Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

Pinho, João Renato Rebello; Fonseca, Luís; Song, Yinggai; Miyamoto, Yoshinori; Carrilho, Flair José; Granato, Celso Francisco Hernandes; Silva, L. C. Da

doi:10.1590/s0036-46651989000500006

Cited by 4 publications

(1 citation statement)

References 21 publications

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“…37,38 Our laboratory has reported a low prevalence of HCV infection in the district studied. 39 The present study showed that no anti-HCV-positive carriers cleared HBsAg, but there was no evidence of HBsAg disappearance influenced by HCV infection because of the very small population with HCV superinfection.…”

Section: Discussionmentioning

confidence: 93%

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: 93%

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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Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection

et al. 1996

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We investigated the frequency of HBsAg clearance and the possible role of viral superinfection in a long-term follow-up of 184 patients with chronic hepatitis B (CHB). Our subjects were 184 patients with chronic hepatitis B and the follow-up was 12-216 months (mean 66.2 +/- 53.7 months). The investigative methods used were: immunoenzymatic assays for HBV, HCV, HDV, and HIV markers; polymerase chain reaction (PCR) for HBV DNA; and liver biopsy and immunoperoxidase. During the follow-up, 20 of the 184 patients cleared serum HBsAg. A comparison of patients with persistent HBsAg(group I) and of those who cleared this marker (group II) showed a significant difference in mortality (P = 0.002) between the two groups and a tendency to a more severe exacerbation (flare) in group II (P = 0.07). Antibodies to hepatitis C and D virus as well as antibodies to HIV were equally distributed in both groups. Thirteen patients (7.9%) from group I, but none from group II, subsequently developed hepatocellular carcinoma. These results suggest that the frequency of spontaneous clearance of HBsAg during chronic HBV infection is low. No determinant factor for the clearance was found, including the presence of liver cirrhosis. Serum HBV DNA was undetectable by PCR after clearance in 16 out of 17 patients.

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Detection of hepatitis B virus DNA by the polymerase chain reaction in anti-HBE positive chronic hepatitis B patients

Pinho

Santos

González

et al. 1993

Rev. Inst. Med. trop. S. Paulo

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Detection of HBV-DNA by PCR was compared with other serological markers (HBsAg, HBeAg and anti-HBe) in a series of49 Chronic Hepatitis B patients, including 12 with a spontaneous clearance of HBsAg. None of these HBsAg negative cases were PCR positive, but 33/37 (89.2%) HBsAg positive cases were PCR positive (p < 0.0001). Among HBsAg positive samples, nine cases were HBeAg positive and anti-HBe negative, all of them PCR positive. Other 3 patients were HBeAg and anti-HBe positive and these cases were also found PCR positive. A third group included 21 patients anti-HBe positive and HBeAg negative: 19 of them were PCR positive and 2 were PCR negative. The last 4 cases were HBeAg and anti-HBe negative, two of them were PCR positive. The detection of anti-HBe viremic cases in the present series suggest that preC variants could occur in our country. In conclusion, the integrated phase o f chronic hepatitis B seems to be less frequent than it was assumed, when only HBeAg or dot blot hybridization techniques were used. The new term "low replication phase" might favorably replace the former "integrated phase".
A detecção do DNA do Vírus da Hepatite B pela Reação em Cadeia da Polimerase (PCR) foi comparada com os outros marcadores sorológicos virais (AgHBs, AgHBe e anti-HBe) numa série de 49 pacientes com hepatite crônica B, incluindo 12 que apresentaram clareamento espontâneo do AgHBs. Nenhum caso AgHBs negativo foi PCR positivo, mas 33/37 (89,2%) dos casos AgHBs positivos foram PCR positivos (p < 0,0001). Entre as amostras AgHBs positivas, 9 foram AgHBc positivas e anti-HBe negativas, todas elas PCR positivas. Outros 3 pacientes foram AgHBe e anti-HBe positivos, todos também PCR positivos. Um terceiro grupo incluía 21 pacientes anti-HBe positivos e anti-HBe negativos: 19 foram PCR positivos e 2 PCR negativos. Os últimos 4 casos foram AgHBe e anti-HBe negativos, sendo 2 destes PCR positivos. A detecção de casos virêmicos anti-HBe positivos sugere que as variantes preC do VHB podem também estar presentes em nosso país. Em conclusão, a "fase de integração viral" da hepatite crônica B parece ser muito menos frequente do que se imaginava previamente, quando apenas se dispunha das técnicas de detecção de AgHBe e DNA por hibridização. O novo termo "fase de baixa replicação baixa" parece ser melhor que o anterior "fase de integração viral"

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Comparison of serum hepatitis B virus replication markers in patients with chronic hepatitis B: studies on HBeAg/Anti-HBe system, viral dna polymerase and HBV-DNA

Cited by 4 publications

References 21 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.

Spontaneous hepatitis B surface antigen clearance in a long-term follow-up study of patients with chronic type B hepatitis. Lack of correlation with hepatitis C and D virus superinfection

Detection of hepatitis B virus DNA by the polymerase chain reaction in anti-HBE positive chronic hepatitis B patients

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