Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance

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

来源：World Journal of Gastroenterology, 2010, 16(37): 4691-4696.

DOI：10.3748/wjg.v16.i37.4691

• Antiviral therapy
• Chronic hepatitis B
• Sensitivity
• Specificity
• YMDD mutants

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.

• 出版日期2010-10-7