Pioneering a Global Cure for Chronic Hepatitis C Virus Infection.

This year's Lasker∼Debakey Clinical Medical Research Award honors Ralf Bartenschlager, Charles Rice, and Michael Sofia, pioneers in the development of curative and safe therapies for the 170 million people with hepatitis C virus infection.

Success of the US Veterans Health Administration's Hepatitis C Virus Care Continuum in the Direct-acting Antiviral Era.

BACKGROUND: Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and subsequent complications. We describe the hepatitis C care continuum within the Veterans Health Administration 1 January 2014 to 31 December 2022. METHODS: We included individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment 1 January 2014 to 31 December 2022. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia. RESULTS: We identified 133 732 Veterans with hepatitis C viremia. Hepatitis C treatment was initiated in 107 134 (80.1%), with sustained virologic response achieved in 98 136 (91.6%). In those who achieved sustained virologic response, 1097 (1.1%) had repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum. CONCLUSIONS: The Veterans Health Administration has treated 80% of Veterans with hepatitis C in care 2021-2022 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders.

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×103 IU per milliliter and 1804.93×103 IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).

Incidence of Etiology-specific Hepatocellular Carcinoma: Diverging Trends and Significant Heterogeneity by Race and Ethnicity.

BACKGROUND & AIMS: The main causes of hepatocellular carcinoma (HCC) include chronic hepatitis C and B viral infections (HCV, HBV), nonalcoholic fatty liver disease (NAFLD), and alcohol-related disease (ALD). Etiology-specific HCC incidence rates and temporal trends on a population-basis are needed to improve HCC control and prevention. METHODS: All 14,420 HCC cases from the Florida statewide cancer registry were individually linked to data from the hospital discharge agency and the viral hepatitis department to determine the predominant etiology of each case diagnosed during 2010 to 2018. Age-adjusted incidence rates (AAIRs) were used to assess the intersection between etiology and detailed race-ethnicity. Etiology-specific temporal trends based on diagnosis year were assessed using Joinpoint regression. RESULTS: HCV remains the leading cause of HCC among men, but since 2017 NAFLD-HCC is the leading cause among women. HCV-HCC AAIRs are particularly high among U.S.-born minority men, including Puerto Rican (10.9 per 100,000), African American (8.0 per 100,000), and U.S.-born Mexican American men (7.6 per 100,000). NAFLD is more common among all Hispanics and Filipinos and HBV-HCC among Asian and Haitian black men. HCV-HCC surpasses HBV-HCC in Asian women. ALD-HCC is high among specific Hispanic male groups. Population-based HCV-HCC rates experienced a rapid decline since 2015 (-9.6% annually), whereas ALD-HCC (+6.0%) and NAFLD-HCC (+4.3%) are rising (P < .05). CONCLUSIONS: New direct acting anti-viral drugs have impacted rates of HCV-HCC, offsetting important increases in both ALD- and NAFLD-HCC. Hispanics may be a group of concern because of higher rates for ALD- and NAFLD-HCC. HCC etiology varies remarkably and may warrant specific interventions by detailed race-ethnicity.

Excellent hepatitis C virus cure rates despite increasing complexity of people who use drugs: Integrated-Test-stage Treat study final outcomes.

Achieving hepatitic C virus (HCV) elimination requires linking people who use drugs (PWUD) into care. We report final direct-acting antivirals (DAAs)-based outcomes from the Integrated-Test-stage -Treat (ITTREAT) study. Project ITTREAT (2013-2021), based at an addiction centre, was a 'one-stop' service with innovative linkage to care strategies. Primary outcome was sustained virological response (SVR12) (intention to treat ITT) including whether individuals were recruited in first (period 1) versus last four (period 2 included the COVID-19 pandemic) years of the study. Number recruited were n = 765, mean age 40.9 ± 10.1 years, 78% males, history of current/past injecting drug use (IDU) and alcohol use being 77% and 90%, respectively. Prevalence of a positive HCV PCR was 84% with 19% having cirrhosis. Comparing those recruited in period 2 versus period 1, there was increasing prevalence of IDU, 90% versus 72% (p < .001); homelessness, 67% versus 50% (p < .001); psychiatric diagnosis, 84% versus 50% (p < .001); overdose history 71% versus 31% (p < .001), receiving opioid agonist treatment (OAT) 75% versus 52% (p < .001) and comorbidity 44% versus 25% (p < .001). Of those treated with DAAs (n = 272), ITT SVR rates were 86% (95% CI: 81%-90%), being similar in period 2 versus period 1. Predictors of non-SVR were receiving OAT (OR 0.33, 95% CI: 0.12-0.87, p = .025) and ≥80% adherence (OR 0.01, 95% CI: 0.003-0.041, p < .001). Reinfection rates period 2 versus period 1 (per 100 person-years) were 1.84 versus 1.70, respectively. In the treated cohort, mortality was 15%, being mostly drug-related. Despite increasing complexity of PWUD, high SVR12 rates are achievable with use of OAT and good adherence.

Effect of previous infection with hepatitis B virus on the incidence of hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection.

Previous infection with hepatitis B virus (HBV), which is assessed by HBV core antibody (HBcAb) or surface antibody (HBsAb) titres, has reportedly been associated with an increased risk of developing hepatocellular carcinoma (HCC). We investigated the influence of previous HBV infection on the incidence of HCC in patients with hepatitis C virus (HCV) infection who achieved eradication of HCV, that is sustained virologic response (SVR). Both HBcAb and HBsAb were measured in a total of 1214 patients with HCV infection who had not been coinfected with HBV, as determined by both negative HBs antigen and HBV DNA, and in whom SVR was confirmed. Patients were followed up for a median of 5.7 years, and the incidence of post-SVR HCC was compared based on HBcAb and/or HBsAb. In both univariate and multivariate analyses, the incidence of post-SVR HCC did not differ based on the presence of HBcAb or HBsAb. In conclusion, previous HBV infection has no impact on the incidence of HCC in patients with HCV after SVR.

Chronic viral hepatitis C micro-elimination program using telemedicine in Guigang city.

Hepatitis C virus (HCV) represents a formidable menace to human health, necessitating urgent attention. The objective of this study was to assess the efficacy and safety of HCV health management in the city of Guigang which consists of five districts, employing a comprehensive multi-modal approach. The study systematically carried out HCV screening in Guigang city which consists of five districts, such as Gangbei District, Gangnan District, Guiping District, Qintang District, and Pingnan District from 1 January 2016 to 30 December 2022. The target population consisted of individuals residing in these aforementioned districts, falling within the age range of 30-75 years. A multidisciplinary HCV management team was established to deliver anti-HCV screening, diagnosis, and direct-acting antiviral (DAA) therapy. The primary outcome of interest was the achievement of sustained virologic response (SVR). A total of 2489 individuals were included as the target population, with 1694 individuals residing in Gangbei District, 202 in Gangnan District, 111 in Qintang District, 167 in Pingnan District, and 315 in Guiping District. Out of these individuals, 2478 were subjected to anti-HCV screening. The screening rates varied across the districts, ranging from a peak of 99.55% in Guigang City to a nadir of 98.41% in Guiping District. Remarkably, within Guigang City, a noteworthy enhancement was observed in the HCV-RNA diagnosis rate from 23.4% prior to program implementation to a remarkable 100% following 7 years of intervention and management. Furthermore, the diagnosis and treatment coordination rate experienced a substantial improvement, rising from 26.8% before program inception to 80%. Importantly, a total of 1180 individuals affected by hepatitis C were successfully cured, equating to a 100% cure rate. Logistic regression analysis revealed a significant association between serological status and factors such as Aging, bilirubin, and glutamic oxalacetic transaminase. The findings from our investigation unveil a pioneering HCV management model, exemplified by the Guigang model, which has contributed crucially to HCV microclearance efforts and serves as an invaluable reference for future initiatives.

Real-world hepatitis C prevalence and treatment uptake at opioid agonist therapy clinics in Ontario, Canada.

Widespread screening for hepatitis C virus (HCV) is necessary for Canada to meet its HCV elimination goals by 2030. People who currently or previously injected drugs are at high risk for HCV. Opioid agonist therapy (OAT, such as methadone and buprenorphine) has been shown to help stabilize the lives of people who are opioid-dependent. The distribution of OAT in North America typically requires daily, weekly, or monthly clinic visits and presents an opportunity for engagement, screening and treatment for those at high-risk of HCV. In this study, HCV screening was conducted by staff at OAT clinics in Ontario from 2016 to 2020 and those with chronic infections were treated on-site with direct-acting antivirals. Point-of-care or dried blood spot (DBS) testing was used for antibodies, DBS or serum for HCV RNA and serum for HCV RNA at SVR12 (sustained virological response). Clinics screened 1954 people (mean age 40 years ±12, 63% male). Forty-five percent were antibody positive, of whom 64% were HCV RNA+. Eighty percent of those RNA+ set an appointment in which 99% attended. Ninety-six percent started treatment with 87% completing treatment. Sixty-eight percent of people who completed treatment submitted a sample for SVR12 testing of which 97% achieved a virological cure. Results suggest that HCV screening and treatment at OAT clinics is feasible, effective and warrants expansion. Data suggest strong treatment adherence due to high rates of SVR12 comparable with other OAT-based HCV treatment programs. The lack of SVR12 sampling could be addressed by either on-site phlebotomy or incentivizing SVR12 sampling.

Clinical and patient-reported outcomes in patients with chronic hepatitis B and C and non-alcoholic fatty liver disease from real-world practices in Saudi Arabia, Turkey and Egypt.

Patients with chronic liver disease (CLD) experience health-related quality of life (HRQoL) and patient-reported outcomes (PROs) impairments. We assessed and identified predictors of HRQoL and PROs in CLD patients from Saudi Arabia (SA), Turkey and Egypt. Patients enrolled in Global Liver Registry™ with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) were included. Clinical data and PRO questionnaires (FACIT-F, CLDQ and WPAI) were compared across countries. Linear regression identified PRO predictors. Of the 4014 included patients, 26.9% had CHB, 26.9% CHC and 46.1% NAFLD/NASH; 19.2% advanced fibrosis. Compared across countries, CHB patients were younger in Egypt (mean age [years] 41.2 ± 11.4 vs. 45.0 ± 10.3 SA, 46.1 ± 12.0 Turkey), most often employed in SA (64.8% vs. 53.2% Turkey) and had the lowest prevalence of obesity in Turkey (26.7% vs. 37.8% SA, 38.5% Egypt). In SA, CHB patients had lowest prevalence of fibrosis and comorbidities (all p < .01). There was a higher frequency of males with NAFLD/NASH in SA (70.0% vs. 49.6% Turkey, and 35.5% Egypt). Among NAFLD/NASH patients, CLDQ-NAFLD/NASH scores were highest in SA (mean total score: 5.3 ± 1.2 vs. 4.8 ± 1.2 Turkey, 4.1 ± 0.9 Egypt, p < .01). Independent predictors of worse PROs included younger age, female sex, advanced fibrosis, non-hepatic comorbidities and lack of regular exercise (all p < .05). Clinical presentation and PRO scores of CLD patients vary across SA, Turkey and Egypt. Impairment of HRQoL is associated with demographic factors, lack of regular exercise, advanced fibrosis and non-hepatic comorbidities.

Screening for hepatitis C virus at the time of mammography using rapid diagnostic tests in women aged between 50 and 74 years (Mamm'OC NCT05067374).

Chronic hepatitis C Virus (HCV) infection presents a global health challenge, with significant morbidity and mortality worldwide. Despite remarkable progress in treatment options, achieving elimination targets by 2030, as set by the World Health Organization, remains elusive. Our study aimed to address this gap by integrating HCV screening into a national breast cancer screening program. Between March 2022 and March 2023, a prospective cross-sectional multicenter study was conducted in four radiology centers in Montpellier, France. We proposed HCV screening to consecutive women undergoing mammography, targeting 1,500 participants aged 50-74 years. A rapid diagnostic test (RDT) for HCV antibodies (HCV Ab) was performed on capillary whole blood, with positive cases undergoing serological and RNA confirmation. Participants also completed a questionnaire on demographic data and risk factors. Acceptance rates, HCV prevalence, and linkage to care were assessed. The acceptance rate for this integrated screening approach was 82.4%. Notably, the seroprevalence of HCV was found to be 0.65%. Linkage to care was prompt, and the cascade of care demonstrated successful treatment outcomes. Importantly, the majority of detected infections were successfully resolved. These findings underscore the feasibility and acceptability of integrating HCV screening with breast cancer screening programs providing updated prevalence data and valuable insights for refining future screening strategies.

Prevalence of HCV infection in Europe in the DAA era: Review.

In 2016, the Global Health Sector Strategy, ratified by the 69th World Health Assembly, set the ambitious goal of eliminating hepatitis C virus (HCV) and hepatitis B virus infections by 2030, emphasizing the importance of national screening programmes. Achieving this goal depends on each country's ability to identify and treat 80% of chronic hepatitis C cases, a critical threshold set by the World Health Organization. Traditionally, estimates of HCV prevalence have been based on interferon era studies that focused on high-risk subgroups rather than the general population. In addition, the incomplete data available from national registries also limited the understanding of HCV prevalence. The 2016 report from the European Centre for Disease Prevention and Control highlighted that HCV rates varied across European counties, ranging from .1% to 5.9%. However, data were only available for 13 countries, making the overall picture less clear. Additionally, the epidemiological data may have underestimated the true burden of HCV due to lack of awareness among those with chronic infection. The main objective of this review is to provide a comprehensive summary of HCV epidemiology in Europe in the current era of direct-acting antivirals (DAAs). The data included in the analysis range from the end of 2013 to December 2023 and have been categorised according to the United Nations Geoscheme. The resulting synthesis underscores the noteworthy impact of DAA treatment on the epidemiological situation.

Socio-economic factors associated with loss to follow-up among individuals with HCV: A Dutch nationwide cross-sectional study.

BACKGROUND AND AIMS: The path to hepatitis C virus (HCV) elimination is complicated by individuals who become lost to follow-up (LTFU) during care, particularly before receiving effective HCV treatment. We aimed to determine factors contributing to LTFU and whether LTFU is associated with mortality. METHODS: In this secondary analysis, we constructed a database including individuals with HCV who were either LTFU (data from the nationwide HCV retrieval project, CELINE) or treated with directly acting antivirals (DAA) (data from Statistics Netherlands) between 2012 and 2019. This database was linked to mortality data from Statistics Netherlands. Determinants associated with being LTFU versus DAA-treated were assessed using logistic regression, and mortality rates were compared between groups using exponential survival models. These analyses were additionally stratified on calendar periods: 2012-2014, 2015-2017 and 2018-2019. RESULTS: About 254 individuals, LTFU and 5547 DAA-treated were included. Being institutionalized (OR = 5.02, 95% confidence interval (CI) = 3.29-7.65), household income below the social minimum (OR = 1.96, 95% CI = 1.25-3.06), receiving benefits (OR = 1.74, 95% CI = 1.20-2.52) and psychiatric comorbidity (OR = 1.51, 95% CI = 1.09-2.10) were associated with LTFU. Mortality rates were significantly higher in individuals LTFU compared to those DAA-treated (2.99 vs. 1.15/100 person-years (PY), p < .0001), while in those DAA-treated, mortality rates slowly increased between 2012-2014 (.22/100PY) and 2018-2019 (2.25/100PY). CONCLUSION: In the Netherlands, individuals who are incarcerated/institutionalized, with low household income, or with psychiatric comorbidities are prone to being LTFU, which is associated with higher mortality. HCV care needs to be adapted for these vulnerable individuals.

Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.

Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center.

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.

Association of Cognitive Impairment With Chronic Viral Hepatitis Among Older Adults in Taiwan.

OBJECTIVE: To evaluate the risk of cognitive impairment among patients with chronic viral hepatitis. DESIGN: A cross-sectional study. SETTING: Population-based. PARTICIPANTS: Individuals 60 years or older were enrolled from the Taiwan Biobank database from 2012. EXPOSURE: Hepatitis B virus and hepatitis C virus infections. MEASUREMENT: Cognitive impairment was evaluated using the mini-mental state examination (MMSE). Logistic regression models were used to calculate odds ratios and 95% confidence intervals (CIs). The effects of APOE ε4 polymorphisms on the association between viral hepatitis and the risk of cognitive impairment were also investigated. RESULTS: We recruited 912 participants with cognitive impairment and 22 869 participants without cognitive impairment. The adjusted odds ratio (aOR) for cognitive impairment was 1.38 (95% CI: 1.03-1.85, p = 0.033) among participants with hepatitis C virus infection and 1.14 (95% CI: 0.91-1.43, p = 0.257) among participants with hepatitis B virus infection. Participants with hepatitis C virus infection and without hepatitis B virus infection had a higher risk of cognitive impairment (aOR: 1.52, 95% CI: 1.13-2.04, p = 0.006). The MMSE subcategories most associated with hepatitis C virus infection were orientation and design copying. The association between hepatitis C virus infection and cognitive impairment was higher among participants with ε4 alleles of the APOE gene than among those without alleles (aOR: 2.18, 95% CI: 1.21-3.91, p = 0.009). CONCLUSIONS: Our findings suggest that individuals 60 years or older with chronic hepatitis C virus infection are at increased risk of cognitive impairment.

Antiviral Treatment and Response are Associated With Lower Risk of Dementia Among Hepatitis C Virus-Infected Patients.

OBJECTIVE: Eradication of hepatitis C virus (HCV) infection has been linked with improvement in neurocognitive function, but few studies have evaluated the effect of antiviral treatment/ response on risk of dementia. Using data from the Chronic Hepatitis Cohort Study (CHeCS), we investigated how antiviral therapy impacts the risk of developing dementia among patients with HCV. METHODS: A total of 17,485 HCV patients were followed until incidence of dementia, death, or last follow-up. We used an extended landmark modeling approach, which included time-varying covariates and propensity score justification for treatment selection bias, as well as generalized estimating equations (GEE) with a link function as multinominal distribution for a discrete time-to-event data. Death was considered a competing risk. RESULTS: After 15 years of follow-up, 342 patients were diagnosed with incident dementia. Patients who achieved sustained virological response (SVR) had significantly decreased risk of dementia compared to untreated patients, with hazard ratios (HRs) of 0.32 (95% CI 0.22-0.46) among patients who received direct-acting antiviral (DAA) treatment and 0.41 (95% CI 0.26-0.60) for interferon-based (IFN) treatment. Risk reduction remained even when patients failed antiviral treatment (HR 0.38, 95% CI 0.38-0.51). Patients with cirrhosis, Black/African American patients, and those without private insurance were at significantly higher risk of dementia. CONCLUSION: Antiviral treatment independently reduced the risk of dementia among HCV patients, regardless of cirrhosis. Our findings support the importance of initiation antiviral therapy in chronic HCV-infected patients.

The oncologic burden of hepatitis C virus infection: A clinical perspective.

Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.

Incidence of cirrhosis in Iceland-impact of the TraP HepC nationwide HCV elimination program.

OBJECTIVE: In 2016, a nationwide elimination program for hepatitis C virus (HCV) was initiated in Iceland, entitled Treatment as Prevention for Hepatitis C (TraP HepC), providing unrestricted access to antiviral treatment. The aims were to describe the changes in etiology and epidemiology of cirrhosis in Iceland and to assess the trends in HCV-related cirrhosis following TraP HepC. METHODS: The study included all patients newly diagnosed with cirrhosis in 2016-2022. Diagnosis was based on liver elastography, histology, or 2 of 4 criteria: cirrhosis on imaging, ascites, varices, or elevated international normalized ratio (INR). RESULTS: Over the study period, 342 new cirrhosis patients were identified, 223 (65%) males, median age 62 years. The crude overall incidence was 13.8 cases per 100,000 inhabitants annually. The most common etiologies were alcohol-related liver disease (ALD) (40%), metabolic dysfunction-associated steatotic liver disease (MASLD) (28%), and HCV with or without alcohol overconsumption (15%). The number of HCV cirrhosis cases was unusually high in 2016 (n = 23) due to intensified case-finding, but decreased significantly over the study period (p < 0.001) to n = 1 (2021) and n = 2 (2022). The overall 5-year survival was 55% (95% CI 48.9-62.3%). The most common causes of death were hepatocellular carcinoma (26%) and liver failure (25%). CONCLUSION: During the past two decades, the incidence of cirrhosis has increased extraordinarily in Iceland, associated with increased alcohol consumption, obesity, and HCV. ALD and MASLD now collectively make up two thirds of cases in Iceland. Following a nationwide elimination program, incidence of HCV cirrhosis has dropped rapidly in Iceland.

Evaluation of patients treated with direct-acting anti-viral therapy for chronic hepatitis C and their risk of hepatocellular carcinoma in Hong Kong.

BACKGROUND & AIM: To evaluate the risk of early hepatocellular carcinoma (HCC) in chronic hepatitis C patients treated with direct-acting antivirals (DAAs) in Hong Kong, as it has not been studied before in this locality. METHODS: Three hundred thirty-three consecutive chronic hepatitis C patients treated with DAAs from two hospitals over the past 6 years were identified. Kaplan-Meier method was used to calculate cumulative HCC incidence. Cox regression was used to identify factors associated with HCC development. RESULTS: During a median follow-up of 23.4 months after DAA started, 15 (5.4%, 95% CI 3.3-8.7%) out of 279 total included patients developed HCC. The overall sustained virological response (SVR) rate was 98.9%. The 1-year cumulative incidence for de-novo HCC and HCC recurrence were 0.8 and 30.9%, respectively (log-rank test p < 0.001). The 1-year cumulative HCC incidence for patients without and with cirrhosis were 0.7 and 5.1%, respectively (log-rank test p = 0.036). Univariate analysis showed that significant factors associated with HCC after DAA were: history of treated HCC, cirrhosis, evidence of portal hypertension, higher AFP at the start or end of DAA therapy, higher bilirubin, lower platelets, lower albumin, and older age. From receiver operating characteristic curve analysis, the optimal cut-off level of AFP for predicting HCC was 10.5 ng/mL at the start and 5.6 ng/mL at the end of DAA therapy. CONCLUSIONS: The risk of early HCC recurrence remains high despite achieving SVR following DAA therapy, whereas the risk of early de-novo HCC occurence is low. AFP levels, both at the start and end of DAA therapy, can be useful in stratifying risks of HCC development.