Hepatitis C Virus Cohort Research Articles

Retrospective study evaluating association of colorectal tumors and hepatitis C virus.

Chronic hepatitis C virus (HCV) has been associated with hepatic and extrahepatic malignancies. Limited studies have shown an association between colorectal adenomas and HCV populations. To study the prevalence of colorectal adenomas in patients with HCV compared to the general population and to evaluate if it is an independent risk factor for colorectal adenomas. Patients were divided into HCV and non-HCV based on their HCV RNA titers. Patients with alcoholic liver disease, hepatitis B infection, and inflammatory bowel disease were excluded. Continuous variables were analyzed using the Mann-Whitney U test, and categorical variables using χ 2 with P < 0.05 were considered statistically significant. The significant covariates (independent variables) were matched in both groups by propensity score matching, followed by multivariate regression analysis. Of the 415 patients screened, 109 HCV patients and 97 non-HCV patients with colonoscopy results were included in the study. HCV patients were older, had a smoking history, had less frequent aspirin use, and had a lower body mass index (BMI) (P < 0.05). The HCV cohort had a significantly increased number of patients with adenomas (adenoma detection rate of 53.2% vs 34%. P = 0.006). We performed a propensity-matched multivariate analysis where HCV infection was significantly associated with colorectal adenoma (OR: 2.070, P = 0.019). Our study shows a significantly higher rate of adenomas in HCV patients compared to the general population. Prospective studies would help determine if the increase in adenoma detection lowers the risk for colorectal cancer.

Hepatitis C Prevalence and Birth Outcomes among Pregnant Women in the United States: A 2010-2020 Population Study.

The rates of hepatitis C virus (HCV) infection have increased in the pregnant population. We aim to describe the age-stratified clinical outcomes and trends for inpatient pregnant women with HCV in the U.S. We utilized hospitalization data from the 2010-2020 National Inpatient Sample. Pregnancy and HCV were identified according to their ICD-9/ICD-10 codes. Demographic and clinical data including cirrhosis, mortality, preterm birth, and stillbirth were extracted. The age groups were defined as ≤18, 19-25, 26-34, and ≥35 years. We identified 195,852 inpatient pregnant women with HCV, among whom 0.7% were ≤18, 26.7% were 19-25, 57.9% were 26-34, and 14.8% were ≥35 years of age. The hospitalization rates of pregnant women with HCV increased overall between 2010 and 2020, with the highest velocity in the 26-34 age group. The 26-34 age group had the highest HCV burden, with an age-standardized hospitalization rate of 660 per 100,000 in 2020. The rates of mortality and cirrhosis were significantly higher in the HCV cohort and increased further with age (p < 0.05). Among the HCV pregnant cohort, 151,017 (77.1%) delivered during hospitalization. Preterm births and stillbirths were significantly higher in the HCV pregnant cohort compared to the controls across multiple age groups (p < 0.05). Minority race/ethnicity was associated with increased mortality, cirrhosis, preterm birth, and stillbirth (p < 0.001). HIV co-infection, hepatitis B co-infection, and diabetes increased the odds of cirrhosis (p < 0.001). Hospitalizations of pregnant women with HCV are escalating, and these women are at increased risk of mortality, cirrhosis, preterm birth, and stillbirth with modifying factors, exacerbating risks further.

Curtailing infection risks in hepatitis C patients: the effect of antiviral treatment in revision shoulder arthroplasty

BackgroundRevision shoulder arthroplasty (RevSA) is a complex procedure that can result in various postoperative complications. However, the impact of hepatitis C virus (HCV) on postoperative complications after RevSA remains unclear due to limited and inconsistent evidence. This study aims (1) to investigate the incidence of postoperative complications in patients with HCV undergoing RevSA, and (2) to evaluate the impact of HCV treatment on complication rates at different time points after the revision procedure, specifically at 90 days, 1 year, and 2 years MethodsWe queried a national, all-payer database to investigate recent trends in the utilization of RevSA among HCV patients to assess postoperative complication rates, including venous thromboembolism, wound complication, transfusion, and prosthetic joint infection. Statistical analyses involved propensity score matching to create balanced cohorts and logistic regression to determine the relative risk of postoperative complications. "Data was analyzed with the SPSS Statistics software (version 24.0 for Windows; IBM, Armonk, NY, USA). The study included patients who underwent partial or total RevSA procedures between January 1, 2010, and December 31, 2020. Patients were identified based on medical claims that included procedural codes for RevSA and associated diagnosis codes for PJI or insertion/removal of an antibiotic spacer. A Bonferroni correction was utilized because many tests were performed and statistical significance was set at p=0.0125. ResultsThe HCV cohort demonstrated higher prosthetic joint infection (PJI) rates at one-year (5.5 vs 3.9%, p=0.006) and two-year follow-ups (6.7 vs 4.6%, p=0.006). However, no significant differences emerged in venous thromboembolism (VTE) and wound complications rates between the HCV and non-HCV cohorts. Comparing untreated and treated HCV patients, the former showed significantly higher PJI rates at two-year p=0.010, while the treated group had significantly lower odds ratios for PJI. When comparing treated HCV patients with the no HCV cohort, minimal differences were found in postoperative outcomes, indicating no significant difference in the risk of complications between the groups ConclusionOur study observed an association between HCV patients who received antiviral treatment prior to RevSA and a reduced incidence of PJI compared to untreated HCV patients. When comparing this group to the non-HCV controls, there was no significant difference in the incidence of PJI, suggesting a potential association between antiviral treatment and the observed risk patterns in HCV patients. Proper management of HCV-positive patients during RevSA is crucial for improving outcomes and reducing complications.

Outcomes of Radiation Segmentectomy for Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease versus Chronic Viral Hepatitis.

To compare the outcomes of radiation segmentectomy for early-stage hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) versus hepatitis C virus (HCV). A retrospective analysis of consecutive patients with NAFLD- or HCV-related HCC treated with radiation segmentectomy from 01/2017-06/2022 was performed. Eligibility criteria included solitary tumor ≤8 cm or up to 3 HCC ≤3 cm, ECOG 0-1, and absence of vascular invasion or extrahepatic spread. Imaging best response was assessed per modified Response Evaluation Criteria in Solid Tumors. Target tumor and overall progression, time-to-progression (TTP), and overall survival (OS) were calculated. All outcomes were censored for liver transplantation (LT). Complete pathologic response (CPN) was assessed in patients who underwent LT. Of 142 patients included (NAFLD: 61; HCV: 81), most had cirrhosis (NAFLD: 87%; HCV: 86%) and small tumors (median size NAFLD: 2.3 cm; HCV: 2.5 cm). Patients with NAFLD had higher BMI (p<0.001) and worse ALBI scores (p=0.003). Patients with HCV were younger (p<0.001) and had higher AFP levels (p=0.034). Median radiation dose (NAFLD: 508 Gy; HCV: 452 Gy) and specific activity (NAFLD: 700 Bq; HCV: 698 Bq) were similar between cohorts. Objective response was 100% and 97% in the NAFLD and HCV cohorts, respectively. Target tumor progression occurred in 1 (2%) NAFLD and 8 (10%) HCV patients. Target tumor TTP was not met for either cohort. Overall progression occurred in 23 (38%) NAFLD and 39 (48%) HCV patients. Overall TTP was 17.4 months (95% CI 13.5-22.2) in NAFLD and 13.5 months (95% CI 0.4-26.6) in HCV patients (p=0.86). LT was performed in 27 (44%) NAFLD and 33 (41%) HCV patients, with a CPN rate of 63% and 54%, respectively. OS was not met in the NAFLD cohort and was 53.9 months (95% CI 32.1-75.7) in the HCV cohort (p=0.15). Although NAFLD and HCV are associated with different mechanisms of liver injury, patients with early-stage HCC treated with radiation segmentectomy achieve comparable outcomes.

Next-generation sequencing analysis of hepatitis C virus resistance-associated substitutions in direct-acting antiviral failure in South Korea.

We used next-generation sequencing (NGS) to analyze resistance-associated substitutions (RASs) and retreatment outcomes in patients with chronic hepatitis C virus (HCV) infection who failed direct-acting antiviral agent (DAA) treatment in South Korea. Using prospectively collected data from the Korean HCV cohort study, we recruited 36 patients who failed DAA treatment in 10 centers between 2007 and 2020; 29 blood samples were available from 24 patients. RASs were analyzed using NGS. RASs were analyzed for 13 patients with genotype 1b, 10 with genotype 2, and one with genotype 3a. The unsuccessful DAA regimens were daclatasvir+asunaprevir (n=11), sofosbuvir+ribavirin (n=9), ledipasvir/sofosbuvir (n=3), and glecaprevir/pibrentasvir (n=1). In the patients with genotype 1b, NS3, NS5A, and NS5B RASs were detected in eight, seven, and seven of 10 patients at baseline and in four, six, and two of six patients after DAA failure, respectively. Among the 10 patients with genotype 2, the only baseline RAS was NS3 Y56F, which was detected in one patient. NS5A F28C was detected after DAA failure in a patient with genotype 2 infection who was erroneously treated with daclatasvir+asunaprevir. After retreatment, 16 patients had a 100% sustained virological response rate. NS3 and NS5A RASs were commonly present at baseline, and there was an increasing trend of NS5A RASs after failed DAA treatment in genotype 1b. However, RASs were rarely present in patients with genotype 2 who were treated with sofosbuvir+ribavirin. Despite baseline or treatment-emergent RASs, retreatment with pan-genotypic DAA was highly successful in Korea, so we encourage active retreatment after unsuccessful DAA treatment.

Hepatitis C Is Associated With Higher Short-Term Complication Rates After Initial Aseptic and Septic Revision Total Hip Arthroplasty: A Matched Cohort Study

BackgroundIt is unclear if hepatitis C virus (HCV) negatively impacts outcomes of revision total hip arthroplasty (rTHA). The purpose of this study is to trend recent rTHA utilization in patients who have HCV and compare postoperative complication rates versus a matched cohort. MethodsAll patients who underwent rTHA were retrospectively identified in a national database. Patients who had HCV (n = 1,746) were matched 1:3 with a matching group (n = 5,238) for age, gender, and several comorbidities. Cochran-Armitage tests were used to analyze trends in the annual proportion of rTHA performed in patients who had HCV from 2010 to 2019. Rates of 90-day medical and prosthesis-related complications within 2 years postoperatively were compared with multivariable logistic regressions. ResultsThe annual proportion of rTHA performed in patients who had HCV significantly increased from 2010 to 2019 (P < .001). Patients who had HCV exhibited significantly higher rates of acute kidney injuries (7.6% versus 4.4%; odds ratio [OR] 1.50), transfusions (20.6% versus 14.6%; OR 1.38), and re-revisions for prosthetic joint infection (10.9% versus 6.5%; OR 1.73). In subgroup analyses, rates of re-revision for prosthetic joint infection after initial aseptic rTHA (7.1% versus 3.8%; OR 1.82) and periprosthetic fracture after initial septic rTHA (4.5% versus 1.6%; OR 2.77) were significantly higher in the HCV cohort. ConclusionSimilar to primary THA, patients who have HCV exhibit significantly increased complication rates after rTHA. With growing utilization in recent years, these data suggest that this population will comprise an increasingly larger proportion of rTHA procedures performed in the coming years.

H1-Antihistamines Reduce the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus, Hepatitis C Virus, or Dual Hepatitis B Virus-Hepatitis C Virus Infection.

PURPOSEH1-antihistamines (AHs) may exert protective effects against cancer. This study investigated the association of AH use with the risk of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV), hepatitis C virus (HCV), or dual HBV-HCV virus infection.MATERIALS AND METHODSPatients with HBV, HCV, or dual HBV-HCV infection were enrolled from Taiwan's National Health Insurance Research Database and examined for the period from January 1, 2006, to December 31, 2015. We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the association between AH use and HCC risk.RESULTSWe included patients with HBV infection (n = 521,071), HCV (n = 169,159), and dual HBV-HCV (n = 39,016). Patients with HBV, HCV, or dual virus infection who used AHs exhibited significantly lower risk of HCC relative to patients who did not use AH, with their adjusted hazard ratio being 0.489 (95% CI, 0.455 to 0.524), 0.484 (95% CI, 0.450 to 0.522), and 0.469 (95% CI, 0.416 to 0.529), respectively. Furthermore, there was a dose-response relationship between AH use and the risk of HCC in the HBV cohort. The adjusted hazard ratios were 0.597 (95% CI, 0.530 to 0.674), 0.528 (0.465 to 0.600), 0.470 (0.416 to 0.531), and 0.407 (0.362 to 0.457) for AH use of 28-42, 43-63, 64-119, and ≥ 120 cumulative defined daily doses, respectively, relative to no AH use. Additionally, there was also a dose-response relationship between AH use and the risk of HCC in the HCV and dual HBV-HCV cohorts.CONCLUSIONAH use may reduce the risk for HCC among patients with HBV, HCV, or dual infection in a dose-dependent manner. Further mechanistic research is needed.

A cost-effectiveness study of universal screening for hepatitis C virus infection in South Korea: A societal perspective.

Background/AimsThis study aimed to evaluate the cost-effectiveness of hepatitis C virus (HCV) screening compared to no screening in the Korean population from societal and healthcare system perspectives.MethodsA published decision-tree plus Markov model was used to compare the expected costs and quality-adjusted life years (QALY) between one-time universal HCV screening and no screening in the population aged 40–65 years using the National Health Examination (NHE) program. Input parameters were obtained from analyses of the National Health Insurance claims data, Korean HCV cohort data, or from the literature review. The population aged 40–65 years was simulated in a model spanning a lifetime from both the healthcare system and societal perspectives, which included the cost of productivity loss due to HCV-related deaths. The incremental cost-effectiveness ratio (ICER) between universal screening and no screening was estimated.ResultsThe HCV screening strategy had an ICER of $2,666/QALY and $431/QALY from the healthcare system and societal perspectives, respectively. Both ICERs were far less than the willingness-to-pay threshold of $25,000/QALY, showing that universal screening was highly cost-effective compared to no screening. In various sensitivity analyses, the most influential parameters on cost-effectiveness were the antibodies to HCV (anti-HCV) prevalence, screening costs, and treatment acceptance; however, all ICERs were consistently less than the threshold. If the anti-HCV prevalence was over 0.18%, screening could be cost-effective.ConclusionsOne-time universal HCV screening in the Korean population aged 40–65 years using NHE program would be highly cost-effective from both healthcare system and societal perspectives.

Epidemiology and treatment status of hepatitis C virus infection among people who have ever injected drugs in Korea: a prospective multicenter cohort study from 2007 to 2019 in comparison with non-PWID.

OBJECTIVESInjection drug use is a major risk factor for hepatitis C virus (HCV) infection; however, limited data on this topic are available in Korea. Thus, this study aimed to investigate the epidemiological and clinical characteristics, treatment uptake, and outcomes of HCV infection among people who inject drugs (PWID).METHODSWe used the data from the Korea HCV cohort, which prospectively enrolled patients with HCV infection between 2007 and 2019. Clinical data and results of a questionnaire survey on lifetime risk factors for HCV infection were analyzed according to a self-reported history of injection drug use (PWID vs. non-PWID group).RESULTSAmong the 2,468 patients, 166 (6.7%) were in the PWID group, which contained younger patients (50.6±8.2 vs. 58.2±13.1 years) and a higher proportion of male (81.9 vs. 48.8%) than the non-PWID group. The distribution of PWID showed significant regional variations. Exposure to other risk factors for HCV infection was different between the groups. The proportion of patients with genotype non-2 infection was higher in the PWID group. Treatment uptake was higher in the PWID group in the interferon era; however, it was comparable between the groups in the direct-acting antiviral era. The rate of sustained virological response did not significantly differ between the groups.CONCLUSIONSAs of 2019, PWID constituted a minority of HCV-infected people in Korea. The epidemiological characteristics, but not treatment uptake and outcomes, were different between the PWID and non-PWID groups. Therefore, active HCV screening and treatment should be offered to PWID in Korea.

Willingness to participate in research among black patients with liver disease: A national cross-sectional study.

In the United States, Black people are disproportionately diagnosed with hepatitis C virus (HCV) compared with White people but are under-represented in HCV studies. In this US-based cross-sectional telephone survey study, we assessed willingness to participate (WTP) in health/medical research and attitudes and beliefs that may influence WTP among Black patients with HCV. Two hundred participants who had current or prior HCV diagnosis and self-identified as Black or African American were recruited from a national HCV cohort study and an outpatient hepatology clinic. WTP responses ranged from 1 (not at all willing) to 5 (very willing). Multivariable models were used to identify factors associated with the overall mean WTP score. In addition, an open-ended question solicited strategies to help increase research participation from the Black community. Overall, participants reported moderate WTP in research (Mean [95% Confidence Interval (CI)]=3.78 [3.68, 3.88]). Of 13 types of research presented, participants reported lowest WTP for randomized controlled trials of medications (Mean [95% CI]=2.31 [2.11, 2.50]). The initial multivariable model identified higher subjective knowledge of research as positively associated with WTP (Parameter estimate [95% CI]=0.15 [0.02, 0.27]). Sensitivity analyses also identified higher perceived benefits of research as an additional factor associated with WTP. Qualitative findings indicate that greater community-based outreach efforts would increase accessibility of research opportunities. When given the opportunity to participate, Black participants with HCV reported moderate WTP in health/medical research. Research sponsors and investigators should employ community-based outreach to expand access and awareness of research opportunities.

Signatures of immune dysfunction in HIV and HCV infection share features with chronic inflammation in aging and persist after viral reduction or elimination

Chronic inflammation is thought to be a major cause of morbidity and mortality in aging, but whether similar mechanisms underlie dysfunction in infection-associated chronic inflammation is unclear. Here, we profiled the immune proteome, and cellular composition and signaling states in a cohort of aging individuals versus a set of HIV patients on long-term antiretroviral therapy therapy or hepatitis C virus (HCV) patients before and after sofosbuvir treatment. We found shared alterations in aging-associated and infection-associated chronic inflammation including T cell memory inflation, up-regulation of intracellular signaling pathways of inflammation, and diminished sensitivity to cytokines in lymphocytes and myeloid cells. In the HIV cohort, these dysregulations were evident despite viral suppression for over 10 y. Viral clearance in the HCV cohort partially restored cellular sensitivity to interferon-α, but many immune system alterations persisted for at least 1 y posttreatment. Our findings indicate that in the HIV and HCV cohorts, a broad remodeling and degradation of the immune system can persist for a year or more, even after the removal or drastic reduction of the pathogen load and that this shares some features of chronic inflammation in aging.

Hepatitis E Infection in a Longitudinal Cohort of Hepatitis C Virus and HCV/HIV Coinfected Persons.

Hepatitis E virus (HEV) is thought to be common in the United States with increased prevalence in those with concomitant hepatitis C virus (HCV) or HCV/HIV coinfection. Little is known regarding true prevalence, incidence, and antibody seroreversion in these populations. We sought to define these rates among HCV and HCV/HIV coinfected persons in the Washington, DC area. Two longitudinal cohorts of HCV and HCV/HIV coinfected subjects from the Washington, DC area were evaluated. Multiple HEV test modalities were deployed including immunoglobulin G (IgG) and immunoglobulin M (IgM) antibody testing, evaluation of antibody avidity, HEV RNA testing, and HEV enzyme-linked immune absorbent spot (ELISPOT) analysis. A total of 379 individuals were evaluated including 196 who were HCV monoinfected and 183 HCV/HIV coinfected. Anti-HEV IgG was detected and confirmed in 18.7% of the cohort at baseline. None demonstrated anti-HEV IgM positive or HEV RNA positive results. Proportions of HEV antibody prevalence did not significantly differ between groups. Longitudinal follow-up samples were available for 226 individuals with a mean follow-up time of 24 months. Seroreversion was noted in 1.8%. One HCV/HIV infected person seroconverted to HEV IgG positivity in the followed cohort. About 40% of the positive population demonstrated high avidity suggestive of more remote exposure. Interferon gamma ELISPOT was performed in 70 subjects and false negative and false positive HEV enzyme-linked immunosorbent assay antibodies were identified. In HIV-infected persons in the United States HEV exposure and seroconversion is frequent enough that HEV should be considered in the differential diagnosis of acute hepatitis. Seroreversion may lead to underestimation of true infection risk.

S1007 Epidemiology of Extrahepatic Manifestations of Chronic Hepatitis C Infection: A National, Population-Based Study

INTRODUCTION: Although primarily an infection of the liver, chronic hepatitis C virus (HCV) infection has been associated with numerous extrahepatic manifestations (EHM). These include autoimmune, lymphoproliferative, dermatologic and renal disorders. Although a direct causal link has not been well established, experimental studies have shown that HCV can disrupt the body’s immune system and induce autoimmunity. Despite being a major cause of morbidity and mortality, large scale studies describing the epidemiologic characteristics of these EHM are limited. METHODS: We evaluated the prevalence of EHM among patients with chronic HCV infection using a large commercial database called Explorys, which is an aggregate of electronic health data from 26 US healthcare systems. We identified patients with chronic HCV infection between June 2015 and June 2020, based on Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Within this cohort, we investigated the prevalence of several well documented EHM associated with chronic HCV (Table 1) and compared it with the control group (active patients without chronic HCV infection). RESULTS: Of the 39,212,680 individuals active in the database, we identified a total of 181,450 individuals with chronic HCV infection. Prevalence of chronic HCV infection was 0.46%, and was higher among African Americans in comparison to Caucasians (prevalence ratio (PR): 1.78, 95 CI 1.76–1.81), and higher among men than women (PR: 1.70; 95 CI 1.68–1.72). Compared to our control, patients with chronic HCV had significantly higher prevalence of various EHM including dermatologic, rheumatoid, hematologic, and autoimmune diseases that were described in our study (Table 1). Notably, relative to the patients without HCV, the prevalence ratio of cryoglobulinemia was the highest compared to other EHM (PR: 102.5; 95 CI 93.1–112.9). Interestingly, we also found no significant difference in prevalence of Hashimoto thyroiditis between the chronic HCV cohort and control group (OR: 0.953; 95 CI 0.88–1.03 P < 0.3). CONCLUSION: This is one of the largest studies to date describing the epidemiological characteristics of EHM among patients with chronic HCV infection. EHM are often the initial presenting complaint among patients with undiagnosed chronic HCV infection. Hence, understanding its prevalence is an integral factor in appropriate screening and treatment of chronic HCV infections.Table 1.: Prevalence ratio of EHM among patients with chronic HCV infection (compared to patients without chronic HCV infection)

Frequent occurrence of low-level positive autoantibodies in chronic hepatitis C

Evidence of autoimmune disease associated with hepatitis C virus (HCV)-infection has important clinical implications. A systematic profile of these autoantibodies in relevant clinical cohorts relative to healthy controls is needed to better inform current standard of care for chronic hepatitis C. Samples from an Australian cohort of chronic HCV-infected subjects (n=127) were tested for the presence of 19 diagnostic autoantibodies and compared with data available from a control cohort representing a general Caucasian population (n=198). Chronic HCV-infected individuals had a greater number of autoantibodies than controls (p<0.0001). Anti-nuclear antibodies (ANA) followed by anti-smooth muscle antibodies (SMA) were the most frequently detected autoantibodies within the HCV cohort and significantly more than in the control cohort (p<0.0001 and p=0.006, respectively). However, for most autoantibody assays the 95th percentile approximated the reference value for positivity. None of the autoantibodies were significantly associated with age or sex for the HCV cohort, except SMA positivity that was significantly higher in chronic HCV-infected male subjects (p<0.0001). Autoantibodies found in chronic HCV-infected subjects were commonly low positive and not disease-specific. Accordingly, general screening for autoimmunity in HCV-infected subjects should not be performed unless there is high clinical suspicion of an underlying autoimmune disease.

Efficacy and Safety of Direct-Acting Antiviral Therapy in Patients With Chronic Hepatitis C Virus Infection: A Real-World Single-Center Experience in Tianjin, China.

ObjectiveToward the limited real-world data concerning the treatment response to brand direct-acting antiviral agents (DAAs) therapy, we proposed to evaluate the efficacy and safety of DAAs for the treatment of chronic hepatitis C virus (HCV) in mainland China.MethodsIn this retrospective, single-center, cohort study, all HCV-infected adult patients treated with brand DAA drugs covered by Tianjin local health insurance (Apr 2018–Sept 2019) and responding to other specific inclusion criteria were recruited. The five available DAA regimens included sofosbuvir + ribavirin (SOF + RBV), elbasvir/grazoprevir (EBR/GZR), ombitasvir/paritaprevir/ritonavir/dasabuvir (OBV/PTV/r/DSV) ± RBV, daclatasvir + asunaprevir (DCV + ASV), and SOF + DCV ± RBV. Demographic, virologic, clinical, and adverse effects data obtained during and after DAAs treatment were collected. We evaluated the rate of sustained virological response at 12 weeks post-treatment (SVR12), the incidence of adverse effects, and assessed the factors associated with SVR12.ResultsFour hundred ninety-four patients finished the treatment and completed the 12-week post-treatment follow-up. The overall SVR12 rate was estimated at 96.96%. SVR rates greater than 95% were achieved in most of the HCV genotypes with the exception of GT1a (0%), GT3a (93.33%), and GT3b (88.24%). SVR12 for patients treated with DCV + ASV, EBR/GZR, OBV/PTV/r/DSV ± RBV, SOF + DCV ± RBV, and SOF + RBV for 12 or 24 weeks was 86.67%, 100%, 98.11%, 97.56%, and 95.06%, respectively. Subjects with compensated cirrhosis (92.73%) and prior treatment experience (77.78%) had significantly lower SVR rates when compared to chronic hepatitis C (98.15%) and treatment-naive (97.69%) groups. In Tianjin, the available DAA regimens were generally well-tolerated, and not a single serious adverse event was reported.ConclusionIn this large real-life single-center HCV cohort from China, oral DAAs were highly effective and well-tolerated. Further and larger-scale studies are needed to evaluate their clinical safety and efficacy.

Lower Likelihood of Post-transplant Graft Failure, Death, and Retransplantation in the Era of Direct-Acting Antivirals

Direct-acting antivirals (DAAs) are expected to improve outcomes for patients with hepatitis C virus (HCV) infection after liver transplantation (LT). We aim to evaluate trends in post-LT outcomes with availability of DAAs. We retrospectively evaluated USadults transplanted from January 1, 2002, to March 31, 2018, using the United Network for Organ Sharing Registry, stratified by pre-DAA (January 1, 2002- to December 31, 2013) vs. post-DAA (January 1, 2014-, to March 31, 2018) eras. Adjusted multivariate Cox regression analyses and competing risk models evaluated likelihood of graft failure, death, and retransplantation (re-LT). Among 97,147 patients, 30.2% had HCV infection and 19.4% had hepatocellular carcinoma (HCC). Of all patients, 31.9% experienced graft failure, 27.1% died after LT, and 4.7% underwent re-LT. The post-DAA era experienced lower likelihood of graft failure (hazard ratio [HR] = 0.69, p<0.001). Although patients with HCV infection (HR = 1.18, p < 0.001) and HCC (HR = 1.11, p < 0.001) had higher likelihood of graft failure in the pre-DAA era, no differences were seen in the post-DAA era. Although patients with HCV infection (HR = 1.20, p < 0.001) and HCC (HR = 1.17, p<0.001) had higher likelihood of death after LT in the pre-DAA era, no differences were seen in the post-DAA era. The post-DAA era had lower likelihood of post-LT death when stratified by non-HCC (HR = 0.70, p < 0.001) and HCC cohorts (HR = 0.67, p < 0.001) or by non-HCV (HR = 0.73, p < 0.001) and HCV (HR = 0.58, p < 0.001) cohorts. Although patients with HCV infection and HCC had higher risk of post-LT graft failure and death in the pre-DAA era, the disparity disappeared in the post-DAA era independently of each other. This likely reflects impact of DAAs on improving post-LT outcomes among patients with HCV infection and improved selection of patients with HCC for LT after 2014.

Low Utilization of Direct-Acting Antiviral Agents in a Large National Cohort of HIV and HCV Coinfected Medicare Patients in the United States: Implications for HCV Elimination.

Hepatitis C virus (HCV) infection is common in people living with HIV/AIDS (PLWHA). The advent of direct-acting antiviral agents (DAAs) has made HCV elimination a realistic goal. We conducted a retrospective cohort study using the US Medicare Fee-For-Service claims data and outpatient prescription drug data to assess the HCV DAA initiation and completion among newly diagnosed HIV-HCV-coinfected Medicare patients enrolled in 2014-2016. DAA initiation was defined as filling at least 1 prescription of DAAs during 2014-2016. DAA completion was defined as taking an 8-week or longer DAA treatment course for patients without cirrhosis and a 12-week or longer treatment duration for those with cirrhosis. Among 12 152 HIV-HCV-coinfected Medicare patients, 20.9% received the DAA treatment in 2014-2016. The average time from HCV diagnosis to DAA initiation was 277 days. The overall DAA completion rate was 92% among 2537 patients who used DAAs. Interventions are needed to improve DAA uptake in PLWHA.

Hepatitis C Virus Infection and the Temporal Trends in the Risk of Liver Cancer: A National Register-Based Cohort Study in Sweden.

In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims of this study were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV infection between 1990 and 2015. The HCV cohort (n = 52,853) was compared with a matched non-HCV comparison cohort (n = 523,649). Both the national Cancer Register (CR) and Cause of Death Register (DR) were used for follow-up. The crude and age-standardized PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as HRs using stratified Cox hazards regression. There were 1,609 with PLC diagnosis in the HCV cohort; the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013 while remaining low and stable in the comparison cohort. In the HCV cohort, the age-standardized PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 [95% confidence interval (CI), 1.54-3.75] in 2000 and 3.31 (2.51-4.12) in 2014. The highest SIR was 73 (65.9-79.5) among those infected for 35 to 40 years; and the highest HR was 65.9 (55.9-77.6) for men and 62.2 (31.9-121.1) for women. There was a considerable increase in PLC incidence over time and an extremely high relative risk in the population with HCV infection for more than 35 years. The national HCV-associated PLC incidence should be monitored in future studies to evaluate the effect of direct-acting antiviral (DAA) treatment.

Long-term morbidity and mortality in a Canadian post-transfusion hepatitis C cohort: Over 15 years of follow-up.

The Federal Government of Canada established a $1.1 billion compensation programme in 1999 to support individuals who acquired hepatitis C virus (HCV) through blood products between January 1986 and July 1990. We aimed to describe the morbidity and mortality of this unique post-transfusion cohort (n=4550) followed for over 15years from 2000 to 2016. The age-standardized mortality rates were compared with that of the Canadian general population and HCV cohorts from other countries. We evaluated all-cause mortality using Kaplan-Meier survival curves and HCV-related and unrelated mortality using competing risk models. The age-standardized all-cause and HCV-related mortality rates per 10000 person-years were 127 (95% CI: 117-138) and 76 (95% CI: 69-85) for males, and 77 (95% CI: 69-87) and 43 (95% CI: 37-51) for females, respectively. The risk of death of the post-transfusion cohort was almost twice as high as the Canadian general population (rate ratio=1.8; 95% CI: 1.7-1.9). All-cause, HCV-related and HCV-unrelated mortality were 20%, 12% and 8%, respectively at 15years of follow-up. By comparison, HCV-related mortality rates per 10000 person-years for population-based HCV cohorts varied from 18 and 11 in Australia to 65 and 43 in Scotland for males and females, respectively. We reported long-term follow-up data for the largest post-transfusion cohort in the literature. The all-cause mortality rates were markedly higher than that of the Canadian general population. We also showed that HCV-related mortality were greater compared to other HCV cohorts. This suggests that continued efforts to identify and treat post-transfusion HCV are warranted.

Efficacy of direct-acting antivirals: UK real-world data from a well-characterised predominantly cirrhotic HCV cohort.

Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C virus (HCV) infection. We describe UK real-world DAA experience. Individuals commencing HCV treatment containing a DAA regimen (Mar 2014-Nov 2016), participating in the National HCV Research UK (HCVRUK) Cohort Study were recruited from 33 UK HCV centers. The data were prospectively entered at sites onto a centralised database. The data were reported as median (Q1-Q3). Of the 1448 treated patients, 1054 (73%) were males, the median age being 54 years (47-60), 900 (62%) being genotype 1 and 455 (31%) genotype 3. The majority, 887 (61%) had cirrhosis, and 590 (41%) were treatment-experienced. DAA regimens utilised: genotype1 sofosbuvir (SOF)/Ledipasvir/±Ribavirin (625/900, 69%) and Ombitasvir/Paritaprevir/Dasabuvir/±RBV (220/900, 24%), and in genotype 3 SOF/Daclatasvir + RBV (256/455, 56%) and SOF/pegylated interferon/RBV (157/455, 35%). Overall, 1321 (91%) achieved sustained virological response (SVR12), genotype 1 vs 3, 93% vs 87%, P < .001. Prior treatment, presence of cirrhosis and treatment regimen did not impact SVR12. Predictors of treatment failure were genotype 3 infection, OR, 2.015 (95% CI: 1.279-3.176, P = .003), and male sex, OR, 1.878 (95% CI: 1.071-3.291, P = .028). Of those with hepatic decompensation at baseline (n = 39), 51% (n = 20) recompensated post-treatment, lower baseline serum creatinine being associated with recompensation (P = .029). There were two liver-related deaths, both having decompensated disease. This real-world UK data, comprising of a predominantly cirrhotic HCV genotype 1/3 cohort, confirms DAA efficacy with an overall 91% SVR12, with 51% recompensating post-treatment. Genotype 3 infection was a predictor of treatment failure.