Long-Term Lamivudine Therapy for Chronic Hepatitis B
Long-Term Lamivudine Therapy for Chronic Hepatitis B
Study Objective: To evaluate the effects and safety of 52-week lamivudine therapy in Korean patients with chronic hepatitis B virus (HBV), with and without cirrhosis.
Design: Long-term retrospective study.
Setting: Ajoo University Medical Center, Soowon, Korea.
Patients: Twenty-seven men and two women who had received oral lamivudine 100 mg/day for 52 weeks for treatment of biopsy-proven chronic HBV; 11 patients had cirrhosis, 18 did not.
Measurements and Main Results: All 29 patients were positive for HBV DNA and hepatitis B surface antigen (HBsAg) before treatment began; 25 (86%) patients were positive for hepatitis B e antigen (HBeAg). Lamivudine therapy suppressed serum HBV DNA to undetectable levels in 26 (90%) patients within a median of 4 weeks. Serum HBV DNA of 28 patients (97%) fell significantly to undetectable levels within 12 weeks and remained undetectable in 24 (83%) patients after 52 weeks, and HBeAg had converted to negative in 10 (40%) of the 25 patients who were positive. Mean serum alanine aminotransferase (ALT) levels of the 29 patients decreased to within the normal range by 12 weeks and remained at 33-48 IU/L thereafter. Differences in responses of HBV DNA and ALT to lamivudine therapy in HBeAg-positive and -negative patients were negligible (p=0.786 and p=0.225, respectively). Pretreatment HBV DNA and ALT levels had no effect on the efficacy of lamivudine (p=0.9116). Furthermore, differences in responses of HBV DNA (p=0.641), HBeAg seroconversion (p=0.386), and ALT (p=0.689) and in development of drug resistance (p=0.617) between patients with and without cirrhosis were negligible. No serious adverse effects were reported.
Conclusion: Lamivudine is an effective and well-tolerated therapeutic agent for treating chronic HBV in patients with and without cirrhosis.
Over 300 million people are estimated to be chronic carriers of hepatitis B virus (HBV) worldwide, and over 25,000 deaths/year are due to HBV-associated liver diseases such as cirrhosis, liver failure, and hepatocellular carcinoma. A higher prevalence of HBV infection, ranging from 8-15% of the population, can be found in eastern Asia. In addition, the natural history of HBV infection differs between Asian and western patients. Asian patients, who usually become infected perinatally, rarely have an acute hepatitis-like clinical syndrome. However, they almost invariably remain chronically infected and are at substantial risk for cirrhosis and hepatocellular carcinoma. In addition, Asian patients demonstrate less response to interferon therapy than western patients. Experts speculate that the poor response is due to immune tolerance to HBV after infection at birth or in early childhood.
Two drugs approved for the treatment of hepatitis by the United States Food and Drug Administration are interferon-
and lamivudine. Lamivudine is a synthetic dideoxynucleoside analog that can be phosphorylated to its active metabolite to inhibit viral reverse transcriptase and viral DNA synthesis. Lamivudine reduces serum HBV and hepatitis B e antigen (HBeAg), stimulates production of hepatitis B e antibody, and returns elevated alanine aminotransferase (ALT) levels to normal. Lamivudine treatment generally results in rapid improvement in symptoms and serum markers; however, short-term administration followed by discontinuation causes relapse of hepatitis, and long-term administration can cause lamivudine resistance to develop.
A study of the safety and efficacy of short-term lamivudine therapy in Asian and Caucasian patients with chronic HBV infection found that mean serum HBeAg concentrations decreased in all patients treated with lamivudine for 6 months. No significant differences between Asian and Caucasian patients were noted. Mean serum ALT concentrations also were decreased by the end of the treatment period. However, serum concentrations of HBV DNA, ALT, HBeAg, and hepatitis B surface antigen (HBsAg) returned to pretreatment concentrations in most patients shortly after completion of treatment. Response to lamivudine did not appear to depend on pretreatment characteristics, as it does with interferon-a treatment. Several studies have reported resistance of HBV to lamivudine. One reported a cumulative 39% incidence of HBV resistance in patients treated with lamivudine for 6 months.
Although lamivudine has shown promise for patients with chronic HBV, long-term data on Korean patients with hepatitis B are lacking. Because data are lacking, we studied the efficacy of 52 weeks of lamivudine therapy for treatment of chronic HBV in Korean patients with and without cirrhosis. We also studied the development of lamivudine resistance with long-term treatment.
Study Objective: To evaluate the effects and safety of 52-week lamivudine therapy in Korean patients with chronic hepatitis B virus (HBV), with and without cirrhosis.
Design: Long-term retrospective study.
Setting: Ajoo University Medical Center, Soowon, Korea.
Patients: Twenty-seven men and two women who had received oral lamivudine 100 mg/day for 52 weeks for treatment of biopsy-proven chronic HBV; 11 patients had cirrhosis, 18 did not.
Measurements and Main Results: All 29 patients were positive for HBV DNA and hepatitis B surface antigen (HBsAg) before treatment began; 25 (86%) patients were positive for hepatitis B e antigen (HBeAg). Lamivudine therapy suppressed serum HBV DNA to undetectable levels in 26 (90%) patients within a median of 4 weeks. Serum HBV DNA of 28 patients (97%) fell significantly to undetectable levels within 12 weeks and remained undetectable in 24 (83%) patients after 52 weeks, and HBeAg had converted to negative in 10 (40%) of the 25 patients who were positive. Mean serum alanine aminotransferase (ALT) levels of the 29 patients decreased to within the normal range by 12 weeks and remained at 33-48 IU/L thereafter. Differences in responses of HBV DNA and ALT to lamivudine therapy in HBeAg-positive and -negative patients were negligible (p=0.786 and p=0.225, respectively). Pretreatment HBV DNA and ALT levels had no effect on the efficacy of lamivudine (p=0.9116). Furthermore, differences in responses of HBV DNA (p=0.641), HBeAg seroconversion (p=0.386), and ALT (p=0.689) and in development of drug resistance (p=0.617) between patients with and without cirrhosis were negligible. No serious adverse effects were reported.
Conclusion: Lamivudine is an effective and well-tolerated therapeutic agent for treating chronic HBV in patients with and without cirrhosis.
Over 300 million people are estimated to be chronic carriers of hepatitis B virus (HBV) worldwide, and over 25,000 deaths/year are due to HBV-associated liver diseases such as cirrhosis, liver failure, and hepatocellular carcinoma. A higher prevalence of HBV infection, ranging from 8-15% of the population, can be found in eastern Asia. In addition, the natural history of HBV infection differs between Asian and western patients. Asian patients, who usually become infected perinatally, rarely have an acute hepatitis-like clinical syndrome. However, they almost invariably remain chronically infected and are at substantial risk for cirrhosis and hepatocellular carcinoma. In addition, Asian patients demonstrate less response to interferon therapy than western patients. Experts speculate that the poor response is due to immune tolerance to HBV after infection at birth or in early childhood.
Two drugs approved for the treatment of hepatitis by the United States Food and Drug Administration are interferon-
and lamivudine. Lamivudine is a synthetic dideoxynucleoside analog that can be phosphorylated to its active metabolite to inhibit viral reverse transcriptase and viral DNA synthesis. Lamivudine reduces serum HBV and hepatitis B e antigen (HBeAg), stimulates production of hepatitis B e antibody, and returns elevated alanine aminotransferase (ALT) levels to normal. Lamivudine treatment generally results in rapid improvement in symptoms and serum markers; however, short-term administration followed by discontinuation causes relapse of hepatitis, and long-term administration can cause lamivudine resistance to develop.
A study of the safety and efficacy of short-term lamivudine therapy in Asian and Caucasian patients with chronic HBV infection found that mean serum HBeAg concentrations decreased in all patients treated with lamivudine for 6 months. No significant differences between Asian and Caucasian patients were noted. Mean serum ALT concentrations also were decreased by the end of the treatment period. However, serum concentrations of HBV DNA, ALT, HBeAg, and hepatitis B surface antigen (HBsAg) returned to pretreatment concentrations in most patients shortly after completion of treatment. Response to lamivudine did not appear to depend on pretreatment characteristics, as it does with interferon-a treatment. Several studies have reported resistance of HBV to lamivudine. One reported a cumulative 39% incidence of HBV resistance in patients treated with lamivudine for 6 months.
Although lamivudine has shown promise for patients with chronic HBV, long-term data on Korean patients with hepatitis B are lacking. Because data are lacking, we studied the efficacy of 52 weeks of lamivudine therapy for treatment of chronic HBV in Korean patients with and without cirrhosis. We also studied the development of lamivudine resistance with long-term treatment.
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