Management of chronic hepatitis B - Defining the role of lamivudine

According to the WHO, approximately 350 million people have chronic hep ati tis B. Individuals with chronic hepatitis B have a highly variable and unpr edictable clinical course and are at risk for developing cirrhosis and hepa tocellular carcinoma. Lamivudine is the only oral antiviral agent approved for the treatment of patients with chronic hepatitis B. Lamivudine is useful in a wide range of patients with chronic hepatitis B a nd ongoing viral replication. In patients with compensated liver disease tr eated for 52 weeks in multicenter randomized, double-blind clinical studies , lamivudine 100 mg/day inhibited hepatitis B virus (HBV) replication, norm alized ALT levels, produced significant reductions in hepatic necroinflamma tory activity and halted the progression of fibrosis compared with placebo. Hepatitis B e antigen (HBeAg) seroconversion rates were also increased dur ing treatment with thr drug compared with placebo. In patients who continued to receive the drug after the completion of these trials improvements in liver histology were maintained and HBeAg seroconve rsion rates increased in proportion to the duration of treatment. Pretreatment ALT levels were predictive of HBeAg seroconversion. In patient s with baseline ALT levels greater than or equal to2-fold higher than the u pper limit of normal, seroconversion rates were significantly higher than i n those with lower baseline values. Data from 2 randomized studies indicate that sequential therapy with lamivu dine for 8 weeks and then lamivudine plus interferon-alpha for 16 weeks pro vides no greater benefit than that of monotherapy with lamivudine for 52 we eks or interferon-cx for 16 weeks. According to data from noncomparative studies, lamivudine 100 or 150 mg/day resulted in clinical stabilization, significant reductions in Child-Pugh-T urcotte scores and loss of HBeAg in many patients with decompensated liver disease. Moreover, some patients have been placed on inactive status for li ver transplantation after treatment with the drug. Lamivudine-resistant HBV variants have been isolated from patients with chr onic hepatitis B during treatment with lamivudine. The prevalence of these variants increases with the duration of treatment; however, their long term clinical significance has not been established. Lamivudine is well tolerated. The frequency of adverse events in lamivudine or placebo recipients was similar in a pooled analysis of clinical trial d ata. Nonetheless, patients must be monitored for the emergence of lamivudin e-resistant variants and elevated liver enzyme levels (ALT flares). In a series of economic models, use of lamivudine was predicted to reduce t he cost per case of cirrhosis prevented and increase mean life expectancy c ompared with use of interferon-alpha in the US. Other analyses, which incor porated a fixed drug budget scenario, concluded that use of lamivudine woul d increase the number of successfully treated patients by 2- to 3-fold comp ared with interferon-alpha because of lower acquisition costs. In conclusion, lamivudine is useful in a wide range of patients with chroni c hepatitis B and ongoing viral replication.