fatty liver inhibition

of progression

Understanding and preventing the progression of liver

disease in Non Alcoholic Fatty Liver Disease (NAFLD)

A European Medium-Scale Project supported through the Seventh Framework Programme

for Research and Technological Development.
 fatty liver inhibition
of progression

What is NAFLD?

NAFLD encompasses a spectrum of liver disease associated with insulin resistance, diabetes and obesity. It ranges from
excess fat in the liver (steatosis), to fat in combination with inflammation and liver cell injury (steatohepatitis), to cirrhosis and
its complications, liver cancer in particular. Cirrhosis describes the fibrosis or scarring that occurs as part of a wound healing
response to non alcoholic steatohepatitis, which is commonly called NASH.

Isolated steatosis (fatty liver Steatohepatitis with Mallory-Denk NASH with advanced fibrosis NASH cirrhosis
without inflammation or scarring) bodies and inflammation

Context / Impact
• NAFLD is a major health problem and rapidly becoming one the most common liver diseases worldwide.
• The prevalence of NAFLD in the general population of Western countries is 20-30%.
The prevalence of NAFLD and NASH is increasing in overweight children and adults but also in insulin-resistant individuals of normal
weight. Due to the rapidly progressing epidemics of obesity and diabetes, a large segment of the population is at risk for NAFLD.
Particulary worrisome is the emergence of NAFLD/NASH with significant fibrotic disease in developing countries, even in patients
of normal weight or who are underweight.

Diagnosis and Prognosis

• Currently the only way of diagnosing NASH is by liver biopsy,
an invasive procedure, unsuitable for the screening of at-risk
individuals.
• The development of non-invasive strategies for diagnosis and
staging is therefore a priority for the optimal management of
this disease, as is the validation of consensual pathological
classification.
• The further characterization of severe complications of NASH
(cirrhosis, hepatocellular carcinoma) and of the interaction
with cardiovascular outcomes is urgently needed.
Objectives
NAFLD
The aim of the FLIP consortium (Fatty Liver Inhibition of Progression)
is to understand and prevent the progression of NAFLD to its more Inflammation (hepatitis) Fibrosis
severe forms. The main outcomes of FLIP will be: • presence of inflammatory cells • scarring of the liver due to
• New insights into its progression, particularly in terms of in the liver excessive accumulation of fibrotic
• change in liver structure matrix and related to continuous
identifying the initiating mechanisms and patients at risk. liver damage, inflammation and
• slowed blood circulation hepatocyte death
• Developing innovative diagnostic methods adapted for large- • hepatocyte necrosis
scale screening and prognostic evaluation. • extent of damage can be

ChroNIC LIver DIseAse

• on-going inflammation leads to evaluated through liver biopsy or
• Characterising the key pathways and molecular targets fibrosis selecting non-invasive procedures
amenable to pharmacological therapy, and finally, the • distortion of hepatic architecture
improvement of implementation of lifestyle changes. with incipient portal hypertension

end-stage liver disease Cirrhosis

• liver becomes permanently
hepatic insufficiency/ scarred
hepatic failure
• clinical portal hypertension
develops
hepatocellular carcinoma (hCC)
• liver function is impaired

Methodology and workflow

SP1
SP8
Overall, FLIP will study mechanisms of progression and suggest NAFLD cohort & database; Results dissemination
histological definition exploitation
preventive and therapeutic strategies. The main deliverables are:
• Creation of a prospective European cohort of patients with
standardised inclusion criteria and histologically proven SP2 SP7
Epidemiology Innovative diagnostic and
NAFLD/NASH of NAFLD pronostic markers
• Creation of a prospective European observatory of hepatocellular
carcinoma in NASH SP6
Improved implementation
• Identification of novel epidemiological determinants for NAFLD of preventive strategies
in adolescence and adulthood
• Identification of clinical correlates and mechanisms of SP3 Metabolic factors SP5 Fibrosis factors & carcinogenesis
progression in NAFLD (spanning all the steps of the disease
and answering key issues dealing with the interplay of SP4 Inflammatory factors
metabolic, inflammatory and fibrotic factors in the initiation Clinical correlates and mechanism of progression in NAFLD
and perpetuation of liver injury)
• Validation of improved diagnostic and prognostic markers SP9 Project management
for NAFLD
• Validation of consensual histological classification of NAFLD/
In the long term, FLIP aims to lay the foundations for the
NASH
future of NAFLD research in Europe and create a European
• Improved implementation of preventative strategies in NAFLD Collaborative Research Network on NAFLD.
Consortium

Institute of
Preventive
Medicine

The FLIP consortium has been built around practising clinical hepatologists, basic scientists and 2 industrial partners with an
established track record, and focus on research into the underlying mechanisms and management of patients with NAFLD.

Acknowledgement
The FLIP project is supported by the European Commission through the Seventh Framework Programme for Research and
Development and has been running since January 1st 2010 (duration 36 months).

Project Coordinator: Assistance Publique - Hôpitaux de Paris (APHP),

fatty liver inhibition
of progression

Prof. Vlad Ratziu, +33 1 42 16 10 20, vratziu@teaser.fr

With the support of: ALMA Consulting Group SAS,
Tania Langon, +33 4 72 35 88 48, tlangon@almacg.com

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