Treatment Of Recurrent Hepatitis Research Articles

Sofosbuvir and daclatasvir are safe and effective in treatment of recurrent hepatitis C virus in Egyptian patients underwent living donor liver transplantation

BackgroundLiver transplant population has been considered as a special population in the treatment of hepatitis C virus infection, not only because of lower sustained virological response (SVR) rates in comparison with pretransplant setting, but also for other aspects (i.e., immunosuppressive therapy, renal function, drug–drug interactions). We aimed to evaluate the efficacy and safety of the combined treatment with sofosbuvir and daclatasvir with or without ribavirin in liver transplant recipients with recurrent hepatitis C following transplantation and screening for the development of hepatocellular carcinoma during treatment, after the end of treatment, or during follow-up. This multicenteric prospective study was conducted in Egypt. This study included 40 patients who underwent living donor liver transplantation that started treatment at least 3 months following transplantation. All participants received 400 mg sofosbuvir once daily plus daclatasvir 60 mg daily ± ribavirin. Treatment lasted for up to 24 weeks, and participants were followed up as outpatients monthly for 12 and 24 weeks and 36 weeks post-treatment to determine sustained virological response (SVR12 and SVR24), considered to be a cure and detection of any changes in tumor markers or radiological imaging during follow-up.ResultsIn the current study, 40 patients (100%) have good response to treatment during treatment and during follow-up (SVR 12 was 100%). No abnormal side effects to treatment were detected; also, no drug–drug interactions were noted during the treatment.ConclusionsTreatment of HCV after living donor liver transplantation with combined sofosbuvir and daclatasvir is safe and well-tolerated and provides high rates of SVR.

Evaluation of different regimens of new direct-acting antiviral drugs for the treatment of recurrent hepatitis C virus infection after liver transplantation

Evaluation of different regimens of new direct-acting antiviral drugs for the treatment of recurrent hepatitis C virus infection after liver transplantation

Efficacy and safety of an interferon-free regimen for treatment of recurrent hepatitis C virus infection following liver transplant

Efficacy and safety of an interferon-free regimen for treatment of recurrent hepatitis C virus infection following liver transplant

Early treatment of recurrent hepatitis C virus infection after liver transplantation in the era of direct-acting antivirals, what we have learned till now?

Early treatment of recurrent hepatitis C virus infection after liver transplantation in the era of direct-acting antivirals, what we have learned till now?

Effectiveness and safety of DAA treatment for recurrent hepatitis C after liver transplantation: The NAVIGATOR Lombardia-Veneto network

Effectiveness and safety of DAA treatment for recurrent hepatitis C after liver transplantation: The NAVIGATOR Lombardia-Veneto network

The use of sofosbuvir for the treatment of recurrent hepatitis C after liver transplantation

The article presents the experience of direct-acting antiviral (DAA) drug treatment for hepatitis C in the patients after liver transplantation. The end-stage liver disease caused by hepatitis C is the main indication for orthotopic liver transplantation (OLT). In 2013, the first agent in the class of antiviral drugs directly acting on hepatitis C virus (HCV) was introduced into clinical practice. That was sofosbuvir, a HCV polymerase inhibitor, that could be used without interferon alfa. Materials and methods . The study enrolled 33 liver transplant recipients with recurrent hepatitis C. Thirty-five courses of antiviral therapy (AT) were conducted with sofosbuvir being one of AT components. Results. By the time of analysis, 21 patients had completed the antiviral therapy. All the patients showed an initial response to the antiviral therapy, HCV aviremia was achieved. In 3 patients, with the evaluable sustained virologic response (SVR), a renewed HCV replication was observed in the first weeks after the AT completion. Conclusion. The new direct-acting antiviral drugs offer an effective antiviral therapy to all liver graft recipients with recurrent HCV.

Prevention and Treatment of Recurrent Hepatitis B after Liver Transplantation.

Chronic hepatitis B is a global health problem that leads to development of various complications, such as cirrhosis, liver cancer, and liver failure requiring liver transplantation. The recurrence of hepatitis B virus (HBV) post-liver transplantation is a major cause of allograft dysfunction, cirrhosis of the allograft, and graft failure. Patients with high viral load at the time of transplantation, hepatitis B e antigen (HBeAg) positivity, or those with a history of anti-viral drug resistance are considered as high-risk for recurrent HBV post-liver transplantation, while patients with low viral load, including HBeAg negative status, acute liver failure, and hepatitis D virus (HDV) co-infection are considered to be at low-risk for recurrent HBV post-liver transplantation. Antivirals for patients awaiting liver transplantation(LT) cause suppression of HBV replication and reduce the risk of recurrent HBV infection of the allograft and, therefore, all HBV patients with decompensated cirrhosis should be treated with potent antivirals with high genetic barrier to resistance (entecavir or tenofovir) prior to liver transplantation. Prevention of post-liver transplantation recurrence should be done using a combination of hepatitis B immunoglobulin (HBIG) and antivirals in patients at high risk of recurrence. Low dose HBIG, HBIG-free protocols, and monoprophylaxis with high potency antivirals can still be considered in patients at low risk of recurrence. Even, marginal grafts from anti-HBc positive donors can be safely used in hepatitis B surface antigen (HBsAg) negative, preferably in anti-hepatitis B core (HBc)/anti-hepatitis B surface (HBs) positive recipients. In this article, we aim to review the mechanisms and risk factors of HBV recurrence post-LT in addition to the various treatment strategies proposed for the prevention of recurrent HBV infection

Genotype 3 and higher low-density lipoprotein levels are predictors of good response to treatment of recurrent hepatitis C following living donor liver transplantation.

Treatment of recurrent hepatitis C after liver transplantation is associated with poor sustained virological response (SVR) in genotype 1, and data on genotype 3 is limited to small numbers. We report one of the largest series of genotype 3 patients treated for recurrent hepatitis C following living donor liver transplantation (LDLT). From January 2002 to November 2013, of 1349 transplants, 359 patients had hepatitis C. Patients with histological recurrence were treated with pegylated interferon in escalating dose regimen for 48weeks and weight-based ribavirin. Virological response was defined as rapid virological response (RVR-4weeks), early virological response (EVR-12weeks), end of treatment response (ETR-48weeks), and SVR (24weeks after end of treatment). SVR and no-SVR groups were compared for age, sex, body mass index (BMI), diabetes, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, ferritin, genotype, and hepatitis C virus (HCV) RNA levels before initiation of treatment. The study included 67 patients who had at least 18months of follow up after treatment initiation (45 males), aged 51 ± 6.3years. Treatment was started after 16months (median); baseline median RNA was 2.7 × 10(6)IU/mL. There was no significant difference between the SVR and no-SVR groups regarding age, sex ratio, follow up period, total cholesterol, triglycerides, HDL, BMI, prevalence of diabetes, HCV RNA, and ferritin levels. Genotype 3, RVR, EVR, ETR, and higher LDL levels were significantly associated with SVR. Genotype 3 had a significantly higher SVR rate of 71% as compared to an SVR rate of only 14% in genotype 1, p = 0.0003. Absence of RVR and EVR predicted treatment failure with a specificity of 88 % and 92%, respectively. Genotype 3 and higher LDL levels predict SVR in patients treated for hepatitis C recurrence following LDLT, whereas absence of RVR and EVR strongly predict treatment failure.

Sofosbuvir and simeprevir is effective for recurrent hepatitis C in liver transplant recipients.

Hepatitis C is the most common indication for liver transplantation (LT). Recurrent infection is universal and can lead to progressive liver disease. Widespread use of interferon-based therapy has been limited by intolerability and adverse effects. We retrospectively evaluated the safety, tolerability, and efficacy of sofosbuvir and simeprevir in the treatment of recurrent hepatitis C in adult (age >18) LT recipients. Seventy-six percent of the recipients were male and the mean age [±standard deviation (SD)] was 61 (±6.0) years. The mean time (±SD) from LT to treatment initiation was 71.8 (±77.1) months. Of the 26 patients with viral levels measured 4weeks after starting antiviral therapy, 58% were undetectable. At the end of therapy, viral load was undetectable in all transplant recipients. The 12week sustained viral response (SVR) was 93%. All recipients were able to complete therapy and no patients required growth factors of blood product transfusion during treatment. No patient required drug interruption of their immunosuppressant therapy. The use of sofosbuvir and simeprevir is efficacious, safe, and tolerable and should be considered in LT recipients with recurrent HCV who are candidates for antiviral therapy.

Treatment of Recurrent Hepatitis C With Interferon-free Regimens: Better Starting Early

Treatment of Recurrent Hepatitis C With Interferon-free Regimens: Better Starting Early

Use of simeprevir following pre-emptive pegylated interferon/ribavirin treatment for recurrent hepatitis C in living donor liver transplant recipients: a 12-week pilot study.

The management of recurrent hepatitis C following liver transplantation remains a challenge. We prospectively investigated the efficacy and safety of simeprevir in combination with pegylated interferon and ribavirin in five patients undergoing living donor liver transplantation (LDLT) with recurrent hepatitis due to hepatitis C virus (HCV) genotype 1b. As the immunosuppressive regimen, four received cyclosporine A (CsA) and one received tacrolimus (FK); no dose adjustment was made prior to the introduction of simeprevir, but the dose was accordingly modified afterwards. All five patients completed the intended 12-week treatment course without significant adverse events greater than grade 2, and no episodes of rejection were detected during the study period. The trough levels of CsA and FK were stably maintained. At week 12, HCV-RNA was not detectable in three of the five patients, whereas the HCV titer of the other two patients, including one with Q80L and V170I mutations at the HCV NS3 position, was at the lower level of quantification (1.2 log10 IU/ml). Based on this pilot study, simeprevir-based triple therapy is safe and somewhat effective within the first 12 weeks in LDLT recipients with HCV recurrence. Further studies are warranted to obtain robust conclusions.

Estrategias para evitar la recidiva viral B después del trasplante hepático

Hepatitis B is currently an excellent indication for liver transplantation due to the highly effective strategies of prophylaxis and treatment for recurrent hepatitis B infection. The combined administration of low-dose hepatitis B hyperimmune gamma globulin and a nucleoside/nucleotide analogue with a high genetic barrier to resistance, such as entecavir (except for patients with lamivudine resistance) or tenofovir, represents the standard for the prophylaxis of recurrent hepatitis B infection and is used in most centers. The drawbacks of long-term administration of hyperimmune gamma globulin have led to research on regimens in which this agent is withdrawn after a certain amount of time in combination treatment, a strategy that appears to be safe in patients with undetectable viremia at the time of liver transplantation if the patients adhere to the treatment. In recent years, there has also been research into regimens of gamma-globulin-free prophylaxis, based only on the administration of oral antiviral drugs, which appear to be safe if antivirals with a high genetic barrier to resistance are used. Hepatitis B prophylaxis should be maintained indefinitely; therefore, the total withdrawal of prophylaxis is not an accepted strategy at present in daily clinical practice if not in the context of a clinical trial.

Prevention and Treatment of Recurrent Hepatitis C after Liver Transplantation

Hepatitis C virus (HCV) is the leading indication for liver transplantation in the United States. Recurrent HCV infection after transplant is nearly universal, and the disease course is accelerated. In select patients, pre-transplant antiviral therapy can be given with the aim of preventing recurrent infection. The more common strategy for managing recurrent HCV, however, is post-transplant antiviral therapy with the aim of achieving sustained virologic response. The limited efficacy and poor tolerability of pegylated-interferon and ribavirin among patients with cirrhosis or after liver transplant have been major barriers to preventing or treating recurrent HCV. Preliminary results suggest that virologic response in this patient population is improved with protease inhibitor (PI)-based triple therapy. Although the efficacy of this regimen at preventing or treating recurrent HCV remains to be seen, serious adverse events are frequent when PI-triple therapy is used in the transplant setting. More tolerable and effective treatment regimens are desperately needed in this patient population.

Pretransplant and posttransplant treatment of hepatitis C virus infection with protease inhibitors

Considering the impact of recurrent hepatitis C after liver transplantation on patient and graft survival, we examine the current and potential use of protease inhibitors in the prevention and treatment of recurrent hepatitis C. In genotype-1-infected patients in the waiting list, triple therapy with boceprevir or telaprevir should be considered in compensated cirrhotics. However, tolerability of therapy is low, and side effects are frequent and potentially life-threatening. In posttransplant hepatitis C, available data suggest that triple therapy substantially increases the virological response. Interactions of protease inhibitors with immunosuppressants are considerable, especially between tacrolimus and telaprevir. Anemia seems to be particularly frequent with triple therapy after liver transplantation. Interferon (IFN)-free regimens seem to achieve a high antiviral effect with an excellent safety profile and will probably replace the current IFN-based treatments in a few years from now. Antiviral therapy with protease inhibitors will substantially increase the number of patients achieving sustained hepatitis C virus eradication, either before or after liver transplantation. However, side effects and drug-drug interactions will possibly hamper their applicability in both settings; thus, a careful selection and management of patients will be crucial. In the near future, combination of direct-acting antivirals will allow shorter, safer, and more effective IFN-free regimens.

Pretransplant Serum Hepatitis C Virus RNA Levels Predict Response to Antiviral Treatment after Living Donor Liver Transplantation

BackgroundGiven the limited efficacy and high adverse event rate associated with treatment of recurrent hepatitis C after liver transplantation, an individualized treatment strategy should be considered. The aim of this study was to identify predictors of response to antiviral therapy for hepatitis C after living donor liver transplantation (LDLT) and to study the associated adverse events.MethodsA retrospective chart review was performed on 125 hepatitis C virus (HCV)-positive LDLT recipients who received interferon plus ribavirin and/or peginterferon plus ribavirin therapy at Kyoto University between January 2001 and June 2011.ResultsSerum HCV RNA reached undetectable levels within 48 weeks in 77 (62%) of 125 patients, and these patients were defined as showing virological response (VR). Of 117 patients, 50 (43%) achieved sustained VR (SVR). Predictive factors associated with both VR and SVR by univariate analysis included low pretransplant serum HCV RNA levels, a non-1 HCV genotype, and low pretreatment serum HCV RNA levels. In addition, LDLT from ABO-mismatched donors was significantly associated with VR, and white cell and neutrophil counts before interferon therapy were associated with SVR. Multivariate analysis showed that 2 variables–pretransplant serum HCV RNA level less than 500 kIU/mL and a non-1 HCV genotype–remained in models of both VR and SVR and that an ABO mismatch was associated with VR. No variables with a significant effect on treatment withdrawal were found.ConclusionsVirological response to antiviral therapy in patients with hepatitis C recurring after LDLT can be predicted prior to transplant, based on pretransplant serum HCV-RNA levels and HCV genotype. LDLT from ABO-mismatched donors may contribute to more efficacious interferon therapy.Trial RegistrationUMIN-CTR UMIN000003286

Virological response for recurrent hepatitis C improves long-term survival in liver transplant recipients

Recurrent hepatitis C virus (HCV) infection occurs universally and is regarded as a major cause of mortality after liver transplantation (LT) for HCV-related end-stage liver disease. We conducted this large, single-center, retrospective study to ascertain the long-term impact of virological response to treatment of recurrent hepatitis C on survival of LT recipients. From August 1987 to October 2011, 285 patients have received interferon-based antiviral therapy for recurrent hepatitis C. Of these 285, 245 patients were enrolled in this study. One hundred and twenty-six patients (51.4%) achieved sustained virological response (SVR). Relapsers (undetectable HCV-RNA at end of treatment, becoming positive afterward) comprised 9.0% (22/245), and nonresponse (NR; never achieving undetectable HCV-RNA) 39.6% (97/245). The median follow-up after completion of antiviral treatment was 2081 days. Using Kaplan-Meier method, patients who achieved SVR were shown to have significantly better 5-year patient survival (95.2%) than the NR group (49.9%) (P < 0.001), and a trend toward better 5-year survival than relapsers (87.5%) (P = 0.14); relapsers had a significantly longer survival than NR group (P = 0.005). When compared with NR, SVR and relapse appeared to be significant predictors of better survival, independent of underlying characteristics. In conclusion, virological response, especially SVR, translates into markedly improved long-term patient outcomes in patients transplanted for hepatitis C.

Treatment of recurrent hepatitis C after liver transplantation

Treatment of recurrent hepatitis C after liver transplantation

Effectiveness and Safety of Everolimus in the Treatment of Autoimmune Hepatitis Related to Anti-Hepatitis C Virus Therapy After Liver Transplant: Three Case Reports

Treatment of recurrent hepatitis C after liver transplantation is indicated in selected cases. During the combined treatment with pegylated interferon and ribavirin, some patients develop immune-mediated liver dysfunction similar to the previously described “de novo” autoimmune hepatitis. Herein we have presented three liver transplant patients who during or after combined antiviral treatment were diagnosed as autoimmune hepatitis related to interferon based on their clinical, biochemical, and liver histology features. There were two women and one man, of ages 49, 52, and 49 years who were transplanted due to cirrhosis related to hepatitis C virus genotype 1. In two patients, elevated liver enzymes occurred during antiviral therapy and in the third, after the therapy. The diagnosis of autoimmune hepatitis was reached after excluding other possible causes. One patient had a sustained viral response; and two cases were nonresponders. Antinuclear antibodies were present in two subjects and antinuclear antibodies and anti-smooth muscle antibodies in the other case. First-line treatment of autoimmune hepatitis with prednisone and azathioprine stabilized clinical and biochemical parameters'. In order to avoid the long-term use of prednisone, everolimus was introduced in the three patients. Interestingly, hepatitis C did not progress and clinical, biochemical, as well as histological parameters stabilized. In one patient, the liver fibrosis stage as assessed by histology showed improvement. However, one subject experienced repeated cerebral hemorrhage and died. Although this is heterogeneous population with partially known characteristics, with a difficult differential diagnosis, the objectives of preserving liver function and avoiding recurrent progressive hepatitis C seemed to be achieved by adding everolimus. In addition, we totally stopped prednisone therapy. In conclusion, treatment with everolimus in combination with cyclosporine achieved a partial remission in two liver transplan cases of autoimmune hepatitis related to interferon therapy.

De novo autoimmune hepatitis subsequent to switching from type 2b to type 2a alpha-pegylated interferon treatment for recurrent hepatitis C after liver transplantation: Report of a case

Interferon (IFN), which is the only possible agent for recurrent hepatitis C after liver transplantation, may cause serious immune-related disorders. We report a case of de novo autoimmune hepatitis (AIH), which developed subsequent to switching from 2b pegylated interferon-α (peg-IFN) to 2a peg-IFN after living donor liver transplantation (LDLT). A 51-year-old man with hepatitis C-associated liver cirrhosis underwent LDLT. About 13 months after the initiation of antiviral therapy, in the form of type 2b peg-IFN with ribavirin, a negative serum hepatitis C virus (HCV)-RNA titer was confirmed. Thereafter, the 2b peg-IFN was switched to 2a peg-IFN, 3 months after which severe liver dysfunction developed, despite a constantly negative HCV-RNA. Liver biopsy showed portal and periportal inflammatory infiltrates including numerous plasma cells, indicating AIH. He was treated with steroid pulse treatment, followed by high-level immunosuppression maintenance, but eventually died of Pneumocystis pneumonitis 4 months after the diagnosis of de novo AIH.

Treatment of Recurrent Hepatitis C in Liver Transplant Recipients With Extended Duration of Pegylated Interferon and Ribavirin

Treatment of Recurrent Hepatitis C in Liver Transplant Recipients With Extended Duration of Pegylated Interferon and Ribavirin