Year : 2005 | Volume
: 2 | Issue : 1 | Page : 93--126
Comparison of lamividine and adefovir dipivoxil in the treatment of chronic hepatitis B
Consultant Physician, Alice Ho Miu Ling Nethersole Hospital Adjunct Associate Professor, The Chinese University of Hong Kong, Hong Kong SAR, China
Nucleot(s)ide analogues are making milestones in the treatment of chronic hepatitis B (CHB). Lamivudine was approved by FDA for the treatment of chronic hepatitis B in adult patients n 1998 (ZeffixTM HeptodinTM HeptovirTM Epivir-HBVTM Glaxo Wellcome). Adefovir dipivoxil was approved by FDA in 2002 (Hepsera, Gilead). Both were licensed and available in many countries. A comparison of their efficacy in the treatment of various subgroups of CHB patients will facilitate management decision and choice between these two agents.
Lamivudine suppresses viral replication and reduces serum HBV DNA level by 3-4 log 10 after one year of therapy, associated with normalization of serum alanine aminotansferase and significant improvement in histologic activity index. In HBeAg positive CHB, HBeAg loss/seroconversion rate at the end of one year of therapy is 18-30%; higher pretreatment serum alanine aminotransferase (ALT) level is associated with higher HBeAg loss/ seroconversion. HBeAg loss/seroconversion increases on extended therapy. The durability of response off therapy declines with time. Clinical efficacy in HBeAg negative CHB is similar. However, the drawback of Lamivudine therapy is increasingly being recognized. The endpoint for therapy is difficult to define and viral response is often not durable. Long-term therapy runs the risk of emergence of lamivudine resistant mutants (YMDDm) at the rate of around 15-30% each year, with a cumulative 70% at the end of year 4. YMDDm viraemia is eventually associated with relapse of hepatitis and occasionally hepatic decompensation. In patients with maintained or sustained response, there was significant improvement in necroinflammatory activity. Reversion of fibrosis has also been observed. In patients with advanced fibrosis and cirrhosis, three years of Lamivudine therapy reduced disease progression and possibly reduced occurrence of hepatocellular carcinoma. Lamivudine has also established its role for patients with hepatic decompensation pending liver transplantation, HBsAg positive patients receiving chemotherapy or organ transplantation. Its role in CHB children and viraemic CHB pregnant mothers is less certain.
The clinical benefit of Adefovir dipivoxil was initially recognized in patients with Lamivudine resistant YMDD mutants. Subsequent pivotal phase 3 placebo-controlled trials showed significant antiviral activity against both wild type and HBeAg negative HBV. Adefovir dipivoxil 10 mg daily showed significant clinical benefit in normalization of serum ALT and histologic improvement in both HBeAg positive and HBeAg negative CHB. One important advantage of Adefovir dipivoxil over Lamivudine in long term therapy is the much lower rate of emergence of drug resistant mutants. No resistant mutation was detected at the end of first year of therapy and around 15% at the end of four years. It has good safety profile except for possible reversible renal toxicity which has been reported in isolated patients on the 10mg dosage. Data and clinical experience in other patient subgroups are pending.
Consultant Physician, Alice Ho Miu Ling Nethersole Hospital Adjunct Associate Professor, The Chinese University of Hong Kong, Hong Kong SAR
|How to cite this article:|
Leung N. Comparison of lamividine and adefovir dipivoxil in the treatment of chronic hepatitis B.Hep B Annual 2005;2:93-126
|How to cite this URL:|
Leung N. Comparison of lamividine and adefovir dipivoxil in the treatment of chronic hepatitis B. Hep B Annual [serial online] 2005 [cited 2021 Oct 16 ];2:93-126
Available from: https://www.hepatitisbannual.org/article.asp?issn=0972-9747;year=2005;volume=2;issue=1;spage=93;epage=126;aulast=Leung;type=0