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Abnormal ALT after HBeAg seroclearance increases liver cancer risk

Patients with hepatitis B had a higher risk for hepatocellular carcinoma after HBV e antigen seroclearance if they were men, had higher levels of HBV DNA, were unable to achieve normalized alanine aminotransferase levels, and were older at the time of HBeAg seroclearance, according to a recently published study.

“Those with persistently normal ALT after [HBeAg seroclearance] had a much more favorable outcome, including a low rate of HCC development, high rate of [HBV surface antigen (HBsAg)] seroclearance, and low liver-related mortality,” James Fung, MD, from the University of Hong Kong, and colleagues wrote. “This highlights the importance of viral suppression with normalization of ALT.”

Fung and colleagues followed 723 patients with HBV who achieved HBeAg seroclearance. Median age at HBeAg seroclearance was 36 years (range, 19-85 years) and median follow-up was 18.3 years (range, 2.8-32.9 years).

After HBeAg seroclearance, 3.5% of patients achieved completely normal ALT and 10.1% had normalized ALT during 90% or more of follow-up. Another 10.1% had persistently elevated ALT, 19.4% of whom had abnormal ALT during 90% or more of follow-up.

The rate of HCC was 4.3% among patients with persistently normal ALT after HBeAg seroclearance, 2.2% among those with normal ALT for 90% to 100% of follow-up, and continued to increase up to 17.3% among those with normal ALT for 10% or less of follow-up, and 37.2% for those who did not achieve normalized ALT (P < .001).

At 20 years follow-up after HBeAg seroclearance, the HCC rate was 11% for those with HBV DNA higher than 4 log IU/mL and 1.2% for those with HBV DNA less than 4 log IU/mL, whereas no patients with HBV DNA less than 3 log IU/mL developed HCC (P = .006).

Multivariate analysis showed that age at HBeAg seroclearance (HR = 1.06; 95% CI, 1.03-1.1), male sex (HR = 3.39; 95% CI, 1.22-9.41), cirrhosis (HR = 6.07; 95% CI, 2.55-14.43), hypoalbuminemia (HR = 4.1; 95% CI, 1.53-10.96), HBV DNA (HR = 1.33; 95% CI, 1.01-1.73) and ALT flares or persistently abnormal ALT (HR = 6.77; 95% CI, 1.98-23.2) were significant factors for HCC development after HBeAg seroclearance.

Additionally, the researchers found the rate of HBsAg seroclearance was 79.4% among patients with persistently normal ALT after HBeAg seroclearance, 25.9% among those with normal ALT for 90% to 100% of follow-up, and continued to decrease to 0% among those with normal ALT for up to 10% of follow-up, and 1.8% among those with persistently abnormal ALT (P < .01).

Multivariate analysis showed that age at HBeAg seroclearance (HR = 1.05; 95% CI, 1.01-1.09), male sex (HR = 2.03; 95% CI, 1.02-4.03), viral load (HR = 0.75; 95% CI, 0.61-0.92), and history of antiviral therapy (HR = 0.15; 95% CI, 0.4-0.51) were significant factors associated with HBsAg seroclearance. – by Talitha Bennett

Disclosure: The authors report no relevant financial disclosures.