Cases Of Chronic Hepatitis B Virus Infection Research Articles

Prevalence of Chronic Hepatitis B Virus Infection in Sierra Leone, 1997-2022: A Systematic Review and Meta-Analysis.

Hepatitis B virus (HBV) infection is a major public health problem in Sierra Leone, yet reliable estimates of cases are lacking. This study aimed to provide an estimate of the national prevalence of chronic HBV infection in the general population and select groups in Sierra Leone. We used the electronic databases PubMed/MEDLINE, Embase, Scopus, ScienceDirect, Web of Science, Google Scholar, and African Journals Online to systematically review articles reporting hepatitis B infection surface antigen seroprevalence estimates in Sierra Leone during 1997-2022. We estimated pooled HBV seroprevalence rates and assessed potential sources of heterogeneity. Of 546 publications screened, 22 studies with a total sample size of 107,186 people were included in the systematic review and meta-analysis. The pooled prevalence of chronic HBV infection was 13.0% (95% CI, 10.0-16.0) (I2 = 99%; Pheterogeneity < 0.01). During the study period, the HBV prevalence rates were as follows: 17.9% (95% CI, 6.7-39.8) before 2015, 13.3% (95% CI, 10.4-16.9) during 2015-2019, and 10.7% (95% CI, 7.5-14.9) during 2020-2022. The use of the 2020-2022 HBV prevalence estimates corresponded to 870,000 cases of chronic HBV infection (uncertainty interval, 610,000-1,213,000), or approximately one in nine people. The highest HBV seroprevalence estimates were among adolescents aged 10-17 years (17.0%; 95% CI, 8.8-30.5), Ebola survivors (36.8%; 95% CI, 26.2-48.8), people living with HIV (15.9%; 95% CI, 10.6-23.0), and those in the Northern Province (19.0%; 95% CI, 6.4-44.7) and Southern Province (19.7%; 95% CI, 10.9-32.8) regions. These findings may help inform national HBV program implementation in Sierra Leone.

Vertical transmission of hepatitis B virus from father to child: what can be concluded about this possibility?

Vertical hepatitis B virus (HBV) transmission is defined as transmission that occurs during pregnancy or postpartum from an HBV-infected mother to her fetus or child. It is an efficient route for the spread of HBV and is responsible for most of the cases of chronic HBV infection in adults. During pregnancy, vertical transmission can occur in the intrauterine phase, by placental infection via peripheral blood mononuclear cells, by placental leakage, or through female germ cells.The detection of HBV DNA in semen and spermatids from HBV-infected men has provided strong evidence that the male genital tract may act as a reservoir of the virus in HBV-infected men, supporting the possibility that vertical HBV transmission from an HBV-infected father to his child may also occur via the germ line at the time of fertilization, as occurs in HBV transmission from mother to child. Furthermore, it has been shown that integration of the HBV genome into the sperm cell genome can compromise sperm morphology and function and even cause hereditary or congenital biological effects in the offspring when an HBV-infected sperm fuses with an ovum.Since vertical HBV transmission from father to child can be a topic of interest and of global importance for controlling the spread of HBV, this article addresses the evidence supporting its occurrence via germ cells, the biological impact of integration of the HBV genome into the male germ cell genome, and the role of maternal immunoprophylaxis in vertical HBV transmission from father to child.

Paving the way towards hepatitis B virus-free generations in Africa

The children of Africa are in desperate need of protection from hepatitis B virus (HBV) infection. Globally, two-thirds of the estimated 1·5 million new cases of chronic HBV infection occurred in Africa in 2019.1 Most of these new infections in Africa are among young children, particularly newborn babies. Of children infected at birth, 90% remain infected with a 25% risk of premature death from HBV-related liver disease, including liver cancer. Despite this risk, less than 10% of newborn babies in Africa receive a timely HBV birth-dose vaccine (ie, within 24 h of birth).

Impact and cost-effectiveness of a national hepatitis B immunisation programme in China: a modelling study

BackgroundHepatitis B is a highly prevalent disease. About 257 million people are infected with hepatitis B virus (HBV), and more than 887 000 annual new acute or chronic cases of hepatitis B are recorded globally. HBV infection is also highly prevalent in China, where around 60 million people are positive for HBV antigens, and about 20 million people have chronic HBV infection. The Chinese government launched the national hepatitis B immunisation programme in 2002 that provides vaccination free of charge. Our study aimed to establish the effects of neonatal hepatitis B vaccine in China. MethodsFor our analysis, we obtained data on HBV infection cases from the China Epidemic Data Collection System and the China Public Health science data centre; data on costs related to HBV infection were acquired from a survey of the Evaluation Project of the National Immunisation Programme of China. We used a mathematical model and a decision tree-Markov model in this modelling study. In the mathematical model, nine compartments were expanded from a typical susceptible-exposed-infected-recovered model. In the decision tree-Markov model, eight Markov states were included to simulate hepatitis B virus infection and progression. We compared various intervention scenarios to establish the effects and cost-effectiveness of hepatitis B vaccination through the primary outcome of the study, incidence of HBV infection cases, which could provide evidence for exploring new prevention and control strategies. FindingsOur study estimated the number of chronic HBV infection cases from 1998 to 2018, and projected the prevalence of the epidemic in the following 30 years. Since the expanded immunisation plan began in 2008, the number of new acute hepatitis B cases decreased by 56·02% in 2018. Comparing the first scenario (status quo) with the second scenario (without any prior intervention), the model estimated that new chronic HBV infection cases have reduced by 95·13%. In other words, about 20·97 million new chronic HBV infection cases were averted because of hepatitis B vaccination. The cost-effectiveness analysis showed that the implementation of the neonatal hepatitis B vaccine strategy could increase effectiveness by 1·77 quality-adjusted life years (QALY) per capita; and although each person obtained a unit of QALY, the cost for the whole of society was a saving of US$8142·29. InterpretationOur findings supported the effectiveness of HBV vaccination in controlling the epidemic of hepatitis B after about 20 years of implementation of the national hepatitis B immunisation programme. Although China has achieved a great deal in hepatitis B prevention, the burden of this disease remains quite heavy in China, especially in terms of mother-to-child transmission. Therefore, more strategies need to be explored for controlling and eventually eliminating hepatitis B. FundingEvaluation Project of the National Immunisation Programme of China.

Association of LIN28B polymorphisms with chronic hepatitis B virus infection

BackgroundLIN28B is involved in multiple cellular developmental processes, tissue inflammatory response and tumourigenesis. The association of LIN28B polymorphisms with hepatitis B virus (HBV) infection remains unknown.MethodsThis study investigated the association of LIN28B rs314277, rs314280, rs369065 and rs7759938 polymorphisms in patients with chronic HBV infection, a major cause of liver disease including hepatocellular carcinoma (HCC). A total of 781 individuals including 515 cases of chronic HBV infection (91 asymptomatic carrier status, 128 chronic hepatitis, 127 cirrhosis and 169 HCC), 97 HBV infection resolvers and 169 healthy controls were investigated.ResultsLIN28 rs314280 genotypes GA + AA were higher in resolver and controls than patients (P = 0.011). Patients had significantly lower rs314280 allele A than resolvers (P = 0.031, OR 0.689, 95%CI 0.491–0.969) or controls (P = 0.034, OR 0.741, 95%CI 0.561–0.978). In dominant model, patients had significantly lower rs314280 genotypes AA+GA than controls (P = 0.008, OR 0.623, 95%CI 0.439–0.884). LIN28 rs7759938 genotypes TC + CC were higher in resolvers and controls than patients (P = 0.015). Patients had significantly lower rs7759938 allele C than resolvers (P = 0.048, OR 0.708, 95%CI 0.503–0.999). In dominant model, patients had significantly lower rs7759938 genotypes TC + CC than controls (P = 0.010, OR 0.632, 95%CI 0.445–0.897). Chronic hepatitis patients had lower frequency of rs369065 genotype TC than asymptomatic carriers, cirrhosis and HCC (P = 0.019).ConclusionsThese results suggest that LIN28 rs314280 and rs7759938 may be related to the susceptibility of chronic HBV infection. Further studies are warranted to examine the association of LIN28B polymorphisms with HBV-related diseases, especially HCC.

P378 Immunisation practices for hepatitis B and response to vaccination in Greek patients with inflammatory bowel disease

Low vaccination rates against hepatitis B virus(HBV) and sub-optimal response to vaccination are reported in patients with IBD. We initiated a multi-centre study in the metropolitan area of Athens, to assess: a)the percentage of IBD patients with protective anti-HBs levels and b)the response to vaccination. We reviewed the clinical records of all IBD patients with regular follow-up at 4 tertiary hospitals in Athens. All patients were tested for HBsAg, anti-HBs and anti-HBc antibodies. Patients with negative tests for both HBsAg and anti-HBc were managed as follows: a)negative anti-HBs without history of vaccination: 3-dose vaccination(0,1,6mo) with 20μg b)history of vaccination: anti-HBs levels >100 IU/l: annual follow-up of anti-HBs levels; anti-HBs 10–100 IU/l, 1–3 20μg doses with anti-HBs measurement after each dose; undetectable anti-HBs, 1–3 20μg doses with anti-HBs measurement after each dose. Vaccination was considered complete when anti-HBs>100 IU/l were detected. In patients with negative anti-HBs levels after 3x20μg doses, vaccination was repeated with a double dose(40μg) with anti-HBs measurement after each dose. Our study population consists of 686 IBD patients. Among those, 575 patients had recent HBV serology(84%). In our cohort we identified 8 cases of chronic HBV infection(HBsAg+) and 38 patients with previous exposure to HBV(HBsAg-, anti-HBc+). Protective immunity due to previous vaccination(HBsAg-, anti-HBc-, anti-HBs+>100 iu/l) was detected in 24%(n = 140). Sub-optimal anti-HBs levels were seen in 12%(n = 70). The majority of patients were negative for all three markers, indicating lack of effective vaccination(n = 319, 56%). Vaccination has been commenced in 243 patients. 206 patients completed their regimens. Response has been assessed in 177 patients: 106(60%) demonstrated sufficient response while 71 failed to develop immunity to HBV. Among non-responders, 39 received repeat vaccination, with 22 having achieved protective anti-HBs levels and 17 failing to respond again. There was a significant correlation between “low-tier”(only 5-ASA or no treatment) therapy at time of vaccination and successful response (p = 0.015). There was also strong association (p < 0.001) between age and presence of protective immunity, probably due to the application of HBV vaccination in the last 2 decades in Greece. A significant percentage of Greek IBD patients lack protective immunity against HBV. Classical vaccination regimen often fails to induce adequate levels of anti-HBs antibodies especially in cases that are receiving “high-tier” treatment (immunomodulation and/or immunosuppression). Increased awareness, intensified vaccination protocols and frequent testing of response may be required in this population.

Interleukin-1 gene cluster Haplotype analysis in the chronic outcome prediction of the Hepatitis B virus infection.

Hepatitis B virus (HBV) infection is well known as an important cause of the chronic liver disease. The screening of the genotype of certain cytokines might be helpful to predict the clinical outcome of an HBV infection. The present study investigates the relationship between the polymorphism and haplotypes of the Interleukin-1 (IL-1) gene family, including IL-1-alpha (IL-1A), IL-1-beta (IL-1B,) and IL-1 receptor antagonist (IL-1RN), with chronic HBV infection. A total of 297 chronic HBV and 333 matched on sex and age control individuals were genotyped using the standard sequence-specific-polymerase chain reaction primer (SSP-PCR) method. Four different haplotype analysis software packages were applied for data interpretation. The results showed excess genotype A1/A1 and A2/A2 at IL-1RN (40.2%, 39.9%), C/T at IL-1A-889 (55.6%), and C/C at IL-1B-511 (41.1%) in controls while A1/A1 at IL-1RN (59.3%), T/T at IL-1B-31 (46.5%), C/T at IL-1B + 3953 (65%), in chronic HBV infection cases. A total of 148 haplotypes were observed overall (96 in the case group and 89 in the control group). The haplotype combination of genotype A1/A1 at IL1-RN along with a C/T for all three IL-1B polymorphic positions and either C/T or T/T at the IL-1A-899 position may increase the probability of the chronic outcome for the HBV infection.

Effective antiviral therapy with entecavir in chronic hepatitis B virus carriers

To evaluate the short-term effect and safety of entecavir for the treatment of chronic hepatitis B (CHB) virus carriers. Ninety-three cases of CHB virus infection (hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-positive, hepatitis B core antibody (HBcAb)-positive, HBV DNA≥1x10(5) copies/mL) were divided into two groups: CHB virus carrier (47 cases) and CHB (46 cases). All of the 93 cases were given 0.5 mg entecavir orally once a day for 48 weeks. Virology, serology and biochemistry tests were perrmed at treatment weeks 0, 4, 12, 24 and 48. Side effects of entecavir and the incidence of liver cirrhosis and hepatocellular carcinoma were recorded. The CHB virus carrier and CHB group had complete virological response rates of 14.9% and 17.4% at week 4, 51.1% and 63.0% at week 12, 76.6% and 89.1% at week 24, and 97.9% and 100% at week 48, respectively; there was no significant difference between the two groups (P>0.05). The CHB virus carrier and CHB group had partial virological response rates of 42.6% and 47.8% at week 4, 57.44% and 65.2% at week 12, 85.0% and 89.1% at week 24, and 100% and 100% at week 48, respectively; there was no significant difference between the two groups (P>0.05). No cases in either group experienced virologic breakthrough during the treatment course. The CHB virus carrier and CHB group had serological response (HBeAg-negative) rates of 0 and 4.3% at week 4, 2.1% and 8.7% at week 12, 4.3% and 13.0% at week 24, and 8.5% and 21.7% at week 48, respectively; there was no significant difference between the two groups (P>0.05). The CHB virus carrier and CHB group had HBeAg seroconversion rates of 0 and 0 at week 4, 0 and 4.4% at week 12, 2.1% and 10.9% at week 24, and 6.4% and 17.4% at week 48, respectively; there was no significant difference between the two groups (P>0.05). No case in either group showed HBsAg-negativity and seroconversion during the treatment course. The CHB group had a biochemical response (alanine aminotransferase normalization) rate of 26.1% at week 4, 65.2% at week 12, 91.3% at week 24, and 97.8% at week 48.No case in either group showed biochemical breakthrough during the treatment course. There were no cases of liver cirrhosis or hepatocellular carcinoma in either group. There were no side effects of the entecavir treatment experienced in either group. Antiviral therapy with entecavir is effective, safe and well tolerated in CHB virus carriers.

Gene variation in IL10 and susceptibility to chronic hepatitis B

To evaluate the correlation between IL-10 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between IL-10 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. This study found that rs3024490 G/T allele, located in the intron 1 region and highly prevalent in Chinese populations, was significantly different between the chronic HBV infection cases and the acute infection controls in single allele analysis, genetic models analysis, and haplotypes analysis. This suggested that the rs3024490 within IL-10 was associated with susceptibility to chronic hepatitis B in a Chinese Han population.

Single nucleotide polymorphisms rs2120131, rs4935047, and rs7095891 in the MBL2 gene show no association with susceptibility to chronic hepatitis B in a Chinese Han population

Thus far, many studies have evaluated the correlation between MBL2 gene polymorphisms and hepatitis B infection. Tag single nucleotide polymorphisms (SNPs) were used to investigate the relationship between MBL2 gene polymorphisms and susceptibility to chronic hepatitis B virus (HBV) infection by comparing 996 chronic HBV infection cases to 301 acute infection controls. There was no significant correlation between rs2120131, rs4935047, and rs7095891 and chronic HBV infection. This suggested that the new SNPs within MBL2 were not associated with susceptibility to chronic hepatitis B in a Chinese Han population.

No association betweenIRF3polymorphism and susceptibility to hepatitis B virus infection in Chinese patients

To investigate the association between three tag single nucleotide polymorphisms (tagSNPs) in interferon regulatory factors (IRF3) and the genetic susceptibility to chronic hepatitis B virus (HBV) infection. We performed a case-control study of 985 Chinese cases of chronic HBV infection and 294 self-limiting HBV-infected individuals as controls. Three tagSNPs in IRF3 (rs10415576, rs2304204, rs2304206) were genotyped with the Multiplex SNaPshot technique. The genotype and allele frequencies were calculated and analyzed. The three SNPs showed no significant genotype/allele associations with chronic HBV infection. Overall allele P values were: rs10415576, P = 0.0908, odds ratio (OR) [95% confidence interval (CI)] = 1.1798 (0.9740-1.4291); rs2304204, P = 0.5959, OR (95% CI) = 1.0597 (0.8552-1.3133); rs2304206, P = 0.8372, OR (95% CI) = 1.0250 (0.8097-1.2976). Overall genotype P values were: rs10415576, P = 0.2106; rs2304204, P = 0.8458; rs2304206, P = 0.8315. There were no statistically significant differences between patients with chronic HBV infection and controls. Haplotypes generated by these three SNPs were also not significantly different between the two groups. The three tagSNPs of IRF3 are not associated with HBV infection in the Han Chinese population.

Tumour necrosis factor‐α‐857T allele reduces the risk of hepatitis B virus infection in an Asian population

Tumour necrosis factor-α (TNF-α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF-α-857 polymorphism and chronic HBV infection have reported conflicting results. So a meta-analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966-March, 2011) and the China Biological Medicine Database (January, 1978-March, 2011) were searched using the keywords TNF-α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta-analysis. All fourteen studies focussed on an Asian population. The overall meta-analysis suggested that TNF-α-857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71-0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy-Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68-0.98, P = 0.043; OR = 0.77, 95% CI: 0.68-0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70-0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF-α-857T allele reduces the risk of chronic HBV infection in this Asian population.

Hepatitis B Virus in the United States

Letters2 August 2011Hepatitis B Virus in the United StatesSu H. Wang, MD, MPH, Perry Pong, MD, and Henry Pollack, MDSu H. Wang, MD, MPHFrom Charles B. Wang Community Health Center, New York, NY 10013, and New York University School of Medicine, New York, NY 10016.Search for more papers by this author, Perry Pong, MDFrom Charles B. Wang Community Health Center, New York, NY 10013, and New York University School of Medicine, New York, NY 10016.Search for more papers by this author, and Henry Pollack, MDFrom Charles B. Wang Community Health Center, New York, NY 10013, and New York University School of Medicine, New York, NY 10016.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-3-201108020-00020 SectionsSupplemental MaterialAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This article has been corrected. The original version (PDF) is appended to this article as a supplement.TO THE EDITOR:We read Ioannou's article (1) with great interest. Accurate estimates of hepatitis B virus (HBV) infection and immunity are important for targeting disease prevention and treatment efforts. Because persons of Asian and Pacific Islander descent account for more than 50% of cases of chronic HBV infection in the United States (2), the underrepresentation of these populations in Ioannou's study should not be downplayed. Asians and Pacific Islanders make up 5% of the U.S. population but are classified as “other race” ...

The tumour necrosis factor‐α‐238A allele increases the risk of chronic HBV infection in European populations

Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966-August, 2010) and China Biological Medicine Database (January, 1978-August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07-4.58, P = 0.032; OR = 4.46, 95% CI: 1.75-11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.

Relationship between TNF-&lt;alpha&gt; Gene Promoter Polymorphisms and Outcomes of Hepatitis B Virus Infections: A Meta-Analysis

BackgroundThe clearance of hepatitis B virus (HBV) is a complex process which may be influenced by many factors including polymorphisms in the tumor necrosis factor <alpha> (TNF-<alpha>) gene promoter. However, previous reports regarding the relationship between polymorphisms in the TNF-<alpha> promoter and HBV clearance have been inconsistent. Therefore, we performed a meta-analysis on a large population to address this inconsistency.MethodsA meta-analysis was performed to examine the association between TNF-<alpha> promoter polymorphisms (-1031T/C, -863C/A, -857C/T, -308G/A and-238G/A) and chronic hepatitis B infection. Odds ratio (OR) and its 95 % confidence interval (CI) were used.ResultsTwelve studies were chosen in our meta-analysis, involving 2,754 chronic HBV infection cases and 1,630 HBV clearance cases. The data showed that TNF-<alpha>-863 CC genotype was significantly associated with HBV clearance (-863 CC vs. AA: OR, 0.64; 95% CI, [0.42, 0.97]; p = 0.04) while patients carrying -308 GG genotype had a significantly increased risk of HBV persistence compared with those with GA or AA genotype (GG vs. GA+AA: OR, 1.35; 95% CI, [1.08, 1.70]; p = 0.01). For the other polymorphisms, no association with HBV infection outcome was found.ConclusionsThe data showed that polymorphisms -863 A and -308 G in the TNF-<alpha> gene promoter region might be risk factors for HBV persistence. Furthermore, ethnicity might play an important role in HBV infection outcome, leading to conflicting results. More studies on individuals from various ethnic groups will be necessary to determine the role of TNF-<alpha> promoter polymorphisms in the outcome of HBV infection.

Liver HLA-G expression is associated with multiple clinical and histopathological forms of chronic hepatitis B virus infection

As the mechanisms leading to the persistence of hepatitis B virus (HBV) infection are poorly understood and as the histocompatibility leucocyte antigen (HLA)-G is well described as a tolerogenic molecule, we evaluated HLA-G expression in 74 specimens of HBV liver biopsies and in 10 specimens obtained from previously healthy cadaver liver donors. HBV specimens were reviewed and classified by the METAVIR score, and HLA-G expression was assessed by immunohistochemistry. No HLA-G expression was observed in control hepatocytes. In contrast, 57 (77%) of 74 HBV specimens showed soluble and membrane-bound HLA-G expression in hepatocytes, biliary epithelial cells or both. No associations between the intensity of HLA-G expression and patient age or gender, HBeAg status, severity of liver fibrosis, and grade of histological findings were observed. Although significance was not reached (P = 0.180), patients exhibiting HLA-G expression presented a higher median HBV DNA viral load (10⁵ copies/mL) than those who did not express HLA-G (10(3.7) copies/mL). These results indicate that HLA-G is expressed in most cases of chronic HBV infection in all stages and may play a role in the persistency of HBV infection.

Tumor necrosis factor-α-308A allele may have a protective effect for chronic hepatitis B virus infection in Mongoloid populations

Previous studies on the tumor necrosis factor-alpha (TNF-alpha)-308 gene promoter polymorphism in chronic hepatitis B virus (HBV) infection have reported conflicting results. We carried out a meta-analysis of 21 studies in relation to the TNF-alpha-308 gene promoter, involving a total of 4230 chronic HBV infection cases and 2905 controls. The overall meta-analysis indicated that -308A heterozygotes (GA) had a significant 27% decreased risk of developing chronic hepatitis B (CHB) (odds ratio (OR) 0.73; 95% confidence interval (CI) 0.57-0.93; p=0.012). For -308A allele homozygotes (AA) and carriers (GA+AA), the pooled odd ratios both indicated a significantly decreased risk of CHB (OR 0.28; 95% CI 0.19-0.43; p=0.0001; and OR 0.70; 95% CI 0.55-0.89; p=0.004, respectively). In subgroup analyses by ethnicity, a significantly decreased risk was associated with -308 variant genotypes (GA and AA) in Mongoloid populations in all genetic models. However, no significant associations were found in Caucasoids. Moreover, in the subgroup analyses by control group, significantly decreased risk was associated with -308 variant genotypes (GA and AA) in the group of spontaneously recovered cases in all genetic models; however, no significant associations were found in the group of healthy cases. The TNF-alpha-308A allele is a protective factor for chronic HBV infection, especially in Mongoloids.

Long‐Term Benefit of Hepatitis B Vaccination among Children in Thailand with Transient Hepatitis B Virus Infection Who Were Born to Hepatitis B Surface Antigen–Positive Mothers

Transmission of hepatitis B virus (HBV) from carrier mothers to their babies appears to be one of the most important factors influencing the prevalence of chronic HBV infection in areas of high hepatitis B endemicity. Infants born to HBV surface antigen (HBsAg)-positive mothers who were or were not positive for HBV e antigen (HBeAg) or to mothers who were negative for both HBsAg and HBeAg have been followed for 17 years for serological evidence of HBV infection. These infants were divided into 2 groups on the basis of their hepatitis B vaccination protocols: group 1 received vaccine at birth and 1, 2, and 12 months later, and group 2 received vaccine at birth and 1 and 6 months later. Follow-up involved annual clinic visits, during which a blood sample was taken and analyzed for the presence of HBsAg, antibody to HBsAg, and antibody to HBV core antigen (HBcAg). Selected blood samples that tested positive for HBV markers during 2 consecutive visits separated by a long interval were further investigated by polymerase chain reaction to detect HBV DNA. Transient presence of HBsAg or transient and/or long-term presence of antibody to HBcAg suggested that this population was heavily exposed to HBV during the follow-up period. Despite these findings, no new cases of chronic HBV infection were observed. None of the subjects with transient presence of HBsAg had any clinical symptoms of liver disease. This study demonstrates the efficacy of the HBV vaccine and its ability to protect against symptomatic disease.

Integrin alpha V polymorphisms and haplotypes in a Korean population are associated with susceptibility to chronic hepatitis and hepatocellular carcinoma

Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin alpha(V) (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV-infected hepatocellular carcinoma (HCC). Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV-infected HCC and 107 cases of acute self-limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip. The ITGAV intron SNPs rs9333289 and rs11685758, the 3'-untranslated region SNP rs1839123 and haplotype 3 (T-T-A) were associated with enhanced susceptibility to HBV-infected HCC (OR=1.75-2.42; P=0.02-0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV-infected HCC (OR=1.73-2.01; P=0.01-0.04). In addition, both rs2290083 and ht1 (C-C-G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39-1.62, P=0.04-0.01) ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV-infected HCC.

Role of serum prothrombin induced by vitamin K absence or antagonist-II in the early detection of hepatocellular carcinoma in patients with chronic hepatitis B virus infection

Objective. The role of serum prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) in the early detection of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection has not yet been clearly identified. The purpose of the study was to evaluate the sensitivity and specificity of PIVKA-II, alone or in combination with alpha-fetoprotein (AFP), for the detection of HCC during surveillance, and to determine whether PIVKA-II was a significant risk factor for patient survival. Material and methods. During surveillance, 106 HCC cases and 100 non-HCC cases of chronic HBV infection were included. Sensitivity and specificity of AFP and PIVKA-II were obtained through cut-off values of 20 ng/ml and 40 mAU/ml, respectively. The Cox proportional hazards model was used to determine whether PIVKA-II would be a significant risk factor for patient survival. Results. The sensitivity rates of AFP and PIVKA-II were 57.5% (61/106) and 51.9% (55/106), respectively. Of 45 patients negative for AFP, 22 were positive for PIVKA-II. A combination of AFP and PIVKA-II increased the sensitivity to 78.3% (83/106). The specificities of AFP and PIVKA-II were 88.0% and 97.0%, respectively. PIVKA-II was not a significant risk factor for patient survival after multivariate analysis. Conclusions. PIVKA-II can be used as a tumor marker for the early detection of HCC in patients with chronic HBV infection, especially in combination with AFP.