Hepatitis B Virus Monoinfection Research Articles

Association of hepatitis delta virus infection and hepatocellular carcinoma, hepatic decompensation, all-cause and liver-related death in a national cohort.

Hepatitis Delta Virus (HDV) infection is the most severe form of chronic hepatitis. However, studies on outcomes and causes of death in a United States-born population, with primarily horizontal transmission of HDV, are lacking. The aim of this study was to conduct a national study of patients with hepatitis D to understand the natural history and outcomes compared to patients with hepatitis B virus (HBV). infection. In a national cohort of 4,817 HBV infected veterans tested for HDV (99.6% US-born, 3.3% HDV positive) over a 23-year period, we used multivariable models to identify the factors associated with a composite outcome of hepatocellular carcinoma (HCC), decompensation, and liver-related mortality (LRM), as well as all-cause mortality of patients with HDV compared to HBV mono-infection. HDV coinfection (vs. HBV monoinfection) was associated with a significantly higher incidence of composite liver-related outcomes at both 5 (23.84 vs. 7.98, p<0.001), and 10 years (19.14 vs. 10.18, p<0.001) respectively. The most common cause of death was liver-related (33.8% for HDV vs. 24.7% for HBV), followed by non-hepatic malignancies, (15.6 vs. 14.8%),cardiac (11.7 vs. 15.2%), and lung disease (5.2 vs. 3.7%). In multivariable models, HDV was associated with an increased risk of composite liver outcomes (aHR 2.57, 95% CI 1.87-3.52, p<0.001), and all-cause mortality (aHR 1.52, 95% CI 1.20-1.93, p<0.001). In a predominantly U.S born cohort of Veterans, HDV co-infection was associated with an increased risk of liver-related outcomes and all-cause mortality. Our findings support widespread testing for early identification of HDV.

Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update.

The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Hepatitis Delta Virus and Hepatocellular Carcinoma.

The hepatitis D virus (HDV) is a compact, enveloped, circular RNA virus that relies on hepatitis B virus (HBV) envelope proteins to initiate a primary infection in hepatocytes, assemble, and secrete new virions. Globally, HDV infection affects an estimated 12 million to 72 million people, carrying a significantly elevated risk of developing cirrhosis, liver failure, and hepatocellular carcinoma (HCC) compared to an HBV mono-infection. Furthermore, HDV-associated HCC often manifests at a younger age and exhibits more aggressive characteristics. The intricate mechanisms driving the synergistic carcinogenicity of the HDV and HBV are not fully elucidated but are believed to involve chronic inflammation, immune dysregulation, and the direct oncogenic effects of the HDV. Indeed, recent data highlight that the molecular profile of HCC associated with HDV is unique and distinct from that of HBV-induced HCC. However, the question of whether the HDV is an oncogenic virus remains unanswered. In this review, we comprehensively examined several crucial aspects of the HDV, encompassing its epidemiology, molecular biology, immunology, and the associated risks of liver disease progression and HCC development.

Contribution of Hepatitis D Virus in Liver Cancer Among Hepatitis B Virus Infected Populations of Central Africa: A Systematic Review and Meta-Analysis

Background and aims: Hepatocellular carcinoma (HCC) is a rampant disease in sub-Saharan Africa. Viral hepatitis is currently the most common factor in the occurrence of HCC in sub-Saharan Africa. Hepatitis B virus (HBV) causes liver disease which may or may not progress to HCC. In a dual infection with Hepatitis D virus (HDV), HCC tends to have a faster turn out. Our aim is to evaluate the influence of HDV on the risk of HCC and elaborate on factors favouring HDV infection. Methods: A review of available literature in English or French was conducted in major data bases with the search terms “liver disease”, “hepatocellular carcinoma”, “hepatitis delta and liver disease”, “hepatitis D virus infection”, “prevalence of HDV”, and “hepatitis D in Central Africa”, and each term was associated to a central African country. A meta-analysis of included publications was then performed. Results: The prevalence of HDV was 28% (95% CI). There was a higher risk of HCC in HBV-HDV dual infection (OR: 0.82 [95% CI: -0.01 to 1.65]) compared to that in HBV mono-infection. HDV genotype 1 was found to be the most prominent in central Africa, with HDV subgenotypes 1a and 1b dominating. Hepatitis delta was more prevalent in rural areas than in urban areas. Conclusion: Hepatitis D is highly prevalent in the HBV population of central Africa. The presence of HDV increases the risk of HCC. More research has to be carried out to understand how HDV speeds up liver disease and hence how to prevent it.

Systemic cytokine and viral antigen-specific responses in hepatitis D virus RNA positive versus HDV RNA negative patients.

Hepatitis B virus (HBV)/Hepatitis D Virus (HDV) co-infection increases the risk of severe liver disease compared to HBV mono-infection. Adaptive immune responses to HDV are weakly detectable, and the involvement of innate immunity in the progression of HDV-related liver fibrosis is suggested. We hypothesize that an overall innate immune activation in HBV/HDV co-infection plays a role in liver disease progression and also impacts virus specific T cell response. Sixteen HBV/HDV-co-infected-patients (median age 42y/7F/6 Asian/4 White/6 Black/15 HBeAg-) and 8 HBV monoinfected-patients (median age 39y/4F/4 Asian/3 Black/1 White/HBeAg-) with median follow-up of 5 years were enrolled. Liver fibrosis was assessed by liver stiffness measurement (LSM, FibroScan®). Proliferation of CD3 + CD4+ T cells in response to viral antigens using CFSE assays and cytokine secreting monocytes was analyzed by flow cytometry. Of 16 HBV/HDV, 11 were HDV-RNA+ (HBV-DNA 0-1,040 IU/mL), 5/11 Interferon (IFN) + Nucleos/tide Analog (NA), 3/11 NA monotherapy, median ALT 77 U/L at the time of sample collection, median LSM of 9.8. In 5 HDV RNA-, median HBV DNA 65 IU/mL, 4/5 prior IFN and/or NA, ALT 31 U/L, and median LSM 8.5 kPa. In 8 HBV controls, median HBV-DNA, ALT, LSM was 69 IU/mL, 33 U/L,5 kPa, respectively. PBMC stimulation with HBV core antigen (HBcAg) and HDV antigen (HDAg) showed weaker CD3 + CD4 + T-cell proliferation in HDV-RNA+ vs. HDV RNA- and HBV-mono-infected patients (p < 0.05). In HDV-RNA+ patients, a correlation between ALT and TNF-α (r = 0.76, p = 0.008), higher IL-10 levels and increased proportion of CD14 + TNF-α+ cells were found. In summary, during HBV/HDV coinfection, HDV RNA+ patients had weaker HBV and HDV specific responses, associated with increased TNF-α + monocytes irrespective of IFN treatment.

Serum Metabolome Signatures Characterizing Co-Infection of Plasmodium falciparum and HBV in Pregnant Women.

Plasmodium falciparum (P. falciparum) and hepatitis B virus (HBV) co-infection is on the rise among pregnant women in northern Ghana. Mono-infection with either of these two pathogens results in unique metabolic alterations. Thus, we aimed to explicate the effects of this co-infection on the metabolome signatures of pregnant women, which would indicate the impacted metabolic pathways and provide useful prognostic or diagnostic markers. Using an MS/MS-based targeted metabolomic approach, we determined the serum metabolome in pregnant women with P. falciparum mono-infection, HBV mono-infection, P. falciparum, and HBV co-infection and in uninfected (control) women. We observed significantly decreased sphingolipid concentrations in subjects with P. falciparum mono-infection, whereas amino acids and phospholipids were decreased in subjects with HBV mono-infection. Co-infections were found to be characterized distinctively by reduced concentrations of phospholipids and hexoses (mostly glucose) as well as altered pathways that contribute to redox homeostasis. Overall, PC ae C40:1 was found to be a good discriminatory metabolite for the co-infection group. PC ae C40:1 can further be explored for use in the diagnosis and treatment of malaria and chronic hepatitis B co-morbidity as well as to distinguish co-infections from cases of mono-infections.

Human immunodeficiency virus coinfection differentially impacts hepatitis B virus viral markers based on hepatitis Be antigen status in patients with suppressed viremia.

Hepatitis B virus (HBV) RNA and hepatitis B core-related antigen (HBcrAg), reflecting transcriptional activity of covalently closed circular DNA, are gaining traction as important markers to assess viral activity. Whether their expression differs under viral suppression by HIV co-infection status is unknown. Among adults with chronic HBV on antiviral therapy, we sought to determine if the expression of HBV markers (specialized and well-established) differs between HBV-HIV co-infection vs. HBV mono-infection. We compared HBV marker levels among 105 participants in the Hepatitis B Research Network (HBRN) HBV-HIV Ancillary Study and 105 participants in the HBRN mono-infected Cohort Study, matched for HBeAg status and HBV DNA suppression on therapy. Among HBeAg+ participants (N = 58 per group), after adjusting for age, sex, race, ALT and HBV DNA, viral markers were higher (p < .05) in the HBV-HIV versus the HBV-only sample (HBeAg: 1.05 vs. 0.51 log10 IU/mL; HBsAg: 3.85 vs. 3.17 log10 IU/mL; HBV RNA: 5.60 vs. 3.70 log10 U/mL; HBcrAg: 6.59 vs. 5.51 log10 U/mL). Conversely, among HBeAg(-) participants (N = 47 per group), HBsAg (2.00 vs. 3.04 log10 IU/mL) and HBV RNA (1.87 vs. 2.66 log10 U/mL) were lower (p < .05) in HBV-HIV vs. HBV-only; HBcrAg levels were similar (4.14 vs. 3.64 log10 U/mL; p = .27). Among adults with chronic HBV with suppressed viremia on antiviral therapy, viral markers tracked with HIV co-infection status and associations differed inversely by HBeAg status. The greater sensitivity and specificity of HBV RNA compared to HBcrAg allows for better discrimination of transcriptional activity regardless of HBeAg status.

Distinct histological patterns in chronic hepatitis D with nucleos(t)ide analogue therapy.

Chronic hepatitis delta virus (HDV) infection leads to a more severe hepatitis than hepatitis B virus (HBV) infection alone. Specific histological staining patterns have been described in HBV mono-infection, however this has not been extensively investigated in HDV co-infection. This study evaluated whether the use of nucleos(t)ide analogs (NAs) for concurrent HBV infection has an impact on the histological appearance of chronic HDV. Liver biopsies of all patients referred for management of HDV infection were reviewed and hepatitis-specific stains for HBV antigens were evaluated. Clinical and histological characteristics were compared between patients on and off-NA therapy. 50 patients were included in our analysis, of which 26 (52%) were on NA therapy at the time of the biopsy. Overall, 8% stained for HBV core antigen and 86% stained for HBV surface antigen. On and off-NA groups had similar degrees of fibrosis and inflammation, however NA patients had an odds ratio of 7.15 for membranous staining and 0.13 for scattered granular staining (p = 0.001). No association was found with markers of disease severity or viral activity, with nonetheless a lower score of total inflammation noted in biopsies with a positive membranous stain (8.5 vs. 10.3 p = 0.04). In chronic HDV infection, patients treated with nucleos(t)ide analogs demonstrate a unique membranous staining pattern for hepatitis B surface antigen, which is not associated with HBV or HDV replicative activity. These findings may help improve the understanding of the role of HBV directed therapy in HDV pathophysiology. Histological staining is associated with viral activity in chronic HBV, however this has been infrequently explored in HDV. In HDV, staining patterns differ based on HBV treatment status and do not appear to be associated with markers of viral activity.

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil.

Evaluate the accuracy and agreement of two-dimensional shear-wave elastography (2D-SWE) LOGIQ-S8 with transient elastography in patients from Rio de Janeiro, Brazil. This retrospective study compared liver stiffness measurements (LSMs) using transient elastography (M and XL probes) and 2D-SWE GE-LOGIQ-S8 performed by a single experienced operator on the same day in 348 consecutive individuals with viral hepatitis or HIV infection. Suggestive and highly suggestive compensated-advanced chronic liver disease (c-ACLD) were defined by transient elastography-LSM ≥10 kPa and ≥15 kPa, respectively. Agreement between techniques and accuracy of 2D-SWE using transient elastography-M probe as the reference was assessed. Optimal cut-offs for 2D-SWE were identified using the maximal Youden index. Three hundred five patients [61.3% male, median age = 51 [interquartile range (IQR), 42-62] years, 24% with hepatitis C virus (HCV) ± HIV; 17% with hepatitis B virus (HBV) ± HIV; 31% were HIV mono-infected and 28% had HCV ± HIV post-sustained virological response] were included. The overall correlation (Spearman's ρ ) was moderate between 2D-SWE and transient elastography-M ( ρ = 0.639) and weak between 2D-SWE and transient elastography-XL ( ρ = 0.566). Agreements were strong ( ρ > 0.800) in people with HCV or HBV mono-infection, and poor in HIV mono-infected ( ρ > 0.400). Accuracy of 2D-SWE for transient elastography-M ≥ 10 kPa [area under the receiver operating characteristic (AUROC) = 0.91 (95% confidence interval [CI], 0.86-0.96); optimal cut-off = 6.4 kPa, sensitivity = 84% (95% CI, 72-92), specificity = 89% (95% CI, 84-92)] and for transient elastography-M ≥ 15 kPa [AUROC = 0.93 (95% CI, 0.88-0.98); optimal cut-off = 7.1 kPa; sensitivity = 91% (95% CI, 75-98), specificity = 89% (95% CI, 85-93)] were excellent. 2D-SWE LOGIQ-S8 system had a good agreement with transient elastography and an excellent accuracy to identify individuals at high risk for c-ACLD.

Management of HBV/HIV Co-Infection

Co-infection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) represents a complex and dispassionate challenge that demands a versatile approach. This abstract specifies a survey of key strategies for the administration of HBV/ HIV co-contamination, accompanied by a devoted effort to antiretroviral healing (ART), the HBV situation, and listening. Antiretroviral therapy is the foundation for directing hepatitis B virus (HBV)/HIV contamination. The incorporation of HIVHBV drugs into ART regimens is essential. Tenofovir-located regimens containing tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have proven to be effective against both viruses. Emtricitabine and lamivudine are frequently used in combination medicine. Monitoring drug opposition and energy abolition is achieved by guaranteeing the influence of the treatment. In HBV mono-infection, nucleotide analogs (NA) are used to restrain energetic copies. However, in cocontamination, NAs concede the possibility of ideally having a two-fold project against both HIV and HBV infection. TDF and TAF meet this necessity, making the ruling class the chosen choice. Regular listening is essential for evaluating the reaction to the situation and the progress of a liver ailment. This involves measuring the CD4 counts, HIV RNA levels, and HBV DNA levels. In addition, liver function tests and liver depictions help label cirrhosis and abnormal hepatocellular growth in animals. HBV immunization is essential for co-infected cells that are not resistant to HBV. Post-vaccination agents that negate the effect of an infection or poison titer should be restrained to ratify exemption. The prevention of broadcasting is another critical aspect of the administration. Safe sexuality practices and harm decline methods, including tease exchange programs for injecting drug use, detract from lowering the risk of transmission of the two viruses together.

Hepatitis B in Africa Collaborative Network: cohort profile and analysis of baseline data.

Approximately 80 million people live with chronic hepatitis B virus (HBV) infection in the WHO Africa Region. The natural history of HBV infection in this population is poorly characterised, and may differ from patterns observed elsewhere due to differences in prevailing genotypes, environmental exposures, co-infections, and host genetics. Existing research is largely drawn from small, single-centre cohorts, with limited follow-up time. The Hepatitis B in Africa Collaborative Network (HEPSANET) was established in 2022 to harmonise the process of ongoing data collection, analysis, and dissemination from 13 collaborating HBV cohorts in eight African countries. Research priorities for the next 5years were agreed upon through a modified Delphi survey prior to baseline data analysis being conducted. Baseline data on 4,173 participants with chronic HBV mono-infection were collected, of whom 38.3% were women and the median age was 34years (interquartile range 28-42). In total, 81.3% of cases were identified through testing of asymptomatic individuals. HBeAg-positivity was seen in 9.6% of participants. Follow-up of HEPSANET participants will generate evidence to improve the diagnosis and management of HBV in this region.

Impact of Hepatitis B Virus Infection, Non-alcoholic Fatty Liver Disease, and Hepatitis C Virus Co-infection on Liver-Related Death among People Tested for Hepatitis B Virus in British Columbia: Results from a Large Longitudinal Population-Based Cohort Study.

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine-Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.

State-of-the-art and emerging antivirals for chronic hepatitis B infection

ABSTRACT Introduction Current treatment options for chronic hepatitis B virus (HBV) infection cannot achieve functional cure [hepatitis B surface antigen (HBsAg) loss]; therefore, new approaches are under investigation. This review summarizes the most promising approaches in emerging antivirals against HBV, after search in Medline (2016–2022) and European and American liver meetings (2019–2022). Areas covered Classes of antivirals include entry inhibitors (bulevirtide), capsid assembly modulators (CAMs), translation inhibitors [small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs)], and HBsAg secretion inhibitors [nucleic acid polymers (NAPs)]. Bulevirtide has good efficacy in hepatitis B and D coinfection, but there is limited data in HBV monoinfection. CAMs profoundly reduce serum HBV DNA/RNA levels, but have minimal effects on antigen levels. siRNAs and ASOs mostly reduce HBsAg levels, but small proportions of patients reach HBsAg seroclearance. NAPs reduce serum HBV DNA and especially HBsAg levels offering substantial HBsAg seroconversion rates, but having limited data over a long period. Combinations of agents of different classes are starting to be evaluated. Expert opinion Continued efforts are required in order to address many unanswered questions about the optimal combined regimens of finite duration which will be safe and well tolerated achieving functional cure in a substantial proportion of chronic HBV patients.

Impact of potent nucleos(t)ide therapy on hepatitis B hospitalisations in Spain.

Chronic hepatitis B virus (HBV) infection is a major cause of decompensated cirrhosis and liver cancer worldwide. Newborn HBV vaccination was implemented in Spain two decades ago, and potent oral antivirals entecavir and tenofovir were introduced around 2007. To assess the clinical benefits of these interventions nationwide. Including HBV as a diagnosis, we performed a retrospective study of all hospitalisations in Spain the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 to 2017. From 73,939,642 nationwide hospital admissions during the study period, 129,634 (0.17%) included HBV as diagnosis. Their number doubled from 2007 to 2017 and the median age increased from 44 to 58 years. Most HBV admissions recorded chronic hepatitis B. In-hospital death occurred in 6.4%. Co-infection with HIV or hepatitis C virus occurred in 11.9% and 23.3%, respectively. Patients with HIV-HBV co-infection had significantly greater mortality than individuals with HBV mono-infection. The rate of HBV hospitalisations significantly increased over time with a transient drop around 2007, coincident with the arrival of new potent oral antivirals. Although the proportion of HBV hepatic decompensation events has declined, the rate of liver cancer continues to rise. The small subset of patients with hepatitis delta superinfection increasingly and disproportionately accounts for hepatic decompensation events and liver cancer. Hospital admissions of individuals with HBV infection are increasing in Spain. While hepatic decompensation events declined following the introduction of potent oral nucleos(t)ide therapy, HBV-related liver cancer is rising. No benefit of oral antiviral therapies is seen on hepatitis delta.

Assessment and validation of the TREAT-B score to assess the treatment eligibility of patients with chronic hepatitis B virus infection.

Access to Hepatitis B virus (HBV) DNA testing to determine treatment eligibility is limited in low-income countries. Therefore, this study aimed to assess and validate the TREAT-B score proposed as the treatment threshold in an Asian cohort in determining the HBV treatment eligibility. A retrospective analysis was conducted on consecutive patients with treatment-naïve chronic HBV mono-infection who visited the liver clinic at Chulalongkorn University Hospital, Bangkok, Thailand, from 2016 to 2020. The 2018 American Association for the Study of Liver Diseases guideline was the reference standard. Overall, 825 patients with chronic HBV infection were enrolled, comprising 409 (50.4%) males, with a median age of 50 (38-58) years. Of these, 216 (26.2%), 565 (68.5%), and 377 (45.7%) were eligible for treatment based on the AASLD, TREAT-B score, and simplified WHO criteria, respectively. The area under the receiver operating characteristics curve (AUROC) of the TREAT-B ≥ 2 was better than the simplified WHO criteria (0.69 vs. 0.62, p = 0.006) for selecting patients eligible for antiviral therapy. The sensitivity and specificity of the TREAT-B ≥ 2 were 96.3% and 41.4%, respectively. Applying the TREAT-B ≥ 3 improved the specificity (89.0%) and AUROC (0.80, 95% CI 0.76-0.84, but reduced the sensitivity (70.8%) for selecting eligible patients for HBV therapy. In resource-constrained countries where HBV DNA is unavailable, the TREAT-B score is an alternative criteria for indicating treatment eligibility. The TREAT-B score of ≥3 is highly accurate and may minimize the number of patients unnecessarily treated in Asian HBV patients.

Prevalence and Predictors of Liver Fibrosis in People Living with Hepatitis B in Senegal.

Hepatitis B virus (HBV) infection is the first cause of liver cirrhosis and cancer in West Africa. Although the exposure to additional environmental and infectious risk factors may lead to the faster progression of liver disease, few large-scale studies have evaluated the determinants of HBV-related liver fibrosis in the region. We used transient elastography to evaluate the prevalence of liver fibrosis and assessed the association between HBV markers and significant liver fibrosis in a cohort of people living with HBV in Dakar, Senegal. The prevalence of significant liver fibrosis was 12.5% (95% confidence interval [CI] 9.6%–15.9%) among 471 people with HBV mono-infection (pwHBV) and 6.4% (95% CI 2.6%–12.7%) in 110 people with HIV/HBV co-infection (pwHIV/HBV) on tenofovir-containing antiretroviral therapy (p = 0.07). An HBV viral load > 2000 IU/mL was found in 133 (28.3%) pwHBV and 5 (4.7%) pwHIV/HBV, and was associated with significant liver fibrosis (adjusted odds ratio (aOR) 1.95, 95% CI 1.04–3.66). Male participants (aOR 4.32, 95% CI 2.01–8.96) and those with elevated ALT (aOR 4.32, 95% CI 2.01–8.96) were especially at risk of having significant liver fibrosis. Our study shows that people with an HBV viral load above 2000 IU/mL have a two-fold increase in the risk of liver fibrosis and may have to be considered for antiviral therapy, independent of other disease parameters.

Different evolutionary dynamics of hepatitis B virus genotypes A and D, and hepatitis D virus genotypes 1 and 2 in an endemic area of Yakutia, Russia

BackgroundThe geographic distribution of the hepatitis B virus (HBV) and the hepatitis D virus (HDV) genotypes is uneven. We reconstructed the temporal evolution of HBV and HDV in Yakutia, one of the regions of Russia most affected by HBV and HDV, in an attempt to understand the possible mechanisms that led to unusual for Russia pattern of viral genotypes and to identify current distribution trends.MethodsHBV and HDV genotypes were determined in sera collected in 2018–2019 in Yakutia from randomly selected 140 patients with HBV monoinfection and 59 patients with HBV/HDV. Total 86 HBV and 88 HDV genomic sequences isolated in Yakutia between 1997 and 2019 were subjected to phylodynamic and philogeographic Bayesian analysis using BEAST v1.10.4 software package. Bayesian SkyGrid reconstruction and Birth–Death Skyline analysis were applied to estimate HBV and HDV population dynamics.ResultsCurrently, HBV-A and HDV-D genotypes are prevalent in Yakutia, in both monoinfected and HDV-coinfected patients. Bayesian analysis has shown that the high prevalence of HBV-A in Yakutia, which is not typical for Russia, initially emerged after the genotype was introduced from Eastern Europe in the fifteenth century (around 600 (95% HPD: 50–715) years ago). The acute hepatitis B epidemics in the 1990s in Yakutia were largely associated with this particular genotype, as indicated by temporal changes in HBV-A population dynamics. HBV-D had a longer history in Yakutia and demonstrated stable population dynamics, indicating ongoing viral circulation despite vaccination. No correlation between HBV and HDV genotypes was observed for coinfected patients in Yakutia (r = − 0.016069332). HDV-2b circulates in Russia in Yakutia only and resulted from a single wave of introduction from Central Asia 135 years ago (95% HPD: 60–350 years), while HDV-1 strains resulted from multiple introductions from Europe, the Middle East, Central Asia, and different parts of Russia starting 180 years ago (95% HPD: 150–210 years) and continuing to the present day. The population dynamics of HDV-1 and HDV-2 show no signs of decline despite 20 years of HBV vaccination. The Birth–Death Skyline analysis showed an increase in the viral population in recent years for both HDV genotypes, indicating ongoing HDV epidemics.ConclusionsTaken together, these data call for strict control of HBV vaccination quality and coverage, and implementation of HBV and HDV screening programs in Yakutia.

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

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. 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. 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%). 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.

Hepatitis B and Hepatitis C Virus Infection Promote Liver Fibrogenesis through a TGF-β1-Induced OCT4/Nanog Pathway.

Hepatitis B virus (HBV)/hepatitis C virus (HCV) coinfection accelerates liver fibrosis progression compared with HBV or HCV monoinfection. Octamer binding transcription factor 4 (OCT4) and Nanog are direct targets of the profibrogenic TGF-β1 signaling cascade. We leveraged a coculture model to monitor the effects of HBV and HCV coinfection on fibrogenesis in both sodium taurocholate cotransporting polypeptide-transfected Huh7.5.1 hepatoma cells and LX2 hepatic stellate cells (HSCs). We used CRISPR-Cas9 to knock out OCT4 and Nanog to evaluate their effects on HBV-, HCV-, or TGF-β1-induced liver fibrogenesis. HBV/HCV coinfection and HBx, HBV preS2, HCV Core, and HCV NS2/3 overexpression increased TGF-β1 mRNA levels in sodium taurocholate cotransporting polypeptide-Huh7.5.1 cells compared with controls. HBV/HCV coinfection further enhanced profibrogenic gene expression relative to HBV or HCV monoinfection. Coculture of HBV and HCV monoinfected or HBV/HCV coinfected hepatocytes with LX2 cells significantly increased profibrotic gene expression and LX2 cell invasion and migration. OCT4 and Nanog guide RNA independently suppressed HBV-, HCV-, HBV/HCV-, and TGF-β1-induced α-SMA, TIMP-1, and Col1A1 expression and reduced Huh7.5.1, LX2, primary hepatocyte, and primary human HSC migratory capacity. OCT4/Nanog protein expression also correlated positively with fibrosis stage in liver biopsies from patients with chronic HBV or HCV infection. In conclusion, HBV and HCV independently and cooperatively promote liver fibrogenesis through a TGF-β1-induced OCT4/Nanog-dependent pathway.

Tenofovir alafenamide: An initial experience at Groote Schuur Hospital, Cape Town, South Africa

Background. Hepatitis B virus (HBV) remains endemic in South Africa (SA), with a concomitantly high prevalence of HIV co-infection. Chronic kidney disease in these subpopulations also has a high prevalence. Tenofovir is an important component of management, but the associated risk of nephrotoxicity makes dosing a challenge in patients with impaired kidney function. A new formulation, tenofovir alafenamide fumarate (TAF), with a more favourable renal toxicity profile, is now available. Objectives. To evaluate our initial experience of TAF use at Groote Schuur Hospital, Cape Town. Methods. We retrospectively reviewed patients with HBV mono-infection and HIV-HBV co-infection who were initiated on TAF since 2018. We recorded all relevant demographic, serological, virological and biochemical data from patient records. Adherence was documented by pill collection at the pharmacy. Results. A total of 26 patients were included in the evaluation, median (interquartile range (IQR)) age 48 (39 - 51) years, 73% (n=19) male, 27% (n=7) hepatitis B e-antigen-positive, and 46% (n=12) HIV co-infected. The median (IQR) duration of treatment with TAF was 13 (9 - 15) months. The median (IQR) baseline creatinine level was 180 (130 - 227) µmol/L, with significant improvement at 12 months, 122 (94 - 143) µmol/L; p=0.017. Reflecting this change, the estimated glomerular filtration rate improved significantly from baseline to month 12 (42 (25 - 52) and 51 (48 - 68) mL/min/1.73 m2, respectively; p=0.023). Similarly, serum alanine aminotransferase (ALT) normalised from a baseline of 33 (18 - 52) to 18 (15 - 24) U/L at month 12 (p=0.012). HBV DNA viral load also declined, from a baseline of log10 4.04 (2.5 - 7.8) IU/mL to a median of &lt;log10 1.3 IU/mL at month 12. HIV viral load was less than the lower level of quantification at months 6 and 12. Conclusions. TAF was well tolerated, with stable and significantly improving kidney function throughout a 12-month follow-up period. Serum ALT normalised, mirrored by declining HBV viral load. HIV viral load remained undetectable at 6 and 12 months.