Dataset Information

Role of Inflammatory/Immune Response and Cytokine Polymorphisms in the Severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAs) Treatment.

ABSTRACT: Host regulatory immune response is involved in the hepatic inflammatory process caused by the hepatitis C virus (HCV). We aimed to determine if HCV clearance with direct-acting antivirals (DAAs) changes the hepatic fibrosis stage, biochemical parameters of liver injury, and inflammatory/immune responses. Sample: 329 chronic hepatitis C (CHC) patients, 134 of them treated with DAAs. Liver fibrosis was evaluated by transient elastography (FibroScan), biochemical and cellular parameters were determined by standard methods, cytokine concentration by enzyme-linked immunoabsorbent assay (ELISA), and genetic polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or endpoint genotyping. Before DAA treatment, severe fibrosis or cirrhosis (F3/4) was associated with higher values of tumor necrosis factor-alpha (TNF-α) and genotypes transforming growth factor-beta-509 C/T_CC (TGF-β-509 C/T_CC), interleukine-10-1082 T/C_CC (IL-10-1082 T/C_CC), and IL-10-592 G/T_GT. After DAA treatment, fewer F3/4 patients and lower values of TNF-α were found. Patients with TNF-α-308 G/A_GG and IL-10-592 G/T_GT were at risk for F3/4. Lack of improvement of liver fibrosis was associated with lower baseline values of platelet count for genotypes TNF-α-308 G/A_GG and haplotype TT/GG of IL-10-1082 T/C and IL-10-592 G/T. Our study showed decreased liver fibrosis/inflammation and normalization of liver injury biomarkers after DAA treatment. It also points to the importance of suppressing the pro-inflammatory response by DAAs in the resolution of hepatitis C, contributing to the improvement of liver damage evaluated by transient elastography.

SUBMITTER: Ferreira J

PROVIDER: S-EPMC9865726 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Role of Inflammatory/Immune Response and Cytokine Polymorphisms in the Severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAs) Treatment.

Ferreira Joana J Oliveira Mariana M Bicho Manuel M Serejo Fátima F

International journal of molecular sciences 20230110 2

Host regulatory immune response is involved in the hepatic inflammatory process caused by the hepatitis C virus (HCV). We aimed to determine if HCV clearance with direct-acting antivirals (DAAs) changes the hepatic fibrosis stage, biochemical parameters of liver injury, and inflammatory/immune responses. Sample: 329 chronic hepatitis C (CHC) patients, 134 of them treated with DAAs. Liver fibrosis was evaluated by transient elastography (FibroScan), biochemical and cellular parameters were determ ...[more]

PMID: 36674897

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Project description:Introduction:Hepatitis C virus (HCV) infection is common among end-stage renal disease patients undergoing hemodialysis. The standard treatment for HCV infection has been interferon-ribavirin combination prior to renal transplantation. However, compared to direct-acting antiviral agents (DAAs), the risk of graft rejection is higher with interferon therapy. Many recent studies have investigated the efficacy and safety of DAAs for treating HCV infection in kidney disease in adults; however, it has not been established in pediatric patients. To the best of our knowledge, this is the first report describing successful treatment using the DAAs sofosbuvir/daclatasvir in two pediatric kidney transplant recipients who had HCV genotype 1a infection without liver fibrosis. Case Presentation:Case 1 describes a 13-year-old Indonesian boy who had undergone hemodialysis since 2014 after being diagnosed with end-stage renal disease (ESRD) secondary to bilateral renal hypoplasia. Later, he had HCV infection and was treated with interferon-based therapy with ribavirin prior to living-related renal transplantation (LRRT). The HCV was undetected and his liver function normalized six months after treatment initiation. However, 10 months after treatment initiation, he had HCV virological breakthrough, leading to cessation of interferon therapy. Plans for LRRT were continued and HCV treatment using DAAs was set up to be given post LRRT. Case 2 describes a 14-year-old Indonesian girl who also had hemodialysis prior to LRRT after she was diagnosed with ESRD secondary to nephrotic syndrome. Later, she had HCV infection and was treated with interferon and ribavirin prior to the live-unrelated renal transplantation. HCV infection did not resolve, in addition, she experienced thrombocytopenia-which is a side effect of interferon-resulting in termination of interferon treatment. Both cases were treated with DAAs one year following renal transplantation after reaching stable graft function, leading to achievement of sustained virological response at 24 weeks. Conclusion:Post-transplantation treatment of chronic HCV is preferred in KTRs. The sofosbuvir/daclatasvir regimen as an interferon-free therapy is a safe, effective option for HCV infection in pediatric KTRs, who can tolerate sofosbuvir/daclatasvir well and respond favorably without significant adverse events.

Project description:ImportanceRecent reports based on the US Food and Drug Administration's voluntary Adverse Events Reporting System raised questions about the safety of direct-acting antivirals (DAAs) for treatment of the hepatitis C virus (HCV).ObjectiveTo assess the rates of adverse events in patients with HCV infection exposed to DAAs compared with those not exposed.Design, setting, and participantsA retrospective cohort study calculated unadjusted adverse event rates for exposed vs unexposed time, using claims and clinical data from 3 health systems between January 1, 2012, and December 31, 2017. Of 82 419 eligible adults, a total of 33 808 who met eligibility criteria (age, 18-88 years; HCV quantitative result or genotype from 2012 or later; continuously enrolled; naive to DAA treatment at baseline) were included. Marginal structural modeling methods were used to adjust time-to-event analyses for characteristics that are associated with both outcomes and probability of treatment.Interventions or exposuresExposure to DAAs compared with no DAA exposure.Main outcomes and measuresDeath, multiple organ failure, liver cancer, hepatic decompensation, acute-on-chronic liver event, acute myocardial infarction, ischemic or hemorrhagic stroke, arrhythmia, acute kidney failure, nonliver cancer, hepatitis B reactivation, hospitalizations, and emergency department visits.ResultsOf the 33 808 patients who met all inclusion criteria, 20 899 (61.8%) were men; mean (SD) age was 57.2 (10.6) years. In unadjusted analyses, DAA exposure was associated with significantly lower rates of death (10.7 vs 33.7 events per 1000 person-years; rate ratio [RR], 0.32, 95% CI, 0.25-0.40). Seven other unadjusted adverse clinical events ratios were below 70% and statistically significant favoring the DAA group: multiple organ failure (RR, 0.56; 95% CI, 0.44-0.72), liver cancer (RR, 0.62; 95% CI, 0.48-0.80), hepatic decompensation (RR, 0.62; 95% CI, 0.52-0.73), acute-on-chronic liver event (RR, 0.68; 95% CI, 0.56-0.84), acute myocardial infarction (RR, 0.64; 95% CI, 0.42-0.97), ischemic stroke (RR, 0.63; 95% CI, 0.42-0.95), and hemorrhagic stroke (RR, 0.47; 95% CI, 0.25-0.89); none favored the non-DAA group. In the marginal structural modeling-adjusted analysis, DAA exposure was associated with statistically significant lower odds of adverse events than non-DAA exposure for death (adjusted odds ratio [aOR], 0.42; 95% CI, 0.30-0.59), multiple organ failure (aOR, 0.67; 95% CI, 0.49-0.90), hepatic decompensation (aOR, 0.61; 95% CI, 0.49-0.76), acute-on-chronic liver event (aOR, 0.71; 95% CI, 0.56-0.91), and arrhythmia (aOR, 0.47; 95% CI, 0.25-0.88).Conclusions and relevanceDirect-acting antiviral exposure may not be associated with higher rates of any serious adverse events, including those related to liver, kidney, and cardiovascular systems. Safety concerns based on previous reports did not appear to be supported in this study with more comprehensive data and rigorous statistical methods.

Dataset Information

Role of Inflammatory/Immune Response and Cytokine Polymorphisms in the Severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAs) Treatment.

Publications

Role of Inflammatory/Immune Response and Cytokine Polymorphisms in the Severity of Chronic Hepatitis C (CHC) before and after Direct Acting Antiviral (DAAs) Treatment.

Similar Datasets

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