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Hepatitis B reactivation and immune check point inhibitors

Published:September 10, 2020DOI:https://doi.org/10.1016/j.dld.2020.08.041

      Abstract

      Background: Liver toxicity during immune checkpoint inhibitor treatment is mostly due to immune mediated hepatitis. Viral hepatitis, as well as auto-immune or metabolic hepatitis, are considered as exclusion criteria for ICI induced immune hepatitis diagnosis. However, considering the high prevalence of viral hepatitis B infection and the increasing prescription of immune checkpoint inhibitors, their use in patients with HBV chronic viral infection may be common, even more if patients are treated for hepatocellular carcinoma. Few clinical studies directly deal with the risk of HBV reactivation during ICI therapy and real-life data is currently based on five reported cases of HBV reactivation, one with fatal outcome.
      In this review, we summarize the current available clinical information about HBV reactivation risk during ICI treatment, its hypothetic mechanism, and propose practical recommendations about verifying and monitoring HBV status throughout the treatment.

      Keywords

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      References

        • Jennings J.J.
        • Mandaliya R.
        • Nakshabandi A.
        • Lewis J.H.
        Hepatotoxicity induced by immune checkpoint inhibitors: a comprehensive review including current and alternative management strategies.
        Expert Opin Drug Metab Toxicol. 2019; 15: 231-244
        • Lleo A.
        • Rimassa L.
        • Colombo M.
        Hepatotoxicity of immune check point inhibitors: approach and management.
        Dig Liver Dis. 2019; 51: 1074-1078
        • Wang D.Y.
        • Salem J.-.E.
        • Cohen J.V.
        • et al.
        Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis.
        JAMA Oncol. 2018; 4: 1721-1728
        • De Martin E.
        • Michot J.-M.
        • Papouin B.
        • et al.
        Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors.
        J Hepatol. 2018; 68: 1181-1190
        • Hsu C.
        • Marshall J.L.
        • He A.R.
        Workup and management of immune‐mediated hepatobiliary pancreatic toxicities that develop during immune checkpoint inhibitor treatment.
        Oncologist. 2020; 25: 105-111
        • El-Khoueiry A.B.
        • Sangro B.
        • Yau T.
        • et al.
        Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.
        Lancet. 2017; 389: 2492-2502
        • Zhang X.
        • Zhou Y.
        • Chen C.
        • et al.
        Hepatitis B virus reactivation in cancer patients with positive hepatitis B surface antigen undergoing PD-1 inhibition.
        J Immunother Cancer. 2019; 7: 322
        • Pu D.
        • Yin L.
        • Zhou Y.
        • et al.
        Safety and efficacy of immune checkpoint inhibitors in patients with HBV/HCV infection and advanced-stage cancer: a systematic review.
        Medicine. 2020; 99: e19013
        • Kothapalli A.
        • Khattak M.A.
        Safety and efficacy of anti-PD-1 therapy for metastatic melanoma and non-small-cell lung cancer in patients with viral hepatitis: a case series.
        Melanoma Res. 2018; 28: 155-158
        • Shah N.J.
        • Al-Shbool G.
        • Blackburn M.
        • et al.
        Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection.
        J Immunother Cancer. 2019; 7: 353
        • Tsimafeyeu I.
        • Gafanov R.
        • Protsenko S.
        • et al.
        Nivolumab in patients with metastatic renal cell carcinoma and chronic hepatitis C virus infection.
        Cancer Immunol Immunother. 2020; 69: 983-988
        • Pandey A.
        • Ezemenari S.
        • Liaukovich M.
        • Richard I.
        • Boris A.
        A rare case of pembrolizumab-induced reactivation of hepatitis B.
        Case Rep Oncol Med. 2018; 2018: 1-3
      1. Lake, A.C.Hepatitis B reactivation in a long-term nonprogressor due to nivolumab therapy: AIDS2017;31(15):2115–8.

        • Koksal A.S.
        • Toka B.
        • Eminler A.T.
        • et al.
        HBV-related acute hepatitis due to immune checkpoint inhibitors in a patient with malignant melanoma.
        Ann Oncol. 2017; 28: 3103-3104
      2. Ragunathan, K., Dadana, S., Huang, C.-H.. Hepatitis B reactivation after administration of pembrolizumab (KEYTRUDA): a unique case report. 2017;112:S1187–8.

        • Lombardi A.
        • Mondelli M.U.
        Review article: immune checkpoint inhibitors and the liver, from therapeutic efficacy to side effects.
        Aliment Pharmacol Ther. 2019; 50: 872-884
        • Riveiro‐Barciela M.
        • Barreira‐Díaz A.
        • Vidal‐González J.
        • et al.
        Immune‐related hepatitis related to checkpoint inhibitors: clinical and prognostic factors.
        Liver Int. 2020; 40: 1906-1916
        • Razavi-Shearer D.
        • Gamkrelidze I.
        • Nguyen M.H.
        • et al.
        Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study.
        Lancet Gastroenterol Hepatol. 2018; 3: 383-403
        • Smalls D.J.
        • Kiger R.E.
        • Norris L.B.
        • Bennett C.L.
        • Love B.L.
        Hepatitis B virus reactivation: risk factors and current management strategies.
        Pharmacother J Hum Pharmacol Drug Ther. 2019; 39: 1190-1203
        • Kotake T.
        • Satake H.
        • Okita Y.
        • et al.
        Prevalence and risk factors of hepatitis B virus reactivation in patients with solid tumors with resolved HBV infection.
        Asia Pac J Clin Oncol. 2019; 15: 63-68
        • Jenne C.N.
        • Kubes P.
        Immune surveillance by the liver.
        Nat Immunol. 2013; 14: 996-1006
        • Ye B.
        • Liu X.
        • Li X.
        • Kong H.
        • Tian L.
        • Chen Y.
        T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance.
        Cell Death Dis. 2015; 6: e1694