Outcomes of early vs late treatment initiation in solid organ transplantation from hepatitis C virus nucleic acid test-positive donors to hepatitis C virus-uninfected recipients: Results from the HCV-TARGET study.

Curative hepatitis C virus (HCV) therapy has increased transplantation from HCV-infected nucleic acid test-positive donors to HCV-uninfected recipients (D+/R-). We evaluated outcomes of early and late HCV treatment among D+/R- nonliver organ transplants. Patients received HCV regimens per local standard (n = 10 sites).

Inpatient Hepatitis C Treatment Coordination and Initiation for Patients Who Inject Drugs.

Background: With hepatitis C (HCV) incidence rising due to injection drug use, people who inject drugs (PWID) are a priority population for direct-acting antivirals (DAA). However, significant barriers exist. At our institution, hospitalized PWID were screened for HCV but not effectively linked to care.

A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

Background And Aims: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable.

Approach And Results: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence.

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

Description: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.

A Quality Improvement Initiative Results in Improved Rates of Timely Postvariceal Bleeding Surveillance Endoscopy.

Objectives: We performed a study to assess the effects of a quality improvement (QI) initiative on the rates of postvariceal bleeding surveillance upper endoscopy (EGD).

Methods: We identified patients with cirrhosis hospitalized with variceal bleeding and assessed the rates of timely (≤4 weeks) EGD before and after a QI initiative.

Results: Preintervention: 16% (5 of 32) of patients underwent timely surveillance EGD.

Treatment Status of Hepatocellular Carcinoma Does Not Influence Rates of Sustained Virologic Response: An HCV-TARGET Analysis.

Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT-HCC) versus completely treated (CT-HCC). HCC status was based on imaging 6 months before or 2 months after start of DAA therapy.

Daclatasvir and sofosbuvir treatment of decompensated liver disease or post-liver transplant hepatitis C virus recurrence in patients with advanced liver disease/cirrhosis in a real-world cohort.

We report the findings of an early access program providing treatment for chronic hepatitis C virus infection (any genotype) with daclatasvir and sofosbuvir with/without ribavirin to patients with Child-Pugh class C cirrhosis or prior liver transplant recipients with recurrent hepatitis C virus infection and advanced fibrosis/cirrhosis. Patients had <12-month life expectancies per the local investigator. Patients received daclatasvir 60 mg and sofosbuvir 400 mg once daily, with/without ribavirin, for 24 weeks.

Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study.

Objective: Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants.

Design: HCV-TARGET, an international, prospective observational study evaluates clinical practice data on novel antiviral therapies at 44 academic and 17 community medical centres in North America and Europe.

Effectiveness of Simeprevir Plus Sofosbuvir, With or Without Ribavirin, in Real-World Patients With HCV Genotype 1 Infection.

Background & Aims: The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America.

Methods: We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET--a prospective observational cohort study of patients undergoing HCV treatment in routine clinical care settings.

High MIG (CXCL9) plasma levels favours response to peginterferon and ribavirin in HCV-infected patients regardless of DPP4 activity.

Background & Aims: Sustained virological response (SVR) following peginterferon (pegIFN) and ribavirin (RBV) treatment in hepatitis C virus (HCV)-infected patients has been linked with the IL28B genotype and lower peripheral levels of the CXCR3-binding chemokine IP-10 (CXCL10). To further improve the understanding of these biomarkers we investigated plasma levels of the other CXCR3-binding chemokines and activity of the dipeptidyl peptidase IV (DPP4, CD26) protease, which cleaves IP-10, in relation to treatment response.

Methods: African-American and Caucasian HCV genotype 1-infected patients (n = 401) were treated with pegIFN/RBV for 48 weeks (ViraHep-C cohort).

Sofosbuvir in combination with peginterferon alfa-2a and ribavirin for non-cirrhotic, treatment-naive patients with genotypes 1, 2, and 3 hepatitis C infection: a randomised, double-blind, phase 2 trial.

Background: Protease inhibitors have improved treatment of infection with hepatitis C virus (HCV), but dosing, a low barrier to resistance, drug interactions, and side-effects restrict their use. We assessed the safety and efficacy of sofosbuvir, a uridine nucleotide analogue, in treatment-naive patients with genotype 1-3 HCV infection.

Methods: In this two-cohort, phase 2 trial, we recruited treatment-naive patients with HCV genotypes 1-3 from 22 centres in the USA.

New and Evolving Management Paradigms for Hepatitis C after Liver Transplantation.

Hepatitis-C induced liver failure is the leading indication for liver transplantation in the United States, and the burden of hepatitis C virus (HCV)-induced liver disease is not expected to peak for at least another decade. 2011 will usher in a new era of directly acting antiviral therapies and personalized medicine that will assist patients and clinicians in choosing the best drug regimen. Specific markers to predict sustained virologic response (SVR) in the posttransplant setting are under development, and the role of graft genetic markers like interleukin-28B and interferon-γ inducible protein-10 have yet to be fully defined.

Quantitation of pretreatment serum interferon-γ-inducible protein-10 improves the predictive value of an IL28B gene polymorphism for hepatitis C treatment response.

Unlabelled: Polymorphisms of the IL28B gene are highly associated with sustained virological response (SVR) in patients with chronic hepatitis C treated with peginterferon and ribavirin. Quantitation of interferon-γ-inducible protein-10 (IP-10) may also differentiate antiviral response. We evaluated IP-10 levels in pretreatment serum from 115 nonresponders and 157 sustained responders in the Study of Viral Resistance to Antiviral Therapy of Chronic Hepatitis C cohort, including African American (AA) and Caucasian American (CA) patients.

Overlap syndrome of autoimmune chronic liver diseases: MRI findings.

Purpose: To describe the MR findings of overlap syndromes of autoimmune chronic liver diseases.

Methods: Review of clinical and radiological databases between March 2001 and July 2008 for patients with a clinical diagnosis and liver biopsy features compatible with overlap syndrome who had also undergone an abdominal MRI yielded 15 adult patients. MR features of overlap syndrome were reviewed by two radiologists by consensus.

Optimizing treatment regimens in hepatitis C.

Scientists and clinicians have made tremendous advances in understanding the pathogenesis of hepatitis C virus (HCV) infection and have developed impressive strategies for treating this hepatotropic virus in the short time since its discovery in 1989. This article goes beyond the current guidelines for the treatment of HCV infection to examine the use of multiple pretreatment factors to predict response; the use of viral kinetics to guide length of treatment; higher dose ribavirin in genotype 1 infection; retreatment of non responders and relapsers; and improving adherence to therapy.

Management and treatment of hepatitis C viral infection: recommendations from the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office.

Chronic hepatitis C virus (HCV) infection affects approximately 1.3% of the general U.S.

Immune responses in hepatitis C: is virus or host the problem?

Purpose Of Review: Hepatitis C virus is an RNA virus that usually establishes persistent infection in its host. As an important cause of cirrhosis and hepatocellular carcinoma worldwide, hepatitis C is a growing public health concern. Despite recent advances in therapy, most people infected with the virus can expect lifelong infection.

Keratin 8 and 18 mutations are risk factors for developing liver disease of multiple etiologies.

Keratin 8 and 18 (K8K18) mutations are found in patients with cryptogenic cirrhosis, but the role of keratin mutations in noncryptogenic cirrhosis and the incidence of keratin mutations in the general population are not known. We screened for K8K18 mutations in genomic DNA isolated from 314 liver explants of patients who primarily had noncryptogenic cirrhosis, and from 349 blood bank volunteers. Seven unique K8K18 mutations were found in 11 independent patients with biliary atresia, hepatitis BC, alcohol, primary biliary cirrhosis, and fulminant hepatitis.

A blood-borne antigen induces rapid T-B cell contact: a potential mechanism for tolerance induction.

Understanding the difference between the development of a productive T-cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self-serum and orally introduced antigens. It is generally toleragenic.