Tuesday, February 7, 2017

Critically ill children can still undergo liver transplantation and survive

Critically ill children can still undergo liver transplantation and survive
National and institutional study findings published in the Journal of the American College of Surgeons show steady improvement in survival for infants and children treated for acute or chronic liver failure

American College of Surgeons DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2016.12.025

CHICAGO (Feb.7, 2017): Advancements in critical care make it possible for even the sickest children to successfully undergo liver transplantation. According to a new study published online as an "article in press" in the Journal of the American College of Surgeons (JACS), children who are sick enough to require mechanical ventilation or dialysis before transplantation achieve the same survival benefit as children who are stable prior to the surgical procedure. The study will appear in a print edition of the Journal this spring.

Since pediatric critical care was recognized as a specialty area of medicine in the 1980s-1990s, survival and disease recovery rates for acutely ill children have improved significantly. Pediatric intensive care units have reduced mortality rates for children with such life-threatening conditions as sepsis, cardiac arrest, and traumatic brain injury. Postoperative critical care systems have improved outcomes after many types of organ transplantation. These advances have increased survival of children with acute liver failure without transplantation and stabilized children with chronic liver failure who are on the wait list for transplantation.

In the present study, surgeons from Texas Children's Hospital and Baylor College of Medicine, Houston, found that pediatric critical care also has led to steady improvements in survival after liver transplantation regardless of the severity of illness of a child.

"Our study suggests that successful outcomes are now possible in the most critically ill patients with liver failure. Every effort should be made to transplant more children and sicker children," said John A. Goss, MD, FACS, professor of surgery, Michael E. DeBakey Department of Surgery and chief of the division of abdominal transplantation at Baylor.

The study is a nationwide evaluation of all children under the age of 18 years who had liver transplantation between 1987 and 2015. Although transplantations were performed in the 1960s, the study began gathering data from 1987 when the United Network for Organ Sharing (UNOS) first established measures for evaluating transplantation outcomes. The study divided data into two segments to compare outcomes of patients treated before and after 2002, when the Pediatric End-Stage Liver Disease system (PELD) was instituted. PELD is a method of scoring severity of liver disease on the basis of age, failure to grow, serum indicators of liver function, and an international normalized ratio. A similar set of data was gathered to reflect outcomes for children treated at Texas Children's Hospital.

Over the course of the study period, 13,723 children underwent liver transplantation across the country and were followed for an average of 6.6 years. A total of 4,248 of these children were in the ICU at the time of transplantation; these patients were followed for an average of 5.7 years. Between 2002 and 2015, 6,746 children had liver transplantation, 1,816 of whom were in the ICU at the time of the surgery.

Survival improved steadily for all patients over time. One-year survival was 66 percent in 1987 and 92 percent in 2015. Survival likewise improved for the sickest patients, as defined by the need for dialysis or mechanical ventilation. The one-year survival rate for patients on dialysis was 50 percent in 1995 and 95 percent in 2013; survival for patients on a ventilator was 49 percent in 1994 and 94 percent in 2013. The same survival benefit was seen in infants; the one-year survival rate increased from 45 percent in 1988 to 88 percent in 2013.

At Texas Children's Hospital, 65 of the 354 patients who had liver transplantation between 2002 and 2015 were ill enough to require admission to the ICU at the time of the operation. Survival at one year was 92 percent for the entire group and 87 percent for ICU patients.

An analysis of clinical and institutional risk factors that may affect survival showed that medical centers performing fewer than five transplants per year had poorer outcomes than high-volume centers.

"As critical care has improved and medical centers can keep seriously ill children alive longer, the question has evolved from can we perform a transplantation to should we do a transplant operation. The answer is yes, we can go ahead and transplant an organ into a critically ill child and expect the same outcome we would see in a stable child. The one caveat is if a medical center does not have the resources to perform a high volume of transplantations, then it should transfer critically ill children to a center that does," Dr. Goss said.

Other study participants were Abbas Rana, MD; Michael Kueht, MD; Moreshwar Desai, MBBS; Fong Lam, MD; Amir Miloh, MD; Jennifer Moffett, MD; N. Thao N. Galvan, MD, MPH; Ronald Cotton, MD; and Christine O'Mahony, MD.

The study was supported by the Cade R. Alpard Foundation. It was presented at the Southern Surgical Association 128th Annual Meeting, Palm Beach, FL, December 2016.

Citation: No Child Left Behind: Liver Transplantation in Critically Ill Children. Journal of the American College of Surgeons. DOI: http://dx.doi.org/10.1016/j.jamcollsurg.2016.12.025

Monday, February 6, 2017

Overcoming Injustice: A Roadmap to Improve Access to HCV Therapy for Our Medicaid Patients

Public Policy Corner
Carter L, et al. Hepatology. 2017

Overcoming Injustice: A Roadmap to Improve Access to HCV Therapy for Our Medicaid Patients

Accepted manuscript online:
DOI: 10.1002/hep.29095

This perspectives piece addresses the common question of both doctors and advocates:
What can I do right now to make a change?

View Article
Download PDF, thank you Henry E. Chang

Full Text Articles
I highly suggest you follow Henry E. Chang on Twitter if you are interested in reading full text articles about the treatment and management of hepatitis C.

Hepatology
Browse Accepted Articles                                   
Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.

Study retraction reignites concern over China’s possible use of prisoner organs

Study retraction reignites concern over China’s possible use of prisoner organs
By Dalmeet Singh Chawla
Feb. 6, 2017 , 4:15 PM

A journal has decided to retract a 2016 study because of concerns that its data on the safety of liver transplantation involved organs sourced from executed prisoners in China. The action, taken despite a denial by the study’s authors that such organs were used, comes after clinical ethicist Wendy Rogers of Macquarie University in Sydney, Australia, and colleagues authored a letter to the editor of Liver International on 30 January, calling for the paper’s retraction in the “absence of credible evidence of ethical sourcing of organs.”

For years, Chinese officials have come under fire for allegedly allowing the use of organs from executed prisoner for transplants, including for foreigners coming to the country for so-called medical tourism. In January 2015, it explicitly banned the practice and set up a volunteer donation system, but doubts persist that much has changed.
Continue reading...

Of Interest:
Feb 7, 2017
China 'mending its ways' on unethical organ transplants, official says
Beijing's top official on transplants said on Tuesday Beijing was "mending its ways" from a murky past when organs were taken from detained or executed prisoners.

Overview
Lawmakers Hear From Organ Harvesting Investigators
Human rights subcommittee urged to help stop organ pillaging from prisoners of conscience in China.

Hepatitis C in Canadian Immigrants and Newcomers: Why Are Hepatitis C Rates Higher in These Populations?

News
Hepatitis C in Canadian Immigrants and Newcomers: Why Are Hepatitis C Rates Higher in These Populations?
By Fozia Tanveer

From Canadian AIDS Treatment Information Exchange

February 6, 2017
The face of hepatitis C in Canada is diverse, with a significant proportion of the burden carried by Canadians from countries where hepatitis C is endemic. This article will explore why hepatitis C rates are higher among Canadian immigrants and newcomers, including common modes of transmission, and barriers related to testing.

Continue reading...

Glecaprevir/pibrentasvir highly effective for treating HCV genotype 1

In the Journals

Glecaprevir/pibrentasvir highly effective for treating HCV genotype 1

Poordad F, et al. Hepatology. 2017;doi:10.1002.hep.29081.
February 6, 2017

Glecaprevir/pibrentasvir was highly effective and well tolerated for the treatment of hepatitis C virus genotype 1 infection in patients who previously failed treatment with direct-acting antivirals, according to the results of the phase 2 open-label MAGELLAN-1 study.

Glecaprevir/pibrentasvir (AbbVie) is an investigational pan-genotypic regimen that combines two antiviral agents — 300 mg of glecaprevir, an NS3/4A protease inhibitor, and 120 mg of pibrentasvir, an NS5A inhibitor — that are administered once daily in three oral tablets.

Continue reading @ Healio.

Related:
Glecaprevir and Pibrentasvir for 12 Wks HCV Genotype 1 and Prior Direct-acting Antiviral Treatment
Accepted manuscript online: 27 January 2017

Experts Reveal Hidden Dangers Behind Supplements

Of Interest
Why most natural remedies seem to work
Roy Benaroch, MD | Meds | February 4, 2017

Rachel had a fair question, and I really haven’t answered it yet:
My daughter and I were talking the other day and saying we would like to ask a doctor what his thoughts are about all these “natural” remedies that are available. Recently a friend made the remark, “I do everything I can to avoid a doctor.” I lean more toward the medical system and the knowledge they have acquired over the years rather than relying on these home remedies.

Herbal and dietary supplements can sometimes cause liver injury, which may be particularly problematic for those with a hep C–damaged liver.

Experts Reveal Hidden Dangers Behind Supplements
Article ID: 668906
Released: 6-Feb-2017 5:05 AM EST
Source Newsroom: Queen's University Belfast

Newswise — Emeritus Professor Duncan Burns, a forensically experienced analytical chemist from the Queen’s University Belfast’s Institute for Global Food Security, has been working with a team of specialists on a peer-reviewed paper to examine the detection of illegal ingredients in the supplements.

The experts included Dr Michael Walker from the Government Chemist Programme at LGC and Professor Declan Naughton from Kingston University.

The research found that over-the-counter supplements - commonly advertised to treat obesity and erectile dysfunction problems - are labelled as fully herbal but often include potentially dangerous pharmaceutical ingredients, which are not listed on the label.

Professor Burns from Queen’s University, who is working to advance knowledge in this area, explained: “Our review looked at research from right across the globe and questioned the purity of herbal food supplements. We have found that these supplements are often not what customers think they are – they are being deceived into thinking they are getting health benefits from a natural product when actually they are taking a hidden drug.

“These products are unlicensed medicines and many people are consuming large quantities without knowing the interactions with other supplements or medicines they may be taking. This is very dangerous and there can be severe side effects.”

The survey raises serious questions about the safety of slimming supplements containing Sibutramine. Sibutramine was licensed as the medicine Reductil until 2010, when it was withdrawn across Europe and the US due to an increased risk of heart attacks and strokes associated with the use of the drug.

Tadalfil and sulfoaildenafil were among the most frequently undeclared ingredients in products for erectile dysfunction. When taken with other medicines containing nitrates, they can lower blood pressure drastically and cause serious health problems.

Professor Burns noted: “This is a real issue as people suffering from conditions like diabetes, hyperlipidemia and hypertension are frequently prescribed nitrate containing medicines. If they are also taking a herbal supplement to treat erectile dysfunction, they could become very ill.

“People who take these products will not be aware they have taken these substances and so when they visit their doctor they may not declare this and it can be difficult to determine what is causing the side effects. It is a very dangerous situation.”

Professor Declan Naughton explained: “This work highlights the vital role research and, in particular, techniques like datamining, can play in informing regulators about current trends in supplement contamination. This is very important to ensure effective testing strategies and, ultimately, to help keep the public safe.”

Dr Michael Walker commented: “The laboratory tests we describe in our paper will assist regulators to tackle this problem proactively to protect consumers and responsible businesses.”

Hepatitis C Genotype Makes a Difference - Genotype 3 Difficult To Treat.

Hepatitis C Genotype Makes a Difference in Liver Disease, Study Shows
Feb 06, 2017 | Catherine Kolonko
A recent analysis suggests that liver disease and treatment costs for people with hepatitis C varies depending on a patient’s genotype—and people with genotype 3 appear to have a greater severity of liver disease....

Patients with genotype 3 had the highest percentage of liver-related comorbidities and advanced liver disease. They were about one-third more likely to have advanced liver disease than were patients with the genotype 1 strain of the virus. The highest rates of steatosis, liver transplant, and hepatocellular carcinoma (the most common form of liver cancer) were also among patients with genotype 3....

Helpful Links
Accepted author version posted online: 27 Jan 2017.
Clinical characteristics, healthcare costs, and resource utilization in hepatitis C vary by genotype
These results suggest that liver disease progression varies by genotype and that CHC patients with GT3 appear to have more severe liver disease. These findings highlight the importance of effective HCV treatment for all patients and support guidelines for treatment of high-risk patients, including those with GT3.

2017-HCV Genotypes/Treatment
Current updates with a focus on treating HCV according to genotype using FDA approved and investigational medicines. Information is extracted from news articles, peer-reviewed journals, as well as liver meetings/conferences, research manuscripts and interactive learning activities. 

HCV Advocate
Read all about hepatitis C medications with information listed clearly by HCV genotype. ​Easy to navigate, easy to read.

Sunday, February 5, 2017

Sofosbuvir and Simeprevir in HCV Genotype 4

Sofosbuvir in Combination with Simeprevir +/- Ribavirin in Genotype 4 Hepatitis C Patients with Advanced Fibrosis or Cirrhosis: A Real-World Experience from Belgium
Delphine Degré , Thomas Sersté, Luc Lasser, Jean Delwaide, Peter Starkel, Wim Laleman, Philippe Langlet, Hendrik Reynaert, Stefan Bourgeois, Thomas Vanwolleghem, Sergio Negrin Dastis, Thierry Gustot, Anja Geerts, Christophe Van Steenkiste, Chantal de Galocsy, Antonia Lepida, Hans Orlent, Christophe Moreno

Received: October 5, 2016
Accepted: January 12, 2017
Published: January 26, 2017

View Full text article
http://dx.doi.org/10.1371/journal.pone.0170933

Media Coverage of this Article

Abstract
Introduction
Hepatitis C virus (HCV) is a major global health issue and successful treatment has been associated with a reduction of risk of all-cause mortality. Advancements have been made in HCV treatment through the use of interferon-free regimens. Most trials have been conducted in HCV genotype (GT) 1 and data for interferon-free regimens in GT4 patients are limited. The aim of this study was to evaluate the safety and efficacy of sofosbuvir plus simeprevir in a real-world cohort of HCV GT4 patients with advanced fibrosis.

Patients and Methods
Eighty-seven GT4 treatment-naïve or –Interferon (IFN) ribavirin (RBV) experienced patients treated with sofosbuvir and simeprevir +/- ribavirin (RBV) were enrolled in this cohort study (41% severe fibrosis, 59% cirrhosis).

Results
Patients were 51.7% male, 78.2% IFN/RBV treatment-experienced, and 37.9% received RBV treatment. The overall sustained virologic response at least 12 weeks after treatment (SVR12) rate was 87.4% while patients treated with and without RBV had rates of 87.9% and 87% (p = 0.593), respectively, and patients with advanced fibrosis (F3) and patients with cirrhosis had SVR12 rates of 94.4% and 82.4% (p = 0.087), respectively. SVR12 rates in treatment-naïve patients and in IFN/RBV -experienced patients were 78.9% and 89.7% (p = 0.191), respectively. Treatment failure occurred most commonly in patients with cirrhosis and severe disease. The treatment was well tolerated and no patient died or discontinued treatment due to adverse events.

Conclusions
Sofosbuvir in combination with simeprevir +/- ribavirin in GT 4 HCV patients with advanced fibrosis achieved high SVR12 rates and was well tolerated. RBV did not appear to increase the rate of SVR12.