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Background: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar., Methods: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses., Results: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior., Conclusion: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries., Competing Interests: Declaration of competing interest All other authors who have taken part in this study have nothing to disclose regarding competing financial or personal interest with respect to the work reported in this manuscript. KWC has received a research grant to the institution from Merck Sharp & Dohme., (Copyright © 2024. Published by Elsevier B.V.)

Background: Proprotein convertase subtisilin/kexin 9 (PCSK9) raises low-density lipoprotein cholesterol (LDL-C) levels and is associated with inflammation, which is elevated in HIV and hepatitis C virus (HCV) infection. We compared PCSK9 levels in people with co-occurring HIV and HCV (HIV/HCV) vs. HIV alone, and evaluated the impact of HCV direct-acting antiviral (DAA) therapy on PCSK9., Design: A prospective, observational cohort study., Methods: Thirty-five adults with HIV/HCV and 37 with HIV alone were evaluated, all with HIV virologic suppression and without documented cardiovascular disease. Circulating PCSK9 and inflammatory biomarkers were measured at baseline and following HCV treatment or at week 52 (for HIV alone) and compared using Wilcoxon tests and Spearman correlations., Results: At baseline, PCSK9 trended higher in HIV/HCV vs. HIV alone (307 vs. 284 ng/ml, P  = 0.06). Twenty-nine participants with HIV/HCV completed DAA therapy with sustained virologic response. PCSK9 declined from baseline to posttreatment 1 (median 7.3 weeks after end of therapy [EOT]) and posttreatment 2 (median 43.5 weeks after EOT), reaching levels similar to HIV alone; median within-person reduction was -60.5 ng/ml ( P  = 0.003) and -55.6 ng/ml ( P  = 0.02), respectively. Decline in PCSK9 correlated with decline in soluble (s)E-selectin and sCD163 ( r  = 0.64, P  = 0.002; r  = 0.58, P  = 0.008, respectively), but not with changes in LDL-C or other biomarkers. No significant change in PCSK9 occurred in the HIV alone group over 52 weeks., Conclusion: PCSK9 declined with DAA therapy in participants with HIV/HCV, correlating with declines in several inflammatory biomarkers but not LDL-C. Elevated PCSK9 with HCV may be linked to particular HCV-associated inflammatory pathways more so than cholesterol homeostasis., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We sought to characterize in people with human immunodeficiency virus (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained., Methods: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection nor reported heavy alcohol use were included. Clinical and demographic characteristics, including medication use, the hepatic steatosis index (HSI), and metabolic syndrome (MetS) were compared between participants with and without ALT elevation., Results: Six hundred sixty-two participants were included; 444 (67%) had ≥1 and 229 (35%) ≥2 consecutive ALT elevations during a median of 4.0 years of follow-up. HSI and Hispanic or other (non-White or Black) race/ethnicity were consistently associated with higher odds of abnormal ALT (odds ratio [OR] 1.1 for HSI as a continuous variable, OR 1.9-2.8 for Hispanic/other race/ethnicity for ≥1 or ≥2 ALT elevations); older age and current smoking were associated with lower odds of abnormal ALT. Associations with metabolic disease, as well as with incident HBV and HCV infection, were strengthened by restricting outcomes to persistent and higher degrees of ALT elevation., Conclusions: ALT elevation was common in this cohort of PWH and associated with metabolic disease and hepatic steatosis markers. Nonalcoholic fatty liver disease is likely a common cause of liver inflammation in PWH receiving suppressive antiretrovirals, deserving targeted diagnosis and intervention., Competing Interests: Potential Conflicts of Interest. K. W. C. has received research funding to the institution from Merck Sharp & Dohme (grant) and Amgen (research contract), and served as a paid consultant for Pardes Biosciences, and reports payments and honoraria for CME presentations by a not-for-profit organization from International Antiviral Society-USA, and participation as Chair of a Safety Monitoring Committee for an investigator-initiated study where the sponsor is UCSF. F. J. P. has received payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from ViiV, Janssen, Gilead, and Merck. S. N. has received research funding to the institution from Gilead Sciences and AbbVie Pharmaceuticals, served as a paid consultant for Pardes Biosciences, Theratechnologies, and Silverback Therapeutics, and served on an Advisory Board for Vir Biotechnology, a Data Safety Monitoring Board (DSMB) for Personal Health Insights, Inc, and an Event Adjudication Committee for Bristol-Myers Squibb/PRA, and reports stocks and stock options from Vir Biotechnology. E. T. O. has received research funding to the institution from Gilead Sciences and ViiV Healthcare, served as a consultant for ViiV Healthcare, Merck, and Theratechnologies, and reports stock or stock options from GSK, and since the completion of the analysis has become an employee of ViiV Healthcare. M. S. has served on a DSMB for Gilead and AbbVie, and on Advisory Boards for Abbvie, Arbutus, Assembly Bio, Antios, Gilead, GSK, Precision Bio, and Virion, and reports other financial or non-financial interests as the Editor, Journal of Viral Hepatitis, Wiley. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lysil oxidase like enzyme-2 (LOXL-2) and TNC-C play important roles in organ fibrosis. We assessed circulating LOXL-2 and TNC-C levels and their relationship to fibrosis severity in HIV- and/or HCV-infected individuals. Methods: Healthy controls (n = 22), HIV mono- (n = 15), HCV mono- (n = 52) and HCV/HIV-co-infected (n = 92) subjects were included. Results: LOXL-2 and TNC-C levels were significantly higher in HCV mono- and HCV/HIV-co-infected individuals with F0 compared to healthy controls. In addition, in HCV/HIV-co-infected individuals, LOXL-2 levels were higher in intermediate fibrosis compared to no/mild fibrosis. Conclusion: In HCV/HIV-co-infected study participants, both LOXL-2 and TNC-C were significantly higher in intermediate fibrosis compared to no/mild fibrosis, but did not further increase with advanced fibrosis. Furthermore, both markers were elevated among HCV/HIV-positive individuals with mild/no fibrosis.

Background: Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine., Methods: Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status., Results: Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2]), social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5]) and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants., Conclusion: QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV., (© 2022. The Author(s).)

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure., (© 2022 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Although viral hepatitis causes paediatric hepatocellular carcinoma and hepatic and extrahepatic cancers in adults, there are few epidemiologic studies on paediatric-cancer risks from parental viral hepatitis. In a nationwide study in a viral hepatitis endemic region and with confirmation in another population-based sample, we examined associations between parental hepatitis B (HBV) and C (HCV) infections and risks of cancers in offspring., Methods: We included all children born in Taiwan in 2004-2014 (N = 2 079 037) with 2160 cancer cases ascertained from the Cancer Registry. We estimated risks for paediatric cancers using Cox proportional-hazard regressions. We checked these associations in a nationwide case-control study in Denmark (6422 cases, 160 522 controls)., Results: In Taiwan, paternal HBV was related to child's hepatoblastoma [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05, 2.97] when identified at any time in the medical record, and when analyses were limited to hepatitis diagnoses occurring before the child's birth, risks increased (HR = 2.08, 95% CI = 1.13-3.80). Paternal HCV was related to child's non-Hodgkin lymphoma (HR = 2.06, 95% CI = 1.13-3.74). Maternal HCV was weakly related to increased risks of all childhood cancers [all types combined; HR = 1.45, 95% CI = 0.95-2.22]. The population-attributable fraction of hepatoblastoma for maternal, paternal and child HBV was 2.6%, 6.8% and 2.8%, respectively., Conclusions: Parental HBV and HCV may be risk factors for hepatic and non-hepatic cancers in children. If associations are causal, then parental screening and treatment with antivirals may prevent some paediatric cancers., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background and Aim: Direct-acting antivirals (DAAs) have increased hepatitis C virus (HCV) treatment opportunities for vulnerable HIV/HCV coinfected persons. The aim of this study was to identify the frequency of and potential barriers to DAA prescription in HIV/HCV patients during the first few years of DAA availability in the United States., Methods: The AIDS Healthcare Foundation electronic medical record system was queried to identify all HCV viremic HIV-infected patients in care at AIDS Healthcare Foundation Healthcare centers in January 2015-August 2017 and compare characteristics by receipt of a DAA prescription. Multivariate logistic regression analyses were conducted to examine factors associated with DAA prescription., Results: Of 826 eligible patients, 355 (43%) were prescribed a DAA; among those not prescribed a DAA, 301 (64%) had well-controlled HIV (HIV RNA ≤ 200 copies per mL). In multivariate logistic regression analysis, patients with a history of substance use (odds ratio [OR], 0.51 [95% confidence interval 0.35-0.73]) or on select HIV antiretroviral regimens were less likely to be prescribed a DAA. Those who had well-controlled HIV (OR, 5.03 [3.06-8.27]), CD4 + T cell count >200 cells per mm 3 (OR, 1.85 [1.04-3.30]), estimated glomerular filtration rate >60 mL/min/1.73 m 2 (OR, 3.32 [1.08-10.15]), or established care prior to January 2015 (OR, 1.57 [1.08-2.29] were more likely to be prescribed a DAA., Conclusions: In addition to lack of HIV suppression, select antiretroviral regimens, substance use, and kidney disease appeared to limit DAA prescription in the early interferon-free DAA era. Many were not prescribed DAAs despite HIV suppression. Further research is needed to determine if the observed associations persist today., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population., (© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: In the United States Hepatitis C virus (HCV) viral clearance is estimated to range between 20 and 30%. The objective of this study was to estimate the frequency of HCV clearance and identify correlates of viral clearance among patients newly identified as HCV antibody positive in a large urban health system in Los Angeles, California., Methods: We identified patients between November 2015 and September 2017 as part of a newly implemented HCV screening and linkage-to-care program at University of California Los Angeles (UCLA) Health System. All patients were eligible for screening, though there were additional efforts to screen patients born between 1945 and 1965. We reviewed Medical records to categorize anti-HCV antibody positive patients as having spontaneously cleared HCV infection (HCV RNA not detected) or not (HCV RNA detected). We excluded those with a prior history of anti-HCV positivity or history of HCV treatment. We compared differences between those with and without detectable HCV RNA using chi-square test, Fisher's exact test, and t-test as appropriate. We assessed factors associated with HCV clearance using logistic regression analysis., Results: Among the 320 patients included in this study, 56% were male. Baby boomers (52-72 years of age) comprised the single largest age group (62%). We found spontaneous HCV clearance in 58% (n = 185). HCV viral clearance was slightly higher among women as compared to men (63% vs. 53%; p value = 0.07) and varied by race/ethnicity: clearance among Blacks/African Americans was 37% vs. 58% among whites (p value = 0.02). After adjusting for age, race/ethnicity, and sex we found that those diagnosed with chronic kidney disease had a tendency of decreased HCV viral clearance (adjusted OR = 0.34; 95% CI 0.14-1.03)., Conclusion: Of those patients newly identified as anti-HCV positive, 58% had cleared HCV virus, while the rest showed evidence of active infection. In addition, we found that clearance varied by race/ethnicity and clinical characteristics.

This study aimed to assess attitudes and potential barriers towards treatment in patients with hepatitis C virus (HCV) infection, comparing those with and without HIV coinfection. A cross-sectional survey of 82 HCV-infected adults with and without HIV was conducted in greater Los Angeles between November 2013 and July 2015. Overall, there were 53 (64.6%) with HIV coinfection, 20 (25.0%) with self-reported cirrhosis, and 22 (26.8%) with a history of prior HCV treatment. Of all, 93.2% wanted HCV treatment, but 45.9% were unwilling/unable to spend anything out of pocket, 29.4% were waiting for new therapies, and 23.5% were recommended to defer HCV treatment. HIV/HCV-coinfected patients were more likely to want treatment within one year (90.2% versus 68.2%, p = 0.02), more willing to join a clinical trial (74.5% versus 8.0%, p < 0.01), more willing to take medications twice daily (86.3% versus 61.5%, p = 0.01), and more likely to prefer hepatitis C treatment by an infectious diseases/HIV physician (36.7% versus 4.0%, p < 0.01). Of all, 77.1% of coinfected patients were willing to change antiretroviral therapy if necessary to treat HCV, but only 48.0% of patients were willing to take a medication if it had not been studied in HIV-positive patients. Treatment preferences differ between HIV/HCV-coinfected and HCV-monoinfected patients. Despite a strong willingness among the study cohort to start HCV treatment, other factors such as cost, access to medications, and provider reluctance may be delaying treatment initiation.

Chronic hepatitis C virus (HCV) infection has been associated with an increased risk for cardiovascular disease (CVD). The recommended Pooled Cohort atherosclerotic cardiovascular disease (ASCVD) risk equation for estimation of 10-year CVD risk has not been validated in HCV-infected populations. We examined the performance of the ASCVD risk score in HCV-infected persons, using the national Electronically Retrieved Cohort of HCV Infected Veterans to derive a cohort of HCV-infected and uninfected subjects without baseline ASCVD, hepatitis B, or HIV infection, and with low-density lipoprotein cholesterol level<190 mg/dL. Performance of the ASCVD risk equation was assessed by Cox proportional hazard regression, C-statistics and Hosmer-Lemeshow statistic. The cohort included 70 490 HCV-infected and 97 766 HCV-uninfected men with mean age of 55 years, 56% White and 29% Black. Incident CVD event rates were similar between the two groups (13.2 and 13.4 events/1000 person-years), with a higher incidence of coronary heart disease events in the HCV-uninfected group and of stroke events in the HCV-infected group. Adjusting for ASCVD risk score, HCV infection was associated with higher risk for an ASCVD event in the subgroup with baseline ASCVD risk ≥7.5% (HR: 1.19, P<.0001). C-statistics were poor in both the HCV-infected and uninfected groups (0.60 and 0.61, respectively). By Hosmer-Lemeshow test, the ASCVD risk equation overestimated risk amongst lower risk patients and underestimated risk amongst higher risk patients in both the HCV-infected and uninfected groups. Further investigation is needed to determine whether a modified equation to accurately predict ASCVD risk in HCV-infected persons is warranted., (© 2017 John Wiley & Sons Ltd.)

Background: Risk of acute myocardial infarction (AMI) among hepatitis C virus (HCV)-positive versus HCV-negative persons with similar lipid levels is unknown. We determined incident AMI rates among HCV-positive and HCV-negative men among various lipid strata., Methods: We created a propensity score matched (PSM) cohort and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident AMI rates by HCV status in each lipid strata using National Cholesterol Program guidelines for lipid strata., Results: We identified 85863 HCV-positive and HCV-negative men in the PSM population. The incidence rates/1000 patient-years (95% confidence interval [CI]) for AMI among total cholesterol (TC) 200-239 stratum were 5.3 (4.89, 5.71) for HCV-positive versus 4.71 (4.42, 5) for HCV-negative men (P = .02) and for TC >240 mg/dL were 7.38 (6.49, 8.26) versus 6.17 (5.64, 6.71) (P = .02). For low-density lipoprotein cholesterol (LDL) of 130-159 mg/dL, AMI rates were 5.44 (4.97, 5.91) for HCV-positive and 4.81 (4.48, 5.14) for HCV-negative men (P = .03). The rise in risk with increasing lipid levels was greater in younger HCV-positive than in HCV-negative men (e.g., TC > 240 mg/dL: age >50 HR 1.38 [HCV-positive] and 1.12 [HCV-negative]; age ≤50 HR 1.6 [HCV-positive] and 1.29 [HCV-negative]), and more profoundly altered in HCV-positive men by lipid lowering therapy (change in HR with lipid-lowering therapy for TC >240 mg/dL from 1.82 to 1.19 [HCV-positive] from 1.48 to 1.03 [HCV-negative])., Conclusions: HCV-positive men have a higher risk of AMI than HCV-negative men at higher TC/LDL levels; this risk is more pronounced at a younger age. Lipid lowering therapy significantly reduces this risk, with more profound reduction among HCV-positive versus HCV-negative men at similar lipid levels., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com)

Background: Geographic and sociodemographic characterization of hepatitis C virus (HCV) transmission amongst men who have sex with men (MSM) has been limited. Our aim was to characterize HCV prevalence, risk factors for HCV co-infection, and patterns of HIV and HCV co-transmission and transmitted drug resistance mutations (DRMs) in newly HIV-diagnosed Los Angeles MSM., Methods: Viral RNA was extracted from stored plasma samples from a Los Angeles cohort of newly diagnosed HIV-infected MSM with well-characterized substance use and sexual behavioral characteristics via computer-assisted self-interviewing surveys. Samples were screened for HCV by qPCR. HCV E1, E2, core, NS3 protease and NS5B polymerase and HIV-1 protease and reverse transcriptase regions were amplified and sequenced. Phylogenetic analysis was used to determine relatedness of HCV and HIV-1 isolates within the cohort and viral sequences were examined for DRMs., Results: Of 185 newly HIV-diagnosed MSM, the majority (65%) were of minority race/ethnicity and recently infected (57.8%), with median age of 28.3 years. A minority (6.6%) reported injection drug use (IDU), whereas 96 (52.8%) reported recent substance use, primarily cannabis or stimulant use. High risk sexual behaviors included 132 (74.6%) with unprotected receptive anal intercourse, 60 (33.3%) with group sex, and 10 (5.7%) with fisting. Forty-five (24.3%) had acute gonorrhea or chlamydia infection. Only 3 (1.6%) subjects had detectable HCV RNA. Amongst these subjects, HIV and HCV isolates were unrelated by phylogenetic analysis and none possessed clinically relevant NS3 or NS5B HCV DRMs., Conclusions: Prevalence of HCV co-infection was low and there was no evidence of HIV-HCV co-transmission in this cohort of relatively young, predominantly minority, newly HIV-diagnosed MSM, most with early HIV infection, with high rates of high risk sexual behaviors, STI, and non-IDU. The low HCV prevalence in a group with high-risk behaviors for non-IDU HCV acquisition suggests an opportune time for targeted HCV prevention measures.