SERO-CLEARANCE OF HEPATITIS-B SURFACE-ANTIGEN IN CHRONIC CARRIERS DOES NOT NECESSARILY IMPLY A GOOD PROGNOSIS

The incidence of delayed hepatitis B surface antigen (HBsAg) clearance in the natural history of chronic hepatitis B virus (HBV)-infected pa tients was low. Previous studies regarding the prognosis in such patie nts were controversial. Among 1,355 chronic carriers from 1985 to 1997 , spontaneous HBsAg clearance was observed in 55 patients. During a me an follow-up period of 23 months, 1.8 (32.7%; all were male subjects) developed serious complications, including 11 with hepatocellular carc inoma (HCC) (9 of them underwent surgical resection), 6 with cirrhosis , and 1 with subfulminant liver failure. The overall cumulative probab ility of complications was 29.8% at 4 years, and it was higher in male s (P =.044) and patients aged 45 years or more (P =.006); the latter c arried an 8.6-fold increased risk (95% CI: 1.2-64.6; P =.037) of adver se events. Histories of acute or chronic infection by hepatitis A viru s, C virus (HCV), or D virus (HDV) were present in 42% of patients. Pa tients seropositive for antibodies against HCV (anti-HCV) or HDV (anti -HDV) had higher alanine transaminase (ALT) levels (>40 U/L; P =,008) after sere-clearance. HBV DNA was detectable in 31% of 51 subjects, in 20% of 20 with antibodies against HBsAg, in 40% of 20 with anti-HCV o r anti-HDV, and also in an HCC patient's serum and tumor. Staining of liver HBsAg was positive in 30% of 10 HCC patients. In conclusion, our results demonstrated that hepatitis B viremia may persist, and advers e complications were not rare in HBsAg-clearance patients. All such pa tients should be closely monitored, which may allow for earlier detect ion of HCC.