MicroRNA levels in patients with chronic hepatitis B virus and HIV coinfection in a high-prevalence setting; KwaZulu-Natal, South Africa.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infection are significant public health issues, despite the availability of an effective HBV vaccine for nearly three decades and the great progress that has been made in preventing and treating HIV. HBV and HIV both modulate micro-ribonucleic acids (microRNA) expression to support viral replication. The aim of this study was to describe the pattern of microRNA expression in patients coinfected with chronic HBV and HIV with varying disease severity, as indicated by Hepatitis B e antigen (HBeAg) status, HBV viral load, alanine transaminase (ALT) levels, and HIV viral load. METHODS: Plasma microRNAs, specific to HBV, were measured by quantitative real-time polymerase chain reaction (qRT-PCR) in HBV and HIV-negative healthy controls (n = 23) and patients coinfected with chronic HBV-HIV (n = 50). MicroRNA expression levels were compared between patients with high vs low HBV viral load, HBeAg positive vs HBeAg negative, high vs low ALT levels, and high vs low HIV viral load. Additionally, HBV viral load, ALT levels, and HIV viral load were correlated with microRNA expression levels. RESULTS: Significantly higher expression levels of selected microRNAs were observed in chronic HBV-HIV coinfected patients compared to healthy controls. Significantly higher expression levels of hsa-miR-122-5p, hsa-miR-192-5p, and hsa-miR-193b-3p were observed in patients with high HBV viral load compared with low HBV viral load patients, and the levels of these microRNAs were correlated with HBV viral load levels. Significantly higher levels of hsa-miR-15b-5p and hsa-miR-181b-5p were observed in HBeAg-negative patients. CONCLUSION: This study demonstrates the potential use of hsa-miR-15b-5p, hsa-miR-122-5p, hsa-miR-181b-5p, hsa-miR-192-5p and hsa-miR-193b-3p as additional diagnostic biomarkers in chronic HBV disease progression.

High prevalence of hepatitis B virus among MSM living with HIV in India.

People living with HIV (PWH) have been shown to bear a higher burden of hepatitis B virus (HBV) due to shared routes and risk factors for transmission. Populations such as men who have sex with men (MSM) are at an increased risk of both being infected with HBV and HIV, that places them at higher risk of hepatocellular carcinoma. Using weighted and adjusted multilevel logistic regression, we characterized the prevalence and correlates of hepatitis B surface antigen (HBsAg) among MSM living with HIV across 12 Indian cities from 2012 to 2013. Overall, the prevalence of HBsAg was 8% (range across cities: 0.5%-19%). Being between the ages of 25-34, and 35-44 increased the odds of having chronic HBV infection compared to MSM 24 years or younger. Daily or seasonal employment and being unemployed increased the odds of HBsAg prevalence compared to those with monthly or weekly wages. Sexual risk behaviours such as having had sex with both men and women in the prior 6 months and history of sex work increased the odds of having HBV. Ever having insertive sex with a man or hijra (assigned male at birth, currently identifies as female/nonbinary) was negatively associated with HBV. Despite the existence of efficacious vaccines, HBV continues to have high prevalence among PWHs. Programmes to increase early screening, vaccinations and HBV literacy are urgently needed. Integrating HBV and HIV programmes for MSM populations could be critical in addressing this dual burden and improving outcomes for both infections.

Seroprevalence of Hepatitis B virus and human immunodeficiency virus co-infection in pregnant women from Osun State, Nigeria.

INTRODUCTION: Hepatitis B virus and human immunodeficiency virus (HBV/HIV) co-infection is a global health concern due to its significant impact on morbidity and mortality. Reports of HBV/HIV co-infections are increasing in Nigeria, but information on the disease burden in pregnant women and its implications on the fetus is scarce. This study aimed to determine the prevalence of HBV/HIV co-infection in pregnant women. In addition, the study identified the risk factors for the disease in pregnant women attending antenatal clinics in Osun State, Nigeria. METHODOLOGY: We collected plasma samples from 303 consenting pregnant women and used enzyme-linked immunosorbent assay (ELISA) to test for HBV (HBsAg) and HIV I/II antigens. We obtained demographic and risk factor data on HBV and HIV transmission using a structured questionnaire. RESULTS: Our analysis revealed a prevalence of 3.96% for HBV/HIV co-infection in pregnant women. Bivariate analysis indicated a history of blood transfusion, oral or anal sex, and multiple sexual partners may be associated with an increased likelihood of HBV/HIV co-infection in pregnant women. After adjusting for other variables in multivariate analysis, none of these risk factors were significant at the 5% level. In contrast, formal education was a potential preventive factor in this population. CONCLUSIONS: Our study provides valuable information on the disease burden of HBV/HIV co-infection in pregnant women in Osun State, Nigeria, highlighting the importance of routine screening for HBV and HIV during antenatal care and emphasizing the importance of implementing preventive measures to reduce the morbidity and mortality associated with HBV/HIV co-infection.

Antenatal hepatitis B virus sero-prevalence, risk factors, pregnancy outcomes and vertical transmission rate within 24 months after birth in a high HIV prevalence setting.

BACKGROUND: Despite the availability of an effective vaccine, chronic hepatitis B virus (HBV) infections remain a major cause of liver cirrhosis and hepatocellular carcinoma. HBV burden in pregnancy, risk factors and the timing of mother to child transmission remain poorly described especially during this era of lifelong use of Tenofovir/Lamivudine/Efavirenz as firstline for HIV treatment. We aimed to determine the burden of HBV in pregnancy and infants receiving their first dose of HBV vaccine 6 weeks after birth in a high HIV-prevalence setting. METHODS: Pregnant women ≥ 20 weeks' gestational age were enrolled and followed up as mother-infant dyads from delivery, 6, 24 and 96 weeks after birth. HBV surface antigen (HBsAg) was tested (fresh plasma, immunochromatography) in pregnancy. Women testing HBsAg-seropositive were further evaluated for other four HBV-biomarkers. Maternally HBV exposed babies were tested for HBsAg from birth and HBs-antibodies from 6 months of age. Maternal-infant factors were tested in univariable and multivariable analyses for predictors of HBsAg-seropositivity. RESULTS: Six hundred HIV-uninfected and 608 HIV-infected women on Tenofovir/Lamivudine/Efavirenz-regimen with median (interquartile range) 350: (87-1477) days of therapy use were enrolled. The overall HBsAg-seroprevalence was 32/1208: 2.65%, 95% confidence interval (CI) [1.74, 3.55]; being 7/600: 1.17%, 95% CI [0.37, 1.97] and 25/608: 4.11%, 95% CI [2.52, 5.68] in HBsAg-monoinfected and HBsAg/HIV-coinfected respectively, disproportionately detected in 31/32: 96.9%, 95% CI [90.8, 100] women presumably HBV-unvaccinated in infancy. HBV exposed babies tended to be born prematurely (< 37 weeks); 15.2% versus 9.9% in the HBV-unexposed, p = 0.009. In multivariate logistic regression-models with variable elimination, HIV-infection and reported tooth extractions predicted antenatal HBsAg-seropositivity; odds ratios (CI): 3.85 (1.61-10.7) and 2.46 (1.07-5.34), respectively. None of the exposed infants were HBsAg-seropositive neither before nor after 6 weeks of age. No HBs-antibodies were detected in 23.3% of HBsAg-exposed infants at two years despite having successfully completed the HBV vaccination schedule. CONCLUSION: Low and moderate HBV endemics were observed in HIV-uninfected and HIV-infected pregnant women, respectively. This underscores the need to routinely screen for HBV in pregnancy, especially the HIV-infected attending antenatal-care. Being HIV-infected and reported tooth extractions were independent risk factors for maternal HBsAg-seropositivity. Vertical and child horizontal transmissions were both absent, probably due to ~ the 50% frequency of antenatal anti-HBe-antibodies observed. Of concern was the absence of anti-HBs-antibodies in 23.3% of fully vaccinated/maternally HBV-exposed infants by two years. Absence of molecular diagnosis may have underestimated HBV burden. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , trial registration number: NCT04087239.

Case report: An occult hepatitis B virus infection reactivation in an HIV/HCV coinfected patient during an immune reconstitution inflammatory syndrome.

The natural history of occult hepatitis B virus infection (OBI) and the mechanism involved in HBV reactivation are only partially understood. As regards people living with HIV (PLWH), HBV reactivation is estimated to occur with an incidence ratio of 0.019 cases per 100 person-year. Here we report the case of OBI reactivation in a HIV/HCV co-infected patient followed for 25 years at our Infectious Diseases Unit, but, unfortunately, lost to follow-up about 19 months after Direct-acting antivirals (DAAs) treatment. At re-engagement, blood tests showed high replication of plasmatic HIV-RNA along with severe immunosuppression and normal levels of liver enzymes. However, 3 months after ART reintroduction, an immune reconstitution inflammatory syndrome (IRIS) was diagnosed with high detectable HBV-DNA load and transaminase elevation. Our case report shows how the balance between the virus and the host immune system is quite a dynamic process that might significantly impact the course of the disease. The aim of this case report is to bring to the attention of physicians that, although OBI reactivation is a rather rare occurrence, even amongst PLWH, its potential consequences compel to a high alertness on the matter. Therefore, especially in patients with an impaired immune system and on a tenofovir or lamivudine-sparing regimen, HBV serological and virological markers should always be strictly monitored, even in the absence of a hepatitis flare.

Hepatitis B Virus Research in South Africa.

Despite being vaccine-preventable, hepatitis B virus (HBV) infection remains the seventh leading cause of mortality in the world. In South Africa (SA), over 1.9 million people are chronically infected with HBV, and 70% of all Black chronic carriers are infected with HBV subgenotype A1. The virus remains a significant burden on public health in SA despite the introduction of an infant immunization program implemented in 1995 and the availability of effective treatment for chronic HBV infection. In addition, the high prevalence of HIV infection amplifies HBV replication, predisposes patients to chronicity, and complicates management of the infection. HBV research has made significant progress leading to better understanding of HBV epidemiology and management challenges in the SA context. This has led to recent revision of the national HBV infection management guidelines. Research on developing new vaccines and therapies is underway and progress has been made with designing potentially curative gene therapies against HBV. This review summarizes research carried out in SA on HBV molecular biology, epidemiology, treatment, and vaccination strategies.

Hepatitis B Virus-related Care Quality in Patients With Hepatitis B/Human Immunodeficiency Virus Coinfection Versus Hepatitis B Monoinfection: A National Cohort Study.

BACKGROUND: Guideline-adherent hepatitis B virus (HBV) care is critical for patients with HBV, particularly patients with HBV-human immunodeficiency virus (HIV) given increased risks of liver-related complications. However, a comprehensive assessment of HBV-related care in patients with HBV-HIV is lacking. METHODS: We retrospectively assessed adherence to HBV-related care guidelines in all patients with HBV-HIV and HBV monoinfection (HBV-M) in the national Veterans Health Administration healthcare system in 2019. RESULTS: We identified 1021 patients with HBV-HIV among 8323 veterans with chronic HBV. Adherence to HBV guidelines was similar or better in HBV-HIV versus HBV-M, including HBV treatment (97% vs 71%), biannual hepatocellular carcinoma (HCC) surveillance (55% vs 55%) for patients with cirrhosis, hepatitis A virus screening (69% vs 56%), hepatitis C virus screening (100% vs 99%), and on-therapy alanine aminotransferase monitoring (95% vs 96%). Compared with those seeing gastroenterology (GI) or infectious diseases (ID) providers, patients without specialty care were less likely to receive antiviral treatment (none, 39%; GI, 80%; ID, 84%) or HCC surveillance (none, 16%; GI, 66%; ID, 47%). These findings persisted in multivariable analysis. Compared with ID care alone, a higher proportion of patients with HBV-HIV seen dually by GI and ID received HCC surveillance (GI + ID 73% vs ID 31%) and on-therapy HBV-DNA monitoring (GI + ID, 82%; ID, 68%). CONCLUSIONS: Patients with HBV-HIV received similar or higher rates of guideline-adherent HBV-related care than patients with HBV-M. Patients with HBV-HIV under dual GI and ID care achieved higher quality care compared with ID care alone. Specialty care was independently associated with higher quality HBV care in patients with HBV-HIV and HBV-M.

Evaluation of Hematological, Biochemical Profiles and Molecular Detection of Envelope Gene (gp-41) in Human Immunodeficiency Virus (HIV) among Newly Diagnosed Patients.

The Human Immunodeficiency Virus (HIV) is a highly morphic, retrovirus that rapidly evolves through mutation as well as recombination. Because of the immunocompromised status in HIV patients, there is often a higher chance of acquiring different secondary infections followed by liver cirrhosis, hepatitis B & C, and HIV-associated nephropathy. The current study was conducted to see the prevalence of secondary infections, hematological and biochemical markers for liver and renal associated diseases, and to detect the envelope gene (GP41) in newly diagnosed HIV patients. A total of 37 samples were collected from HIV-positive patients registered in different hospital settings under the National AIDS control program. The collected samples were processed for hepatitis B, hepatitis C, hematological analysis, and biochemical analysis. To identify the envelope gene in newly diagnosed HIV patients, polymerase chain reaction (PCR) was performed using four gene-specific primers. The HIV infections were seen more in male as compared to females. A significant decrease in complete blood count was observed in HIV patients when compared to healthy individuals. There was a significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine observed in HIV patients. No significant difference was observed in alkaline phosphatase (ALP), total bilirubin, and albumin levels when compared to healthy control. Anemia was observed in 59.4% of HIV patients. A total of three (8.1%) patients were found to be co-infected with hepatitis B and one (2.7 %) was co-infected with hepatitis C. Out of these 37 tested samples, a total of four showed the successful amplification of the envelope gene. This study provides platform for the health care facilitators to regularly monitor the signs, symptoms and clinical biomarkers of HIV-associated infections to prevent toxicity at an early stage to improve the quality of life (QoL) and minimize the mortality rate in HIV patients. Envelope gene mutating frequently results in drug resistance, and thus future research on polymorphism analysis will reveal points of substitutions to improve drug designing.

Hepatitis B virus genetic multiplicity and the associated HBV lamivudine resistance mutations in HBV/HIV co-infection in Western Kenya: A review article.

BACKGROUND: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) co-infections are common as the two viruses use same routes of transmission. Studies show that HIV infection modifies the natural course of chronic HBV infection, leading to more severe and progressive liver disease, and a higher incidence of cirrhosis, liver cancer and mortality. Therefore, determining HBV status and genotypes among HIV co-infected patients would improve their therapeutic management. OBJECTIVE: This article reviewed the HBV genetic multiplicity and the associated HBV Lamivudine resistance mutations in HBV/HIV co-infection in western Kenya. METHODS: Comprehensive literature searches and analysis were performed in peer-reviewed journals in the National council for biotechnology information (NCBI), PubMed, and Web of science using key words of HIV, Hepatitis B genotypes, HBV/HIV co-infection and Lamivudine resistance. RESULTS: HBV genotype A is predominant. D and E are also present in Kenya and neighboring countries in the region. HBV polymerase rtV173L, rtL180M, and rtM204V major substitutional mutations were identified. Currently, TDF + 3TC + DTG are recommended for treatment of HBV/HIV co-infection. CONCLUSION: Evidence shows that HBV/HIV co-infection places a heavy burden to the society. Along with ART regimen, HBV genotype is a major factor determining the course of disease and treatment outcome. Treating HIV in HBV/HIV co-infection with antiretroviral agents may result in a very high prevalence of HBV 3TC-resistance mutations. Therefore, improved screening for HBV and extended follow-up of HBV/HIV co-infected individuals is needed to better understand the impact of different ART regimens on clinical outcomes.

Performance of Serum-Based Scores for Identification of Mild Hepatic Steatosis in HBV Mono-infected and HBV-HIV Co-infected Adults.

BACKGROUND: There are limited data on noninvasive methods to identify hepatic steatosis in coexisting hepatitis B virus (HBV) infection. AIMS: To evaluate the diagnostic performance of noninvasive serum-based scores to detect steatosis using two distinct chronic HBV cohorts with liver histology evaluation. METHODS: Chronic HBV cohorts with untreated HBV mono-infection (N = 302) and with treated HBV-HIV (N = 92) were included. Liver histology was scored centrally. Four serum-based scores were calculated: hepatic steatosis index (HSI), nonalcoholic fatty liver disease Liver Fat Score (NAFLD-LFS), visceral adiposity index (VAI), and triglyceride glucose (TyG) index. Optimal cutoffs (highest sensitivity + specificity) to detect ≥ 5% HS, stratified by cohort, were evaluated. RESULTS: HBV-HIV (vs. HBV mono-infected) patients were older (median 50 vs. 43 years), and a higher proportion were male (92% vs. 60%), were black (51% vs. 8%), had the metabolic syndrome (41% vs. 25%), and suppressed HBV DNA (< 1000 IU/mL; 82% vs. 9%). Applying optimal cutoffs, the area under the receiver operator curve for detecting ≥ 5% steatosis in HBV-only and HBV-HIV, respectively, was 0.69 and 0.61 for HSI, 0.70 and 0.76 for NAFLD-LFS, 0.68 and 0.64 for TyG, and 0.68 and 0.69 for VAI. The accuracy of optimal cutoffs ranged from 61% (NAFLD-LFS) to 67% (TyG) among HBV-only and 56% (HSI) to 76% (NAFLD-LFS) among HBV-HIV. Negative predictive values were higher than positive predictive values for all scores in both groups. CONCLUSION: The relative utility of scores to identify steatosis in chronic HBV differs by co-infection/anti-HBV medication status. However, even with population-specific cutoffs, several common serum-based scores have only moderate utility. ClinicalTrials.gov NCT01924455.

Prevalence of Overt and Occult Hepatitis B Virus Infection among HIV-Positive People Referring to Consultation Center for Behavioral Diseases, Kurdistan Province, Iran

Background: Based on evidence, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) have common transmission routes; co-infection of HBV/HIV can dramatically increase disease progression. The present study aimed to determine the prevalence of overt HBV infection and occult hepatitis B virus infection (OBI) in HIV-positive people. Methods: In this descriptive study, whole blood samples were collected from 184 HIV-positive subjects referring to the Consultation Center for Behavioral Diseases, Sanandaj, Iran, during 2014 to 2016. ELISA was used for the determination of HBV serologic markers (hepatitis B surface antigen [HBsAg] and antibodies to hepatitis B virus core antigen [anti-HBc]). To evaluate OBI, DNA was extracted only from HBsAg-negative and anti-HBc-positive samples and tested for HBV DNA by real-time PCR. Test results and patients' data were analyzed by SPSS software. Results: The mean age of the study population was 39.2 ± 9.4 (SD) years, of whom 140 (76%) were male. Overall, 43 (23.3%) samples were positive for HBsAg (overt HBV infection), and 50 (27.2%) for anti-HBc. Among 31 HBsAg-negative and anti-HBc-positive samples (suspected OBI), one (3.2%) sample was positive for HBV DNA (verified seropositive OBI). HBV infection was higher among males (n = 37; 86.05%), jobless people (n = 23; 53.49%), and those with an injection HIV transmission route (n = 32; 74.43%). Conclusion: We observed a high prevalence of overt HBV and one OBI among the study population. A serologic marker such as anti-HBc indicates resolved or past HBV infection. Molecular screening for HBV is valuable for the management of HIV-infected people.

Epidemiology and Challenges of HBV/HIV Co-Infection Amongst HIV-Infected Patients in Endemic Areas: Review.

With the introduction of highly active antiretroviral treatment, HIV-related morbidity and mortality have declined. But underlying hepatitis B virus infection remains the major cause of AIDS-defined illness and liver-related disease progression mainly in endemic settings. Moreover, HBV-HIV co-infection is the leading cause of cirrhosis, hepatocellular carcinoma, and liver-related death. This review paper emphasizes reviewing the burden and impact of HBV-HIV co-infection in liver-related disease progression, immune recovery, and therapeutic management of HIV-infected individuals on ART regimen.

Impact of Immune Reconstitution-Induced Hepatic Flare on Hepatitis B Surface Antigen Loss in Hepatitis B Virus/Human Immunodeficiency Virus-1 Coinfected Patients.

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is an ideal goal for chronic hepatitis B patients. Antiretroviral therapy (ART) in hepatitis B virus/human immunodeficiency virus-1 (HBV/HIV-1)-coinfected patients can lead to hepatic flare (HF) caused by immune reconstitution-induced inflammatory syndrome (IRIS). Here, we investigated the impact of IRIS-HF on HBsAg loss. METHODS: This was a retrospective study of 58 HBV/HIV-1-coinfected subjects HBsAg-positive for ≥6 months before ART initiation and followed for ≥1 year (median 9.9 years) after ART initiation. We examined humoral factors in sera from healthy volunteers, HIV-monoinfected patients, and HBV/HIV-1-coinfected patients with IRIS-HF or acute hepatitis B infection. RESULTS: During ART, HBsAg loss was observed in 20 of 58 HBV/HIV-1-coinfected patients (34.5%). Of the 58 patients, 15 (25.9%) developed IRIS-HF within 12 months of ART initiation. HBsAg loss was more frequent among patients who developed IRIS-HF (11/15, 73.3%) than those who did not (9/43, 20.9%). Multivariate analysis showed IRIS-HF was an independent predictor of subsequent HBsAg loss. Younger age and higher baseline HBV DNA titer were associated with IRIS-HF. Elevation of sCD163, not CXCL9, CXC10, CXCXL11, or CXCL13, was observed at IRIS-HF. CONCLUSIONS: IRIS-HF was associated with HBsAg loss in HBV/HIV-1-coinfected patients.

Sero-prevalence of human immunodeficiency virus-hepatitis B virus (HIV-HBV) co-infection among pregnant women attending antenatal care (ANC) in sub-Saharan Africa (SSA) and the associated risk factors: a systematic review and meta-analysis.

BACKGROUND: There is plenitude of information on HIV infection among pregnant mothers attending antenatal care (ANC) in sub-Saharan Africa. However, the epidemiology of HBV-HIV co-infections in the same cohort is not clear despite the common route of transmission of both viruses. The aim of our study was to synthesize data on the prevalence of HBV-HIV co-infection among pregnant women attending ANC in Sub-Saharan Africa to assist in the design of public health interventions to mitigate the challenge. METHODS: The study was done in tandem with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) standards and the Cochran's Q test, I2 statistics for heterogeneity and the prevalence were calculated using commercially available software called MedCalcs ( https://www.medcalc.org ). A random effect model was used to pool the prevalence since all the heterogeneities were high (≥ 78%) and Phet < 0.05 indicated significant heterogeneities. The risk factors and risk differences for HBV-HIV co-infection were analyzed. Any likely sources of heterogeneity were analyzed through sensitivity analysis, meta-regression and sub-group analysis. All analyses were done at 95% level of significance and a P < 0.05 was considered significant. RESULTS: The overall pooled prevalence of HBV-HIV co-infection among pregnant mothers in sub-Saharan Africa was low 3.302% (95%CI = 2.285 to 4.4498%) with heterogeneities (I2) of 97.59% (P > 0.0001). Within regional sub group meta-analyses, West Africa had significantly higher prevalence of 5.155% (95% = 2.671 to 8.392%) with heterogeneity (I2) of 92.25% (P < 0.0001) than any other region (P < 0.001). Articles published from 2004-2010 had significantly higher prevalence of 6.356% (95% = 3.611 to 9.811%) with heterogeneity (I2) 91.15% (P < 0.0001) compared to those published from 2011 to 2019 (P < 0.001). The HIV positive cohort had significantly higher prevalence of HBV-HIV co-infection of 8.312% (95% CI = 5.806 to 11.22%) with heterogeneity (I2)94.90% (P < 0.0001) than the mothers sampled from the general population with a prevalence of 2.152% (95% CI = 1.358 to 3.125%) (P < 0.001). The overall and sub group analyses had high heterogeneities (I2 > 89%, P < 0.0001) but was reduced for South Africa (I2) = 78.4% (P = 0.0314). Age, marital status and employment were independent factors significantly associated with risk of HBV-HIV co-infection (P < 0.001) but not extent of gravidity and education level (P > 0.05). After meta-regression for year of publication and sample size for HBsAg positivity, the results were not significantly associated with HBV pooled prevalence for sample size (P = 0.146) and year of publication (P = 0.560). Following sensitivity analysis, the HBsAg pooled prevalence slightly increased to 3.429% (95% CI = 2.459 to 4.554%) with heterogeneity I2 = 96.59% (95% CI = 95.93 to 97.14%), P < 0.0001 CONCLUSION: There is an urgent need for routine HBV screening among HIV positive pregnant mothers attending antenatal care in sub-Saharan Africa to establish the extent of HBV-HIV co-infection in this cohort. Future studies need to investigate the putative risk factors for HBV-HIV co-infection and prioritize plausible control strategies.

Evaluation of HBV serological markers in treatment-naïve HBV mono-infected patients and HBV-HIV co-infected patients.

OBJECTIVES: Many studies have investigated the utility of hepatitis B virus (HBV) serological markers in HBV-infected patients. However, only a few studies have examined HBV serological markers in HBV-human immunodeficiency virus (HIV) co-infected patients. Here, we conducted a cross-sectional study to evaluate correlations of HBV serological markers in treatment-naïve HBV mono-infected patients and HBV-HIV co-infected patients. METHODS: HBsAg, HBV DNA, HBV RNA, and HBcrAg were quantified in 51 HBV mono-infected patients and 33 HBV-HIV co-infected patients recruited at Tianjin Second People's Hospital from 2016 to 2019. RESULTS: There was no significant difference in serum levels of HBV DNA (P = 0.056), HBV RNA (P = 0.387), HBcrAg (P = 0.714) and HBsAg (P = 0.165) between the patient groups. In HBV mono-infected patients, strong positive correlations were confirmed between HBV RNA and HBV DNA (r=0.620, P < 0.01), HBcrAg and HBV DNA (r=0.802, P < 0.001), and HBcrAg and HBV RNA (r=0.727, P < 0.01). In HBV-HIV co-infected patients, serum HBsAg was very strongly correlated with HBcrAg (r=0.838, P < 0.001). In HBeAg-positive HBV mono-infected patients, all HBV serological markers correlated with each other, whereas only HBV RNA correlated with HBcrAg in HBeAg-negative HBV mono-infected patients (r=0.688, P = 0.007). In HBeAg-positive HBV-HIV co-infected patients, only HBsAg correlated with HBcrAg (r=0.725, P<0.001), whereas HBcrAg and HBV RNA correlated with each other in HBeAg-negative patients (r = 0.683, P=0.010). Moreover, CD4 T-cell counts were not significantly associated with HBsAg, HBV DNA, HBV RNA, and HBcrAg levels. CONCLUSION: Compared with HBsAg and HBV DNA, which are widely used in clinical settings, our study confirmed that new HBV serological markers, such as HBV RNA and HBcrAg, have some utility in HBV mono-infected patients and HBV-HIV co-infected patients for monitoring the progression of liver disease.

Seroprevalence of hepatitis B virus: Findings from a population-based household survey in KwaZulu-Natal, South Africa.

BACKGROUND: Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality; however, little is known about the prevalence and distribution of HBV in some populations and regions. METHODS: A total of 9791 participants, 15-49 years old, were enrolled in a household survey in KwaZulu-Natal, South Africa. Peripheral blood samples were tested for markers of HBV (hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), antibody to HBeAg (anti-HBe)) and analysed, accounting for multilevel sampling and weighted to represent the population. RESULTS: Overall HBsAg prevalence was 4.0% (95% confidence interval (CI) 3.4-4.5%): 4.8% (95% CI 3.8-5.8%) in men and 3.2% (95% CI 2.5-3.9%) in women (p=0.01). Among HBsAg-positive participants, 35.2% (95% CI 29.2-41.2%) were HBeAg-positive and 66.3% (95% CI 60.1-72.4%) were anti-HBe-positive. HBsAg prevalence was 6.4% (95% CI 5.3-7.5%) among HIV-positive participants compared to 2.6% (95% CI 1.9-3.2%) among HIV-negative participants (p<0.01), and was higher among HIV-positive men (8.7%, 95% CI 6.3-11.2%) than among HIV-positive women (5.0%, 95% CI 3.8-6.2%) (p<0.01). CONCLUSIONS: HBV infection among HIV-positive men remains an important public health problem in communities in KwaZulu-Natal, South Africa. The prevalence of HBsAg and HBeAg highlight the importance of surveillance and an important missed opportunity for the scale-up of programmes to achieve the goal of controlling HBV for public health benefit.

HBV and HIV/HBV Infected Patients Have Distinct Immune Exhaustion and Apoptotic Serum Biomarker Profiles.

BACKGROUND: Hepatitis B virus (HBV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Due to their shared routes of transmission, approximately 10% of HIV-infected patients worldwide are chronically coinfected with HBV. Additionally, liver disease has become a major cause of morbidity and mortality in HBV/HIV coinfected patients due to prolonged survival with the success of antiretroviral therapy. The relationship between immune exhaustion markers (PD-1/PD-L1) and apoptotic markers such as Fas/FasL, TGFß1, TNF-α, and Th1/Th2 cytokines are not clearly delineated in HBV/HIV coinfection. METHODS: Levels of soluble Fas/FasL, TGFß1, TNF-α, and sPD-1/sPD-L1 as well as Th1 and Th2 cytokines were evaluated in the sera of HBV-monoinfected (n = 30) and HBV/HIV-coinfected (n = 15) patients and compared to levels in healthy controls (n = 20). RESULTS: HBV-monoinfected patients had significantly lower levels of the anti-inflammatory cytokine IL-4 (P < 0.05) and higher levels of apoptotic markers sFas, sFasL, and TGFß-1 (P < 0.001) compared to healthy controls. Coinfection with HIV was associated with higher levels of sFas, TNF-α, and sPD-L1 (P < 0.005), and higher levels of the pro-inflammatory cytokines IL-6, IL-8, and IL-12p70 (P < 0.05) compared to healthy controls. Patients with HBV infection had a unique biomarker clustering profile comprised of IFN-γ, IL12p70, IL-10, IL-6, and TNF-α that was distinct from the profile of the healthy controls, and the unique HIV/HBV profile comprised GM-CSF, IL-4, IL-2, IFN-γ, IL12p70, IL-7, IL-10, and IL-1ß. In HBV monoinfection a significant correlation between sFasL and PD1(r = 0.46, P = < 0.05) and between sFas and PDL1 (r = 0.48, P = <0.01) was observed. CONCLUSION: HBV-infected and HBV/HIV-coinfected patients have unique apoptosis and inflammatory biomarker profiles that distinguish them from each other and healthy controls. The utilization of those unique biomarker profiles for monitoring disease progression or identifying individuals who may benefit from novel immunotherapies such as anti-PD-L1 or anti-PD-1 checkpoint inhibitors appears promising and warrants further investigation.

Risk of Liver Fibrosis in Hepatitis B Virus and HIV Coinfected Youths Receiving Tenofovir-Containing Antiretroviral Regimen.

BACKGROUND: Hepatitis B virus (HBV) and HIV coinfection is associated with risk of progression to chronic liver disease. We assessed liver stiffness in HBV-HIV coinfected youths. METHODS: A cross-sectional study in HBV-HIV coinfected youths aged 18 to 25 years who received a tenofovir (TDF)-containing antiretroviral therapy regimen for >96 weeks. Measurements included HBV DNA level, HBV serology profiles, and transient elastography (TE). The cutoff for TE results included ≥5.9 kPa for F2-moderate fibrosis, ≥7.4 kPa for F3-severe fibrosis, and ≥9.6 kPa for F4-cirrhosis. RESULTS: From March to December 2016, 15 HBV-HIV coinfected youths with a median duration on TDF-containing regimens of 3.3 years were enrolled. Five (33%) youths had significant liver fibrosis, 3 with F2-moderate, 1 with F3-advanced fibrosis, and 1 with F4-cirrhosis. Other 5 without liver fibrosis had hepatitis B surface e antigen (HBsAg) and hepatitis B surface e antigen (HBeAg) loss. Higher mean alanine transaminase (ALT) was observed among the group with F2-F4 when compared to those with F0. CONCLUSION: Liver fibrosis was evidenced in HBV-HIV coinfected youths in Thailand. Transient elastography might be considered for those who do not achieve HBsAg loss or have persistent ALT elevation while on treatment.

Lamivudine plus tenofovir combination therapy versus lamivudine monotherapy for HBV/HIV coinfection: a meta-analysis.

BACKGROUND: Currently, there is no consensus on the efficacy and safety of lamivudine (LAM) plus tenofovir disoproxil fumarate (TDF) combination therapy versus lamivudine monotherapy in HBV/HIV coinfected patients. METHODS: A comprehensive literature search was performed in English and Chinese databases. Both relevant dichotomous and continuous variables were extracted, and the combined outcomes were expressed as a risk ratio (RR) or a standard mean difference (SMD). RESULTS: Eleven eligible studies were included in our analysis. For HBV-relevant outcomes, the proportion of patients with undetectable HBV, the rates of serum alanine aminotransferase (ALT) normalization and hepatitis B e antigen (HBeAg) loss were higher in the combination therapy group than the monotherapy group (RR = 1.42, 95% CI: 1.14-1.76, P = 0.002; RR = 1.36, 95% CI: 1.17-1.58, P < 0.0001; RR = 2.74, 95% CI: 1.20-6.22, P = 0.02). In addition, the rate of HIV RNA-negative conversion was higher in the combination therapy group than the monotherapy group (RR = 1.26, 95% CI: 1.11-1.42, P = 0.0003). CONCLUSION: LAM plus TDF combination therapy was more efficacious than LAM monotherapy in HBV/HIV coinfected patients. As time passes, this difference becomes more pronounced.

Management of hepatitis B in special populations.

Special populations infected with chronic HBV include those with decompensated cirrhosis, coinfections (HIV, HCV, HDV), hemodialysis and renal failure, immunosuppressed including transplant patients, children and women in pregnancy. These populations differ in their natural history and risk for liver-related complications, the indications for anti-HBV therapy as well as the recommendations regarding the HBV drugs used, duration of therapy and anticipated endpoints. Reflecting the special populations with substantive changes in management in recent years, this review focuses on HBV-HIV coinfected patients, immunosuppressed patients at risk for reactivation, liver transplant recipients and pregnant women. Management of women in the context of pregnancy and post-partum requires consideration of risks to mother and fetus/infant, including the risk of mother-to-child transmission. HBV-HIV coinfected patients require initiation of treatment concurrent with their HIV therapy and the HBV drugs used must by selected to minimize HIV and HBV resistance long-term. Increasing recognition of the risk for HBV reactivation with immunosuppressive therapy has led to recommendations to use prophylactic HBV therapy in patients with moderate to high risk of reactivation. Liver transplant recipients with HBV require life-long therapy to prevent or treat HBV infection but with current therapies, graft and patient survival are excellent.