Spontaneous Increases in Alanine Aminotransferase Levels in Asymptomatic Chronic Hepatitis B Virus-Infected Patients

Background & Aims: 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 >= 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 >= 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 2:30 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.