Neonatal hepatitis B vaccination protects mature adults from occult virus infection

Wang, Ruijun; Liu, Chang; Chen, Taoyang; Wang, Yuting; Chen, Fan; Lu, Lingling; Lu, Fengmin; Qu, Chunfeng

doi:10.1007/s12072-021-10156-z

Cited by 7 publications

(7 citation statements)

References 27 publications

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“…Since the introduction of hepatitis B vaccination in the 1980s, the coverage of vaccination has increased year by year, and more than 185 (185/194, 95%) countries have included it in their national immunization schedules. Results in previous research indicated that hepatitis B vaccination can not only dramatically reduced the prevalence of HBsAg-positive [39][40][41], but also effectively reduce the incidence of OBI [42,43]. It is also consistent with our ndings that the positive rates of OBI decreased signi cantly with the popularization of hepatitis B vaccination, including both HBcAb-positive and HBcAb-negative groups.…”

Section: Discussionsupporting

confidence: 91%

The risk of occult HBV infection in HBcAb-positive general population: a systematic review and meta-analyses

Yang

Xing

et al. 2022

Preprint

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Background & Aim: Hepatitis B is still a significant public health concern worldwide. The disease burden of occult HBV infection (OBI) has received more widespread attention. Hepatitis B core antibody (HBcAb)-positive is the seromarker of past HBV infection. Whether HBcAb can be used as the surrogate for OBI screening remains controversial. A meta-analysis is performed to evaluate the risk of OBI in HBcAb-positive general population. Method We search published studies in electronic databases which evaluated the prevalence of OBI in HBcAb-positive general population from January 1990 to April 2022, including Pubmed, Web of science, Embase, and Cochrane Library Central through April 18, 2022. The scope of this search was restricted to article published in English. Results Forty-three studies were including in the study, involving 19,777 individuals, 39 (39/43, 91%) original researches with blood detection, and 4 (4/43, 9%) with liver tissue samples. We found the pooled estimated incidences of OBI were 8% (95% CI: 4–13) in HBcAb-positive and 2% (95% CI: 0–4) in HBcAb-negative with blood sample detection, 66% [95% CI: 36–91]) and 0% (95% CI: 0–2) with liver tissue detection, respectively; variable sensitivities and specificities of HBV DNA detection methods were used in different studies. Conclusion The risk of OBI is significantly higher in HBcAb-positive general population than HBcAb-negative. It is necessary to consider HBcAb as a serological surrogate for OBI screening. Establishing standardized and validated confirmation assays for OBI diagnosis are warranted to support the goal of eliminating of HBV infection worldwide.

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Section: Discussionsupporting

confidence: 91%

The risk of occult HBV infection in HBcAb-positive general population: a systematic review and meta-analyses

Yang

Xing

et al. 2022

Preprint

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“…Many OBIs are associated with PreS variant infections, including in some adults who received the HBV vaccine at infancy [ 8 , 12 , 38 ]. MAFLD is becoming the most common cause of chronic liver diseases and an important risk factor for HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Following our previous reports, we sequenced and analysed the HBV PreS/S regions [ 13 ] with the primers provided in Additional file 1 : Table S1, examined the 3D structure of envelop protein using RaptorX structure prediction server [ 26 ] and determined HBV relaxed circular DNA (rcDNA) in the sera of HBsAg-seronegative HCC patients [ 12 ]. We detected HBV cccDNA in tissues using specific pan-genotypic primers following the protocol reported by Caviglia [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

“…Certain mutations, such as deletion or introduction of a stop codon in PreS1 or PreS2, cause an imbalance in the synthesis and secretion of the envelope protein, which results in HBsAg retention within hepatocyte ER, leading to ER stress and different liver diseases [ 8 , 10 ]. We followed the cohort of individuals who received HBV vaccine at neonates [ 11 ] for 30 years and identified certain adults having replication-component HBV at serum levels of < 10,000 copies/ml with various PreS/S mutations [ 12 , 13 ]. The outcome of OBI is largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Occult infection with hepatitis B virus PreS variants synergistically promotes hepatocellular carcinoma development in a high-fat diet context by generating abnormal ceramides

Liu

Chen

Zhao

et al. 2022

BMC Med

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Background Some occult hepatitis B virus (HBV) infections are resulted from PreS mutations that reduce secretion of envelope protein (HBsAg). We investigated the ceramide amounts and species in hepatocytes infected with PreS variants that were isolated from HBsAg-seronegative patients with hepatocellular carcinoma (HCC) and the ceramide effects on autochthonous HCC development in murine models. Methods HBV PreS/S regions from 35 HBsAg-seronegative HCC patients were sequenced. Hepatocyte cell lines and male C57BL/6J mouse livers were transfected with two PreS variant representatives. The ceramides with variated lengths of fatty acyl chains were quantified. Tumour development was examined in the HBV-transfected mice fed different diet types. Results In HBsAg-seronegative HCC patients, nonneoplastic liver tissues harboured HBsAg and replication-competent HBV. The most frequently detected PreS/S variants carried mutations of altered amino acid properties in HBsAg compared with an isolate from one HBsAg-seronegative HCC patient. Hepatocyte infection with PreS variants caused HBsAg retention within the endoplasmic reticulum and generated more amounts of ceramides with C16:0 ceramide elevated the highest. Saturated fatty acids aggravated the PreS variant-infected hepatocytes to generate abnormal amounts and species of ceramides, which with HBV proteins synergistically activated NLRP3 inflammasome in liver inflammatory macrophages. Liver tumours were only detected in HBV-transfected mice fed high-fat diet, with higher tumour loads in the PreS variant-transfected, associated with abnormal ceramide generation. Conclusions HBV PreS mutations which altered amino acid properties of envelope proteins inhibited HBsAg secretion. Hepatocyte infection with PreS variants generated abnormal ceramides which with HBV proteins coactivated NLRP3 inflammasome in liver macrophages to promote autochthonous HCC development.

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“…That is, in patients with cryptogenic cirrhosis or advanced liver fibrosis, the prevalence of OBI ranges from 4% to 38%, in the case of parenteral blood exposure, it is about 45%, in patients with chronic hepatitis C, it is estimated at 52%, in HIV-infected patients, it ranges from 0% to 45%, in blood donors from 0% to 22.7% and in hemodialysis patients, it ranges from 0% to 54% ( 9 ). In local areas of China, the prevalence of OBI was 19.48% (640/3100 cases) in the young people without the hepatitis B vaccine and 4.70% (170/3615 cases) in that vaccinated with the hepatitis B vaccine ( 10 ). Our research team estimates at least 20 million OBI patients in China ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

The Investigation of Hepatitis B Vaccine Immune Responses in Occult Hepatitis B Virus-Infected Patients

et al. 2022

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ObjectivesThere is no effective treatment for occult hepatitis B virus infection (OBI) patients, and immunotherapy may be one of the most promising options. We aim to investigate the underlying mechanism and therapeutic potential of hepatitis B vaccine immunotherapy for OBI patients.MethodsOutpatient OBI patients were screened and randomly divided into treatment (Group A) and control (Group B) groups. At weeks 0, 4, and 24, patients in Group A received a subcutaneous/intramuscular injection of hepatitis B vaccine (Engerix-B, 20 μg/time) according to the standard vaccination schedule; patients in Group B served as blank control. The patients were followed for 36 weeks, with clinical, biochemical, virological, immunological, and imaging data collected and analyzed at weeks 0, 12, 24, and 36, respectively, and the relation between the virology and immunology results was analyzed.ResultsOf the 228 OBI patients, 28 were excluded, and 200 were enrolled for observation. In the end, 44 patients were included in Group A and 39 in Group B after excluding lost cases. At week 0 (baseline), some patients in two groups had liver disease symptoms, HBV-related liver function damage, and liver fibrosis. 86.36% (38/44) and 82.05% (32/39) patients were positive for serum hepatitis B surface antibodies (anti-HBs) in Group A and Group B, respectively, with the median (quartile) of 42.47 (16.85, 109.1) and 39.27 (16.06, 117.4) mIU/ml, respectively. Reduced peripheral blood CD4+T, CD8+T, and B lymphocytes were found in some patients in two groups. These results were not statistically different between Group A and Group B (P>0.05). At week 36, all patients were serum anti-HBs (+) in Group A, with a median (quartile) of 1000 (483.9, 1000) mIU/ml, which was significantly higher than that at week 0 (P<0.05) and that in Group B (P<0.05). Compared to week 0, the number of CD8+ T and B lymphocytes increased significantly and were significantly higher than Group B at the same point. Two patients in Group B were found to have hepatitis B virus reactivation from week 12 to week 36.Correlation AnalysisAnti-HBs in Group A patients were positively correlated with B lymphocytes (r=0.3431, 0.3087, and 0.3041, respectively) and positively correlated with CD8+ T lymphocytes (r=0.4954, 0.3054, and 0.3455, respectively) at weeks 12, 24, and 36.ConclusionVirological reactivation is a risk for OBI patients. Serum hepatitis B surface antibodies were significantly increased after hepatitis B vaccine treatment, the same as the numbers of peripheral blood B and CD8+ T lymphocytes; changes in hepatitis B surface antibody levels were positively correlated with the changes in peripheral blood B and CD8+ T lymphocytes.

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Neonatal hepatitis B vaccination protects mature adults from occult virus infection

Cited by 7 publications

References 27 publications

The risk of occult HBV infection in HBcAb-positive general population: a systematic review and meta-analyses

The risk of occult HBV infection in HBcAb-positive general population: a systematic review and meta-analyses

Occult infection with hepatitis B virus PreS variants synergistically promotes hepatocellular carcinoma development in a high-fat diet context by generating abnormal ceramides

The Investigation of Hepatitis B Vaccine Immune Responses in Occult Hepatitis B Virus-Infected Patients

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