Natural History of Liver Disease in Chronic Hepatitis B Surface Antigen Carriers

Viola, Luis; Coleman, John; Fluker, J. L.; Barrison, I. G.; Paradinas, F. J.; Evans, B A; Murray-Lyon, I M

doi:10.1016/s0140-6736(81)90600-0

Cited by 117 publications

(30 citation statements)

References 26 publications

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“…The disappearance of HBsAg has been reported in several studies from non-Asian countries, where HBV infection usually occurs in adults 4,11,12 and from Asian countries, 7,[13][14][15] where HBV infection is hyperendemic and usually occurs during early childhood through either perinatal or child-tochild transmission. 8,[19][20][21][22] Annual rates of HBsAg disappearance have been estimated to be from 0.5%/year to 1.7%/ year.…”

Section: Discussionmentioning

confidence: 89%

“…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. 10 Although various investigators have reported the disappearance of HBsAg, 4,7,[11][12][13][14][15] there has been no documentation on the relationship between the natural course of chronic HBV infection and the HBsAg subtype. We recently reported the relationship between HBsAg disappearance and its subtype in residents of a small area of Iriomote Island, part of the district studied in this paper.…”

mentioning

confidence: 99%

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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.

Furusyo¹,

Hayashi²,

Sawayama³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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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.

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Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

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.

Furusyo¹,

Hayashi²,

Sawayama³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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“…Thus, the discovery of HDV has improved the understanding of the "natural" history of chronic HBV infection. These studies, however, were conducted primarily in drug addicts and male homosexuals, in whom HBV infection runs a different course, especially with respect to viral replication reflected in a decreased spontaneous HBeAg to anti-HBe seroconversion rate [Viola et al, 1981;Andersson et al, 19851.…”

Section: Introductionmentioning

confidence: 99%

Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan

Ishiguro¹,

Tamura²,

Tsubakio³

et al. 1988

Journal of Medical Virology

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To elucidate the influence of hepatitis delta virus (HDV) superinfection on the clearance of hepatitis B virus (HBV) associated antigens in HBV carriers, we examined for antibody to hepatitis delta antigen (anti-HD) serial sera collected from 1,029 HBV carriers in Kure, Japan. Of the 242 HBV carriers with hepatitis B e antigen (HBeAg), 28 became seropositive for anti-HD, of whom 18 (64.3%) cleared HBeAg; 214 did not become seropositive for anti-HD, of whom 70 (32.7%) cleared HBeAg. Thus, HBeAg clearance was observed in a significantly higher proportion of HDV-superinfected carriers as compared with carriers without HDV infection (P less than 0.005). In the 56 HBV carriers who cleared hepatitis B surface antigen (HBsAg), anti-HD was detected in three cases with increased serum alanine aminotransferase activity preceding HBsAg clearance. The duration of anti-HD seropositive state was less than 5 years, and the titer of anti-HD was relatively low in every case. These data suggest that the HDV infection rate in Japan is higher than previously reported, that HDV superinfection can be one of the factors that induce the HBeAg clearance and HBsAg clearance in HBV carriers, and also that the most likely outcome of HDV superinfection in HBV carriers in Japan may be acute self-limited infection.

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“…Subsequently, the patient must wait several weeks (8 weeks in our study) before interferon administration is started in order to validate the inclusion criteria of the trial. It may well be that in the interval preceding the start of therapy the spontaneous exacerbation has resulted in immunemediated decrease in HBV replication [Viola et al, 1981;Fattovich et al, 1986]. From our data we cannot assess whether the HBeAg seroconversion that occurred during treatment was interferon supported or not.…”

Section: Discussionmentioning

confidence: 86%

Interferon-alpha therapy for chronic hepatitis B: Early response related to pre-treatment changes in viral replication

et al. 2001

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Chronic hepatitis B patients with low pre-treatment HBeAg (and HBV-DNA) levels are more likely to respond to interferon-alpha therapy. In retrospect, this low level of HBeAg may have been reached just before the start of therapy. Pre-treatment changes in HBeAg levels were studied in 121 patients undergoing interferon-alpha 2B therapy. HBeAg was monitored by the AxSYM HBe 2.0 Quantitative (Abbott Laboratories) and HBV-DNA by liquid hybridisation (Abbott Laboratories). At the end of treatment (week 16) 24 patients had responded (HBeAg and HBV-DNA below the level of detection). Response was significantly (P = 0.007) related to a decrease in HBeAg level before the start of therapy. Eight of the 24 (33%) responding patients exhibited a > 50% decrease in HBeAg level just before the start of therapy compared to 7 of the 97 (7%) non-responding patients. The geometric mean titre of HBeAg decreased significantly (P < 0.005; 8-week period before start) among responding patients (271 ( 98 PEI U/ml) in contrast to non-responding patients (737 ( 724 PEI U/ml). Planning the start of interferon treatment just after a spontaneous decrease in HBV replication may increase the response rate for interferon-alpha therapy.

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Natural History of Liver Disease in Chronic Hepatitis B Surface Antigen Carriers

Cited by 117 publications

References 26 publications

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.

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.

Influence of hepatitis delta virus superinfection on the clearance of hepatitis B virus (HBV) markers in HBV carriers in Japan

Interferon-alpha therapy for chronic hepatitis B: Early response related to pre-treatment changes in viral replication

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