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Background and Aims: Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV., Methods: This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg., Results: Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p < 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels., Conclusion: HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Background & Aims: The contribution of the novel biomarkers, hepatitis B virus (HBV) RNA and HBV core-related antigen (HBcrAg), to characterization of HBV-human immunodeficiency virus (HIV) coinfection is unclear. We evaluated the longitudinal dynamics of HBV RNA and HBcrAg and their association with classical HBV serum biomarkers and liver histology and viral staining., Methods: HBV-HIV co-infected adults from 8 North American centers entered a National Institutes of Health-funded prospective cohort study. Demographic, clinical, serological, and virological data were collected at entry and every 24 to 48 weeks for up to 192 weeks. Participants with HBV RNA and HBcrAg measured ≥2 times (N = 95) were evaluated; 56 had paired liver biopsies obtained at study entry and end of follow-up., Results: Participants had a median age of 50 years; 97% were on combination anti-viral therapy. In hepatitis B e antigen (HBeAg)+ participants, there were significant declines in HBV RNA and HBcrAg over 192 weeks that tracked with declines in HBeAg, hepatitis B surface antigen, HBV DNA, and hepatitis B core antigen (HBcAg) hepatocyte staining grade (all P < .05). In HBeAg- participants, there were not significant declines in HBV RNA (P = .49) and HBcrAg (P = .63), despite modest reductions in hepatitis B surface antigen (P < .01) and HBV DNA (P = .03). HBV serum biomarkers were not significantly related to change in hepatic activity index, Ishak fibrosis score, or hepatocyte HBcAg loss (all P > .05)., Conclusions: In HBV-HIV coinfected adults on suppressive dually active antiviral therapy, the use of novel HBV markers reveals continued improvement in suppression of HBV transcription and translation over time. The lack of further improvement in HBV serum biomarkers among HBeAg- patients suggests limits to the benefit of combination anti-viral therapy and provide rationale for additional agents with distinct mechanisms of action., (Copyright © 2023. Published by Elsevier Inc.)

Background: Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients., Methods: We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients., Results: Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients., Conclusion: Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents "low hanging fruit," given the clear benefits of antiviral therapy in mitigating disease progression., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hepatitis B coinfection is common in HIV-positive individuals and as antiretroviral therapy has made death due to AIDS less common, hepatitis has become increasingly important. Several drugs are available to treat hepatitis B. The most potent and the one with the lowest risk of resistance appears to be tenofovir (TDF). However there are several questions that remain unanswered regarding the use of TDF, including the proportion of patients that achieves suppression of HBV viral load and over what time, whether suppression is durable and whether prior treatment with other HBV-active drugs such as lamivudine, compromises the efficacy of TDF due to possible selection of resistant HBV strains., Methods: A systematic review and meta-analysis following PRISMA guidelines and using multilevel mixed effects logistic regression, stratified by prior and/or concomitant use of lamivudine and/or emtricitabine., Results: Data was available from 23 studies including 550 HBV/HIV coinfected patients treated with TDF. Follow up was for up to seven years but to ensure sufficient power the data analyses were limited to three years. The overall proportion achieving suppression of HBV replication was 57.4%, 79.0% and 85.6% at one, two and three years, respectively. No effect of prior or concomitant 3TC/FTC was shown. Virological rebound on TDF treatment was rare., Interpretation: TDF suppresses HBV to undetectable levels in the majority of HBV/HIV coinfected patients with the proportion fully suppressed continuing to increase during continuous treatment. Prior treatment with 3TC/FTC does not compromise efficacy of TDF treatment. The use of combination treatment with 3TC/FTC offers no significant benefit over TDF alone.

Relatively little is known about the role of hepatitis B virus (HBV) genotype G (HBV/G) in patients co-infected with human immunodeficiency virus (HIV) and HBV. This study examined the prevalence and association of HBV/G to liver fibrosis in co-infected patients. HBV genotypes were determined by direct sequencing of the HBV surface gene or Trugene® HBV 1.0 assay in 133 patients infected with HIV/HBV. Quantitative testing of HBV-DNA, HBeAg, and anti-HBe were performed using the Versant® HBV 3.0 (for DNA) and the ADVIA®Centaur assay. The non-invasive biomarkers Fib-4 and APRI were used to assess fibrosis stage. Genotype A was present in 103/133 (77%) of the cohort, genotype G in 18/133 (14%) with genotypes D in 8/133, (6%), F 2/133 (1.5%), and H 2/133 (1.5%). Genotype G was associated with hepatitis B e antigen-positivity and high HBV-DNA levels. Additionally, HBV/G (OR 8.25, 95% CI 2.3-29.6, P = 0.0012) was associated with advanced fibrosis score using Fib-4, whereas, being black was not (OR 0.19, 95% CI 0.05-0.07, P = 0.01). HBV/G in this population exhibited a different phenotype than expected for pure G genotypes raising the question of recombination or mixed infections. The frequent finding of HBV/G in co-infected patients and its association with more advanced fibrosis, suggests that this genotype leads to more rapid liver disease progression. Further studies are needed to understand why this genotype occurs more frequently and what impact it has on liver disease progression in patients with HBV/HIV., (Copyright © 2011 Wiley-Liss, Inc.)

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

Hepatitis B virus (HBV) increases morbidity and mortality among people with HIV (PWH). We retrospectively analyzed HBV incidence among 5785 PWH. Fourteen had newly positive hepatitis B s antigen (mean 5.2 person-years of follow-up, 46.4/100 000 infections/year). These data show gaps in HBV vaccination and in the preventative efficacy of HBV-specific antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) infection is one of the leading causes of hepatocellular carcinoma and mortality among people living with HIV (PLWH). HBV vaccination provides protection from infection; however, vaccination rates are low. We conducted a retrospective analysis at three HIV centres in Texas to determine the proportion of PLWH who received the recommended 3 doses of hepatitis B vaccine within 1 year. Factors associated with vaccination completion were explored. In our sample of three sites in a state with high HIV transmission and high rates of liver disease from 2011 to 2021, showed low rates of hepatitis B vaccination. Among eligible PLWH, only 9% completed the 3‐dose hepatitis B vaccine series in 1 year. There is an urgent need to improve HBV vaccination to reach 2030 target for hepatitis B elimination. [ABSTRACT FROM AUTHOR]

Objective: Tenofovir disoproxil fumarate (TDF) is a common component of antiretroviral therapy in hepatitis B virus (HBV)‐HIV co‐infected adults but few studies have evaluated worsening renal function and bone turnover, known effects of TDF. Methods: Adults from eight North American sites were enrolled in this cohort study. Research assessments were conducted at entry and every 24 weeks for ≤192 weeks. Bone markers were tested at baseline, week 96 and week 192 from stored serum. We evaluated changes in markers of renal function and bone turnover over time and potential contributing factors. Results: A total of 115 patients were prospectively followed; median age 49 years, 91% male and 52% non‐Hispanic Black. Duration of HIV was 20.5 years. TDF use ranged from 80% to 92% throughout follow‐up. Estimated glomerular filtration rate (eGFR) (ml/min/1.73m2) decreased from 87.1 to 79.9 over 192 weeks (p < 0.001); however, the prevalence of eGFR <60 ml/min/1.73m2 did not appear to differ over time (always <16%; p = 0.43). From baseline to week 192, procollagen type I N‐terminal propeptide (P1NP) (146.7 to 130.5 ng/ml; p = 0.001), osteocalcin (14.4 to 10.2 ng/ml; p < 0.001) and C‐terminal telopeptides of type I collagen (CTX‐1) (373 to 273 pg/ml; p < 0.001) decreased. Younger age, male sex and overweight/obesity versus normal weight predicted a decrease in eGRF. Black race, healthy weight versus underweight, advanced fibrosis, undetectable HBV DNA, and lower parathyroid hormone level predicted worsening bone turnover. Conclusion: In this HBV‐HIV cohort with high prevalence of TDF use, several biomarkers of renal function and bone turnover indicated worsening status over approximately 4 years, highlighting the importance of clinical awareness in co‐infected adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background New therapies to achieve hepatitis B surface antigen (HBsAg) clearance are under development. However, gaps in knowledge exist in understanding the incidence and predictors of HBsAg clearance in a racially diverse HIV population. Methods We examined the incidence and risk of HBsAg clearance in a retrospective cohort of people with HIV/hepatitis B virus (HBV). Included patients had sufficient data to establish chronic infection based on Centers for Disease Control and Prevention guidelines. We examined the incident rate for HBsAg loss and hazard rate ratios to evaluate predictors for HBsAg clearance in a multivariable model. Results Among 571 HIV/HBV patients, 87% were male, 61% were Black, 45% had AIDS, 48% were HBeAg positive, and the median follow-up was 88 months. Incident HBsAg clearance was 1.5 per 100 person-years. In the multivariate model, those with AIDS at baseline (adjusted hazard ratio [aHR], 2.43; 95% CI, 1.37–4.32), Hispanics (aHR, 3.57; 95% CI, 1.33–9.58), and those with injection drug use as an HIV risk factor (aHR, 3.35; 95% CI, 1.26–8.89) were more likely to lose HBsAg, whereas those who were HBeAg positive (aHR, 0.34; 95% CI, 0.19–0.63) were less likely to lose HBsAg. The median change in CD4 cell count during the observation period was 231 cells/mm3 in those with HBsAg loss vs 112 cells/mm3 in those with HBsAg persistence (P  = .004). Conclusions HBsAg loss occurs in about 10% of those with chronic HBV infection. Being Hispanic, having AIDS at baseline, having an injection drug use history, and having HBeAg-negative status at baseline predicted the likelihood of HBsAg loss. Immune restoration may be a mechanism through which HBsAg loss occurs in HIV patients. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver-related complications such as hepatocellular carcinoma (HCC) are a major cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), particularly among those also infected with hepatitis B or hepatitis C viruses. There is a lack of consensus regarding the clinical presentation, treatment options, and outcomes in HIV-infected patients with HCC. We compared the clinical presentation, treatment, and survival of patients with HCC, with and without HIV infection. Methods: We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large safety-net hospital between January 2005 and December 2010. Patients without known HIV serologic status were excluded. Demographic features, tumor characteristics, treatment regimens, and survival were compared between patients (n = 26) with and without HIV infection (n = 164). Survival curves were generated by using Kaplan–Meier plots and compared by using the log-rank test. Results: A higher percentage of HIV-infected patients presented with compensated liver disease (Child–Turcotte–Pugh stage A) than those without HIV infection (62% vs 32%, respectively; P = .01), as well as those with early-stage tumors (Barcelona Clinic Liver Cancer stage A, 39% vs 17%, respectively; P = .04 and Okuda stage I, 50% vs 21%, respectively; P < .01). HIV-infected patients were more likely to be cured of HCC than uninfected patients (27% vs 4%, respectively; P = .01), but median overall survival times were similar between groups (9.6 vs 5.2 months, respectively; P = .85). The 1-year rates of survival for HIV-infected and uninfected patients were 40% and 38%, respectively. Conclusions: HIV-infected patients present with earlier-stage HCC and more preserved liver function than uninfected patients, resulting in more curative treatment options. Despite this difference, overall survival was similar between patients with HCC with and without HIV infection. [Copyright &y& Elsevier]

Background. The common occurrence of hepatitis B virus (HBV) infection in patients who carry the human immunodeficiency virus (HIV) demands that both viruses be recognized, evaluated, and treated when appropriate. Methods. We identified 357 HIV- and hepatitis B surface antigen-positive patients who underwent testing from 1999 to 2003; 155 patients who were new to our clinic and who initiated therapy for HIV and HBV coinfection were considered for inclusion in the study. The frequency of HIV testing (to determine HIV load and CD4+ cell count) performed during the first year of therapy was compared with the frequency of HBV measurements (to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load), abdominal ultrasound examination, and measurement of levels of α-fetoprotein in serum. Results. HBV load data were obtained for only 16% of patients before initiation of antiretroviral therapy (ART), whereas HIV load was determined for 99% of patients before initiation of ART. The total number of HIV load measurements obtained during the first year after ART initiation was 497 (median number of HIV load measurements per patient, 3.0), compared with 85 measurements of HBV load (median number of HBV load measurements per patient, <1; P<.001). The percentage of patients who received any level of HBV monitoring (i.e., tests to determine hepatitis B e antigen, antibody to hepatitis B e antigen, and HBV load) after ART initiation increased from 7% in 1999 to 52% in 2001 (P<.001), whereas the percentage of patients who underwent HIV load testing remained at 80%-90% during the same period. Conclusions. Health care providers treating patients with HIV infection during the period 1999-2003 infrequently monitored HBV response in coinfected patients, but they systematically monitored HIV response after ART initiation. Improved physician adherence to guidelines that better delineate HBV treatment and monitoring for patients with HIV-HBV coinfection is needed. [ABSTRACT FROM AUTHOR]