Hepatitis C Virus Treatment Research Articles

Liver-related complications before and after successful treatment of chronic hepatitis C virus infection in people with inherited bleeding disorders.

With availability of direct-acting antivirals (DAA), most persons with inherited bleeding disorders are currently cured of hepatitis C virus (HCV) infection. The risk of liver-related complications following HCV cure has not been reported for this population. Reporting liver-related complications during long-term chronic HCV infection and following sustained virological response (SVR) in this population. Retrospective follow-up of a prospective single-centre cohort of HCV antibody-positive persons with inherited bleeding disorders. Primary endpoint was liver-related complications [hepatocellular carcinoma (HCC), decompensated cirrhosis, bleeding gastroesophageal varices]. Liver-related complications were reported separately during chronic HCV and following SVR, stratified for interferon-based and DAA-based SVR. In total 309/381 (81%) HCV antibody-positive individuals developed chronic HCV infection. Median follow-up was 44years [interquartile range (IQR): 34-50]. Liver-related complications occurred in 36/309 (12%) of individuals with chronic HCV infection after median 31 years of chronic infection. Of 199 individuals with SVR, 97 were cured with interferon-based regimens and 102 with DAA after median infection durations of 29 and 45years, respectively. At end of follow-up, respectively, 21% and 42% had advanced fibrosis or cirrhosis. Post-SVR, seven (4%) individuals had a liver-related complication, mainly HCC (n=4). Incidence of liver-related complications per 100 patient-years post-SVR follow-up was .2 for interferon-cured and 1.0 for DAA-cured individuals (p=.01). Successful HCV treatment does not eliminate the risk of liver-related complications in persons with inherited bleeding disorders. Due to higher baseline risk, incidence was higher after DAA than interferon-based SVR. We advise continuing HCC surveillance post-SVR in all with advanced fibrosis or cirrhosis.

Certification program of Addiction Centres for hepatitis C virus elimination in Spain. HepCelentes Project.

Microelimination strategies for the hepatitis C virus (HCV) in vulnerable populations, such as users of Addiction Centres (AC), are key for the elimination of hepatitis C. The aim of the HepCelentes project was to design a certification program for AC from the generation of a guide with the criteria to favour the prevention, diagnosis, control, and treatment of HCV in Spain. The project was structured in 4 phases: normalisation, implementation, certification, and communication. In the first phase, developed between July and December 2020, a Steering Committee was created (formed by representatives of scientific societies, healthcare professionals from AC, primary care centres and hospital units, and patient associations) that, from of an exhaustive bibliographic review, generated by consensus an accreditation guide for AC. The guide consists of 22 criteria (15 mandatory and 7 recommended) structured based on the requirements to be met by AC, justification for the selection, level of action (management, prevention, diagnosis and treatment/follow-up), measurement of the indicator, objective level to be achieved, evidence of compliance, clarifications to improve understanding, and mandatory / recommendation (depending on their relevance to achieve HCV elimination and its feasibility for implementation in real practice). The development of a certification system for the AC, based on consensus and coordination of multidisciplinary teams, is intended to favour the management of hepatitis C and its elimination in AC users, supporting the international, national, and regional elimination strategies.

S3234 A Cancer Encasing the Porta Hepatis: An Aggressive Intra-Abdominal B Cell Lymphoma Presenting as a Post-Obstructive Jaundice With Reactivation of Hepatitis C Virus

Introduction: Hepatitis C virus (HCV) is a lymphotropic virus that promotes HCV-mediated B-cell proliferation and transformation to Non-Hodgkin Lymphoma (NHL). Here we present a case of reactivation of HCV presenting as an aggressive intra-abdominal B cell lymphoma. Case Description/Methods: A 68-years-old-male with history of eradicated HCV with recombinant interferon-alfa and resolved HBV infection presented with painless jaundice and pruritus. CT abdomen revealed a 9.6 x 11.5 x 9.5 cm heterogeneous mass causing CBD and intrahepatic biliary duct dilation. Labs revealed reactivation of HCV infection with worsening of liver function tests with total bilirubin of >40mg/dl. FNA biopsy confirmed mature B-cell lymphoma. Given persistent worsening jaundice despite biliary stent, trial of high dose steroid was initiated to improve lymphoma burden in order to get a window to initiate chemotherapy. After tumor board discussion, he received radiation therapy for tumor shrinkage for this aggressive lymphoma. Prior to initiation of planned R-CHOP chemotherapy, he developed severe sepsis with hepatic abscess. Patient and family opted for hospice care and comfort care was initiated. Discussion: Chronic HCV is a fast-growing epidemic in the U.S.A which carries an enormous threat to general population and healthcare. HCV becomes chronic in >70% of infected patients with risk for cirrhosis, hepatocellular carcinoma and lymphoma. HCV can cause NHL via lymphocyte proliferation from viral antigenic stimulation, HCV replication inside B-cell and mutation via B-cell damage. Among patient who achieve sustained viral response (SVR), reactivation occurs in 1%, 11% and 15% among low-risk monoinfected HCV, high-risk monoinfected HCV and HIV/HCV coinfected group respectively. Treatment of HCV with resolution of NHL has been reported and there is some literature with sequential chemotherapy followed by antiviral therapy (AVT) showing promising results in HCV-NHL cases. Concurrent use of AVT and chemotherapy is primarily discouraged due to hematological toxicity. More evidence and studies need to be explored for such aggressive HCV-NHL management. Patient with SVR should have at least an annual testing and periodic follow-up to access for HCV reactivation or reinfection. Hepatitis C education regarding risk factors reduction and transmission prevention should be encouraged at every healthcare level and in general community and only then we can achieve WHO aim of eradication by 2030.

S276 Does Hepatitis C Independently Increase the Risk of Colorectal Adenoma?

Introduction: Hepatitis C virus (HCV) infection has been associated with extrahepatic malignancies, one such is colorectal carcinoma (CRC). The majority of CRC arise from adenomatous polyps, it is not known if HCV infection influences the growth of these precancerous lesions. This study evaluates the prevalence of colorectal adenomas in HCV patients compared to the general population and if HCV is an independent risk factor for the detection of colorectal adenomas. Methods: This case-control study included patients who underwent screening colonoscopy at our hospital. Patients were divided into cases (HCV) and controls (non-HCV). Patients with no biopsy reports, hepatitis B, and inflammatory bowel disease were excluded. Colonoscopy findings were stratified on the biopsy results i.e., hyperplastic, adenomatous, CRC or normal mucosa. Continuous variables were analyzed using Mann Whitney U test and categorical variables using Chi-square and Fisher's exact test with p< 0.05 considered statistically significant. After 1:1 propensity score matching (PSM), a matched cohort of cases and controls was generated. A multivariate regression analysis to compute an odds ratio for colorectal adenoma detection rate was done. Results: 415 patients were screened, of which 109 HCV patients and 97 controls were included. Descriptive analysis showed that age (p = 0.03), BMI (p = 0.001), aspirin (p = 0.01), smoking (p = 0.004), alcohol use (p = 0.01) and adenoma detection (p = 0.006) were significantly different between both groups. After propensity matching, multivariate regression analysis showed patients with HCV had odds ratio (OR) = 2.06 (p = 0.03), and aspirin use had OR = 0.38 (p = 0.01) in having colorectal adenoma. (Table) Conclusion: Our study shows a significantly higher rate of adenomas in chronic HCV patients. On multivariate analysis with and without propensity score matching, HCV infection was found to be an independent risk factor for colorectal adenoma. Current guidelines do not recommend earlier screening for CRC for such patients. Prospective studies would be required to assess if treatment of HCV leads to lower adenoma detection rates. Table 1. - Multivariate logistic regression for colorectal adenoma detection Variables p value Odds ratio Lower Limit of 95% CI Upper Limit of 95% CI Age ( >60, median) 0.0295* 1.043 1.034 2.125 Hepatitis C 0.0314* 2.152 1.125 3.810 Family history of CRC 0.220 1.984 0.665 5.922 Aspirin use 0.0116* 0.387 0.253 0.89 Smoking 0.499 1.229 0.677 2.231 Alcohol use 0.293 1.527 0.694 3.359 Female Gender 0.869 1.050 0.586 1.882 Diabetes Mellitus 0.529 1.244 0.630 2.459 HIV 0.895 1.148 0.150 8.806

Neurocognitive Changes in Chronic Hepatitis C Patients Receiving Combination Therapy of Interferon and Ribavirin: A Systematic Review

Background: Approximately 3% of the world’s total population is affected by the Hepatitis C virus (HCV). The treatment for HCV differs widely across countries, and one of the therapies used is the combination of interferon (INF) and ribavirin (RBV). Few studies have shown that this combination increases the rate of sustained virological response in HCV patients, resulting in beneficial effects on cognition, while other studies report that it leads to cognitive decline. Thus, this systematic review aims to assess the effects of INF+RBV therapy on neurocognitive changes in HCV patients. Methods: Studies reporting the effect of INF+RBV on neurocognitive changes were searched using Scopus, PubMed, Academia, Google Scholar, Science Direct, and Cochrane. The studies were retrieved till August 23, 2021. The quality assessment of the included studies was done using Cochrane’s bias assessment tool. Results: A total of 6380 articles were found in the initial search. After removing the duplicates, 619 articles were screened on the basis of titles. Further, after the screening, 54 articles were screened on the basis of abstract, and finally, 16 articles were included in this study. Nine studies reported a decline in cognitive function post-INF+RBV therapy, while 7 articles reported improvement in cognitive functions. Conclusion: In conclusion, the combination therapy of INF and RBV may result in cognitive decline in HCV patients.

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.

Investigation of Antiviral Potential of Food Carotenoids and Apocarotenoids against RNA-dependent RNA Polymerase of Hepatitis C Virus

Hepatitis C disease have been a global health threat and affects a significant portion of world population. Hepatitis C have also been a silent health threat for Turkiye, where there are around half million people infected with Hepatitis C Virus (HCV). Disease burden and mortality are expected to increase gradually in the next 20 years in Turkiye. Unavailability of enough data on the currently-available drugs in routine clinical practice, their side effects and interactions with other drugs, and their efficacies on the less common genotypes indicates the necessity of alternative treatment options. Natural products from herbal and medicinal plants can indeed provide an alternative as being drug-like dietary supplements. In particular, the carotenoids and apocarotenoids are underexplored in their antiviral potential, including anti-HCV activities. Therefore, we focused on the virtual screening of various carotenoids and apocarotenoids against the RNA-dependent RNA polymerase (RdRp) of HCV. Molecular docking experiments showed strong binding affinities of the ligands to both palm and thumb domains of RdRp of HCV. In fact, some of them such as neoxanthin, crocin, canthaxanthin and cryptoflavin bound quite strongly to both domains compared to native ligands and current antiviral drugs. MD simulation for neoxanthin-RdRp complex confirmed the stability of the ligand within the binding cavity of RdRp throughout 100 ns simulation. This clearly indicated the potential of carotenoids, specifically neoxanthin, as RdRp inhibitor in treating HCV. Thus, this study not only discovered anti-HCV drug candidates with the properties of easy-to-access and low cost, but also paved the way for the development of carotenoid or apocarotenoid based dietary supplement candidates for the prevention and treatment of HCV.

Treatment of hepatitis C in children and adolescents: how far have we reached?

Hepatitis C virus (HCV) infection is a global public health problem and also generates a significant case load in children and adolescents. With the introduction of directly acting antivirals (DAA), the treatment and care of HCV-infected patients have progressed significantly. The available treatment options in children are limited, and this review aims to provide an overview of treatment of HCV infection in children and adolescents with the current available DAA regimens. This comprehensive review was undertaken after searching the PubMed/Medline and Embase databases for the available up-to-date literature on pediatric HCV infection and treatment using hepatitis C virus infection/HCV, directly acting antivirals/DAA, natural history, treatment, pediatrics, children, and adolescents as keywords. Combination therapies with highly effective DAA regimes, such as sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir, sofosbuvir/daclatasvir, sofosbuvir/ribavirin and others, are available for use in children. Most of the DAA regimens have either received or are pending to receive regulatory approval by different medical/drug agencies for use in children and adolescents. Pan-genotypic regimens are also available in children and adolescents, and these regimens can be used while skipping genotype testing. The literature on different DAA regimens for use in children shows that these regimens have higher cure rates with minimal side effects and shorter duration of therapy.

Factors Associated with Sustained Virologic Response to Hepatitis C Treatment in a Homeless-Experienced Cohort in Boston, 2014-2020.

Engaging people experiencing homelessness or unstable housing in hepatitis C virus (HCV) treatment is critical to achieving HCV elimination. To describe HCV treatment outcomes, including factors associated with retention through the treatment cascade, for a cohort of individuals treated in a homeless health center in Boston. Retrospective cohort study. All individuals who initiated HCV treatment with Boston Health Care for the Homeless Program's HCV treatment program between January 2014 and March 2020 (N = 867). The primary outcome was sustained virologic response (SVR), defined as an HCV ribonucleic acid (RNA) level ≤ 15 IU/mL at least 12 weeks after treatment completion. We used multivariable logistic regression to examine the association between baseline variables and SVR. Process-oriented outcomes included treatment completion, assessment for SVR, and achievement of SVR. Of 867 individuals who started HCV treatment, 796 (91.8%) completed treatment, 678 (78.2%) were assessed for SVR, and 607 (70.0%) achieved SVR. In adjusted analysis, residing in stable housing (OR 3.83, 95% CI 1.85-7.90) and age > 45 years old (OR 1.53, 95% CI 1.04-2.26) were associated with a greater likelihood of achieving SVR. Recent drug use (OR 0.63, 95% CI 0.41-0.95) was associated with a lower likelihood of SVR. Age, housing status, and drug use status impacted retention at every step in the treatment cascade. A large proportion of homeless-experienced individuals engaging in HCV treatment in a homeless health center achieved SVR, but enhanced approaches are needed to engage and retain younger individuals, those with recent or ongoing substance use, or those experiencing homelessness or unstable housing. Efforts to achieve HCV elimination in this population should consider the complex and overlapping challenges experienced by this population and aim to address the fundamental harm of homelessness itself.

Late hepatitis C virus diagnosis among patients with newly diagnosed hepatocellular carcinoma: a case–control study

BackgroundNew direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan.MethodsWe conducted a population-based unmatched case–control study. 2008–2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis.ResultsA decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis.ConclusionsElderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.

Assessing the proportion of patients with hepatitis C treated before and after initiation of an ambulatory pharmacist-led hepatitis C program: A retrospective analysis

BackgroundIn a community with rates of hepatitis C virus (HCV) 10 times greater than the national average, a pharmacist-led HCV clinic creates a unique opportunity to make an extensive impact on a large population. This study aimed to describe the impact of an ambulatory pharmacist-led HCV clinic on successful HCV treatment initiation. ObjectivesThe primary objective was to determine HCV treatment initiation before and after introduction of a pharmacist-led HCV clinic. Secondary objectives include identifying benefits of the clinic through barriers that exist pre-and postclinic, average time to HCV treatment initiation, and current and last known points of care in the treatment process. Practice descriptionThe ambulatory program was established in 2018 with a collaborative practice agreement with gastroenterologists in the health system, allowing for providers to refer patients to the pharmacy clinic for HCV medication initiation and monitoring. Practice innovationThrough maintaining relations with providers, the local health department, and emergency department staff, pharmacists aimed to connect more patients to HCV treatment. Clinical pharmacists work with patients to refer them to specialty pharmacies, ensuring quick treatment start and financial coverage. Evaluation methodsA single-center, retrospective chart review was conducted to assess treatment initiation in patients with a positive HCV antibody in 2016 (preclinic) or 2019 (postclinic). ResultsA statistically significant difference was found for the proportion of patients that started treatment before versus after clinic initiation (P < 0.001). For secondary objectives, a statistically significant difference was found between the number of patients who completed the treatment process in 2016 and those in 2019 (P < 0.001). The average time from diagnosis to treatment initiation was reduced from 66.75 weeks ± SD 13.22 in 2016 to 22.87 weeks ± SD 4.19 in 2019. ConclusionAn ambulatory pharmacist-led HCV clinic results in a higher proportion of patients starting treatment for hepatitis C, better linkage to care, and shorter treatment duration.

Changes in the Epidemiology of Hepatocellular Carcinoma in Asia.

Simple SummaryThe incidence and mortality of hepatocellular carcinoma (HCC) in Asia are among the world leaders. By understanding the changes in prevalence and influencing factors of HCC, we can better understand the current situation in Asia and take measures to reduce the incidence.Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high morbidity and mortality, and the incidence is on the rise. HCC imposes a heavy healthcare burden on Asian countries due to the presence of multiple HCC risk factors in this area. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic liver disease (NAFLD), aflatoxin and alcohol intake are the causes of HCC that cannot be ignored. Compared with the pre-vaccination era, universal vaccination of newborns reduces the incidence of HCC. Anti-viral therapy with nucleos(t)ide analogues also causes a decline in HCC incidence. Early screening and direct-acting antiviral agent are beneficial to the prevention and treatment of HCV. For HCC caused by NAFLD and other reasons, lifestyle changes are imperative. This paper introduces the epidemiological trends of HCC in Asia and highlight future efforts. Focusing on prevention may be the most effective way to improve the prognosis of this hard-to-treat cancer.

Healthcare resource utilization in Hepatitis C-infected patients completing eight versus twelve weeks of treatment: A retrospective cohort study

BackgroundThe objective of this study was to examine differences in healthcare utilization among patients receiving eight vs. 12-weeks of treatment for infection with the Hepatitis C Virus (HCV).MethodsWe conducted a retrospective cohort study among 282 treatment-naïve, HCV-infected patients. Those eligible were uninfected with the Human Immunodeficiency Virus, non-cirrhotic, and treated between 2016 and 2019 as part of an extensive, urban, university-affiliated healthcare system. Electronic medical data were abstracted starting from HCV treatment initiation and up to one year post-initiation or achievement of post-treatment sustained virologic response, whichever occurred first. The primary outcome of interest was healthcare utilization, defined by the number and type of healthcare encounters. Differences in healthcare utilization between those receiving eight vs. 12-weeks of treatment were examined using Student’s t-test, Fisher’s exact test, Pearson’s chi-square test, and the Wilcoxon rank-sum test.ResultsA total of 282 eligible patients were analyzed. At baseline, the average age was 59 years (standard deviation=12), and the majority were male (55%) and white/Caucasian (58%). There were no baseline demographic or clinical differences between those completing 8 (n=59) or 12 (n=223) weeks of treatment. While no overall difference in healthcare encounters was observed between those receiving the 8-weeks (median encounters 6; IQR 4-11) and 12-weeks of treatment (median encounters 8; IQR 5-12; P value=0.07), a notable difference was seen in the number of laboratory visits between the groups (median 1 vs. 2; P value=0.04).ConclusionsOur findings indicate modest reductions in healthcare utilization among those receiving shorter treatment regimens for HCV infection, specifically regarding laboratory testing. These findings suggest that shorter treatment regimens may improve treatment expansion in settings that are otherwise too resource-constrained to deliver HCV care successfully.

Integrated hepatitis C treatment is associated with improved retention and success in outpatient treatment for opioid use disorder at a private clinic.

BackgroundDirect acting antiretrovirals (DAA) are effective for individuals who are infected with chronic hepatitis C virus (HCV), yet many people go without access to these lifesaving treatments.Materials and methodsWe conducted a non-randomized study evaluating treatment data for patients in outpatient treatment for opioid use disorder (OUD) at a private clinic. Patients who were HCV-positive, had been in OUD treatment for at least 4 weeks, and engaged in integrated HCV treatment with DAA (co-located within their treatment for OUD) were compared to patients with HCV who only received OUD treatment. We evaluated HCV cure; OUD medication adherence, treatment utilization and retention; and illicit substance use for those engaged in treatment between 9/2016 and 1/2018.ResultsSeventy-four patients completed integrated HCV-OUD treatment with DAA, with 87.8% achieving cure. Of the 66 who completed treatment and were subsequently evaluated for sustained viral response 98.5% were cured. Patients who received integrated HCV and OUD treatment in our clinic, stayed in OUD treatment longer, demonstrated higher OUD medication adherence, and used less opioids or cocaine compared to HCV-infected patients (n = 572) being treated only for OUD.DiscussionWe have reported on a reproducible intervention that lends itself to outpatient OUD treatment. Analyses demonstrate the potential positive impact HCV treatment has on OUD recovery, including reduction in opioid and cocaine use and increased retention in careConclusionCo-locating HCV treatment with existing OUD treatment is feasible, effective, and demonstrates positive outcomes for the treatment of both conditions.

Pattern of HCV Genotypes in HIV/HCV Co-Infected Patients on Antiretroviral Therapy in Nigeria

At least 33 million people worldwide are living with human immunodeficiency virus (HIV) infection, and about 20-30% of these are also infected with hepatitis C virus (HCV). Co-infection with HIV and HCV is a major public health concern. Co-infected persons develop cirrhosis and end-stage liver disease more quickly than individuals infected with HCV only. The particular HCV strain or genotype is a major factor for HCV prognosis. The pattern of HCV genotypes in a cohort of HIV/HCV co-infected patients was investigated. One hundred (100) adult patients were recruited from the Nigerian Institute of Medical Research (NIMR), Yaba, Lagos, with age ranging from 18 to 65 years (58% male). Upon recruitment, they were placed on appropriate antiretroviral drugs; 300 mg tenofovir (TDF), 200 mg emtricitabine (FTC) plus 600 mg efavirenz (EFV) once daily dosage. HCV genotyping was done using the Linear Array hepatitis C virus genotyping kit (Roche Molecular Systems, Inc. USA). HCV genotyping revealed prevalence of genotypes 1 (65.6%) and 4 (34.4%), respectively. These are the hard-to-treat genotypes that previously required a long duration of HCV therapy until newer drugs were introduced. The nature of HCV genotypes in HIV/HCV co-infected people has serious implications for further HCV therapy. These findings are pertinent for decisions about the best possible time for and kind of HCV treatment in the setting of co-morbid HIV infection.

Causes and outcomes of hepatic fibrosis in persons living with HIV.

The epidemiology of liver disease in people living with HIV has evolved since the arrival of effective hepatitis C virus (HCV) treatment. Nonalcoholic fatty liver disease (NAFLD) in HIV patients is highly prevalent while hepatitis D, hepatitis E, and occult hepatitis B remain underappreciated. We discuss mechanisms of fibrosis in HIV and review clinical outcomes of HIV-associated liver diseases. HIV-HCV co-infection is receding as a cause of progressive liver disease, but fibrosis biomarkers after HCV treatment remain elevated. Antiretroviral therapy (ART) with anti-hepatitis B virus (HBV) activity promotes stable liver disease, but oversimplifying ART regimens in unrecognized suppressed HBV may lead to activation of HBV. A high prevalence of fibrosis and rapid progression of fibrosis are seen in HIV-associated NAFLD, with visceral fat as a major risk factor. Newer ART such as integrase strand inhibitors may have limited intrinsic hepatoxicity but do increase weight, which may secondarily lead to hepatic steatosis. Promising therapies for HIV-associated NAFLD include tesamorelin and CCR5 blockade agents. Our understanding of the natural history and pathogenesis of liver diseases in HIV has advanced and adapted to the changing landscape of liver disease in this population. Future research should evaluate long-term clinical and histological outcomes, prevention strategies, and treatment options to improve morbidity and mortality in HIV-related liver diseases.

HCV hotline facilitates Hepatitis C elimination during the COVID-19 pandemic.

The COVID-19 pandemic necessitates healthcare restrictions that also affected ongoing hepatitis C virus (HCV) elimination efforts. We assessed the value of a physician-operated HCV hotline on treatment and cure rates throughout the pandemic. All HCV patients undergoing HCV therapy at the Vienna General Hospital from 2019 to 2021 were included. An HCV hotline was established in 2019 and provided services including phone calls, text messages and voicemails. Patients were stratified by date of HCV therapy: 2019 (pre-COVID) vs. 2020/2021 (during-COVID) and use of the HCV hotline: users vs. non-users. Overall, 220 patients were included (pre-COVID: n=91 vs. during-COVID: n=129). The prevalence of intravenous drug use (60.5%) and alcohol abuse (24.8%) was high during COVID. During COVID, the number of DAA treatment starts declined by 24.2% (n=69) in 2020 and by 34.1% (n=60) in 2021 vs. pre-COVID (n=91, 100%). Significantly more patients used the HCV hotline during-COVID (95.3%) vs. pre-COVID (65.9%; p < .001). Sustained virologic response (SVR) was 84.6% pre-COVID and 86.0% during-COVID. HCV hotline users achieved higher SVR rates during-COVID (88.2% vs. 33.3%, p=.004), but also pre-COVID (96.7% vs. 61.3%, p < .001) compared with non-users. Considering only patients with completed DAA treatments, SVR rates remained similarly high during-COVID (96.9%) versus pre-COVID (98.1%). HCV treatment initiations decreased during-COVID but importantly, nearly all DAA-treated HCV patients used the HCV hotline during the COVID pandemic. Overall, the SVR rate remained at 88.2% during COVID and was particularly high in HCV phone users-most likely due to facilitation of adherence.

Patients with Hepatitis C on Direct-Acting Antiviral Agents' Response to the Elimination Program in Dammam City within 2018-2020

Background: Hepatitis C virus (HCV) is a worldwide health challenge that imposes urgent interventions for prevention and control. We aimed to assess the response rate for the direct-acting antiviral agents (DAAs) regimen in HCV-infected patients attending the public health centers/hospitals in the Western region of Saudi Arabia. Methods and Results: A retrospective study was followed, including data from the electronic medical records of HCV-infected adult patients in the period 2018-2020. Patients underwent HCV health education and treatment with DAAs according to the regional protocols. The type of treatment regimens provided to the included patients was recorded with the outcome (respondent vs. non-respondent) after 12 weeks post completion of treatment (SVR12) based on negative results (or less than the minimum detection levels using the specified assay) of HCV-RNA detected by polymerase chain reaction. The SVR12 was used for predicting SVR as it was reported to be applicable as SVR24. All cases with discontinuations, treatment modifications, and/or deaths were excluded. Included were a total of 505 adult patients recorded in 13 primary healthcare units and hepatitis treatment specialty clinics of hospitals in the Eastern region of Saudi Arabia during the specified period of the study. The patients were aged 30–73 years (mean age of 48.1±9.1 years), of which 229(45.3%) were females and 276(54.7%) males. Most patients received sofosbuvir/daclatasvir (86.1%), followed by glecaprevir/pibrentasvir (11.5%), and elbasvir/grazoprevir (2.4%). Overall, the SVR rate was 97.4% in the study population. Sofosbuvir/daclatasvir had an SVR12 of approximately 98.4%, while the rate of glecaprevir/pibrentasvir was 93.1%. Conclusion: The present findings show an overall HCV cure rate of 97.4% of patients with HCV in response to the elimination program with DAAs in the Eastern region of Saudi Arabia, as indicated by high SVR12. This is an example of treating patients with HCV in a structured, supportive setting to help in the HCV elimination program.

Interleukin 28B Polymorphism as a Predictor of Sustained Virological Response to Sofosbuvir-Based Therapy for Hepatitis C Virus Patients.

In various genome-wide correlation studies, interleukin (IL)28B gene polymorphism has been strongly correlated with both the therapeutic and spontaneous mediated clearance of hepatitis C virus (HCV). Therefore, this study aimed to evaluate the genotype and allele frequency distributions of IL28B (rs12979860) in patients with chronic hepatitis C and assess the IL28B polymorphisms as predictors of sustained virological response to SOF-based therapy for HCV in Egyptian patients. This retrospective case-control study was conducted on 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and responded to treatment with SVR12 (the responder group) as a control group, and 54 chronic HCV patients who completed treatment with SOF/DCV ± RBV for 12 weeks and did not respond to treatment and failed to achieve SVR12 (the non-responder group) as a case group. The CC genotype frequency of IL-28B (rs12979860) was greater in the responder group (51.9%). In contrast, the TT genotype frequency was higher in the non-responder group (48.1%) (p < 0.001), and the T allele significantly increased the risk of non-responses by 3.13 fold. Therefore IL-28B (rs12979860) SNP could be used as a genetic predictor of sustained virological response to SOF+DCV ± RBV-based HCV treatment in Egyptian patients.

Changes in alcohol use during hepatitis C treatment in persons who inject drugs.

People who inject drugs (PWID) are a vulnerable population at high risk for acquiring hepatitis C virus (HCV) and frequently suffer from comorbid alcohol use. This study examines the characteristics and correlates of alcohol use among study participants, the association between alcohol consumption and sustained virologic response (SVR) in patients receiving HCV treatment, changes in drinking behaviours during HCV treatment and associations of drinking over time with specific models of HCV treatment. Participants were 150 PWID with HCV who were receiving opioid agonist therapy (OAT) and enrolled in a randomized clinical trial exploring the effectiveness of three models of care for HCV treatment. The addiction severity index was the primary measure of alcohol consumption. Days of alcohol intake were evaluated longitudinally and across three treatment groups. At baseline, 31% (47/150) reported having at least one drink in the last 30 days including 24% (36/150) who reported drinking to intoxication in the last 30 days. There was no difference in SVR rates between groups. There was a significant decrease in overall days of drinking from baseline (7.78 ± 7.86) to follow-up at Week 24 (5.78 ± 8.83) (p=0.041), but there were no significant changes among those who drank to intoxication; modified directly observed therapy (mDOT) was the only group with a significant decline in days of alcohol consumption (p=0.041). In this cohort of PWID on OAT, baseline alcohol consumption did not affect SVR rates. HCV treatment was overall associated with decreased alcohol consumption. In particular, mDOT was associated with decreased alcohol consumption. Given the additive effect of alcohol and HCV on the development of cirrhosis, studies should be done to investigate the complimentary effects of the mDOT model of care on alcohol cessation.