Sofosbuvir induced leucocytoclasic vasculitis: a case report.

Background: We describe a case of leucocytoclasic vasculitis induced by Sofosbuvir and its disappearence after the end of the therapy. The hepatitis C virus, firstly described in 1989, is a major global health problem, with high morbidity and mortality. We observed a temporal relationship between the treatment and the onset of vasculitis.

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens.

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR.

Study Design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR.

Complete hepatitis B virus prophylaxis withdrawal in hepatitis B surface antigen-positive liver transplant recipients after longterm minimal immunosuppression.

Tailored approaches have been attempted to prevent hepatitis B virus (HBV) reinfection in antibodies against hepatitis B surface antigen (HBsAg)-positive liver transplantation (LT) recipients in order to minimize the use of hepatitis B immune globulin (HBIG) and nucleoside analogues (NAs). We report the results of complete HBV prophylaxis withdrawal after a follow-up of at least 6 years in LT recipients with undetectable serum HBV DNA and intrahepatic total HBV DNA and covalently closed circular DNA at LT. We included 30 HBsAg positive, hepatitis B e antigen-negative recipients, 6 with hepatitis C virus and 7 with hepatitis D virus coinfection, who had received HBIG plus NA for at least 5 years after LT.

Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome.

Background: Triple therapy with telaprevir/boceprevir + pegylated-interferon+ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure.

Aims: To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors.

Methods: HCV-RNA was prospectively quantified in 158 patients receiving pegylated-interferon+ribavirin+telaprevir (N = 114) or+boceprevir (N = 44), at early time-points and during per protocol follow-up.

An a priori prediction model of response to peginterferon plus ribavirin dual therapy in naïve patients with genotype 1 chronic hepatitis C.

Background: Aim was to select naïve patients with genotype 1 chronic hepatitis C having a high probability of response to Peg-interferon+ribavirin therapy.

Methods: In 1073 patients (derivation cohort), predictors of rapid and sustained virological response were identified by logistic analysis; regression coefficients were used to generate prediction models for sustained virological response. Probabilities at baseline and treatment week 4 were utilized to develop a decision rule to select patients with high likelihood of response.

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

Background: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival.

Aim: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence.

Methods: 436 Liver transplant recipients (74.

Treatment of genotype-1 hepatitis C recurrence after liver transplant improves survival in both sustained responders and relapsers.

The aim of this study was to evaluate the factors affecting the response to treatment and how it could affect survival in a large series of genotype-1 HCV-transplanted patients. Three-hundred and twenty six genotype-1 HCV patients were enrolled. One hundred and ninety-six patients (60.

A randomized controlled trial of sequential pegylated interferon-α and telbivudine or vice versa for 48 weeks in hepatitis B e antigen-negative chronic hepatitis B.

Background: Short-term treatment for hepatitis B e antigen (HBeAg)-negative chronic hepatitis B remains unsatisfactory. The aim of our study was to compare the efficacy and safety of two sequential regimens of pegylated interferon (PEG-IFN)-α and telbivudine (LdT).

Methods: Adult patients with biopsy-proven HBeAg-negative chronic hepatitis B, elevated alanine aminotransferase (ALT) and serum HBV DNA ≥ 2,000 IU/ml were randomized 1:1 at baseline to receive PEG-IFN 180 μg/week for 24 weeks followed by LdT 600 mg/day for 24 weeks (PEG-IFN first), or vice versa (LdT first), plus 24-week follow-up; individuals with HCV, HDV or HIV coinfections and lamivudine resistance were excluded.

HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors.

Background: Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs).

Methods: The study includes 1568 NS3-protease sequences, isolated from PI-naive patients infected with HCV-genotypes 1a (N = 621), 1b (N = 474), 2 (N = 72), 3 (N = 268), 4 (N = 54) 5 (N = 6), and 6 (N = 73). Genetic-barrier was calculated as the sum of nucleotide-transitions (score = 1) and/or nucleotide-transversions (score = 2.

Treatment of recurrent genotype 4 hepatitis C after liver transplantation: early virological response is predictive of sustained virological response. An AISF RECOLT-C group study.

Introduction: Hepatitis C virus genotype 4 is predominant in the Middle East and Northern Africa, even if it has recently spread to Southern Europe. Data about the treatment of post-liver transplantation (LT) genotype 4 hepatitis C recurrence are scarce. We report a retrospective analysis of post-LT genotype 4 hepatitis C treatment in 9 Italian transplant centres, focusing on the overall survival rates and treatment outcome.

Treatment of hepatitis C recurrence is less successful in female than in male liver transplant recipients.

It has been recently suggested that the risk of graft loss after liver transplantation (LT) may increase in female HCV patients. The aim of the study was to examine gender differences in HCV therapy tolerance and outcome in LT patients treated for HCV recurrence. A retrospective study was conducted on liver recipients with HCV recurrence, who were given antiviral therapy from 2001 to 2009 in 12 transplant centers in Italy.

Liver transplantation for the treatment of nodular regenerative hyperplasia.

Background: Nodular regenerative hyperplasia (NRH) is the leading cause of non-cirrhotic portal hypertension in Western countries. Although some patients are successfully managed medically or with shunting procedures, others require liver transplantation. The aim of this review was to assess the overall results obtained with liver transplantation and to better define its role in this setting.

Safety of complete and sustained prophylaxis withdrawal in patients liver-transplanted for HBV-related cirrhosis at low risk of HBV recurrence.

Background & Aims: HBV reactivation after liver transplantation may be related to persistence of covalently closed circular (ccc) DNA. We investigated the safety of HBV prophylaxis withdrawal in selected HBV transplanted patients.

Methods: Thirty patients transplanted 64-195months earlier (23 males, median age 56yrs), HBsAg-positive, HBeAg, and HBV-DNA negative at transplant (43% HCV/HDV co-infected), with undetectable intrahepatic total and ccc-DNA were enrolled.

Plasma/erythrocyte ribavirin x100 ratio as an indicator of sustained virological response in HCV genotype 1 patients with early virological response.

Background: On-treatment predictors during antiviral therapy of HCV are useful because they allow discontinuation of an unnecessary treatment in non-responders. Our aim was to evaluate the usefulness of plasma and erythrocyte ribavirin levels in predicting sustained virological response (SVR) in HCV genotype 1 patients undergoing antiviral treatment.

Methods: A total of 40 HCV genotype 1 patients treated with pegylated interferon-alpha2a 180 microg weekly plus ribavirin 1,000 or 1,200 mg daily (according to body weight) were included in the study.

One-year vaccination against hepatitis B virus with a MPL-vaccine in liver transplant patients for HBV-related cirrhosis.

Conflicting results have been reported on vaccination against hepatitis B virus (HBV) as a prophylaxis against viral recurrence after liver transplantation. We investigated the efficacy of 1-year, monthly vaccination using an adjuvant 3-deacylated monophosphoryl-lipid-A (MPL) recombinant S vaccine initially administered together with hepatitis B immunoglobulins (HBIg) in 18 patients transplanted for HBV-related cirrhosis. All received 12 vaccine doses (HBsAg, 20 mcg plus MPL, 50 mcg): the initial six doses (phase I) were administered within 7days after intravenous HBIg (2000IU), while the last 6 (phase II) following HBIg withdrawal.

Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis.

Background: Life-long prophylaxis against HBV recurrence is recommended in patients transplanted for HBV-related disease. The risk of HBV reactivation is due to persistence of covalently closed circular (ccc) DNA in hepatocytes. Whether cccDNA persists in livers of long-term transplant survivors who received conventional prophylaxis is unknown.

Patterns of chronic hepatitis B in Central Italy: a cross-sectional study.

We investigated the patterns of chronic hepatitis B virus (HBV)-related disease in a large cohort of HBsAg-positive patients, in Central Italy, by collecting a screening form with demographic, clinical and laboratory data. Overall, 737 HBsAg-positive cases were included (70% male; median age 52 years): 30% were inactive HBsAg carriers, 51% had chronic hepatitis B (CHB) and 19% had HBV-related cirrhosis. Patients from non-European Union (EU) countries (n = 65) were significantly younger, had a higher prevalence of HBeAg-positive infection and hepatitis delta virus (HDV) co-infection than patients of Italian origin.

Assembly of biliary lipids in native hepatic bile after orthotopic liver transplantation: A biochemical and ultra-structural study in humans.

Background: In gallbladder bile, lipids aggregate as micelles and vesicles, yet the presence of lamellae remains controversial. Little is known on lipid assembly in dilute hepatic bile. Liver transplantation represents a condition in which bile is diluted immediately after transplant and tends to normalize thereafter.

Low-dose hepatitis B immunoglobulin given "on demand" in combination with lamivudine: a highly cost-effective approach to prevent recurrent hepatitis B virus infection in the long-term follow-up after liver transplantation.

Background: Cost of long-term prophylaxis with high-dose human hepatitis B immune globulin (HBIg) after liver transplantation is extremely high. The aim of the present study was to assess consumption rates of high (5,000 IU) and low (2,000 IU) doses of HBIg given intravenously "on demand", and determine their cost-effectiveness compared with conventional fixed monthly schedules.

Methods: The study included 11 male patients (mean age 53 years) who received transplants for hepatitis B virus (HBV)-related cirrhosis 29 to 96 months earlier, all receiving lamivudine (100 mg/day) prophylaxis.

Failure of a reinforced triple course of hepatitis B vaccination in patients transplanted for HBV-related cirrhosis.

Long-term immunoprophylaxis with anti-HBs immunoglobulins (HBIg) is used to prevent hepatitis B (HBV) reinfection after liver transplantation for HBV-related cirrhosis. This approach is highly expensive. A recent report proposed posttransplant HBV vaccination with a reinforced schedule as an alternative strategy to allow HBIg discontinuation.