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Metabolic hepatic steatosis and alcohol-associated liver disease

Pictogramme horloge December 2021

Metabolic steatopathies are the most frequent cause of disrupted liver function. They should be considered when faced with hepatic steatosis on imaging, an increase in transaminases or hyperferritinaemia in a patient with a metabolic condition.

Alcohol-associated liver diseases must also be screened and handled to prevent evolution towards cirrhosis and the risk of associated hepatocellular carcinoma. The French Association for the Study of the Liver (AFEF) published recommendations on the non-invasive follow-up and diagnosis of chronic liver diseases in July 2020[1] and updated its recommendations regarding the invasive and non-invasive diagnosis of steatosis fibrosis during alcohol-associated liver disease in January 2021[2] (Table 1).


Metabolic hepatic steatosis or metabolic steatopathies or NAFLD (Non-Alcoholic fatty-liver disease) are defined by a continuum of liver lesions linked to insulin resistance and metabolic inflammation and are associated with being overweight or obese. They tend to be observed in subjects consuming fewer than three (or three) glasses of alcoholic beverages per day in men and fewer than two (or two) glasses of alcoholic beverages per day in women.

Alcohol-associated liver disease is also characterised by a continuum of liver lesions, linked, in this case, to a chronic excessive consumption of alcohol (improper use). The danger threshold varies from one individual to another but is seen above three glasses of alcoholic drinks per day in men and two glasses of alcoholic drinks per day in women.


NAFLD is defined by the presence of hepatic steatosis without excessive alcohol consumption, steatogenic treatment or other cause of chronic liver disease [1].

In 80% of cases, it is an isolated, benign hepatic steatosis. However, approximately 20% of patients suffering from NAFLD also show liver cell lesions and inflammation, defining what is termed Non-Alcoholic SteatoHepatitis or NASH (Non-Alcoholic SteatoHepatitis) and, of these 10%, 10% will develop cirrhosis.

In France, it is estimated that approximately 30 to 50% of people are overweight and 15% obese. NAFLD is the primary cause of chronic liver disease. It involves 18 to 25% of the general population and NASH approximately 3% (0.5% at an advanced fibrosis stage).

By the same token, in patients with alcohol-associated liver disease, 70 to 80% are seen in consultation at simple steatosis stage (Alcoholic Fatty Liver – AFL); 20 to 30% have Alcoholic SteatoHepatitis (ASH) with associated liver inflammation and lesions.

Improper use of alcohol affects 20 to 25% of the population; around 18% suffer from alcoholic steatosis (1% at an advanced stage of steatohepatitis or alcoholic cirrhosis)

Natural history

The natural history of metabolic or alcoholic hepatic steatosis is recent: they evolve from simple steatosis to cirrhosis (F4), via steatohepatitis and fibrosis (F1 to F3). However, patients with metabolic hepatic steatosis die more often from cardiovascular and non-liver cancer causes, taking into account the predominant metabolic context. Those with severe alcoholic hepatitis die more from cancer, violent death or infection.

For metabolic hepatic steatosis, risk factors include excessive an imbalanced calorie consumption, lack of physical activity, a sedentary lifestyle; for alcohol-associated liver disease patients, disorders in the use of alcohol, whose toxic action is directly on the liver as well as multi-systemic. Genetic factors have also been described (various polymorphisms involved). Finally, a deregulation of the liver-intestine axis with modification of gut microbiota associated with a modification to the intestinal permeability would also appear to be common to the two pathologies.

Suggestive diagnostic symptoms and handling

Table 1. Suggestive diagnostic symptoms and handling.

Metabolic hepatic steatosisAlcohol-associated liver disease
Major points:
raised gamma glutamyl transferase (GGT), ferritin and triglycerides
ultrasound hepatic steatosis
Hepatic cytolysis
Physical examination and interview
Weight history: body mass index (BMI) and increased waist circumference, high blood pressureChronic alcohol consumption, physical signs of chronic alcohol intoxication, raised CDT and MCV
Non-liver symptoms

Fatigue, anxiety, depression

Sleep apnoea/hypopnoea syndrome


Cardiovascular complications (primary cause of death in non-cirrhotic patients), type 2 diabetes, renal impairment

Cancer: colon, breast, liver (second cause of death in non-cirrhotic patients)

Psychiatric disorders, addiction, anxiety-depression, suicide, central and peripheral neurological disorders, social disorders, violence

Alcoholic heart disease

Acute/chronic pancreatitis, secondary diabetes

IgA nephropathy

Cancer: upper airway-digestive tracts, breast, colon

Non-invasive assessment of liver fibrosis

Hepatic elastography: FibroScan®, ARFI, MRI, etc.

Patented blood tests: Fibrotest®, Fibrometer®, ELF®, etc.

“Free” blood tests: FIB-4, NAFLD Fibrosis score

Hepatic elastography: FibroScan®

Patented blood tests: Fibrotest®, Fibromètre®

Alcohol (diagnostic thresholds established according to AST and bilirubin values [2])

“Free” blood test: FIB-4

Treatment of the cause

Weight loss: hygiene-nutrition rules

Bariatric surgery, bariatric endoscopy?

Optimal treatment of type 2 diabetes and metabolic anomalies

Stopping alcohol consumption

Handling the addiction, psychological, psychiatric side

Drugs reducing alcohol uptake

Present and future handling, prevention of relapse

Specific treatments (to come) targeting the metabolism, inflammation, stress/cell death, fibrosis and liver-intestine axis

Modulation of the gut microbiota (to come: pre-, pro-, syn-, anti-biotic, faecal transplant?

Addressing the complications of cirrhosis: portal hypertension, hepatocellular carcinoma

Treatment of liver failure

Liver transplant

Therapeutic trials in progress: FXR agonists, TRH agonistsb, GLP1 agonists ± GIP ± glucagon, PPAR agonists, etc.

Risk of recurrence of NASH: liver transplant

Corticotherapy in the case of severe alcoholic hepatitis

Liver transplant: risk of recurrence of alcoholism post-liver transplant

ALAT: alanine aminotransferase, AST: aspartate aminotransferase, MRI: magnetic resonance imaging, NASH: Non-Alcoholic SteatoHepatitis, FIB-4: Fibrosis-4 index

Screening for chronic liver disease: interest of FIB-4

All doctors handling a patient with at least one hepatic steatosis risk factor should, at the very least, prescribe a liver ultrasound examination and laboratory tests with the calculation of the FIB-4 (Fibrosis-4 index).
FIB-4 is a screening test for hepatic fibrosis, calculated from platelet count, patient age and transaminases, available on the internet and free of charge[3].

An FIB-4 index < 1.45 eliminates the diagnosis of cirrhosis with a negative predictive value of 90%;

An FIB-4 index > 3.25 is in favour of this diagnosis (positive predictive value 65%)[3].

Just as the calculation of filtration flow features in laboratory records, so should FIB-4 for all adults whose platelet count and transaminases dosage are requeste[4].


Metabolic hepatic steatosis and alcohol-associated liver disease are frequent pathologies associated with significant hepatic and non-hepatic morbidity-mortality. They share common points and differences in their physiopathology and handling with crucial improvements in their care paths, notably with non-invasive tests assessing hepatic fibrosis and therapeutic innovations.



[1] Association française pour l’étude du foie. Recommandations pour le diagnostic et le suivi non-invasif des maladies chroniques du foie. July 2020. https://afef.asso.fr/wp-content/uploads/2020/07/DNI-VERSION-FINALE-RECO-2020.pdf

[2] Association française pour l’étude du foie. Recommandations pour le diagnostic invasif et non invasif de la fibrose et de la stéatose au cours de la maladie du foie liée à l’alcool. January 2021.

[3] http://sdbio.eu/images/stories/3_DOCS_SDB/sdb_%20fib-4F_ok.pdf

[4] Communication de Rodolphe Anty (CHU Nice), lors du forum du foie Siemens Healthcare, 03 September 2020.

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