Hepatitis C Virus Antiviral Therapy Research Articles

Predictors of liver disease outcomes in individuals with hemophilia and HCV infection

AbstractHemophilia is an X-linked congenital bleeding disorder for which factor replacement is life-saving but complicated by the sequelae of chronic hepatitis C virus (HCV) infection acquired decades ago. Although antiviral therapy clears HCV and reduces end-stage liver disease (ESLD), it may not reverse cirrhosis or prevent hepatocellular cancer (HCC). This was a retrospective cohort study of 121 men with hemophilia and HCV infection cared for at the Hemophilia Center of Western Pennsylvania to determine the incidence and predictors of ESLD and HCC. ESLD and HCC predictors were analyzed using Fisher exact test, and HCV-associated outcomes by Kaplan-Meier time-to-event and Cox proportional hazards regression analyses. At a mean 54 years (36-80) duration of HCV, ESLD occurred in 24 (19.8%), 0.365 per 100 person-years (py); and HCC in 7 (5.8%), 0.106 per 100 py. All 46 (38.0%) alive when HCV antiviral therapy became available, received it. Overall, 31 (25.6%) were HIV+. The leading causes of death were ESLD in 11 (32.3%), bleeding in 9 (26.5%), and HCC in 6 (17.6%). Major risk factors for ESLD included platelets <100 × 103/μL (odds ratio [OR], 6.009; P = .012) and HIV infection (OR, 3.883; P = .001). The major predictors of HCC were ESLD (OR, 11.476; P = .003) and platelets <100 000/μL (OR, 6.159; P = .014). No antiviral-treated patient developed ESLD, P = .001. For men with hemophilia, the sequelae of chronic HCV infection were significant. The major risk factors for ESLD were platelets <100 000/μL and HIV infection. Despite antiviral therapy, ESLD is the most significant predictor of HCC, and ESLD is the leading cause of death.

The Interplay Between Schistosomiasis and Hepatitis C Virus: Battling on Two Fronts

Abstract Schistosomiasis is a prevalent health issue in numerous countries in Africa, Asia, and South America. Data regarding the coinfection of schistosomiasis with hepatitis C virus (HCV) is limited, yet this coinfection is prevalent in regions where schistosomiasis is endemic. The extent of the coinfection issue is evident in countries with a high prevalence of both diseases, such as Egypt. Coinfections with schistosomiasis result in more pronounced liver damage compared with an HCV infection alone. Schistosomiasis has been found to disrupt HCV-specific T-cell responses, resulting in high viral load, increased likelihood of HCV chronicity, and accelerated development of comorbidities in individuals with coinfection. Introducing new, directly acting antivirals for HCV treatment resulted in a marked shift in the disease landscape. This shift may have an impact on the incidence of coinfection with schistosomiasis. This review emphasizes the notable influence of schistosomiasis on the vulnerability to HCV coinfection, the gravity of the consequent liver pathology, and the effectiveness of HCV antiviral therapy.

Sofosbuvir (+) daclatasvir (+) ribavirin in Egyptian patients with hepatitis C virus: Therapeutic outcomes and the prognostic role of natural killer cells

BackgroundOne of the prominent causes of chronic liver disease worldwide is the hepatitis C virus (HCV). HCV believed that innate immunity contributes to a sustained virological response (SVR) to the treatment of Sofosbuvir (SOF) (+) Daclatasvir (DCV) (+) Ribavirin (RBV). This study aimed to evaluate the impact of SOF (+) DCV (+) RBV therapy and persistent HCV infection on the subset of natural killer cells (NK) in HCV genotype four patients from Egypt. Materials and MethodsOne hundred and ten patients with persistent HCV infections requiring SOF (+) DCV (+) RBV therapy were grouped, and a flow cytometry (FCM) study of the NK cell subset in peripheral blood was performed. The assessment was performed before and after three and/or six months of the cessation of viral suppression therapy when a patient had a long-term viral response (SVR). One hundred and ten volunteers from the National Liver Institute’s (NLI) blood bank were selected as controls. ResultsPatients with chronic HCV infection before therapy had considerably lower CD16+ and CD3− CD56+ cells than controls. Their levels increase during SOF (+) DCV (+) RBV therapy. In patients with SVR during treatment, CD16+ and CD3– CD56+ cells increased significantly compared to those who did not get SVR. Furthermore, CD56+ cells were significantly higher in patients with persistent infection before treatment than controls but diminished with the response to treatment. Conclusion: NK cell activation following SOF (+) DCV (+) RBV therapy and polarization to cytotoxicity occurred early in HCV antiviral therapy and was elevated in the respondents. Our data illustrated that establishing an inhibitory cytotoxic NK profile is related to therapeutic outcomes.

Hepatitis C associated membranoproliferative glomerulonephritis treated with directly acting antivirals for hepatitis C

Hepatitis C virus (HCV) infection affects kidneys with different histopathological patterns on kidney biopsy, which commonly include membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy and small to medium vessel vasculitis. Type 1 MPGN associated with type II mixed CG is the most common glomerulopathy associated with hepatitis C infection. Treatment of these glomerulopathies and cryoglobulinemic renal disease associated with HCV infection includes antiviral therapy for HCV, B-cell depletion therapy for prevention of immune complexes and cryoglobulins or nonspecific immunosuppressive therapy. We describe a patient who presented to us with HCV associated MPGN type 1 with cryogloblinemia and detectable HCV RNA, who recovered completely with directly acting antiviral agents (DAA) alone without immunosuppression.

Antiviral Treatment for Hepatitis C Is Associated With a Reduced Risk of Periprosthetic Joint Infection: A Meta-Analysis of Observational Studies

BackgroundRecently, preoperative antiviral therapies for hepatitis C virus (HCV) have become available for total joint arthroplasty (TJA) patients. The objective of this meta-analysis is to investigate the impact of anti-HCV treatment on the incidence of postoperative complications after primary TJAs. MethodsWe searched PubMed, EMBASE, Scopus, Web of Science, and Cochrane Library databases for relevant studies from inception to March 5, 2022. The pooled odds ratios with 95% CI of the risk of postoperative complications were calculated using the random effects model. Subgroup analyses were conducted on the basis of surgery type, antiviral regimes, and duration of follow-up. ResultsEight retrospective cohort studies fulfilled the inclusion and exclusion criteria, involving 9,703 subjects. Overall, antiviral therapy for HCV was associated with a reduced risk of all-type complications and surgical complications. Moreover, we found that HCV-infected patients without treatment had substantially higher rates of periprosthetic joint infection at any surgery type and follow-up time point. There was a tendency for favoring a lower pooled revision/reoperation rate and mechanical complication rate in treated patients compared with untreated patients, but the differences failed to reach statistical significance. When limiting analysis to patients receiving preoperative direct acting antiviral-based therapy, untreated patients still had a higher surgical complication rate and joint infection rate. ConclusionThis meta-analysis demonstrated that antiviral therapy for HCV appears to be associated with a reduced risk of surgical complications in TJA patients, particularly periprosthetic joint infection. Thus, direct-acting antiviral therapy could be recommended for patients diagnosed with HCV.

An on-site community-based model for hepatitis C screening, diagnosis, and treatment among people who inject drugs in Kerman, Iran: The Rostam study.

People who inject drugs (PWID) are at high risk for hepatitis C virus (HCV) infection and its complications in many countries, including Iran. This pilot study aimed to evaluate the effect of a community-based HCV model of care on HCV testing and treatment initiation among PWID in Kerman, Iran. This study is part of the Rostam study and is a non-randomized trial evaluating the effect of on-site HCV- antibody rapid testing, venipuncture for HCV RNA testing, and treatment eligibility assessment on HCV testing and treatment initiation among PWID. Recruitment, interviews, and HCV screening, diagnosis, and treatment were all conducted at a community-based drop-in center (DIC) serving PWID clients. A total of 171 PWID (median age of 39 years and 89.5% male) were recruited between July 2018 and May 2019. Of 62 individuals who were HCV antibody positive, 47 (75.8%) were HCV RNA positive. Of RNA-positive individuals, 36 (76.6%) returned for treatment eligibility assessment. Of all the 36 participants eligible for treatment, 34 (94.4%) initiated HCV antiviral therapy. A sustained virologic response at 12 weeks post-treatment was 76.5% (26/34) in the intention-to-treat (ITT group) analysis and 100% (23/23) in the per-protocol (PP group) analysis. Our integrated on-site community-based HCV care model within a DIC setting suggested that HCV care including HCV testing and treatment uptake can be successfully delivered outside of hospitals or specialized clinics; a model which is more likely to reach PWID and can provide significant progress towards HCV elimination among this population.

From Screening to Therapy: Anti-HCV Screening and Linkage to Care in a Network of General Practitioners and a Private Gastroenterology Practice

(1) Background: Low rates of hepatitis C virus (HCV) diagnosis and sub-optimal linkage to care constitute barriers toward eliminating the infection. In 2012/2013, we showed that HCV screening in primary care detects unknown cases. However, hepatitis C patients may not receive further diagnostics and therapy because they drop out during the referral pathway to secondary care. Thus, we used an existing network of primary care physicians and a practice of gastroenterology to investigate the pathway from screening to therapy. (2) Methods: HCV screening was prospectively included in a routine check-up of primary care physicians who cooperated regularly with a private gastroenterology practice. Anti-HCV-positive patients were referred for further specialized diagnostics and treatment if indicated. (3) Results: Seventeen primary care practices screened 1875 patients. Twelve individuals were anti-HCV-positive (0.6%), six of them reported previous antiviral HCV therapy, and one untreated patient was HCV-RNA-positive (0.05% of the population). None of the 12 anti-HCV-positive cases showed up at the private gastroenterology practice. Further clinical details of the pathway from screening to therapy could not be analyzed. (4) Conclusions: The linkage between primary and secondary care appears to be problematic in the HCV setting even among cooperating partners, but robust conclusions require larger datasets.

Direct-acting antiviral treatment for Hepatitis C Virus in geriatric patients: a real-world retrospective comparison between early and late elderly patients.

IntroductionChronic hepatitis C virus (HCV) infection rates are high in the geriatric population considering that interferon-based therapy is usually intolerable. With the introduction of oral antiviral therapy for HCV, increased treatment tolerability and good treatment responses have been observed. However, treatment data regarding the geriatric population have been limited. Therefore, this retrospective study aimed to evaluate the efficacy and safety of direct-acting antiviral therapy for HCV in the geriatric population.Materials and MethodsThe primary end point was sustained virologic response (SVR) 12 weeks after treatment completion, whereas the secondary end points were treatment-related side effects and short-term survival rate following treatment.ResultsIn total, 492 patients (median age, 73 years; 43.9% males), including 278 early elderly patients, were enrolled. Among the included patients, 45% had cirrhosis. HCV genotypes 1 (72.4%) and 2 (25.4%) were the most common. The overall SVR rate was 96.7%, with no difference in SVR rates observed between early and late elderly groups (96.8% vs. 96.7%; p = 0.983). Both groups showed similar side effects, including dizziness (11.4%), and fatigue (8.7%), with three patients discontinuing therapy owing to side effects. Both groups had a similar 3-year survival rate. Significant factors associated with post-treatment survival included cirrhosis, albumin, and creatinine level.ConclusionsOur real-world data showed that both early and late elderly patients could undergo direct-acting antiviral treatment for HCV with excellent treatment outcomes.

Addressing HCV Elimination Barriers in Italy: Healthcare Resource Utilization and Cost Impact Using 8Weeks' Glecaprevir/Pibrentasvir Therapy.

IntroductionIn Italy, hepatitis C virus (HCV) elimination is achievable; however, barriers remain to achieving the World Health Organization’s elimination targets, and have become more pronounced with the spread of COVID-19. Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral therapy for HCV, approved for 8-week treatment in patients without cirrhosis, and with compensated cirrhosis (CC). Previously, 12 weeks of therapy was recommended for patients with CC. Shortened treatment may reduce the burden on healthcare resources, allowing more patients to be treated. This study presents the benefits that 8-week vs 12-week treatment with G/P may have in Italy.MethodsA multicohort Markov model was used to assess the collective number of healthcare visits and time on treatment with 8-week vs 12-week G/P in the HCV-infected population of Italy from 2019 to 2030, using healthcare resource data from post-marketing observational studies of G/P. Increased treatment capacity and downstream clinical and economic benefits were also assessed assuming the reallocation of saved healthcare visits to treat more patients.ResultsModeled outcomes showed that by 2030, 8-week treatment saved 27,006 years on therapy compared with 12-week treatment, with 21,065 fewer hepatologist visits. Reallocating these resources to treat more patients could increase capacity to treat 5064 (1.4%) more patients with 8 weeks of G/P, all with CC. This increased treatment capacity would further avoid 2257 cases of end-stage liver disease, 893 liver-related deaths, and provide net savings to the healthcare system of nearly €70 million.ConclusionThe modeled comparisons between 8- and 12-week treatment with G/P show that shorter treatment duration can lead to greater time and resource savings, both in terms of healthcare visits and downstream costs. These benefits have the potential to enable the treatment of more patients to overcome elimination barriers in Italy through programs aimed to engage and treat targeted HCV populations.

Hepatitis C virus infection characteristics and treatment outcomes in Canadian immigrants

BackgroundThere are multiple obstacles encountered by immigrants attempting to engage hepatitis C virus (HCV) care and treatment. We evaluated the diversity and treatment outcomes of HCV-infected immigrants evaluated for Direct Acting Antiviral (DAA) therapy in Canada.MethodsThe Canadian Network Undertaking against Hepatitis C (CANUHC) Cohort contains demographic information and DAA treatment information prospectively collected at 10 Canadian sites. Information on country of origin and race are collected. Characteristics and outcomes (sustained virological response; SVR) were compared by immigration status and race.ResultsBetween January 2016 and May 2018, 725 HCV-infected patients assessed for DAA therapy were enrolled in CANUHC (mean age: 52.66 ± 12.68 years); 65.66% male; 82.08% White, 5.28% Indigenous, 4.64% South East Asian, 4.64% East Indian, 3.36% Black). 18.48% were born outside of Canada. Mean age was similar [immigrants: 54.36 ± 13.95 years), Canadian-born: 52.27 ± 12.35 years); (p = 0.085)]. The overall baseline fibrosis score (in kPa measured by transient elastography) was similar among Canadian and foreign-born patients. Fibrosis score was not predicted by race or genotype. The proportion initiating DAA therapy was similar by immigrant status (56.72% vs 49.92%). SVR rates by intent-to-treat analysis were similar (immigrants-89.47%, Canadian-born-92.52%; p = 0.575).ConclusionA diverse immigrant population is engaging care in Canada, initiating HCV antiviral therapy in an equitable fashion and achieving SVR proportions similar to Canada-born patients. Our Canadian experience may be of value in informing HCV elimination efforts in economically developed regions.

Genome-wide capture sequencing to detect hepatitis C virus at the end of antiviral therapy

BackgroundViral relapse is a major concern in hepatitis C virus (HCV) antiviral therapy. Currently, there are no satisfactory methods to predict viral relapse, especially in the era of direct acting antivirals in which the virus often quickly becomes undetectable using PCR-based approaches that focus on a small viral region. Next-generation sequencing (NGS) provides an alternative option for viral detection in a genome-wide manner. However, owing to the overwhelming dominance of human genetic content in clinical specimens, direct detection of HCV by NGS has a low sensitivity and hence viral enrichment is required.MethodsBased on template-dependent multiple displacement amplification (tdMDA), an improved method for whole genome amplification (Wang et al., 2017. Biotechniques 63, 21–27), we evaluated two strategies to enhance the sensitivity of NGS-based HCV detection: duplex-specific nuclease (DSN)-mediated depletion of human sequences and HCV probe-based capture sequencing.ResultsIn DSN-mediated depletion, human sequences were significantly reduced in the two HCV serum samples tested, 65.3% → 55.6% → 33.7% (#4727) and 68.6% → 56% → 21% (#4970), respectively for no normalization, self- and driver-applied normalization. However, this approach was associated with a loss of HCV sequences perhaps due to its micro-homology with the human genome. In capture sequencing, HCV-mapped sequencing reads occupied 96.8% (#4727) and 22.14% (#4970) in NGS data, equivalent to 1936x and 7380x enrichment, respectively. Capture sequencing was then applied to ten serum samples collected at the end of HCV antiviral therapy. Interestingly, the number of HCV-mapped reads was significantly higher in relapsed patients (n = 5) than those from patients with sustained virological response (SVR) (n = 5), 102.4 ± 72.3 vs. 2.6 ± 0.55, p = 0.014.ConclusionsOur data provides concept evidence for a highly sensitive HCV detection by capture sequencing. The abundance difference of HCV sequencing reads at the end of HCV antiviral therapy could be applied to predict treatment outcomes.

Wirelessly Observed Therapy to Optimize Adherence and Target Interventions for Oral Hepatitis C Treatment: Observational Pilot Study.

BackgroundA fixed-dose combination of ledipasvir/sofosbuvir (LDV/SOF) is efficacious in treating chronic hepatitis C virus (HCV) infection; however, objective adherence to prescribed regimens in real-world clinical settings has not been well studied.ObjectiveThis study aimed to evaluate adherence and virologic outcomes in patients with chronic HCV infection treated with LDV/SOF using a novel digital medicine program that directly measures drug ingestion adherence.MethodsThis prospective, observational, open-label, single-arm pilot study was conducted at 2 clinical research sites and followed patients with HCV infection who were prescribed LDV/SOF along with an ingestible sensor. Patients were treated for 8 or 12 weeks. The main outcomes were ingestion adherence, medical interventions, virologic response, safety, and patient satisfaction.ResultsOf the 28 patients (mean 59 years, SD 7), 61% (17/28) were male, 61% (17/28) were non-Caucasian, and 93% (26/28) were treatment naïve. All 28 had genotype 1 HCV, and of these, 27 completed an 8- or 12-week treatment. Patients used the digital medicine program for 92% of the expected days; the overall mean ingestion adherence rate was 97%. Providers used the digital medicine program data for same-day medication therapy management in 39% (11/28) of patients. End-of-treatment response was achieved in all the available 21 of 28 patients. Sustained virologic response at 12 weeks or more was achieved in 26 of 28 patients; of the 2 patients who relapsed, one had less than 90% adherence and the other had greater than or equal to 95% adherence, lending insights into reasons for treatment failure. A total of 4 subjects reported nonserious adverse events, which were resolved.ConclusionsThe findings of this study suggest that digital medicines can be used for wirelessly observed therapy to support adherence to antiviral HCV therapy, reduce unnecessary medication wastage and retreatment costs, and potentially optimize sustained virologic response rates, especially in populations at high risk for nonadherence.

Virologic Clearance of Hepatitis C Is Associated with Improved Outcomes in African American Patients with Lymphoma

Background: Association of hepatitis C virus (HCV) infection and B-cell non-Hodgkin Lymphoma (B-NHL) is well-established. Directly-acting antiviral HCV therapy (DAA) results in very high rates of sustained viral response (SVR) and HCV cure. Studies of the impact of successful antiviral therapy on lymphoma outcomes in HCV-infected patients can have important implications for patient management and for understanding of the biology of different lymphomas. The strongest evidence of positive impact of HCV antiviral therapy on lymphoma regression is available for indolent lymphomas, especially marginal zone lymphoma. Impact of antiviral therapy on HCV-associated aggressive B-NHL is still under investigation. Furthermore, there is no data on outcomes for HCV-associated B-NHL in African-American (AA) patients. The aim of this study was to evaluate lymphoma characteristics and outcomes in HCV-associated B-NHL, in a predominantly AA population. Methods: All consecutive patients with lymphoma and reactive HCV Antibody (HCV Ab+) diagnosed and treated at our center between January 2003 and December 2017 were studied. Patients with HCV-associated mixed cryoglobulinemia without any overt lymphoma, HCV-associated paraproteinemia and patients who did not have antiviral treatment history available were excluded. All information was obtained by review of electronic medical records. Baseline patient characteristics including age, sex, race, comorbidity including HIV infection, lymphoma stage, histology, prognostic score and baseline lactate dehydrogenase (LDH) were recorded. Lymphomas were classified according to the 2016 WHO classification. Prognostic score was calculated using International Prognostic Index (IPI) for aggressive lymphomas, Follicular Lymphoma International Prognostic Index (FLIPI) for indolent lymphomas other than chronic lymphocytic leukemia (CLL) and CLL-IPI for CLL. Details of lymphoma treatment and antiviral therapy were recorded. Virologic clearance (VC) was used to collectively describe both SVR (undetectable HCV RNA 12 weeks after completion of antiviral treatment) and spontaneous clearance of HCV without treatment. Study outcomes were overall response rate (ORR), complete response rate (CR), overall survival (OS) and progression free survival (PFS). Results: We found 397 patients with lymphoma at our institution, of which, 40 patients had HCV. Thirty-eight patients had complete lymphoma and antiviral treatment history available and were included in the analysis. Median age was 58 years, 90% were AA; 68% were men. Diffuse large B-cell lymphoma (DLBCL) was the predominant histology (50%). Advanced stage (64%), aggressive lymphoma (60%), good prognostic score (74%) and elevated LDH (66%) were common. A total of 21 patients were treated, 18 with DAA and 3 with interferon-based therapy. Twenty-two patients had VC, either spontaneous or with antiviral therapy. Patients with VC, had significantly higher ORR (95% vs 69%, RR 2.4, CI95 1.3-4.4, p&lt;0.05) and CR (73% vs 38%, 2.29, CI95 1.1-5.0.0, p&lt;0.05) compared to patients without VC. Median OS was also significantly higher in patients with VC than patients without VC (not reached vs 89 months, RR 0.4, CI95 0.2-0.6, p&lt;0.05) . Median PFS was not significantly different between two groups. We analyzed ORR and CR in subgroups of aggressive lymphoma, indolent lymphoma and DLBCL. Patients with VC had significantly higher CR then patients without VC in the subgroups of aggressive lymphoma and DLBCL (100% vs 46% and 100% vs 45% respectively, p&lt;0.05), while ORR was not different. Conclusions: Hepatitis C VC is associated with improved CR and OS in predominantly AA lymphoma patients including patients with aggressive B-NHL. The precise role and timing of HCV antiviral therapy in HCV-associated aggressive B-NHL should be assessed in large prospective studies that include AA patients. Disclosures No relevant conflicts of interest to declare.

362. Hepatitis C Virus (HCV) Co-Infection in Women Living with Human Immunodeficiency Virus (HIV) in Northwest Louisiana

BackgroundHIV and HCV infection are emerging global public health problems. People living with untreated HIV infection have higher HCV viral loads and more rapid HCV disease progression with twice the rates of perinatal HCV transmission. Data are lacking in HCV coinfected women living with HIV. Our study reviewed underrepresented minority group of women living with HIV/HCV in Northwestern Louisiana to better understand epidemiology, risk factors and access to care among this cohort.MethodsWomen with HIV/HCV coinfection aged 18–70 years who presented to an academic medical center between November 2011 and November 2018 were included for analysis. A retrospective chart review was conducted. Data were collected and analyzed on demographics (age, race), risk factors (sexual history, drug use), HIV (viral load, CD4 count, antiretroviral treatment (ART)), and HCV (viral load level and antibody, genotype, alanine transaminase, liver fibrosis, liver cirrhosis, referral, and treatment).ResultsA total of 41 patients met our inclusion criteria. The mean age was 52 years. Of these HIV/ HCV coinfected women, 27 (66%) were African American and 14 (34%) Caucasian. 18 (44%) had history of Injection drug use. Thirty-nine out of 41 (95%) were linked to HIV care and on antiretroviral therapy with 36 (88%) with CD4 count >200. Twenty-three out of 41 (56%) was referred for HCV treatment but only 11 (26%) co-infected patients received treatment for HCV.ConclusionIn this cohort of HCV/HIV coinfected women, only 26% of the women received HCV treatment. Some of the barriers include access to providers, linkage to care and behavioral and socioeconomic factors. The lack of timely appropriate HCV care in this underserved high-risk population is alarming especially in the current era of highly effective direct-acting antiviral therapy for HCV. Despite improved HIV care, further work needs to focus on optimizing HCV screening, linkage and treatment uptake in order to overcome multiple barriers to HCV elimination in this patient population.Disclosures All authors: No reported disclosures.

Naturally occurring NS5A and NS5B resistant associated substitutions in HCV and HCV/HIV patients in iranian population

The introduction of direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment promises shorter treatment duration, higher cure rates and fewer side effects. Naturally, occurring Resistance Associated Substitutions (RASs) are major challenge to the success of the HCV antiviral therapy. To determine the naturally occurring NS5A and NS5B RASs in Iranian HCV and HCV/human immunodeficiency virus (HIV) patients. A total of 209 DAA-naïve chronic HCV patients including 104 HCV mono-infected and 105 HCV/HIV co-infected cases were enrolled. Amplification and Sanger population sequencing of NS5A and NS5B regions of HCV genome were carried out. The amino acid sequence diversity of the NS5A and NS5B regions were analyzed using geno2pheno HCV. NS5A RASs were detected in 25.5% of HCV and 16.9% of HCV/HIV subjects. In HCV cases, clinically relevant RASs were L28M followed by M28Vand Q30H and Y93H/N. In HCV/HIV subjects, clinically relevant RASs were Y93H/N followed by L28M and P58T and M28V/T and Q30R. NS5B RASs were observed in 11.8% of HCV and 5.9% of HCV/HIV subjects. Clinically relevant substitutions were included V321A/I, C316Y, S282R and L159F. The major S282T mutation was not observed. The emergence of RASs is a growing issue in the setting of current treatment with DAAs. Although currently, screening of RASs is recommended before specific DAA regimens, it should be consider in patients with therapeutic failure and in the cases of retreatment.

Incidence and risk factors for hepatocellular cancer in individuals with haemophilia: A National Inpatient Sample Study.

Among haemophilic (H) men, hepatitis C virus (HCV) is the leading cause of liver disease and mortality, but demographics and risks of hepatocellular carcinoma (HCC) in H are not well known. Adult discharges in H and non-haemophilic (NH) men, with and without HCC were identified in the National Inpatient Sample (NIS) between 1998 and 2014, using ICD-9 codes. Analyses included NIS-provided discharge-level weights to reflect national estimates. Categorical variables were assessed by Rao-Scott chi-square and continuous variables by weighted simple linear regression. HCC predictors were determined by weighted multivariable logistic regression. Of 18098 H, 144 (0.79%) had HCC between 1998 and 2014. Adjusted rates of HCC increased 3.0-fold in H vs 1.7-fold in NH (P=0.484). Among HCV+, HCC rates adjusted for HIV, increased 2.2-fold in H vs 1.7-fold in NH (P=0.740), while among HIV+, HCC increased 1.4-fold in H vs 0.2-fold in NH (P=0.448). Among those with HCC, H were older than NH (P<0.001), Caucasian (P=0.006), platelet transfusion recipients (P<0.001), with greater comorbidity (P<0.001) and mortality (P<0.006). H with HCC also had greater rates of HCV and HIV (each P<0.001), lower rates of alcoholism and hyperlipidemia (each P<0.001), and similar rates of HBV (P=0.866), smoking (P=0.507) and obesity (P=0.502). In multivariable logistic regression, HCV was a strong predictor for HCC in haemophilia, (OR: 15.42, 95% CI: 8.75-27.16). Haemophilic men have increasing rates of HCC, similar to men without haemophilia. HCV is the major predictor of HCC in haemophilia. Future trends in HCC will depend on the impact of newer HCV antiviral therapy.

Incidence of Hepatocellular Carcinoma After Direct Antiviral Therapy for HCV in Patients With Cirrhosis Included in Surveillance Programs

Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN). Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n= 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n= 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n= 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC. Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P= .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCCscreening than the other 2 groups (P= .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR0.89; 95% CI 0.46-1.73; P= .73). Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity.

Comparison between Different Lines of Antiviral Combination Therapies against Hepatitis C Virus Genotype 4 in Egyptian Patients

Background: hepatitis C virus (HCV) infection in one of worldwide chief causes chronic liver illness. The extended effect of it is highly inconstant, ranging from least histological changes to broad fibrosis and cirrhosis with possibility of hepatocellular carcinoma (HCC). The morbidity and mortality of this global infection are growing. The estimated worldwide prevalence of HCV is a by the World Health Organization (WHO) affecting >170 million people worldwide. There is a varied distribution of HCV infection with about 23 million people likely to have it in the countries of Eastern Mediterranean Region. This is nearly number of infected people in both Americas and Europe. Egypt is considered to have highest prevalence worldwide with an expected 14.7% of total population seropositive for HCV. Aim of the Work: to compare the different new lines of antiviral combination therapies against hepatitis C virus genotype 4 in Egyptian patients as regards efficacy and safety. Material and Methods: an open label, single-center, parallel-groups, randomized controlled clinical study, comparing the different lines of antiviral combination therapies against hepatitis C virus in Egyptian patients as regards efficacy reflected by the sustained virological response and safety through reporting adverse effects occur with each drug combination. This study was conducted on confirmed HCV chronically infected patients with diagnosis based on HCV-RNA PCR. The cases were collected from viral hepatitis treatment unit in Electricity hospital, one of the centers of National Committee for Control of Viral Hepatitis (NCCVH). All cases in this study were assessed and managed according to updated guidelines by NCCVH in parallel with the European Association for Study of Liver (EASL) and the American European Association for Study of Liver (AASLD). Results: this study was conducted on 1000 patients with confirmed diagnosis of chronic HCV with positive serum HCV RNA by PCR technique. The cases were collected for this study had chronic hepatitis either without cirrhosis or with compensated cirrhosis differentiated by using the FIB-4 score. They could be INF-naive or INF-experienced. The antiviral regimens used were SOF/SIM, SOF/LDV±RBV, SOF/DCV±RBV, PAR/OMB/RBV, and IFN/SOF/RBV. Out of 1737 patients who underwent initial evaluation, 531 patients were not eligible for therapy due to the presence of one or more exclusion criteria. The main causes for treatment exclusion were advanced liver decompensation, inadequately controlled diabetes and HBV co-infection. The total number of patients enrolled and eligible for antiviral treatment was 1206, 1000 of them started the treatment course, while 206 patients did not start it due to receiving treatment in other centres or died before starting the treatment. Conclusion: 1000 patients started antiviral therapy for HCV, they showed good adherence to treatment and high SVR rates compared to other recently published real-life studies. We used seven different treatment regimens, all of which proved to be efficacious and safe with no clear preference for each over others.

Decreased hepatocellular carcinoma tumor burden with the achievement of hepatitis C virus sustained virologic response: unlocking the potential of T-cell-mediated immunosurveillance.

We describe two cases of patients with hepatitis C virus (HCV) treated with direct-acting antiviral (DAA) therapy who had dramatic improvement in hepatocellular carcinoma (HCC) tumor burden with DAA therapy alone. Both patients were diagnosed with HCC on screening magnetic resonance imaging shortly after beginning DAA therapy. Both patients achieved sustained virologic response (SVR) with dramatic improvement in HCC tumor burden on follow-up imaging without HCC treatment. Patients with multifocal or advanced HCC are infrequently treated with antiviral therapy for HCV. As a result, these cases provide unique insight into the ongoing debate regarding the impact of SVR on existing and recurrent HCC. We review the current literature regarding this debate, as well as the theory of immunosurveillance. We postulate that DAA therapy activates CD8+ T cells to induce a T-cell-mediated response and increased immunosurveillance to virus-induced liver cancer.

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