)
      • Kruse C.S.
      • Lee K.
      • Watson J.B.
      • et al.
      Measures of effectiveness, efficiency, and quality of telemedicine in the management of alcohol abuse, addiction, and rehabilitation: systematic review.
      Telemedicine for AUDSystematic reviewSystematic review of 22 studies examining the impact of telemedicine on treatment of AUD16 studies (73%) reported a statistically significant reduction in alcohol consumption.
      Yau et al. (2021)
      • Yau M.T.K.
      • Bromley L.
      • Treuil K.
      • et al.
      The management of alcohol-use disorder during the COVID-19 pandemic: evaluating the efficacy of virtual care in patients with alcohol-related liver disease.
      Multidisciplinary virtual clinic for patients with AUD and ALDExperimental cohort studyAdults ≥ 18 years of age with ALD at receiving care through a multidisciplinary virtual clinic for AUD and ALD in Canada (N = 61)Clinic retention rate was 75%. 70% of patients were started on anti-craving medications and 45% of patients remained abstinent from alcohol during the study period.
      Response to Rising Alcohol Consumption and Burden of Alcohol-Associated Liver Disease
      Aslam et al. (2021)Impact of alcohol taxes on waitlisting for liver transplantationRetrospective Cohort StudyUNOS adult liver transplant waitlist additions for ALD from 2007 to 2016 (N = 24,316)Associated between lower beer tax and higher ALD transplant waitlisting.
      Bush et al. (1998)
      • Bush K.
      • Kivlahan D.R.
      • McDonell M.B.
      • et al.
      The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking.
      Evaluation of AUDIT and AUDIT-C screening toolsCross-sectional studyVeterans Affairs patients from 3 general medicine clinics were administered with AUDIT and AUDIT-C (N = 243)AUDIT-C outperformed full AUDIT for detecting heavy drinking. A cutoff of ≥3 had a sensitivity of 98% and specificity of 57%, and ≥4 had a sensitivity of 91% and specificity of 70% for heavy drinking.
      Elder et al. (2010)
      • Elder R.W.
      • Lawrence B.
      • Ferguson A.
      • et al.
      The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
      Impact of tax policies on alcohol consumption and related harmsSystematic Review72 papers and technical reports includedNearly all studies found an inverse relationship between tax/price of alcohol on heavy alcohol use and harmful alcohol-related outcomes.
      O'Donnell et al. (2014)
      • O'Donnell A.
      • Anderson P.
      • Newbury-Birch D.
      • et al.
      The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews.
      Brief alcohol interventions in primary careSystematic review of reviews24 systematic reviews includedBrief alcohol interventions were consistently effective and reducing hazardous and harmful drinking in primary care.
      Ponicki et al. (2006)
      • Ponicki W.R.
      • Gruenewald P.J
      The impact of alcohol taxation on liver cirrhosis mortality.
      Impact of alcohol taxes on cirrhosis mortalityRetrospective population-based study30 U.S. states from 1971 to 1998 (N = 840 state-by-year observations)Cirrhosis mortality was significantly related to taxes on distilled spirits, but not to taxation of wine and beer.
      Rogal et al. (2020)
      • Rogal S.
      • Youk A.
      • Zhang H.
      • et al.
      Impact of alcohol use disorder treatment on clinical outcomes among patients with cirrhosis.
      Impact of AUD treatment of ALD outcomesRetrospective cohort studyAdults receiving care in the VA health system with cirrhosis and AUD (N = 35,682)12% of patients received behavioral treatment alone, 1% received pharmacotherapy and behavior treatment, and 0.4% received pharmacotherapy alone. Treated was associated with lower risk of hepatic decompensation and lower short and long-term mortality.
      Rush et al. (1986)
      • Rush B.
      • Steinberg M.
      • Brook R
      The relationships among alcohol availability, alcohol consumption and alcohol-related damage in the Province of Ontario and the State of Michigan 1955-1982.
      Impact of alcohol tax policy on alcohol consumption mortality from cirrhosisRetrospective population-based studyAlcohol sales data and state-wide mortality dataIn Michigan, from 1955 to 1982, the relative price of alcohol decreased by more than 50%, and per capita consumption and death due to cirrhosis increased substantially.
      Vickers Smith et al. (2019)
      • Vickers Smith R.
      • Kranzler H.R.
      • Justice A.C.
      • et al.
      Longitudinal drinking patterns and their clinical correlates in million veteran program participants.
      Trajectories associated with AUDIT-C scoresProspective cohort studyMillion Veteran Program cohort who were administered the AUDIT-C (N = 495,178)Successful implementation of AUDIT-C for yearly alcohol use screening. Higher-risk AUDIT-C score groups were associated with increased prevalence of AUD, cirrhosis and hepatitis C.
      Watkins et al. (2017)
      • Watkins K.
      • Ober A.
      • Lamp K.
      • et al.
      Collaborative care for opioid and alcohol use disorders in primary care: the summit randomized clinical trial.
      Collaborative care models in primary care for treatment of AUD and opioid use disorderRandomized clinical trial377 primary care patients in 2 federally qualified health centers in the US.Patients randomized to collaborative care model were more likely to receive treatment for their AUD, report abstinence and higher engagement.
      AC; alcohol-associated cirrhosis. ACLF; acute-on-chronic liver failure. AH; alcohol-associated hepatitis. ALD; alcohol-associated liver disease. AOR; adjusted odds ratio. AUD; alcohol use disorder. AUDIT-C; Alcohol Use disorders Identification test – Consumption. CLD; chronic liver disease. CP; Childs-Pugh. EHR; electronic health record. ICU; intensive care unit. OR; odds ratio. SUD; substance use disorder.

      2. Alcohol consumption and alcohol use disorder

      Prior to the onset of the COVID-19 pandemic, harmful alcohol consumption and alcohol use disorder were rising in the United States [
      • Grant B.F.
      • Chou S.P.
      • Saha T.D.
      • et al.
      Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      ]. In 2001–2002, the 12 month prevalence of AUD was 8.5%; a decade later in 2012–2013, this rose to 12.7%, a 49% increase [
      • Grant B.F.
      • Chou S.P.
      • Saha T.D.
      • et al.
      Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      ]. The reasons underlying these trends are not well understood. While some of the increases may reflect improved screening and diagnosis, they have coincided with increases in ALD mortality, likely reflective of true increase in alcohol consumption [
      • Moon A.M.
      • Yang J.Y.
      • Barritt A.S.
      • et al.
      Rising mortality from alcohol-associated liver disease in the United States in the 21st century.
      ].
      In the first few months of the pandemic starting in March 2020, concerns emerged that the pandemic could exacerbate rising substance use disorders (SUDs) [
      • Pfefferbaum B.
      • North C.S
      Mental health and the Covid-19 pandemic.
      ,
      • Rodriguez L.M.
      • Litt D.M.
      • Stewart S.H
      Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
      . Prior evidence has shown that increasing financial insecurity, unemployment, and psychological distress are associated with increased harmful substance use [
      • Keyes K.M.
      • Hatzenbuehler M.L.
      • Hasin D.S
      Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors.
      ,
      • de Goeij M.C.M.
      • Suhrcke M.
      • Toffolutti V.
      • et al.
      How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.
      . During the first year of the pandemic, alcohol sales rose substantially within the United States, from $7.1 billion in 2019 to $9.5 billion in 2020 [
      • Lee B.P.
      • Dodge J.L.
      • Leventhal A.
      • et al.
      Retail alcohol and tobacco sales during COVID-19.
      ]. These trends were mirrored internationally; China witnessed a more than two-fold increase in harmful alcohol consumption [
      • Ahmed M.Z.
      • Ahmed O.
      • Aibao Z.
      • et al.
      Epidemic of COVID-19 in China and associated psychological problems.
      ], and England observed increases in high-risk drinking in particular [
      • Jackson S.E.
      • Garnett C.
      • Shahab L.
      • et al.
      Association of the COVID-19 lockdown with smoking, drinking and attempts to quit in England: an analysis of 2019-20 data.
      ]. As alcohol sales increased, the United States also observed increases in alcohol-related hospitalizations [
      • Sharma R.A.
      • Subedi K.
      • Gbadebo B.M.
      • et al.
      Alcohol withdrawal rates in hospitalized patients during the COVID-19 pandemic.
      ] and alcohol-related mortality [
      • White A.M.
      • Castle I.-.J.P.
      • Powell P.A.
      • et al.
      Alcohol-related deaths during the COVID-19 pandemic.
      ].
      Several reasons underlie these trends in alcohol consumption. Previous studies have shown that mass traumatic events/experiences are associated with short-term increases in alcohol use [
      • Keyes K.M.
      • Hatzenbuehler M.L.
      • Hasin D.S
      Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors.
      ]. Although the COVID-19 pandemic was indeed a mass traumatic event, it was not a finite experience, and has now continued for more than two years. During the pandemic, many Americans lost their jobs and experienced financial insecurity, both of which are associated with heavy alcohol consumption and rising prevalence of AUD [
      • de Goeij M.C.M.
      • Suhrcke M.
      • Toffolutti V.
      • et al.
      How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.
      ]. Furthermore, the psychological distress and isolation that came with the pandemic and quarantines may have provoked heavier alcohol use [
      • Rodriguez L.M.
      • Litt D.M.
      • Stewart S.H
      Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
      ,
      • Le T.M.
      • Wang W.
      • Zhornitsky S.
      • et al.
      The neural processes interlinking social isolation, social support, and problem alcohol use.
      . In fact, during the pandemic, subjective feelings of distress were associated with increased harmful alcohol use [
      • Stewart S.D
      COVID-19, coronavirus-related anxiety, and changes in women's alcohol use.
      ].
      Another reason alcohol consumption and AUD may have increased is the pandemic's unique impact on SUD treatment. Many AUD/SUD treatment modalities involve group meetings and group settings. During the pandemic, support groups like Alcoholics Anonymous or Narcotics Anonymous and intensive outpatient treatment understandably became less accessible amidst efforts to reduce COVID-19 spread [
      With meetings banned, millions struggle to stay sober on their own.
      ]. These impacts were also seen in residential treatment settings, which are also vital components of SUD treatment [
      • Polcin D.L.
      • Mahoney E.
      • Wittman F.
      • et al.
      Understanding challenges for recovery homes during COVID-19.
      ]. Patients with SUDs even reported decreased use of residential treatment and decreased access to SUD treatment overall in the earlier stages of the COVID-19 pandemic [
      • Aponte-Melendez Y.
      • Mateu-Gelabert P.
      • Fong C.
      • et al.
      The impact of COVID-19 on people who inject drugs in New York City: increased risk and decreased access to services.
      ]. Increased barriers to care may have both increased risk of relapse of those in recovery, and prevented early intervention among those with harmful alcohol use.

      3. Impact on epidemiology of alcohol-associated liver disease

      With increasing trends in alcohol consumption, the prevalence of ALD was also increasing prior to the onset of the COVID-19 pandemic. National data on privately insured patients indicated that the prevalence of alcohol-associated cirrhosis (AC) increased 43% between 2009 and 2015 [
      • Mellinger J.L.
      • Shedden K.
      • Winder G.S.
      • et al.
      The high burden of alcoholic cirrhosis in privately insured persons in the United States.
      ]. These increases were higher in women and in adults < 45 years old.
      Rising prevalence of ALD prior to COVID-19 translated into increased healthcare utilization. Hospitalizations for AC and alcohol-associated hepatitis (AH) increased by approximately 20% from 2007 to 2014 [
      • Shirazi F.
      • Singal A.K.
      • Wong R.J
      Alcohol-associated Cirrhosis and Alcoholic Hepatitis Hospitalization Trends in the United States.
      ]. In fact, between 2002 and 2014, total inpatient charges for AC in the United States doubled, and AC accounted for more than half of all inpatient charges related to cirrhosis [
      • Barritt A.S.
      • Jiang Y.
      • Schmidt M.
      • et al.
      Charges for alcoholic cirrhosis exceed all other etiologies of cirrhosis combined: a national and state inpatient survey analysis.
      ]. The United States also observed marked increases in liver transplantation (LT) for ALD and AH [
      • Cholankeril G.
      • Ahmed A
      Alcoholic liver disease replaces hepatitis c virus infection as the leading indication for liver transplantation in the United States.
      ,
      • Wong R.J.
      • Singal A.K
      Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014-2019.
      . While some of this may reflect expanding criteria for LT for AH in recent years [
      • Herrick-Reynolds K.M.
      • Punchhi G.
      • Greenberg R.S.
      • et al.
      Evaluation of early vs standard liver transplant for alcohol-associated liver disease.
      ], this likely also reflects true increases in burden of disease as the ALD mortality increased substantially over the same time period [
      • Moon A.M.
      • Yang J.Y.
      • Barritt A.S.
      • et al.
      Rising mortality from alcohol-associated liver disease in the United States in the 21st century.
      ].
      The COVID-19 pandemic has exacerbated these trends in ALD disease burden and mortality. Early in the pandemic, one modeling study predicted significant increases in ALD disease burden and mortality based on short term increases in alcohol consumption [
      • Julien J.
      • Ayer T.
      • Tapper E.B.
      • et al.
      Effect of increased alcohol consumption during covid-19 pandemic on alcohol-related liver disease: a modeling study.
      ]. Subsequent observational data confirmed many of the predictions in this model. In a large health system in Michigan, AH admissions increased over 50% after May 2020 [
      • Gonzalez H.C.
      • Zhou Y.
      • Nimri F.M.
      • et al.
      Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.
      ]. Another study from California witnessed a 51% increase in AH hospital admissions from 2019 to 2020, with the highest relative increases observed in women and adults younger than the age of 40 years [
      • Sohal A.
      • Khalid S.
      • Green V.
      • et al.
      The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
      ]. US mortality data coincided with increases in hospitalizations. From 2019 to 2020, ALD-related mortality increased by 21% in males and 27% in females, with highest increases also in females and young adults [
      • Deutsch-Link S.
      • Jiang Y.
      • Peery A.F.
      • et al.
      Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      ]. Similar trends were also observed in other countries outside the US. For example, hospitalizations for alcohol-associated liver disease and alcohol-related pancreatitis in Japan increased by 20% during the pandemic [
      • Itoshima H.
      • Shin J.-.H.
      • Takada D.
      • et al.
      The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.
      ]. Studies from Canada and England also reported a near doubling of hospital admissions for AH after the onset of the COVID-19 pandemic [
      • Shaheen A.A.
      • Kong K.
      • Ma C.
      • et al.
      Impact of the COVID-19 pandemic on hospitalizations for alcoholic hepatitis or cirrhosis in Alberta, Canada.
      ,
      • Cargill Z.
      • Kattiparambil S.
      • Hansi N.
      • et al.
      Severe alcohol-related liver disease admissions post-COVID-19 lockdown: canary in the coal mine?.
      .

      4. Impact on outcomes of alcohol-associated liver disease

      Alcohol consumption, particularly heavy use, has a detrimental impact on ALD-related outcomes. Among patients with AC, heavy alcohol use is associated with increased mortality and hepatic decompensation [
      • Pearson M.M.
      • Kim N.J.
      • Berry K.
      • et al.
      Associations between alcohol use and liver-related outcomes in a large national cohort of patients with cirrhosis.
      ]. In another study, heavy alcohol consumption in patients with cirrhosis was associated with about two folds risk of death, upper gastrointestinal bleeding, and infection [
      • Santos SGR dos
      • Mattos A.A.
      • Guimarães M.M.
      • et al.
      Alcohol consumption influences clinical outcome in patients admitted to a referral center for liver disease.
      ]. In 2020, after the onset of the pandemic, Görgülü and colleagues [
      • Görgülü E.
      • Gu W.
      • Trebicka J.
      • et al.
      Acute-on-chronic liver failure (ACLF) precipitated by severe alcoholic hepatitis: another collateral damage of the COVID-19 pandemic?.
      ] observed a modest increase in intensive care unit admissions for acute on chronic liver failure (ACLF), from 12 to 13% in 2017–2019 to 15.9% in 2020. However the distribution of underlying etiologies for ACLF changed more dramatically; in 2017–2019 24–27% of intensive care unit admissions for ACLF were precipitated by AH, whereas in 2020, this increased by over 100% to 57% of ACLF admissions contributed by AH [
      • Görgülü E.
      • Gu W.
      • Trebicka J.
      • et al.
      Acute-on-chronic liver failure (ACLF) precipitated by severe alcoholic hepatitis: another collateral damage of the COVID-19 pandemic?.
      ].
      Heavy alcohol consumption also has a detrimental impact on the immune system [
      • Szabo G.
      • Saha B
      Alcohol's effect on host defense.
      ]. One network meta-analysis suggested that ethanol exposure augments SARS-CoV2 induced inflammation [
      • Huang W.
      • Zhou H.
      • Hodgkinson C.
      • et al.
      Network meta-analysis on the mechanisms underlying alcohol augmentation of COVID-19 pathologies.
      ]. A large observational study also demonstrated that individuals with AUD have a higher risk of COVID-19 infection, and presence of any SUD was associated with increased COVID-19 mortality [
      • Wang Q.Q.
      • Kaelber D.C.
      • Xu R.
      • et al.
      COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
      ].
      Patients with ALD and particularly decompensated cirrhosis are more likely to experience severe illness and death from COVID-19 [
      • Iavarone M.
      • D'Ambrosio R.
      • Soria A.
      • et al.
      High rates of 30-day mortality in patients with cirrhosis and COVID-19.
      ,
      • Moon A.M.
      • Webb G.J.
      • Aloman C.
      • et al.
      High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: preliminary results from an international registry.
      ,
      • Kim D.
      • Adeniji N.
      • Latt N.
      • et al.
      Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study.
      ]. Early studies on COVID-19 in cirrhosis demonstrated over a 30% case fatality rate, with over a 50% case fatality rate in decompensated cirrhosis [
      • Iavarone M.
      • D'Ambrosio R.
      • Soria A.
      • et al.
      High rates of 30-day mortality in patients with cirrhosis and COVID-19.
      ,
      • Moon A.M.
      • Webb G.J.
      • Aloman C.
      • et al.
      High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: preliminary results from an international registry.
      . About a third of patients with cirrhosis can develop acute on chronic liver failure when infected with COVID-19 [
      • Iavarone M.
      • D'Ambrosio R.
      • Soria A.
      • et al.
      High rates of 30-day mortality in patients with cirrhosis and COVID-19.
      ]. Among patients with chronic liver disease (CLD), patients with ALD have the highest risk of COVID-19-related mortality compared to other etiologies of CLD, with a case-fatality rate of around 30–35% [
      • Kim D.
      • Adeniji N.
      • Latt N.
      • et al.
      Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study.
      ,
      • Marjot T.
      • Moon A.M.
      • Cook J.A.
      • et al.
      Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study.
      . After adjusting for several covariates, Kim et al. found that ALD was associated with more than double the odds of COVID-19-related mortality compared to other etiologies of CLD [
      • Kim D.
      • Adeniji N.
      • Latt N.
      • et al.
      Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study.
      ].

      5. Impact on treatment of alcohol-associated liver disease and liver transplantation

      During the first two months of the pandemic, cirrhosis and ALD-related hospitalizations declined, likely due to fear of contracting COVID-19 from visiting emergency rooms [
      • Mahmud N.
      • Hubbard R.A.
      • Kaplan D.E.
      • et al.
      Declining cirrhosis hospitalizations in the wake of the COVID-19 pandemic: a national cohort study.
      ]. Patients requiring hospitalization had higher MELD-Na scores suggesting delays in presenting to the hospital. These delays in care may have impacted disease trajectory and the ability to intervene earlier in the course of AUD and ALD.
      Early in the pandemic there were also significant concerns regarding use of corticosteroids for AH [
      • Zelman S.
      • Holzwanger E.
      • Malik R.
      • et al.
      Alcoholic hepatitis and COVID-19: the question of steroids.
      ]. Although, real world data on use of recommended treatment with corticosteroids for AH is unavailable during the Covid-19 pandemic, dexamethasone emerging as an evidence-based treatment for severe COVID-19 may have mitigated these concerns [
      Dexamethasone in hospitalized patients with Covid-19.
      ]. Access to outpatient hepatology clinics and early alcohol treatment may have also been impacted, preventing early detection of decompensation and disease.
      The pandemic also appeared to have a profound impact on LT. Very early in the pandemic access to living donor transplantation was more limited, however this was mitigated fairly quickly [
      • Cholankeril G.
      • Goli K.
      • Rana A.
      • et al.
      Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
      ]. Throughout the pandemic, the prevalence of ALD patients on LT waitlists have been approximately 40%, higher than non-alcoholic fatty liver disease (NAFLD) and HCV combined [
      • Cholankeril G.
      • Goli K.
      • Rana A.
      • et al.
      Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
      ]. Transplants for severe AH increased by more than 50% during the COVID era and the median MELD-Na at listing and transplant also increased [
      • Cholankeril G.
      • Goli K.
      • Rana A.
      • et al.
      Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
      ,
      • Bittermann T.
      • Mahmud N.
      • Abt P
      Trends in liver transplantation for acute alcohol-associated hepatitis during the COVID-19 pandemic in the US.
      . The increases in waiting list registrations and deceased donor liver transplantation for AH surpassed previously forecasted trends (pre-COVID 19 by more than 50%), whereas trends for non-ALD transplants remained more stable [
      • Anderson M.S.
      • Valbuena V.S.M.
      • Brown C.S.
      • et al.
      Association of COVID-19 with new waiting list registrations and liver transplantation for alcoholic hepatitis in the United States.
      ]. Although some of these changes reflect a changing landscape in LT for AH/ALD [
      • Bangaru S.
      • Pedersen M.R.
      • MacConmara M.P.
      • et al.
      Survey of liver transplantation practices for severe acute alcoholic hepatitis.
      ], epidemiological data on disease burden, hospitalizations, and mortality suggest changing criteria isn't the only underlying factor behind this trend.
      COVID-19 infection presents unique challenges to pre and post-LT care. Pre-transplant patients with end-stage liver disease appear to have markedly worse outcomes after COVID-19 infection, though vaccination has certainly improved these outcomes [
      • Belli L.S.
      • Duvoux C.
      • Cortesi P.A.
      • et al.
      COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.
      ]. Further, current infection delays transplant until recovery from COVID-19, though very limited data exists on transplant outcomes shortly after COVID-19 infection. LT after recovery from COVID-19 has been reported in individual cases in the literature and has been successful in some cases [
      • Martini S.
      • Patrono D.
      • Pittaluga F.
      • et al.
      Urgent liver transplantation soon after recovery from COVID-19 in a patient with decompensated liver cirrhosis.
      ,
      • Gonzalez A.
      • Zervos X.
      • Pinna A.
      • et al.
      Orthotopic liver transplantation in a cirrhotic patient with recent COVID-19 infection.
      , however another case reported severe complications including extensive thrombosis [
      • Gambato M.
      • Germani G.
      • Perini B.
      • et al.
      A challenging liver transplantation for decompensated alcoholic liver disease after recovery from SARS-CoV-2 infection.
      ].
      Post-transplant care may also be impacted by COVID-19. Patients who are post-LT have better outcomes from COVID-19 infection than patients with decompensated cirrhosis, however they are still immunocompromised compared to the general population and may experience more severe infection manifestations. An early case series evaluated 24 LT recipients who were hospitalized for COVID-19 in 2020 who had a high prevalence of metabolic comorbidities [
      • Lee B.T.
      • Perumalswami P.V.
      • Im G.Y.
      • et al.
      COVID-19 in liver transplant recipients: an initial experience from the US epicenter.
      ]. In this case series, 79% of patients had their immunosuppression decreased empirically, and overall, 29% died. However this was later evaluated in a systematic review by Kulkarni et al. [
      • Kulkarni A.V.
      • Tevethia H.V.
      • Premkumar M.
      • et al.
      Impact of COVID-19 on liver transplant recipients–a systematic review and meta-analysis.
      ] who found that mortality was similar across LT recipients and non-LT patients (17.4%) when accounting for age and other comorbidities. There was no significant difference in mortality between those infected within one year versus after one year from LT.
      Post-transplant care should focus on evidence-based preventive care. Vaccination is recommended for all adults in the United States, however there has been concern that immunocompromised individuals may not mount the same protective response to vaccination. Therefore, full-dose boosters have been recommended for solid-organ transplant recipients [
      • Lee A.R.Y.B.
      • Wong S.Y.
      • Chai L.Y.A.
      • et al.
      Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis.
      ].

      6. Demographic trends and increasing inequities

      Racial and social inequalities in AUD and ALD existed prior to the COVID-19 pandemic. Prevalence of AUD continues to be highest in American Indian/Alaska Native populations [
      • Grant B.F.
      • Chou S.P.
      • Saha T.D.
      • et al.
      Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      ], likely due to a long history of oppression, isolation, and social and economic exclusion. Although White Americans have had the second highest prevalence of AUD [
      • Grant B.F.
      • Chou S.P.
      • Saha T.D.
      • et al.
      Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      ,
      • Vaeth P.A.C.
      • Wang-Schweig M.
      • Caetano R
      Drinking, alcohol use disorder, and treatment access and utilization among U.S. racial/ethnic groups.
      , the gap between White Americans and Black and Hispanic/Latinx Americans seems to be narrowing while all racial and ethnic demographics experience increases in AUD [
      • Grant B.F.
      • Chou S.P.
      • Saha T.D.
      • et al.
      Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
      ]. Among individuals at risk of developing ALD, racial and ethnic minority groups tend to have higher severity and worse overall outcomes, likely due to various inequities in social environments, treatment opportunities, and the criminal justice system [
      • Vaeth P.A.C.
      • Wang-Schweig M.
      • Caetano R
      Drinking, alcohol use disorder, and treatment access and utilization among U.S. racial/ethnic groups.
      ].
      ALD outcomes have also demonstrated marked inequality across race, ethnicity, and socioeconomic status before the pandemic began. For instance, a study examining cirrhosis hospital admissions from the National Inpatient Sample found that in-hospital mortality was highest for Black patients [
      • Singal A.
      • Yong-Fang K.
      • Arab J.
      • et al.
      Racial and health disparities among cirrhosis-related hospitalizations in the USA.
      ]. This study also examined ALD burden in cirrhosis admissions, and the authors demonstrated that ALD was disproportionately prevalent in American Indian/Alaska Native individuals (64%) compared to other racial and ethnic groups (44–53%). Social and racial disparities also impact access to transplant. Patients with higher psychosocial risk profiles are more likely to be declined for transplant wait-listing [
      • Deutsch-Link S.
      • Weinberg E.M.
      • Bittermann T.
      • et al.
      The stanford integrated psychosocial assessment for transplant is associated with outcomes before and after liver transplantation.
      ], and Medicaid insurance has the most restrictive alcohol abstinence policies [
      • Lee B.P.
      • Vittinghoff E.
      • Pletcher M.J.
      • et al.
      Medicaid policy and liver transplant for alcohol-associated liver disease.
      ].
      The COVID-19 pandemic uncovered and magnified existing inequities in health, housing, job security, and countless other social and economic resources. Racial and ethnic minority groups, individuals without access to housing, immigrants, those who were incarcerated, and essential workers experienced a disproportionate burden of disease from COVID-19 [
      • Webb Hooper M.
      • Nápoles A.M.
      • Pérez-Stable E.J
      COVID-19 and racial/ethnic disparities.
      ]. Black, Hispanic/Latinx, and American Indian individuals experienced a higher risk of infection and mortality from COVID-19 [
      • Moore J.T.
      • Ricaldi J.N.
      • Rose C.E.
      • et al.
      Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 States, February-June 2020.
      ]. Patients with substance use disorders were also at higher risk of COVID-19 infection, hospitalization, and death [
      • Wang Q.Q.
      • Kaelber D.C.
      • Xu R.
      • et al.
      COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
      ]. And among the SUD population, Black patients had a higher risk of infection with COVID-19 compared to White patients, as well as worse outcomes with significantly higher risk of death and hospitalization [
      • Wang Q.Q.
      • Kaelber D.C.
      • Xu R.
      • et al.
      COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
      ].
      During the COVID era, we have also witnessed accelerating disparities in ALD-related outcomes. Among patients with CLD, Black and Hispanic/Latinx individuals represented a disproportionate number of COVID-19 infections compared to the general CLD population [
      • Adeniji N.
      • Carr R.M.
      • Aby E.S.
      • et al.
      Socioeconomic factors contribute to the higher risk of COVID-19 in racial and ethnic minorities with chronic liver diseases.
      ]. A large study of United States claims data found that the prevalence of AH and alcohol-associated pancreatitis increased substantially during the COVID-pandemic, with a higher relative increase in women and Black patients [
      • Damjanovska S.
      • Karb D.B.
      • Cohen S.M
      Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
      ]. National mortality data from The Centers for Disease Control Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) demonstrated a marked acceleration in ALD-related deaths after the onset of the COVID-19 pandemic, with the highest relative increase in American Indian/Alaska Native and Asian men, and among American Indian/Alaska Native and Hispanic/Latina women [
      • Deutsch-Link S.
      • Jiang Y.
      • Peery A.F.
      • et al.
      Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      ]. Alcohol consumption patterns aligned with ALD mortality patterns. In a study examining post-pandemic alcohol purchases, (American Indian/Alaska Native individuals not included), Asian, Black, and Hispanic/Latinx individuals experienced the highest relative increase in alcohol purchases, however the absolute increase was still highest amongst White individuals [
      • Lee B.P.
      • Dodge J.L.
      • Leventhal A.
      • et al.
      Retail alcohol and tobacco sales during COVID-19.
      ]. Reports of alcohol consumption during the pandemic revealed the highest relative increases in alcohol use in women and Black individuals [
      • Barbosa C.
      • Cowell A.J.
      • Dowd W.N
      Alcohol consumption in response to the COVID-19 pandemic in the United States.
      ].
      Trends in ALD disease burden and mortality have also indicated significant gender inequities. Historically, AUD and ALD have been more prevalent in men, however the gender gap is currently closing [
      • McHugh R.K.
      • Votaw V.R.
      • Sugarman D.E.
      • et al.
      Sex and gender differences in substance use disorders.
      ]. During the COVID-19 pandemic, women have experienced higher relative increases in alcohol consumption compared to men [
      • Rodriguez L.M.
      • Litt D.M.
      • Stewart S.H
      Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
      ,
      • Barbosa C.
      • Cowell A.J.
      • Dowd W.N
      Alcohol consumption in response to the COVID-19 pandemic in the United States.
      and higher reported stress [
      • Connor J.
      • Madhavan S.
      • Mokashi M.
      • et al.
      Health risks and outcomes that disproportionately affect women during the Covid-19 pandemic: a review.
      ]. Women reported increased loneliness and exposure to intimate partner violence, both of which were associated with higher alcohol consumption [
      • Devoto A.
      • Himelein-Wachowiak M.
      • Liu T.
      • et al.
      Women's substance use and mental health during the COVID-19 pandemic.
      ]. Among working individuals, women are disproportionately prevalent among essential workers [
      • Robertson C.
      • Gebeloff R
      How millions of women became the most essential workers in America.
      ], and women in jobs involving non-essential work were more likely to lose jobs than men during the pandemic [
      • Kochhar R
      Unemployment rose higher in three months of COVID-19 than it did in two years of the great recession.
      ]. All of these factors contribute to covid-related psychological distress, which has been associated with disproportionately heavier alcohol consumption in women [
      • Rodriguez L.M.
      • Litt D.M.
      • Stewart S.H
      Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
      ].
      Differential impact on alcohol consumption may explain some of the higher relative increases in ALD observed in women compared to men during the COVID pandemic. Women experienced higher relative increases in hospital admissions due to AH [
      • Sohal A.
      • Khalid S.
      • Green V.
      • et al.
      The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
      ,
      • Damjanovska S.
      • Karb D.B.
      • Cohen S.M
      Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
      , overall ALD admissions [
      • Cargill Z.
      • Kattiparambil S.
      • Hansi N.
      • et al.
      Severe alcohol-related liver disease admissions post-COVID-19 lockdown: canary in the coal mine?.
      ], and alcohol-associated pancreatitis [
      • Damjanovska S.
      • Karb D.B.
      • Cohen S.M
      Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
      ]. Women also experienced a higher relative increase in ALD mortality from 2019 to 2020 compared to men, and experienced a higher monthly rate of increase in mortality after the onset of the COVID pandemic [
      • Deutsch-Link S.
      • Jiang Y.
      • Peery A.F.
      • et al.
      Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      ].

      7. Improving AUD and ALD care during the COVID-19 pandemic: novel technologies and care delivery

      The COVID-19 pandemic has substantially impacted AUD and ALD in the United States. Rising disease burden and mortality warrants coordinated efforts to mitigate these troubling trends. Several aspects of AUD and ALD care can be targeted in the context of the pandemic and its aftermath in order to reduce disease burden and improve disease-related outcomes.
      First, during surges of COVID-19 cases, telehealth programs should be leveraged to continue providing care for patients while reducing risk of infection. Previous studies have shown that telehealth is effective in providing specialty hepatology care [
      • Serper M.
      • Cubell A.W.
      • Deleener M.E.
      • et al.
      Telemedicine in liver disease and beyond: can the COVID-19 crisis lead to action?.
      ], and helps patients reduce alcohol consumption [
      • Kruse C.S.
      • Lee K.
      • Watson J.B.
      • et al.
      Measures of effectiveness, efficiency, and quality of telemedicine in the management of alcohol abuse, addiction, and rehabilitation: systematic review.
      ]. In a Cochrane review, digital interventions were shown to be helpful in reducing harmful alcohol consumption [
      • Kaner E.F.
      • Beyer F.R.
      • Garnett C.
      • et al.
      Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.
      ]. During the COVID-19 pandemic, one web-based therapy program was effective in treating patients with AUD and ALD [
      • Bossi M.M.
      • Tufoni M.
      • Zaccherini G.
      • et al.
      A web-based group treatment for patients with alcoholic liver diseases at the time of the COVID-19 pandemic.
      ]. Although this study was small, it reported excellent adherence to treatment and high rates of alcohol abstinence. Another intervention delivered during the pandemic reported by Yau et al. [
      • Yau M.T.K.
      • Bromley L.
      • Treuil K.
      • et al.
      The management of alcohol-use disorder during the COVID-19 pandemic: evaluating the efficacy of virtual care in patients with alcohol-related liver disease.
      ] offered a virtual multi-disciplinary clinic for AUD and ALD patients. The authors found that during the study period, 70% of patients were started on anti-craving medications and 45% of patients remained abstinent from alcohol during the follow-up period.
      While telemedicine programs represent important advances in care delivery models and expand access to patients with geographic challenges, transportation issues, or who are at risk of severe COVID-19, they may neglect at-risk populations who may not have stable housing or internet access [
      • Scott Kruse C.
      • Karem P.
      • Shifflett K.
      • et al.
      Evaluating barriers to adopting telemedicine worldwide: a systematic review.
      ]. As such, in-person treatment and residential care (when appropriate) should remain available to those in need. Identifying patients that need resources and who may be unable to fully engage in virtual-based treatment can be assessed using socioeconomic screening tools. The PRAPARE (Protocol for Responding to and Assessing Patients’ Assess, Risks, and Experiences) screening tool has been used during the COVID-19 pandemic to screen for socioeconomic insecurity [
      • Luzius A.
      • Dobbs P.D.
      • Hammig B.
      • et al.
      Using the PRAPARE Tool to examine those tested and testing positive for COVID-19 at a community health center.
      ]. This tool assesses patients on 4 domains (personal characteristics, family and home life, money and resources, and social and emotional health) with structured and validated questions. This tool could be used in the evaluation of patients with AUD and ALD to better identify types of care that may meet their current psychosocial needs circumstances.
      Other aspects of ALD care that should be considered include prevention and treatment of COVID-19 infection. As mentioned above, patients with ALD are at higher risk for severe COVID-19 and COVID-19-related mortality. Healthcare providers should counsel patients with ALD about this risk and strongly recommend vaccinations and boosters. It appears that vaccine uptake in ALD patients may be excellent, with one Italian study reporting extremely high vaccine adherence (99.1%), higher than the general public [
      • Testino G.
      • Pellicano R
      Sars-Cov-2 vaccination in alcohol related liver disease.
      ], however, this study may not be generalizable to the United States. Medications and treatment for COVID-19 need to be considered and understood in the context of liver dysfunction, as they may be metabolized differently [
      • Khalatbari A.
      • Aghazadeh Z.
      • Ji C.
      Adverse effects of anti-COVID-19 drug candidates and alcohol on cellular stress responses of hepatocytes.
      ]. The impact of COVID-19 treatments in patients with liver dysfunction should be investigated in future studies.

      8. Response to rising alcohol consumption, alcohol use disorder, and alcohol-associated liver disease

      AUD and ALD were certainly rising before COVID-19 and have continued to do so at an even faster rate after the pandemic [
      • Lee B.P.
      • Dodge J.L.
      • Leventhal A.
      • et al.
      Retail alcohol and tobacco sales during COVID-19.
      ,
      • Deutsch-Link S.
      • Jiang Y.
      • Peery A.F.
      • et al.
      Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
      . Even short-term increases in alcohol consumption seen at the beginning of the pandemic are projected to have a substantial impact on ALD disease burden and mortality in the coming years [
      • Julien J.
      • Ayer T.
      • Tapper E.B.
      • et al.
      Effect of increased alcohol consumption during covid-19 pandemic on alcohol-related liver disease: a modeling study.
      ]. Continued increases in alcohol consumption and projections like these necessitate urgent efforts to curtail this troubling trend.
      One important intervention includes addressing early heavy and harmful alcohol consumption before patients develop AUD or ALD. This can encompass various intervention modalities including public health messaging, changes in tax policies, and improved outpatient screening. Some experts reported that during the COVID-19 pandemic public health messaging in the United States on healthy alcohol use lagged behind cultural messages promoting alcohol as a way to cope with pandemic-related stress [
      • Sugarman D.E.
      • Greenfield S.F
      Alcohol and COVID-19: how do we respond to this growing public health crisis?.
      ]. Public health messaging should be leveraged to education the public about unhealthy alcohol consumption.
      Screening for harmful alcohol consumption should be expanded and improved in primary care settings. Historically, screening for AUD has been inaccurate in primary settings, with a sensitivity of less than 50% based on current practices [
      • Mitchell A.J.
      • Meader N.
      • Bird V.
      • et al.
      Clinical recognition and recording of alcohol disorders by clinicians in primary and secondary care: meta-analysis.
      ]. Screening is also highly variable across clinic settings [
      • McNeely J.
      • Adam A.
      • Rotrosen J.
      • et al.
      Comparison of methods for alcohol and drug screening in primary care clinics.
      ], and evidence-based screening tools are under-utilized [
      • Friedmann P.D.
      • McCullough D.
      • Chin M.H.
      • et al.
      Screening and intervention for alcohol problems. A national survey of primary care physicians and psychiatrists.
      ]. Screening tools like the AUDIT-C (Alcohol Use Disorders Identification Test – Consumption), can be short and efficient (i.e. the AUDIT-C is comprised of 3 questions), with good sensitivity and specificity, and should be more widely adopted [
      • Bush K.
      • Kivlahan D.R.
      • McDonell M.B.
      • et al.
      The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking.
      ]. In fact, the US Preventive Services Task Force (USPSTF) recommends that all adults over the age of 18 receive screening for alcohol use disorder in primary care settings, and recommend either the AUDIT-C or the Single Alcohol Screening Question (SASQ), though recommendations on screening frequency have yet to be determined [
      • Curry S.J.
      • Krist A.H.
      • et al.
      US Preventive Services Task Force
      Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: us preventive services task force recommendation statement.
      ]. The U.S. Veterans Affairs Health System has successfully implemented an AUDIT-C based screening program, in which all primary care patients receive the AUDIT-C yearly and are referred for further evaluation and treatment if they screen positive [
      • Vickers Smith R.
      • Kranzler H.R.
      • Justice A.C.
      • et al.
      Longitudinal drinking patterns and their clinical correlates in million veteran program participants.
      ].
      Alcohol taxation policies may also have an important role in prevention of AUD and its associated harms. A previous study showed that higher maximum unit price and taxes on alcohol purchase is effective in reducing alcohol consumption in the general population [
      • Elder R.W.
      • Lawrence B.
      • Ferguson A.
      • et al.
      The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
      ]. A systematic review by Elder et al. [
      • Elder R.W.
      • Lawrence B.
      • Ferguson A.
      • et al.
      The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
      ] reported significant elasticity in alcohol consumption with tax increases across all age groups including adolescents. Elder and colleagues also observed consistent reductions in motor-vehicle crashes and decreased overall mortality with increasing alcohol taxes [
      • Elder R.W.
      • Lawrence B.
      • Ferguson A.
      • et al.
      The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
      ]. Alcohol taxation may also have a substantial impact of the prevalence of cirrhosis. Rush and colleagues reported almost a doubling of the prevalence of cirrhosis in Michigan as the relative alcohol price declined over the course of three decades [
      • Rush B.
      • Steinberg M.
      • Brook R
      The relationships among alcohol availability, alcohol consumption and alcohol-related damage in the Province of Ontario and the State of Michigan 1955-1982.
      ]. More recent studies have confirmed these relationships, though with conflicting data on which specific type of alcohol (beer, wine, spirits) may be more impactful [
      • Ponicki W.R.
      • Gruenewald P.J
      The impact of alcohol taxation on liver cirrhosis mortality.
      ,
      • Aslam S.
      • Buggs J.
      • Melo S.
      • et al.
      The association between alcoholic liver disease and alcohol tax.
      . Palatability for alcohol taxes is an area of concern, as they are often not supported by the public, however public support does increase when revenues are specifically directed toward prevention and treatment programs [
      • Wagenaar A.C.
      • Harwood E.M.
      • Toomey T.L.
      • et al.
      Public opinion on alcohol policies in the United States: results from a national survey.
      ]. Given broad evidence that taxation may reduce alcohol consumption and alcohol-related harms, consideration should be given to updated tax policies that could mitigate increasing population alcohol consumption.
      Once a person develops ALD, treating AUD or other harmful alcohol consumption is essential. Alcohol cessation can slow down progression of liver disease and even reverse it [
      • Thiele M.
      • Rausch V.
      • Fluhr G.
      • et al.
      Controlled attenuation parameter and alcoholic hepatic steatosis: diagnostic accuracy and role of alcohol detoxification.
      ,
      • Rogal S.
      • Youk A.
      • Zhang H.
      • et al.
      Impact of alcohol use disorder treatment on clinical outcomes among patients with cirrhosis.
      . In a large retrospective cohort study of veterans with AUD and cirrhosis, treatment of AUD reduced incident hepatic decompensation and decreased long-term all cause mortality [
      • Rogal S.
      • Youk A.
      • Zhang H.
      • et al.
      Impact of alcohol use disorder treatment on clinical outcomes among patients with cirrhosis.
      ]. However, a disturbing treatment gap persists in the United States; only 9% of Americans with substance use disorders receive SUD treatment [

      Lipari R.N. Key substance use and mental health indicators in the united states: results from the 2018 national survey on drug use and health. 2018:82.

      ]. Among VA patients with AUD and cirrhosis, only 14% received any form of AUD treatment, and national data indicates that only 19.8% of all adults with AUD receive any treatment for AUD in their lifetime [
      • Lucey M.R.
      • Singal A.K
      Integrated treatment of alcohol use disorder in patients with alcohol-associated liver disease: an evolving story.
      ]. While some of this gap in care may reflect patient disinterest [
      • Probst C.
      • Manthey J.
      • Martinez A.
      • et al.
      Alcohol use disorder severity and reported reasons not to seek treatment: a cross-sectional study in European primary care practices.
      ], barriers to receiving treatment currently exist and should be addressed [
      • DiMartini A.F.
      • Leggio L.
      • Singal A.K
      Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.
      ].
      Patients with dual ALD and AUD require complex, multidisciplinary care. Treatment of AUD can be challenging in the setting of liver dysfunction given hepatic metabolism of several AUD medications and lack of good data for their use in patients with cirrhosis [
      • Singal A.K.
      • Mathurin P
      Diagnosis and treatment of alcohol-associated liver disease: a review.
      ]. Gastroenterologists and hepatologists are well-suited to provide medication management to patients with liver dysfunction, however comfort specifically around prescribing pharmacotherapy for AUD is low among providers [
      • Im G.Y.
      • Mellinger J.L.
      • Winters A.
      • et al.
      Provider attitudes and practices for alcohol screening, treatment, and education in patients with liver disease: a survey from the American association for the study of liver diseases alcohol-associated liver disease special interest group.
      ]. As such, integrated care may be helpful, with a team-based approach to ALD and AUD care [
      • DiMartini A.F.
      • Leggio L.
      • Singal A.K
      Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.
      ].
      There is a profound shortage of mental health and SUD treatment providers in the United States. One study noted that only 15% of Americans had an outpatient mental health specialty practice in their community [
      • Cummings J.R.
      • Allen L.
      • Clennon J.
      • et al.
      Geographic access to specialty mental health care across high- and low-income US communities.
      ]. Rural communities had near half the access of urban or suburban communities. Thomas and colleagues have reported severe shortages of mental health providers in 75% of US counties [
      • Thomas K.C.
      • Ellis A.R.
      • Konrad T.R.
      • et al.
      County-level estimates of mental health professional shortage in the United States.
      ]. While we need to expand training of specialists in addiction medicine and addiction psychiatry, this could take years or decades, but we need to act sooner. One potential option is to expand SUD treatment in the context of primary care delivery. A systematic review and meta-analysis demonstrated that standardized screening, brief interventions or advice, referral to treatment (SBIRT) [
      • O'Donnell A.
      • Anderson P.
      • Newbury-Birch D.
      • et al.
      The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews.
      ] in primary care can be highly effective, however in practice, SBIRT has been under-utilized in primary care settings for several reasons including lack of education, lack of financial reimbursement, lack of time, and fear of losing patients [
      • Rehm J.
      • Anderson P.
      • Manthey J.
      • et al.
      Alcohol use disorders in primary health care: what do we know and where do we go?.
      ]. One could conceive of a similar model in gastroenterology office settings. Addressing barriers to implementation of SBIRT in primary care and gastroenterology office settings could help improve integration into primary care workflow.
      Collaborative care models for AUD in primary care have also been effective in treating AUD. The SUMMIT trial compared collaborative care models for AUD and opioid use disorder treatment to standard care, and demonstrated improve abstinence in the collaborative care group [
      • Watkins K.
      • Ober A.
      • Lamp K.
      • et al.
      Collaborative care for opioid and alcohol use disorders in primary care: the summit randomized clinical trial.
      ]. These models offload some of the burden on specialty providers in addiction medicine or addiction psychiatry and allow their expertise to reach higher numbers of patients. These models can be integrated into primary care offices to improve access to SUD treatment for those in need.

      9. Conclusion

      The COVID-19 pandemic has had a substantial impact on AUD and ALD outcomes. The early stress and isolation led to increased alcohol use and exacerbated already present AUD. The pandemic burdened healthcare delivery and treatment, which impacted access to AUD and ALD care. The infection itself disproportionately harmed the AUD and ALD population. The continued rise in AUD and ALD disease burden portends a troubling rise in prevalence of end-stage liver disease. In the US, we need a united and collaborative effort to prevent harmful alcohol use and treat prevalent alcohol use disorder in patients with and without liver disease.

      Conflict of interest

      SDL is supported in part by NIH grant T32 DK007634. AKS reports outside the submitted work personal fees from Gilead, Medscape Gastroenterology, Chronic Liver Disease Foundation, Up-to-Date, and ACG; non-financial support from AASLD and American Porphyria Foundation; and grants from NIAAA and NIDDK outside the submitted work.

      References

        • Grant B.F.
        • Chou S.P.
        • Saha T.D.
        • et al.
        Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the united states, 2001-2002 to 2012-2013: results from the national epidemiologic survey on alcohol and related conditions.
        JAMA Psychiatry. 2017; 74: 911-923
        • Moon A.M.
        • Yang J.Y.
        • Barritt A.S.
        • et al.
        Rising mortality from alcohol-associated liver disease in the United States in the 21st century.
        Am J Gastroenterol. 2020; 115: 79-87
        • Pfefferbaum B.
        • North C.S
        Mental health and the Covid-19 pandemic.
        New Eng J Med. 2020; 383: 510-512
        • Rodriguez L.M.
        • Litt D.M.
        • Stewart S.H
        Drinking to cope with the pandemic: the unique associations of COVID-19-related perceived threat and psychological distress to drinking behaviors in American men and women.
        Addict Behav. 2020; 110106532
        • Keyes K.M.
        • Hatzenbuehler M.L.
        • Hasin D.S
        Stressful life experiences, alcohol consumption, and alcohol use disorders: the epidemiologic evidence for four main types of stressors.
        Psychopharmacology (Berl). 2011; 218: 1-17
        • de Goeij M.C.M.
        • Suhrcke M.
        • Toffolutti V.
        • et al.
        How economic crises affect alcohol consumption and alcohol-related health problems: a realist systematic review.
        Soc Sci Med. 2015; 131: 131-146
        • Lee B.P.
        • Dodge J.L.
        • Leventhal A.
        • et al.
        Retail alcohol and tobacco sales during COVID-19.
        Ann Intern Med. 2021; 174: 1027-1029
        • Ahmed M.Z.
        • Ahmed O.
        • Aibao Z.
        • et al.
        Epidemic of COVID-19 in China and associated psychological problems.
        Asian J Psychiatr. 2020; 51102092
        • Jackson S.E.
        • Garnett C.
        • Shahab L.
        • et al.
        Association of the COVID-19 lockdown with smoking, drinking and attempts to quit in England: an analysis of 2019-20 data.
        Addiction. 2021; 116: 1233-1244
        • Sharma R.A.
        • Subedi K.
        • Gbadebo B.M.
        • et al.
        Alcohol withdrawal rates in hospitalized patients during the COVID-19 pandemic.
        JAMA Network Open. 2021; 4e210422
        • White A.M.
        • Castle I.-.J.P.
        • Powell P.A.
        • et al.
        Alcohol-related deaths during the COVID-19 pandemic.
        JAMA. 2022; e224408
        • Le T.M.
        • Wang W.
        • Zhornitsky S.
        • et al.
        The neural processes interlinking social isolation, social support, and problem alcohol use.
        Int J Neuropsychopharmacol. 2021; 24: 333-343
        • Stewart S.D
        COVID-19, coronavirus-related anxiety, and changes in women's alcohol use.
        JGWH. 2021; 20: 1-12
      1. https://www.nytimes.com/2020/03/26/health/coronavirus-alcoholics-drugs-online.html Accessed April 19,.
        • Polcin D.L.
        • Mahoney E.
        • Wittman F.
        • et al.
        Understanding challenges for recovery homes during COVID-19.
        Int J Drug Policy. 2021; 93102986
        • Aponte-Melendez Y.
        • Mateu-Gelabert P.
        • Fong C.
        • et al.
        The impact of COVID-19 on people who inject drugs in New York City: increased risk and decreased access to services.
        Harm Reduct J. 2021; 18: 118
        • Mellinger J.L.
        • Shedden K.
        • Winder G.S.
        • et al.
        The high burden of alcoholic cirrhosis in privately insured persons in the United States.
        Hepatology. 2018; 68: 872-882
        • Shirazi F.
        • Singal A.K.
        • Wong R.J
        Alcohol-associated Cirrhosis and Alcoholic Hepatitis Hospitalization Trends in the United States.
        J Clin Gastroenterol. 2021; 55: 174-179
        • Barritt A.S.
        • Jiang Y.
        • Schmidt M.
        • et al.
        Charges for alcoholic cirrhosis exceed all other etiologies of cirrhosis combined: a national and state inpatient survey analysis.
        Dig Dis Sci. 2019; 64: 1460-1469
        • Cholankeril G.
        • Ahmed A
        Alcoholic liver disease replaces hepatitis c virus infection as the leading indication for liver transplantation in the United States.
        Clin Gastroenterol Hepatol. 2018; 16: 1356-1358
        • Wong R.J.
        • Singal A.K
        Trends in liver disease etiology among adults awaiting liver transplantation in the United States, 2014-2019.
        JAMA Network Open. 2020; 3e1920294
        • Herrick-Reynolds K.M.
        • Punchhi G.
        • Greenberg R.S.
        • et al.
        Evaluation of early vs standard liver transplant for alcohol-associated liver disease.
        JAMA Surg. 2021; 156: 1026-1034
        • Julien J.
        • Ayer T.
        • Tapper E.B.
        • et al.
        Effect of increased alcohol consumption during covid-19 pandemic on alcohol-related liver disease: a modeling study.
        Hepatology. 2021; (Epub ahead of print)
        • Gonzalez H.C.
        • Zhou Y.
        • Nimri F.M.
        • et al.
        Alcohol-related hepatitis admissions increased 50% in the first months of the COVID-19 pandemic in the USA.
        Liver Int. 2022; 42: 762-764
        • Sohal A.
        • Khalid S.
        • Green V.
        • et al.
        The pandemic within the pandemic: unprecedented rise in alcohol-related hepatitis during the COVID-19 pandemic.
        J Clin Gastroenterol. 2022; 56: e171-e175
        • Deutsch-Link S.
        • Jiang Y.
        • Peery A.F.
        • et al.
        Alcohol-associated liver disease mortality increased from 2017 to 2020 and accelerated during the COVID-19 pandemic.
        Clin Gastroenterol Hepatol. March 2022; S1542-3565 (-0): 00292
        • Itoshima H.
        • Shin J.-.H.
        • Takada D.
        • et al.
        The impact of the COVID-19 epidemic on hospital admissions for alcohol-related liver disease and pancreatitis in Japan.
        Sci Rep. 2021; 11: 14054
        • Shaheen A.A.
        • Kong K.
        • Ma C.
        • et al.
        Impact of the COVID-19 pandemic on hospitalizations for alcoholic hepatitis or cirrhosis in Alberta, Canada.
        Clin Gastroenterol Hepatol. 2022; 20: e1170-e1179
        • Cargill Z.
        • Kattiparambil S.
        • Hansi N.
        • et al.
        Severe alcohol-related liver disease admissions post-COVID-19 lockdown: canary in the coal mine?.
        Frontline Gastroenterol. 2021; 12: 354-355
        • Pearson M.M.
        • Kim N.J.
        • Berry K.
        • et al.
        Associations between alcohol use and liver-related outcomes in a large national cohort of patients with cirrhosis.
        Hepatology Communications. 2021; 5: 2080-2095
        • Santos SGR dos
        • Mattos A.A.
        • Guimarães M.M.
        • et al.
        Alcohol consumption influences clinical outcome in patients admitted to a referral center for liver disease.
        Ann Hepatol. 2018; 17: 470-475
        • Görgülü E.
        • Gu W.
        • Trebicka J.
        • et al.
        Acute-on-chronic liver failure (ACLF) precipitated by severe alcoholic hepatitis: another collateral damage of the COVID-19 pandemic?.
        Gut. 2022; 71: 1036-1038
        • Szabo G.
        • Saha B
        Alcohol's effect on host defense.
        Alcohol Res. 2015; 37: 159-170
        • Huang W.
        • Zhou H.
        • Hodgkinson C.
        • et al.
        Network meta-analysis on the mechanisms underlying alcohol augmentation of COVID-19 pathologies.
        Alcohol Clin Exp Res. 2021; 45: 675-688
        • Wang Q.Q.
        • Kaelber D.C.
        • Xu R.
        • et al.
        COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States.
        Mol Psychiatry. 2021; 26: 30-39
        • Iavarone M.
        • D'Ambrosio R.
        • Soria A.
        • et al.
        High rates of 30-day mortality in patients with cirrhosis and COVID-19.
        J Hepatol. 2020; 73: 1063-1071
        • Moon A.M.
        • Webb G.J.
        • Aloman C.
        • et al.
        High mortality rates for SARS-CoV-2 infection in patients with pre-existing chronic liver disease and cirrhosis: preliminary results from an international registry.
        J Hepatol. 2020; 73: 705-708
        • Kim D.
        • Adeniji N.
        • Latt N.
        • et al.
        Predictors of outcomes of COVID-19 in patients with chronic liver disease: US multi-center study.
        Clin Gastroenterol Hepatol. 2021; 19 (e19): 1469-1479
        • Marjot T.
        • Moon A.M.
        • Cook J.A.
        • et al.
        Outcomes following SARS-CoV-2 infection in patients with chronic liver disease: an international registry study.
        J Hepatol. 2021; 74: 567-577
        • Mahmud N.
        • Hubbard R.A.
        • Kaplan D.E.
        • et al.
        Declining cirrhosis hospitalizations in the wake of the COVID-19 pandemic: a national cohort study.
        Gastroenterology. 2020; 159 (e3): 1134-1136
        • Zelman S.
        • Holzwanger E.
        • Malik R.
        • et al.
        Alcoholic hepatitis and COVID-19: the question of steroids.
        ACG Case Rep J. 2020; 7: e00504
      2. Dexamethasone in hospitalized patients with Covid-19.
        New Eng J Med. 2021; 384: 693-704
        • Cholankeril G.
        • Goli K.
        • Rana A.
        • et al.
        Impact of COVID-19 pandemic on liver transplantation and alcohol-associated liver disease in the USA.
        Hepatology. 2021; 74: 3316-3329
        • Bittermann T.
        • Mahmud N.
        • Abt P
        Trends in liver transplantation for acute alcohol-associated hepatitis during the COVID-19 pandemic in the US.
        JAMA Netw Open. 2021; 4e2118713
        • Anderson M.S.
        • Valbuena V.S.M.
        • Brown C.S.
        • et al.
        Association of COVID-19 with new waiting list registrations and liver transplantation for alcoholic hepatitis in the United States.
        JAMA Netw Open. 2021; 4e2131132
        • Bangaru S.
        • Pedersen M.R.
        • MacConmara M.P.
        • et al.
        Survey of liver transplantation practices for severe acute alcoholic hepatitis.
        Liver Transpl. 2018; 24: 1357-1362
        • Belli L.S.
        • Duvoux C.
        • Cortesi P.A.
        • et al.
        COVID-19 in liver transplant candidates: pretransplant and post-transplant outcomes - an ELITA/ELTR multicentre cohort study.
        Gut. 2021; 70: 1914-1924
        • Martini S.
        • Patrono D.
        • Pittaluga F.
        • et al.
        Urgent liver transplantation soon after recovery from COVID-19 in a patient with decompensated liver cirrhosis.
        Hepatol Commun. July 2020;
        • Gonzalez A.
        • Zervos X.
        • Pinna A.
        • et al.
        Orthotopic liver transplantation in a cirrhotic patient with recent COVID-19 infection.
        ACG Case Rep J. 2021; 8: e00634
        • Gambato M.
        • Germani G.
        • Perini B.
        • et al.
        A challenging liver transplantation for decompensated alcoholic liver disease after recovery from SARS-CoV-2 infection.
        Transpl Int. 2021; 34: 756-757
        • Lee B.T.
        • Perumalswami P.V.
        • Im G.Y.
        • et al.
        COVID-19 in liver transplant recipients: an initial experience from the US epicenter.
        Gastroenterology. 2020; 159 (e2): 1176-1178
        • Kulkarni A.V.
        • Tevethia H.V.
        • Premkumar M.
        • et al.
        Impact of COVID-19 on liver transplant recipients–a systematic review and meta-analysis.
        eClinicalMedicine. 2021; 38
        • Lee A.R.Y.B.
        • Wong S.Y.
        • Chai L.Y.A.
        • et al.
        Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis.
        BMJ. 2022; 376e068632
        • Vaeth P.A.C.
        • Wang-Schweig M.
        • Caetano R
        Drinking, alcohol use disorder, and treatment access and utilization among U.S. racial/ethnic groups.
        Alcohol Clin Exp Res. 2017; 41: 6-19
        • Singal A.
        • Yong-Fang K.
        • Arab J.
        • et al.
        Racial and health disparities among cirrhosis-related hospitalizations in the USA.
        J Clin Transl Hepatol. 2022; (Published Online)
        • Deutsch-Link S.
        • Weinberg E.M.
        • Bittermann T.
        • et al.
        The stanford integrated psychosocial assessment for transplant is associated with outcomes before and after liver transplantation.
        Liver Transpl. 2021; 27: 652-667
        • Lee B.P.
        • Vittinghoff E.
        • Pletcher M.J.
        • et al.
        Medicaid policy and liver transplant for alcohol-associated liver disease.
        Hepatology. 2020; 72: 130-139
        • Webb Hooper M.
        • Nápoles A.M.
        • Pérez-Stable E.J
        COVID-19 and racial/ethnic disparities.
        JAMA. 2020; 323: 2466-2467
        • Moore J.T.
        • Ricaldi J.N.
        • Rose C.E.
        • et al.
        Disparities in incidence of COVID-19 among underrepresented racial/ethnic groups in counties identified as hotspots during June 5-18, 2020 - 22 States, February-June 2020.
        MMWR Morb Mortal Wkly Rep. 2020; 69: 1122-1126
        • Adeniji N.
        • Carr R.M.
        • Aby E.S.
        • et al.
        Socioeconomic factors contribute to the higher risk of COVID-19 in racial and ethnic minorities with chronic liver diseases.
        Gastroenterology. 2021; 160 (e3): 1406-1409
        • Damjanovska S.
        • Karb D.B.
        • Cohen S.M
        Increasing prevalence and racial disparity of alcohol-related gastrointestinal and liver disease during the COVID-19 pandemic: a population-based national study.
        J Clin Gastroenterol. January 2022;
        • Barbosa C.
        • Cowell A.J.
        • Dowd W.N
        Alcohol consumption in response to the COVID-19 pandemic in the United States.
        J Addict Med. 2021; 15: 341-344
        • McHugh R.K.
        • Votaw V.R.
        • Sugarman D.E.
        • et al.
        Sex and gender differences in substance use disorders.
        Clin Psychol Rev. 2018; 66: 12-23
        • Connor J.
        • Madhavan S.
        • Mokashi M.
        • et al.
        Health risks and outcomes that disproportionately affect women during the Covid-19 pandemic: a review.
        Soc Sci Med. 2020; 266113364
        • Devoto A.
        • Himelein-Wachowiak M.
        • Liu T.
        • et al.
        Women's substance use and mental health during the COVID-19 pandemic.
        Women's Health Issues. January 2022;
      3. https://www.nytimes.com/2020/04/18/us/coronavirus-women-essential-workers.html Published April 18 Accessed May 2, 2022.
      4. https://www.pewresearch.org/fact-tank/2020/06/11/unemployment-rose-higher-in-three-months-of-covid-19-than-it-did-in-two-years-of-the-great-recession/ Accessed May 2.
        • Serper M.
        • Cubell A.W.
        • Deleener M.E.
        • et al.
        Telemedicine in liver disease and beyond: can the COVID-19 crisis lead to action?.
        Hepatology. 2020; 72: 723-728
        • Kruse C.S.
        • Lee K.
        • Watson J.B.
        • et al.
        Measures of effectiveness, efficiency, and quality of telemedicine in the management of alcohol abuse, addiction, and rehabilitation: systematic review.
        J Med Internet Res. 2020; 22: e13252
        • Kaner E.F.
        • Beyer F.R.
        • Garnett C.
        • et al.
        Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.
        Cochrane Database Syst Rev. 2017; 9CD011479
        • Bossi M.M.
        • Tufoni M.
        • Zaccherini G.
        • et al.
        A web-based group treatment for patients with alcoholic liver diseases at the time of the COVID-19 pandemic.
        Dig Liver Dis. 2020; 52: 956-957
        • Yau M.T.K.
        • Bromley L.
        • Treuil K.
        • et al.
        The management of alcohol-use disorder during the COVID-19 pandemic: evaluating the efficacy of virtual care in patients with alcohol-related liver disease.
        Virtual. 2021; 4 (2): 193-194
        • Scott Kruse C.
        • Karem P.
        • Shifflett K.
        • et al.
        Evaluating barriers to adopting telemedicine worldwide: a systematic review.
        J Telemed Telecare. 2018; 24: 4-12
        • Luzius A.
        • Dobbs P.D.
        • Hammig B.
        • et al.
        Using the PRAPARE Tool to examine those tested and testing positive for COVID-19 at a community health center.
        J Racial Ethn Health Disparities. June 2021; : 1-8
        • Testino G.
        • Pellicano R
        Sars-Cov-2 vaccination in alcohol related liver disease.
        Minerva Gastroenterol (Torino). November 2021;
        • Khalatbari A.
        • Aghazadeh Z.
        • Ji C.
        Adverse effects of anti-COVID-19 drug candidates and alcohol on cellular stress responses of hepatocytes.
        Hepatology Communications. 2022; 6: 1262-1277
        • Sugarman D.E.
        • Greenfield S.F
        Alcohol and COVID-19: how do we respond to this growing public health crisis?.
        J Gen Intern Med. 2021; 36: 214-215
        • Mitchell A.J.
        • Meader N.
        • Bird V.
        • et al.
        Clinical recognition and recording of alcohol disorders by clinicians in primary and secondary care: meta-analysis.
        Br J Psychiatry. 2012; 201: 93-100
        • McNeely J.
        • Adam A.
        • Rotrosen J.
        • et al.
        Comparison of methods for alcohol and drug screening in primary care clinics.
        JAMA Network Open. 2021; 4e2110721
        • Friedmann P.D.
        • McCullough D.
        • Chin M.H.
        • et al.
        Screening and intervention for alcohol problems. A national survey of primary care physicians and psychiatrists.
        J Gen Intern Med. 2000; 15: 84-91
        • Bush K.
        • Kivlahan D.R.
        • McDonell M.B.
        • et al.
        The AUDIT alcohol consumption questions (AUDIT-C): an effective brief screening test for problem drinking.
        Arch. Intern. Med. 1998; 158: 1789-1795
        • Curry S.J.
        • Krist A.H.
        • et al.
        • US Preventive Services Task Force
        Screening and behavioral counseling interventions to reduce unhealthy alcohol use in adolescents and adults: us preventive services task force recommendation statement.
        JAMA. 2018; 320: 1899-1909
        • Vickers Smith R.
        • Kranzler H.R.
        • Justice A.C.
        • et al.
        Longitudinal drinking patterns and their clinical correlates in million veteran program participants.
        Alcohol, Clin Experiment Res. 2019; 43: 465-472
        • Elder R.W.
        • Lawrence B.
        • Ferguson A.
        • et al.
        The effectiveness of tax policy interventions for reducing excessive alcohol consumption and related harms.
        Am J Prev Med. 2010; 38: 217-229
        • Rush B.
        • Steinberg M.
        • Brook R
        The relationships among alcohol availability, alcohol consumption and alcohol-related damage in the Province of Ontario and the State of Michigan 1955-1982.
        Adv Alcohol Subst Abuse. 1986; 5: 33-45
        • Ponicki W.R.
        • Gruenewald P.J
        The impact of alcohol taxation on liver cirrhosis mortality.
        J Stud Alcohol. 2006; 67: 934-938
        • Aslam S.
        • Buggs J.
        • Melo S.
        • et al.
        The association between alcoholic liver disease and alcohol tax.
        Am Surg. 2021; 87: 92-96
        • Wagenaar A.C.
        • Harwood E.M.
        • Toomey T.L.
        • et al.
        Public opinion on alcohol policies in the United States: results from a national survey.
        J Public Health Policy. 2000; 21: 303-327
        • Thiele M.
        • Rausch V.
        • Fluhr G.
        • et al.
        Controlled attenuation parameter and alcoholic hepatic steatosis: diagnostic accuracy and role of alcohol detoxification.
        J Hepatol. 2018; 68: 1025-1032
        • Rogal S.
        • Youk A.
        • Zhang H.
        • et al.
        Impact of alcohol use disorder treatment on clinical outcomes among patients with cirrhosis.
        Hepatology. 2020; 71: 2080-2092
      5. Lipari R.N. Key substance use and mental health indicators in the united states: results from the 2018 national survey on drug use and health. 2018:82.

        • Lucey M.R.
        • Singal A.K
        Integrated treatment of alcohol use disorder in patients with alcohol-associated liver disease: an evolving story.
        Hepatology. 2020; 71: 1891-1893
        • Probst C.
        • Manthey J.
        • Martinez A.
        • et al.
        Alcohol use disorder severity and reported reasons not to seek treatment: a cross-sectional study in European primary care practices.
        Subst Abuse Treat Prev Policy. 2015; 10: 32
        • DiMartini A.F.
        • Leggio L.
        • Singal A.K
        Barriers to the management of alcohol use disorder and alcohol-associated liver disease: strategies to implement integrated care models.
        Lancet Gastroenterol Hepatol. 2022; 7: 186-195
        • Singal A.K.
        • Mathurin P
        Diagnosis and treatment of alcohol-associated liver disease: a review.
        JAMA. 2021; 326: 165-176
        • Im G.Y.
        • Mellinger J.L.
        • Winters A.
        • et al.
        Provider attitudes and practices for alcohol screening, treatment, and education in patients with liver disease: a survey from the American association for the study of liver diseases alcohol-associated liver disease special interest group.
        Clin Gastroenterol Hepatol. 2021; 19 (e8): 2407-2416
        • Cummings J.R.
        • Allen L.
        • Clennon J.
        • et al.
        Geographic access to specialty mental health care across high- and low-income US communities.
        JAMA Psychiatry. 2017; 74: 476-484
        • Thomas K.C.
        • Ellis A.R.
        • Konrad T.R.
        • et al.
        County-level estimates of mental health professional shortage in the United States.
        PS. 2009; 60: 1323-1328
        • O'Donnell A.
        • Anderson P.
        • Newbury-Birch D.
        • et al.
        The impact of brief alcohol interventions in primary healthcare: a systematic review of reviews.
        Alcohol Alcohol. 2014; 49: 66-78
        • Rehm J.
        • Anderson P.
        • Manthey J.
        • et al.
        Alcohol use disorders in primary health care: what do we know and where do we go?.
        Alcohol Alcohol. 2016; 51: 422-427
        • Watkins K.
        • Ober A.
        • Lamp K.
        • et al.
        Collaborative care for opioid and alcohol use disorders in primary care: the summit randomized clinical trial.
        JAMA Intern Med. 2017; 177: 1480-1488