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Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation.

ABSTRACT: Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of HCV in patients who are liver transplant recipients. In the present study, we investigated HCV eradication via interferon-free therapies with DAAs in two HCV patients with advanced liver fibrosis following renal transplantation. In both cases, the interferon-free regimens with DAAs were effective in eradicating HCV in the patients after kidney transplantation. No adverse events caused by interferon were identified with the exception of anemia. Interferon-free regimens with DAAs for recurrent HCV in patients following kidney transplantation are relatively safe and effective. However, attention should be focused on anemia during these treatments.

SUBMITTER: Sasaki R

PROVIDER: S-EPMC4939684 | biostudies-literature | 2016 May-Aug

REPOSITORIES: biostudies-literature

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Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation.

Sasaki Reina R Kanda Tatsuo T Yasui Shin S Haga Yuki Y Nakamura Masato M Yamato Mutsumi M Wu Shuang S Nakamoto Shingo S Arai Makoto M Mikami Shigeru S Miyauchi Hideaki H Matsubara Hisahiro H Yokosuka Osamu O

Case reports in gastroenterology 20160527 2

Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively ...[more]

PMID: 27462193

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Project description:Patients' experience during treatment may affect treatment adherence. Our aim was to assess the impact of patient-reported outcomes (PROs) on adherence to different anti-hepatitis C virus (HCV) regimens.Clinical, demographic, and PRO data (short form-36 [SF-36], chronic liver disease questionnaire-hepatitis C version [CLDQ-HCV], functional assessment of chronic illness therapy-fatigue [FACIT-F], work productivity and activity impairment: specific health problem [WPAI:SHP]) from 13 multinational clinical trials of anti-HCV treatment were available. Treatment adherence was defined as >80% of prescribed doses taken.Included were 4825 HCV patients. Regimens were grouped into: interferon- and ribavirin (RBV)-containing (±sofosbuvir [SOF]), interferon-free RBV-containing (RBV?+?SOF?±?ledipasvir [LDV]), and interferon-free RBV-free (LDV/SOF). The adherence to these regimens were 77.6%, 84.3%, and 96.2%, respectively (P?<?0.0001). Nonadherent patients were more likely to be unemployed and to have a greater PRO impairment at baseline (up to -5.3% lower PRO scores, P?<?0.0001). During treatment with interferon- or RBV-based regimens, nonadherent patients experienced lower PROs and had larger decrements from their baseline PRO scores. In contrast, there were no significant declines in PRO scores (all P?>?0.05) for the small number of patients who were nonadherent to LDV/SOF. In multivariate analysis, being treatment-naive, longer treatment duration, and receiving an interferon- or RBV-containing regimen were associated with a lower likelihood of adherence (all P?<?0.003). Better baseline and on-treatment PRO scores were associated with a higher likelihood of adherence to interferon and RBV.The use of interferon and/or RBV, longer duration of treatment, and lower baseline and on-treatment PRO scores were linked to a decreased likelihood of being adherent to interferon?+?RBV-containing or interferon-free RBV-containing antiviral regimens. Interferon- and RBV-free regimens were associated with excellent adherence.

Project description:Background & aimsChronic hepatitis C virus infection activates an intrahepatic immune response, leading to increased expression of interferon (IFN)-stimulated genes and activation of natural killer (NK) cells-the most prevalent innate immune cell in the liver. We investigated whether the elimination of hepatitis C virus with direct-acting antiviral normalizes expression of IFN-stimulated genes and NK cell function.MethodsWe used multicolor flow cytometry to analyze NK cells from the liver and blood of 13 HCV-infected patients who did not respond to treatment with pegylated interferon and ribavirin. Samples were collected before and during IFN-free treatment with daclatasvir and asunaprevir and compared with samples from the blood of 13 healthy individuals (controls). Serum levels of chemokine C-X-C motif ligand (CXCL) 10 or CXCL11 were measured by enzyme-linked immunosorbent assay.ResultsBefore treatment, all patients had increased levels of CXCL10 or CXCL11 and a different NK cell phenotype from controls, characterized by increased expression of HLA-DR, NKp46, NKG2A, CD85j, signal transducer and activator of transcription 1 (STAT1), phosphorylated STAT1, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). NK cells from patients also had increased degranulation and decreased production of IFNγ and tumor necrosis factor α compared with NK cells from controls. Nine patients had an end-of-treatment response (undetectable virus) and 4 had virologic breakthrough between weeks 4 and 12 of therapy. A rapid decrease in viremia and level of inflammatory cytokines in all patients was associated with decreased activation of intrahepatic and blood NK cells; it was followed by restoration of a normal NK cell phenotype and function by week 8 in patients with undetectable viremia. This normalized NK cell phenotype was maintained until week 24 (end of treatment).ConclusionsDirect-acting antiviral-mediated clearance of HCV is associated with loss of intrahepatic immune activation by IFNα, which is indicated by decreased levels of CXCL10 and CXCL11 and normalization of NK cell phenotype and function.

Dataset Information

Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation.

Publications

Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation.

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