Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease
- 1 July 2002
- journal article
- Published by Wolters Kluwer Health in Hepatology
- Vol. 36 (1) , 219-226
- https://doi.org/10.1053/jhep.2002.33894
Abstract
We studied the course of virologic breakthroughs detected by a quantitative polymerase chain reaction (PCR) assay in 32 of 78 patients with hepatitis B e antigen (HBeAg)-negative precore mutant hepatitis B virus (HBV) chronic liver disease under long-term lamivudine monotherapy. Serum HBV DNA levels were measured every 3 months and on every biochemical breakthrough. YMDD mutants were detected in 30 of the 32 patients with virologic breakthroughs. Among these 32 patients, biochemical remission rate was 44% at 6 months, 21% at 12 months, and 0% at 24 months after the onset of virologic breakthrough. Development of biochemical breakthroughs was associated with a significant increase of serum HBV DNA levels, which exceeded 100,000 copies/mL in 19 of 20 patients (95%) with biochemical breakthroughs and in only 1 of 8 patients (12.5%) remaining in biochemical remission for at least 6 months after the onset of virologic breakthrough (P < .001). Alanine aminotransferase (ALT) level peaked within 0 to 3 months after the onset of biochemical breakthrough and decreased at 6 months but remained abnormal in all but 2 patients. Follow-up liver histologic lesions in patients with biochemical breakthroughs did not differ from baseline findings, although they were significantly improved in patients remaining in virologic and biochemical remission. In conclusion, the frequent emergence of viral resistance under long-term lamivudine monotherapy in HBeAg-negative precore mutant HBV chronic liver disease is followed by increasing viremia levels culminating in the development of biochemical breakthroughs in most cases. ALT activity peaks close to the onset of biochemical breakthrough, decreasing thereafter but remaining persistently abnormal with fluctuating levels.Keywords
This publication has 24 references indexed in Scilit:
- Diagnosis and management of pre‐core mutant chronic hepatitis BJournal of Viral Hepatitis, 2001
- Management of hepatitis B: 2000—Summary of a workshopGastroenterology, 2001
- Efficacy of long-term lamivudine monotherapy in patients with hepatitis B e antigen-negative chronic hepatitis BHepatology, 2000
- Long-term therapy of chronic hepatitis B with lamivudineHepatology, 2000
- Effects of extended lamivudine therapy in Asian patients with chronic hepatitis BGastroenterology, 2000
- Long-term follow-up of patients with anti-HBe/HBV DNA-positive chronic hepatitis B treated for 12 months with lamivudineJournal of Hepatology, 2000
- Acute exacerbation and hepatitis B virus clearance after emergence of YMDD motif mutation during lamivudine therapyHepatology, 1999
- Efficacy of Lamivudine in Patients With Hepatitis B E Antigen-Negative/Hepatitis B Virus Dna-Positive (Precore Mutant) Chronic Hepatitis Befficacy of Lamivudine in Patients With Hepatitis B E Antigen-Negative/Hepatitis B Virus Dna-Positive (Precore Mutant) Chronic Hepatitis Befficacy of Lamivudine in Patients With Hepatitis B E Antigen-Negative/Hepatitis B Virus Dna-Positive (Precore Mutant) Chronic Hepatitis Befficacy of Lamivudine in Patients With Hepatitis B E Antigen-Negative/Hepatitis B Virus Dna-Positive (Precore Mutant) Chronic Hepatitis BbHepatology, 1999
- Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapyHepatology, 1998
- Hepatitis B virus mutants associated with 3TC and famciclovir administration are replication defectiveHepatology, 1998