A seroepidemiological survey of the effect of hepatitis B vaccine and hepatitis B and C virus infections among elementary school students in Siem Reap province,Cambodia

Aim

This study aimed to survey the prevalence and incidence of hepatitis B (HBV) and hepatitis C virus (HCV) infection among elementary school students in Siem Reap province, Cambodia and to evaluate the effects of a national infant HBV vaccination program introduced in 2001.

Methods

Students in 3rd grade during the 2011, 2012, and 2013 academic years were enrolled in this study; at the time of the second examination, in the 2014–2015 academic year, the students were in 5th or 6th grade. The incidence and prevalence rates of HBV and HCV infection were estimated and full HBV sequences were analyzed.

Results

Among 248 students (107 male and 141 female) born between 1999 and 2005, five students were HBV surface antigen (HBs‐Ag) positive (2.02%), and all of them were infected with genotype C. Among them, subgenotype C1 was found in four students and, unexpectedly, complete genetic sequence identity of subgenotype C1 was found in two students from different families. The anti‐HBV core (HBc) and anti‐HBs prevalence rates were 10.89% and 16.13%, respectively. Twenty‐five students were positive for anti‐HBs and negative for both HBsAg and anti‐HBc (10.08%; estimated serological vaccination rate); this rate increased significantly with the birth year (P = 0.0229). Prevalence of anti‐HCV was 2.82%, and HCV RNA was not detected. The estimated incidence of HBV and HCV infection were both 0/1000 person‐years (PY) (95% confidence interval, 0–20.61/1000 PY and 0–14.50/1000 PY, respectively).

Conclusion

Hepatitis B virus full‐genome sequencing and serological analysis revealed the possibility of horizontal transmission of HBV among Cambodian schoolchildren. However, the anti‐HBc positivity rate decreased along with increasing age and estimated serological vaccination rates.     

Production of antibody to hepatitis A virus and hepatitis B surface antigen measured after combined hepatitis A/ hepatitis B vaccination in 242 adult volunteers

Two batches of a new hepatitis A/hepatitis B combined vaccine were tested in 242 healthy students. Three injections, given at 0, 1 and 6 months, produced seroconversion rates and hepatitis A virus (HAV) and hepatitis B surface antigen (HBsAg) antibody levels comparable to those reported after administration of separate monocomponent vaccines. The vaccine proved to be safe and well-tolerated. Influence of host factors, such as elevated body mass index or gender, were investigated and proven to be of little influence on the immunoresponse.     

162例慢性乙型重型肝炎医院感染调查分析

目的 分析总结慢性乙型重型肝炎患者发生医院感染的特点,为加强医院感染的防控提供帮助.方法 调查分析我院2008年1月至2011年10月收治的慢性乙型重型肝炎患者162例发生医院感染的情况.结果 162例慢性乙型重型肝炎患者中发生医院感染35例,医院感染率为21.6％.感染部位以腹腔感染和呼吸道感染最多,其次为肠道感染.病原菌以大肠埃希茵和肺炎克雷伯杆菌常见.医院感染主要发生在住院时间15-30d,占72.09％.医院感染组治疗无效率(20％)显著高于非医院感染组(7.09％)(P＜0.05).结论 慢性乙型重型肝炎医院感染发生率高,应积极治疗原发病,改善肝功能,严格遵守消毒隔离制度,加强医院感染的防控,从而提高生存率.     

HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma

This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen (HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg-negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti-HBc and anti-HBs, four (18%) had anti-HBc alone, and four (18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface (S), core (C), polymerase (P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/or adjacent nontumorous liver in 22 of 30 (73%) patients [detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver (two cases) or only in the nontumorous liver (one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg-negative HBV infection. Thus, HBV DNA was detectable in 22 (73%) HBsAg-negative, anti-HCV-positive HCCs, including three (10%) who were also negative for anti-HBc and anti-HBs. HBV mutations at both nucleotides 1762 (A-GT) and 1764 (G-A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV-associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs.     

Precore and X region mutants in hepatitis B virus infections among renal dialysis patients

SUMMARY. Hepatitis B virus (HBV) variants containing mutations within the X and the precore regions of the viral genome were demonstrated by polymerase chain reaction (PCR) amplification and DNA sequencing in renal dialysis patients with different serological patterns of HBV infection. Among carriers, X region deletion mutants predominated in patients who lost hepatitis B e antigen (HBeAg), or developed anti-HBe, but not in persistently HBeAg-positive patients. The precore region remained wild type in all carriers whether or not they seroconverted from HBeAg to anti-HBe. The frequency of precore and X region mutants was greatest among non-carrier patients with viral antibodies as the only indication of infection and among patients with non-A, non-B hepatitis (NANBH), suggesting an inverse relationship between the presence of wild type HBV markers and the presence of HBV mutants. Furthermore, the detection of one but not the other mutation in many serum samples suggests that these mutations are independently selected for during infection. Finally, the absence of HBV DNA in 21 'uninfected' dialysis patients with normal transaminases and no viral serology, suggests that replication of these mutants is associated with hepatitis. These results have important implications for HBV screening and treatment, as well as for the pathogenesis of chronic infection.     

Hepatitis B surface antigenaemia following vaccination with a combined vaccine against hepatitis A and B

Summary.  We report a case of transient hepatitis B surface antigenaemia (HBsAg) following vaccination with a combined vaccine against hepatitis A and B in healthy adults. This phenomenon has been observed following administration of recombinant hepatitis B (monovalent) vaccine, mainly in newborns or dialysis patients. Reports on healthy adults are much less frequent and mostly concern blood donors. The frequency of its occurrence is largely unknown but its duration does not exceed 28 days. It is not detected by all available assays. It is caused by a passive tranfer of antigen by vaccination, and not by viral replication; hence there is no risk for vaccination-induced infection. An important implication resulting from our findings is that the results of HBsAg assays should be interpreted according to the time elapsed since the last administration of a recombinant monovalent vaccine against hepatitis B or a combined vaccine against hepatitis A and B.     

Analysis of hepatitis A virus protein 2B in sera of hepatitis A of various severities

Background In our recent study of the full-length hepatitis A virus (HAV) genome from some patients with fulminant hepatitis and acute hepatitis, possible associations were suggested between the severity of hepatitis A and the amino acid substitutions in the nonstructural protein 2B. We therefore analyzed HAV 2B from many patients with various clinical disease severities. Methods Serum samples from 30 Japanese patients with sporadic hepatitis A from five widely separated regions of Japan, comprising nine patients with fulminant hepatitis (FH), six with severe acute hepatitis (AHs), and 15 with acute hepatitis (AH), were examined for HAV RNA. The entire sequences of HAV 2B were analyzed. Results Compared with the sequence of the wild-type HAV strain GBM, nucleotide sequences of 2B had homology of 94.5 ± 1.0% in FH, 95.2 ± 1.2% in AHs, and 95.1 ± 1.8% in AH. Deduced amino acid sequences had homology of 97.5 ± 2.1% in FH, 97.9 ± 2.4% in AHs, and 98.5 ± 1.3% in AH. Differences were not statistically significant among the three groups. The average number of amino acid mutations between amino acids 100 and 200 was 5.0 ± 5.2 per case in FH, 4.0 ± 6.0 in AHs, and 1.9 ± 2.9 in AH. The differences between FH and AH, AHs and AH, and between severe cases (FH and AHs) and nonsevere cases (AH) were not statistically significant (P = 0.13, P = 0.45, and P = 0.10, respectively). Conclusions There were no obvious differences in the sequences among FH, AHs, and AH throughout the 2B region, but there seemed to be more mutations in the strains obtained from FH and AHs patients than in those obtained from AH patients in the central part of HAV 2B.     

Immune response after hepatitis A vaccination in haemodialysis patients: Comparison with hepatitis B vaccination

This study evaluates the immune response of 20 haemodialysis (HD) patients vaccinated with hepatitis A (HA) vaccine and eight patients vaccinated with hepatitis B (HB) vaccine. Twenty patients and 22 healthy adults were immunized three times (months 0, 1 and 6) intramuscularly with a 0.5 μg dose. All members of both groups were positive for the antibody to hepatitis A virus (anti-HAV) after three vaccinations. The geometric mean titres at 7 months were similar in both groups. No serious side effects were observed. Eight of the HD patients with HA vaccination were injected with yeast-derived hepatitis B vaccine. The three doses of 10 μg were administered intramuscularly at 0, 1 and 6 months. The occurrence of antibody to hepatitis B surface antigen (anti-HBs) was late in HD patients and the anti-HBs level in HD patients was lower than that in healthy subjects. These results indicate that this HA vaccine has good immunogenicity compared with the HB vaccine and that the standard three doses of HA vaccine given at 0, 1 and 6 months are safe and effective even in HD patients.     

Needlestick injuries and hepatitis B immunization in florida paramedics: A statewide survey

STUDY OBJECTIVES: To determine the incidence of needlestick injury among paramedics working in Florida during 1987, to describe the circumstances surrounding such injuries, and to assess the hepatitis B vaccination status of this group. DESIGN: Survey of a systematic random sample of paramedics using a self-administered questionnaire. SETTING: Florida. TYPE OF PARTICIPANTS: Paramedics. MAIN RESULTS: A completed questionnaire was returned by 300 of 500 paramedics (60%) who received the mailed questionnaire. Sixty-nine paramedics (23%) reported a total of 110 needlestick injuries. More than one third of injuries occurred in conjunction with recapping needles. Almost 62% of reported injuries could have been prevented had proper needle disposal technique been used. Sixty-two percent of paramedics reported having had at least one dose of the hepatitis B vaccine. Sixty-five percent of the unvaccinated paramedics said they would take the hepatitis B vaccine if it was offered free. CONCLUSION: The majority of needlestick injuries among paramedics in Florida could be prevented with proper needle disposal. Offering the hepatitis B vaccine at no charge to paramedics in Florida could increase the vaccination rate substantially.     

Hepatocyte hepatitis B surface antigen expression in chronic hepatitis B virus carriers in Singapore: Correlation with viral replication and liver pathology

The hepatocyte hepatitis B surface antigen (HBsAg) expression in 149 liver biopsies from 124 chronic hepatitis B virus (HBV) carriers was correlated with serum HBV DNA status and histologic activity. Hepatocyte HBsAg was stained by the peroxidase-antiperoxidase method and serum HBV DNA was determined by dot blot hybridization. Sixty-five biopsies (44%) showed minimal changes (MC), 82 biopsies (55%) showed chronic liver disease (CLD) and 2 biopsies (1%) showed hepatocellular carcinoma. Hepatocyte HBsAg was found in 144 biopsies (97%). It was present in the cytoplasm of 141 specimens (95%) and/or plasma membrane of 48 specimens (32%). Approximately half (45%) of the cytoplasmic HBsAg-positive biopsies showed discrete distribution, while the other half (55%) were grouped. Fifty-five per cent (77 of 141) of cytoplasmic HbsAg-positive biopsies had CLD, while 44% (62 of 141) showed MC. There was no relationship between the presence of cytoplasmic HBsAg or its topographic distribution with disease activity. Membrane HBsAg distribution was similar for both groups of patients (MC vs CLD: 25 of 65 (38%) vs 23 of 82 (28%); P = NS). Serum HBV DNA was detected in 98 patients (66%) and was seen mostly in association with CLD (CLD vs MC: 61% vs 39%, P less than 0.001). It was also detected more often in the sera of patients with membrane HBsAg than in those with cytoplasmic HBsAg staining (41 of 48 (85%) vs 97 of 141 (67%); P less than 0.02). However, discrete distribution of cytoplasmic HBsAg was associated with positive serum HBV DNA when compared with grouped distribution (52 of 63 (83%) vs 43 of 78 vs (55%); P less than 0.005).     

Acute hepatitis A and acquired immunity to hepatitis A virus in hepatitis B virus (HBV) carriers and in HBV- or hepatitis C virus-related chronic liver diseases in Thailand

A number of studies have suggested that the clinical course of hepatitis A virus (HAV) infection is more severe in patients with chronic liver disease (CLD). A study was undertaken to determine the impact of acute HAV in asymptomatic hepatitis B surface antigen (HBsAg) carriers (n = 20) and patients with hepatitis B virus (HBV)-(n = 8) or hepatitis C virus (HCV)-related (n = 4) CLD. Disease progression was compared with that in 100 patients with isolated HAV infection. No patient with HAV infection alone developed complications, and all recovered fully. Fulminant or submassive hepatitis occurred in 55% of HBsAg carriers and 33% of patients with HBV- or HCV-related CLD. The mortality rate in HBsAg carriers (25%) was not significantly different from that in the patients with CLD (33%). The seroprevalence of anti-HAV immunoglobulin G in 820 individuals was also determined. Approximately 50% of the individuals had acquired HAV infection between the ages of 21 and 30 years. It was demonstrated that HAV infection may have a more severe clinical course in patients with underlying CLD, particularly among older individuals. Vaccination for such patients should be considered.     

Hepatitis A,hepatitis B,and combination hepatitis vaccines for immunoprophylaxis: an update

Since the publication of the last extensive review of hepatitis vaccines, use of inactivated hepatitis A vaccines has been extended to high-risk regions of the United States and specific patient groups, such as those with chronic liver disease, and use of the recombinant hepatitis B vaccines has been recommended for older adolescents. A combination hepatitis A and B vaccine, recently approved for licensure by the US Food and Drug Administration, should increase convenience and compliance, reduce the costs of vaccination, and provide prolonged and dual protection for those at risk for hepatitis. Although commercially available vaccines for hepatitis C, D, and E remain a distant goal, advances in vaccine and adjuvant technology, including immunization with DNA-based vaccines, hold promise for the future.     

慢性乙型肝炎重叠HAV与HEV感染的临床分析

目的研究慢性乙型肝炎患者重叠甲型肝炎与重叠戊型肝炎病毒的临床特点及其对病情转归的影响。方法采用ELISA法检测甲、乙、丙、戊型肝炎病毒血清标记物,选择慢性乙型肝炎重叠甲型肝炎52例与慢性乙型肝炎重叠戊型肝炎267例进行对比分析。结果慢性乙型肝炎重叠戊型肝炎患者较慢性乙型肝炎重叠甲型肝炎患者总胆红素水平高、重型肝炎发生率高、病死率高,两组白蛋白水平和平均住院日无明显差异。结论慢性乙型肝炎患者重叠戊型肝炎病毒感染较重叠甲型肝炎病毒感染病情更重、预后差。     

慢性乙型肝炎患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系

目的 探讨慢性乙型肝炎（CHB）患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系.方法 回顾性分析250例CHB肝穿刺患者,按血清HBV DNA水平,分为A组（＜3 log10 IU/ml）45例,B组（3～6 log10 IU/ml）138例,C组（＞6 log10 IU/ml）67例.按HBeAg阴阳性不同分为阳性组142例,阴性组108例.分别与肝组织中HBcAg水平、肝组织炎症分级进行比较,分析彼此的相关性,率的比较用卡方检验及确切概率法,相关性分析采用直线相关分析.结果 血清HBV DNA不同水平与肝组织HBcAg免疫组化比较差异有统计学意义（χ2=11.1,P=0.05）,两者之间呈正相关（r=0.75,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=13.3,P=0.075）,两者之间也无相关性（r=0.04,P=0.325）.HBeAg阳性和阴性分组与肝组织中HBcAg水平比较差异有统计学意义（χ2=6.64,P=0.01）,两者之间呈正相关（r=0.56,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=8.43,P=0 065）,两者之间也无相关性（r=0.06,P=0.415）.结论 CHB患者肝组织HBcAg表达更能反映出肝内HBV复制状态,患者血清中测不出病毒标志物时,可以考虑肝穿刺以观察肝组织中HBcAg表达来判断HBV复制状态具有重要意义.