Treatment of chronic hepatitis B: interferon alfa first.
(1) Chronic hepatitis B is defined by the persistence of circulating HBs antigen for more than 6 months.  Between 15 and 25% of chronic HBV carriers die prematurely of complications (mainly cirrhosis and hepatocellular carcinoma).  (2) Patients with chronic hepatitis B rarely clear the virus spontaneously, but viral replication ceases in approximately 10% of patients annually, with disappearance of HBe and viral DNA, and emergence of anti-HBe antibodies.  (3)  Active viral replication and histologically proven liver necrosis are risk factors for progression to cirrhosis.  (4) Antiviral treatments have been assessed only in patients with active viral replication.  (5) Interferon alfa has been widely tested in the clinical setting.  In one trial, in which patients were followed for 7 years, mortality was lower in the treatment group than in untreated controls.  (6) Interferon alfa must be injected, and its administration may be followed by adverse effects such as a 'flu-like syndrome (frequently), psychiatric problems and potentially severe thyroid disorders.  (7) Interferon alfa monotherapy for 4-6 months (possibly extended to 8-9 months) remains the first-line treatment for chronic hepatitis B.  (8) Lamivudine has documented antiviral efficacy but its effect is only temporary in many patients.  In the only trial comparing lamivudine with interferon alfa, lamivudine was no more effective than interferon in the short term (on the basis of serological and histological end points), despite a bias in its favour.  Trials of lamivudine + interferon alfa in patients who fail to respond to interferon monotherapy have given unfavourable results.  (9) Adverse effects are infrequent on lamivudine, but pharmacovigilance is required to assess potential hepatic and pancreatic effects at the dose used in this indication.  (10) The long-term effects of lamivudine are unknown, especially on the risks of cirrhosis, hepatocarcinoma and the selection of resistant mutants.  (11) Pending further data, lamivudine should be used only in clinical trials and cohort studies.
D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004359:Drug Therapy, Combination; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000998:Antiviral Agents; D016898:Interferon-alpha; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine