Non-alcoholic steatohepatitis: Get informed

Definition

NASH, a complication of NAFLD

Non-alcoholic fatty liver disease (NAFLD) is also called fatty liver disease. It occurs when a significant amount of fat accumulates in the liver (5 to 10% of the weight of the organ). It causes little damage if it stays at this stage.

However, non-alcoholic steatohepatitis (NASH) is a more severe form derived from NAFLD. At this stage, the liver cells have lesions that may form hepatic fibrosis (the cells can no longer repair the lesions and then create scar tissue that replaces the cells but has no function and can interfere with blood circulation). The main risk of NASH is progression to cirrhosis (a chronic liver disease that causes many complications) and hepatocellular carcinoma (HCC), i. e. liver cancer.

A few figures

The prevalence of non-alcoholic steatohepatitis is estimated at between 20 and 30% in the Western world and that of NASH at between 2 and 3%. Estimates are much higher in obese people with 65-75% hepatic steatosis (85-95% in morbid obesity) and 15-20% NASH.

The risk of progression to cirrhosis is estimated at 12% in 8 years. The risk of liver cancer is known but not quantified. More than half of people with NASH have type 2 diabetes and about 80% have dyslipidemia.

How to detect NAFLD?

The symptoms

Patients with NAFLD generally do not experience symptoms, but may sometimes have:

- fatigue

- sensitivity of the right hypochondrium (hypochondrules are the parts of the abdomen located on either side of the abdomen, above the line formed by the navel)

- hepatomegaly (an increase in liver volume that can be noticed by palpation)

The exams

Standard imaging tests, including ultrasound and MRI, can detect hepatic steatosis to varying degrees but do not distinguish between NASH and simple steatosis. Biological markers and fibroscan (a technique that determines the elasticity and hardness of the liver by vibration) are two innovative approaches to differentiate them but are still being evaluated.

Currently, the only way to diagnose NASH, and therefore a potential risk of cirrhosis and liver cancer, is by liver biopsy, which means taking a sample from the liver for analysis. Given the risks and costs of this test, several algorithms have been developed in recent years to try to distinguish between patients at high risk of NASH for whom a diagnostic PBH would be useful.

The main risk factors considered are an age greater than 45 years, obesity, type 2 diabetes and an ASAT/ALAT ratio greater than 1 (ratio between two types of enzymes mainly present in the liver). Hepatic biopsy puncture (HBP) should also be considered in patients with persistent elevations of hepatic enzymes despite adequate treatment of their metabolic syndrome. This puncture allows the liver tissue to be removed and a histological (and therefore tissue) examination of the liver cells to be carried out.

NAFLD and NASH treatments

No drugs or surgical procedures are recommended for the treatment of NAFLD. The risk of developing diabetes and cardiovascular risk should be reduced by increasing physical activity, improving nutrition and controlling blood lipids and high blood pressure. It is also necessary to limit or even stop smoking, because all these actions reduce the level of liver enzymes.

Obesity reduction surgery and some drugs such as metformin, pioglitazone, ARBs II and statins could have a similar impact, but these results should be interpreted with caution and further studies are needed.

It is also recommended to take vitamin E (800 IU/d). However, it is not yet clear whether this catch is not harmful in the long term. An increased risk of stroke and prostate cancer is reported.

Pioglitazone is also categorised by these same international recommendations, but its long-term use is associated with weight gain, a risk of osteoporosis and even a risk of bladder cancer.

Medical research

The search for new drugs is currently very active in the field of hepatic steatosis, all the more as the decreased physical activity of populations will probably increase the number of cases of obesity.

Potential drugs include obeticholic acid (selective Farnesoid X receptor agonist), elafibranor (double agonist of Peroxisome proliferator-activated receptor -PPAR- alpha and PPAR delta), Cenicriviroc (C-C chemokine receptor antagonist type 2 -CCR2- and CCR5) and selonsertib (apoptosis signal-regulating kinase 1 inhibitor) are in Phase 3 international therapeutic trials.

Modulation of the intestinal microbiota (the microorganisms that live in the intestine) using prebiotics, probiotics, symbiotics, antibiotics, or even fecal transplantation is a possibility currently under evaluation.

Sources

http://www.worldgastroenterology.org/

Non-alcoholic fatty liver disease : an overview of prevalence, diagnosis, pathogenesis and treatment considerations. Preiss D, Sattar N. Clin Sci (Lond). 115(5):141-50

Association Française de Formation Médicale Continue en Hépato-Gastro-Entérologie