Epidemiology and Synergistic Hepatopathology of Malaria and Hepatitis C Virus Coinfection.
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ABSTRACT:
SUBMITTER: Nasir IA
PROVIDER: S-EPMC5546637 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:: HIV infection has a significant impact on the natural history of chronic hepatitis B virus (HBV) infection, with increased levels of HBV DNA, accelerated progression of liver disease and increased liver-associated mortality compared with HBV monoinfection. Widespread uptake and early initiation of HBV-active antiretroviral therapy has substantially improved the natural history of HIV-HBV coinfection but the prevalence of liver disease remains elevated in this population. In this paper, we review recent studies examining the natural history and pathogenesis of liver disease and seroconversion in HIV-HBV coinfection in the era of HBV-active antiretroviral therapy and the effects of HIV directly on liver disease. We also review novel therapeutics for the management of HBV with a particular emphasis on clinical strategies being developed for an HBV cure and an HIV cure and their impact on HIV-HBV coinfected individuals.
| S-EPMC5661989 | biostudies-literature
Project description:Hepatitis B virus (HBV) is an enveloped partial double-stranded DNA virus that can cause acute and chronic hepatitis. According to the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), 257 million people are living with HBV. Moreover, 20,900 acute hepatitis B cases were reported in 2016. Hepatitis B is highly prevalent in the African, Western Pacific, Eastern Mediterranean, South-East Asia, and European regions, respectively. Due to the high mutational rate of HBV and lack of reverse transcriptase proofreading activity, ten different genotypes with different geographical distributions have been identified. HBV pathogenesis and severity of infection depend on several host and viral factors, particularly, the genetic variability of both the host and virus. Although HBV infection is a global health concern, there is a lack of adequate studies and reports in the Middle East and North Africa (MENA) region. Here, we provide a review on HBV epidemiology, pathogenesis, host-pathogen interactions, coinfection with selected viruses, and laboratory diagnosis, focusing on studies conducted in the MENA region to determine the current situation of the HBV infection and outline the future study areas.
| S-EPMC6630671 | biostudies-literature
Project description:Extrahepatic replication has important implications for the transmission and treatment of hepatitis C virus (HCV). We analyzed longitudinal HCV diversity in peripheral-blood mononuclear cells (PBMCs) and serum during HCV monoinfection and HCV/HIV coinfection to determine whether distinct amino acid signatures characterized HCV replicating within PBMCs. Analysis of E1-HVR1 sequences demonstrated higher serum genetic distances among HCV/human immunodeficiency virus (HIV)-coinfected persons. Moreover, consensus PBMC sequences were rarely identical to those in the corresponding serum, suggesting divergence in these 2 compartments. Three of 5 HCV/HIV-coinfected participants showed evidence of HCV compartmentalization in PBMCs. Additionally, signature sequence analysis identified PBMC-specific amino acids in all HCV/HIV-coinfected persons. To our knowledge, this is the first study to identify specific amino acids that may distinguish HCV variants replicating in PBMCs. It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection.
| S-EPMC3210030 | biostudies-literature
Project description:Chronic hepatitis C infection frequently coexists with human immunodeficiency virus (HIV) and together are associated with increased hepatic steatosis. Steatosis is a risk factor for progression of liver disease and may persist despite a sustained virologic response to hepatitis C treatment. Therefore, therapies to target hepatic steatosis are important for individuals with HIV and hepatitis C virus (HCV) coinfection. We completed a 48-week, randomized, double-blind, placebo-controlled trial of pioglitazone (45?mg/day) in 13 subjects with HIV/HCV coinfection. The primary outcome variable was hepatic fat content, measured by magnetic resonance spectroscopy (MRS) imaging. Individuals randomized to pioglitazone had a significant decrease in hepatic fat content measured by MRS from baseline (15.1?±?7.0%) to week 48 (7.6?±?3.9%), with a mean difference of -7.4% (p?=?0.02, n?=?5). There was no significant change in hepatic fat content with placebo. Glycemic control as measured by oral glucose challenge improved significantly with pioglitazone (p?=?0.047). Though not statistically significant, there were trends toward improved alanine aminotransferase (ALT) and histopathologic grade of steatosis in subjects who received pioglitazone. Pioglitazone was well tolerated and no one discontinued due to side effects. This study demonstrates that 48 weeks of pioglitazone therapy, and not placebo, results in significant reductions in hepatic fat content as measured by MRS in subjects with HIV and HCV coinfection and hepatic steatosis. This small study shows that pioglitazone helps ameliorate steatosis in the context of HIV/HCV coinfection.
| S-EPMC4576938 | biostudies-literature
Project description:BackgroundHepatitis B virus (HBV) is a leading cause of liver failure and hepatocellular carcinoma. Approximately 10% of people with HIV also have HBV and are at higher risk of liver disease progression than in HBV monoinfection. Antivirals, common to HIV and HBV, suppress HBV DNA levels but do not eradicate virus because the transcriptional template, covalently closed circular DNA (cccDNA), is long lived in infected hepatocytes.MethodsUsing single-cell laser capture microdissection, we isolated >1100 hepatocytes from 5 HIV/HBV coinfected persons with increasing exposure to HBV antivirals (HB1-HB5; no exposure to >7 years exposure), quantifying cccDNA and pregenomic RNA (pgRNA) in each cell using droplet digital polymerase chain reaction.ResultsThe proportion of infected hepatocytes decreased with antiviral exposure from 96.4% (HB1) to 29.8% (HB5). Upper cccDNA range and median pgRNA decreased from HB1 to HB5 (P < .05 for both). The amount of pgRNA transcribed per cccDNA also decreased from HB1 to HB5 (P < .05). Cells with inactive pgRNA transcription were enriched from 0% (HB1) to 14.3% (HB5) of infected hepatocytes.ConclusionscccDNA transcription is reduced in HIV/HBV coinfected people with longer antiviral duration. Understanding HBV transcriptional regulation may be critical to develop a functional cure.
| S-EPMC7137881 | biostudies-literature
Project description:Hepatitis C virus (HCV) infection has been associated with reduced bone mineral density, but its association with fracture rates is unknown, particularly in the setting of human immunodeficiency virus (HIV) coinfection. Our aims were to determine whether persons with HCV infection alone are at increased risk for hip fracture, compared to uninfected individuals, and to examine whether the risk of hip fracture is higher among HCV/HIV-coinfected persons, compared to those with HCV alone, those with HIV alone, and those uninfected with either virus. We conducted a cohort study in 36,950 HCV/HIV-coinfected, 276,901 HCV-monoinfected, 95,827 HIV-monoinfected, and 3,110,904 HCV/HIV-uninfected persons within the U.S. Medicaid populations of California, Florida, New York, Ohio, and Pennsylvania (1999-2005). Incidence rates of hip fracture were lowest among uninfected persons (1.29 events/1,000 person-years), increased with the presence of either HIV infection (1.95 events/1,000 person-years) or HCV infection (2.69 events/1,000 person-years), and were highest among HCV/HIV-coinfected individuals (3.06 events/1,000 person-years). HCV/HIV coinfection was associated with an increased relative hazard (adjusted hazard ratio [HR] [95% confidence interval; CI]) of hip fracture, compared to HCV-monoinfected (HR, 1.38; 95% CI: 1.25-1.53), HIV-monoinfected (females: HR, 1.76; 95% CI: 1.44-2.16; males: HR, 1.36; 95% CI: 1.20-1.55), and HCV/HIV-uninfected persons (females: HR, 2.65; 95% CI: 2.21-3.17; males: HR, 2.20; 95% CI: 1.97-2.47). HCV monoinfection was associated with an increased risk of hip fracture, compared to uninfected individuals, and the relative increase was highest in the youngest age groups (females, 18-39 years: HR, 3.56; 95% CI: 2.93-4.32; males, 18-39 years: HR, 2.40; 95% CI: 2.02-2.84).Among Medicaid enrollees, HCV/HIV coinfection was associated with increased rates of hip fracture, compared to HCV-monoinfected, HIV-monoinfected, and HCV/HIV-uninfected persons. HCV-monoinfected patients had an increased risk of hip fracture, compared to uninfected individuals.
| S-EPMC3433632 | biostudies-literature
Project description:Background. The purpose of this study was to assess the prevalence of anti-hepatitis C virus (HCV) antibodies (Abs) and active HCV infection in human immunodeficiency virus (HIV)-infected (HIV+) patients in Spain in 2015. This was a cross-sectional study. Methods. The study was performed in 41 centers in 2015. Sample size was estimated for an accuracy of 2%, the number of patients from each hospital was determined by proportional allocation, and patients were selected using simple random sampling. Results. The reference population was 35 791 patients, and the sample size was 1867 patients. Hepatitis C virus serostatus was known in 1843 patients (98.7%). Hepatitis C virus-Abs were detected in 695 patients (37.7%), in whom the main route of HIV acquisition was injection drug use (75.4%). Of these 695 patients, 402 had HCV RNA, 170 had had a sustained viral response (SVR) after anti-HCV therapy, and 102 cleared HCV spontaneously. Hepatitis C virus-ribonucleic acid results were unknown in 21 cases. Genotype distribution (known in 367 patients) was 1a in 143 patients (39.0%), 4 in 90 (24.5%) patients, 1b in 69 (18.8%) patients, 3 in 57 (15.5%) patients, 2 in 5 (1.4%) patients, and mixed in 3 (0.8%) patients. Liver cirrhosis was present in 93 patients (23.1%) with active HCV infection and in 39 (22.9%) patients with SVR after anti-HCV therapy. Conclusions. The prevalence of HCV-Abs and active HCV infection in HIV+ patients in Spain is 37.7% and 22.1%, respectively; these figures are significantly lower than those recorded in 2002 and 2009. The predominant genotypes in patients with active HCV infection were 1a and 4. A high percentage of patients had cirrhosis. Cirrhosis is also common in patients with SVR after anti-HCV therapy.
| S-EPMC4866570 | biostudies-literature
Project description:The nucleic acid polymer REP 2139 inhibits assembly/secretion of hepatitis B virus (HBV) subviral particles. Previously, REP 2139-Ca and pegylated interferon (pegIFN) in HBV/hepatitis delta virus (HDV) coinfection achieved high rates of HDV RNA and hepatitis B surface antigen (HBsAg) loss/seroconversion in the REP 301 study (NCT02233075). The REP 301-LTF study (NCT02876419) examined safety and efficacy during 3.5 years of follow-up. In the current study, participants completing therapy in the REP 301 study were followed for 3.5 years. Primary outcomes were safety and tolerability, and secondary outcomes were HDV functional cure (HDV RNA target not detected [TND], normal alanine aminotransferase [ALT]), HBV virologic control (HBV DNA ≤2,000 IU/mL, normal ALT), HBV functional cure (HBV DNA TND; HBsAg <0.05 IU/mL, normal ALT), and HBsAg seroconversion. Supplemental analysis included high-sensitivity HBsAg (Abbott ARCHITECT HBsAg NEXT), HBV pregenomic RNA (pgRNA), HBsAg/hepatitis B surface antibody (anti-HBs) immune complexes (HBsAg ICs), and hepatitis B core-related antigen (HBcrAg). Asymptomatic grade 1-2 ALT elevations occurred in 2 participants accompanying viral rebound; no other safety or tolerability issues were observed. During therapy and follow-up, HBsAg reductions to <0.05 IU/mL were also <0.005 IU/mL. HBsAg ICs declined in 7 of 11 participants during REP 2139-Ca monotherapy and in 10 of 11 participants during follow-up. HDV functional cure persisted in 7 of 11 participants; HBV virologic control persisted in 3 and functional cure (with HBsAg seroconversion) persisted in 4 of these participants. Functional cure of HBV was accompanied by HBV pgRNA TND and HBcrAg <lower limit of quantitation. Conclusion: REP 2139-Ca + pegIFN is not associated with long-term safety or tolerability issues. The establishment of HDV functional cure and HBV virologic control/functional cure and HBsAg seroconversion are durable over 3.5 years and may reflect removal of integrated HBV DNA from the liver. Further investigation is warranted in larger studies.
| S-EPMC7850315 | biostudies-literature
Project description:The effect of hepatitis B virus (HBV) coinfection in patients with hepatitis C virus (HCV) remains unclear. We used the National Veterans Affairs HCV Clinical Case Registry to identify patients with confirmed HCV viremia during 1997-2005. We defined HBV coinfection as a positive test for hepatitis B surface antigen, HBV DNA, or hepatitis B e antigen. We defined cirrhosis and hepatocellular carcinoma (HCC) based on the validated ICD-9 codes and determined mortality through the end of 2009. We performed Cox proportional hazard regression analyses to examine the effect of HBV coinfection stratified by HBV DNA status (positive or negative) on the risk of cirrhosis, HCC, and death adjusting for patients' age, gender, race, human immunodeficiency virus (HIV) infection, alcohol or drug use, Deyo Score, and antiviral treatment. Among 99,548 patients with HCV infection, 1,370 patients (1.4%) had HBV coinfection. Of the coinfected patients, 677 (49.4%) patients had at least one HBV DNA test done and 303 patients (44.7%) tested positive for HBV DNA. The incidence rates of cirrhosis, HCC, and death were significantly higher in patients with HBV coinfection and detectable HBV DNA compared to HCV monoinfection (36.8, 6.9, and 41.7 versus 17.4, 3.6, and 31.4 per 1,000 person-years, respectively; P < 0.05 for all comparisons). After adjustment for demographic, clinical, and treatment factors, patients with detectable HBV DNA had a significantly higher risk for cirrhosis (hazard ratio [HR]?= 1.89 95% confidence interval [CI]?= 1.46-2.45), HCC (HR = 2.12, 95% CI = 1.26-3.60), and death (HR = 1.62, 95% CI = 1.33-1.99) compared to HCV monoinfected patients. There were no differences in the risk of cirrhosis, HCC, or overall mortality between coinfected patients with undetectable HBV DNA and those with HCV monoinfection (HR = 1.18, 95% CI = 0.90-1.55; 1.54, 95% CI = 0.93-2.56; 1.08, 95% CI = 0.88-1.33, respectively).We found that while only a small number of HCV patients were coinfected with HBV, patients with documented HBV viremia were at a significantly higher risk for cirrhosis, HCC, and overall death than HCV monoinfected patients. Absence of HBV replication was associated with a clinical course similar to that of HCV monoinfected patients.
| S-EPMC4245372 | biostudies-literature
Project description:ObjectiveTo explore the relationship between hepatitis C virus (HCV)/HIV coinfection and responses to initial antiretroviral treatment (ART).MethodsFour AIDS Clinical Trials Group HIV treatment studies' data were combined to compare initial ART responses between HCV/HIV-coinfected and HIV-monoinfected patients as evaluated by virologic failure, CD4 cell measures, occurrence of AIDS/death and grade 3/4 safety events, using Kaplan-Meier estimates and proportional hazard, regression and mixed effects models, adjusting for baseline covariates.ResultsOf the 3041 included participants, 81% were men, 19% had prior history of AIDS, the median (25th, 75th percentile) baseline HIV RNA was 4.72 (4.38-5.18) log10 copies/ml, and the median (25th, 75th percentile) baseline CD4 cell count was 216.0 (76.5-327.0) cells/μl. The 279 HCV/HIV-coinfected individuals were older (44 vs. 37 years), more likely to be black non-Hispanic (47 vs. 36%), and previous/current intravenous drug user (52 vs. 5%) than the 2762 HIV-monoinfected patients (all P values <0.001). HCV/HIV coinfection was associated with earlier virologic failure, hazard ratio (95% confidence interval): 1.43 (1.07-1.91); smaller mean CD4 cell increase and CD4% increase [-33.8 (-52.2 to -15.4) cells/μl and -1.16% (-1.43 to -0.89%), respectively] over a median of 132 weeks of follow-up; earlier occurrence of grade 3/4 safety event, hazard ratio 1.51 (1.26-1.81); and increased AIDS/mortality, hazard ratio 2.10 (1.31-3.37). Treatment effects comparing antiretroviral regimens were not significantly different by HCV/HIV coinfection status.ConclusionHCV/HIV coinfection is associated with attenuated response to ART. Results support earlier initiation of HIV therapy and increased monitoring of those initiating ART with HCV/HIV coinfection.
| S-EPMC4214386 | biostudies-literature