Treatment of chronic HCV with sofosbuvir and simeprevir in patients with cirrhosis and contraindications to interferon and/or ribavirin.

Objectives: Patients with chronic hepatitis C virus (HCV) and cirrhosis are in critical need of treatment that is both effective and tolerable. The combination of simeprevir (SMV), a protease inhibitor, and sofosbuvir (SOF), a polymerase inhibitor, without peginterferon and/or ribavirin (PEGINF/RBV) has been shown to achieve sustained virologic response (SVR) exceeding 90% in patients with HCV genotype 1 with prior nonresponse and/or cirrhosis. The present report describes the efficacy of SMV and SOF in patients with cirrhosis, prior or current hepatic decompensation, and other contraindications to PEGINF/RBV.

Extended treatment with pegylated interferon alfa/ribavirin in patients with genotype 2/3 chronic hepatitis C who do not achieve a rapid virological response: final analysis of the randomised N-CORE trial.

Background And Aims: The combination of pegylated interferon alfa/ribavirin will likely remain the treatment of choice for HCV genotype 2/3 patients in financially constrained countries for the foreseeable future. Patients with poor on-treatment response may benefit from treatment extension. This study examined the effect of 48 versus 24 weeks of peginterferon alfa-2a/ribavirin on the sustained virological response (SVR) in patients with HCV genotype 2/3 who did not achieve rapid virological response (RVR).

Cure of HCV related liver disease.

Chronic hepatitis C virus (HCV) causes chronic liver injury and can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV can also interact with the immune system to cause several HCV related disorders including essential mixed cryoglobulinemia, vasculitis, dermatitis, glomerulonephritis and lymphoma. A strong association between HCV and diabetes mellitus also exists.

Cardiac dysfunction associated with a nucleotide polymerase inhibitor for treatment of hepatitis C.

Unlabelled: Treatment for chronic hepatitis C virus (HCV) infection is evolving from interferon (IFN)-based therapy to direct-acting antiviral (DAA) agents, yet some safety concerns have arisen involving cardiac toxicity. In this study, we sought to better understand the potential off-target toxicities of new DAAs. We retrospectively evaluated the clinical and pathological findings of the sentinel case in a phase II study that led to clinical development discontinuation for BMS-986094, an HCV nucleotide polymerase (nonstructural 5B) inhibitor.

A randomized phase 2b study of peginterferon lambda-1a for the treatment of chronic HCV infection.

Background & Aims: Peginterferon lambda-1a (Lambda) is a type-III interferon with similar antiviral activity to alfa interferons but with a diminished extrahepatic receptor distribution, reducing the risk for extrahepatic adverse events.

Methods: This was a randomized, blinded, actively-controlled, multicentre phase 2b dose-ranging study in patients chronically infected with HCV genotypes 1-4. Treatment-naive patients received Lambda (120/180/240 μg) or peginterferon alfa-2a (alfa; 180 μg) once-weekly with ribavirin for 24 (genotypes [GT] 2,3) or 48 (GT1,4) weeks.

Long term changes in liver histology following treatment of chronic hepatitis C virus.

Background And Aims: The histologic hallmarks of chronic HCV include inflammation and fibrosis. The impact of interferon therapy on liver histology was evaluated.

Material And Methods: The study population consisted of 348 patients with chronic HCV who underwent a baseline liver biopsy, received either no treatment or a single course of interferon based therapy, were followed for 5 years without any treatment or additional treatment and then underwent a repeat liver biopsy.

My treatment approach to chronic hepatitis C virus.

The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV).

ABT-450/r-ombitasvir and dasabuvir with ribavirin for hepatitis C with cirrhosis.

Background: Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis.

Methods: We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight.

Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis.

Background: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.

Methods: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks.

Hepatitis C virus therapy in the direct acting antiviral era.

Purpose Of Review: The evolution of treatment for patients with chronic hepatitis C virus (HCV) is evolving at a rapid pace. Two new oral antiviral agents, simeprevir and sofosbuvir, have already been approved and are now available for treatment of patients with chronic HCV. Other antiviral agents will be available during 2014.

HCV F1/F2 patients: treat now or continue to wait.

The treatment of chronic HCV is evolving rapidly. In 2014, three new oral antiviral agents, simeprevir, faldeprevir and sofosbuvir will become available for patients with HCV genotype 1. These agents have far less side effects than the first generation protease inhibitors telaprevir and boceprevir.

Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.

Background & Aims: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV.

Methods: Patients with HCV infection and thrombocytopenia (platelet count <75,000/μL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer.

Patients with HCV and F1 and F2 fibrosis stage: treat now or wait?

The current standard of care (SOC) for patients with chronic HCV genotype 1 is a combination of either boceprevir or telaprevir with peginterferon (PEG-IFN) and ribavirin (RBV). Although it is effective in a high percentage of patients, this treatment is associated with significant adverse events (AEs). The next generation of protease inhibitors, simeprevir and faldaprevir, will also be used with PEG-IFN/RBV.

Triple therapy for HCV genotype 1 infection: telaprevir or boceprevir?

Boceprevir and telaprevir are the first two protease inhibitors available for the treatment of patients infected with hepatitis C virus (HCV) genotype 1. A sustained virological response (SVR) of 70-80% is observed when either of these protease inhibitors is utilized with pegylated interferon (PEG-IFN) and ribavirin (RBV) in treatment naïve patients. Both agents are also highly effective in patients who failed to achieve a SVR during previous treatment with PEG-IFN/RBV.

Interferon-free regimens: the near future, the likely and the not so likely.

Remarkable progress has been achieved in the treatment of chronic hepatitis C virus (HCV) since interferon was first used to treat this pathogen more than 20 years ago. This article reviews the mechanisms through which interferon is believed to suppress HCV and lead to SVR. These observations are used to speculate as to whether an all-oral antiviral cocktail could "cure" HCV in the near future.

Treatment of hepatitis C in 2011: what can we expect?

Treatment for chronic hepatitis C virus (HCV) infection is the combination of a peginterferon and ribavirin. Although a fixed duration of treatment (24 weeks for patients with genotypes 2 and 3 and 48 weeks for patients with all other genotypes) has been advocated, the best results are likely to be achieved when the duration of therapy is adjusted based on the time to response. According to the principles of response-guided therapy, patients with rapid virologic response have a high rate of sustained virologic response (SVR) and a low rate of relapse, and can be treated for 24 weeks regardless of genotype.

Management of acute hepatitis B.

Acute hepatitis B virus (HBV) is a common cause of acute icteric hepatitis in adults. The vast majority of these patients resolve this acute infection and develop long-lasting immunity. In contrast, the vast majority of patients who develop chronic HBV have minimal symptoms and do not develop jaundice after becoming infected with HBV.