at Time of HBeAg Seroconversion Predicts Chronic Hepatitis B
years or decades, chronic hepatitis B can progress to advanced
liver disease including cirrhosis and hepatocellular carcinoma
(HCC). People who start out with HBeAg negative disease have
better overall outcomes than initially HBeAg positive people.
HBeAg seroconversion is associated with improved prognosis,
but the relationship between time of seroconversion and outcomes
is not well defined.
Yi-Cheng Chen from Chang Gung University College of Medicine
in Taipei and colleagues studied long-term outcomes among 508
initially HBeAg positive patients with documented spontaneous
(without treatment) HBeAg seroconversion.
Follow-up evaluations included liver biochemistry (e.g., ALT
level), alpha-fetoprotein (a biomarker of liver cancer), and
ultrasound scans every 3 to 6 months, or more frequently if
clinically indicated. The incidence of HBeAg negative hepatitis,
cirrhosis, HCC, and hepatitis B surface antigen (HBsAg) clearance
were compared between patients in different age groups.
483 patients who had no evidence of cirrhosis or HCC at
the time of seroconversion, HBeAg seroconversion occurred
at the following ages:
age 30 in 218 patients;
the ages of 31 and 40 in 199 patients;
age 40 in 66 patients.
15-year cumulative incidences of HBeAg negative hepatitis,
cirrhosis, and HCC rose with increasing age at the time
of HBeAg seroconversion.
the youngest group, 31.2% developed HBeAg negative hepatitis,
3.7% developed cirrhosis, and 2.1% developed HCC;
the oldest age group, the corresponding incidence rates
were 66.7%, 42.9%, and 7.7%.
of HBeAg negative hepatitis and cirrhosis were significantly
higher in the age > 40 group compared with the < 30
group (P < 0.0001 for both), but the difference did not
reach statistical significance for HCC (P = 0.29).
hazard ratio of HBeAg negative hepatitis in the oldest group
relative to the youngest group was 2.95, or about a 3-fold
cirrhosis, the corresponding hazard ratio was 17.6, or nearly
18-fold higher risk.
HCC, the hazard ratio was 5.22.
on these findings, the study authors concluded, "Patients
with HBeAg seroconversion before age 30 have excellent prognosis,
whereas patients with delayed HBeAg seroconversion after age
40 have significantly higher incidences of HBeAg negative hepatitis,
cirrhosis, and HCC."
Liver Research Unit, Chang Gung Memorial Hospital, Chang
Gung University College of Medicine, Taipei, Taiwan.
Chen, CM Chu, and YF Liaw. Age-specific prognosis following
spontaneous hepatitis B e antigen seroconversion in chronic
hepatitis B. Hepatology 51(2): 435-444 (Abstract).