Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance

作     者：Lee Guan Lim Myat Oo Aung Bee Leng Seet Cindy Tan Yock Young Dan Yin Mei Lee Dede Selamat Sutedja Mark Fernandes Guan Huei Lee Evelyn Koay Seng Gee Lim 

作者机构：Department of Gastroenterology and Hepatology National University Health System Yong Yoo Lin School of Medicine National University of Singapore Department of Medicine National University Health System Yong Yoo Lin School of Medicine National University of Singapore Molecular Diagnostic Centre National University Health System Yong Yoo Lin School of Medicine National University of Singapore Investigative Medicine Unit National University Health System Yong Yoo Lin School of Medicine National University of Singapore 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2010年第16卷第37期

页      面：4691-4696页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：Supported by (in part) Grant 02/N01 from the Health Services Development Program  Ministry of Health  Singapore 

主　　题：Antiviral therapy Chronic hepatitis B Sensitivity Specificity YMDD mutants 

摘      要：AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ***: This was a retrospective study of chronic hepatitis B patients on lamivudine therapy who were followed for 3-mo with liver function tests and hepatitis B virus (HBV) DNA measurement. Lamivudine resistance was defined as HBV DNA ≥ 1 log from nadir on at least 2 occasions, confirmed by genotyping. Serum ALT levels in patients with lamivudine resistance were compared to serum ALT levels in those without lamivudine resistance. RESULTS: There were 111 patients with and 117 without lamivudine resistance. The area under the receiver operating characteristic of serum ALT to diagnose lamivudine resistance was 0.645 ± 0.037. Serum ALT 42.5 U/L gave the best diagnostic accuracy with sensitivity = 61%, specificity = 60%, positive predictive value = 60%, negative predictive value = 61%, positive likelihood ratio = 1.53 and negative likelihood ratio = 0.65 for predicting lamivudine resistance, missing 39% of resistant patients. Using other serum ALT cutoffs, diagnostic accuracy was lower. By multivariate analysis, baseline abnormal serum ALT was associated with abnormal ALT during resistance (OR = 5.98, P = 0.003), and males were associated with serum ALT flares during resistance (OR = 8.9, P = 0.016). CONCLUSION: Serum ALT is inadequate for diagnosing lamivudine resistance and has implications where viral resistance testing is suboptimal and for reimbursement of rescue therapy.