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Age at Time of HBeAg Seroconversion Predicts Chronic Hepatitis B Prognosis

SUMMARY: People with chronic hepatitis B virus infection who experience hepatitis B "e" antigen (HBeAg) seroconversion before age 30 have better long-term outcomes -- including lower rates of cirrhosis and liver cancer -- than those who seroconvert 10 years later, according to study findings reported in the February 2010 issue of Hepatology.

By Liz Highleyman

Over 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.


Among 483 patients who had no evidence of cirrhosis or HCC at the time of seroconversion, HBeAg seroconversion occurred at the following ages:
Before age 30 in 218 patients;
Between the ages of 31 and 40 in 199 patients;
After age 40 in 66 patients.
The 15-year cumulative incidences of HBeAg negative hepatitis, cirrhosis, and HCC rose with increasing age at the time of HBeAg seroconversion.
In the youngest group, 31.2% developed HBeAg negative hepatitis, 3.7% developed cirrhosis, and 2.1% developed HCC;
In the oldest age group, the corresponding incidence rates were 66.7%, 42.9%, and 7.7%.
Incidences 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).
The hazard ratio of HBeAg negative hepatitis in the oldest group relative to the youngest group was 2.95, or about a 3-fold risk.
For cirrhosis, the corresponding hazard ratio was 17.6, or nearly 18-fold higher risk.
For HCC, the hazard ratio was 5.22.

Based 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.


YC 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). February 2010.























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