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Background & Aims Sustained virological response (SVR) by direct‐acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non‐tumoral PVT in patients with cirrhosis after HCV eradication. Methods Patients with HCV‐related cirrhosis, consecutively enrolled in the multi‐center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan‐Meier and competing risk regression analyses were performed. Results During a median time of 38.3 months (IQR: 25.1–48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/μL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB‐4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33–24.99) and pre‐treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36–13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre‐treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16–27.53 and subHR: 5.50; CI 95% 1.67–18.13, respectively). Conclusions In patients with HCV‐related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

To report the sociodemographic and clinical profile of patients treated with direct-action antivirals (DAAs). Patients infected with hepatitis C virus in current treatment were followed up in a pharmaceutical office. Sociodemographic, clinical and medicines uses characteristics were obtained. A total of 62 patients were enrolled, with a higher proportion of men, aged between 40 and 69 years, low schooling, and workers. Were predominant the HCV virus genotype 1 (45.2%) and 3 (48.4%), and 19.4% were cirrhotic. Of the referred comorbidities, stood out those diseases related to the cardiovascular system (19.8%), psychiatric disorders (17.6%), endocrine and metabolic disorders (14.5%). Co-infections represented 5.2%, and were distributed between acute hepatitis A (1.0%), chronic viral hepatitis B (2.1%), and HIV (2.1%). Previous or current use of licit / illicit substances was reported by 33.9% of patients. A significant difference was identified in the youngest age group (25 to 39 years, p = 0.02), with a lower average viral load compared to the other age groups. The pharmacotherapeutic follow-up carried out in the period resulted in 157 pharmaceutical consultations. Patients with hepatitis C using DDAs were mostly men, aged between 40 and 69 years. Type 3 HCV genotype was most frequently identified. The presence of cirrhosis and other comorbidities serves as an alert for health professionals in the implementation of public health policies.

The increased life expectancy of persons infected with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) has resulted in renewed attention to non-HIV-related diseases exacerbated by HIV infection. Coinfection with hepatitis C virus (HCV) is a particular area of concern, as the global prevalence has been estimated at 2.5–5 million people. In this article, we discuss the epidemiology of HCV infection and reinfection, HCV-related liver disease progression in the era of effective ART, and the efficacy of emerging HCV treatment strategies in persons with HIV/HCV coinfection. New data regarding treatment of persons with HIV/HCV coinfection suggest that HCV treatment should be a priority in those with HIV. Results from recent studies using all-oral HCV regimens have shown high rates of sustained virologic response in both clinical trials and real-world settings. A multidisciplinary approach to HCV treatment in those with HIV is recommended for optimal patient management. Following HCV cure, practitioners also need to be mindful of the risks for HCV reinfection and educate patients on protective measures.

Direct‐acting antivirals (DAAs) have dramatically improved sustained virological response (SVR) rates in patients with hepatitis C virus (HCV) infection. However, the risk of hepatocellular carcinoma (HCC) remains even after achieving SVR. We previously reported that alpha‐fetoprotein (AFP) levels at the end of treatment (EOT) were associated with the occurrence of HCC after achieving sustained virologic response (SVR). Here, to improve predictive accuracy by incorporating the Agile 3+ score among 502 patients who received DAA therapy for HCV infection between September 2017 and July 2024, we excluded those who developed HCC within 1 year of treatment and included 337 patients with chronic hepatitis or compensated cirrhosis, who had no prior HCC and underwent transient elastography before treatment. A scoring system was developed by assigning 1 point for Agile 3+ score ≥ 0.9398 and 1 point for EOT‐AFP ≥ 3.8 ng/mL. The cumulative HCC incidence was analyzed in relation to the total score. Cox proportional hazards models were used to assess independent risk factors. During follow‐up, 15 patients (4.5%) developed HCC. Patients with a score of ≥ 1 had a significantly higher HCC risk (p < 0.001). Agile 3‐AFP score ≥ 1 (hazard ratio (HR) 12.65, 95% CI 1.38–115.49, p = 0.02) and GGT (HR 1.00, 95% CI 1.00–1.01, p = 0.02) remained independent predictors of HCC occurrence. A simple scoring system combining the pretreatment Agile 3+ score and EOT‐AFP levels may be useful for long‐term risk stratification of HCC after DAA therapy in HCV‐infected patients.

Background and Objectives: HCV infection represents a main risk factor for type 2 diabetes (T2D). This real-world analysis investigated the HCV-positive (HCV+) population with a T2D co-diagnosis in Italy. Methods: From 2017 to 2021, HCV+ patients were identified from administrative databases and stratified into T2D-HCV+ and HCV+-only cohorts in the presence/absence of a T2D diagnosis. Both cohorts were further divided by treatment with direct-acting antivirals (DAAs). The subgroups were compared for demographic variables, comorbidity profiles, most frequent hospitalizations, and drug prescriptions before inclusion. A sensitivity analysis was performed on patients included after 2019, the year of widespread use of pangenotypic DAAs. Results: Considering HCV+ patients aged ≥55 years, T2D-HCV+ patients (N = 1277) were significantly (p < 0.001) older than HCV+-only (N = 6576) ones and burdened by a worse comorbidity profile (average Charlson index: 1.4 vs. 0.3, p < 0.05). Moreover, regardless of T2D presence, DAA-treated patients were older (p < 0.001) and had a worse Charlson index than the untreated ones. T2D-HCV+ patients showed tendentially higher hospitalization rates and co-medication prescriptions compared to the HCV+-only patients. After 2019, a trend towards reduced co-medication use in DAA-treated patients was noticed, especially antibiotics and cardiovascular drugs. Conclusions: The co-presence of T2D in HCV+ patients resulted in a worse clinical status, as confirmed by the more frequent requirement of hospitalizations and complex polypharmacy regimens.

Direct‐acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha‐fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well‐tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies. Virologic response rates to the various DAA regimens, by genotype. Panel (a) shows the virologic response for genotype 1; panel (b) for genotype 6; panel (c) for genotype 2; and panel (d) for mixed or unspecified genotypes. The colors represent different treatment regimens. SOF/LDV: sofosbuvir/ledipasvir; SOF/VEL: sofosbuvir/velpatasvir; SOF/DCV: sofosbuvir/daclatasvir, GZR/EBR: grazoprevir/elbasvir.

With the introduction of direct‐acting antivirals, elimination of hepatitis C virus (HCV) infection is becoming possible. People who inject drugs (PWID) represent a population with a high risk for HCV infection, which has been reported as high as 90% in Taiwanese PWID. To reach the goal of HCV elimination, PWID is a key population deserving special attention. Barriers in HCV care cascade still exist in PWID, and interventions to promote access to HCV diagnosis, link‐to‐care, treatment, and prevention for PWID are warranted. Although HCV micro‐elimination can be achieved in some prisons and opioid substitution therapy (OST) centers by a multidisciplinary team and integrated care in Taiwan, there are still several unmet needs for HCV elimination in PWID. Continuous efforts, such as the participation of OST specialists and the continuum of care for HCV among PWID, are needed to achieve HCV elimination in Taiwan. In addition, the combination of harm reduction services, treatment as prevention and regular posttreatment HCV surveillance is critical to substantially reduce HCV transmission and prevalence in PWID.

Background Current trends in complications and mortality among individuals with chronic liver disease and cirrhosis are largely unknown. Objective To explore changes in mortality trends among patients with cirrhosis and chronic liver disease based on etiology in the Veneto Region (Italy), to differentiate mortality between liver‐related and non‐liver‐related causes before and during the COVID‐19 pandemic, and to determine trends in the development of cirrhosis complications. Methods Three subsequent population‐based cohorts of individuals with chronic liver disease/cirrhosis were identified in Veneto (North‐eastern Italy, 4.9 million residents): the first enrolled before introduction of direct‐acting antivirals (DAA); the second corresponding to full availability of DAA treatment; and the last enrolled at the beginning of the pandemic. Risks of liver decompensation and death—liver and non‐liver related—were recorded for each cohort during a 3‐year follow‐up. Changes in the risk of death across cohorts were measured by risk ratios (RR) obtained through Poisson regression models with robust error variance. Results Across the cohorts spanning over 10 years, we found that the number of individuals with CLD and cirrhosis remained stable at about 40,000 and 10,000, respectively. The 3‐year risk of ascites, hepatic encephalopathy, and hepatocellular carcinoma decreased across the study period, largely due to individuals with HCV‐related liver disease. The overall 3‐year mortality risk declined by 14% (liver cirrhosis, subjects enrolled in 2020 vs. 2013: RR = 0.86, 95% CI 0.83–0.89), especially among those with viral etiology. In contrast, mortality due to alcohol‐related chronic liver disease/cirrhosis was stable or increasing during the COVID‐19 pandemic, especially for non‐liver causes of death. Conclusions Despite increased awareness and proactive enrollment into patient care, chronic liver disease and cirrhosis remain significant health‐challenges. The reduction in HCV‐related mortality underscores the impact of antiviral treatments, while the persistently high mortality risk of alcohol‐related disease highlights the need for targeted interventions. Key Points Summarize the established knowledge on this subject: Chronic liver disease is a global major health care concern, but the epidemiology of chronic liver disease in Italy is poorly known. Understanding the evolving trends of outcomes and mortality in chronic liver disease will help plan the next actions to mitigate the healthcare burden associated with this condition. What are the significant and/or new findings of this study? In Veneto region, Italy, the prevalence of chronic liver disease and cirrhosis has remained stable over the past decade. The incidence of ascites, hepatic encephalopathy, and hepatocellular carcinoma has decreased over the last 10 years, primarily due to the reduced burden of HCV. In contrast to chronic viral hepatitis, mortality from alcohol‐related chronic liver disease and cirrhosis has remained stable or increased, highlighting the necessity for focused preventive measures and treatment strategies.

Roughly one-third of individuals living with the human immunodeficiency virus (HIV) are coinfected with the hepatitis C virus (HCV) due to shared routes of transmission. HIV accelerates the progression of HCV disease; thus, coinfected individuals are at high priority for HCV treatment. Several new HCV therapies, called direct-acting antiviral agents (DAAs), are available that achieve cure rates of >90% in many patient populations including individuals with HIV. The primary consideration in treating HCV in HIV-infected persons is the potential for drug interactions. We describe the clinical pharmacology and drug interaction potential of the DAAs, review the interaction data with DAAs and antiretroviral agents, and identify the knowledge gaps in the pharmacologic aspects of treating HCV in individuals with HIV coinfection. This review will focus on DAAs that have received regulatory approval in the United States and Europe and agents in late stages of clinical development.

Backgrounds The success of direct‐acting antiviral (DAA) therapy provides a cure for patients chronically infected with hepatitis C virus (HCV); however, outcomes after hepatectomy for HCV‐associated hepatocellular carcinoma (HCC) before and after DAA introduction remain poorly studied. Methods Patients who underwent R0/R1 hepatectomy for HCV‐associated HCC were retrospectively analyzed. Two time periods were defined: Pre‐DAA (2007–2011, December 2013 was defined as the end of follow‐up) and Post‐DAA groups (2014–2018, December 2020 was defined as the end of follow‐up). Propensity score matching (PSM) analyses were performed to highlight the effect of DAA therapy. Results A total of 155 patients with HCV‐associated HCC were included in this study (Pre‐DAA group, n = 103 and post‐DAA group, n = 52). In the Post‐DAA group, DAA therapy was performed in 26 patients (50.0%), and all of these patients achieved sustained virologic response (SVR) (preoperative SVR, n = 7; postoperative SVR, n = 19). There was no significant difference between the two groups regarding surgical settings and tumor pathology. There was no significant difference in the 5‐year overall survival (OS) rate (61.1% and 64.8%, pre‐ and post‐DAA group, respectively, p = 0.441); meanwhile, the 5‐year recurrence‐free survival (RFS) rate in the post‐DAA group was better than the pre‐DAA group (21.1% and 40.2%, p = 0.073) with a trend toward significance. After PSM except for the postoperative SVR status, there were no significant differences in OS (p = 0.586) and RFS (p = 0.888). Conclusions This study showed that survival outcomes were not changed in hepatectomized cases of HCV‐associated HCC before and after the introduction of DAA therapy. This study investigated the trends in survival outcomes of patients with HCV‐associated HCC who underwent hepatectomy before and after the introduction of DAA therapy at a tertiary referral center for hepatobiliary surgery. We found that survival outcomes were not changed before and after introduction of DAA therapy. Although some papers emphasize the “oncologic” benefit of DAA therapy, its effect was skeptical based on this study.