Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Eradication of HCV infection in patients With cirrhosis reduces risk of liver and non-liver complications
In this prospective study patients with cirrhosis treated with interferon-based therapy or interferon-free regimens who achieved sustained virologic response (SVR) reduced; overall mortality and risk of death from liver-related and non–liver-related causes.......

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Abstract

Eradication of Hepatitis C Virus Infection in Patients With Cirrhosis Reduces Risk of Liver and Non-Liver Complications

Abstract
Background & Aims
We performed a prospective study to investigate the effects of a sustained viral response (SVR) on outcomes of patients with hepatitis C virus (HCV) infection and compensated cirrhosis.

Methods
We collected data from 1323 patients included in the prospective ANRS CirVir cohort, recruited from 35 clinical centers in France from 2006 through 2012. All patients had HCV infection and biopsy-proven cirrhosis, were Child Pugh class A, and had no prior liver complications. All patients received anti-HCV treatment before or after inclusion (with interferon then direct antiviral agents) and underwent ultrasound examination every 6 months, as well as endoscopic evaluations. SVR was considered as a time-dependent covariate; its effect on outcome was assessed by the Cox proportional hazard regression method. We used a propensity score to minimize confounding by indication of treatment and capacity to achieve SVR.

Results
After a median follow-up period of 58.2 months, 668 patients (50.5%) achieved an SVR. SVR was associated with a decreased incidence of hepatocellular carcinoma (HCC; hazard ratio [HR] compared to patients without an SVR=0.29; 95% CI, 0.19–0.43; P< .001) and hepatic decompensation (HR=0.26; 95% CI, 0.17–0.39; P<.001). Patients with SVRs also had a lower risk of cardiovascular events (HR=0.42; 95% CI, 0.25–0.69; P=.001) and bacterial infections (HR=0.44; 95% CI, 0.29–0.68; P<.001). Metabolic features were associated with higher risk of HCC in patients with SVRs, but not in patients with viremia. SVR affected overall mortality (HR=0.27 compared to patients without SVR; 95% CI, 0.18–0.42; P<.001) and death from liver-related and non–liver-related causes. Similar results were obtained in a propensity score-matched population.

Conclusions
We confirmed a reduction in critical events, liver-related or not, in a prospective study of patients with HCV infection and compensated cirrhosis included in the CirVir cohort who achieved an SVR. We found an SVR to reduce overall mortality and risk of death from liver-related and non–liver-related causes. A longer follow-up is required to accurately describe and assess specific risk factors for complications in this population.

A Review of Daclatasvir Drug-Drug Interactions

Review article
A Review of Daclatasvir Drug-Drug Interactions.
Garimella T, et al. Adv Ther. 2016

Adv Ther. 2016 Sep 23. [Epub ahead of print]

Download - Full text review article

Abstract
The treatment of hepatitis C virus (HCV) infection has been revolutionized in recent years by the development of direct-acting antiviral regimens that do not contain peginterferon (pegIFN) and/or ribavirin (RBV). While direct-acting antiviral-based regimens have been shown to be greatly superior to pegIFN/RBV-based regimens in terms of efficacy and safety, they have a greater susceptibility to drug–drug interactions (DDIs).

Daclatasvir (DCV)—the benchmark pangenotypic nonstructural protein 5A inhibitor—has been shown to be efficacious and generally well tolerated in partnership with other HCV direct-acting antivirals, including sofosbuvir, asunaprevir (ASV), and ASV plus beclabuvir. DCV may be the object of a DDI via the induction or inhibition of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein (P-gp) by the concomitant medication, or the precipitant of a DDI via DCV-based induction/inhibition of CYP 3A4 or inhibition of P-gp, organic anion transporting polypeptide 1B1/B3, and/or breast cancer resistance protein.

This article presents an overview of the drug interaction studies conducted during the clinical development of DCV, the findings of these studies that led to the guidance on concomitant medication use and dosage along with any required DCV dose modifications, and the use of the known metabolic pathway of DCV to guide concomitant dosing where direct drug–drug studies have not been conducted. The robust characterization of the DCV clinical pharmacology program has demonstrated that DCV has few or no clinically relevant DDIs with medications with which it is likely to be co-administered, and the majority of DDIs that do occur can be predicted and easily managed.

Funding: Bristol-Myers Squibb.

KeywordsConcomitant medications Daclatasvir Drug–drug interactions Hepatitis C virus Infectious diseases

Link To - Full text review article

UK patients who have liver transplants abroad get poorer management

UK patients who have liver transplants abroad get poorer management      
News Type: Clinical News
     
A small number of UK citizens are undergoing liver transplants abroad but their management is of a lower standard than in the UK.

These were the conclusions of researchers at Sheffield’s Royal Hallamshire Hospital, who sent questionnaires to all seven UK liver transplant units enquiring about liver patients receiving transplant abroad. Six of the seven centres responded.

A total of 12 patients were identified as having undergone liver transplantation overseas. The top destinations were India, China and Egypt.

Four units responded to questions regarding pre-transplant screening. One unit reported HBV and HCV screening not taking place. Four units responded to questions regarding post-transplant antimicrobial therapy. This revealed examples of patients inappropriately not receiving valganciclovir, co-trimoxazole, anti-fungal treatment and HBV immunoglobulins.

The researchers add that information transfer between overseas and UK based transplant teams is poor.

Reference
A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad. Winter BK, Odedra A, Green S. Travel Med Infect Dis. 2016 Sep 14 [Epub ahead of print]

Abstract
A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad.
Travel Med Infect Dis. 2016 Sep 14. pii: S1477-8939(16)30122-3. doi: 10.1016/j.tmaid.2016.09.004. [Epub ahead of print]

A questionnaire based assessment of numbers, motivation and medical care of UK patients undergoing liver transplant abroad.
Kerr Winter B1, Odedra A2, Green S2.

1Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF, England, UK. Electronic address: Ben.kerrwinter@gmail.com.
2Department of Infection and Tropical Medicine, Royal Hallamshire Hospital, Sheffield, S10 2JF, England, UK.

Abstract
BACKGROUND:
Medical tourism, where patients travel abroad intentionally to access medical treatment, is a growing trend. Some of these patients travel to undergo organ transplantation. This study aims to quantify the number of UK patients who undergo liver transplantation abroad, assessing their motivations and management.

METHODS:
Questionnaires were sent to all seven UK liver transplant units enquiring about liver patients receiving transplant abroad. Included were questions on destination, motivation, and pre and post-transplant care.

RESULTS:
Responses were received from six of the seven transplant centres (86%). A total of 12 patients were identified as having undergone liver transplantation overseas. The top destinations were India, China and Egypt. Four units responded to questions regarding pre-transplant screening. One unit reported Hepatitis B and C screening not taking place. Four units responded to questions regarding post-transplant antimicrobial therapy. This revealed examples of patients inappropriately not receiving valganciclovir, co-trimoxazole, anti-fungal treatment and Hepatitis B immunoglobulins.

CONCLUSIONS:
UK patients are undergoing liver transplant abroad, albeit in small numbers. Pre and post-transplant management of these patients is of a lower standard than that provided to those undergoing transplantation in the UK. Information transfer between overseas and UK based transplant teams is poor.

Copyright © 2016. Published by Elsevier Ltd.

KEYWORDS:

Hepatology; Infectious diseases; Medical tourism; Transplantation
PMID: 27640117 DOI: 10.1016/j.tmaid.2016.09.004

Drugmakers racing each other on treatment for liver disease

Drugmakers racing each other on treatment for liver disease

By CAROLINE CHEN and JARED S. HOPKINS BLOOMBERG NEWS

Nonalcoholic steatohepatitis occurs when fat accumulates in the liver along with inflammation and damage, and as much as a quarter of the U.S. population may have a precursor condition called nonalcoholic fatty liver disease. The ailment develops slowly, and patients often don't show symptoms until their livers are heavily damaged. It's most common in people who are overweight or have diabetes, and doctors mainly prescribe diet changes and weight loss.

While doctors need to perform a biopsy to diagnose nonalcoholic steatohepatitis, between 6 and 15 million people in the U.S. alone are estimated to have the condition, and about 20 percent of them will go on to develop life-threatening cirrhosis. It will be the leading cause of liver transplants by 2020, according to Allergan. Drugs that treat it will likely command high prices, said Elizabeth Krutoholow, an analyst at Bloomberg Intelligence.

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We should aim to achieve complete elimination of hepatitis C

We should aim to achieve complete elimination of hepatitis C
Clinical Pharmacist
26 SEP 2016

Chair of the British Viral Hepatitis Group and Consultant in Infectious Diseases, North Manchester General Hospital

I read the letters from Charles Gore (Clinical Pharmacist 2016;8:232) and Anja St. Clair Jones (Clinical Pharmacist 2016;8:264) on the therapies and new services for hepatitis C with interest. The points made are valid and important.

The key issues highlighted by Gore were related to the fact that there are real restrictions placed on accessing the newer therapies for this infection that have not been imposed in other disease areas, with other medicines, in other patients. Resources are limited; however, denying individuals timely access to National Institute for Health and Care Excellence-approved, evidence-based, cost-effective therapies is, indeed, exceptional.

New Perspectives in HCV Infection

October 2016 Volume 65, Issue 1, Supplement, S1-S156
Journal Of Hepatology

New Perspectives in HCV Infection
Edited by Thomas Berg, Xavier Forns

Highlights

Assessment of HCV Disease
Benjamin Maasoumy, Johannes Vermehren
DOI: http://dx.doi.org/10.1016/j.jhep.2016.07.023
S67–S81
Published in issue: October 2016

Treatment and Remaining Challenges
Reversion of disease manifestations after HCV eradication
Adriaan J. van der Meer, Marina Berenguer
DOI: http://dx.doi.org/10.1016/j.jhep.2016.07.039
S95–S108
Published in issue: October 2016

Norah A. Terrault, Tarek I. Hassanein
DOI: http://dx.doi.org/10.1016/j.jhep.2016.08.001
S120–S129
Published in issue: October 2016

HCV Perspectives
Jordan J. Feld, Graham R. Foster
DOI: http://dx.doi.org/10.1016/j.jhep.2016.07.007
S130–S142
Published in issue: October 2016
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Future landscape of hepatitis C research – Basic, translational and clinical perspectives
Darius Moradpour, Arash Grakoui, Michael P. Manns
DOI: http://dx.doi.org/10.1016/j.jhep.2016.07.026
S143–S155
Published in issue: October