Detectable Hepatitis C Virus RNA Research Articles

Biomarkers in Detection of Hepatitis C Virus Infection.

The hepatitis C virus (HCV) infection affects 58 million people worldwide. In the United States, the incidence rate of acute hepatitis C has doubled since 2014; during 2021, this increased to 5% from 2020. Acute hepatitis C is defined by any symptom of acute viral hepatitis plus either jaundice or elevated serum alanine aminotransferase (ALT) activity with the detection of HCV RNA, the anti-HCV antibody, or hepatitis C virus antigen(s). However, most patients with acute infection are asymptomatic. In addition, ALT activity and HCV RNA levels can fluctuate, and a delayed detection of the anti-HCV antibody can occur among some immunocompromised persons with HCV infection. The detection of specific biomarkers can be of great value in the early detection of HCV infection at an asymptomatic stage. The high rate of HCV replication (which is approximately 1010 to 1012 virions per day) and the lack of proofreading by the viral RNA polymerase leads to enormous genetic diversity, creating a major challenge for the host immune response. This broad genetic diversity contributes to the likelihood of developing chronic infection, thus leading to the development of cirrhosis and liver cancer. Direct-acting antiviral (DAA) therapies for HCV infection are highly effective with a cure rate of up to 99%. At the same time, many patients with HCV infection are unaware of their infection status because of the mostly asymptomatic nature of hepatitis C, so they remain undiagnosed until the liver damage has advanced. Molecular mechanisms induced by HCV have been intensely investigated to find biomarkers for diagnosing the acute and chronic phases of the infection. However, there are no clinically verified biomarkers for patients with hepatitis C. In this review, we discuss the biomarkers that can differentiate acute from chronic hepatitis C, and we summarize the current state of the literature on the useful biomarkers that are detectable during acute and chronic HCV infection, liver fibrosis/cirrhosis, and hepatocellular carcinoma (HCC).

Liver Insights: Probing Molecular Signatures of Hepatitis C Patients in Hospitals of Lahore- Navigating the Clinical Landscape of Viral Infection and Organ Profiling

Background: Hepatitis C virus (HCV) infection is a major public health problem, leading to chronic liver diseases, cirrhosis, and hepatocellular carcinoma. The disease burden is particularly high in developing countries, with significant gender disparities and varied outcomes across different clinical settings. Objective: The study aimed to assess the prevalence of HCV infections, analyze the clinical correlation of demographic factors with patient outcomes, and examine the age-related duration of hospital stays in a Pakistani cohort. Methods: A cross-sectional retrospective study was conducted on 230 symptomatic liver patients from three major hospitals in Lahore. Inclusion criteria were based on HCV-related liver conditions, excluding post-liver transplant patients. Data on viral load detections were obtained via semi-automated RT-PCR with commercially available kits. Statistical analysis was performed using SPSS version 25 and GraphPad Prism 9.0 to determine frequency distributions, cross-tabulation analyses, and Pearson correlation coefficients. Results: Out of the 230 patients, 69% (158) were male, and 31% (72) were female. Age distribution showed 36.7% (58) of males were over 60 years, and 63.3% (100) under 60 years; 55.6% (40) of females were over 45 years, with 44.4% (32) under 45 years. Most referrals came from the Pulmonary ward (35%), followed by the Surgery (30%) and Gastroenterology (20%) wards. HCV RNA detection was positive in 67% (154) of the patients. Cross-tabulation analysis indicated a mortality rate of 39% in the Pulmonary ward. A significant positive correlation (r=0.494, p<0.000) was observed between patient age and days of hospital stay. Conclusion: The study demonstrates a higher prevalence of HCV in males and a notable age-related impact on the duration of hospitalization. Interdisciplinary approaches and gender-sensitive healthcare interventions are essential for effective HCV management.

Up-to-date Epidemiology of Chronic Hepatitis C Virus Infection among Bulgarian Patients: a Single Centre Experience

Epidemiological data about chronic infection with Hepatitis C virus (HCV) are limited in Bulgaria. The aim of this study was to determine the Viremic Rate and the distribution of HCV genotypes in one centre for diagnosis and treatment of chronic liver diseases. Geographic patterns of genotype distribution and associations of genotype with viral load, gender and age were investigated. Serum samples from 1731 individuals with a positive HCV Antibody Test, collected between 2016 and 2019, were analysed. HCV RNA levels were determined by HCV quantitative RNA real time polymerase chain reaction. Individuals with detectable HCV RNA further underwent HCV genotyping analysis using the Versant HCV Genotype Assay (LiPA) 2.0. The mean age of all patients was 52.9±15.3 (17–87). Among those, 54.1% were men and 45.9% women. Most patients came from the south-western region of Bulgaria (21.7%). Viral load was proven in 1385 out of 1731 individuals (VR=80%). Genotype 1 (G1) was the predominant genotype (89.8%), followed by G3 (8.5%), G2 (0.9%), G4 (0.6%) and G5 (0.1%). Among individuals with G1, infection with subtype 1b was seen in 77.4% and with subtype 1a in 22.6%. Viral load was not found to be dependent on age or gender. Viral load was higher in patients with G1 compared to G3 ($$p=0.001$$). Finally, patients with G1b were significantly older than patients with G1a ($$p<0.001$$) and G3 ($$p<0.001$$). VR in the studied population (80%) appears to be higher than the VR reported for Central Europe (73.3%). In Bulgaria, the most prevalent genotype is G1 (89.8%). This is a higher rate in comparison to the observed G1 rate in Central Europe (70%). The second most prevalent genotype is G3 (8.5%), with fewer cases identified than in Central Europe (21%).

Testing, diagnosis, and treatment following the implementation of a program to provide dried blood spot testing for HIV and hepatitis C infections: the NSW DBS Pilot

BackgroundDried blood spot (DBS) testing provides an alternative to phlebotomy and addresses barriers to accessing healthcare experienced by some key populations. Large-scale evaluations of DBS testing programs are needed to understand their feasibility. This study evaluated the implementation of a state-wide DBS HIV and hepatitis C virus (HCV) testing pilot.MethodsThe New South Wales (NSW) DBS Pilot is an interventional cohort study of people testing for HIV antibody and/or HCV RNA from DBS samples in NSW, Australia. Participants at risk of HIV/HCV participated in testing via: 1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or 2) assisted DBS sample collection at 36 community health sites (including drug treatment and harm-minimisation services) and prisons. Participants received results by text (HIV antibody/ HCV RNA not detected) or a healthcare provider (HIV antibody/ HCV RNA detected). The RE-AIM framework was used to evaluate reach, effectiveness, adoption, and implementation.ResultsReach: Between November 2016 and December 2020, 7,392 individuals were tested for HIV and/or HCV (21% self-registration, 34% assisted in community, and 45% assisted in prison). Effectiveness: Of 6,922 people tested for HIV (19% men who have sex with men, 13% living outside major cities, 21% born outside Australia), 51% (3,521/6,922) had no HIV test in the past two years, 0.1% (10/6,922) were newly diagnosed with HIV, and 80% (8/10) initiated HIV treatment within six months. Of 5,960 people tested for HCV (24% women, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs), 15% had detectable HCV RNA (878/5,960), and 45% (393/878) initiated treatment within six months. Adoption: By the end of 2020, DBS via assisted registration was available at 36 community sites and 21 prisons. Implementation: 90% of DBS cards arriving at the laboratory had the three full spots required for testing; the proportion was higher in assisted (94%) compared to online (76%) registration.ConclusionsThis study demonstrated the feasibility of DBS testing for HIV and HCV in key populations including Aboriginal and Torres Strait Islander peoples, men who have sex with men, people who inject drugs, and demonstrated the utility of DBS in the prison setting.

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.

Patient-centered and integrated outreach care for chronic hepatitis C patients with serious mental illness in Taiwan.

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population.

Development of simple, rapid, and sensitive methods for detection of hepatitis C virus RNA from whole blood using reverse transcription loop-mediated isothermal amplification.

Hepatitis C virus (HCV) infection is an underdiagnosed global health problem. Diagnosis of current HCV infections typically requires testing for HCV RNA using high-complexity laboratory tests. Methods for the detection of HCV RNA that are simple, inexpensive, rapid, and compatible with use outside of a laboratory setting are very important in order to improve access to hepatitis C diagnostic testing and facilitate accelerated linkage to care. We developed and evaluated three simple workflows for extracting HCV RNA from small volumes of whole blood for use in a sensitive, pan-genotypic RT-LAMP assay. The water workflow uses osmotic stress to release HCV RNA and has a limit of detection of 4.3 log10(IU/mL) (95% CI 4.0-4.9). The heat workflow uses a heating step to release HCV RNA and has a limit of detection of 4.2 log10(IU/mL) (95% CI 3.8-5.1). The bead workflow, which uses chemical lysis of the sample and a streamlined paramagnetic solid phase reversible immobilization bead procedure for nucleic acid purification, has a limit of detection of 2.8 log10(IU/mL) (95% CI 2.5-3.4). When used to test whole blood spiked with HCV RNA-positive plasma samples in which most HCV levels were below 5.0 log10(IU/mL), the water, heat, and bead workflows detected HCV RNA in 69%, 75%, and 94% of samples, respectively. These workflows are compatible with visual lateral flow dipsticks, and each takes less than 60 min from sample to result. Each workflow can be performed with minimal and inexpensive equipment. With further procedural simplifications, these workflows may form the basis of assays for the point-of-care diagnosis of HCV infections.

Hepatitis C Virus Elimination Program among Prison Inmates, Israel.

The Israeli Prison Services implemented a hepatitis C virus (HCV) elimination program in 2020. Inmates considered high risk for HCV were offered serology; HCV-seropositive participants were offered HCV RNA testing. Among participants, 7.0% had detectable HCV RNA and were offered antiviral drug therapy. This program reduced HCV burden among incarcerated persons.

Hepatitis C Treatment Uptake Following Dried Blood Spot Testing for Hepatitis C RNA in New South Wales, Australia: The NSW DBS Pilot Study.

Dried blood spot (DBS) testing for hepatitis C virus (HCV) RNA provides a sampling option that avoids venepuncture and can be carried out in a nonclinical setting. Large-scale evaluations are needed to understand how DBS testing can reduce HCV burden. This study estimated prevalence of, and factors associated with, HCV RNA and treatment initiation among people enrolled in a state-wide pilot of people testing in the NSW DBS Pilot in New South Wales, Australia. People at risk of HIV/HCV could participate via (1) self-registration online with a DBS collection kit delivered and returned by conventional postal service; or (2) assisted DBS sample collection at a community site or prison. Logistic regression was used to identify factors associated with detectable HCV RNA and treatment initiation within 6 months of testing. Between September 2017 and December 2020, 5960 people were tested for HCV (76% men, 35% Aboriginal and/or Torres Strait Islander, 55% recently injected drugs): 21% online self-registration, 34% assisted registration in the community, 45% assisted registration in prison. Fifteen percent had detectable HCV RNA (878/5960). Overall, 44% (n = 386/878) of people with current HCV initiated treatment within 6 months (13% online self-registration, 27% assisted registration in the community, 61% assisted registration in prison). Testing in prison compared with the community (adjusted odds ratio [aOR], 4.28; 95% CI, 3.04-6.03) was associated with increased odds of treatment initiation. Being a woman compared with a man (aOR, 0.68; 95% CI, 0.47-0.97) was associated with reduced treatment initiation. The NSW DBS Pilot demonstrates the feasibility of using DBS to promote HCV testing and treatment in community and prison settings.

Peer-delivered point-of-care testing and linkage to treatment for hepatitis C virus infection among marginalized populations through a mobile clinic in Copenhagen, Denmark

BackgroundGlobally, many people with hepatitis C virus (HCV) infection are marginalized and have very limited access to traditional healthcare services, including HCV testing and treatment. Models of care attuned to the needs of the marginalized population at risk are needed. This study aimed to evaluate the testing and treatment uptake of a community-based, peer-led model of care offering point-of-care testing. MethodsIn this interventional cohort study, people at risk of HCV infection were recruited between May 2019 and December 2021 at a community-based, peer-led mobile clinic. During a single visit, participants were offered a point-of-care HCV antibody test, and, if antibodies were detected, an additional RNA test. Participants with detectable HCV RNA were linked with peer-assisted referral to a ‘fast-track’ clinic at a major hospital. The primary outcomes were the number of people engaged in testing and the proportion who initiated treatment and achieved a sustained virologic response (SVR). ResultsWe tested 728 individuals. Of those, 208 (29%) were positive for HCV antibodies, and 114 (15%) were HCV RNA detectable. Of the 114, 80 (70%) initiated treatment, and 79 (99%) achieved SVR. The main reason for not initiating treatment was non-Danish citizenship with no legal access to health care. ConclusionThis study found that a peer-led point-of-care service is a model of care that can engage marginalized groups in HCV testing and linkage to treatment.

On assessing the viral safety of individual units of the substance "Human plasma for fractionation" by nucleic acid amplification

Scientific relevance. The absence of blood-borne viruses in human plasma-derived medicinal products must be ensured by the control of raw materials and the manufacturing process.Aim. This study aimed to analyse system suitability criteria for analytical procedures to assess the viral safety of individual units of the substance "Human plasma for fractionation" in terms of the content of nucleic acids of blood-borne viruses, considering the requirements of the European Pharmacopoeia.Materials and methods. The authors analysed individual units of the substance "Human plasma for fractionation" (hereinafter, plasma). The study used the International Standards (ISs) for human immunodeficiency virus RNA, hepatitis A virus (HAV) RNA, hepatitis C virus (HCV) RNA, hepatitis B virus (HBV) DNA, and parvovirus B19 DNA, as well as nucleic acid detection kits for these viruses based on polymerase chain reaction (PCR).Results. HCV RNA was not detected in any of the eight plasma samples studied, and parvovirus B19 DNA was detected in one of the samples at a concentration not exceeding 104 IU/mL. Three tests with the corresponding ISs showed that the studied reagent kits detected HCV RNA at a concentration of 102 IU/mL and parvovirus B19 DNA (M1 genotype) at a concentration of 104 IU/mL. In additional tests that were conducted in two samples considering the requirements of the European Pharmacopoeia for the detection of HCV RNA and parvovirus B19 DNA, a new batch of reagent kit I detected the HCV RNA IS at a concentration of 102 IU/mL only in one of three replicates, which did not correspond to the claimed sensitivity of the reagent kit. HCV RNA was not detected in either replicate in one of two plasma samples spiked with the HCV RNA IS at concentrations of 102 and 103 IU/mL, possibly because of plasma inhibitory properties. The sensitivity of the reagent kits to parvovirus B19 DNA corresponded to the label claims; the study did not show any inhibitory properties of the plasma samples.Conclusions. Polymerase chain reaction testing of the viral safety of plasma intended for manufacturing medicinal products should include control samples calibrated in IU/mL. Further research and appropriate pharmacopoeial reference materials are needed to set system suitability criteria for analytical procedures using such control samples.

Hepatitis C Screening in Post–Baby Boomer Generation Americans: One Size Does Not Fit All

ObjectivesTo analyze the impact of access to routine health care, as estimated by health insurance coverage, on hepatitis C virus (HCV) infection prevalence in US adults born after 1965 (post–baby boomer birth cohort [post-BBBC]) and to use the data to formulate strategies to optimize population screening for HCV. Patients and MethodsAdult examinees in the National Health and Nutrition Examination Survey with available anti-HCV data were divided into era 1 (1999-2008) and era 2 (2009-2016). The prevalence of HCV infection, as defined by detectable serum HCV RNA, was determined in post-BBBC adults. In low prevalence groups, prescreening modalities were considered to increase the pretest probability. ResultsOf 16,966 eligible post-BBBC examinees, 0.5% had HCV infection. In both eras, more than 50% had no insurance. In era 2, HCV prevalence was 0.26% and 0.83% in those with and without insurance, respectively (P<.01). As a prescreening test, low alanine aminotransferase level (<23 U/L in women and 32 U/L in men) would identify 54% of post-BBBC adults with an extremely low (0.02%) HCV prevalence. Based on these data, a tiered approach that tests all uninsured directly for HCV and prescreens the insured with alanine aminotransferase would reduce the number to test by 56.5 million while missing less than 1% infections. ConclusionFor HCV elimination, passive “universal” screening in routine health care settings is insufficient, although the efficiency of screening may be improved with alanine aminotransferase prescreening. Importantly, for individuals with limited access to health care, proactive outreach programs for HCV screening are still needed.

Impact of storage time in dried blood samples (DBS) and dried plasma samples (DPS) for point-of-care hepatitis C virus (HCV) RNA quantification and HCV core antigen detection.

The scale-up of hepatitis C virus (HCV) diagnosis and treatment requires affordable and simple tools to improve access to care, especially in low- and middle-income settings with limited infrastructure or high-risk populations. Dried blood and plasma samples (DBS and DPS) are useful alternative for hepatitis C detection in settings lacking adequate infrastructure. We evaluated the performance of DBS and DPS vs plasma in a point-of-care HCV RNA quantitative assay (Xpert HCV Viral Load-Cepheid), and compared HCV core antigen (HCVcAg) detection by the Architect HCV core antigen assay (Abbott) in DBS vs serum. The dried samples were stored at room temperature for different storage times to reproduce the time from sampling to testing in settings with centralized diagnosis or when testing mobile populations. HCV RNA quantification in DBS and DPS presented 100% sensitivity and specificity and a high correlation for up to 3 months of storage. HCV viremia showed a mean decrease of 0.5 log10 IU/mL (DBS) and 0.3 log10 IU/mL (DPS) for storage times up to 1 month. Architect HCVcAg detection presented high sensitivity/specificity (96%/100%) in DBS tested immediately after sampling, decreasing to 86% sensitivity after 7 days of storage. However, sensitivity increased when an optimized cut-off was applied for each storage time. We conclude that DBS and DPS are suitable samples for HCV RNA detection and quantification, being DPS more reliable for shorter storage times. DBS can be also used for HCVcAg qualitative detection and the sensitivity can be increased when adjusting the cut-off values. IMPORTANCE Hepatitis C infection remains a global burden despite the effectiveness of antivirals. In the WHO roadmap to accomplish HCV elimination by 2030, HCV diagnosis is one of the main targets. However, identifying patients in resource-limited settings and high-risk populations with limited access to healthcare remains a challenge and requires innovative approaches that allow decentralized testing. The significance of our research is in verifying the good performance of dried samples for HCV diagnosis using two different diagnostics assays and considering the effect of room temperature storage in this sample format. We confirmed dried samples are an interesting alternative for HCV screening and reflex testing in resource-limited settings or high-risk populations.

Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV Infections in Hemodialysis Patients at Kano Kidney Center.

Background Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections are more prevalent in hemodialysis patients compared to the general population. The objective of this study was to evaluate the prevalence of HBV, HCV, and HIV infections in hemodialysis patients dialyzing regularly at Kano Kidney Center (KKC) in the Eastern Health Cluster of Saudi Arabia in 2022. Methods This retrospective study included all hemodialysis patients who were dialyzed regularly at KKC during 2022. Their electronic medical records were reviewed for the results of HBV, HCV, and HIV along with the patient's demographics, comorbid conditions, and dialysis history. The study was approved and monitored by the Institutional Review Board of Dammam Medical Complex. Results A total of 239 regular hemodialysis patients were included, consisting of 142 males and 97 females (59.41% and 40.59%, respectively), with a mean age of 52.71±15.83 years. Most of the patients were Saudis (156 patients, 65.27%) with the non-Saudi patients being composed mostly of Arabian patients.Nine patients (3.77%) tested positive forhepatitis B surface antigen (HBsAg), the serologic hallmark of HBV infection. Two patients (0.84%) had resolved HBV infections as evidenced by positive hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs). However, the majority (226 patients, 94.56%) were never tested for anti-HBc. Anti-HBs, which can imply long-term immunity against HBV from prior immunizations or infections, were positive in 165 patients (69.04%). A protective anti-HBs level of ≥ 10 IU/L was detected in 158 patients (66.11%) including 104 patients (43.51%) having ≥ 100 IU/L. Eighteen patients (7.53%) had reactive HCV antibodies. Four patients (1.67%) had chronic HCV infection as they had detectable HCV RNA. The remaining 14 patients (5.86%) cleared HCV either spontaneously (seven patients, 2.93%) or by medications (seven patients, 2.93%). HIV screening tests were negative in all 239 patients (100%). HBsAg-positive patients did not have any statistically significant differences from HBsAg-negative patients. On the other hand, the patients who were positive for HCV antibodies were older than the patients who were negative for HCV antibodies (60.66 vs 52.05 years on average, p-value <0.05). They also contained a statistically larger proportion of non-Saudi patients than the patients with no evidence of prior infections (61.11% vs 32.13%, p-value <0.05). Conclusions The study found that the prevalence of HBV and HCV infections among hemodialysis patients in KKC at 3.77% and 1.67%, respectively, is higher than that reported in the general populationin Saudi Arabia, with non-Saudis having a higher prevalence rate of HCV infection than Saudis.However, the current prevalence rate is lower compared to the previous studies that were conducted in Saudi Arabia in the first decade of the 21st century, and there were no cases of HIV infections. Nevertheless, a significant proportion of patients had unprotective or negative anti-HBs antibody titers, indicating the need for strict vaccination protocols and monitoring of antibody titers to ensure optimal protection.

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.

Prevalence of risk factors for liver fibrosis and associations of serum biomarkers with liver fibrosis in a Houston community clinic.

e22518 Background: Liver fibrosis may lead to hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, metabolic syndrome, and alcohol use disorder (AUD) are risk factors for fibrosis. Early screening for fibrosis using serum biomarkers in community settings is not well established. Methods: Adult patients at the HOPE Clinic, a federally qualified health care center in Houston, were enrolled from January 2021 through January 2023 and surveyed about risk factors for liver fibrosis. We measured vital signs and waist circumference, calculated body mass index (BMI), and performed blood testing. We defined chronic HBV infection as positivity for hepatitis B surface antigen; chronic HCV infection as detectable HCV RNA; metabolic syndrome as the presence of at least 3 of 4 conditions: hyperglycemia, hypertension, dyslipidemia, and obesity; and AUD as an AUDIT-C score of ≥4 for men and ≥3 for women. Transient elastrography was performed to assess for fibrosis, with scores ≥8 kPa indicating ≥F2 fibrosis. Serum biomarkers of fibrosis were defined as Fibrosis-4 (FIB-4) score ≥2.67 (based on ALT, AST, platelets, age); NAFLD Fibrosis Score (NFS) ≥0.675 (based on ALT, AST, platelets, albumin, age, BMI, diabetes); and Fatty Liver Index (FLI) ≥30 (based on triglycerides, gamma-glutamyl transferase, waist circumference, BMI). We described the prevalence of fibrosis risk factors and tested the associations of risk factors and serum biomarkers with ≥F2 fibrosis using Fisher’s exact test. Results: We enrolled 904 patients, 378 men (42%) and 526 women (58%). The median age was 48 years. A total of 456 patients (51%) were White, 245 (27%) were Asian, and 187 (21%) were Black. Among all patients, 365 (41%) were Hispanic. Forty-two percent of patients (n = 377) had BMI ≥30. Five percent of patients (46/869) had chronic HBV infection, &lt; 1% (1/863) had chronic HCV infection, 49% (417/849) had metabolic syndrome, and 13% (115/896) had AUD. Of 826 patients who completed transient elastrography, 79 (10%) had ≥F2 fibrosis. Metabolic syndrome was significantly associated with ≥F2 fibrosis (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.5-4.1) but chronic HBV infection, chronic HCV infection, and AUD were not. Serum biomarkers were predictive of ≥F2 fibrosis: FIB-4 score ≥2.67 (OR 19.1, 95% CI 7.3-50.2); NFS ≥0.675 (OR 12.0, 95% CI 4.2-34.2); and FLI ≥30 (OR 5.9, 95% CI 1.4-25.0). Among patients with metabolic syndrome, FIB-4 score ≥2.67 (OR 22.0, 95% CI 4.3-112.0) and NFS ≥0.675 (OR 11.9, 95% CI 2.8-51.4) were predictive of ≥F2 fibrosis, but FLI ≥30 (OR 4.5, 95% CI 0.7-27.5) was not. Conclusions: In this ongoing community-based study, 1 in 10 patients had fibrosis. Metabolic syndrome was a significant risk factor for ≥F2 fibrosis, along with FIB-4 and NFS among patients with metabolic syndrome. Incorporating biomarkers into clinical algorithms will be useful to prevent HCC. Clinical trial information: NCT04785534 .

Efficacy of Daclatasvir and Half Dose Sofosbuvir in the Treatment of Hepatitis –C Virus Infection in Patients of Maintanance Hemodialysis-3 Years Trial in A Tertiary Renal Center

Background: Hepatitis C virus (HCV) infection in end-stage renal disease (ESRD) heralds a bad outcome. Directly acting antiviral (DAA) drugs sofosbuvir along with daclatasvir are very effective in the management of HCV infection. Sofosbuvir is excreted mainly through the kidneys. There is sparse data worldwide on the use of sofosbuvir based drug regimens in ESRD patients having chronic hepatitis C (CHC) virus infection.This study was designed to evaluate the efficacy of half dose sofosbuvir in the management of HCV infection in ESRD patients on maintenance hemodialysis (MHD). Methods: This clinical trial was conducted among 125 ESRD patients on MHD at Gonoshasthaya dialysis center, Dhanmondi, Dhaka from July 2019 to June 2022. Total 125 HCV positive patient with ESRD on MHD were included in this study; all the patients underwent HCV-RNA PCR test. Patients with detectable HCV RNA were observed for six months without antiviral drugs to identify the occurrence of spontaneous clearance of virus. Patients who had detectable HCV-RNA after six months were treated with sofosbuvir(200 mg) and daclatasvir (60 mg), irrespective of genotype. The drugs were given daily for 12 weeks. All the patients were on regular follow up at two weeks interval. Blood counts, liver function, creatinine phosphokinase and serum amylase values were evaluated periodically; virological response was assessed by HCV-RNA after 12 weeks of antiviral treatment. Results: During the observation period, 29 (23.2%) patients had spontaneous virus clearance with an undetectable HCV-RNA. In the remaining 96 patients, the median HCV-RNA level was 2.76×104 (1.56 ×103– 1.89×106)I IU. Twelve weeks after the treatment, 91 (94.8%) patients achieved sustained virological response (SVR) with undetectable HCV-RNA. All patients tolerated the DAAs well and none of the patients reported any serious adverse events. No patient discontinued antiviral therapy due to side effects. Patients who attained SVR with DAA, after 6 months we repeated HCV-RNA in 30 patients, in majority of them (28, 93.3%), HCV-RNA were undetected but in 2 (6.7%) patients,HCV-RNA were detected again. Conclusion: Daclatasvir along with half-dose sofosbuvir are safe and effective in the treatment of CHC patients with ESRD on MHD. Half dose sofosbuvir regimen can reduce the cost of treatment of HCV in ESRD patients in developing countries like Bangladesh, where cost is a significant barrier to HCV treatment. J Bangladesh Coll Phys Surg 2023; 41: 102-107

Prevalence of hepatitis B virus and hepatitis C virus infection in patients with inflammatory bowel disease: a systematic review and meta-analysis.

The data on the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in patients with inflammatory bowel disease (IBD) are conflicting. The present systematic review was thus conducted to study the prevalence of HBV and HCV markers in patients with IBD. A comprehensive literature search of 3 databases was conducted from 2000 to April 2022 for studies evaluating the prevalence of HBV or HCV in patients with IBD. Pooled prevalence rates across studies were expressed with summative statistics. A total of 34 studies were included in the final analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) and hepatitis B core antibodies were 3.3% and 14.2%, respectively. In HBsAg positive IBD patients, hepatitis B e antigen positivity and detectable HBV DNA were seen in 15.3% and 61.0% of patients, respectively. Only 35.6% of the IBD patients had effective HBV vaccination. The pooled prevalence of anti-HCV and detectable HCV RNA were 1.8% and 0.8%, respectively. The pooled prevalence of markers of HBV infection was higher in Asian studies, while the prevalence of markers of HCV infection was higher in European studies. The prevalence of viral hepatitis markers was similar between IBD patients and the general population and that between ulcerative colitis and Crohn's disease. The prevalence of markers of viral hepatitis remains same as the general population with significant regional variations, although the quality of evidence remains low due to publication bias. Only a small proportion of IBD patients had an effective HBV vaccination, requiring improvement in screening and vaccination practices.

Rapid detection of hepatitis C virus using recombinase polymerase amplification.

Over 71 million people are infected with hepatitis C virus (HCV) worldwide, and approximately 400,000 global deaths result from complications of untreated chronic HCV. Pan-genomic direct-acting antivirals (DAAs) have recently become widely available and feature high cure rates in less than 12 weeks of treatment. The rollout of DAAs is reliant on diagnostic tests for HCV RNA to identify eligible patients with viremic HCV infections. Current PCR-based HCV RNA assays are restricted to well-resourced central laboratories, and there remains a prevailing clinical need for expanded access to decentralized HCV RNA testing to provide rapid chronic HCV diagnosis and linkage to DAAs in outpatient clinics. This paper reports a rapid, highly accurate, and minimally instrumented assay for HCV RNA detection using reverse transcription recombinase polymerase amplification (RT-RPA). The assay detects all HCV genotypes with a limit of detection of 25 copies per reaction for genotype 1, the most prevalent in the United States and worldwide. The clinical sensitivity and specificity of the RT-RPA assay were both 100% when evaluated using 78 diverse clinical serum specimens. The accuracy, short runtime, and low heating demands of RT-RPA may enable implementation in a point-of-care HCV test to expand global access to effective treatment via rapid chronic HCV diagnosis.

Results of a Model of Delivering Hepatitis C Care in a Homeless Metropolitan Population in England.

Given the hepatitis C virus (HCV) burden and despite curative treatments, more efforts focused on scaling-up testing and treatment in homeless populations are needed. This project aimed to implement education and flexible on-site HCV testing, treatment, and follow-up for a homeless population in south London and to evaluate engagement, therapy initiation, and cure rates. A mobile unit (van) for on-site HCV education, screening, treatment, and follow-up was placed on the street in a well-known homeless population areas from January 2018 to September 2021. Homeless was defined as living in temporary housing (hostel/hotel-based) or living on the street (street-based). Sociodemographic status, risk factors, comorbidities, concomitant medication, and data related with HCV treatment were recorded. Univariable and multivariable modeling were performed for treatment initiation and sustained virological response (SVR). Nine hundred forty homeless people were identified and 99.3% participated. 56.2% were street-based, 243 (26%) tested positive for HCV antibody, and 162 (17.4%) were viremic. Those with detectable HCV RNA had significantly more frequent psychiatric disorders, active substance use disorders, were on opioid agonist treatment, had advanced fibrosis, and had lower rates of previous treatment in comparison with undetectable HCV RNA. Overall treatment initiation was 70.4% and SVR was 72.8%. In the multivariable analysis, being screened in temporary housing (odds ratio [OR] 3.166; P = 0.002) and having opioid agonist treatment (OR 3.137; P = 0.004) were positively associated with treatment initiation. HCV treatment adherence (OR 26.552; P < 0.001) was the only factor associated with achieving SVR. Promoting education and having flexible and reflex mobile on-site testing and treatment for HCV in the homeless population improve engagement with the health care system, meaning higher rates of treatment initiation and SVR. However, street-based homeless population not linked with harm reduction services are less likely to initiate HCV treatment, highlighting an urgent need for a broad health inclusion system.