Antibody to hepatitis B core antigen in patients with hepatocellular carcinoma.

Hepatitis B surface antigen (HBsAg), anti-HBs, and anti-HB core (HBc) were measured in 124 patients with hepatocellular carcinoma (HCC) in comparison with 299 control subjects of comparable ages, and in 48 cases of chronic hepatitis and 52 cases of hepatic cirrhosis. It was found that 72.6% of the HCC patients were positive for anti-HBc, and 80.6% were positive for at least one test, whereas in the control, anti-HBc was positive in 30.1% and 34.1% were positive for at least one test, the differences between the two groups being significant (P less than 0.01). The frequencies of positive tests for HBsAg and anti-HBc were the highest in HCC followed in decreasing order by cirrhosis, chronic hepatitis and the control group. A possible role of HB virus infection in hepatocellular carcinoma is discussed in relation to other factors.     

乙型肝炎病毒表面抗原定量与肝癌的关系探讨

目的结合HBVDNA载量、HBeAg阳性与HBeAg阴性,评价HBsAg在原发性肝癌(HCC)发生、发展中的意义。方法采用化学发光法检测306例HBV感染所致肝硬化及肝硬化合并HCC的两组患者血清乙型肝炎病毒标志物(HBVM)滴度,采用荧光定量PCR技术检测患者血清HBVDNA载量。结果肝硬化组:血清HBsAg滴度≥250IU/ml者占67.5%;HBeAg阳性者占23.8%;HBeAg阴性者占76.2%;HBVDNA≥104copies/ml者占79.5%。肝硬化合并HCC组:血清HBsAg滴度≥250IU/ml者占81.9%;HBeAg阳性者占38.1%;HBeAg阴性者占61.9%;HBVDNA≥104copies/ml者占61.3%。两组中HBsAg≥250IU/ml与HBVDNA≥104copies/ml病例比较差异有统计学意义(P<0.05)。结论在HBV感染所致肝硬化患者中,长期高滴度状态的HBsAg在评价肝硬化发展为HCC中同样起到预警信号的作用。     

IgM antibody to hepatitis B core antigen in Korean patients with hepatocellular carcinoma

Primary hepatocellular carcinoma (PHC) has been linked etiologically to persistent hepatitis B virus (HBV) infections by epidemiologic, serologic and molecular lines of evidence. To evaluate the frequency of IgM antibody to the viral core antigen (IgM anti-HBc) detected by a highly sensitive radioimmunoassay, we compared 110 Korean patients with PHC to a group of 63 age- and sex-matched control patients with other tumors. Results were correlated with those of commercially available HBV assays. IgM anti-HBc was found in 74 of 110 PHC patients (67%), but only 1 of 63 (1.6%) control patients. Although HBsAg was found in a larger percentage of PHC patients (81%), it was also present in more control patients (14%). Thus, IgM anti-HBc was more specifically associated with PHC than was the presence of HBsAg. IgM anti-HBc was found in 91% of PHC patients with detectable HBeAg and 74% of PHC patients with positive anti-HBe tests (p less than 0.04). The frequency of IgM anti-HBc was similar among HBsAg-positive PHC patients with and without anti-HBs, or those with low or high levels of serum alpha-fetoprotein. In 18 patients with PHC, IgM anti-HBc was further characterized by rate-zonal centrifugation of sera, all were found to have 19S IgM anti-HBc although 6 also had greater or equal IgM anti-HBc reactivity in the low molecular weight region. The presence of IgM anti-HBc in adult Korean HBsAg carriers may indicate an especially high risk for the development of PHC, and this should be evaluated in prospective studies.     

Risk of hepatic decompensation but not hepatocellular carcinoma decreases over time in patients with hepatitis B surface antigen loss

1. Download : Download high-res image (317KB)
2. Download : Download full-size image

     

Hepatitis B surface antigen levels in hepatitis B virus-related hepatocellular carcinoma: a retrospective crosssectional study

正Objective To investigate the distribution of serum hepatitis B surface antigen(HBs Ag)levels in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC).Methods A total of 226 cases of HBV-related HCC were collected from June 2009 to December 2013.Demographic characteristics of patients     

Systematic review of risk factors of hepatocellular carcinoma after hepatitis B surface antigen seroclearance

There is no consensus about factors that increase risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B who have achieved seroclearance of hepatitis B surface antigen (HBsAg). To assess the available evidence about risk factors for HCC after HBsAg seroclearance, Scopus, EMBASE, PubMed and Cochrane Library databases were systematically searched for relevant studies published through 15 September 2017. A total of 28 studies involving more than 105 411 patients with chronic hepatitis B were included. HBsAg seroclearance occurred spontaneously in 7656, while it occurred after interferon or nucleos(t)ide analogue therapy in 1248. The rate of HBsAg seroclearance was 6.77%. Incidence of HCC was significantly lower among patients who experienced HBsAg seroclearance than among those who remained HBsAg‐positive (1.86% vs 6.56%, P < .001). Risk factors of HCC occurrence included cirrhosis (incidence with vs without: 9.51% vs 1.66%), male gender (2.34% vs 0.64%) and age ≥ 50 year at HBsAg seroclearance (2.34% vs 0.63%) (all P < .001). The available evidence suggests that HCC can develop at a low rate after HBsAg seroclearance, so periodic surveillance is recommended, especially for male patients, patients with cirrhosis and patients who experience HBsAg seroclearance when at least 50 years old.     

Vertical transmission of the hepatitis B surface antigen.

Vertical transmission implies transmission of the hepatitis B virus from mother to infant. This occurs with great frequency (70 to 100 per cent) when the mother has acute hepatitis B near delivery. Studies indicate that transmission may occur transplacentally or during the birth process, Once infected, the infants apparently remain hepatitis B surface antigen carriers with persistent hepatitis indefinitely; The rate of transmission of the hepatitis B surface antigen from asymptomatic carrier mothers to their infants varies from 0 to 40 per cent in different areas of the world. The highest rate is in Taiwan where it was found that neonatal infection correlated with the height of complement fixation of surface antigen in the maternal serum. In our series of carrier mother-infant pairs, three infants became surface antigen positive as neonates; two became positive between three and six months; and one became positive between six and 12 months of age; Two babies developed extremely high titers of antibody to hepatitis B surface antigen the first year of life. In addition, 33 infants who were followed for from three to 42 months developed neither antigen nor antibody positivity.     

乙型肝炎表面抗原和乙型肝炎e抗原双阳性的乙型肝炎病毒携带产妇进行母乳喂养的安全性

目的探讨乙型肝炎表面抗原(hepatitis B surface antigen,HBsAg)和乙型肝炎e抗原(hepatitis B e antigen,HBeAg)双阳性的乙型肝炎病毒(hepatitis B virus,HBV)携带产妇采用母乳喂养对其所生婴儿HBV感染率的影响.方法采用前瞻性队列研究方法,纳入2016年2月至2018年5月在浙江大学医学院附属妇产科医院进行产前检查及分娩的HBsAg和HBeAg双阳性携带HBV产妇及其所生的婴儿各323例,将其分为母乳喂养组和人工喂养组.采用化学发光免疫分析法和聚合酶链反应-荧光探针法,分别检测两组婴儿在出生<24 h及7月龄时的血清HBV标志物和HBV DNA的阳性率.统计学方法采用x2检验.结果最终纳入297例患者,其中母乳喂养组149例,人工喂养组148例.母乳喂养组与人工喂养组婴儿在出生<24 h及7月龄时的HBsAg、抗-HBs、HBeAg、HBV DNA>100 IU/mL的阳性率比较,差异均无统计学意义(均P>0.05).母乳喂养组出生<24 h新生儿抗-HBs阳性率为58.39%(87/149),低于7月龄时的95.97%(143/149);母乳喂养组出生<24 h新生儿HBeAg阳性率为65.10%(97/149),高于7月龄时的13.42%(20/149);差异均有统计学意义(x2=59.75、40.49,均P<0.01).母乳喂养组出生<24 h新生儿的HBsAg和HBV DNA>100 IU/mL阳性率分别为2.01%(3/149)和2.68%(4/149),其7月龄时的HBsAg和HBV DNA>100 IU/mL阳性率分别为2.68%(4/149)和2.68%(4/149),两个时间点比较差异均无统计学意义(均P>0.05).人工喂养组出生<24 h新生儿抗-HBs阳性率为47.97%(71/148),低于7月龄时的95.94%(142/148);人工喂养组出生<24 h新生儿HBeAg阳性率为55.41%(82/148),高于7月龄时的19.59%(29/148);差异均有统计学意义(x2=85.37、39.84,均P<0.01).人工喂养组出生<24h新生儿的HBsAg和HBV DNA>100IU/mL阳性率分别为4.73%(7/148)和1.35%(2/148),其7月龄时的HBsAg和HBV DNA>100 IU/mL阳性率分别为1.35%(2/148)和1.35%(2/148),两个时间点比较差异均无统计学意义(均P>0.05).结论母乳喂养不是增加HBsAg和HBeAg双阳性HBV携带产妇垂直传播风险的决定性因素,建议这类产妇在正规预防的前提下进行母乳喂养.     

Maternal breast feeding safety of hepatitis B virus carrying parturient women with hepatitis B surface antigen and hepatitis B e antigen double positive

正Objective To explore hepatitis B virus (HBV)infection rate of breast feeding to newborn babies of HBV carrying parturient women with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg)double positive.Methods A prospective cohort study was conducted to include HBsAg and HBeAg double-positive HBV carrying parturient women and their babies born from February 2016 to May 2018 at the Women’s Hospital,Zhejiang University School of Medicine,and     

Prevention of hepatocellular carcinoma in patients with chronic hepatitis B

Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma(HCC). Globally,over half a million people each year are diagnosed with HCC,with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus(HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC,the molecular basis for this association has not been fully elucidated. In addition,a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis,recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agentsin achieving profound and durable suppression of HBV DNA levels while improving liver function and histology,robust evidence of other long-term clinical outcomes,such as prevention of HCC,are limited.     

Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues

AIM： To investigate the correlation between hepatitis B virus surface antigen （HBsAg）, hepatitis C virus （HCV） expression in hepatocellular carcinoma （HCC）, the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein （AFP） level.
METHODS： The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immunohistochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index （HAIl score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups： patients positive for HBsAg （HBsAg group）, patients positive for HCV （HCV group）, patients negative for both HCV and HBsAg （NBNC group） and patients positive for both HBsAg and HCV （BC group）.
RESULTS： The BC group had significantly higher HAI scores than the other three groups. （BC 〉 HCV 〉 HBsAg 〉 NBNC）. HBV and HCV virus infection was positively correlated with HAI （rs = 0.39, P = 0.00011. The positive rate of AFP （85.7%） and the value of AFP （541.2 ng/mL） in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate （53.3%） of AFP and the value of AFP （ 53.3 ng/mL） in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP（rs = 0.38, P = 0.0001）.
CONCLUSION： The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The-serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman＇s rank correlation analysis, we can conclude that the severity of virally induced     

Expression of hepatitis B surface antigen subtypes in liver of patients with hepatocellular carcinoma; comparison of subtypes in serum and liver

ABSTRACT— To clarify the discrepancy in hepatitis B surface antigen (HBsAg) subtypes present in the serum and liver, as well as among hepatocytes, liver specimens which were resected from 37 HBsAg-positive patients with hepatocellular carcinoma (HCC) were examined. We evaluated HBsAg and the subtypic determinants of HBsAg and hepatitis B core antigen (HBcAg) using the peroxidase-antiperoxidase (PAP) staining method. Hepatitis B antigens were more frequently detected in small tumors (HBsAg in 67%, HBcAg in 40%) than in large ones (HBsAg in 36%, HBcAg in 14%). The prevalence of each subtypic determinant in the HBsAg positive non-tumorous vs. tumorous areas was 100% vs. 67% in a, 100% vs. 57% in d, 100% vs. not tested in y, 100% vs. 53% in r and 25% vs. 0% in w (a, d, y, r and w represent subtypic determinants). There was virtually no difference in a set of subtypic determinants between the serum and liver. However, there were some variations in a set of subtypic determinants among the hepatocytes. On the other hand, liver tissue of compound subtype adyr in serum contained both cells with a,d,r and with a,y,r as well as a few cells with a,d,y,r. These findings suggest that HBV genomes in hepatocytes of type B chronic liver disease may differ genetically among cells even in the same liver tissue.     

Clearance of hepatitis B surface antigen (HBsAg) after surgical resection of hepatocellular carcinoma

The serum HBsAg in 4 chronic HBsAg carrier patients with hepatocellular carcinoma (HCC) cleared within 4-38 months after surgical resection of their hepatic tumors. Two patients developed anti-HBs. During the follow-up period from 21 to 28 months after HBsAg clearance, none of the patients regained positive serum HBsAg. Two patients who had had tissue HBsAg present, exclusively in the tumor, showed quick HBsAg clearance after resection. The other 2 patients had a delayed HBsAg clearance. One had tissue HBsAg in both the tumor and nontumoral liver. Only 1 patient had tissue HBsAg in the liver, but not in the tumor. During the same period of observation of 323 chronic HBsAg carriers, who had a variety of histologically-verified chronic liver diseases and were followed for more than 6 months, only 1 cleared the antigen. The spontaneous HBsAg clearance in our HBsAg carriers (1/323) was significantly lower than that (4/64) of HBsAg-positive HCC patients with tumor resection, P less than 0.004. The mechanisms of HBsAg clearance in HCC patients after surgical resection of tumors are discussed.     

Long-term outcome after hepatitis B surface antigen seroclearance in patients with chronic hepatitis B

Purpose

The aim of this study was to elucidate the long-term outcome after hepatitis B surface antigen (HBsAg) seroclearance in a large number of Japanese patients.

Methods

We studied the biochemical, virologic, histologic, and prolonged prognoses of 231 Japanese patients with HBsAg seroclearance (median follow-up, 6.5 years). Serum alanine aminotransferase, serum hepatitis B virus (HBV) markers, liver histology, and clinical aspects were monitored. HBV-DNA levels were measured with the qualitative polymerase chain reaction assay. The mean age of patients with HBsAg seroclearance was 52 years.

Results

After HBsAg seroclearance, 203 patients (87.9%) had normal alanine aminotransferase levels 1 year after HBsAg seroclearance. HBV-DNA showed positive results in 4 patients (1.7%) 1 year after HBsAg seroclearance. Thirteen patients were examined for histologic changes of the liver after HBsAg seroclearance. All patients showed marked improvement of necroinflammation of the liver, but only 2 of the 13 patients showed no liver fibrosis. Liver cirrhosis and hepatocellular carcinoma did not develop in any of the 164 patients without evidence of liver cirrhosis at the time of HBsAg seroclearance. Hepatocellular carcinoma developed in 2 of the 67 patients with liver cirrhosis at the time of HBsAg seroclearance. During the observation period, 15 patients died. However, the cause of death of these 15 patients was not related to liver disease, such as hepatocellular carcinoma, decompensated liver cirrhosis, and rupture of esophageal varices.

Conclusion

Our results suggest that HBsAg seroclearance confers favorable long-term outcomes in patients without hepatocellular carcinoma or decompensated liver cirrhosis at the time of HBsAg seroclearance     

Kinetics of serum O-glycosylated M-hepatitis B surface antigen with hepatocellular carcinoma history and nucleos(t)ide analogue therapy in hepatitis B patients

A newly developed O-glycosylated M-hepatitis B surface antigen (HBsAgGi) measurement system can detect hepatitis B surface antigen (HBsAg) associated with infectious particles. We investigated the association of HBsAgGi levels with clinical parameters and a history of hepatocellular carcinoma (HCC) development in a cross-sectional cohort analysis (Study 1) as well as the quantitative changes in HBsAgGi during nucleos(t)ide analogue (NA) therapy in a longitudinal cohort analysis (Study 2). A total of 124 patients with genotype C chronic HBV infection were analysed in Study 1 to evaluate correlations of HBsAgGi with conventional HBV markers and HCC history. Among those, 36 patients receiving NA therapy were enrolled in Study 2 for quantitative comparisons between pre-treatment baseline and 48 weeks of NA therapy. In Study 1, serum HBsAgGi was significantly associated with HBsAg (r = .5857, p < .00001) and weakly but significantly correlated with HBV DNA (r = .2936, p = .001). Although HBsAgGi (p = .111) was comparable between HCC history (+) group and HCC history (−) group, the HBsAgGi/HBsAg ratio (p = .011) was significantly higher in HCC history (+) patients. In Study 2, HBsAgGi was significantly decreased after 48 weeks of NA therapy (p < .001). HBsAg findings were similar (p = .005) along with an HBV DNA reduction (p < .001). In the baseline hepatitis B e antigen (HBeAg) (+) subgroup, HBsAgGi decreased significantly between baseline and 48 weeks of NA (p = .005), while HBsAg was comparable (p = .051). Low HBsAg and high HBsAgGi were associated with a history of HCC development. HBsAgGi decreased significantly by 48-week NA therapy.