Hepatitis B surface antigen disappearance and hepatitis B surface antigen subtype: a prospective, long-term, follow-up study of Japanese residents of Okinawa, Japan with chronic hepatitis B virus infection.

Abstract

Abstract. To determine the natural course of hepatitis B surface antigen (HBsAg) disappearance in chronic hepatitis B virus (HBV) infection and the factors related to its disappearance, 946 HBsAg carriers in Okinawa, Japan were prospectively followed for up to 19 years (mean ϭ 9.2 years). The disappearance of HBsAg, as determined by radioimmunoassay (RIA), was observed in 62 (6.6%) and the overall annual disappearance rate was 0.79%/year. Its disappearance was more frequent in 60 (7.4%) of 815 serum samples negative for hepatitis B e antigen (HBeAg) by RIA at entry compared with only two (1.5%) of 131 serum samples that were HBeAg positive by RIA at entry (P Ͻ 0.05). Stepwise logistic regression analysis showed that age and HBsAg subtype were significantly associated with HBsAg disappearance (both P Ͻ 0.05), and that carriers with subtype adr (odds ratio ϭ 2.87) had an increased probability of clearing HBsAg compared with carriers with subtype adw. Conversely, HBeAg disappearance was earlier in those with the adw subtype than in those with adr. Hepatitis B virus DNA was not detected by the polymerase chain reaction after HBsAg disappearance in any of the 62 from whom it had disappeared. The HBsAg titer, as measured by reverse passive hemagglutination, was related to the time to its disappearance; the higher the titer, the longer the time to disappearance. These findings suggest that HBeAg negativity, a more advanced age, and low titers of HBsAg are favorable factors for HBsAg disappearance in the natural course of chronic HBV infection. Moreover, HBsAg subtype adr was a predictive factor for HBsAg disappearance, whereas subtype adw was predictive of early HBeAg disappearance.It has been conservatively estimated that there are 350 million chronic hepatitis B virus (HBV) carriers throughout the world.1 This virus is a serious problem in many countries since it causes chronic liver disease and hepatocellular carcinoma. [2][3][4] Diagnosis is made by the detection of hepatitis B surface antigen (HBsAg) in serum. The disappearance of HBsAg and the appearance of antibody to HBsAg (anti-HBs) in sera have been reported to indicate the clearance of HBV particles and the cessation of hepatocyte injury. [5][6][7] Our laboratory previously reported that the Yaeyama District of Okinawa, Japan was highly endemic for HBV infection, 8 and that the number of newly infected residents has decreased there, as estimated in our long-term study. 9 In another Okinawa study, we found that the rate and age of seroconversion from hepatitis B e antigen (HBeAg) to antibody to HBeAg (anti-HBe) were higher and younger in cases with the HBsAg subtype adw than in those with subytpe adr, suggesting that the HBsAg subtype may be closely associated with the HBeAg/anti-HBe status.

Clinical outcomes of hepatitis B virus (HBV) genotypes B and C in Japanese patients with chronic HBV infection.

“…The HBV genotypes were determined in sera by an enzyme-linked immunosorbent assay (ELISA) in December 2000. This and our previously reported prospective HBV study 17 of Okinawa have continued since 1978. Blood samples were collected from residents reporting for free health examinations and who were available for follow-up.…”

“…12 Moreover, it is difficult to relate the different clinical courses of HBV infection classified by HBsAg subtype because there are several compound HBsAg subtypes, such as adyr, adwr, or undetermined subtypes. 17,18 Since 1994, it has been possible to determine HBV genotypic differences reflected in the genome sequence by the polymerase chain reaction. 13 Restriction fragment length polymorphism of the S gene sequence testing was later introduced for HBV genotyping.…”

“…One hundred fifty-eight Japanese patients with chronic HBV infection, 97 followed as outpatients at the Department of General Medicine, Kyushu University Hospital (Fukuoka Prefecture) and 61 who have had part in our HBV survey of the Yaeyama District of Okinawa Prefecture since 1978, 4,7,17 were retrospectively studied. The HBV genotypes were determined in sera by an enzyme-linked immunosorbent assay (ELISA) in December 2000.…”

Gender Difference in Alcoholic Liver Disease

“…In a prospective follow-up study of up to 19 years on HBsAg carriers in Okinawa in Japan, clearance of HBsAg was found more frequently in females (7.8%) than in males (5.8%) (Furusyo et al, 1999). Seroconversion from HBeAg to its antibody (anti-HBe) occurs more frequently in females than in males (Zacharakis et al, 2005).…”

“…In other words, overproduced collagens are deposited in injured areas instead of destroyed hepatocytes. Moreover, females, especially before menopause, produce antibodies against hepatitis B virus (HBV) surface antigen (HBsAg) and HBV e antigen (HBeAg) at higher frequency than males (Furusyo et al, 1999;Zacharakis et al, 2005). In chronic infection with hepatitis C virus (HCV), the clearance rate of blood HCV RNA appears to be higher in females (Bakr et al, 2006).…”