Lamivudine resistance in patients with chronic hepatitis B: role of clinical and virological factors.

BACKGROUND: Lamivudine resistance is associated with long-term monotherapy for chronic hepatitis B and can lead to potentially serious clinical consequences. Scant information exists regarding the influence of hepatitis B virus variants in the development of resistance. The present study was designed to identify factors predictive of lamivudine resistance, with a particular focus on the role of precore and basal core promoter variants in the setting of hepatitis B e antigen-negative disease. METHODS: Eighty-five patients, representing four major genotypes, were followed prospectively on lamivudine therapy. Resistance was defined as an increase in viral load, with polymerase gene sequencing confirming a lamivudine resistance mutation. Median follow up was 19 months (6-54 months). The Cox proportional hazards model was used to determine variables independently predicting for the early onset of lamivudine resistance. RESULTS: The rate of lamivudine resistance was 6%, 31% and 51% at 12, 24 and 48 months, respectively. Multivariate analysis identified the precore variant, high baseline alanine aminotransferase (ALT), and persistent viremia (at 6 months) as independent predictors of the early development of lamivudine resistance, with rate ratios of 4.93 (95% confidence interval [CI]: 1.32-18.5), 1.22 (95%CI: 1.08-1.49), and 4.73 (95%CI: 1.49-15.0), respectively (P < 0.05). Female sex predicted early resistance (rate ratio 5.27 [95%CI: 1.23-22.5, P < 0.05]) although numbers were small (n = 12). Genotype did not influence treatment response nor time to onset of resistance. CONCLUSION: Patients with precore variant hepatitis B virus are likely to develop lamivudine resistance early and should be considered for alternate first-line monotherapy. In the future, combination antiviral therapy may limit the development of resistance.

Surgeon, test (and heal) thyself: sharps injuries and hepatitis C risk.

Sharps injuries experienced by surgeons are common, but are under-recognised and under-reported. The overall risks of transmission of blood-borne viruses to surgeons are low, with hepatitis C posing the greatest transmission risk. Recent trials show that early treatment of acute hepatitis C results in a cure rate approaching 100%. Surgeons and theatre staff should be encouraged to report and follow up sharps injuries to allow early detection and treatment. Additionally, because exposures to blood-borne viruses may be unrecognised, surgeons should have regular tests for blood-borne viruses. There should be no restriction of practice in the "window period" between potential exposure and obtaining results of testing, because of the overall low risk of transmission.