Epidemiology,Risk Factors and Genotypes of HBV in HIV-Infected Patients in the Northeast Region of Colombia: High Prevalence of Occult Hepatitis B and F3 Subgenotype Dominance

Introduction

Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission.

Objectives

Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city.

Methods

A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009–2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection.

Results

Participants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4–16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI.

Conclusions

The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients.     

Occult Hepatitis B Virus Infection in Anti-HBs-Positive Infants Born to HBsAg-Positive Mothers in China

Objective

To investigate the prevalence of occult HBV infection (OBI) among children and to characterize virology of occult HBV, we conducted an epidemiological survey.

Methods

186 HB-vaccinated infants born to HBsAg-positive mothers were included in the study. Serological tests for HBV markers were performed using commercial ELISA kits. Real-time quantitative PCR and nested PCR were used to detect HBV DNA. PCR products of the C and pre-S/S regions were sequenced and analyzed.

Results

1.61% (3/186) infants were HBsAg positive, and 4.92% (9/183) infants were considered as occult infection. The viral load of mothers was associated with occult infection (P = 0.020). Incomplete three-dose injections of HB vaccine was associated with HBV infection (P = 0.022). Six OBI infants were positive for anti-HBs, but their titers were not greater than 100 mIU/mL. Seven isolated HBV pre-S/S sequences were obtained from nine OBI infants. Three of the sequences were genotype C, and four of the sequences were genotype C/D. Escape mutation S143L was found in the four sequences of genotype C/D. All seven sequences lacked G145R and other escape mutation in S region.

Conclusions

Occult HBV infection was detected in anti-HBs positive infants born to HBsAg-positive mothers in China. Occult infection was associated with absent anti-HBs or with low anti-HBs level, high maternal viral loads and escape mutations in the S gene.     

A Bayesian Meta-Analysis on Prevalence of Hepatitis B Virus Infection among Chinese Volunteer Blood Donors

Background

Although transfusion-transmitted infection of hepatitis B virus (HBV) threatens the blood safety of China, the nationwide circumstance of HBV infection among blood donors is still unclear.

Objectives

To comprehensively estimate the prevalence of HBsAg positive and HBV occult infection (OBI) among Chinese volunteer blood donors through bayesian meta-analysis.

Methods

We performed an electronic search in Pub-Med, Web of Knowledge, Medline, Wanfang Data and CNKI, complemented by a hand search of relevant reference lists. Two authors independently extracted data from the eligible studies. Then two bayesian random-effect meta-analyses were performed, followed by bayesian meta-regressions.

Results

5957412 and 571227 donors were identified in HBsAg group and OBI group, respectively. The pooled prevalence of HBsAg group and OBI group among donors is 1.085% (95% credible interval [CI] 0.859%∼1.398%) and 0.094% (95% CI 0.0578%∼0.1655%). For HBsAg group, subgroup analysis shows the more developed area has a lower prevalence than the less developed area; meta-regression indicates there is a significant decreasing trend in HBsAg positive prevalence with sampling year (beta = −0.1202, 95% −0.2081∼−0.0312).

Conclusion

Blood safety against HBV infection in China is suffering serious threats and the government should take effective measures to improve this situation.     

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania

Background

Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania.

Methods

Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA.

Results

Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32–47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97–439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2–13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8–99.6%) and specificity at 100% (95% CI, 98.9–100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0–6.4%) of patients.

Conclusion

This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.     

Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial

Background

Hepatitis B virus (HBV) infection is endemic in South Africa however, there is limited data on the degree of liver disease and geographic variation in HIV/HBV coinfected individuals. In this study, we analysed data from the CIPRA-SA ‘Safeguard the household study’ in order to assess baseline HBV characteristics in HIV/HBV co-infection participants prior to antiretroviral therapy (ART) initiation.

Methods

812 participants from two South African townships Soweto and Masiphumelele were enrolled in a randomized trial of ART (CIPRA-SA). Participants were tested for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and HBV DNA. FIB-4 scores were calculated at baseline.

Results

Forty-eight (5.9%) were HBsAg positive, of whom 28 (58.3%) were HBeAg positive. Of those with HBV, 29.8% had an HBV DNA<2000 IU/ml and ALT<40 IU/ml ; 83.0% had a FIB-4 score <1.45, consistent with absent or minimal liver disease. HBV prevalence was 8.5% in Masiphumelele compared to 3.8% in Soweto (relative risk 2.3; 95% CI: 1.3–4.0). More participants in Masiphumelele had HBeAg-negative disease (58% vs. 12%, p = 0.002) and HBV DNA levels ≤2000 IU/ml, (43% vs. 6% p<0.007).

Conclusion

One third of HIV/HBV co-infected subjects had low HBV DNA levels and ALT while the majority had indicators of only mild liver disease. There were substantial regional differences in HBsAg and HbeAg prevalence in HIV/HBV co-infection between two regions in South Africa. This study highlights the absence of severe liver disease and the marked regional differences in HIV/HBV co-infection in South Africa and will inform treatment decisions in these populations.     

Hepatitis B Virus Infection in HIV-Positive Individuals in the UK Collaborative HIV Cohort (UK CHIC) Study

Background

Hepatitis B virus (HBV) infection is an increasingly important cause of morbidity and mortality in HIV-infected adults. This study aimed to determine the prevalence and incidence of HBV in the UK CHIC Study, a multicentre observational cohort.

Methods and Findings

12 HIV treatment centres were included. Of 37,331 patients, 27,450 had at least one test (HBsAg, anti-HBs or anti-HBc) result post-1996 available. 16,043 were white, 8,130 black and 3,277 other ethnicity. Route of exposure was homosexual sex 15,223 males, heterosexual sex 3,258 males and 5,384 females, injecting drug use 862 and other 2,723. The main outcome measures used were the cumulative prevalence and the incidence of HBV coinfection. HBV susceptible patients were followed up until HBsAg and/or anti-HBc seroconversion incident infection, evidence of vaccination or last visit. Poisson regression was used to determine associated factors. 25,973 had at least one HBsAg test result. Participants with HBsAg results were typically MSM (57%) and white (59%) (similar to the cohort as a whole). The cumulative prevalence of detectable HBsAg was 6.9% (6.6 to 7.2%). Among the 3,379 initially HBV-susceptible patients, the incidence of HBV infection was 1.7 (1.5 to 1.9)/100 person-years. Factors associated with incident infection were older age and IDU. The main limitation of the study was that 30% of participants did not have any HBsAg results available. However baseline characteristics of those with results did not differ from those of the whole cohort. Efforts are on-going to improve data collection.

Conclusions

The prevalence of HBV in UK CHIC is in line with estimates from other studies and low by international standards. Incident infection continued to occur even after entry to the cohort, emphasising the need to ensure early vaccination.     

High Prevalence of HIV, HCV, HBV and Co-Infection and Associated Risk Factors among Injecting Drug Users in Yunnan Province, China

Objective

To estimate the prevalence of HIV, HCV, HBV and co-infection with 2 or 3 viruses and evaluate risk factors among injecting drug users (IDUs) in Yunnan province, China.

Methods

2080 IDUs were recruited from 5 regions of Yunnan Province, China to detect the infection status of HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV). Statistical analysis was performed to evaluate risk factors related to HIV, HCV and HBV infections.

Results

The infection rates among all participants were 25.5% for HIV, 77.7% for HCV, 19.2% for HBV, 15% for HIV/HCV, 0.3% for HIV/HBV, 7.8% for HCV/HBV and 7.1% for HIV/HCV/HBV. The prevalence of virus infection varied widely by region in Yunnan of China. Statistical analyses indicated that high prevalence of HIV and HCV among IDUs was positively associated with the duration of drug injection and sharing needles/syringes; besides, HCV infection was associated with the frequency of drug injection.

Conclusions

HIV, HCV, HBV infections and co-infections were still very prevalent among IDUs in Yunnan province because of drug use behaviors.     

Correlation between Vertical Transmission of Hepatitis B Virus and the Expression of HBsAg in Ovarian Follicles and Placenta

Background

The aim of this study was to investigate the correlation between the expression of hepatitis B surface antigen (HBsAg) in human ovary and placenta and the vertical transmission of hepatitis B virus (HBV).

Methodology/Principal Fidnings

Ovarian and placental tissue specimens of pregnant women infected with HBV were collected during cesarean section and immunostained for HBsAg. The sera of the corresponding newborns were tested for HBV markers and HBV DNA. HBsAg was detected in 15 out of 33 (45%) placental tissues and was further detected in capillary endothelial cells in 4 specimens (26%), of which 3 (75%) corresponding infants were infected with HBV in utero. Out of the 33 ovarian tissues, 7 (21%) were positive for HBsAg, of which 2 (28%) showed HBsAg in ovarian follicles and the 2 corresponding infants (100%) had intrauterine HBV infection.

Conclusions/Significance

HBsAg expression in cells of the ovarian follicle or placental capillary endothelium signal a higher risk for intrauterine HBV infection.     

Effectiveness of HBV Vaccination in Infants and Prediction of HBV Prevalence Trend under New Vaccination Plan: Findings of a Large-Scale Investigation

Background

Hepatitis B virus (HBV) infection remains a severe public health problem. Investigating its prevalence and trends is essential to prevention.

Methods

To evaluate the effectiveness of HBV vaccination under the 1992 Intervention Program for infants and predicted HBV prevalence trends under the 2011 Program for all ages. We conducted a community-based investigation of 761,544 residents of 12 counties in Zhejiang Province selected according to their location, population density, and economic development. The HBV prevalence trends were predicted by a time-shifting approach. HBV surface antigen (HBsAg) and alanine amino transferase (ALT) were determined.

Results

Of the 761,544 persons screened for HBsAg, 54,132 were positive (adjusted carrier rate 6.13%); 9,455 had both elevated ALT and a positive HBsAg test (standardized rate 1.18%). The standardized HBsAg carrier rate for persons aged ≤20 years was 1.51%. Key factors influencing HBV infection were sex, age, family history, drinking, smoking, employment as a migrant worker, and occupation. With the vaccination program implemented in 2011, we predict that by 2020, the HBsAg carrier rate will be 5.27% and that for individuals aged ≤34 years will reach the 2% upper limit of low prevalence according to the WHO criteria, with a standardized rate of 1.86%.

Conclusions

The national HBV vaccination program for infants implemented in 1992 has greatly reduced the prevalence of HBV infection. The 2011 program is likely to reduce HBV infection in Zhejiang Province to a low moderate prevalence, and perinatal transmission is expected to be controlled by 2020.     

Association of T-Cell Immunoglobulin and Mucin Domain-Containing Molecule 3 (Tim-3) Polymorphisms with Susceptibility and Disease Progression of HBV Infection

Purpose

T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) plays an important role in regulating T cells in hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). However, few researches have reported the association of Tim-3 genetic variants with susceptibility and progression of HBV infection. In this study, we focused on the association of Tim-3 polymorphisms with HBV infection, HBsAg seroclearance and hepatocellular carcinoma.

Methods

A total of 800 subjects were involved in this study. Four groups were studied here, including HBV, HBsAg seroclearance, HBV-associated HCC and healthy controls. Three single-nucleotide polymorphisms (SNPs) of Tim-3, rs246871, rs25855 and rs31223 were genotyped to analyze the association of Tim-3 polymorphisms with susceptibility and disease progression of HBV infection.

Results

Our study found that rs31223 and rs246871 were associated with disease progression of HBV infection, while none of the three SNPs was relevant to HBV susceptibility. The minor allele “C” of rs31223 was found to be associated with an increased probability of HBsAg seroclearance (P = 0.033) and genotype “CC” of rs246871 to be associated with an increased probability of HBV-associated HCC (P = 0.007). In accordance, haplotypic analysis of the three polymorphisms also showed that the haplotype block CGC* and TGC* were significantly associated with HBsAg seroclearance (P<0.05) while haplotype block CAT*, CGT*, TAC* and TGT* were significantly associated with HBV-associated HCC (all P<0.05).

Conclusions

Genetic variants of Tim-3 have an important impact on disease progression of HBV infection. With specific Tim-3 polymorphisms, patients infected with HBV could be potential candidates of HCC and HBsAg seroclearance.     

Virus-Specific Immune Response in HBeAg-Negative Chronic Hepatitis B: Relationship with Clinical Profile and HBsAg Serum Levels

Background & Aims

The immune impairment characterizing chronic hepatitis B (cHBV) infection is thought to be the consequence of persistent exposure to viral antigens. However, the immune correlates of different clinical stages of cHBV and their relation with different levels of HBsAg have not been investigated. The aim of the present study was to evaluate the relationship between HBV-specific T cells response and the degree of in vivo HBV control and HBsAg serum levels in HBeAg-HBeAb+ cHBV.

Methods

Peripheral blood mononuclear cells from 42 patients with different clinical profiles (treatment-suppressed, inactive carriers and active hepatitis) of cHBV, 6 patients with resolved HBV infection and 10 HBV-uninfected individuals were tested with overlapping peptides spanning the entire HBV proteome. The frequency and magnitude of HBV-specific T cell responses was assessed by IFNγ ELISPOT assay. Serum HBsAg was quantified with a chemiluminescent immunoassay.

Results

The total breadth and magnitude of HBV-specific T cell responses did not differ significantly between the four groups. However, inactive carriers targeted preferentially the core region. In untreated patients, the breadth of the anti-core specific T cell response was inversely correlated with serum HBsAg concentrations as well as HBV-DNA and ALT levels and was significantly different in patients with HBsAg levels either above or below 1000 IU/mL. The same inverse association between anti-core T cell response and HBsAg levels was found in treated patients.

Conclusions

Different clinical outcomes of cHBV infection are associated with the magnitude, breadth and specificity of the HBV-specific T cell response. Especially, robust anti-core T cell responses were found in the presence of reduced HBsAg serum levels, suggesting that core-specific T cell responses can mediate a protective effect on HBV control.     

A common HLA-DPA1 variant is associated with hepatitis B virus infection but fails to distinguish active from inactive Caucasian carriers

Background and Aims

Chronic infection with the hepatitis B virus (HBV) is a major health issue worldwide. Recently, single nucleotide polymorphisms (SNPs) within the human leukocyte antigen (HLA)-DP locus were identified to be associated with HBV infection in Asian populations. Most significant associations were observed for the A alleles of HLA-DPA1 rs3077 and HLA-DPB1 rs9277535, which conferred a decreased risk for HBV infection. We assessed the implications of these variants for HBV infection in Caucasians.

Methods

Two HLA-DP gene variants (rs3077 and rs9277535) were analyzed for associations with persistent HBV infection and with different clinical outcomes, i.e., inactive HBsAg carrier status versus progressive chronic HBV (CHB) infection in Caucasian patients (n = 201) and HBsAg negative controls (n = 235).

Results

The HLA-DPA1 rs3077 C allele was significantly associated with HBV infection (odds ratio, OR = 5.1, 95% confidence interval, CI: 1.9–13.7; p = 0.00093). However, no significant association was seen for rs3077 with progressive CHB infection versus inactive HBsAg carrier status (OR = 2.7, 95% CI: 0.6–11.1; p = 0.31). In contrast, HLA-DPB1 rs9277535 was not associated with HBV infection in Caucasians (OR = 0.8, 95% CI: 0.4–1.9; p = 1).

Conclusions

A highly significant association of HLA-DPA1 rs3077 with HBV infection was observed in Caucasians. However, as a differentiation between different clinical courses of HBV infection was not possible, knowledge of the HLA-DPA1 genotype cannot be translated into personalized anti-HBV therapy approaches.     

Molecular Epidemiology and Genotyping of Hepatitis B Virus of HBsAg-Positive Patients in Oman

Background

Hepatitis B virus (HBV) infection is a major global health burden with distinct geographic public health significance. Oman is a country with intermediate HBV carrier prevalence; however, little is known about the incidence of HBV variants in circulation. We investigated the HBV genotype distribution, the occurrence of antiviral resistance, and HBV surface antigen (HBsAg) escape mutations in HBsAg-positive patients in Oman.

Methods

Serum samples were collected from 179 chronically HBV-infected patients enrolled in various gastroenterology clinics in Oman. HBV genotypes were determined by sequencing and phylogenetic analysis. Mutations in the HBV polymerase and the HBsAg gene were characterized by mutational analysis.

Results

HBV genotypes D (130/170; 76.47%) and A (32/170; 18.28%) are predominant in Oman. The HBV genotypes C and E were less frequent (each 1.18%), while the HBV genotypes B, G, F, and H were not detected. Four patients revealed HBV genotype mixtures (HBV-A/D and D/C). The analyses of vaccine escape mutations yield that 148/170 (87.06%) HBV sequences were wild type. 22/170 (12.94%) HBV sequences showed mutations in the “a” determinant of the HBsAg domain. Two patients showed the described HBV vaccine escape mutation sP120T. 8/146 (5.48%) HBV isolates harbored mutations in the HBV polymerase known to confer resistance against antiviral therapy. Especially the lamivudine resistance mutations rtL180M/rtM204V and rtM204I were detected.

Conclusion

This study shows the distribution of HBV genotypes, therapy resistance, and vaccine escape mutations in HBV-infected patients in Oman. Our findings will have a major impact on therapy management and diagnostics of chronic HBV infections in Oman to control HBV infection in this intermediate HBV-endemic country.     

Longitudinal Change of HBsAg in HBeAg-negative Patients with Genotype B or C Infection

Background & Aims

Quantitative HBsAg has been recognized to assist in the management of chronic hepatitis B virus (HBV) infection. However, its role in disease monitoring of HBeAg-negative patients remains unclear. We aimed to investigate the longitudinal HBsAg change in HBeAg-negative carriers with HBV genotype B or C infection.

Methods

This is a retrospective cohort study conducted in a university hospital. Treatment-naïve HBeAg-negative carriers followed for more than 3 years were recruited. Their hepatitis activities were categorized by longitudinal HBV-DNA levels into high viral-load (HVL: HBV-DNA >/ = 2000 IU/mL persistently), low viral-load (LVL: HBV-DNA <2000 IU/mL persistently) and fluctuated viral-load (FVL: HBV-DNA between HVL and LVL). The baseline and end-of-follow-up (EOF) HBsAg levels were quantified for analyses.

Results

We recruited 187 patients with a median follow-up of 8 years. LVL patients had a significantly lower HBsAg at baseline and EOF and a significantly greater annualized HBsAg decline compared with the FVL and HVL. The longitudinal HBsAg change was independent of genotype B or C. The lower baseline HBsAg level predicted the HBsAg decline and HBsAg loss, whereas the higher baseline HBV-DNA predicted the hepatitis flare. A baseline HBsAg <50 IU/mL predicted subsequent HBsAg loss with a sensitivity of 82% and specificity of 67%. The annualized HBsAg decline appeared non-linear, and accelerated as the HBsAg level lowered (0.054, 0.091, 0.126 log₁₀ IU/mL in patients with baseline HBsAg >1000, 100–999, <100 IU/mL, respectively, P for trend = .014).

Conclusions

In genotype B or C HBeAg-negative carriers, baseline HBsAg levels correlate with future disease activities and help to predict HBsAg decline or loss. Inactive carriers with lower baseline HBsAg levels have a greater and accelerating HBsAg decline over time, regardless of HBV genotypes.     

Investigation of Hepatitis B Virus and Human Immunodeficiency Virus Transmission among Severely Mentally Ill Residents at a Long Term Care Facility

Background

A high prevalence of hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections have been reported among persons with severe mental illness. In October, 2009, the Cook County Department of Public Health (CCDPH) initiated an investigation following notification of a cluster of HBV infections among mentally ill residents at a long term care facility (LTCF).

Methods

LTCF staff were interviewed and resident medical records were reviewed. Residents were offered testing for HBV, HCV, and HIV. Serum specimens from residents diagnosed with HBV or HIV infection were sent to the Centers for Disease Control and Prevention (CDC) for analysis.

Results

Eleven newly diagnosed HBV infections were identified among mentally ill residents at the LTCF. Of these 11 infections, 4 serum specimens were available for complete HBV genome sequencing; all 4 genomes were found to be closely related. Four newly diagnosed HIV infections were identified within this same population. Upon molecular analysis, 2 of 4 HIV sequences from these new infections were found to be nearly identical and formed a tight phylogenetic cluster.

Conclusions

HBV and HIV transmission was identified among mentally ill residents of this LTCF. Continued efforts are needed to prevent bloodborne pathogen transmission among mentally ill residents in LTCFs.     

Blood-Borne Hepatitis in Opiate Users in Iran: A Poor Outlook and Urgent Need to Change Nationwide Screening Policy

Objective

Iran has the highest rate of opiate use worldwide. However, most opiate users are not screened for hepatitis virus infections. This study aimed to provide accurate, detailed data on the size of the opiate user population at risk of developing these infections.

Method

This seroprevalence study was conducted in the city of Shiraz, southern Iran. All participants were screened for HBV, HCV and HIV infection. The data were analyzed with SPSS.

Result

Among 569 participants, 233 (40.9%) were injection drug users (IDU), 369 (64.8%) were heterosexual, 84 (14.7%) were bisexual and 15 (2.6%) were homosexual. One hundred nine (19.1%) were HCV antibody-positive, 18 (3.1%) were HBS antigen-positive, 72 (12.6%) were HBc antibody-positive and 23 (4%) were HIV-positive. Among IDU compared to non-IDU, positivity rates for HBS antigen (5.5 vs 1.4%), HBc antibody (22.7 vs 5.6%), HCV antibody (40.3 vs 4.4%) and HIV (7.7 vs 1.4%) were higher (P < 0.05). Most patients with HBV (80.7%) and HCV infection (83.4%) were HIV-negative. In the cumulative analysis, only history of imprisonment was a statistically significant determinant of infection by HCV or HBV in opiate users.

Conclusion

The current policy of screening only HIV-positive drug users for HBV and HCV in Iran misses most cases of HBV and HCV infection. We therefore recommend urgent revision of the nationwide protocol by the Ministry of Health in Iran to implement routine screening of all opiate users and especially IDU for these viruses, regardless of their HIV status.     

Inverse Association between Hepatitis B Virus Infection and Fatty Liver Disease: A Large-Scale Study in Populations Seeking for Check-Up

Background

Although many studies have attempted to clarify the association between hepatitis B virus (HBV) infection and fatty liver disease, no prior studies have emphasized the relationship of HBV and fatty liver regarding different demographics of age and body mass index (BMI).

Aim

To investigate the correlation of HBV and fatty liver in the different demographics of age and BMI.

Methods

We enrolled consecutive subjects who had received health check-up services at the Taipei Veterans General Hospital from 2002 to 2009 and ultrasonography was used to diagnose fatty liver according to the practice guidelines of the American Gastroenterological Association.

Results

Among the 33,439 subjects enrolled in this study, fatty liver was diagnosed in 43.9% of the population and 38.9% of patients with chronic HBV infection. Multivariate analysis showed that BMI, age, waist circumference, systolic blood pressure, fasting glucose, cholesterol, alanine aminotransferase (ALT) levels, and platelet counts were positively associated, while hepatitis B surface antigen (HBsAg) positivity was inversely associated with fatty liver, especially for subjects with BMI>22.4 kg/m² and age>50 years. On the contrary, HBV infection was positively correlated with the presence of elevated serum ALT levels in subjects with fatty liver disease regardless of their age and BMI.

Conclusions

Metabolic factors are important determinants for the prevalence of fatty liver. Patients with HBV infection were inversely associated with fatty liver disease than the general population, especially in older and obese patients. Furthermore, metabolic factors and HBV infection were associated with elevated serum ALT levels in fatty liver disease.     

HIV Induces TRAIL Sensitivity in Hepatocytes

Background

HIV infected patients have an increased susceptibility to liver disease due to Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), alcoholic, and non-alcoholic steatohepatitis. Clinically, this results in limited options for antiretroviral therapy and accelerated rates of liver disease, causing liver disease to be the second leading cause of death for HIV infected patients. The mechanisms causing this propensity for liver dysfunction during HIV remains unknown.

Methodology/Principal Findings

We demonstrate that HIV and/or the HIV glycoprotein gp120 ligation of CXCR4 on hepatocytes selectively up-regulates TRAIL R2 expression and confers an acquired sensitivity to TRAIL mediated apoptosis which is mediated by JNK II, but not p38 nor G-proteins.

Conclusions/Significance

These findings suggest that HIV infection renders hepatocytes more susceptible to liver injury during disease states associated with enhanced TRAIL production such as HBV, HCV, or steatohepatitis.