100% sustained virological response and fibrosis improvement in real-life use of direct acting antivirals in genotype-1b recurrent hepatitis C following liver transplantation (original) (raw)
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Digestive and Liver Disease, 2012
Backgrounds/aims: We evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score ≥ 4 and Staging score up to 3 (Ishak) at 1 year after liver transplantation. Methods: Seventy-three consecutive patients with mild/moderate recurrence were randomized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks. Liver biopsies obtained at baseline (1 year after transplantation) and 2 years afterwards were evaluated for assessment of disease progression, defined as worsening of at least 2 staging points or progression to stage 4 or higher. Results: As for these two major histological end points there were no statistically significant differences between the 2 groups (36.1% vs. 50%, p = 0.34 and 36.1% vs. 38.9%, p = 1). Fifteen treated patients (41%) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients (p = 0.04). Conclusions: Although antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response, the majority of the overall population of our patients with mild-moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment (EudraCT number: 2005-005760).
Transplantation Proceedings, 2018
Background. Direct-acting antivirals (DAAs) have revolutionized the treatment of hepatitis C, including transplant recipients with an advanced fibrosis stage. Our aim in this study was to assess the clinical and functional benefits and improvement in liver fibrosis after treatment with DAAs in liver transplant recipients with chronic hepatitis C virus who achieved sustained virologic response (SVR). Methods. We retrospectively analyzed 42 patients who underwent liver transplantation (LT) at our institution and were treated with DAAs from June 2014 to December 2015. Two patients died, so we ultimately included 40 transplant patients with chronic hepatitis C who received DAAs and achieved SVR. We assessed liver function, fibrosis stage, and clinical features at the start of the treatment, and then at 6 and 12 months after SVR. The indication for LT was hepatocellular carcinoma in 8 patients (20%) and Child-Pugh score B/C in 32 patients (80%). Results. The DAAs regimens were sofosbuvir plus daclatasvir (45.0%), simeprevir plus sofosbuvir (42.5%), sofosbuvir plus ledipasvir (7.5%), and ombitasvir/paritaprevir/ritonavir (5%). The mean Modified End-stage Liver Disease (MELD) score pretreatment was 10.78, and was 8.46 at 1 year after treatment (P < .05). In addition, fibrosis stage decreased significantly from 14.81 kPa to 9.07 kPa (FibroScan) at 12 months after SVR. Clinically, there was a significant improvement, including control of ascites and chronic hepatic encephalopathy. Conclusion. DAAs were used successfully in the treatment of hepatitis C after orthotopic liver transplantation and resulted in significant improvement in liver function as measured by MELD score, fibrosis level, and cirrhotic clinical condition, even in patients with very advanced disease.
Liver Transplantation, 2008
Antiviral therapy after liver transplantation (LT) using interferon (IFN) and ribavirin (RBV) can achieve a sustained virological response (SVR) rate ranging from 20% to 45%. The aims of our study were to assess efficacy and tolerability of therapy, effect on fibrosis progression and the importance of the initial fibrosis stage to outcome. A total of 113 hepatitis C virus (HCV)-infected LT patients received 133 courses of IFN (standard, n ϭ 29, pegylated IFN [pegIFN], n ϭ 104) and RBV (75% genotype 1). Early virological response (EVR), end-of-treatment (EOT), and SVR were obtained in 74%, 55%, and 38%, respectively. EVR, completion of treatment, viral load before therapy, genotype non-1, and use of pegIFN were predictive of SVR, but only EVR remained in the multivariate analysis. SVR was obtained in 45% patients who received a second course of therapy. Paired biopsies at baseline, at EOT and at long-term were available in 42 patients. The mean fibrosis stage remained stable in patients with SVR and increased in patients without response. Rejection episodes were observed in 6% of patients. Tolerability of therapy decrease in patients with fibrosis stage Ն3 on baseline liver biopsy. A total of 20% of them died or were retransplanted due to liver failure as opposed to 1% of patients who had fibrosis stage Ͻ3. In conclusion, IFN and RBV achieved SVR in 38% of patients. EVR is independently associated with SVR. Fibrosis stage remained stable in patients with SVR and increased in nonresponders. Fibrosis stage Ն3 was associated with a high rate of liver failure, arguing for an early introduction of antiviral therapy.
Gastroenterology, 2007
Patients with mild hepatitis C recurrence (fibrosis stage F0 to F2, n ؍ 54) were randomized to no treatment (group A, n ؍ 27) or peginterferon alfa-2b/ ribavirin for 48 weeks (group B, n ؍ 27). Patients with severe recurrence (F3 to F4, cholestatic hepatitis) were treated (group C, n ؍ 27). All patients (n ؍ 81) underwent a liver biopsy at baseline and after followup; paired hepatic venous pressure gradient (HVPG) measurements were available in 51 patients. Results: Thirteen (48%) patients of group B and 5 (18.5%) of group C achieved sustained virological response. Liver fibrosis progressed >1 stage in 40 (49%) of 81 patients: 19 (70%) of group A versus 7 (26%) of group B (P ؍ .001) and in 14 (54%) of group C. HVPG increased (6.5 to 13 mm Hg, P < .01) in patients in whom fibrosis worsened, whereas it decreased (5 to 3.5 mm Hg, P ؍ .017) or remained unchanged in those with fibrosis improvement or stabilization, respectively. The only variable independently associated with fibrosis improvement/stabilization was treatment (odds ratio [OR] ,7.3؍ 95% confidence interval [CI] 1.3 to 10, P ؍ .009). Among treated patients, alanine aminotransferase (ALT) normalization and viral clearance were independently associated with histological or hemodynamic improvement/stabilization (OR 5.3, 95% CI 1.5 to 18, P < .01; OR 7.4, 95% CI 1.4 to 38, P ؍ .01; respectively). Conclusions: Our data demonstrate that in liver transplantation recipients, antiviral therapy slows disease progression (particularly in sustained virological responders), as shown by its effects on liver histology and on HVPG.
Clinical transplantation, 2018
Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. The current study aimed at evaluation of hepatic fibrosis changes among long term responders to DAAs therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n=52). Hepatic fibrosis status was assessed, non-invasively, by calculation of fibrosis-4 score (FIB-4) and aspartate aminotransferase platelet ratio (APRI) index and by measurement of graft stiffness using FibroScan at baseline and 12- and 18-months post-treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12- and 18-months post-treatment. Patients were classified into 2 groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n=28) and advanced fibrosis groups (≥ F3). Over 18 months...
Journal of Gastroenterology and Hepatology, 2005
Aim: Recurrent hepatitis C virus (HCV) is universal following liver transplantation. Patients are often treated with interferon and ribavirin in an attempt to eradicate the virus. We describe our experience with 38 patients with recurrent HCV from a single liver transplant program. Methods: Between October 2000 and November 2001, 38 patients with recurrent HCV were treated with interferon alpha 2b 3 million units three times a week and ribavirin 1000-1200 mg per day. HCV RNA and liver biopsies were performed before treatment at the end of treatment (EOT), and 6 months after EOT in patients who were HCV RNA negative at EOT. Results: There were 29 males and nine females. Median age was 49 years. In total, 34 patients were genotype 1 and two each were genotype 3 and 4. Six patients received HCV positive donors and 24 patients (63%) completed treatment. The most common indication for discontinuation of treatment was severe fatigue in 14 patients (37%). On intention to treat analysis, a sustained biochemical and virological response occurred in 10 patients (26%). Unchanged or improved fibrosis scores were present in 37% of patients, of whom 71% were non-responders to therapy. Conclusions: Interferon alpha 2b and ribavirin were poorly tolerated in this series of recurrent HCV patients, with sustained HCV eradication occurring in only 26% of patients. However, the majority of non-responders demonstrated unchanged or improved fibrosis scores, suggesting that a subset of patients may benefit from maintenance antiviral therapy to prevent the development of cirrhosis.
Liver Transplantation, 2002
, with histological recurrence developing in at least 50% of patients within the first year. The aim of this study is to assess the safety and efficacy of interferon alfa-2b plus ribavirin in treating histological recurrent HCV after LT. Since 1998, patients with HCV with significant histological recurrence (fibrosis > 3 and/or histological activity index > 5) or progressive cholestatic disease after LT were treated with interferon alfa-2b (3 million units subcutaneously three times weekly) plus ribavirin (800 to 1,000 mg/d) for 12 months. Immunosuppression was tapered to cyclosporine/FK506 monotherapy. HCV RNA was assessed at entry, week 24, end of treatment, and 6 months after therapy. The primary end point was loss of HCV RNA 6 months after therapy, whereas the secondary end point was histological response. Fifty-four patients met criteria for treatment and have completed follow-up. Patients were mainly men (71% men; mean age, 51 ؎ 5 years) with genotype 1 infection (88%) and high viral load (mean HCV RNA, 38 ؎ 9 mEq/mL). Dose modification was required in 72% of patients because of cytopenia or side effects. Intent-totreat analysis showed that serum HCV RNA was undetectable in 19 patients (35%) week 24, 21 patients (38%) week 48, and 16 patients (30%) at the 6-month follow-up. Paired liver biopsy results (before and within 6 months after treatment) were available for 35 patients. Patients who achieved viral eradication had no significant progression of fibrosis after 1 year of therapy. In summary, combination therapy is a reasonable antiviral option for recurrent HCV infection for established post-LT hepatitis and appears to prevent histological progression of disease if viral eradication is successful. (Liver Transpl 2002;8:
Drug Design, Development and Therapy
Background: Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) has been a frequent and relevant problem in the past two decades. This analysis evaluated the efficacy and safety of new interferon (IFN)-free direct-acting antiviral (DAA) therapies in a large real-world cohort of HCV patients after LT. Methods: We retrospectively analyzed a cohort of 157 patients infected with HCV who underwent deceased donor LT between 1997 and 2014. Patient survival, outcome, and side effects of antiviral therapy were assessed. Results: Survival with recurrent HCV genotype 1 (GT1) infection was inferior to other HCV GTs (P=0.01). The overall sustained virological response (SVR) rate with new DAA therapy was 94.6% (n=37). Patients with both GT1 and other GTs reached SVR rates .90%. We noticed a few side effects, mainly caused by ribavirin, and only one discontinuation in DAA-treated patients. Conclusion: DAA therapy was effective and safe in previous hard-to-treat patients after LT in this real-world cohort.
Alimentary Pharmacology & Therapeutics, 2013
This uncommissioned review article was subject to full peer-review. SUMMARY Background Recently, the therapeutic landscape with regard to anti-HCV therapy has changed dramatically. The new directly acting anti-virals (DAAs) have demonstrated improved sustained virological response (SVR) compared with pegylated-interferon and ribavirin. Aim To examine and present the latest data with regard to anti-viral therapy in genotype 1 HCV-positive transplant candidates and recipients. Methods An electronic search using Medline was performed. Search terms included 'HCV, DAA and protease inhibitor' in combination with 'treatment pretransplantation' and 'treatment post-transplantation'. Results Patients with advanced fibrosis and cirrhosis have inferior SVR rates compared with patients with minimal fibrosis. A low accelerating dose regimen (LADR) of pegylated interferon and ribavirin (PR) appears to be a safe therapeutic option. Side effects also appear to be more pronounced in patients with advanced disease. Data from the large registration studies with triple therapy (boceprevir or telaprevir plus PR) demonstrated improved SVR rates even in patients with advanced disease, although virological relapse rates were highest amongst these patients. In transplant recipients, initial data are being reported on the use of triple therapy, and although no SVR data are available, promising results are accruing. The drug-drug interactions appear to be manageable. Side effects in particular anaemia appear to be markedly increased in the posttransplant setting. Conclusions The use of the new DAAs in patients with advanced fibrosis/cirrhosis pretransplant and posttransplant appears possible, with manageable side effects and drug-drug interactions, and improved early virological response rates. We recommend that these patients are managed in centres with the appropriate expertise.