Elsevier

The Lancet Oncology

Volume 3, Issue 6, June 2002, Pages 333-340
The Lancet Oncology

Review
Reactivation of replication of hepatitis B and C viruses after immunosuppressive therapy: an unresolved issue

https://doi.org/10.1016/S1470-2045(02)00773-8Get rights and content

Summary

The liver is susceptible to the toxic effects of many cytotoxic or immunosuppressive treatments. However, in carriers of hepatitis B virus (HBV) and, less frequently, of hepatitis C virus, liver damage due to reactivation of viral replication can occur after withdrawal of immuno-suppressive drugs. These reactivations, which are associated with fulminant forms of hepatitis in up to 25% of cases, are observed both in symptom-free chronic carriers of hepatitis B surface antigen and in patients who have chronic hepatitis B or C and concurrent haematological tumours or solid neoplasms or who have received transplants. HBV-related complications may cause delays or modifications of therapy, and the chance of cure is reduced. In this review, we analyse clinical, biochemical, and serological issues in reactivation of viral replication and examine the role of immune reactions in the pathogenesis and the possible toxicity of immunosuppressive drugs. We emphasise the importance of identifying predictive markers of a clinically relevant reactivation, review difficulties in drug prevention and treatment, indicate studies that are needed to address the key clinical issues, and give practical recommendations to practising physicians and oncologists

Section snippets

Reactivation of chronic HBV infection

The first descriptions of adverse effects of immunosuppressive therapies in chronic HBV infection were published 27 years ago.12, 13, 14 The first study12 found that anti-HB-surface-antigen titres tended to decrease during chemotherapy given for myeloproliferative and lymphoproliferative diseases, and in many patients this fall was followed by reappearance of hepatitis B surface antigen (HBsAg). In patients who were HBsAg-positive before therapy, HBsAg concentrations increased. Significant

Reactivation of chronic HCV infection

HCV infection is highly prevalent (8–32%) in patients with B-cell non-Hodgkin lymphoma and other lympho-proliferative disorders in Italy48 and in some areas of the USA. For unknown reasons, this is not the case in other countries (UK,49 France,50 Germany,51 Slovenia18) and in different areas of USA. Although the precise mechanisms underlying hepatocellular injury in HCV infection are largely unknown, immune-mediated mechanisms are thought to contribute to hepatic damage, despite inability to

Hepatitis B

Clinically relevant reactivations of hepatitis b secondary to cancer chemotherapy and other immunosuppressive drugs are detected quite late in many cases. Antiviral therapy given after major biochemical abnormalities have been detected may have little effect on ameliorating liver injury, because the immunological mechanisms causing the flare have already been activated and viral elimination is continuing. Thus, the key to proper management is in preventing the occurrence of reactivation, or at

Prophylaxis

Recent studies have shown that improved prognosis or even cure can be achieved by high-dose chemotherapy followed by stem-cell transplantation for patients with aggressive non-Hodgkin lymphoma. However, HBV carriers may be given lower doses of chemotherapy, or it may be discontinued because of development of hepatitis or fulminant liver failure as a result of HBV reactivation. Hence, the chance of cure is reduced. HBV reactivation is most commonly observed after the first two cycles of

Unresolved issues

Exacerbation of a chronic HBV or HCV infection after withdrawal of antiblastic drugs raises two fundamental and still unresolved problems. First, we do not yet know why there is no hepatitis exacerbation after withdrawal of cytotoxic or immunosuppressive therapy in a high proportion of HBsAg carriers, and in an even higher proportion of HCV carriers. Second, available studies on prevention and therapy have assessed few patients and are therefore anecdotal and have conflicting results.

Despite

Recommendations for future studies and practical management

Because experience in individual centres is limited, well-designed, multicentre international trials are urgently needed for identification of factors underlying reactivation of hepatitis B after withdrawal of immunosuppression and implementation of prevention and treatment. Such studies should follow prospectively all HBsAg-positive or anti-HCV-positive patients undergoing immunosuppressive treatments (including chemotherapy); liver histology should be done in all cases (even when the results

Search strategy and selection criteria

Data for this review were identified by searches of Medline, Current Contents, and references from relevant articles; many articles were identified through searches of the extensive files of the authors. Searches used the combination of the terms “HBV” or “HCV” and “chemotherapy”, “immunosuppression”, “lymphomas”, “leukaemias”, and “transplantation”. Papers were selected on the basis of the best level of available evidence for each specific issue discussed. In the absence of randomised or

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