Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting approximately 25% of the population in Western countries. NAFLD is a continuum of disease states ranging from simple steatosis to non-alcoholic fatty liver disease (NASH) which can progress to fibrosis, cirrhosis and may lead to liver transplantation.

Metabolic steatopathy is defined by the presence of steatosis (accumulation of intrahepatic fat) in the presence of metabolic risk factors and in the absence of secondary causes of steatosis (excessive alcohol consumption of more than 20g/day for women and 30 g/day for men, taking medication, etc). It can coexist with other causes of chronic liver disease (eg viral hepatitis, etc.).

Key figures

Ref. Serfaty Gastroenterology 2020, CONSTANCES cohort


New cases of NASH in France
in 2016


New cases of NASH in Europe
in 2016


Mean age of NASH onset, mostly male


of the adult population concerned by NAFLD in France


of the adult population concerned by NAFLD in the world


of the adult population concerned by NAFLD in the United States


deaths / year in France by NASH


death / year in Europe by NASH


death / year in the USA by NASH

Metabolic risk factors

  • Obesity
  • Type 2 diabetes
  • Elevated transaminases (enzymes found in liver cells)

Symptoms / Severity

Fatty liver disease (NASH) is a silent disease. It is most often diagnosed incidentally.

Gravity factors:

  • Steatosis visible on ultrasound in the presence of metabolic risk factors
  • Increased transaminases and steatosis on ultrasound
  • Elevated transaminases and metabolic risk factors
  • Hyperferritinemia associated with metabolic risk factors
  • Diagnosis sometimes at the stage of cirrhosis

Gravity spectrum:

  • Isolated steatosis: interesting accumulation of intrahepatic fat> 5% of hepatocytes
  • Steatohepatitis (NASH): accumulation of intrahepatic fat associated with necro-inflammation, with or without fibrosis
  • Cirrhosis: 15% to 30% of NASH patients
  • Decompensated cirrhosis, hepatocellular carcinoma and liver transplantation

Causes / Risk factors

Closely related to insulin resistance and metabolic risk factors, the most important of which are:

  • Obesity (particularly visceral obesity – Waist circumference> 102/88cm men/women)
  • Type 2 diabetes (steatosis is present in> 70% of diabetic patients; diabetes is an established risk factor for the progression of fibrosis)
  • High blood pressure
  • Dyslipidemia
  • sleep apnea
  • Aging
  • Genetic (PNPLA3, TM6SF2) and epigenetic factors (case of familial aggregation in relation to environmental and epigenetic factors)

The risk of NAFLD increases in the presence of multiple risk factors (eg. prevalence of steatosis> 91% in the presence of diabetes and obesity

Evolution / Consequences

  • Patients with isolated steatosis progress little or not at all and have a mortality comparable to the general population.
  • Patients with NASH are at risk of disease progression: progression of fibrosis by about 1 stage every 7 years; cirrhosis (15% to 30% of patients with NASH); hepatocellular carcinoma; liver transplantation (currently the 2nd leading cause of liver transplantation in the US).
  • Overall mortality increases with the severity of liver damage and becomes higher than in the general population from stage 2 of fibrosis.
  • Liver-related mortality is the first cause of death in cirrhotic patients (2 to 3 times increase compared to the general population in the case of compensated cirrhosis, and> 10 times vs. the general population in cases of decompensated cirrhosis).
  • In non-cirrhotic patients the leading cause of death is cardiovascular disease and extrahepatic cancers

How is it treated?

Hygieno-dietetic measures (diet, physical exercise) and optimal control of risk factors, in particular diabetes control and weight loss, are strongly recommended in all patients regardless of the severity of the disease. hepatic.

Bariatric surgery, for obese patients, allows a significant improvement of liver damage in patients without advanced fibrosis. On the other hand, the results of bariatric surgery are more modest in patients with cirrhosis or with advanced fibrosis (≥ F3)

Currently, there is no approved effective treatment for NASH. Only dynamic and innovative research will improve patient care.

Is there research on this pathology?

The IHU-ICAN teams are collaborating on several research projects against NASH:

  • CORONASH for natural history and diagnostic tools
  • EU-PEARL for processing.

ICAN's response

The AP-HP and ICAN teams created the NASH clinic to offer patients an innovative, multidisciplinary and personalized care pathway. This course aims to anticipate and intercept the complications of NASH (early atherosclerosis, arterial hypertension, diabetes, etc.) and to offer personalized care to each patient.

The NASH clinic is the first hospital structure for the diagnosis and multidisciplinary management of patients with metabolic steatosis in France.

Discover the NASH clinic