Antiviral therapy and fibrosis progression in patients with mild–moderate hepatitis C recurrence after liver transplantation. A randomized controlled study (original) (raw)
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Liver international : official journal of the International Association for the Study of the Liver, 2015
Patients who achieve sustained virological response (SVR) following treatment of post-liver transplant (LT) recurrence of hepatitis C virus (HCV) infection have improved outcomes. The full impact of eradication of HCV on allograft histology is, however, not clearly known. We studied allograft histology in protocol-based paired liver biopsies in consecutive LT recipients who underwent post-LT treatment of recurrence of HCV. A total 116 patients were treated with interferon-based therapy for recurrent HCV. Paired pre-treatment baseline biopsies and post-treatment biopsies were available in 83.2% of patients. SVR was achieved in 37.9% of patients. Among patients who achieved SVR 20.5% had progression of fibrosis on post treatment biopsies vs. 65.5% of patients with non-response/relapse (p<0.001). The impact of virologic response on fibrosis progression was sustained and similar outcome was observed in the subset of patients who had 4-5 year post treatment biopsies available. In the ...
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.
Journal of gastrointestinal and liver diseases : JGLD, 2018
Nowadays, interferon-free therapy using new direct-acting antivirals (DAA) has dramatically increased the cure rate across different HCV-infected patient populations, including groups traditionally viewed as difficult-to-treat (patients with co-infections, cirrhosis and liver transplant - LT recipients) with marked improvement in safety and tolerability. To present our experience with DAA therapy in LT recipients, as well as to compare pre- and post-treatment liver stiffness (LS) and noninvasive fibrosis scores. Our cohort consisted of 89 patients with genotype 1 (GT1) recurrent hepatitis C after LT. Seventy six patients received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin and 13 sofosbuvir/ledipasvir+/-ribavirin. Fibroscan®, FIB4 and APRI scores were performed in all patients before and 12 weeks after DAA therapy. We analyzed 45 (50.5%) males and 44 (49.5%) females with a mean age of 55+/-7.7 years. Median time since LT was 20.9 months. At baseline, 53 (59.6%) of patients...
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, 2004
Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis, and graft loss following orthotopic liver transplantation. Treatment for posttransplant recurrence of hepatitis C with interferon-based therapy is difficult but results in loss of detectable virus in up to 30% of patients. However, the durability of viral clearance and the associated histologic response in this setting is unknown. The aim of this study was to determine whether viral loss in response to antiviral therapy is durable and associated with improvement in liver histology. All liver transplant recipients who received interferonbased treatment for recurrent hepatitis C virus (HCV) at the University of Florida from 1991 to 2002 were included in this study. Patients who lost detectable HCV after treatment with interferon alone or in combination with ribavirin were followed to assess the durability of viral response and its impact on liver histology. One hundred nineteen transplant recipients were treated with interferon or combination therapy. Twenty-nine (20 men, 9 women; mean age, 54 yrs [range, 42-74 yrs]) lost detectable HCV RNA and remained virus negative for at least 6 months after discontinuing therapy (sustained viral response[SVR]). The mean follow-up after discontinuing therapy was 24.7 months (range, 6-70 mos). Our study cohort included one patient with SVR following interferon monotherapy and 28 patients with SVR following combination therapy with interferon plus ribavirin. All patients remained HCV RNA negative (assessed by polymerase chain reaction or branched-DNA assay) during follow-up of up to 5 years. Liver histology assessed 2 years after treatment showed less inflammation compared with before treatment in 50% and showed no change in 38%. By 3 to 5 years post-treatment (n ؍ 15 recipients), inflammation was reduced in 60% and remained unchanged in 33%. Fibrosis stage at 2 years improved by > 1 stage in 27 %, remained unchanged in 38 %, and worsened in 35% despite viral clearance. At 3 to 5 years, the fibrosis stage had improved in 67%, remained unchanged in 13%, and worsened in 20%. Both grade of inflammation and fibrosis stage improved by 3 to 5 years posttreatment compared with baseline histology (p < 0.05). In conclusion, loss of HCV after treatment of recurrent chronic hepatitis C with interferon and ribavirin is durable, and the durability of the SVR is associated with improvement in hepatic inflammation and regression of fibrosis.
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: