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Background: Eradication of hepatitis C virus (HCV) promotes an improvement in liver disease and the deactivation of the immune system. Here, we aimed to evaluate the changes in liver disease scores and plasma biomarkers following HCV clearance with direct-acting antivirals (DAAs) in HIV-infected patients with advanced HCV-related cirrhosis. Methods: We performed an observational study of 50 patients with advanced cirrhosis who received DAAs therapy. Variables were assessed at baseline and 48 weeks after HCV treatment completion. Epidemiological and clinical data were collected through an online form. Liver stiffness measurement (LSM), hepatic venous pressure gradient (HVPG), and Child-Pugh-Turcotte (CTP) were evaluated by physicians. Plasma biomarkers were measured by multiplex immunoassay. Results: We found significant decreases in severity scores of liver disease [LSM ( q -value < 0.001), HVPG ( q -value = 0.011), and CTP ( q -value = 0.045)] and plasma biomarkers [LBP ( q -value < 0.001), IP-10 ( q -value < 0.001), IL-8 ( q -value < 0.001), IL-18 ( q -value < 0.001), IL-1RA ( q -value = 0.013), OPG ( q -value < 0.001), sVCAM-1 ( q -value < 0.001), sICAM-1 ( q -value < 0.001), PAI-1 ( q -value = 0.001), and VEGF-A ( q -value = 0.006)]. We also found a significant direct association between the change in LSM values and the change in values of LBP ( q -value < 0.001), IP-10 ( q -value < 0.001), MCP-1 ( q -value = 0.008), IL-8 ( q -value < 0.001), IL-18 ( q -value < 0.001), OPG ( q -value = 0.004), sVCAM-1 ( q -value < 0.001), sICAM-1 ( q -value < 0.001), and PAI-1 ( q -value = 0.002). For CTP values, we found significant positive associations with IP-10 ( q -value = 0.010), IL-6 ( q -value = 0.010), IL-1RA ( q -value = 0.033), and sICAM-1 ( q -value = 0.010). Conclusion: The HCV eradication with all-oral DAAs in HIV/HCV-coinfected patients with advanced cirrhosis promoted an improvement in the severity of advanced cirrhosis and plasma biomarkers (inflammation, coagulopathy, and angiogenesis). The decrease in plasma biomarkers was mainly related to the reduction in LSM values.

The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors.

(1) Background: Direct-acting antiviral therapy for chronic hepatitis C virus (HCV) infection is associated with high sustained virologic response (SVR) and overcomes negative predictive factors, including steatosis, in patients without human immunodeficiency virus (HIV) coinfection. The impact of steatosis on SVR in patients with HIV–HCV coinfection is unknown. (2) Methods: A retrospective analysis of patients treated with direct-acting antivirals was performed. Demographic, laboratory and direct-acting antiviral regimen data were prospectively collected. Metabolic syndrome and its components—diabetes mellitus, hypertension, dyslipidemia and obesity—were assessed. Hepatic steatosis (≥5%) was defined by liver biopsy or controlled attenuation parameter (CAP) measurement during vibration-controlled transient elastography (VCTE). (3) Results: A total of 151 HIV–HCV-coinfected patients on combined antiretroviral therapy and direct-acting antiviral therapy were included in this analysis. Prevalence of steatosis by liver biopsy (n = 34) or CAP (≥263 db/m) during VCTE (n = 92) was 27% and was independently associated with obesity (OR 3.11; 95% CI 1.43–6.82; p = 0.004) and the metabolic syndrome (OR 1.08; 95% CI 1.01–0.15; p = 0.01). The overall SVR rate (n = 148) was 95% and was not impacted by the presence of steatosis (p = 0.42). (4) Conclusions: Hepatic steatosis is common in HIV–HCV coinfection, correlates with obesity and the metabolic syndrome and does not impact SVR.

Background In January 2015, the first interferon-free direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection was approved for inclusion in Israel’s national basket of health services. During 2015, HCV genotype 1 patients with advanced liver fibrosis (stage F3-F4) were eligible for treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir (OMB/PTV/r + DSV) provided through the four national health plans. As all health plans committed to identifying eligible patients nationwide, risk-sharing agreements created an additional incentive to develop an innovative model for rapid treatment delivery. Aim This article aims to describe the development and implementation of a multi-disciplinary patient-centered model for the expedited provision of costly therapies in a community setting, based on experience delivering new HCV therapy in 2015. Methods We present the case of the Central District in Maccabi Healthcare Services (MHS), one of five districts in a 2-million-member healthcare provider. We describe the dimensions of the model and its implementation, including the composition and responsibilities of the multi-disciplinary team, screening for patient eligibility, provision of care, and barriers and facilitators identified at each stage. Results The experience of the MHS Central District indicates that good communication between all stakeholders was the key driver of successful implementation of the model. Overall, monthly treatment uptake increased following the intervention and by the end of 2015 a total of 99 patients were treated with OMB/PTV/r + DSV in this district. Early data indicate high effectiveness in this population and evaluation in ongoing. Conclusions This multi-disciplinary patient-centered model enabled rapid integration of screening and disease staging to identify and treat eligible HCV patients in the MHS central district. The model forms the basis of the 2017 project to deliver DAAs according to broader health basket criteria and may be adapted for the provision of other innovative health technologies in different healthcare settings.

Background. Persistent infection with hepatitis C virus (HCV) causes profound alterations of the cytokine and chemokine milieu in peripheral blood. However, it is unknown to what extend these alterations affect the progression of liver disease and whether HCV clearance normalizes soluble inflammatory mediators. Methods. We performed multianalyte profiling of 50 plasma proteins in 28 patients with persistent HCV infection and advanced stages of liver fibrosis or cirrhosis and 20 controls with fatty liver disease. The patients were treated for 24 weeks with sofosbuvir and ribavirin and underwent sampling longitudinally. Ten patients experienced viral relapse after treatment cessation. Results. The cytokine and chemokine expression pattern was markedly altered in patients with chronic HCV infection as compared to healthy controls and patients with nonalcoholic steatohepatitis. Distinct soluble factors were associated with the level of fibrosis/cirrhosis, viral replication, or treatment outcome. The baseline expression level of 10 cytokines distinguished patients with a sustained viral response from those who experienced viral relapse. While the majority of upregulated analytes declined during and after successful therapy, HCV clearance did not lead to a restoration of parameters that were suppressed. Conclusions. Chronic HCV infection appears to disrupt the milieu of soluble inflammatory mediators even after viral clearance. Thus, HCV cure does not lead to complete immunological restitution.

Extrahepatic manifestations are a feature of chronic hepatitis C virus (HCV) infection. In the course of chronic HCV infection, about 70% of patients have one or more extrahepatic manifestations. The latter are often the first and only clinical sign of infection. Experimental and clinical data support a causal association for many extrahepatic manifestations and HCV infection, which include mixed cryoglobulinemia, non-Hodgkin lymphomas (NHL), cardiovascular disease, insulin resistance, type 2 diabetes, neurological and psychiatric disease and other rheumatic diseases. All these extrahepatic conditions influence the morbidity, quality of life and mortality of HCV-infected patients. Currently, interferon-free therapeutic regimens with direct-acting antiviral agents (DAA) offer the possibility of treatment to almost the entire infected population, irrespective of stage of cirrhosis and associated serious comorbidities, always maintaining a high efficacy and tolerability. Several studies have shown a close association between HCV clearance by DAAs and an improvement or reduction in the risk of extrahepatic manifestations. Patients with HCV after a sustained virologic response (SVR) by DAA treatment have a lower risk than non-responders of developing cryoglobulinemic vasculitis and B-cell non-Hodgkin’s lymphomas. Furthermore, the SVR by DAA also reduces the risk of acute coronary syndrome, cardiovascular disease, insulin resistance and type 2 diabetes, and it improves atherosclerosis. HCV clearance by DAA also improves the quality of life and survival of patients with chronic HCV infection with associated extrahepatic diseases. Thus, DAAs should be initiated as early as possible in HCV patients with extrahepatic manifestations.

Background Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC). Patients and Methods A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2–10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy. Results HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2–3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively ( P  < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively ( P  = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191–0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time. Conclusions DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.

Hepatitis C virus (HCV) is a primary hepatotropic pathogen responsible for acute and chronic hepatitis C, however, it can also cause “occult” infection (OCI), defined as the presence of the virus’ genetic material in hepatocytes and/or peripheral blood cells, but not in plasma/serum. Assessment of the sustained virologic response (SVR) after treatment with direct-acting antivirals (DAA) is based exclusively on HCV-RNA testing in plasma/serum, which may preclude the diagnosis of post-treatment OCI. Possible clinical consequences of OCI were described previously, but its occurrence after DAA-based antiviral treatment programs and determinants of the virus persistence are not fully elucidated. The aim of this study was to assess the incidence of post-treatment OCI after successful DAA-based treatment and to identify clinical and immunological factors associated with this phenomenon. In 97 patients treated with DAA, HCV-RNA was tested by RT-PCR in peripheral blood mononuclear cells (PBMC) at baseline (i.e., before the onset of treatment) and at the time of SVR assessment. Before treatment, HCV-RNA was detectable in all patients’ PBMC. All subjects responded to therapy according to the clinical criteria, but 9 (9.3%) patients revealed the HCV-RNA in PBMC at SVR. In most of these cases, post-DAA OCI was related to switch of the dominant infecting genotype. Post-treatment OCI was characterized by significantly lower pre-treatment HCV viral load and lower expression of Tim-3 (T-cell immunoglobulin and mucin domain-containing protein 3) on CD8 + T-cells. Our results imply that post-treatment OCI may be related to lower pretreatment viral load as well as distinct pre-existing immune exhaustion status.

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.

BackgroundShort-time usage of direct-acting antiviral agents (DAA) limited knowledge regarding histological outcomes and predictive values of noninvasive measurements in patients with hepatitis C virus (HCV) after sustained virologic response (SVR) with DAA.AimsThis study aimed to indicate histological changes and assess predictive value of noninvasive measurements for fibrosis in these patients.MethodsHCV patients who achieved SVR by DAA were identified. Pre- and post-SVR clinical and histological data were collected.ResultsOf patients, 83% (33/40), 38% (15/40) and 83% (33/40) achieved inflammation improvement, fibrosis regression and histological improvement, respectively. Liver stiffness measurements (LSM), APRI, and FIB-4 could predict post-SVR fibrosis well without significant differences. Areas under receiver operating characteristic curves of LSM, APRI, and FIB-4 were 0.78, 0.81, and 0.87 for post-SVR advanced fibrosis (≥ F4) and 0.86, 0.86, and 0.85 for post-SVR cirrhosis (≥ F5), respectively. Pre-SVR LSM, APRI, and FIB-4 values were significantly lower in patients with fibrosis regression (P = 0.003–0.012), while FIB-4 was significantly lower in patients with histological improvement (P = 0.012–0.033). Patients with higher pre-SVR Ishak scores tended to have bigger decline in APRI (P = 0.025) and FIB-4 (P = 0.024) after SVR.ConclusionsDAA could improve liver inflammation and fibrosis of HCV patients in a short time after SVR. LSM, APRI, and FIB-4 predict fibrosis well even after SVR by DAA. Most of the cutoff values for advanced fibrosis (≥ F4) and cirrhosis (≥ F5) of these noninvasive measurements decreased significantly after SVR, maybe because of the inflammation improvement.