Simple scoring system predicting genotypic resistance during rescue therapy for Lamivudine-resistant chronic hepatitis B.

Abstract

GOAL:

In this study, we aimed to devise a simple scoring system predicting the risk of genotypic resistance (GR) to current rescue therapies for patients with lamivudine (LAM)-resistant chronic hepatitis B.

BACKGROUND:

LAM and adefovir (ADV) combination therapy should be recommended for an initial rescue therapy against LAM-resistant hepatitis B virus (HBV). However, there still are many LAM-resistant patients being treated with entecavir (ETV) or ADV monotherapy.

STUDY:

This retrospective cohort study included consecutive patients treated for LAM-resistant chronic hepatitis B with ETV or ADV monotherapy, or LAM/ADV combination therapy. The cumulative probabilities of GR and virological responses and breakthrough according to clinical variables were analyzed by survival analyses and derived an index for future GR.

RESULTS:

A total of 224 patients were included (median treatment duration=117.9 wk). Using risk factors indentified on multivariable analyses, a simple index for future GR (Antiviral Resistance Prediction Index, ARPI) was developed with 3 clinical variables: the rescue therapy regimens (+0, ADV; +1, ETV; +2, LAM/ADV), HBV DNA reduction at 12 weeks (+0, <3 log10 copies/mL; +1, >3 log10 copies/mL), and the initial HBV DNA level (+0, >10 copies/mL; +1, <10 copies/mL). No patient with ARPI ≥2 exhibited GR, whereas 47% of the patients with an ARPI <2 developed GR by week 144 (P=0.005).

CONCLUSIONS:

The results of this study suggest that the ARPI is a simple and early index that can be used to determine the risk for subsequent GR during rescue therapy for LAM-resistant chronic hepatitis B.

• Authors: Jeong-Hoon Lee, Jung-Hwan Yoon, Eun Ju Cho, Hyo Joon Yang, Eun Sun Jang, Min-Sun Kwak, Sang Youn Hwang, Su Jong Yu, Chang-Hoon Lee, Yoon Jun Kim, Chung Yong Kim, Hyo-Suk Lee
• Journal: Journal of clinical gastroenterology (J Clin Gastroenterol) Vol. 46 Issue 3 Pg. 243-50 (Mar 2012) ISSN: 1539-2031 [Electronic] United States
• PMID: 21716122 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Organophosphonates
• Lamivudine
• entecavir
• Guanine
• adefovir
• Adenine

Topics

• Adenine (analogs & derivatives, therapeutic use)
• Adult
• Aged
• Antiviral Agents (pharmacology, therapeutic use)
• Cohort Studies
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• Guanine (analogs & derivatives, therapeutic use)
• Hepatitis B virus (drug effects, genetics)
• Hepatitis B, Chronic (drug therapy, mortality, virology)
• Humans
• Lamivudine (pharmacology, therapeutic use)
• Male
• Middle Aged
• Organophosphonates (therapeutic use)
• Predictive Value of Tests
• Retrospective Studies
• Survival Analysis
• Treatment Outcome
• Young Adult