Showing posts with label Nonalcoholic Steatohepatitis (NASH). Show all posts
Showing posts with label Nonalcoholic Steatohepatitis (NASH). Show all posts

Monday, June 18, 2018

Hepatitis C Weekend Video: NASH What Is It?


Weekend Video
Welcome, this weekend we start with a few articles on a "silent" but potentially serious condition called nonalcoholic fatty liver disease (NAFLD), followed by a new seven part video series on nonalcoholic steatohepatitis (NASH), the most severe form of NAFLD.

What Is NAFLD? 
Non-alcoholic fatty liver disease (NAFLD) is the build up of extra fat in liver cells that is not caused by alcohol. It is normal for the liver to contain some fat. However, if more than 5% – 10% percent of the liver’s weight is fat, then it is called a fatty liver (steatosis), learn more, here

While the burden of liver disease from HCV decreases - lowering the number of patients waiting or undergoing liver transplant - the waitlist for nonalcoholic steatohepatitis (NASH) has increased. In addition, NASH is the Fastest Growing Cause of Hepatocellular Carcinoma in Liver Transplant Candidates.

Research Articles:

The Effects of Physical Exercise on Fatty Liver Disease
For people with HCV (without fatty liver disease) research shows weight reduction leads to a decrease in steatosis and liver enzymes, and also to an improvement in fibrosis, despite persistence of the virus. Previous research also indicates HCV patients who participated in a diet and exercise program lowered their grade of steatosis and remarkably their fibrosis score, according to a study published in Nutrition 2013. Whether you have fatty liver disease, HCV or both read; The Effects of Physical Exercise on Fatty Liver Disease, published in Gene Expression 2018, to learn more about the effects of exercise on NAFLD and NASH.

2016
NAFLD & Type 2 Diabetes 
Published in World J Gastroenterology 2016
"NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."
Also noted in the article, prevalence of Nonalcoholic Steatohepatitis (NASH) in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

2018
NAFLD Is a Growing Problem
NAFLD is the most common form of liver disease in Western countries.[4] Men are affected more than women.[5] Persons with a "high body mass index in late adolescence" are at risk for advanced liver disease and hepatocellular carcinoma (HCC)..

The term "NAFLD" describes both hepatic steatosis with hepatocyte fat accumulation in a liver lacking inflammation, whereas NASH is associated with fat accumulation, hepatic inflammation, and hepatocyte injury with or without fibrosis or cirrhosis..

Not every patient with NAFLD is obese. Seven percent of lean patients have NAFLD,[18] especially in the presence of metabolic syndrome.[19] Lean patients with fatty liver also are observed among those with polycystic ovary syndrome.[20] Compared with lean patients, obese patients with NAFLD are more likely to have greater fibrosis and a worse clinical prognosis.[21] Nonobese patients with NAFLD have a lower prevalence of hypertension, diabetes mellitus, metabolic syndrome, and steatohepatitis than obese patients[22] but remain at risk for development of advanced liver disease[23] and associated metabolic abnormalities and cardiovascular disease.[22] 
Continue reading @ Medscape
Free registration may be required. 

2017
The International Liver Congress 2017
NASH: It's Fibrosis, Not Fat, that Matters
Analysis sheds new light on what drives disease progression
AMSTERDAM -- It isn't fat but rather fibrosis that drives disease progression in people with advanced non-alcoholic steatohepatitis (NASH), a researcher said here
Continue reading....
Free registration may be required. 

2017
HCV & Steatosis
Given the development of steatosis is well-known in people with HCV, the following articles may be of interest to you, lets start with an article published in Clinical Liver Disease 2017; Metabolic Manifestations of Hepatitis C Virus
Out of excessive consumption, steatosis should be classified into 2 types according to hepatitis C virus (HCV) genotypes: metabolic steatosis, which is associated with features of metabolic syndrome and insulin resistance in patients infected with nongenotype 3, and viral steatosis, which is correlated with viral load and hyperlipemia in patients infected with genotype 3.
Download the article, here

2016
Published in the 2016 issue of International Journal of Molecular Sciences; NAFLD and NASH in HCV Infection: Prevalence and Significance in Hepatic and Extrahepatic Manifestations, researchers investigated factors associated with NAFLD/NASH in chronic HCV, and the role of “viral steatosis” associated with HCV genotype 3 infection. 

2018
Of Interest
HCV Treatment Genotype 3
The International Liver Congress, 2018
Treatment for hepatitis C genotype 3 infection can be completed in 8 weeks in people without cirrhosis, three real-world studies presented at the conference confirmed. 

2018
Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR 
According to data published March 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals. 
Core tip: This is the first prospective study to assess the prevalence of fatty liver in hepatitis C patients who have achieved a sustained virological response with direct-acting antivirals. The study’s findings that fatty liver is present in 47.5% of these patients and that some steatotic patients have clinically significant fibrosis despite normal liver enzymes should raise awareness of the post-sustained virological response (SVR) prevalence of fatty liver and the importance of post-SVR assessment of steatosis and fibrosis and long-term follow up with these patients.
Full-text, here

2018
NASH Leading Cause of Liver Transplant in Women
"NASH is currently the second leading cause for LT waitlist registration/liver transplantation overall, and in females, the leading cause. Given the rate of increase, NASH will likely rise to become the leading indication for LT in males as well" according to a June 2018 study published in The American Journal of Gastroenterology.

Videos
7 sequences about NASH
On June 12, 2018, the 1st International NASH Day was launched by The NASH Education Program, along with their seven part educational program to help patients understand this serious liver disease. Listen to expert interviews, learn about symptoms, non-invasive tests used to measure liver inflammation and fibrosis, and hear from patients struggling with the disease.

NASH What Is It?
The video is the first part of a WEBTV of 7 sequences about NASH
Published June 12, 2018
Speakers: Pr Stephen Harrison, Pr Sven Francque
In this first TV show you will understand – thanks to a worldwide overview – how little-known NASH is and why this situation has to be changed. Liver experts will go over non-alcoholic steatohepatitis (NASH) details, its mechanisms, consequences, symptoms and stigmas. These will also be highlighted by a patient testimony at the end of the video footage.

Part One



SUBTITLES ARE AVAILABLE IN 6 LANGUAGES, using settings of the video (Gear Icon at the bottom right of the video): English - Spanish - French - Italian - German - Portugese

Full Playlist:
PART 1 NASH What Is It?  
https://www.youtube.com/watch?v=ND3AV...
In this first TV show you will understand – thanks to a worldwide overview – how little-known NASH is and why this situation has to be changed. Liver experts will go over non-alcoholic steatohepatitis (NASH) details, its mechanisms, consequences, symptoms and stigmas. These will also be highlighted by a patient testimony at the end of the video footage.

PART 2 NASH How Common Is It?
https://www.youtube.com/watch?v=luYVh...
In this second TV show, you will understand how widespread NASH is, with prevalence figures and future projections exposed. During the interviews, livers experts will bring up information on NASH frequency, genetic predispositions, how children are now subject to this preventable disease, and which populations are most commonly affected.

PART 3 NASH: Who is at risk?  
https://www.youtube.com/watch?v=nAjMR...
In this third TV show, you will discover that NASH is much more than just a liver disease and that it is related to metabolic disorders – such as diabetes and obesity – and closely linked to modern lifestyles: unhealthy diets and lack of physicial activity. The diverse speaker panel will explain why some people are more at risk than others and how much exercise can help, if sufficient and sustained. Lastly, the video will follow patients associations in their mobilizations against NASH.

PART 4 NASH: Getting Diagnosed 
https://www.youtube.com/watch?v=x_nwF...
In this fourth TV show, you will discover how much of challenge NASH diagnosis is – mainly because NASH is a silent disease (no symptoms) which makes it difficult to diagnose – and how current procedures can be a bottleneck in the patient journey. Liver experts will explain the current invasive and non-invasive diagnostic techniques used when NASH is suspected, as well as latest research in novel diagnostic tools and what the future holds in terms of diagnosis.

PART 5 NASH: Disease evolution and consequences  
https://www.youtube.com/watch?v=Sl9Fu...
In this fifth TV show, you will learn more about the consequences of non-alcoholic steatohepatitis in the liver, but also in the rest of the body, with associated conditions. A French sports journalist will share his testimony as a NASH patient that overcame a liver transplant and a kidney as the last resort to survive, and a representative from The Liver Forum will explain how experts work to research the best patient clinical management solutions. In the end, you will know more about the consequences on health, the consequences on the economy, stigmas, lessons learned and the dire need for awareness.

PART 6 NASH: Patient care and clinical management 
https://www.youtube.com/watch?v=rWS-c...
In this sixth video, you will discover how much of a challenge patient management is, and especially, how to answer this burning question: “how can we care for patients in the absence of treatment?” – Today, on top of the lifestyle change (weight loss and exercise) ongoing research on therapeutic solutions paves the way for a better patient care. Moreover, you’ll discover how physicians are all working hand in hand to cover all the aspects of this multi-faceted disease. Finally, you will have the opportunity to hear the American Liver Foundation’s CEO’s perspectives on NASH.

PART 7 NASH: What perspectives?
https://www.youtube.com/watch?v=vDt5k...
In this seventh video, you will learn more about the next key challenges in the field of NASH, and about the crucial need for awareness and for public policy. Experts will give some forecast about NASH, ongoing research and the shed light on future management solutions You will get insights on the economic burden of NASH and the need for all stakeholders to be involved in NASH awareness. To conclude these seven sequences, there will be a special focus on how street art can help increase awareness and what we can hope for in the future.

Elsewhere
Non-alcoholic fatty liver disease: risks, prevention, and more
June 11, 2018
Lauren Phinney
Doctor Rohit Loomba appeared on KUSI News in San Diego to discuss Non-alcoholic fatty liver disease and how to prevent it. 
Watch his informative interview here.

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases
A recent publication from the American Association for the Study of Liver Diseases (AASLD) provides guidance for the evaluation and management of patients with NAFLD.
This guidance provides a data‐supported approach to the diagnostic, therapeutic, and preventive aspects of nonalcoholic fatty liver disease (NAFLD) care. A “Guidance” document is different from a “Guideline.” Guidelines are developed by a multidisciplinary panel of experts and rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations, Assessment Development, and Evaluation system. A guidance document is developed by a panel of experts in the topic, and guidance statements, not recommendations, are put forward to help clinicians understand and implement the most recent evidence. 

On This Blog 

Maybe this weekend you might think about eating right or even start walking, two key elements for keeping your liver healthy. 
Tina

Wednesday, June 13, 2018

Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030

Modeling NAFLD Disease Burden in China, France, Germany, Italy, Japan, Spain, United Kingdom, and United States for the period 2016-2030
https://doi.org/10.1016/j.jhep.2018.05.036

Full-Text
View Online
Download PDF

Highlights
•Fatty liver disease is a growing cause of cirrhosis and liver cancer globally.
•Disease burden is expected to increase with the epidemics of obesity and diabetes.
•Modeling shows slow growth in total cases and greater increase in advanced cases.
•Mortality and advanced liver disease will more than double during 2016-2030.

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) with resulting nonalcoholic steatohepatitis (NASH) are increasingly a cause of cirrhosis and hepatocellular carcinoma (HCC) globally. This burden is expected to increase as epidemics of obesity, diabetes and metabolic syndrome continue to grow. The goal of this analysis was to use a Markov model to forecast NAFLD disease burden using currently available data.

Methods
A model was used to estimate NAFLD and NASH disease progression in 8 countries based on data for adult prevalence of obesity and type 2 diabetes mellitus (DM). Published estimates and expert consensus were used to build and validate the model projections.

Results
If obesity and DM level off in the future, we project a modest growth in total NAFLD cases (0-30%), between 2016-2030, with the highest growth in China as result of urbanization and the lowest growth in Japan as result of a shrinking population. However, at the same time, NASH prevalence will increase 15-56%, while liver mortality and advanced liver disease will more than double as result of an aging/increasing population.

Conclusions
NAFLD and NASH represent a large and growing public health problem and efforts to understand this epidemic and to mitigate the disease burden are needed. If obesity and DM continue to increase at current and historical rates, both NAFLD and NASH prevalence are expected to increase. Since both are reversible, public health campaigns to increase awareness and diagnosis, and to promote diet and exercise can help manage the growth in future disease burden.

Lay summary
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) can lead to advanced liver disease, and are occurring in increasing numbers in tandem with epidemics of obesity and diabetes. A mathematical model was built to understand how the disease burden associated with NAFLD and NASH will change over time. Results suggest increasing numbers of cases of advanced liver disease and liver-related mortality in the coming years.

Continue to article: View Online

Tuesday, June 12, 2018

NASH - Israeli company Galmed gets positive trial results for liver drug

Israeli company Galmed gets positive trial results for liver drug
Last Updated: 2018-06-12
By Reuters Staff
TEL AVIV (Reuters) - Galmed Pharmaceuticals said on Tuesday patients in a mid-stage trial for its treatment for non-alcoholic steatohepatitis (NASH), a fatty liver disease linked to obesity, showed a statistically significant reduction in liver fat. The results will allow Galmed to meet with regulators as soon as possible and discuss a pivotal Phase 3 study design, Galmed CEO Allen Baharaff said.

Press Release
Galmed's 600 mg Aramchol™ Achieved a Regulatory Approvable Endpoint Showing NASH Resolution Without Worsening of Fibrosis, in NASH Patients, in the Global Phase 2b ARREST 52-Week Study

Data Strongly Support Advancement of Aramchol™ 600mg to Phase 3

TEL AVIV, Israel, June 12, 2018 /PRNewswire/ --
Statistically significant reduction in liver fat was demonstrated by Magnetic Resonance Spectroscopy (MRS) in patients completing 52 weeks of treatment with Aramchol 400mg vs. placebo. Post hoc analysis of MRS responders, defined by a reduction of =5% absolute change from baseline, demonstrated a clinically and statistically significant effect of Aramchol 600mg vs. placebo.

Significantly more patients treated with Aramchol 600mg vs. placebo showed NASH resolution without worsening of fibrosis in the 52-week biopsy, a regulatory approvable endpoint.

A higher proportion of patients with at least one-point improvement in fibrosis score without worsening of NASH was demonstrated in Aramchol 600mg vs. placebo, in the 52-week biopsy, a regulatory approvable endpoint.

Statistically significant reductions in ALT and AST were demonstrated in Aramchol 400mg and 600mg vs. placebo.

Aramchol continues to show favorable safety and tolerability profile.

Monday, April 30, 2018

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Journal Of Hepatology
May 2018 Volume 68, Issue 5, Pages 1063–1075

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease
Thomas Jensen , Manal F. Abdelmalek, Shelby Sullivan, Kristen J. Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk-Hee Kang, Dean R. Tolan, Laura G. Sanchez-Lozada, Hugo R. Rosen, Miguel A. Lanaspa, Anna Mae Diehl, Richard J. Johnson

Full-Text

TAKE-HOME MESSAGE
While we have known for many years that fructose and beverages sweetened with high fructose corn syrup can contribute to nonalcoholic fatty liver disease, this is an excellent review of the literature to date on this topic. In addition, it postulates the potential mechanisms that could be contributing to fructose's contribution to the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. It also highlights the factors that can potentiate the effect that fructose has on the liver, including genetic mechanisms, the role of fructokinase, high-fat diets, and alcohol.

While certainly more research is needed, this review is beneficial when speaking to our patients and providing guidance on dietary changes that may improve their disease.

– Natasha VonRoenn, MD

Summary
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

Monday, April 23, 2018

HCV, type 2 diabetes & fatty liver disease - Importance of diet and exercise

Importance of diet and exercise 

This Michigander is announcing winter might just be over. I am so done walking on my ugly, hated, overrated treadmill, looking forward to moving my morning routine outside.

If you too are feeling a bit of spring fever, or preparing for a lifestyle change, check out the links provided below and learn about the importance of diet and exercise for people with HCV, type 2 diabetes or fatty liver disease.

On The Radio
To get you started we begin with Dr Norman Swan, the host of Health Report, along with his guest Professor Mike Lean, lead author in a study investigating the impact of weight loss on type 2 diabetes, published in the Lancet 10 February 2018; Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The study found after a year, participants who lost weight (around 30 pounds) on a 800 calorie diet, no longer had type 2 diabetes. The diet may be too difficult or not recommended for some people, in the trial patients were followed closely, however, the outcome is amazing. The interview starts at 8:29, listen to the program, here, read the transcript below or visit Health Report.

Transcript
Norman Swan: There's good news, for once, from the west of Scotland where a trial in general practice of an extremely low calorie diet has reversed type 2 diabetes in a large percentage of participants. Mike Lean is Professor of Human Nutrition at the University of Glasgow and is on the line. Welcome to the Health Report.

Mike Lean: Hello, how are you?

Norman Swan: Fine. You say in the paper that this is the first trial of its kind in type 2 diabetes, which is extraordinary.

Mike Lean: We've known about type 2 diabetes and thought of it as a distinct disease growing enormously in numbers and costing perhaps more than any other single disease for about 100 years, and it has been noted in a number of studies that some people if they lose enough weight will get rid of their diabetes. But no study has previously gone out to actually try and do that, to actually get as many people as possible to become non-diabetic, to get rid of their diabetes completely.

Norman Swan: So what did you do in this study?

Mike Lean: Well, this is not rocket science. What we did was we recruited people in primary care, in general practice, who were overweight, BMI over 27, so not enormously overweight but overweight, with type 2 diabetes. And we ask them to follow a formula diet, not a very low calorie but and 800-odd calorie diet for as long as it took, and it took quite a long time in some cases, to lose enough weight to become non-diabetic. And we aimed to get 15 kg weight loss because we knew from other observations that that was likely to do it. And of course not everybody managed, sadly, a lot of people found it really hard. A lot of people did manage. In the end we got about a quarter of our patients to lose that amount of weight. And those who lost 15 kg, almost 90% were no longer diabetic after a year, they were off all their medication, they were off all their diabetic medication and their antihypertensive medication, and they felt a lot better, their quality of life went up.

The remainder who didn't lose 15 kg, none of them got worse. Of those who lost over 10 kg, over half of them were non-diabetic. So you don't need to lose 15 kg but it's much better if you do. And I think what we've learnt from this is what we've regarded as a distinct disease, type 2 diabetes, is actually all part and parcel of obesity when you think about obesity as a disease process…

Norman Swan: We'll come back to the diet in a minute. And what was the recidivism rate, if you want to call it that, in terms of people gaining weight again and returning to diabetes?

Mike Lean: Yes, so that is of course…we've only published the one-year results and there's a lot more to find out. What we did find out was that the proportion of people with diabetes who wanted to have a go at this was very high. It was probably no great surprise because being diabetic is a penalty and it carries terrible medical risks as well as financial. The number within a year who put on any weight was really quite small, but we know very well from earlier studies that it's hard to maintain…the biggest problem is not losing the weight, it's actually maintaining it long term, and that's where our big research effort needs to go.

Norman Swan: So the diet itself…an 800 calorie diet is not something you try yourself at home because you can go into nutritional deficiency. This was a shakes and bars diet, wasn't it, it was a meal plan diet.

Mike Lean: That's correct, it was a formula diet which made sure it had all the vitamins and minerals, everything that was necessary, provided the patients actually followed this. And they didn't have to pay for it, they were given it for the study. And so they did that, so it was perfectly safe, there was no…

Norman Swan: That's my point, so it's one of these things you can buy in the chemist and it comes in various boxes, but we won't talk about the branding.

Mike Lean: The branding doesn't matter, all these things are pretty much the same. What matters is not what comes in the box or out of the packet, it's the support that is given with it, because people who go and get these type of diets from the chemist or from a supermarket generally do it for two or three or four weeks and then they peel off. If you are going to get rid of your diabetes you've got to stick in for probably 12 weeks if you do it full time. There are plenty of people who do it off and on for 12 weeks and need to carry on doing it off and on for a bit longer to lose their 10 or 15 kg. So there are different routes to getting there, you don't half to lose it all in one go but it works better if you do.

Norman Swan: What about complications, like if you lose weight fast when you are overweight you can get gallbladder disease…

Mike Lean: Ah, you're well informed!

Norman Swan: You can low blood sugar if you're on insulin, or diabetes complications. What sort of complications did people get?

Mike Lean: Well, the first thing was for this particular study we didn't include people who were already on insulin, partly because their likelihood of getting a remission is much lower. It had probably done damage to their pancreas by that stage. And what we did on day one was that we stopped all our anti-diabetes medication, so there's no risk of hypoglycaemia at all, and nobody had hypoglycaemia. And the same thing went for the blood pressure tablets, we stopped all their blood pressure tablets on day one because otherwise if you lose weight there is a risk of possible hypotension, and just to pick up your other point, there was one patient amongst the 150 who started, one who developed abdominal pains and we think that was probably by gallstones. That's a common complication of obesity, very common in people with diabetes anyway, and it can be made worse during weight loss.

Norman Swan: These are similar findings to bariatric surgery.

Mike Lean: Oddly the remission rate was actually a tiny bit better than bariatric surgery if you can lose 15 kg. If you lose 15 kg you will almost certainly get rid of your diabetes, whether or not it's done with surgery. There are of course many fewer hazards doing it without surgery. They produce very similar results, yes.

Norman Swan: Mike, thanks very much for joining us, a fascinating study.

Mike Lean: Thank you very much.

Norman Swan: Mike Lean is Professor of Human Nutrition at the University of Glasgow.

Fatty Liver Disease & Type 2 Diabetes 
"Given the increasing worldwide incidence of obesity and metabolic syndrome, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. Recent developments in the field have shown that NAFLD not only is a “liver disease” but also is the underlying cause of an increasing number of extrahepatic manifestations; thus, it should be treated as a multisystem disease. NAFLD is most prominently linked to chronic kidney disease, mellitus type 2 and cardiovascular disease, as well as a number of other severe chronic diseases. These findings demonstrate that NAFLD ranks amongst the most serious public health problems of our time."

Also noted in the article; The prevalence of Nonalcoholic Steatohepatitis (NASH), in people who are obese and have type 2 diabetes may be as high as 40%, whereas it is less than 5% in people without type 2 diabetes.
Read the article, here.

Presented at Liver Congress 2018
Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA
Two independent studies presented at the conference reported; that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.
Read the article, here.

Hepatitis C & Diabetes
Several studies have demonstrated the risk for development of diabetes is increased in people with chronic hepatitis C infection (HCV), for instance people with HCV have a 2.3 fold increased chance of having type 2 diabetes. According to a 2013 study published in Alimentary Pharmacology Therapeutics; Chronic hepatitis C virus infection is independently associated with presence of metabolic conditions (insulin resistance, type 2 diabetes mellitus and hypertension) and congestive heart failure.

HCV Treatment & Type 2 Diabetes
The good news is with today's high sustained viral response rates using direct antiviral medications to treat HCV, people who successfully reach SVR, or achieve a cure, lower their risk for the development of type 2 diabetes, the recent study was published in the Journal of Viral Hepatitis [published online February 25, 2018]. A quick overview of the study can be found online, here.

Fatty liver is very common in hepatitis C virus (HCV) patients post-SVR
This particular study may be of interest to people with HCV, according to data published Mar 21, 2018 in the online journal World J Gastroenterology, evidence of steatosis was reported to be found in close to half of patients who achieve a sustained virologic response after treating with direct-acting antivirals. Full-text, here....

Tips - Eating Right
Eating better tied to lower risk of liver disease
April 27, 2018
(Reuters Health) - People who make an effort to improve their diet may be more likely to have less fat in their livers and a lower risk of liver disease than individuals who stick to unhealthy eating habits, a U.S. study suggests.

The Liver Loving Diet
"The Liver Loving Diet" is a book that will help you learn to eat well during all phases of liver disease. Karen Hoyt, the author, also blogs about living with and treating hepatitis C, cirrhosis, liver cancer and liver failure.

Mediterranean diet reduces liver fat, risk for NAFLD
March 30, 2018
Improved diet quality based on the Mediterranean-style diet score and Alternative Healthy Eating Index score correlated with less liver fat accumulation and a reduced risk for new-onset nonalcoholic fatty liver, according to a recently published study.
Continue reading @ Healio

Bottom Line
Spring is a great time to start again, experts agree two key elements in the prevention and management of type 2 diabetes and fatty liver disease is weight loss and exercise. In the end, its all good for your liver!

See you soon,
Tina

Saturday, April 21, 2018

Clinical Insights in NAFLD and NASH for 2018

Clinical Liver Disease (CLD) is a digital educational resource published on behalf of the American Association for the Study of Liver Diseases (AASLD). CLD publishes easy to read reviews on relevant topics for clinicians diagnosing and managing patients with liver disease.

LATEST ISSUE > Volume 11, Issue 4
Pages: 81-104
April 2018

Clinical Insights in NAFLD and NASH for 2018
Guest Edited by Arun Sanyal, MD

An update on the pharmacological treatment of nonalcoholic fatty liver disease: Beyond lifestyle modifications
Naim Alkhouri M.D.
Andrea Scott B.S.
Pages: 82-86
First Published:20 April 2018
Watch a video presentation of this article
Abstract
Full text
PDF
References

Kara Wegermann M.D.
Anna Mae Diehl M.D.
Cynthia A. Moylan MD, MHS
Pages: 87-91
First Published:20 April 2018

Watch a video presentation of this article
Abstract
Full text
PDF
References

Free Access
The epidemiology of nonalcoholic steatohepatitis

Zobair M. Younossi M.D., M.P.H., F.A.A.S.L.D.
Pages: 92-94
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
Full text
PDF
References

Pediatric nonalcoholic fatty liver disease

Tania Mitsinikos M.D.
Rohit Kohli M.B.B.S., M.S.
Pages: 95-97
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
Full text
PDF
References

Diagnostic challenges of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Erin Cleveland M.D.
Andrew Bandy M.D.
Lisa B. VanWagner M.D., M.Sc.
Pages: 98-104
First Published:20 April 2018
Watch a video presentation of this article
Watch the interview with the author
Abstract
Full text
PDF
References 

Monday, April 16, 2018

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

World J Gastroenterol. Apr 14, 2018; 24(14): 1491-1506
Published online Apr 14, 2018. doi: 10.3748/wjg.v24.i14.1491

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?
Ivana Mikolasevic, Tajana Filipec-Kanizaj, Maja Mijic, Ivan Jakopcic, Sandra Milic, Irena Hrstic, Nikola Sobocan, Davor Stimac, Patrizia Burra

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a primary cause of macrovesicular steatosis and has several impacts on liver transplantation (LT), which is transmitted to transplant recipients and organ donors. Current data indicate a new trend in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT.

Friday, April 13, 2018

Gilead Presents Data on Multiple Investigational Regimens for the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH) and Advanced Fibrosis at The International Liver CongressTM 2018

Gilead Presents Data on Multiple Investigational Regimens for the Treatment of Patients With Nonalcoholic Steatohepatitis (NASH) and Advanced Fibrosis at The International Liver CongressTM 2018

-- Combination Therapy Data Presented from First 12-Week Study --
-- Enrollment Complete for Phase 3 STELLAR Trials of ASK1 Inhibitor Selonsertib --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Apr. 13, 2018-- Gilead Sciences, Inc. (Nasdaq: GILD) today presented data from a proof-of-concept study of investigational combination therapies for patients with advanced fibrosis due to nonalcoholic steatohepatitis (NASH), combining the apoptosis signal-regulating kinase 1 (ASK1) inhibitor selonsertib with either the Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 or the selective, non-steroidal Farnesoid X receptor (FXR) agonist GS-9674. The data were presented at The International Liver CongressTM 2018 in Paris.

More than 25 additional Gilead abstracts on NASH and other fibrotic liver diseases are also being presented, including data from predictive modeling studies using noninvasive tests for the diagnosis and monitoring of NASH that aim to reduce the need for liver biopsy.

"Gilead is focused on addressing the greatest unmet need in NASH, which is in patients with advanced fibrosis. Reflective of this unmet need, the STELLAR-3 and STELLAR-4 studies of selonsertib in patients with F3 and F4 fibrosis have completed enrollment ahead of schedule. We expect data from these Phase 3 studies in the first half of 2019," said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer at Gilead. "We are now exploring combination therapy approaches with compounds with distinct and potentially complementary mechanisms of action. The initial data presented today are important advances toward our goal of improving outcomes for patients with advanced fibrosis due to NASH."

Investigational Combination Therapies in Patients with NASH
The proof-of-concept study (Oral #105) included 70 patients treated with either selonsertib 18 mg plus GS-0976 20 mg (n=20), selonsertib 18 mg plus GS-9674 30 mg (n=20), or each monotherapy (n=10 per group) once daily for 12 weeks. All patients in the study were diagnosed with NASH and liver fibrosis stages F2 to F3 based on biopsy, or by magnetic resonance elastography (MRE) and MRI proton density fat fraction (MRI-PDFF). The greatest changes observed after 12 weeks of treatment in the study were decreases in liver fat content (measured by MRI-PDFF), which occurred in regimens containing GS-0976. Improvements in liver biochemistry and/or markers of fibrosis were also observed across both combination arms of the study compared to baseline. In patients treated with selonsertib plus GS-0976, kinetic labeling revealed the largest reduction in the fractional synthesis rate of lumican, a marker of fibrogenesis. Similar rates of adverse events were observed between patients treated with single-agent and combination therapies. No patient discontinued treatment prematurely.

"These encouraging results suggest that combination therapy with selonsertib and either GS-0976 or GS-9674 warrants further exploration in longer-term studies in patients with NASH and F3 and F4 fibrosis," said Stephen Harrison, MD, presenting author and Visiting Professor of Hepatology at the Radcliffe Department of Medicine, University of Oxford, UK. "Patients with advanced fibrosis due to NASH urgently need effective therapeutic options because they may face more serious health risks, including development of complications of end-stage liver disease, liver cancer and the need for liver transplantation. Combination therapy may be a way forward to achieving greater benefit for this patient population."

Gilead also presented data from a pre-clinical study of another combination treatment approach for NASH, evaluating GS-9674 and GS-0976 together and as single-agents in rodent models of NASH and liver fibrosis (Poster #077). The data indicate that combining agents had greater anti-fibrotic and anti-steatotic effects and led to greater improvements in liver biochemistry and fibrosis markers, compared with either agent alone.
Based on these promising pre-clinical results and data from the proof-of-concept clinical study, Gilead has initiated a larger Phase 2b study of combination treatment with selonsertib, and/or GS-0976, and/or GS-9674 in patients with advanced fibrosis due to NASH.

Data from Noninvasive Tests Help Predict Histological Severity and Clinical Outcomes in Patients with NASH
Currently, the diagnosis and monitoring of NASH requires liver biopsy, an invasive and costly procedure with the potential for serious complications. At the meeting, Gilead presented results from two studies utilizing machine learning techniques which suggest that noninvasive tests perform as effectively as liver biopsy for predicting clinical outcomes in patients with advanced fibrosis due to NASH. Both studies utilized data from two previous Phase 2b trials of simtuzumab that involved 477 NASH patients with F3-F4 fibrosis. While simtuzumab was ineffective, data from these trials have revealed important insights into the natural history of disease progression and the potential utility of noninvasive fibrosis markers.
One study (Poster #466) showed that models using noninvasive testing data can predict the risk of clinical disease progression in patients with advanced fibrosis due to NASH. Another study (Oral #178) identified models that can predict which patients are most likely to experience spontaneous fibrosis improvement. Both studies incorporated noninvasive tests such as Enhanced Liver Fibrosis (ELF) score, FIB-4 and NAFLD fibrosis score.
Additional presentations at The International Liver CongressTM describe the accuracy of other noninvasive markers, including proteomics (Poster #432), serum bile acids (Poster #422), micro-RNAs (Poster #463), and the stool microbiome (Poster #004) to predict liver histology and/or its change over time. These novel approaches will be evaluated in future Gilead studies.

About Gilead's Clinical Programs in NASH
NASH is a chronic and progressive liver disease characterized by the accumulation of fat in the liver, as well as inflammation, which can lead to liver damage and fibrosis. Gilead is advancing multiple novel investigational compounds for the treatment of advanced fibrosis due to NASH.
Gilead is currently planning or conducting Phase 2 and 3 clinical trials evaluating single-agent and combination therapy approaches against multiple biologically relevant pathways associated with NASH - metabolic dysregulation, inflammation and fibrosis. Compounds in development include:
  • Selonsertib (formerly GS-4997) - A small-molecule inhibitor of apoptosis signal-regulating kinase 1 (ASK1), which promotes inflammation, apoptosis and fibrosis in settings of increased oxidative stress, which is characteristic of NASH and associated with its pathogenesis.
  • GS-9674 - A selective, non-steroidal agonist of the Farnesoid X receptor (FXR), a nuclear hormone receptor that is highly expressed in the gastrointestinal tract and liver. FXR is the primary regulator of bile acid synthesis and plays important roles in glucose and lipid metabolism.
  • GS-0976 - A small-molecule inhibitor of Acetyl-CoA carboxylase (ACC), an enzyme that is involved in de novo lipogenesis, which is the synthesis of lipids, including mediators of inflammation and fibrosis. ACC also upregulates the burning of fat in the liver through beta oxidation.
Selonsertib, GS-9674 and GS-0976, alone and in combination, are investigational therapies and their efficacy and safety have not been determined.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 35 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead's ability to complete its Phase 2 and Phase 3 clinical trial programs evaluating single-agent and combination therapy approaches, including selonsertib, and/or GS-9674 and/or GS-0976, in patients with NASH in the currently anticipated timelines or at all. In addition, there is the possibility of unfavorable results from further clinical trials involving these compounds. Further, it is possible that Gilead may make a strategic decision to discontinue development of selonsertib, and/or GS-9674 and/or GS-0976 if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. As a result, the compounds may never be successfully commercialized. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Annual Report on Form 10-K for the year ended December 31, 2017, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000 

Germany: compensated cirrhosis substantially increases comorbidities and healthcare costs for patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

Germany: compensated cirrhosis substantially increases comorbidities and healthcare costs for patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

European Association for the Study of the Liver

13 April 2018, Paris, France: An analysis of outcomes and costs for German patients with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) who develop compensated cirrhosis was presented today at The International Liver Congress™ 2018 in Paris, France. Healthcare costs for this population spiked in the first year after compensated cirrhosis diagnosis. Comorbidities were common and one in five patients died within a year of cirrhosis diagnosis, highlighting the need for new treatment options to improve outcomes in these patients.

NAFLD is a major cause of liver disease worldwide with a global prevalence of 25% that is, alarmingly, thought to be rising, fueled by the global epidemic of obesity.9 The progression from NAFLD to NASH to advanced fibrosis is well established.9 For patients with NAFLD/NASH, increased morbidity and mortality is associated with increasing fibrosis. 10

'We know that compensated cirrhosis is often caused by NASH, but data on the associated morbidity, mortality, healthcare utilization and costs within the population of Germany are lacking', explained Dr Ali Canbay from the University of Magdeburg Medical School in Germany, and lead author of the study. 'We were able to extract these data from a large, anonymized billing database'.

The study presented by Dr Canbay obtained retrospective claims data for adult patients with a NAFLD/NASH diagnosis between 2011 and 2016 using the InGef FDB database (which contains anonymized billing data for about 6.3 million persons in about 60 health insurances in Germany).11,12 A total of 800 patients who had a subsequent diagnosis of compensated cirrhosis were included in the analysis. Of these, 245 (30.6%) individuals progressed to end-stage liver diseases (ESLDs) (progressors) and 555 (69.4%) remained cirrhotic (non-progressors) within 1 year of follow-up after their cirrhosis index diagnosis. Comorbidities, all-cause mortality within 1 year of the cirrhosis index diagnosis, annual healthcare utilization, annual mean costs (1 year pre-index to 1 year post-index period) and cumulative mean costs (1 year to maximum 5 years pre-index and post-index period) were presented.

In the 1-year pre-index period, the most prevalent comorbidities were hypertension (78.8 %), type-2 diabetes mellitus (52.6%), cardiovascular diseases (48.8%) and hyperlipidaemia (47.5%). In the first year of the post-index period, 19.4% of the patients died. This percentage was significantly higher for progressors (46.1%) than non-progressors (7.6%) (p<0.05). Following the cirrhosis diagnosis, the mean annual number of all-cause hospitalizations and emergency room visits increased significantly by 91% and 106.8%, respectively (p<0.05).

During the 1-year pre-index period, the mean of annual all-cause healthcare cost was €6,146 per patient. In the first post-index year there was a substantial and significant increase (93%, p<0.05) in annual all-cause healthcare cost per patient to a mean of €11,877. The primary driver of healthcare costs was the inpatient setting, which accounted for 42.0% of pre-index costs and 68.4% of post-index costs. Cumulative mean costs for cirrhosis patients increased 143% over the 5-year period of the study (p<0.05).

'We demonstrated that German patients with NAFLD/NASH who develop compensated cirrhosis have a substantial burden of comorbidities and that their healthcare costs jump with the development of cirrhosis', said Dr Canbay. 'Novel treatment options are needed to improve patient outcomes'. 'This study highlights the burden of NASH cirrhosis on healthcare systems and reinforces the need for new therapies to tackle the epidemic currently affecting many European countries', said Prof. Phil Newsome from the Queen Elizabeth Hospital and University of Birmingham, UK, and EASL Governing Board Member.

References
9. Younossi ZM, et al. Global epidemiology of nonalcoholic fatty liver disease - meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84.
10. Hagström H, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67(6):1265-73.
11. Andersohn F, Walker J. Characteristics and external validity of the German Health Risk Institute (HRI) Database Pharmacoepidemiol Drug Saf. 2016;25(1):106-9.
12. The Institute for Applied Health Research (InGef). Health research: methods. Available from: http://www.ingef.de/gesundheitsforschung/methoden/. Last accessed: February 2018.

Thursday, April 12, 2018

Cirius Therapeutics' Preclinical Data Demonstrates Potential for Lead Drug Candidate MSDC-0602K in NASH

Cirius Therapeutics' Preclinical Data Demonstrates Potential for Lead Drug Candidate MSDC-0602K in NASH 

SAN DIEGO, CA and KALAMAZOO, MI, USA I April 12, 2018 I Cirius Therapeutics announced today that it presented a late-breaking poster describing the activity of the company's lead drug MSDC-0602K in a three-dimensional bioprinted human tissue model of NASH at The International Liver Congress™ – occurring in Paris, France from April 11-15, 2018.

The poster, entitled "A human in vitro three-dimensional bioprinted tissue system can be used to model nutritional damage and protective effects of MSDC-0602K, a novel modulator of the mitochondrial pyruvate carrier" presented work performed using Organovo's (NASDAQ: ONVO) 3D bioprinted human liver tissue and was presented by Dr. Jerry Colca from Cirius Therapeutics.

The research demonstrated that adding fructose (sugar) and fatty acids to three-dimensional bioprinted human liver tissue produced NASH-type liver pathology, including steatosis, inflammation, ballooning and fibrosis. Addition of MSDC-0602K to the tissue showed evidence of reduced disease progression, including reductions in collagen deposition and stellate cell activation, in the liver model.

"The data shown in this human liver model demonstrates conclusively that oversupply of nutrients leads directly to NASH-like pathology, including fibrosis," said Dr. Colca. "In addition, we see in this 3-D tissue model evidence that treatment with MSDC-0602K, which modulates metabolism by slowing the transport of the important metabolic intermediate pyruvate into the mitochondria, reduces signs of NASH. This supports our thesis that restoring nutritional balance on a cellular level has potential to treat NASH."

This work follows recently published work demonstrating that attenuation of pyruvate metabolism with MSDC-0602K via modulation of the mitochondrial pyruvate carrier (MPC) can both prevent and reverse liver fibrosis.

"The ability to model human liver disease and drug intervention with our technology is a powerful tool for helping companies such as Cirius evaluate their drug candidates for the treatment of NASH," Paul Gallant, general manager, Organovo. "As the results of this research show, it can also yield valuable insights about potential biomarkers that can be monitored during liver disease progression."

SOURCE: Cirius Therapeutics

Wednesday, April 11, 2018

#ILC2018 Alcoholic liver disease replaces hepatitis C infection as leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA

Alcoholic liver disease replaces hepatitis C infection as the leading cause of liver transplantation in patients without hepatocellular carcinoma in the USA

European Association for the Study of the Liver
11 April 2018, Paris, France: Two independent studies have today reported that alcoholic liver disease has now replaced hepatitis C virus (HCV) infection as the leading cause of liver transplantation in the USA in patients without HCC. Non-alcoholic steatohepatitis (NASH) is also on the increase, now ranking second as a cause of liver transplantation due to chronic liver disease.

Chronic HCV infection has remained the leading indication for liver transplantation in the USA for the last two decades.1 However, the availability of second-generation direct-acting antiviral agents (DAAs) in late 2013 led to a decline in the number of HCV-related liver transplant waiting list registrations and surgeries from 2015 onwards.2,3 Alcohol consumption began to increase markedly in the US during the 1990s and early 2000s, with data highlighting dramatic rises in alcohol use and high-risk drinking in recent years.4

The two studies presented this week at The International Liver Congress™ 2018 in Paris, France, were conducted to evaluate recent trends in the aetiology of liver disease among liver transplant recipients in the USA in view of the changing landscape of potential risk factors. In the first study, data from the United Network for Organ Sharing (UNOS) between 2005-2016 were analyzed, looking at four indications for chronic liver disease: alcoholic liver disease (ALD), NASH, HCV infection, and HCV/ALD combined. According to the results of the study, the number of liver transplant recipients with HCV peaked in 2014 (1,905 individuals) and has been declining ever since. In contrast, the number of liver transplants due to ALD and NASH has been steadily increasing and, in 2016, there were 1,624 liver transplants performed as a result of ALD, compared with 1,535 due to HCV, 1,334 due to NASH, and 424 due to HCV/ALD.

'Although we found that, overall, alcoholic liver disease became the leading indication for liver transplantation in the US in 2016, NASH was not far behind', said Dr Jennifer Wang from the California Pacific Medical Center in San Francisco, USA, who presented the study findings. 'Importantly, NASH is now the leading cause of liver transplantation in women, which is not entirely surprising given the higher rates of metabolic syndrome in women and the resultant increased risk of non-alcoholic fatty liver disease'.

'In African Americans and those with hepatocellular carcinoma, HCV remains the leading cause of transplantation and a major burden'.

The second study presented today also evaluated data from the UNOS registry, looking at first liver transplants performed in individuals without HCC between January 2012 and October 2017. As in the first study, HCV infection remained the leading aetiology for liver transplant recipients until 2016, when ALD surpassed it, accounting for 24% of liver transplants performed compared with 19% for NASH and 18% for HCV. In 2017, ALD, NASH, and HCV were responsible for 24%, 18%, and 17% of liver transplants, respectively, according to the results of this study.

'One of our most worrying findings was that patients with ALD are being listed for liver transplantation at a much younger age and with more severe disease than patients with either HCV infection or NASH', said investigator, Dr George Cholankeril from Stanford University Medical Center, California, USA. 'These are very ominous trends and we need to take aggressive action to address these rising rates of liver transplantation in patients with alcoholic liver disease'.

'So far, alcoholic liver disease has received much less attention with regards to clinical and basic research than either hepatitis B or C',5 said Prof. Helena Cortez-Pinto from the University Hospital of Santa Maria, Lisbon, Portugal, and EASL Governing Board Member. 'It is time to change and turn our attention to ALD, both in research and of course in policies that have been shown to reduce consumption, such as increases in taxation, in order to decrease affordability'.

About The International Liver Congress™
This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Attending specialists present, share, debate and conclude on the latest science and research in hepatology, working to enhance the treatment and management of liver disease in clinical practice. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. The International Liver Congress™ 2018 will take place from 11¬-15 April 2018 at the Paris Convention Centre, Paris, France.

About The European Association for the Study of the Liver (EASL)
Since its foundation in 1966, this not-for-profit organization has grown to over 4,000 members from all over the world, including many of the leading hepatologists in Europe and beyond. EASL is the leading liver association in Europe, having evolved into a major European association with international influence, and with an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Onsite location reference
Session title: Poster presentations Time, date and location of session: Poster area (Hall 7.2) Presenters: Jennifer Wang and George Cholankeril, USA Abstracts: Alcoholic liver disease surpasses hepatitis C virus in 2016 to become the leading indication for liver transplantation among adults without hepatocellular carcinoma in the United States (13 April 2018 9:00-17:00) and Alcoholic liver disease replaces HCV infection as the leading indication for liver transplantation in the United States (14 April 09:00-17:00)

Author disclosures
Jennifer Wang: None reported
Robert Gish: Dr. Gish has received Grants/Research Support from AbbVie, Benitec Biopharma, Gilead Sciences, and Merck & Co. Dr. Gish has performed as Consultant and/or Advisor to AbbVie, Akshaya Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, Genentech, Gilead Sciences, Hoffman-LaRoche, Ltd., Ionis Pharmaceuticals, Janssen, Merck & Co., Nanogen Biopharmaceutical, and Presidio Pharmaceuticals. Dr. Gish has current activity with the scientific or clinical advisory boards of AbbVie, AstraZeneca, Genentech, Gilead Sciences, Janssen, Merck & Co., and Nanogen Biopharmaceutical. Dr. Gish is a member of the Speakers Bureau for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Dr. Gish is a minor stock shareholder of Cocrystal Pharma.

Benny Liu: None reported Taft Bhuket: None reported
Robert Wong: Dr Wong receives research funding from Gilead Sciences and AbbVie, has served as a consultant and member of the advisory board for Gilead Sciences, and serves on the speaker's bureau for Gilead Sciences, Salix, and Bayer. Dr Wong is also funded by an AASLD Foundational Clinical and Translational Research Award in Liver Diseases.

George Cholankeril and co-authors: None reported
References 1. Cholankeril G, Ahmed A. Alcoholic liver disease replaces hepatitis C virus infection as the leading indication for liver transplantation in the United States. Clin Gastroenterol Hepatol. 2017; doi: 10.1016/j.cgh.2017.11.045 [Epub ahead of print].

2. Goldberg D, et al. Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation. Gastroenterology. 2017;152(5):1090-9.e1.

3. Flemming JA, et al. Reduction in liver transplant wait-listing in the era of direct-acting antiviral therapy. Hepatology. 2017;65(3):804-12.

4. Grant BF, et al. Prevalence of 12-month alcohol use, high-risk drinking, and DSM-IV alcohol use disorder in the United States, 2001-2002 to 2012-2013: results from the National Epidemiologic Survey on Alcohol and Related Conditions. JAMA Psychiatry. 2017;74(9):911-23.

5. Ndugga, N, et al. Disparities between research attention and burden in liver diseases: implications on uneven advances in pharmacological therapies in Europe and the USA. BMJ Open. 2017;7(3):e013620; doi: 10.1136/bmjopen-2016-013620 [Epub ahead of print].