The achievement of high rates of sustained virological response (SVR) with direct-acting antivirals (DAAs) in hepatitis C virus (HCV) infected patients will reduce decompensating terminal events.
To investigate whether hepatocellular carcinoma (HCC) occurrence could change due to the DAA-induced increase in life-expectancy.
A Markov model was built on clinical data of 494 cirrhotic patients and available literature to estimate probabilities of “death before HCC” and of “HCC occurrence” without and with DAA.
In comparison to untreated patients, DAA therapy reduced the 20-year mortality before HCC by 21.9% in patients without varices and by 21.5% in those with varices, considering an SVR of 95% and no direct effect on hepatocarcinogenesis. Tumour occurrence increased by 5%–8.2% and the proportion of HCCs diagnosed in compensated stages increased to >98%. If we consider DAA as having “anti-tumoral” effects, the benefit becomes greater, achieving a 20-year survival of 81.5% in patients without varices, and 52.2% in patients with varices. Instead, if we consider DAA as having a “pro-tumoral” effect, then, the increased incidence of HCC nullifies the survival benefits.
DAAs drastically reduce the mortality caused by the liver function worsening, increasing the proportion of HCCs diagnosed in compensated stages. Knowledge of the DAA effect on hepatocarcinogenesis remains pivotal.
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- Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies.Ann Intern Med. 2013; 158: 329-337
- Efficacy and safety of ombitasvir, paritaprevir, and ritonavir in an open-label study of patients with genotype 1b chronic hepatitis C virus infection with and without cirrhosis.Gastroenterology. 2015; 149: 971-980
- Lack of evidence of an effect of direct acting antivirals on the recurrence of hepatocellular carcinoma: the ANRS collaborative study group on hepatocellular carcinoma (ANRS CO22 HEPATHER, CO12 CIRVIR and CO23 CUPILT cohorts).J Hepatol. 2016; 65: 734-740
- Hepatocellular carcinoma recurrence after treatment with direct-acting antivirals: first, do no harm by withdrawing treatment.J Hepatol. 2016; 65: 862-864
- Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis.J Hepatol. 2016; 64: 1224-1231
- Unexpected early tumor recurrence in patients with hepatitis C virus-related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution.J Hepatol. 2016; 65: 719-726
- Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct acting antivirals.J Hepatol. 2016; 65: 727-733
- Direct acting antiviral therapy and tumor recurrence after liver transplant for hepatitis C-associated hepatocellular carcinoma.J Hepatol. 2016; 65: 859-860
- Prevention of hepatocellular carcinoma recurrence with alpha-interferon after liver resection in HCV cirrhosis.Hepatology. 2006; 44: 1543-1554
- Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis.JAMA. 2012; 308: 2584-2593
- Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients.Aliment Pharmacol Ther. 2014; 39: 1180-1193
- Hepatocellular carcinoma in cirrhosis: incidence and risk factors.Gastroenterology. 2004; 127: S35-S50
- Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection.N Engl J Med. 2014; 370: 1483-1493
- Practical meta-analysis.SAGE Publications, Inc., Thousand Oaks, California, US2001
- Statistical power analysis for the behavioral sciences.2nd ed. Erlbaum, USA, Hillsdale, NJ1988
- Confidence intervals for the number needed to treat.BMJ. 1998; 317: 1309-1312
- Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study.Lancet. 2014; 384: 1756-1765
- Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.J Hepatol. 2016; 65: 692-699
- The number needed to treat to prevent mortality and cirrhosis-related complications among patients with cirrhosis and HCV genotype 1 infection.J Viral Hepat. 2014; 21: 568-577
- Outcomes after successful direct-acting antiviral therapy for patients with chronic hepatitis C and decompensated cirrhosis.J Hepatol. 2016; 65: 741-747
- Immunity, inflammation, and cancer.Cell. 2010; 140: 883-899
- Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.J Viral Hepat. 2016; 23: 496-505
- Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.Aliment Pharmacol Ther. 2017; 45: 160-168
- Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.J Hepatol. 2016; 64: 1217-1223
- Harm and benefits of primary liver resection and salvage transplantation for hepatocellular carcinoma.Am J Transplant. 2010; 10: 619-627
- Impact of virus eradication in patients with compensated hepatitis C virus-related cirrhosis: competing risks and multistate model.Liver Int. 2016; 36: 1765-1773
Published online: October 18, 2017
Accepted: October 9, 2017
Received in revised form: October 9, 2017
Received: April 27, 2017
© 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.