Brief Article
Copyright ©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 7, 2010; 16(37): 4691-4696
Published online Oct 7, 2010. doi: 10.3748/wjg.v16.i37.4691
Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance
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
Lee Guan Lim, Myat Oo Aung, Yock Young Dan, Yin Mei Lee, Dede Selamat Sutedja, Mark Fernandes, Guan Huei Lee, Seng Gee Lim, Department of Gastroenterology and Hepatology, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 128791, Singapore
Bee Leng Seet, Cindy Tan, Yock Young Dan, Seng Gee Lim, Department of Medicine, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 128791, Singapore
Evelyn Koay, Molecular Diagnostic Centre, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 128791, Singapore
Seng Gee Lim, Investigative Medicine Unit, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 128791, Singapore
Author contributions: Lim LG and Lim SG conceived and designed the study, evaluated the patients, collected, analyzed and interpreted the data; Lim LG wrote and drafted the article; Lim LG and Lim SG revised the paper critically for important intellectual content; Aung MO performed the statistical analysis of the data; Seet BL, Tan C, Dan YY, Lee YM, Sutedja DS, Fernandes M and Lee GH evaluated the patients and collected the data; Koay E also collected the data.
Supported by (in part) Grant 02/N01 from the Health Services Development Program, Ministry of Health, Singapore
Correspondence to: Seng Gee Lim, Professor, Chief, Department of Gastroenterology and Hepatology, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, Singapore 128791, Singapore. mdclimsg@nus.edu.sg
Telephone: +65-67724369 Fax: +65-67751518
Received: March 13, 2010
Revised: April 24, 2010
Accepted: May 1, 2010
Published online: October 7, 2010
Abstract

AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ALT.

METHODS: 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.

Keywords: Antiviral therapy, Chronic hepatitis B, Sensitivity, Specificity, YMDD mutants