NGS data for a study "Persistence of hepatitis C virus in peripheral blood mononuclear cells of patients who achieved sustained virological response following treatment with direct-acting antivirals is associated with a distinct pre-existing immune exhaustion status"
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB87205 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aims: The purpose of this study was to assess the changes in hepatic morphology evaluated by computed tomography (CT) examination in patients with hepatitis C virus (HCV)-related compensated cirrhosis who achieved sustained virologic response (SVR) after direct-acting antivirals (DAAs) treatment. Methods: CT examination was performed in 56 patients with HCV-related compensated cirrhosis before and within 6-18 months after the treatment with Ombitasvir/Paritaprevir/ritonavir + Dasabuvir. The liver CT changes were assessed by measuring liver volume, caudate-right lobe ratio (C/RL), hepatic vessels diameters, periportal widening space, and right posterior notch. Portal trunk, splenic and superior mesenteric vein diameters, as well as spleen volume were assessed as part of portal hypertension. Results: Right hepatic vein diameter was significantly wider after treatment (median: 8.12 mm; IQR: 4.20) than before treatment (median: 6.36 mm; IQR: 3.94) z = -3.894; p < 0.001. The liver volume was significantly higher prior to the treatment (median: 1786.77 mm3; IQR: 879.23) than after treatment (median: 1716.44 mm3; IQR: 840.50), z = -1.970; p = 0.049. Splenic volume was considerably higher before treatment (median: 564.79 mm3; IQR: 342.54) than after (median: 474.45 mm3; IQR: 330.00), z = -2.500; p = 0.012. The other parameters, such as C/RL, periportal space widening, and right hepatic notch showed no significant changes. Conclusions: SVR in patients with HCV-related compensated cirrhosis treated with DAAs is associated with some improvements of hepatic morphology detectable by CT, the most constant being the increase of right hepatic vein diameter.
| S-EPMC7231305 | biostudies-literature
Project description:BackgroundThe histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA.MethodsThis retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2 binding protein glycosylation isomer, autotaxin, and Fibrosis-4 index) were assessed before and 5 years after treatment. Transient elastography using the FibroScan® device was performed 5 years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively.ResultsHistological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75 kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment.ConclusionsLong-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.
| S-EPMC11794422 | biostudies-literature
Project description:IntroductionThe genomic characteristics of hepatocellular carcinoma (HCC) after a sustained virological response (SVR) and its differences according to whether an SVR was achieved by treatment with direct-acting antivirals (DAA) or interferon (IFN) are still not fully understood.MethodsSixty-nine surgically resected HCCs from patients with hepatitis C virus infection were analyzed by gene expression profiling and whole-exome sequencing.ResultsAmong the 69 HCC patients, 34 HCCs in which an SVR was not achieved at the time of surgery were classified as HCV-positive, and 35 HCCs in which an SVR was achieved at the time of surgery were classified as HCV-SVR. According to the HCV treatment, 35 HCV-SVR HCCs were classified into two groups: eight tumors with DAA (HCV-SVR-DAA) and 24 tumors with interferon (HCV-SVR-IFN). The frequency of samples with ARID2 mutations was significantly lower in HCV-SVR than in HCV-positive tumors (p = 0.048). In contrast, the frequency of samples with PREX2 mutations was significantly higher in HCV-SVR samples than in HCV-positive samples (p = 0.048). Among the patients with HCV-SVR, the frequency of samples with TP53 mutations was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors (p = 0.030). TP53 inactivation scores in HCV-SVR-DAA tumors were found to be significantly enhanced in comparison to HCV-SVR-IFN tumors (p = 0.022). In addition, chromosomal instability and PI3K/AKT/mTOR pathway signatures were enhanced in HCV-SVR-DAA tumors. HCV-SVR-DAA was significantly associated with portal vein invasion (p = 0.003) in comparison to HCV-SVR-IFN.ConclusionOur dataset potentially serves as a fundamental resource for the genomic characteristics of HCV-SVR-DAA tumors. Our comprehensive genetic profiling by WES revealed significant differences in the mutation rate of several driver genes between HCV-positive tumors and HCV-SVR tumors. Furthermore, it was revealed that the frequency of samples with mutations in TP53 was significantly higher in HCV-SVR-DAA tumors than in HCV-SVR-IFN tumors.
| S-EPMC9041076 | biostudies-literature
Project description:The role of liver stiffness measurement (LSM) after sustained virological response (SVR) in HCV patients treated by direct-acting antivirals (DAAs) remains unclear. We aimed to evaluate LSM regression value after SVR and to identify risk factors associated with liver related complications (LRC) or death. This retrospective study analyzed patients with LSM ≥ 10 kPa with LSM by transient elastography pre-DAAs and post-SVR. Patients with previous hepatic decompensation were excluded. Medical records were reviewed to identify primary outcomes. Kaplan-Meier curves and time-to-event Cox proportional-hazard models were performed. 456 patients [65% female, 62 years (IQR 57-68)] were included. During a follow-up of 2.3 years (IQR 1.6-2.7), 28 patients developed 37 outcomes [rate = 29.0 (95% CI 20.0-42.0) per 1000 person-years]. The cumulative incidence of outcomes was significantly lower in patients who regressed LSM ≥ 20% [3.4% (95% CI 1.8-7.0) vs. 9.0% (5.5-14.5), p = 0.028]. In a multivariate Cox-model [HR(95% CI)], male gender [HR = 3.00 (1.30-6.95), p = 0.010], baseline albumin < 3.5 mg/dL [HR = 4.49 (1.95-10.34), p < 0.001] and baseline unfavorable Baveno-VI [HR = 4.72 (1.32-16.83), p = 0.017] were independently associated and LSM regression ≥ 20% after SVR had a trend to reduce the risk of LRC or death [HR = 0.45 (0.21-1.02), p = 0.058]. The use of simple parameters before DAAs and repetition of LSM post-SVR can identify patients with different risks for severe outcome after HCV eradication.
| S-EPMC8175552 | biostudies-literature
Project description:Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.
| S-EPMC8254542 | biostudies-literature
Project description:Background and aimThe pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with hepatitis C virus (HCV) who have received direct-acting antiviral (DAA) therapy and achieved sustained virological response (SVR). This study validated a composite predictive model for HCC in these patients.MethodsThis study included 3058 patients in whom HCV was eradicated with DAA therapy. After DAAs recommendation for surveillance (ADRES) score, which is based on sex, FIB-4 index, and α-fetoprotein, was used as a composite predictive model for HCC development.ResultsThe 1-, 3-, and 5-year cumulative incidence rates of HCC were 0.9, 4.5, and 15.2%, respectively. Multivariate analysis with Cox proportional hazards models showed that male sex (hazard ratio [HR], 2.646; 95% confidence interval [CI], 1.790-3.911), FIB-4 index >3.25 (HR, 2.891; 95% CI, 1.947-4.293), and α-fetoprotein >5 ng/mL (HR, 2.835; 95% CI, 1.914-4.200) are independently associated with HCC development. The incidence of HCC differed significantly by ADRES score (P < 0.001). Cox proportional hazards models showed that compared to the ADRES score 0 group, the HR for HCC development was 2.947 (95% CI, 1.367-6.354) in the ADRES score 1 group, 9.171 (95% CI, 4.339-19.380) in the ADRES score 2 group, and 20.630 (95% CI, 8.641-49.230) in the ADRES score 3 group. ADRES score had superior predictive power for HCC development compared with the FIB-4 index and α-fetoprotein according to time-dependent receiver operating characteristic analysis.ConclusionThe ADRES score is useful for predicting HCC development after SVR.
| S-EPMC8762616 | biostudies-literature
Project description:The introduction of generic direct-acting antivirals (DAAs) in Egypt is associated with a superior cure rate of hepatitis C virus (HCV) infection. However, the course of progressive liver damage and developing liver related complications in patients with sustained virologic response (SVR) remain unclear. This study was designed to examine the long-term outcomes of generic DAA-induced virological cure in a real-life cohort of HCV patients with or without comorbid schistosomiasis. We prospectively enrolled a cohort of 506 recently cured HCV patients (437 Child-Pugh class A [Child-A] and 69 Child-Pugh class B [Child-B]). All patients were clinically evaluated at different time points during a 2-year follow-up (November 2018 to February 2021). Over the course of treatment and follow-up, 77 (15.2%) patients (42 [9.6%] Child-A and 35 [50.7%] Child-B) experienced complications at different time points. The overall mortality rate was approximately 1/1,000 person-years. The incidence of hepatic insufficiency was approximately 5.5/1,000 person-years, and that of de novo hepatocellular carcinoma (HCC) was approximately 8.3/1,000 person-years. A sustained improvement in liver indices up to 2 years of follow-up was observed. In the Cox regression model, pretreatment decompensated cirrhosis predicted the occurrence of adverse liver events and HCC after therapy. In conclusion, in HCV patients with advanced cirrhosis or coexisting hepatic schistosomiasis, generic DAA-induced SVR remains robust with favorable clinical outcomes although the risk of hepatocarcinogenesis cannot be eliminated. Surveillance of patients with treated HCV infection is an important aspect of postcure care for early detection and management of liver disease-related adverse events.
| S-EPMC9128674 | biostudies-literature
Project description:PurposeHepatitis C virus infection is a major health problem in hemodialysis patients. Occult HCV infection is defined as the presence of HCV-RNA in hepatocytes or peripheral blood mononuclear cells without the detection of HCV-RNA in the serum. We aimed to evaluate the prevalence and predictors of occult HCV infection among hemodialysis patients after treatment with direct-acting antiviral agents.MethodsThis research is a cross-sectional study that included 60 HCV patients maintained on regular HD patients who achieved 24 weeks of sustained virological response after treatment with direct-acting antiviral agents. Real-time PCR was performed to detect HCV-RNA in peripheral blood mononuclear cells.ResultsHCV-RNA was detected in peripheral blood mononuclear cells of three patients (5%). Occult HCV infection cases were treated by Interferon/ribavirin before direct-acting antiviral agents and two of them had raised pre-treatment alanine aminotransferase levels. Logistic regression analyses revealed that high pre-treatment viral load and raised pre-treatment alanine aminotransferase were associated with an increased risk of occult HCV infection with p value of 0.041 and 0.029, respectively.ConclusionsOccult HCV infection in hemodialysis patients who achieved sustained virological response after treatment with direct-acting antiviral agents may occur, and this may necessitate dual testing for HCV in both serum and peripheral blood mononuclear cells to ensure viral clearance.Clinical trials registrationClinicalTrials.gov NCT04719338.
| S-EPMC10776497 | biostudies-literature
Project description:Background & aimsThe risk for hepatitis C virus (HCV) recurrence persists after HCV eradication with direct-acting antivirals (DAAs), particularly in patients with ongoing high-risk behaviours. Our aim was to assess the risk of HCV recurrence (late relapse and/or reinfection) post-sustained virological response (SVR).MethodsWe searched the literature for studies reporting HCV recurrence rates post-SVR in PubMed, Web of Science and the Cochrane Library. Identified publications were divided into groups based on patient risk for HCV reinfection: low-risk HCV mono-infection, high-risk HCV mono-infection and a human immunodeficiency virus (HIV)/HCV coinfection. The HCV recurrence rate for each study was calculated by using events divided by the person-years of follow-up (PYFU). HCV recurrence was defined as confirmed, detectable HCV RNA post-SVR.ResultsIn the 16 studies of low-risk patients, the pooled recurrence rate was 0.89/1000 PYFU (95% confidence interval [CI], 0.16-2.03). For the 19 studies of high-risk patients, the pooled recurrence rate was 29.37/1000 PYFU (95% CI, 15.54-46.91). For the eight studies of HIV/HCV-coinfected patients, the pooled recurrence rate was 23.25/1000 PYFU (95% CI, 4.24-53.39). The higher pooled estimates of recurrence in the high-risk and HIV/HCV-coinfected populations were predominantly driven by an increase in reinfection rather than late relapse.ConclusionsThe HCV recurrence risk after achieving SVR with all-oral DAAs therapy is low, and the risk of HCV recurrence in high-risk and HIV/HCV-coinfected populations was driven by an increase in reinfection rather than late relapse.
| S-EPMC8455436 | biostudies-literature
Project description: Not available
| S-EPMC7752158 | biostudies-literature