Spontaneous increases in alanine aminotransferase levels in asymptomatic chronic hepatitis B virus-infected patients.
OBJECTIVE
No information is available about the frequency or factors that predict spontaneous increases in alanine aminotransferase (ALT) levels in asymptomatic Indian patients with chronic hepatitis B virus (HBV) infection who are HB e antigen (HBeAg) negative and have normal ALT levels.


METHODS
We followed 217 asymptomatic patients with chronic HBV who were HBeAg negative, anti-HBe antigen (anti-HBe) positive, and had normal ALT levels. Spontaneous increases in ALT levels (ALT flares) were considered to be >2-fold the upper limit of normal (ULN) and were accompanied by HBV DNA levels>or=10(5) copies/mL or a 100-fold increase from the previously measured level.


RESULTS
During a median follow-up period of 69.0 months, spontaneous ALT flares occurred in 43 patients (an annual rate of 4.3%), with cumulative probabilities of 10.8% and 47.3% after 5 and 10 years, respectively. Based on multinomial logistic regression, the probability of an ALT flare correlated with age>or=30 years at presentation (odds ratio [OR], 5.31; 95% confidence interval [CI]: 1.53-18.39; P=.008), male sex (OR, 4.54; 95% CI: 1.01-20.76; P=.05), and presence of a precore mutation (OR, 10.99; 95% CI: 3.67-32.92; P<.001). The median time to spontaneous ALT flare after enrollment was 25 months (range, 1-128 months; 10th percentile=3.4 months).


CONCLUSIONS
In asymptomatic patients with chronic HBV infection who have normal ALT levels and are HBeAg negative, the annual rate of ALT flares was 4.3%. Precore mutants, male sex, and age>or=30 years at presentation are independent predictors for an ALT flare. A follow-up every 3 months can capture up to 90% of flares and would help identify patients who require antiviral therapy.
Kumar
Manoj
M
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Chauhan
Ranjit
R
Gupta
Nitin
N
Hissar
Syed
S
Sakhuja
Puja
P
Sarin
Shiv K
SK
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001706:Biopsy; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000208:ethnology / Q000235:genetics; D006801:Humans; D007194:India; D008099:Liver / Q000201:enzymology / Q000473:pathology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies
D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000410:Alanine Transaminase