Showing posts with label Fatty Liver. Show all posts
Showing posts with label Fatty Liver. Show all posts

Thursday, August 9, 2018

Even light drinking may make fatty liver disease worse

Even light drinking may make fatty liver disease worse 
Study In Hepatology
July 17, 2018
Non‐heavy drinking and worsening of non‐invasive fibrosis markers in nonalcoholic fatty liver disease: A cohort study

Reuters Health
Lisa Rapaport
For the current study, researchers examined data on 58,927 Korean young and middle aged adults with NAFDL who had low levels of fibrosis, or scarring on the liver. After following half of these patients for at least 8.3 years, 5,630 people had progressed from low to more advanced levels of fibrosis.

Moderate drinkers were 29 percent more likely to have worse fibrosis by the end of the study than people who didn’t drink at all. Men were considered moderate drinkers when they had up to about two drinks a day, while women could have up to about 1.5 drinks daily.

But “light drinkers” who averaged less than 10 grams of alcohol (less than one drink) daily, were also 6 percent more likely to have their fibrosis become more advanced than people who avoided alcohol altogether, the study team reports in Hepatology.
Continue reading: https://in.reuters.com/article/us-health-liver-drinking/even-light-drinking-may-make-fatty-liver-disease-worse-idINKBN1KT2V7

Monday, July 9, 2018

Targeting non-alcoholic fatty liver disease

In Case You Missed It
In the July Issue of the patient-friendly HCV Advocate newsletter, Lucinda Porter, RN., writes a must read article about: Avoiding Fatty Liver.

Targeting non-alcoholic fatty liver disease
Erreportajeak
One of the lines of research of the UPV/EHU's Lipids & Liver group, which focusses on the mechanisms involved in the development and progression of non-alcoholic fatty liver disease, is achieving significant advances in a range of aspects; these include the identification of proteins that alter the metabolic pathways in the development and progression of liver disease, and even cancer, and the seeking of targets to enable the disease to be reversed.

According to the latest figures, non-alcoholic fatty liver disease affects 30% of the general population, and this percentage rises to between 70% and 80% in certain risk groups, such as obese patients, patients with diabetes, etc., due to the fact that the latter is linked to metabolic diseases. The disease begins with a simple build-up of fat or lipid in the liver which in principle may be benign but which in some patients may progress and lead to hepatitis, steatohepatitis, because of its inflammation, and this is a risk factor for developing hepatic cirrhosis and even liver cancer. Right now, there is no specific treatment for this disease, and owing to the current high prevalence of obesity and diabetes, it is forecast that within a few years liver cancer cases caused by this fat storage could soar, as could the number of transplants caused by non-alcoholic steatohepatitis.

The Lipids & Liver research group in the department of Physiology at the UPV/EHU’s Faculty of Medicine and Nursing is working to find out what mechanisms are involved in the development and progression of liver diseases, and mainly the mechanisms related to alterations linked to lipid (fat) metabolism. Specifically, one of the group’s lines of research, which focusses on the study of non-alcoholic fatty liver disease, is involved in research that aims to “find out why the disease develops in some patients and not others; to find evolution markers that can provide us with a prognosis as to which patients are going to develop the disease; and to find not only hepatic markers (that can be obtained through biopsy) but also serum markers, which by means of simple blood tests can say which phase the patient is in”, explained Dr Patricia Aspichueta, head of the line of research.
The liver is the metabolic centre of the whole body

Basically, the members of the research group are focusing on the study of lipid metabolism in the liver, in other words, on the chemical reactions in which they are formed or consumed. To do this, they work with animal models in which a gene has been silenced and to which different diets and treatments designed to induce the disease are given, and once a target in the animal model has been confirmed or identified, they proceed to validate it in human samples. What is more, they also work with in vitro or cell models, “because there it is easier to find out in which cell the metabolism has been damaged, modified or altered, we can play around with different drugs, different inducers, and it is easier to silence specific metabolic pathways, etc.”, explained Aspichueta.

The members of the group are studying different molecules or targets involved in various liver disease processes. Aspichueta specifies some of the pathways that they have open in the research group: “Firstly, we want to identify the proteins that alter the metabolic pathways and which supply the liver with more lipid. We want to find out why this lipid store forms, and why the store causes the disease to progress to phases such as cancer, even. It is important to know which players are involved in these processes to be able to silence them and see if the disease is reversed.” They are also exploring the involvement of lipids in liver regeneration, “a hugely important perspective with respect to patients who have had a portion of their liver removed, because the liver is the only organ that regains its normal size”. In another of the studies they are exploring “how the liver controls adipose tissue, and how by modulating liver function we can get animals to lose weight”.

Aspichueta confirms that they have found “an important therapeutic target that modulates the metabolism and the progression of the disease”. They have induced the development of liver cancer associated with obesity in animal models in which this protein has been silenced and “we have seen that the animals do not develop the disease at all: neither liver cancer nor the fat store. It’s amazing,“ said the doctor. Now “we are working on human samples of non-alcoholic fatty liver disease to validate the involvement of these proteins in human pathology”. The researchers are aiming to find targets that control several metabolic pathways at the same time, “because the metabolic alteration does not take place in a single pathway, rather a decompensation takes place, the metabolism becomes unbalanced and various pathways are affected,” she concluded. The liver is the metabolic centre, and if we control the liver we can control many disorders associated with this liver disease”.
Additional information

The Lipids & Liver research group has been recognised as a Consolidated Group by the Department of Education of the Basque Government since 2007. Its research work relating to the Physiopathology of Lipid Metabolism comes within the strategic Health and Life Quality line of the Spanish Ministry of the Economy and Competiveness and of the Basque Government, in the sphere of the Euskampus biomedicine and healthy Ageing and life quality.

The group works in close collaboration with various research groups at the UPV/EHU as well as external ones with which they have had numerous publications in various scientific journals. The group is part of the Biocruces Institute for Health in which it broadens its research to the disorder in humans. It also collaborates with CIC bioGUNE, the University of Santiago de Compostela, other groups in Madrid, the Hospital of Valdecilla (Santander), as well as with the University of South Carolina and Yale University. It also works with an American pharmaceutical company in the quest for treatment targets.

Saturday, June 30, 2018

HepCure Webinar Series - Hep C & Fatty Liver, Treatment, Alcohol Use, Elderly Patients and More

Watch experts discuss important HCV related topics in this easy to access webinar series presented by HepCure.

June 26, 2018
Transplant & HCV
On Tuesday, June 26th, Dr. Thomas Schiano of Mount Sinai Medical Center presented on: “Transplant & HCV”
Watch, here….
Download Slides, here.....

June 19, 2018
Nonalcoholic Fatty Liver Disease and Hepatitis C
On June 19th Dr. Amon Asgharpour of the Icahn School of Medicine at Mount Sinai. Dr. Asgharpour presented “Nonalcoholic Fatty Liver Disease and Hepatitis C.”


Watch, here.….
Download Slides, here...…

Of Interest
Michael Carter
Published: 18 June 2018
Fatty liver improves rapidly after hepatitis C cure
Liver stiffness and liver fat (steatosis) in people with chronic hepatitis C virus (HCV) infection both improve significantly after treatment with direct-acting antivirals (DAAs) resulting in sustained virological response (SVR), investigators from Japan report in Alimentary Pharmacology and Therapeutics. Both measures of liver health were assessed six months after SVR. Improvement was associated with a reduction in ALT levels and an increase in platelet count.

On This Blog
June 18, 2018
Hepatitis C Weekend Video: NASH What Is It

Elsewhere
July 1, 2018
In the July Issue of the patient-friendly HCV Advocate newsletter, Lucinda Porter, RN., writes a must read article about: Avoiding Fatty Liver.

June 2018
Hepatitis C and Alcohol
On Tuesday, June 5th, Peter Hauser, MD, Director of the National VA Telemental Health Hub Long Beach presented on: “Hepatitis C and Alcohol”.


Watch, here...
Download Slides, here....

May 2018 - HCV Treatment
“Ace the Case” 

Program presented last month led by Dr. Douglas Dieterich of the Icahn School of Medicine at Mount Sinai. This webinar is patient based, with question and answer participation.

Topics
Late relapse in people with HCC
Reinfection
Chemo On HCV
Treating Patients with HCV & Depression & More....
Watch, here.....

HCV in the Elderly Patient
On May 29th, Dr. Roxana Bodin of Westchester Medical Center Health presented on: “HCV in the Elderly Patient”


Watch, here...
Download Slides here.....

Of Special Interest
"Innovation as Usual: Sustainable Financing for Viral Hepatitis Elimination" with Dr. Henry Chang. This webinar will discuss the global target to eliminate viral hepatitis as a major public health problem by the year 2030.
Watch, here.....
Download Slides, here...

Additional Topics
The HCV-Opioid Syndemic in Appalachia: Evidence from a Cohort of Rural Drug Users
Hepatitis C in Children and Adolescents
Cirrhosis & HCV

View All
Webinar Archive

Follow On Twitter
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HepCure Patient App
The patient app is a free resource for patients with hepatitis C, which allows them to track medication adherence, symptoms, and gain access to resources. It is available to download for free on iOS (App Store) and Android (Google Play) operating systems. While the app can be used by patients independently from the dashboard, it can also be linked with the provider dashboard. Providers can push lab data to patients and track treatment adherence and symptom data input by patients in real time.
Learn more here...…

Thursday, June 21, 2018

60,000 adults in the UK have cirrhosis, nearly 75% percent don't know it


7 in 10 people with liver disease in the UK don’t even know they have it 
Although over 60,000 adults in the UK have cirrhosis (scarring) of the liver, nearly 75% percent don't know it, according to research published in the Lancet. For many, the first indication is following admission to Accident and Emergency when the disease is advanced and chance of survival is very low. This week, 18th to 24th June, is Love Your Liver week, and the British Liver Trust has launched a new version of an online screening tool so that people can find out if they are at risk.

Although over 60,000 adults in the UK have cirrhosis (scarring) of the liver, nearly 75% percent don't know it, according to research published in the Lancet. For many, the first indication is following admission to Accident and Emergency when the disease is advanced and chance of survival is very low. This week, 18th to 24th June, is Love Your Liver week, and the British Liver Trust has launched a new version of an online screening tool so that people can find out if they are at risk.

Liver disease is one of the leading causes of premature death in England and is responsible for more than 1 in 10 deaths of people in their 40s.

Professor Nick Sheron, a liver expert from the University of Southampton involved in the research, said: "Liver disease develops silently with no signs or symptoms and is the second leading cause of years or working life lost. If current trends continue it become the leading cause of premature mortality in the UK. Yet, most people with fatal advanced liver disease only become aware that they have a liver problem when they are admitted as an emergency. We MUST diagnose these people much earlier."

Liver problems develop silently with no obvious symptoms in the early stages yet the disease is largely preventable through lifestyle changes. The Love Your Liver awareness campaign, promoted by the British Liver Trust, aims to reach the one in five people in the UK who may have the early stages of liver disease, but are unaware of it.

More than 90% of liver disease is due to three main risk factors: obesity, alcohol and viral hepatitis.

Judi Rhys, Chief Executive, British Liver Trust said, “Helping people understand how to reduce their risk of liver damage is vital to address the increase in deaths from liver disease. Although the liver is remarkably resilient, if left too late damage is often irreversible. I would urge everyone to take our online screener on our website to see if they are at risk.”

The British Liver Trust’s Love Your Liver campaign focuses on three simple steps to Love Your Liver back to health:

- Drink within recommended limits and have three consecutive alcohol-free days every week
- Cut down on sugar, carbohydrates and fat and take more exercise
- Know the risk factors for viral hepatitis and get tested or vaccinated if at risk

Finding out your risk of liver disease only takes a few minutes. It could be the most important thing you do today. Take the British Liver Trust’s screener here

Liver disease is one of the leading causes of premature death in England and is responsible for more than 1 in 10 deaths of people in their 40s.

Professor Nick Sheron, a liver expert from the University of Southampton involved in the research, said: "Liver disease develops silently with no signs or symptoms and is the second leading cause of years or working life lost. If current trends continue it become the leading cause of premature mortality in the UK. Yet, most people with fatal advanced liver disease only become aware that they have a liver problem when they are admitted as an emergency. We MUST diagnose these people much earlier."

Liver problems develop silently with no obvious symptoms in the early stages yet the disease is largely preventable through lifestyle changes. The Love Your Liver awareness campaign, promoted by the British Liver Trust, aims to reach the one in five people in the UK who may have the early stages of liver disease, but are unaware of it.

More than 90% of liver disease is due to three main risk factors: obesity, alcohol and viral hepatitis.

Judi Rhys, Chief Executive, British Liver Trust said, “Helping people understand how to reduce their risk of liver damage is vital to address the increase in deaths from liver disease. Although the liver is remarkably resilient, if left too late damage is often irreversible. I would urge everyone to take our online screener on our website to see if they are at risk.”

Finding out your risk of liver disease only takes a few minutes. It could be the most important thing you do today. Take the British Liver Trust’s screener here

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, June 4, 2018

June Newsletters - Hepatitis C in Colorado & Liver Congress 2018 Coverage

June Hepatitis Newsletters
Welcome, we start with a few June publications, followed by events you may have missed last month. Next, sift through the June index of newsletters, and finish off with a list of well written blogs with extremely useful information on the topic of viral hepatitis.

June Updates
A Guide to Understanding Hepatitis C (HCV)
HCV Advocate: We have completely updated and given our most popular publication and a new look. To download, click here

Despite the availability of new DAA regimens and changes in restrictions of these therapies, absolute denials of DAA regimens by insurers have remained high and increased over time, regardless of insurance type.

Updated Guidelines - Hepatitis C testing recommended for Canadians born between 1945 and 1975
More than 250,000 Canadians are believed to be infected with hepatitis C, but 40 to 70 per cent are unaware they harbour the blood-borne virus. The Canadian Association for the Study of the Liver, a national group of health-care providers and researchers, published its guidelines on testing and treating hepatitis C in Monday’s edition of the Canadian Medical Association Journal.

When to Initiate HCV Therapy and Overview Of New Drugs
Sit back, grab your favorite beverage and review; Making a Decision on When to Initiate HCV Therapy, updated a few days ago, published by Hepatitis C Online.

What You Missed In May
Screening for Hepatitis C Climbs in Colorado

Each year, more Coloradans are contracting hepatitis C, the infectious liver disease spread by contact with infected blood. The state’s hep C death rate is heading higher as well. An analysis by the Colorado Health Institute of newly available information from the state’s All Payer Claims Database (APCD) reveals the rate of Coloradans getting screened for the hepatitis C virus nearly tripled between 2011 and 2016.

Key Takeaways:
The rate of screening for hepatitis C among Coloradans nearly tripled between 2011 and 2016, a Colorado Health Institute analysis of newly available data shows.

Baby boomers between ages 55 and 64 saw the largest increase in screening rates during that time; millennials between 25 and 34, had the highest screening rate each year.

Medical advances, federal and state policy changes and fallout from the opioid epidemic have contributed to the rise in screening.  
Download the report.

Full of Life: The Stories of People Affected by Hepatitis C
The Institute’s Hepatitis Policy Project has released a new report that features the stories of people affected by hepatitis C. The report was authored by Sonia Canzater and Jeffrey S. Crowley. “Full of Life: The Stories of People Affected by Hepatitis C,” underscores the impact of hepatitis C and the potential for improving the lives of those with the disease.

Real people make up the HCV epidemic, and their experiences and the full lives they lead offer motivation and resolve to work to eliminate HCV as a public health threat. But, as this report will show, the reality of what is happening to respond to HCV in the United States (US) falls short of the possibility of what we could make happen to save lives and strengthen communities, read it here....
This project is supported by a grant from Gilead Sciences.

AASLD online HCV guide update includes key at-risk populations

May 31, 2018
The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America recently updated their hepatitis guideline website, HCVguidelines.org, to include several new testing and management recommendations for pregnant women, men who have sex with men, people who inject drugs and incarcerated individuals. Kristen M. Marks, MD, assistant professor of medicine at Weill Cornell Medical College in New York and HCV Guidance co-chair, discussed the new updates with HCV Next, read it here...

New Hepatitis C Virus Guidelines and Lyme Disease Prevention



Perspective - New England Journal Of Medicine 
The FDA and the Next Wave of Drug Abuse — Proactive Pharmacovigilance
In response to the opioid crisis, the Food and Drug Administration (FDA) has taken action on multiple fronts. We have approved better measures for treating opioid use disorder and preventing deaths from overdose, have launched efforts to inform more appropriate prescribing as a way to limit clinical exposure to opioids, have taken actions to reduce the excess opioids available for abuse, and are working to facilitate development of new therapeutics that can effectively and safely help patients suffering from pain. Going forward, the FDA needs to remain vigilant to recognize shifting trends in the addiction landscape. Taking a systematic approach to monitoring such trends should allow us to intervene promptly and appropriately and protect the public from associated risks, read the article here...…

Surrey develops hepatitis C model that could help improve treatment
The University of Surrey has created a new mathematical model that details how the hepatitis C (HCV) infection develops and behaves more accurately than previous models, read the press release, here.....

New strategy to cure chronic hepatitis B infection
Scientists from Karolinska Institutet and Hannover Medical School have published two studies that provide insights into how the immune system responds and helps to clear a hepatitis B infection after treatment interruption. The findings offer a framework for future tailored treatment strategies and are published in The Journal of Infectious Diseases and Journal of Hepatology, read it here....

Conditions Related To HCV
Listen - Hepatitis C: It’s About More than Liver Disease
The National Viral Hepatitis Roundtable is pleased to present a webinar to discuss the health effects of hepatitis C virus (HCV) infection that occur outside the liver. Learn more about how conditions such as kidney disease, depression, certain types of cancer, and diabetes are related to HCV infection. The webinar will feature clinician and patient perspectives to facilitate discussion about the importance of recognizing these conditions as part of HCV management and the implications for early HCV treatment.
This webinar is now archived. Click here for the slides. Click here for the recording. (Click the link and then enter the requested information to view the webinar).

Fatigue & Achieving SVR

Do fatigue and quality of life improve after hepatitis C is cured?
Patient-reported outcomes such as fatigue, vitality and mental health improve substantially in the two years following hepatitis C cure for people with cirrhosis, but people with cirrhosis are less likely than others to experience rapid resolution of severe fatigue after successful hepatitis C treatment, according to two studies from the Center for Outcomes Research in Liver Diseases reported last month at the 2018 International Liver Congress in Paris, read it here...

Fibrosis
Can anti-viral therapy reduce liver fibrosis and steatosis in patients with chronic hepatitis C virus?
In this study, changes in liver stiffness and steatosis as determined by MRI in patients with chronic HCV genotype 1 or 2 infection who received direct-acting anti-viral therapy and achieved SVR is investigated, read the article here....

Screening & Treating HCV
HCV From Screening to Cure
The following video presentation; "HCV From Screening to Cure: A Closer Look at Changing At-Risk Populations and an Evolving Treatment Landscape" with Ira M. Jacobson, MD., and provided by Medical Learning Institute, Inc. and PVI, PeerView Institute for Medical Education, will discuss screening strategies, stigma, patient-related barriers to treatment, hepatitis C testing for identifying current infection, and tests used to stage fibrosis. Also discussed is treatment for HCV patients with cirrhosis, as well as treatment adherence, duration, treatment according to HCV genotype, ending with "How Much Care Do The Cured Need?" Watch the video, here....

Supervised injection sites are coming closer to reality in several cities in the United States.
U.S. Cities Consider Supervised Injection Sites
Safe injection facilities can reduce overdoses, disease transmission, and public drug use.

Prospective Study: No psychiatric side effects with new IFN-free treatment for HCV 
Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence, read the article here....

The Truth about Hepatitis C Treatment long term Side Effects
Karen Hoyt is devoted to offering support and accurate information to people coping with the effects of liver disease through a series of informative videos, topics include ascites, hepatic encephalopathy and other liver-related complications.
Here is the latest video: The Truth about Hepatitis C Treatment long term Side Effects.

AASLD Special Collection: Treating Liver Disease in 2018
Topics include: Hepatitis C virus reactivation in patients receiving cancer treatment, drug‐drug interactions in hepatitis C virus treatment and more. Start here...…

Fatty Liver
Journal of Gastroenterology and Hepatology
Special Issue: Burden of Nonalcoholic Fatty Liver Disease in Australia.
In this review, we present available data on the prevalence of NAFLD in Australia, its associated health burden in terms of hepatic and extrahepatic complications, common presentations, and evidence‐based therapeutic options. We also outline a research agenda highlighting gaps in knowledge that are needed to improve diagnosis and management of people with NAFLD specific to the Australian context. Full-text available here.....  

Behind The Headlines
Most multivitamins and supplements are a 'waste of money' 
The review found that taking the most widely used supplements – multivitamins, vitamin D, vitamin C and calcium – had no significant effect on the risk of heart-related illnesses. And some supplements, such as vitamin B3 (niacin) may do more harm than good, read it here.... 

HIV
A new edition of our 'Antiretroviral drugs chart' is now available online. This one-page reference guide lists all the anti-HIV drugs licensed for use in the European Union, with information on formulation, dosing, key side-effects and food restrictions, read it here ….

The Controversy 
Do direct acting antivirals cure chronic hepatitis C?
A controversial review by the Cochrane Collaboration published June 6, 2017/updated September 8 2017, cast doubt on the effectiveness of new hepatitis C treatments, on May 12, 2018, BMJ published; Do direct acting antivirals cure chronic hepatitis C ? by Cochrane author Janus Christian Jakobsen. BMJ talk medicine also aired a follow-up podcast with Jakobsen; New antivirals for Hepatitis C - what does the evidence prove? On May 16, 2018 experts weighed in on the program, read what they had say: Experts Respond To Latest BMJ Article: Do direct acting antivirals cure chronic hepatitis C?

June Newsletters
HCV Advocate
The HCV Advocate newsletter is a valuable resource designed to provide the hepatitis C community with monthly updates on events, clinical research, and education.
Newsletter
June Issue
We are continuing our conference coverage of the International Liver Congress 2018 and we have the following posters and presentations:
More of Lucinda’s Highlights from the 2018 International Liver Congress:
STUDY Abstract: THU-099 Lowering the upper limit of serum alanine aminotransferase levels may detect significant liver disease in the elderly – H. Schmilovitz-Weiss, et al.
STUDY Abstract: THU-100 Hepatitis C patients with HIV co-infection demonstrate unique liver-related complications and health behaviors compared to HCV mono-infected patients – M. Lu, et al.
STUDY Abstract: THU-399 Incidence and prevalence of extrahepatic manifestations of HCV – H. El-Serag, et al.
STUDY Abstract: THU-418 Lymphomas incidence in HIV/HCV coinfected versus HIV monoinfected patients over twenty-one years of follow up (1993–2014) – A.M. de Cea, et al.
STUDY Abstract: FRI-368 Long-term immunological and clinical impact of HCV eradication with directacting antivirals in patients with HCV-associated cryoglobulinemia vasculitis – M. Bonacci, et. al.
STUDY Abstract: THU-412 Among 1945–1965 birth cohort patients with at least one additional hepatitis C virus risk factor, one in eight were positive for HCV antibody: an underserved safety-net population experience – G. Hirode, et. al.
STUDY Abstract: THU-429 Strong increase of acute HCV infections in HIV-negative men having sex with men – L. Cotte, et. al.

More of Alan’s Highlights from the 2018 International Liver Congress:
STUDY Abstract: GS-018 Long-term follow-up of patients with chronic HCV infection and compensated or decompensated cirrhosis following treatment with sofosbuvir-based regimens – A. Mangia, et. al.
STUDY Abstract: LBO-008 A phase 3b, open-label, randomized, pragmatic study of glecaprevir/ pibrentasvir +/− ribavirin (RBV) for HCV genotype 1 subjects who previously failed an NS5A inhibitor + sofosbuvir (SOF) therapy – A. Lok, et. al.
STUDY Abstract: THU-121 Track, Trace & Treat: Results from a retrieval strategy to identify lost to follow-up chronic hepatitis c patients – I. Munsterman, et. al.
STUDY Abstract: LBP-0231 The percentage of patients with HCV infection in need of a liver transplant is rapidly declining while their survival after transplantation is improving: a study based on European Liver Transplant Registry – G. Perricone, et al.
STUDY Abstract: FRI-028 Liver transplant waitlist mortality, transplantation rates and post-liver transplant outcomes in Hispanics – P.J. Thuluvath, et al.
STUDY ABSTRACT: FRI-374 The impact of sustained virologic response on severe fatigue in patients with chronic hepatitis C: the role of HCV viremia and co-morbidities – Z. Younossi, et. al.
STUDY Abstract: THU-075 hepatitis C screening within the National Elimination Program in the country of Georgia – A. Gamkrelidze, et. al. 

BRIEFLY…
STUDY Abstract: THU-075 hepatitis C screening within the National Elimination Program in the country of Georgia – A. Gamkrelidze, et. al.
STUDY Abstract: THU-104 The first result from the general population hepatitis screening in Mongolia: 38% of 40– 65-year-olds screened and anti-HCV prevalence of 15.6% among 40– 65-year-olds – B. Dashtseren, et. al.
STUDY Abstract: PS-090 Direct-acting antiviral treatment in sub-Saharan Africa: A prospective trial of ledipasvir/ sofosbuvir for chronic hepatitis C infection in Rwanda (The SHARED Study) – N. Gupta, et. al.

Hepatitis Materials Available:

We have a limited supply of free materials available. They are pre-packaged in the following quantities:
A Box of 1,500 Palm cards
A box of 1,000 Palm cards, 500 Baby Boomer postcards, & 500 website cards.

Please email us at Rosanne1956@hotmail.com if you have a need for materials to distribute.

Pack Health
Don’t forget to check out Pack Health: a free resource to help patients navigate their HCV treatment journey from applying for treatment to cure.
Enter your contact info
Use promo code: HCV2017
Get 3 months of membership free! As easy as 1-2-3!

Questions? Call us at 885-255-2362 8am-5pm | Monday-Friday 
• Get a personal Health Advisor to coach you on your journey 
• Develop a personalized plan – you set the goals, we’ll help you get there 
• Find answers and accountability to get the results you want 
• Use the tools and guides we send you to track your progress.
View all newsletters here....

Hep - Your Guide to Hepatitis
Hep is an award-winning print and online brand for people living with and affected by viral hepatitis. Offering unparalleled editorial excellence since 2010, Hep and HepMag.com are the go-to source for educational and social support for people living with hepatitis.

June - Hep Summer Issue 2018
Alive and Kicking
A photographer helps his mom get cured of hep C after reading Hep magazine.

Mother and Child Reunion 
Connie Dewbre’s son convinced her to get cured of HCV again after visiting our Hep magazine website.
Read the news
Check out the talented people who blog at Hep.

The National Viral Hepatitis Roundtable
The National Viral Hepatitis Roundtable (NVHR) is national coalition working together to eliminate hepatitis B and C in the United States.

The New York City Hepatitis C Task Force
The New York City Hepatitis C Task Force is a city-wide network of service providers and advocates concerned with hepatitis C and related issues. The groups come together to learn, share information and resources, network, and identify hepatitis C related needs in the community. Committees form to work on projects in order to meet needs identified by the community.
View all: Hep Free NYC Newsletters

HCV Action
HCV Action brings together hepatitis C health professionals from across the patient pathway with the pharmaceutical industry and patient representatives to share expertise and good practice.
View recent newsletters

Healio: International Liver Congress 2018
HCV Next is a monthly publication offering patients the latest research, news and commentary on liver disease and viral hepatitis, published online at Healio.
Read a nice summary of the liver meeting in the May/June issue.

World Hepatitis Alliance
We run global campaigns, convene high-level policy events, build capacity and pioneer global movements, ensuring people living with viral hepatitis guide every aspect of our work.
Read all updates
Newsletters - World Hepatitis Alliance (WHA) presents hepVoice, a monthly magazine with updates on the latest projects, news from WHA members and key developments in the field of hepatitis.

GI & Hepatology News
Over 17,000 gastroenterologists and hepatologists rely on GI & Hepatology News every month to cover the world of medicine with breaking news, on-site medical meeting coverage, and expert perspectives both in print and online.
View all updates here....

Weekly Bull

HepCBC is a Canadian non-profit organization offering awareness with basic information about HCV and a weekly digest of news.
Read the highly successful Weekly Bull.

Pacific Hepatitis C Network (PHCN)

Welcome to the Pacific Hepatitis C Network (PHCN)‘s Hepatitis C News in Review Newsletter. This is where we review all of the major current issues and events around hepatitis C and hep C treatments. It is an email that includes links to our recent blog posts—including links to blog posts about Public Health Agency of Canada funding.
View all updates
Newsletter Sign Up

CATIE
CATIE strengthens Canada’s response to HIV and hepatitis C by bridging research and practice. We connect healthcare and community-based service providers with the latest science, and promote good practices for prevention and treatment programs.
Sign up for CATIE Email Newsletters
Updates - News

CanHepC - Canadian Network on Hepatitis C
CanHepC is a collaborative research network funded by the Canadian Institutes of Health Research (CIHR) and the Public Health Agency of Canada (PHAC) dedicated to translational research linking over 100 researchers, trainees, knowledge-users (community members, community-based organizations, policy and decision makers) in the field of Hepatitis C (HCV) from across Canada as well as international partners.
View all newsletters here.....

Hepatitis Victoria
Hepatitis Victoria is the peak not-for-profit community organisation working across the state for people affected by or at risk of viral hepatitis.
GOOD LIVER MAGAZINE is our quarterly newsletter, providing in-depth articles, interviews and reports, as well as detailing upcoming events, support groups, liver clinics, and other items likely to be of interest to our members. HepChat is our monthly electronic newsletter sharing news and information about hepatitis and the projects and activities we're working on, subscribe to HepChat. We also produced short podcasts interviewing health experts and practioners on topics related to viral hepatitis - come have a listen!

British Liver Trust
The British Liver Trust is the leading UK liver disease charity for adults – we provide information and support; increase awareness of how liver disease can be prevented and promote early diagnosis; fund and champion research and campaign for better services.
View all Newsletters here.

Hepatitis B Foundation
Hepatitis B Foundation is a national nonprofit dedicated to finding a cure and improving the quality of life for people affected by hepatitis B worldwide.
All newsletters, sign up
Blog & News

Hepatitis A - Voice of San Diego
Voice of San Diego is an award-winning nonprofit news organization based in San Diego, California.
The Hep A Fallout Continues: On this week’s San Diego Explained, Voice of San Diego’s Jesse Marx and NBC 7’s Monica Dean take a look back at San Diego’s response to last year’s hepatitis A outbreak, listen here.

National Institutes of Health
A monthly newsletter from the National Institutes of Health, part of the U.S. Department of Health and Human Services
June Newsletter
View all newsletters: https://newsinhealth.nih.gov/

Blogs
The Best Of The Best
HCV Advocate - Hepatitis C Blog - Daily Updates
HepatitisC.net - Updated with about 5 posts per week
Lucinda K. Porter - Updated about once a week
Hep - Updated with 5 or more posts per week
ADRLF (Al D. Rodriguez Liver Foundation) - Updated monthly
Hepatitis NSW Updated about twice or more per month
Life Beyond Hepatitis C - Updated with about 3 posts per week
I Help C - Updated about twice or more per month
CATIE Blog - Updated about twice or more per month
Canadian Liver Foundation - Updated about twice or more per month
AGA Journals - Updated once a week
Hepatitis B Foundation - Updated once a week or more.
HIV and ID Observations - Updated once a week
The Hepatitis C Mentor and Support Group - (News) Updated once a week or more

Wellness
Live Fit Liver Fit Get Fit (American Liver Foundation) - Monthly updates
Harvard Health Blog - Updated with about 3 posts per week
ACP Internist and American College of Physicians - Weekly & monthly updates
Healio Med Blog- Monthly updates

Conference 
Digestive Disease Week® (DDW) 2018
June 2-5, 2018
Website - Digestive Disease Week® (DDW)
DDW Blog
DDW Daily News
Topics at DDW:
AASLD’s annual Hepatology Update: The Year in Review session will feature recent advances in hepatitis C, hepatitis B, nonalcoholic fatty liver disease, and liver transplantation. Other sessions include Functional GI and Motility Disorders; Irritable Bowel Syndrome, Functional Dyspepsia.

Updates
On This Blog

Meeting Coverage
Healio 
Healio staff will report live on breaking news presented at the meeting and capture video interviews with experts to gain their perspectives on important presentations. 
Free registration may be required

Thanks for stopping by!
Tina

Friday, May 11, 2018

Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications

As a side note, according to the HCV treatment guidelines published by the American Association for the Study of Liver Diseases, the Infectious Diseases Society of America and the International Antiviral Society, the only contraindication to current chronic HCV treatment is in a patient with a short life expectancy that cannot be lengthened with treatment, with liver transplant, or with any other treatments. Overtime we have learned that treating people with lower-stage fibrosis increases SVR rates, and for persons who inject drugs, adherence and efficacy rates are comparable to those of patients who do not use injected drugs. In other words, treat all.

Patients with stage 3 compared to stage 4 liver fibrosis have lower frequency of and longer time to liver disease complications
Page Axley, Sandhya Mudumbi, Shabnam Sarker, Yong-Fang Kuo, Ashwani Singal
Published: May 10, 2018
https://doi.org/10.1371/journal.pone.0197117

Full-Text

Abstract
Background and aims
Advanced liver fibrosis is an important predictor of liver disease progression and mortality, and current guidelines recommend screening for complications of cirrhosis once patients develop F3 fibrosis. Our study compared liver disease progression and survival in patients with stage 3 (F3) and stage 4 (F4) fibrosis on liver biopsy.

Methods
Retrospective study of patients with F3 or F4 on liver biopsy followed for development of liver disease complications (variceal bleeding, ascites, and hepatic encephalopathy); hepatocellular carcinoma, and survival (overall and transplant free survival).

Results
Of 2488 patients receiving liver biopsy between 01/02 and 12/12, a total of 294 (171 F3) were analyzed. Over a median follow up period of 3 years, patients with F4 (mean age 53 years, 63% male) compared to F3 (mean age 49 years, 43% male) had higher five year cumulative probability of any decompensation (38% vs. 14%, p<0.0001), including variceal bleed (10% vs. 4%, p = 0.014), ascites (21% vs. 9%, p = 0.0014), and hepatic encephalopathy (14% vs. 5%, p = 0.003). F4 patients also had lower overall 5-year survival (80% vs. 93%, p = 0.003) and transplant free survival (80% vs. 93%, p = 0.002). Probability of hepatocellular carcinoma in 5 years after biopsy was similar between F3 and F4 (1.2% vs. 2%, p = 0.54).

Conclusions
Compared to F4 stage, patients with F3 fibrosis have decreased risk for development of liver disease complications and better survival. Prospective well designed studies are suggested with large sample size and overcoming the limitations identified in this study, to confirm and validate these findings, as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.

Discussion Only
View full text article @ PLOS ONE

The main findings of our study are that patients with F4 fibrosis compared to those with F3 stage have a) higher probability of developing decompensation of liver disease including ascites, variceal bleeding, and hepatic encephalopathy and b) lower overall and transplant-free survival.

In patients with chronic HCV infection, several previous studies have reported increased rate of liver disease complications related to advanced fibrosis stage. In a study of 1050 HCV patients, 57% with Ishak stage 4 to 6, there was cumulative incidence of first liver-disease complication of 19.3% for stage 4, 37.8% for stage 5, and 49.3% for stage 6 in the 6 year follow up period.[8] The probability of liver disease complication, death, or liver transplant increased with successive fibrosis stages. Stages 4 and 5 of the Ishak system represent advanced bridging fibrosis and/or early nodule formation and have shown excellent correlation with F3 in the METAVIR system.[9]

Another study based on four large US-integrated health systems retrospectively examined 917 chronic HCV patients with F3 and F4 fibrosis for 5 years after liver biopsy.[10] For liver disease related complications comparing F4 vs. F3 fibrosis, there was increased risk for ascites (14 vs. 7.1%), esophageal varices with bleeding (4.4 vs. 1.2%), and hepatic encephalopathy (3.9 vs. 1.4%) in the 5 year observation period after liver biopsy. The 5-year survival was 77% in F4 fibrosis compared to 91% in F3 fibrosis. The 5-year probability for HCC development was 3.1% in F3 fibrosis and 8.8% in F4 fibrosis.

Huang et al. evaluated 153 patients with F3 fibrosis (mean age 45, 54% male) and F4 fibrosis (mean age 51, 54% male) over a mean follow up period of 9 years and found that F4 had significantly higher risk of liver-related complications, hepatocellular carcinoma, and death than F3 (p < 0.001).[11] Very similar to our findings, the 5-year survival in patients with F4 fibrosis was 83% compared to 96% in patients with F3 fibrosis. The 5-year probability for development of HCC patients with F3 fibrosis was 0% compared to 6% in F4 patients. At year 7, probabilities for HCC development jumped to 16% in patients with F4 fibrosis and increased to 2% in patients with F3 fibrosis. Unlike these previous 2 studies described, our study failed to show a difference in the risk for development of HCC in F3 compared to F4 fibrosis, likely because of the shorter follow up period of only 5 years and the inclusion of non-HCV patients who have lower risk for HCC development.

In NAFLD, advanced fibrosis has also been identified as leading to higher rates of liver-disease related complications and mortality.[12, 13] In a recent study of 646 patients (mean age 48, 62% male) with well-defined NAFLD followed for a mean of 20 years, patients with F4 fibrosis had a 3-fold increase in liver disease related complications and a 2-fold increase in overall mortality compared to those with F3 fibrosis.[14] The average time for patients with F3 fibrosis to develop severe liver disease as defined by the ICD-code diagnosis of cirrhosis, liver failure, HCC, or decompensated liver disease was 6 years (95% CI 2.3–9.6), however the study did not differentiate between these outcomes or provide data on HCC incidence. In another large multi-center cohort study of 619 NAFLD patients (11.5% with stage 3 or 4 fibrosis) followed for a median of 12.6 years, F4 patients compared to F3 patients had a four-fold increased probability for liver disease related complications overall and two-fold increased risk of liver-related mortality.[13] Only 3 patients in the study developed HCC, and fibrosis stage for these patients was not reported.

To our knowledge, this is the first study showing that patients with F3 compared to F4 fibrosis have lower frequency of and longer time to development of liver disease complications irrespective of liver disease etiology. Our large cohort is also well characterized with liver fibrosis stage confirmed by two separate pathologists. Further, studies have shown good inter- and intraobserver reproducibility on the fibrosis staging using any classification including the Metavir fibrosis staging system.[5] Also, potential confounders of alcohol use and HCV treatment were equally distributed in the two groups ruling out to a great extent their impact on the outcomes. However, apart from inherent limitations of a retrospective study design, our study does suffer from potential selection bias as not everyone presenting for liver disease evaluation at our center underwent a liver biopsy examination. Further, our study excluded patients with F2 fibrosis, which could be used as a control group and compare with F3 fibrosis on development of outcomes. Although for analysis on decompensation and liver disease complications, we only analyzed patients developing the respective event after 30 days from liver biopsy, it is possible that some of the F3 patients may have transitioned to F4 on follow up, and it is difficult to ascertain the stage of fibrosis at which the decompensation occurred. Repeat liver biopsy or non-invasive imaging with transient elastography was not performed and limits us from identifying the patients that may have progressed from F3 to F4 fibrosis stage.

Regardless of underlying liver disease etiology, advanced hepatic fibrosis portends increased liver-associated complications and mortality.[1013, 1521] However, physicians need to be vigilant as these patients unpredictably may transition to F4 stage. In this regard, data are needed on the use of non-invasive serum and radiological markers including fibroscan and transient elastography, as basis for cost-effective management of these patients in clinical practice.

In summary, our study shows lower rate of and slower development of decompensation and liver disease complications, with better overall and transplant free survival among patients with biopsy conformed bridging or advanced fibrosis (F3) as compared to patients with cirrhosis (F4) irrespective of liver disease etiology. We suggest larger multicenter prospective studies overcoming the limitations identified in this study, to confirm and validate these findings as basis for modifying guidelines and recommendations on follow up of patients with advanced fibrosis and stage 3 liver fibrosis.