Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance.
OBJECTIVE
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).


CONCLUSIONS
Serum ALT is inadequate for diagnosing lamivudine resistance and has implications where viral resistance testing is suboptimal and for reimbursement of rescue therapy.
Lim
Lee Guan
LG
Department of Gastroenterology and Hepatology, National University Health System, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore 128791, Singapore.
Aung
Myat Oo
MO
Seet
Bee Leng
BL
Tan
Cindy
C
Dan
Yock Young
YY
Lee
Yin Mei
YM
Sutedja
Dede Selamat
DS
Fernandes
Mark
M
Lee
Guan Huei
GH
Koay
Evelyn
E
Lim
Seng Gee
SG
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012680:Sensitivity and Specificity
D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D019259:Lamivudine; D000410:Alanine Transaminase