Long-term outcome of chronic hepatitis B in Caucasian patients: mortality after 25 years.

Objective: To assess risk factors for liver-related death,
we re-evaluated, after a median follow-up of 25 years, a
cohort of 70 Caucasian patients with hepatitis B e antigen
(HBeAg) positive chronic hepatitis (CH) at presentation.
Methods: Follow-up studies included clinical and ultrasound
examinations, biochemical and virological tests,
and cause of death.
Results: Sixty-one (87%) patients underwent spontaneous
HBeAg seroconversion. During a median period of
22.8 years after HBeAg seroclearance, 40 (66%) patients
became inactive carriers, whereas the remaining 21
(34%) showed alanine aminotransferase elevation: one
(1%) had HBeAg reversion, nine (15%) detectable serum
HBV DNA but were negative for HBeAg, eight (13%)
concurrent virus(es) infection and three (5%) concurrent
non-alcoholic fatty liver disease. Liver-related death
occurred in 11 (15.7%) patients, caused by hepatocellular
carcinoma in five and liver failure in six. The 25-year
survival probability was 40% in patients persistently
HBeAg positive, 50% in patients with HBeAg negative CH
or HBeAg reversion and 95% in inactive carriers. Older
age, male sex, cirrhosis at entry and absence of sustained
remission predicted liver-related death independently. The
adjusted hazard ratios (95% CI) for liver related death
were 33 (3.01–363) for persistently HBeAg positive
patients and 38.73 (4.65–322) for those with HBeAg
negative CH or HBeAg reversion relative to inactive
carriers.
Conclusion: Most patients with HBeAg seroconversion
became inactive carriers with very good prognosis. The
risk of liver-related mortality in Caucasian adults with CH
is strongly related with sustained disease activity and
ongoing high level of HBV replication independently of
HBeAg status.