Active Hepatitis C Virus Infection Research Articles

Population pharmacokinetics of ravidasvir in adults with chronic hepatitis C virus infection and impact of antiretroviral treatment.

Ravidasvir (RDV) is a novel NS5A inhibitor that exhibits potent pan-genotypic inhibition of hepatitis C virus (HCV) replication. Sofosbuvir (SOF) plus RDV was demonstrated to be efficacious and safe in adults with active HCV infection, including those living with HIV (LWHIV), in the STORM-C-1 trial. We assessed the population pharmacokinetics (PK) of RDV in a sub-study nested within STORM-C-1 conducted in Thailand and Malaysia. SOF (400 mg) plus RDV (200 mg) was administered orally once daily for 12 weeks to adults with chronic HCV infection, but without cirrhosis and for 24 weeks to those with compensated cirrhosis. Intensive and sparse PK samples were collected at 4, 8, and 12 weeks after treatment initiation. Population PK parameters of RDV and the impact of covariates were evaluated using nonlinear mixed-effects modeling. Five hundred ninety-four participants were included, 235 (40%) had compensated cirrhosis, and 189 (32%) were LWHIV. RDV plasma concentrations were best described by a two-compartment model with first-order elimination. Oral clearance (CL/F) and volume of distribution (Vd/F) parameters were allometrically scaled on fat-free mass. Concomitant antiretroviral treatment (ART) increased RDV CL/F by 30%-60%, with efavirenz-based ART having the largest impact. Females had 16% lower RDV CL/F than males, and higher albumin levels reduced RDV central volume of distribution. While several covariates impact RDV CL/F and Vd/F, the effect on RDV exposures was not clinically relevant based on the efficacy data reported in this diverse Asian adult population. There were no meaningful drug-drug interactions in adults LWHIV on ART.

Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

Dynamic changes in the prevalence of markers of hepatitis C virus infection among the conditionally healthy population of the Tyva Republic

The aim is to determine the dynamic changes in the prevalence of hepatitis C virus (HCV) infection among various age groups of the conditionally healthy population of the Tyva Republic over the past 11 years.Material and methods. 1163 serum samples collected in 2019 from the healthy volunteers living in the Tyva Republic of were tested for HCV markers. The study included people of 10 age cohorts: less than 1 year, 1-4, 5-9, 10-14, 15-19, 20-29, 30-39, 40-49, 50-59 years, and 60 years or older. Anti-HCV antibodies were detected using commercially available enzyme immunoassay. HCV RNA was detected in anti-HCV positive samples by means of RT-PCR. The dynamic changes in HCV prevalence were assessed based on a comparison of the results with data of the seroservey of the same design conducted in this region in 2008 in similar age cohorts of healthy volunteers (n=910).Results and discussion. The prevalence of anti-HCV antibodies among general population of the Tyva Republic in 2019 was 2.0%. This indicator slightly decreased by 1.7 times over 10 years (3.3% in 2008, p =0.1629). The prevalence of active HCV infection in the Tyva Republic also decreased not significantly (1.1% in 2019 vs. 1.3% in 2008, p = 0.6901). The proportion of people with active infection among anti-HCV positives in 2019 was 56.5%.The decrease in the prevalence of HCV infection over 11 years was associated with a significant reduction in the detection rates of hepatitis C markers in age cohort 40-49 years (0.9% in 2019 vs. 3.6% in 2008 for HCV RNA, p<0.05, and 1.8% in 2019 vs. 9.1% in 2008 for anti-HCV, p<0.05, respectively). The highest rates of detection of anti-HCV and HCV RNA were observed among participants aged 60 years and over (8.0% and 7.0%, respectively, in 2019 and 11.0 and 6.3%, respectively, in 2008), which significantly exceeded detection rates in other age groups, both in 2008 and 2019 (<0.05).Conclusion. A decrease in the prevalence of HCV infection in general population of the Tyva Republic was observed over last 11 years, primarily due to a decrease in the proportion of unidentified cases of infection among people aged 40-49 years. At the same time, the proportion of unidentified cases of HCV infection in persons aged 60 years and older remains consistently high, which is apparently due to insufficient screening coverage in this age cohort. This age-associated risk cohort should be benefited from the inclusion in HCV screening program.

Cytokines in hepatitis C-infected patients with or without opioid maintenance therapy.

Both chronic hepatitis C virus (HCV) infection and opioids cause altered blood levels of cytokines. Previous studies have investigated levels of selected groups of cytokines in patients on opioid maintenance treatment. Little is known about the levels of multiple cytokines in patients with chronic HCV infection on opioid maintenance treatment. Our aim was to investigate the cytokine profile in patients with active HCV infection with and without opioid maintenance treatment. We conducted a cross-sectional study in an out-patients population included upon referral for antiviral hepatitis C infection treatment. The level of 27 cytokines was measured in serum using multiplex technology. Patients were interviewed using a modified version of the European addiction severity index. Data pertaining to weight, height, current medication, smoking habits, allergies, previous medical history and ongoing withdrawal symptoms were collected. Non-parametric testing was used to investigate differences in levels of cytokines between the two groups. A 3-model hierarchical regression analysis was used to analyse associations between cytokines and confounding variables. Out of 120 included patients, 53 were on opioid maintenance treatment. Median duration of opioid treatment was 68.4 months. There were no demographical differences between the two groups other than age. IL-1β was lower and eotaxin-1 higher in the group on opioid maintenance treatment than in the non-opioid group. No other inter-group differences in the remaining cytokine levels were found. In HCV infection patients, the impact of chronic opioid administration on peripheral circulating cytokine level is minimal.

Adult Patients with Hemophilia B and with a History of Chronic HCV/HBV Infection Receiving Liver-Directed Gene Therapy Demonstrated Long-Term Bleeding Protection and Sustained FIX Activity: Efficacy and Safety Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec

Introduction: Liver-targeted recombinant adeno-associated virus (rAAV) gene therapy for hemophilia B has recently become a real-world therapeutic option for an adult population burdened with prevalent co-morbid chronic hepatitis C virus (HCV) and hepatitis B virus (HBV). The pivotal phase 3 HOPE-B trial (NCT03489291) evaluated the efficacy and safety of etranacogene dezaparvovec (CSL222, formerly AMT-061), an AAV5 vector, containing a codon-optimized, highly active factor IX (FIX) Padua R338L transgene under the control of the liver-specific promoter LP-1. Here we evaluate the efficacy and safety of etranacogene dezaparvovec in the subset of HOPE-B participants with a history of chronic HCV and/or HBV. Methods: Adult male participants with hemophilia B (FIX ≤2%), were infused with a single dose of etranacogene dezaparvovec (2x10 13 gc/kg), following a ≥6-month lead-in period receiving their usual FIX prophylaxis. Relevant exclusion criteria included baseline liver chemistries > 2X the upper limit of normal (ULN); active HCV (HCV RNA detectable), HBV (HBV DNA detectable or HBV sAg reactive) or uncontrolled HIV infection; or advanced liver fibrosis (FibroScan™ score of ≥9 kPa). Regular liver ultrasound screening, serum chemistries, and alphafetoprotein (AFP) were collected along with FIX expression and bleeding data. During the first months post-treatment, alanine aminotransferase (ALT) increase to 2X the subject's baseline or >ULN was treated with a per-protocol tapering course of oral corticosteroids. Results: Among 54 HOPE-B trial participants, 31 (57.4%) had history of co-morbid chronic HCV, without active disease and with undetectable HCV RNA. Of these 31 subjects, 7 had a history of chronic HBV infection without active disease (HBV DNA undetectable; HBV sAg neg). Two subjects were HCV/HIV co-infected (HIV DNA neg; CD4+ T-cell count >200). Two subjects were HBV+ (HBV env AB reactive, HBV sAg non-reactive, HBV DNA undetectable)/HCV-/HIV-. The mean age in the HCV+ and/or HBV+ subgroup (HCBV n=33) was 50.0 years (range 31-75). All HCBV participants had central lab (CL) ALT <ULN (ULN=41 U/L) on the day of dosing except one subject who had a CL ALT of 48 U/L. The mean screening fibroscan (liver elastography) score for this subgroup was 5.2 kPa (range 2.8-8.0). In HCBV participants 16/33 (48.5%) had pre-existing AAV5 neutralizing antibodies (NAb), with titers ranging from 8.5-3232; all NAb+ HCBV patients had titer ≤678 except one participant who had a titer of 3212 and never demonstrated FIX expression; as a result his prophylactic FIX infusions were never discontinued and his efficacy outcomes reflect exogenous FIX therapy. One HCBV participant returned to continuous routine prophylaxis 30 months post treatment. In the HOPE-B trial 11/54 (20.4%) of participants had 12 adverse events of ALT elevation of 2X above baseline or >ULN within 12 weeks after etranacogene dezaparvovec treatment, which triggered immunosuppressive therapy with corticosteroids in 9/54 (16.7%) participants. In the HCBV subgroup, 5/33 (15.2%) participants had ALT elevations of which 4/33 (12.1%) participants received corticosteroids. As reported previously (Schmidt M, et al. Blood Advances. 2023), one HCBV subject maintained normal AFP levels however per-protocol screening ultrasound at one year after gene therapy this participant developed a hepatocellular carcinoma (HCC); molecular characterization demonstrated the HCC was not related to etranacogene dezaparvovec treatment. Factor IX expression was stably increased above baseline throughout 36 months after the single CSL222 infusion. History of chronic HCBV did not impact FIX expression (Table 1). After excluding the subject with the pre-existing AAV5 NAb titer 3212 whose continued prophylaxis use confounds analysis, the mean annualized bleeding rate (ABR) decreased after gene therapy compared to lead-in standard of care FIX prophylaxis. HCBV participants demonstrated an ABR rate ratio of 0.31 (95% CI 0.13, 0.72) indicating 69% reduction in all bleeding, sustained from months 7-36 following etranacogene dezaparvovec treatment. Conclusions: The majority of HOPE-B trial participants were adults with a history of chronic HCV and/or HBV infection without active viral disease or evident pre-existing liver fibrosis. Safety and efficacy are observed in the HCBV participants.

Neural epidermal growth factor-like 1 protein (NELL1)-associated membranous nephropathy with heterogeneous underlying diseases: a case report.

Neural epidermal growth factor-like 1 protein (NELL1) is a target antigen of membranous nephropathy (MN). NELL1-associated MN (NELL1-MN) was originally described as a primary form but has subsequently been associated with other diseases, including malignancies, pre-exposure to certain drugs, hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, and rheumatoid arthritis (RA). We present a case of a 78-year-old woman with long-standing RA who developed persistent proteinuria and was diagnosed with MN. Evaluation of the underlying cause revealed chronic active HCV infection and past HBV infection. The underlying cause was less likely to be drug-related; however, there was no evidence of malignancy. The patient was diagnosed with HCV-associated MN. At 4 years after the diagnosis of MN, the patient died of breast cancer with multiple metastases. Subsequent immunohistological analysis revealed that she had NELL1-MN, and her breast cancer tissue stained positive for NELL1. Our case illustrates the difficulty in establishing the underlying cause of NELL1-MN, even after diagnosis. However, the incidence of malignancies, particularly breast and prostate cancers, is higher in NELL1-MN than in MN with other target antigens. Therefore, malignancies are considered a priority for investigation because of their frequency and prognosis among patients with NELL1-MN.

ESTIMATION OF PREVALENCE OF HEPATITIS C VIRUS INFECTION BY SEROLOGICAL TEST AND REAL TIME RT-PCR TEST AMONG SUSPECTED VIRAL HEPATITIS CASES ATTENDING TERTIARY CARE HOSPITAL, KOLKATA

Objective: Hepatitis C virus (HCV) infection is a major public health problem in India and worldwide. Majority remain asymptomatic until they develop serious complications like liver cirrhosis or hepatocellular carcinoma with fatal outcome. Hence, early diagnosis of active HCV infection and prompt initiation of treatment is important. Treatment with directly acting antivirals (DAAs) resulted in high sustained virological response (SVR) rates of >95% globally. This study was done to estimate seroprevalence and prevalence of active HCV infection among study population. After initiation of treatment, SVR rates were estimated. Methods: This was hospital-based, cross-sectional, and observational study. Screening was done by third-generation Enzyme-linked immunosorbent assay to detect anti-HCV antibody, then confirmatory real-time reverse transcription-polymerase chain reaction (RT-PCR) test was done for detection of active cases and determining their viral load. Treatment of 12-week duration was initiated by DAAs and followed up to estimate SVR by doing real-time RT-PCR after 12 weeks of treatment completion. Result: Among 17,752 consecutive non-repetitive blood samples, seroprevalence was 1.78%. The prevalence of active cases was 1.52%. HCV active infection was prevalent more among male (64.21%) and among 40–60 years age group. History of multiple blood transfusion (58%) was the most common risk factor, followed by multiple sex partners (13.3%). Coinfections with Hepatitis B virus and Human immunodeficiency virus were seen in 13.65% of cases. About 92% of patients completed their treatment. SVR was 97.87%. Conclusion: High SVR of 97.87% is evidence-based data that support that proper treatment can eliminate HCV infection. Detection by real-time RT-PCR and highly effective DAA has made a paradigm shift to approach of HCV diagnosis and management in recent times

Prevalence and risk factors for hepatitis C virus infection among HIV positive patients at the Lagos University Teaching Hospital, Nigeria

Background: Worldwide, an estimated 58 million people have chronic hepatitis C virus (HCV) infection, with about 1.5 million new infections occurring per year. About 2.3 million people living with HIV globally have serological evidence of past or present HCV infection. The aim of this study was to determine the prevalence of active HCV infection and associated risk factors among HIV positive patients attending the HIV clinic, Lagos University Teaching Hospital (LUTH), Idi-Araba, Lagos, Nigeria.
 Methodology: A cross sectional study was conducted to determine the prevalence of and risk factors for HCV infection among randomly selected HIV positive patients at the LUTH HIV clinic. Socio-demographic, clinical and laboratory data were collected from the participants using a structured questionnaire. Blood samples were collected and tested for HCV antibodies with an enzyme linked immunosorbent assay (CTK Biotech USA) and HCV RNA was detected using reverse transcriptase polymerase chain reaction assay.
 Results: One hundred and ninety-five HIV infected participants were recruited into the study of which 134 (68.7%) were females and 61 (31.3%) were males. The mean age of participants was 40.1±7.8 years. Of the 195 participants, 5 tested positive for antibody to HCV, giving a seroprevalence rate of 2.6% (95% CI = 0.8-5.9%). Of the 5 seropositive participants, HCV RNA was detected in 1 (20.0%), giving a prevalence of 0.5% (1/195) for active HCV infection. The seroprevalence of HCV in males of 4.9% (3/61) and females of 1.5% (2/134) was not significantly different (OR=3.41, 95% CI=0.56-20.98%, p=0.18). The mean log10 HIV viral load was significantly higher among participants seropositive for HCV (5.1±0.9 log copies/ml) than those seronegative (2.7±1.2 log copies/ml) (p < 0.001). The mean duration of antiretroviral therapy was significantly lower among participants seropositive for HCV (2.6±1.3 years) than those seronegative (5.6±3.1 years) (p=0.004). The seroprevalence of HCV was significantly higher in those with CD4 count <350 cells/mm3 (8.5%) than those with CD4 count >350cells/mm3 (p=0.02). The seroprevalence of HCV in the HIV-positive participants was significantly associated with sexual partners (p=0.0473), with highest seroprevalence in those with ≥ 3 sexual partners (OR=11.625, 95% CI=1.049-128.83). Other risk factors were not significantly associated with seroprevalence of HCV (p>0.05), while risk factors associated with active HCV infection could not be evaluated with the only one HCV RNA positive participant
 Conclusion: Although the prevalence of active HCV infection in HIV infected individuals in this study was apparently low (0.5%), screening with HCV antibody test and confirmation with HCV RNA PCR assay are recommended.

An amino acid substitution in HCV core antigen limits its use as a reliable measure of HCV infection compared with HCV RNA.

Hepatitis C virus (HCV) is a viral pathogen that causes chronic hepatitis, which can lead to cirrhosis and hepatocellular carcinoma. Detection of HCV RNA is the standard method used to diagnose the disease and monitor antiviral treatment. A quantification assay for the HCV core antigen (HCVcAg) has been proposed as a simplified alternative to the HCV RNA test for predicting active HCV infection, with the aim of achieving the global goal of eliminating hepatitis. The objective of this study was to determine the correlation between HCV RNA and HCVcAg, as well as the impact of amino acid sequence heterogeneity on HCVcAg quantification. Our findings demonstrated a strong positive correlation between HCV RNA and HCVcAg across all HCV genotypes (1a, 1b, 3a, and 6), with correlation coefficients ranging from 0.88 to 0.96 (p < 0.001). However, in some cases, samples with genotypes 3a and 6 exhibited lower HCVcAg levels than expected based on the corresponding HCV RNA values. Upon the core amino acid sequence alignment, it was observed that samples exhibiting low core antigen levels had an amino acid substitution at position 49, where threonine was replaced by either alanine or valine. Core mutation at this position may correlate with one of the epitope regions recognized by anti-HCV monoclonal antibodies. The present findings suggest that the utilization of HCVcAg as a standalone marker for HCV RNA might not provide adequate sensitivity for the detection of HCV infection, especially in cases where there are variations in the amino acid sequence of the core region and a low viral load of HCV RNA.

HIV and HCV screening by non-infectious diseases physicians: can we improve testing and hidden infection rates?

Missed opportunities for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) testing remain high. We aimed to ascertain the knowledge of screening guidelines and attitudes of non-infectious disease (ID) hospital physicians and assess the impact of a 1-h session on screening rates and diagnoses. This interventional study consisted of a 1-h training session on HIV and HCV epidemiology and testing guidelines for non-ID physicians. Pre-and post-session questionnaires compared the knowledge of the guidelines and attitudes toward screening before and after the session. Rates of screening and diagnoses were compared in three 6 months periods: before, immediately after, and 24 months ±4 after the session. A total of 345 physicians from 31 departments participated in these sessions. Before the session, 19.9% (28% medical, 8% surgical) and 17.9% (30% medical, 2.7% surgical) were aware of HIV and HCV testing guidelines, respectively. The willingness to routinely test increased from 5.6 to 22%, whereas not ordering tests decreased from 34.1 to 2.4%. HIV screening rates significantly increased by 20% after the session (7.7 vs. 9.3 tests per 103 patients; p < 0.001), and the effect persisted until the long-term period. The HIV diagnosis rate increased globally (3.6 vs. 5.2 HIV diagnoses per 105 patients; p = 0.157), mainly because of medical services (4.7 vs. 7.7 per 105 patients; p = 0.082). The HCV screening rate increased significantly immediately and in the long term only in medical services (15.7 and 13.6%, respectively). The new active HCV infection rates increased immediately and declined steeply thereafter. A short session for non-ID physicians can improve HIV/HCV screening, increase diagnosis, and contribute to disease elimination.

Targeting ER stress/PKA/GSK-3β/β-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients

BackgroundChronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/β-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/β-catenin signaling is needed.MethodsCell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3β (GSK-3β)/β-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection.ResultsBoth chronic HCV infection and replicon-induced Wnt/β-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3β-mediated Wnt/β-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3β-mediated Wnt/β-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection.ConclusionTargeting ER stress/PKA/GSK-3β-dependent Wnt/β-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/β-catenin signaling by DAA treatment.3KsUMj7wB7yx5QgLH83TLMVideo

Diagnostic performance of hepatitis C core antigen assay to identify active infections: A systematic review and meta-analysis.

Hepatitis C virus (HCV) core antigen (HCVcAg) assay is an alternative for diagnosing HCV infection in a single step. This meta-analysis aimed to evaluate the Abbott ARCHITECT HCV Ag assay's diagnostic performance (validity and utility) for diagnosing active hepatitis C. PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library were searched until 10 January 2023. The protocol was registered at the prospective international register of systematic reviews (PROSPERO: CRD42022337191). Abbott ARCHITECT HCV Ag assay was the test for evaluation, and nucleic acid amplification tests with a cut-off ≤50IU/mL were the gold standard. Statistical analysis was performed using STATA with the MIDAS module and random-effects models. The bivariate analysis was conducted on 46 studies (18,116 samples). The pooled sensitivity was 0.96 (95% CI=0.94-0.97), specificity 0.99 (95% CI=0.99-1.00), positive likelihood ratio 141.81 (95% CI=72.39-277.79), and negative likelihood ratio 0.04 (95% CI=0.03-0.06). The area under the summary receiver operating characteristic curve was 1.00 (95% CI=0.34-1.00). For active hepatitis C prevalence values of 0.1%-15%, the probability that a positive test was a true positive was 12%-96%, respectively, indicating that a confirmatory test should be necessary, particularly with a prevalence ≤5%. However, the probability that a negative test was a false negative was close to zero, indicating the absence of HCV infection. The validity (accuracy) of the Abbott ARCHITECT HCV Ag assay for screening active HCV infection in serum/plasma samples was excellent. Although the HCVcAg assay showed limited diagnostic utility in low prevalence settings (≤1%), it might help diagnose hepatitis C in high prevalence scenarios (≥5%).

Qualitative hepatitis C virus RNA assay identifies active infection with sufficient viral load for treatment among Phetchabun residents in Thailand.

The World Health Organization envisions the elimination of viral hepatitis by 2030 through reducing prevalence and transmission, increasing diagnostic screening, and expanding treatment coverage. Efforts to micro-eliminate hepatitis in Phetchabun province in Thailand, a region where the prevalence of hepatitis C virus (HCV) infection and liver cancer is higher than elsewhere in the country, began with evaluating the province-wide burden of HCV. Here, we describe a feasibility study to assess active HCV infection by screening Phetchabun residents ages 35 to 69 years for anti-HCV antibodies by using a rapid diagnostic test (RDT) at the point of care. Positive anti-HCV results were further evaluated for active infection using qualitative HCV RNA assay, followed by quantitative HCV viral load determination in a subset of samples. Currently, we have identified 6.2% (10,621/170,163) anti-HCV positive individuals, of whom 74.9% (3,930/5,246) demonstrated detectable viral RNA. Quantitative test found that 97.5% (1,001/1,027) had HCV viral load ≥5,000 IU/mL. Thus, primary screening with anti-HCV RDT followed by qualitative HCV RNA evaluation could identify active and chronic HCV infection in almost all individuals with a viral load ≥5,000 IU/mL, which is the current threshold for treatment dictated by Thailand's National Health Security Office. Our data suggest that qualitative HCV RNA evaluation may obviate the need for the more expensive quantitative HCV viral load test and reduce a significant barrier toward HCV elimination in a middle-income country.

Prevalence of active HCV infection and genotypic distribution among the general population of district Mardan, Pakistan.

Hepatitis C virus (HCV) is the serious global public health burden of liver disease. Approximately 170 million people in the world are infected with (HCV). In Pakistan, where the disease has high occurrence rate. The present study envisages an up-to-date prevalence of HCV and genotypic distribution in the general population of Mardan District, Khyber Pakhtunkhwa (KP), Pakistan. The blood samples from 6,538 individuals including 3,263 males and 3,275 females were analyzed for hepatitis C surface antigen by Immuno-chromatographic test (ICT), Enzyme-linked immunosorbent assay (ELISA), and reverse transcription-polymerase chain reaction (PCR). It was found that 396 (12.13%) out of 3263 individuals contained antibodies in their blood against HCV, while among the different age groups, the highest incidences of HCV antibodies were found in the 31-40 age group (11.01%). The ICT positive samples were further screened by nested PCR to determine the existence of active HCV-RNA. It was identified that 7.11% (3263) of the total population (6538) tested was positive, among which the 461 (14.07%) females possessed antibodies in their blood against HCV. Our data showed total HCV infection in the investigated population was 5.78%. Higher percentage of HCV prevalence was detected in males than females in the age group 31-40 and 41-50. To compare the prevalence of HCV genotypes age-wise in male and female genotype 3a was found most prevalent genotype followed by 1a, 2a and 3b, respectively.

Diagnostic Performance of the HCV Core Antigen Test To Identify Hepatitis C in HIV-Infected Patients: a Systematic Review and Meta-Analysis.

The standard algorithm for diagnosing hepatitis C virus (HCV) infection has two steps, an HCV antibody test for screening and a nucleic acid amplification test (NAAT) for confirmation. However, the HCV core antigen (HCVcAg) detection assay is an alternative for one-step diagnosis. We aimed to evaluate the diagnostic performance of the Abbott ARCHITECT HCV Ag assay to detect active hepatitis C in serum/plasma in people living with HIV/AIDS (PLWHA), through a systematic review and meta-analysis. PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library were searched until 20 September 2022 (PROSPERO, CRD42022348351). We included studies evaluating Abbott ARCHITECT HCV Ag assay (index assay) versus NAATs (reference test) in PLWHA coinfected with HCV who did not receive antiviral treatment for HCV. Meta-analysis was performed with the MIDAS module using Stata and random-effects models. The QUADAS-2 tool evaluated the risk of bias. The bivariate analysis was conducted on 11 studies with 2,407 samples. Pooled sensitivity was 0.95 (95% CI = 0.92 to 0.97), specificity 0.97 (95% CI = 0.93 to 0.99), positive likelihood ratio 37.76 (95% CI = 12.84 to 111.02), and negative likelihood ratio 0.06 (95% CI = 0.04 to 0.09). The area under the curve was 0.97 (95% CI = 0.20 to 1.00). For low prevalence (≤5%), the posttest probability that an individual with a positive test was a true positive ranged from 4% to 67%, whereas, at high prevalence (≥10%), the posttest probability was between 81% and 87%, indicating that a confirmatory test should be necessary, particularly with prevalence values of ≤1%. Regardless of prevalence, the probability that an individual with a negative test was a false negative was close to zero, indicating that the individual was not infected with HCV. In conclusion, the accuracy of the Abbott ARCHITECT HCV Ag assay was very good for HCV screening in serum/plasma samples from PLWHA. The clinical utility to confirm HCV infection was acceptable in high-prevalence settings (≥10%) but poor in low-prevalence settings (≤1%). Furthermore, it was excellent in excluding active HCV infection.

Non-invasive tests for clinically significant portal hypertension after HCV cure.

Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH; hepatic venous pressure gradient [HVPG] ≥10mmHg) have predominantly been studied in patients with active HCV infection. Investigations after HCV cure are limited and have yielded conflicting results. We conducted a pooled analysis to determine the diagnostic/prognostic utility of liver stiffness measurement (LSM)/platelet count (PLT) in this setting. A total of 418 patients with pre-treatment HVPG ≥6mmHg who achieved sustained virological response (SVR) and underwent post-treatment HVPG measurement were assessed, of whom 324 (HVPG/NIT-cohort) also had paired data on pre-/post-treatment LSM/PLT. The derived LSM/PLT criteria were then validated against the direct endpoint decompensation in 755 patients with compensated advanced chronic liver disease (cACLD) with SVR (cACLD-validation-cohort). HVPG/NIT-cohort: Among patients with cACLD, the pre-/post-treatment prevalence of CSPH was 80%/54%. The correlation between LSM/HVPG increased from pre- to post-treatment (r= 0.45 vs. 0.60), while that of PLT/HVPG remained unchanged. For given LSM/PLT values, HVPG tended to be lower post- vs. pre-treatment, indicating the need for dedicated algorithms. Combining post-treatment LSM/PLT yielded a high diagnostic accuracy for post-treatment CSPH in cACLD (AUC 0.884; 95% CI 0.843-0.926). Post-treatment LSM <12kPa & PLT >150G/L excluded CSPH (sensitivity: 99.2%), while LSM ≥25kPa was highly specific for CSPH (93.6%). cACLD-validation-cohort: the 3-year decompensation risk was 0% in the 42.5% of patients who met the LSM <12kPa & PLT >150G/L criteria. In patients with post-treatment LSM ≥25kPa (prevalence: 16.8%), the 3-year decompensation risk was 9.6%, while it was 1.3% in those meeting none of the above criteria (prevalence: 40.7%). NITs can estimate the probability of CSPH after HCV cure and predict clinical outcomes. Patients with cACLD but LSM <12kPa & PLT>150G/L may be discharged from portal hypertension surveillance if no co-factors are present, while patients with LSM ≥25kPa require surveillance/treatment. Measurement of liver stiffness by a specific ultrasound device and platelet count (a simple blood test) are broadly used for the non-invasive diagnosis of increased blood pressure in the veins leading to the liver, which drives the development of complications in patients with advanced liver disease. The results of our pooled analysis refute previous concerns that these tests are less accurate after the cure of hepatitis C virus (HCV) infection. We have developed diagnostic criteria that facilitate personalized management after HCV cure and allow for a de-escalation of care in a high proportion of patients, thereby decreasing disease burden.

Effectiveness of hepatitis C antiviral treatment and feasibility of hepatitis C elimination goal

ABSTRACT Objectives Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population. Methods In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021. Results Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR. Conclusion With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Economic evaluation of the Hepatitis C virus elimination program in the country of Georgia, 2015 to 2017.

In 2015, the country of Georgia launched an elimination program aiming to reduce the prevalence of Hepatitis C virus (HCV) infection by 90% from 5.4% prevalence (~150 000 people). During the first 2.5 years of the program, 770 832 people were screened, 48 575 were diagnosed with active HCV infection, and 41 483 patients were treated with direct-acting antiviral (DAA)-based regimens, with a >95% cure rate. We modelled the incremental cost-effectiveness ratio (ICER) of HCV screening, diagnosis and treatment between April 2015 and November 2017 compared to no treatment, in terms of cost per quality-adjusted life year (QALY) gained in 2017 US dollars, with a 3% discount rate over 25 years. We compared the ICER to willingness-to-pay (WTP) thresholds of US$4357 (GDP) and US$871 (opportunity cost) per QALY gained. The average cost of screening, HCV viremia testing, and treatment per patient treated was $386 to the provider, $225 to the patient and $1042 for generic DAAs. At 3% discount, 0.57 QALYs were gained per patient treated. The ICER from the perspective of the provider including generic DAAs was $2285 per QALY gained, which is cost-effective at the $4357 WTP threshold, while if patient costs are included, it is just above the threshold at $4398/QALY. All other scenarios examined in sensitivity analyses remain cost-effective except for assuming a shorter time horizon to the end of 2025 or including the list price DAA cost. Reducing or excluding DAA costs reduced the ICER below the opportunity-cost WTP threshold. The Georgian HCV elimination program provides valuable evidence that national programs for scaling up HCV screening and treatment for achieving HCV elimination can be cost-effective.

Missed opportunities for hepatitis C treatment at a tertiary care hospital in South Australia.

BACKGROUNDHepatitis C is a global epidemic and an estimated 230 000 Australians were living with chronic hepatitis C in 2016. Through effective public health policy and state commitment, Australia has utilised the advent of direct acting antiviral (DAA) therapy to transform the therapeutic landscape for hepatitis C virus (HCV). However, treatment rates are falling and novel public health approaches are required to maintain momentum for HCV elimination. Contemporary discourse in cascades of care have focused on expanding testing capabilities but less attention has been given to linking previously diagnosed patients back to care. Our simple and focused study rests on the premise that hospital admissions are an excellent opportunity to identify and refer previously diagnosed patients for HCV treatment.AIMTo assess whether inpatients with HCV are appropriately referred on for treatment.METHODSWe conducted a retrospective single centre cohort study that examined all patients with HCV presenting to The Queen Elizabeth Hospital (QEH) inpatient service between January 1 and December 31, 2017. QEH is a tertiary care hospital in South Australia. The main inclusion criteria were patients with active HCV infection who were eligible for DAA therapy. Our study cohort was identified using a comprehensive list of diagnosis based on international classification of diseases-10 AM codes for chronic viral hepatitis. Patients were excluded from the analysis if they had previously received DAA therapy or spontaneously cleared HCV. Patients presenting with decompensated liver cirrhosis or other systemic medical conditions conferring poor short-term prognosis were also excluded from the analysis. The primary outcome of our study was referral of patients for HCV treatment. Secondary outcomes included assessment of factors predicting treatment referral.RESULTSThere were 309 inpatients identified with hepatitis C as a principal or additional diagnosis between January 1 and December 31, 2017. Of these patients, 148 had active HCV infection without prior treatment or spontaneous clearance. Overall, 131 patients were deemed eligible for DAA treatment and included in the main analysis. Mean patient age was 47.75 ± 1.08 years, and 69% of the cohort were male and 13% identified as Aboriginal or Torres Strait Islander. Liver cirrhosis was a complication of hepatitis C in 7% of the study cohort. Only 10 patients were newly diagnosed with HCV infection during the study period with the remainder having been diagnosed prior to the study.CONCLUSIONUnder 25% of hepatitis C patients presenting to an Australian tertiary hospital were appropriately referred for treatment. Advanced age, cirrhosis and admission under medical specialties were predictors of treatment referral.

Prevalence of Hepatitis C Virus Infection, Genotypes and Subtypes in Migrants from Pakistan in Barcelona, Spain.

BackgroundHepatitis C virus (HCV) is a major cause of chronic liver infection with 71 million people infected worldwide. Pakistan has the second highest prevalence of HCV infection and more than half (52%) of Pakistani living in Spain reside in Barcelona. The aim of this study was to analyse the seroprevalence and viraemic rate and determine the genotypes and subtypes of HCV among Pakistanis living in the southern metropolitan area of Barcelona.MethodsWe included all Pakistani patients seeking primary healthcare in the southern metropolitan area of Barcelona from August 2011 to July 2014. Serum samples were screened for HCV antibodies. HCV viral load was determined by reverse transcription polymerase chain reaction and genotypes and subtypes were performed using Versant HCV Genotype and/or deep-sequencing. Screening for hepatitis B virus (HBV) was also carried out.ResultsAmong 5877 Pakistani patients, 565 (9.61%) were screened for anti-HCV antibodies, with 68 (12.04%) being positive. The viral load was determined in 65, with 31 presenting active infection and the viraemic rate was 47.69% (95% confidence interval 36.02–59.62). HCV genotyping and subtyping were performed in 24 individuals. Most infections corresponded to HCV genotype 3 (91.67%), and high resolution HCV subtyping was performed in 18 samples, 16 of which presented subtype 3a. One subject presented HBV coinfection with undetectable HBV DNA. During the study period, we identified a possible case of HCV vertical transmission followed by spontaneous viraemia clearance in a chronically infected mother with a C/T IL28B genetic polymorphism.ConclusionThese results suggest that general HCV screening protocols in patients from high prevalence countries, such as Pakistan, would be helpful to identify and treat active HCV infections. This could avoid further transmission and contribute to building targeted health policies for micro-elimination of HCV infection in specific communities.