[PDF] Non-alcoholic steatohepatitis (NASH): Definition natural history and





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HEPAMAP: A Roadmap For Hepatology Research In Europe: An

Research from EASL and other liver organizations reveals that up to 44% of these people are likely to suffer from non-alcoholic fatty liver disease (NAFLD).



Non-alcoholic steatohepatitis (NASH): Definition natural history and

3 déc. 2018 A roadmap for hepatology research in Europe: An overview for policy makers. EASL 2015. 3% NASH. (EU: ~10 M). 1974 mean BMI ?.



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EASL now undertakes considerable efforts to work with the Commission and European Parliament not only to place greater emphasis on liver disease research.



EASLs response to the European Commission call for evidence on

17 févr. 2022 Mortality from liver cancer has increased in most European ... Liver (EASL) and European Organisation for Research and Treatment of Cancer.



European Association for the Study of the Liver – Annual Report 2016

EASL is a medical association driven by Governing Board members dedicated to pursuing excellence in liver research clinical practice of liver disorders



Year of the Nurse

liver research clinical practice of liver disorders



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23 juin 2022 EASL is a medical association dedicated to pursuing excellence in liver research clinical practice of liver disorders



European Reference Network (ERN) RARE- LIVER

16 avr. 2019 The European Commission and the Agency do not accept any ... EASL Clinical Practice Guidelines on nutrition in chronic liver disease .



50 years of EASL – From a European to a global perspective

launch of HEPAMAP just last month in the European Parliament in Brussels. We presented the roadmap for liver disease research in Europe to our policy makers 



ERN-RARE-LIVER

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HEPAMAP - easleu

ROADMAP FOR HEPATOLOGY RESEARCH IN EUROPE: AN OVERVIEW FOR POLICY MAKERS Hepamap includes the following subject areas: EASL has taken steps to accompany Hepamap with a number of collaborative approaches: 1) Viral hepatitis: basic science 2) Viral hepatitis: clinical / translational 3) Alcoholic Liver Disease and Non-Alcoholic Liver Disease



About EASL - EASL-The Home of Hepatology

EASL the European Association for the Study of the Liver founded in 1966 is a medical association dedicated to pursuing excellence in liver research to the clinical practice of liver disorders and to providing education to all those interested in hepatology As of 2021 EASL serves more than 4200 members



THE INTERNATIONAL LIVER CONGRESS™ VIENNA AUSTRIA 10-14

interested in hepatology Whilst the roots of the association were founded in Europe in 1966 EASL continues to engage globally with all stakeholders in the liver field wherever they are based Our aim is to spread knowledge expertise and best practice as well as the latest scientific breakthroughs in hepatology and the International Liver



Searches related to a roadmap for hepatology research in europe easl filetype:pdf

The European Association for the Study of the Liver (EASL): Promoting liver research and education across Europe since 1966 EASL is Europe’s foremost organisation dedicated to advancing scientific medical and public understanding of the liver and liver disease Since its foundation in 1966 EASL has established itself as a

How has HCV-related liver disease changed clinical care?

    Clinical care for patients with HCV-related liver disease has advanced considerably during the last couple of decades, thanks to an enhanced understanding of the pathophysiology of the disease, and because of developments in diagnostic procedures and radical improvements in therapy and pre- vention.

What are the EASL-Aleh clinical practice guidelines?

    EASL-ALEH Clinical Practice Guidelines: non- invasive tests for evaluation of liver disease severity and prognosis. J Hepatol 2015;63:237–264.

How is cirrhosis assessed in patients with chronic hepatitis C?

    Patients with cirrhosis need to be assessed for portal hypertension, including oesophageal varices. In chronic hepatitis C, non-invasive methods should be used instead of liver biopsy to assess liver disease severity prior to therapy.
Non-alcoholic steatohepatitis (NASH): Definition natural history and

Non-alcoholic steatohepatitis (NASH):

Definition

, natural history and current therapeutic interventions

Frank Tacke

University Hospital Aachen, Germany

EMA Workshop on Liver Diseases

London, Dec 3rd, 2018

Disclosures Frank Tacke

•Research support (materials, funding):

Tobira/Allergan, Galapagos, Inventiva, BMS

•Speaker/Consulting:

Tobira/Allergan, Gilead, AbbVie, BMS, Falk,

Boehringer, Galapagos, Intercept, Inventiva

Non-alcoholic Fatty Liver Disease:

The epidemiological challenge

Total population 20 30
% NAFLD (EU: ~116 M) 0.2%-0.5% HCC (EU 200,000 -

500,000

HEPAMAP. A roadmap for hepatology research in Europe: An overview for policy makers. EASL 2015

3% NASH

(EU: ~10 M) 1974
m

BMI (kg/m²)

NCD Risk Factor Collaboration, Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698

population-based measurement studies with 19·2 million participants. Lancet. 2016; 387(10026):1377-96 105 millions BMI>30 641 millions BMI>30

Non-alcoholic Fatty Liver Disease:

The epidemiological challenge

Total population 20 30
% NAFLD (EU: ~116 M) 0.2%-0.5% HCC (EU 200,000 -

500,000

HEPAMAP. A roadmap for hepatology research in Europe: An overview for policy makers. EASL 2015

3% NASH

(EU: ~10 M)

Projection for Germany

NAFLD NASH 2016
2030
NASH + 42% NASH-

Zirrhose

x 2.5

Estes C, et al. J Hepatol. 2018; 69(4):896-904

18.4 15.9 1.2 0.7 0.4 0.2 0.0 5.0 10.0 15.0 20.0 25.0

TotalF0F1F2F3F4

Millions

20.9
17.0 1.6 1.1 0.8 0.5 0.0 5.0 10.0 15.0 20.0 25.0

TotalF0F1F2F3F4

Millions

Non-alcoholic Fatty Liver Disease:

The epidemiological challenge

Total population 20 30
% NAFLD (EU: ~116 M)

0.2%-0.5% HCC

(EU 200,000 -

500,000

HEPAMAP. A roadmap for hepatology research in Europe: An overview for policy makers. EASL 2015

3% NASH

(EU: ~10 M)

Projection for UK

NAFLD NASH 2016
2030
NASH + 43% NASH-

Zirrhose

x 2

Estes C, et al. J Hepatol. 2018; 69(4):896-904

14.1 12.1 0.9 0.5 0.3 0.2 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0

TotalF0F1F2F3F4

Millions

16.9 13.8 1.2 0.8 0.6 0.4 0.0 2.0 4.0 6.0 8.0 10.0 12.0 14.0 16.0 18.0

TotalF0F1F2F3F4

Millions

Non-alcoholic Fatty Liver Disease:

The clinical challenge

•Old(er) age, high(er) body-mass index •Many comorbidities (diabetes, kidney, cardiovascular...) •Substantial proportion unaware of their liver condition •High(er) rate of malignancies

Non-alcoholic Fatty Liver Disease:

The clinical challenge

https://broadly.vice.com

PCOS (Polycystic Ovary Syndrome)

Hypothyroidism

Colorectal cancer

Cardiovascular Disease

Type 2 Diabetes

Chronic Kidney Disease

OSAS (Sleep Apnea)

NAFLD

Osteoporosis

Byrne CD & Targher G, J Hepatol 2015;

62
: S47-S64

Extrahepatic complications of

non-alcoholic fatty liver disease

Management of fatty liver disease:

EASL multidisciplinary Clinical Practice Guideline EASL-EASD-EASO CPG NAFLD. J Hepatol 2016; 64:1388-402 •Chairs -EASL: Giulio Marchesini -EASD: Michael Roden -EASO: Roberto Vettor •Panel members

-EASL: Christopher P Day, Jean-François Dufour, Ali Canbay, Valerio Nobili, Vlad Ratziu, Herbert Tilg

-EASO: Gema Frühbeck, Lisbeth Mathus-Vliegen •Reviewers -Elisabetta Bugianesi, Helena Cortez-Pinto, Stephen Harrison

Natural history of fatty liver disease:

Definitions of NAFLD, NAFL and NASH

*According to histological analysis or proton density fat fraction or >5.6% by proton MRS or quantitative fat/water-selective MRI;

NAFLD •Excessive hepatic fat accumulation with IR •Steatosis in >5% of hepatocytes* •Exclusion of secondary causes and AFLD NASH NAFL •Pure steatosis •Steatosis and mild lobular inflammation

Cirrhotic

F4 fibrosis Fibrotic

2 3 fibrosis Early

F0/F1 fibrosis

HCC Definitive diagnosis of NASH requires a liver biopsy EASL-EASD-EASO CPG NAFLD. J Hepatol 2016; 64:1388-402

Diagnosis and staging of fatty liver disease:

Role of liver biopsy

*Should not be used for initial diagnosis •Liver biopsy is essential for the diagnosis of NASH -Clinical, biochemical or imaging measures cannot distinguish NASH from steatosis •NAFL encompasses -Steatosis alone plus ONE of lobular or portal inflammation OR ballooning •NASH requires -Steatosis AND -Lobular or portal inflammation AND -Ballooning •NAS scoring indicates disease severity*

Recommendations

NASH has to be diagnosed by a liver biopsy showing steatosis, hepatocyte ballooning and lobular inflammation A 1

Grade of evidence

Grade of recommendation

EASL-EASD-EASO CPG NAFLD. J Hepatol 2016; 64:1388-402

Diagnosis and staging of fatty liver disease:

Role of liver biopsy

Courtesy of Dr. Thomas Ritz, Institute of Pathology, University Hospital Aachen normal

NAFLD NASH

fibrosis

NAFLD / NASH

NASH-fibrosis

cirrhosis HCC 0.25 3% /year 0.3-2.6% /year 0.04 0.3% /year

Natural history of fatty liver disease:

Estimated progression rates

NAFLD

1240% NASH

~10% NASH-fibrosis (F3) 30
-50% NASH-cirrhosis

PYF, patients years of follow-up

Mortality rate ratio = actual mortality versus expected mortality

05101520253035404550

Stage 1Stage 2Stage 3Stage 4

All CauseLiver Related

Dulai

PS, et al. Hepatology 2017; 65: 1557-1565.

Mortality rate by fibrosis stage

Mortality

rate per 1 000 PYF •Meta-analysis of 5 studies on fibrosis-related mortality •1,495 NAFLD patients with 17,452 patient years of follow-up

05101520253035404550

Stage 1Stage 2Stage 3Stage 4

All CauseLiver Related

Mortality rate ratio by fibrosis stage

Mortality rate ratio

1.58 (1.19 -2.11) 2.52 (1.85-3.42) 3.48 (2.51-4.83) 6.40 (4.11 -9.95) 1.41 (0.17-11.95) 9.57 (1.67 -54.93) 16.69 (2.92 -95.36) 42.30 (3.51 -510.34)

Fibrosis determines the prognosis of

non-alcoholic fatty liver disease Vilar-Gomez E, et al. Gastroenterology. 2018; 155(2):443-457. •458 NAFLD patients (bridging fibrosis, F3, n=159; Child A5 cirrhosis, n=222; Child A6 cirrhosis, n=77); 4 tertiary centers, mean follow-up 5.5 years •Deaths: n=37, Liver Transplant: n=37, decompensation: n=88, Liver Cancer (HCC): n=41, Cardiovascular events: n=14, non-liver cancer: n=30

Fibrosis determines the prognosis of

non-alcoholic fatty liver disease Vilar-Gomez E, et al. Gastroenterology. 2018; 155(2):443-457.

Fibrosis determines the prognosis of

non-alcoholic fatty liver disease •458 NAFLD patients (bridging fibrosis, F3, n=159; Child A5 cirrhosis, n=222; Child A6 cirrhosis, n=77); 4 tertiary centers, mean follow-up 5.5 years •Deaths: n=37, Liver Transplant: n=37, decompensation: n=88, Liver Cancer (HCC): n=41, Cardiovascular events: n=14, non liver cancer: n=30 Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016; 13:196-205.

Low-risk profile

BMI < 29.9

Age < 40 yrs

No T2DM or

metabolic syndrome features

Noninvasive fibrosis estimation:

•FIB-4 < 1.30 •APRI < 0.5 •NFS < -1.455

FibroScan < 5 kPa

Intermediate-risk profile

BMI > 29.9

Age > 40 yrs

Multiple features of the metabolic syndrome

Noninvasive fibrosis estimation:

•FIB-4 1.30-2.67 •APRI 0.5-1.5 •NFS -1.455-0.675

FibroScan 6-11 kPa

High risk profile

ALT level > AST level

Platelets < 150,000

Noninvasive fibrosis estimation:

•FIB-4 > 2.67 •APRI > 1.5 •NFS > 0.675

FibroScan > 11 kPa

Hepatic steatosis on imaging

± elevated serum ALT levels

Evaluate alcohol

consumption Confirm NAFLD Exclude alternate

Follow and reassess as

risk factors evolve Consider liver biopsy

Consider liver biopsy or

confirmatory testing for cirrhosis (eg, MRE)

A potential

algorithm for risk assessment in non- alcoholic fatty liver disease

Low-risk profile

BMI < 29.9

Age < 40 yrs

No T2DM or

metabolic syndrome features

Noninvasive fibrosis estimation:

•FIB-4 < 1.30 •APRI < 0.5 •NFS < -1.455

FibroScan < 5 kPa

Intermediate-risk profile

BMI > 29.9

Age > 40 yrs

Multiple features of the metabolic syndrome

Noninvasive fibrosis estimation:

•FIB-4 1.30-2.67 •APRI 0.5-1.5 •NFS -1.455-0.675

FibroScan 6-11 kPa

High risk profile

ALT level > AST level

Platelets < 150,000

Noninvasive fibrosis estimation:

•FIB-4 > 2.67 •APRI > 1.5 •NFS > 0.675

FibroScan > 11 kPa

Hepatic steatosis on imaging

± elevated serum ALT levels

Evaluate alcohol

consumption Confirm NAFLD Exclude alternate

Follow and reassess as

risk factors evolve Consider liver biopsy

Consider liver biopsy or

confirmatory testing for cirrhosis (eg, MRE)

A potential

algorithm for risk assessment in non- alcoholic fatty liver disease

EASL-Guideline 2016:

Recommendation for liver biopsy, if

NASH or fibrosis is suspected

Rinella ME, Sanyal AJ. Nat Rev Gastroenterol Hepatol. 2016; 13:196-205.

NAFLD / NASH

NASH-fibrosis

cirrhosis HCC 0.25 3% /year 0.3-2.6% /year 0.04 0.3% /year

Natural history of fatty liver disease:

Estimated progression rates

NAFLD / NASH

NASH-fibrosis

cirrhosis HCC 0.25 3% /year 0.3-2.6% /year 0.04 0.3% /year

Natural history of fatty liver disease:

Progression and Regression

NAFLD / NASH

NASH-fibrosis

cirrhosis HCC 0.25 3% /year 0.3-2.6% /year 0.04 0.3% /year

Progression of fatty liver disease:

Relevance of cofactors and lifestyle

Diabetes

Obesity

Genetic

factors (PNPLA3, TM6SF2...) Age

Alcohol

Lifestyle

Coffee

Exercise

Mediterranean diet

Vegetables

Normal

Steatosis

NASH

Cirrhosis

-Weight reduction (nutrition,

GLP1-agonists, bariatric surgery)

-Lifestyle changes -optimal diabetes therapy (metformin, GLP1-agonists etc.) NASH-

Fibrosis

Current therapeutic strategies in non-alcoholic

fatty liver disease

Physical

activity

Aerobic & Resistance activity

independently: -Reduce liver fat -NASH and fibrosis - little evidencequotesdbs_dbs30.pdfusesText_36
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