Metabolic dysfunction–associated steatotic liver disease

Metabolic dysfunction–associated steatotic liver disease
Specialty	Gastroenterology

Non-alcoholic fatty liver disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome, and may respond to treatments originally developed for other insulin resistant states (e.g. diabetes mellitus type 2), such as weight loss, metformin, thiazolidinediones. Non-alcoholic steatohepatitis (NASH) is the most extreme form of NAFLD, which is regarded as a major cause of cryptogenic cirrhosis of the liver.

Signs and symptoms

Symptoms and associations

Most patients with NAFLD have no or few symptoms. Infrequently patients may complain of fatigue, malaise and dull right upper quadrant abdominal discomfort. Mild jaundice can rarely be noticed. More commonly it is diagnosed as a result of abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day excludes the condition.

NAFLD is associated with insulin resistance and the metabolic syndrome (obesity, combined hyperlipidemia, diabetes mellitus (type II) and high blood pressure).

Secondary causes

NAFLD can also be caused by the following medications (termed secondary NAFLD):

• Amiodarone
• Antiviral drugs (nucleoside analogues)
• Aspirin / NSAIDS
• Corticosteroids
• Methotrexate
• Nifedipine
• Perhexiline
• Tamoxifen
• Tetracycline
• Valproic acid

Diagnosis

Disturbed liver enzymes are common, and liver ultrasound may show steatosis; it may also be used to exclude gallstone problems (cholelithiasis). A biopsy (tissue examination) of the liver is the only widely accepted test which can distinguish NASH from other forms of liver disease, and can be used to assess the severity of the inflammation and resultant fibrosis.

Other tests generally performed are other blood tests (erythrocyte sedimentation rate, glucose, albumin, renal function etc.) As the liver is important in coagulation, some coagulation studies will generally be done, especially the INR (international normalized ratio). To distinguish this disease from viral hepatitis, blood tests (serology) are generally done (hepatitis A, B, C, EBV, CMV and herpes viruses, as well as rubella) to ensure these are not playing a role. Additionally, autoimmune causes are ruled out with serology. TSH is warranted, as hypothyroidism is more prevalent in NASH patients.

Pathophysiology

NAFLD is considered a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic steatosis). A fatty liver can remain without disturbing the function of the liver, but by varying mechanisms and possible insults to the liver, may progress to outright inflammation of the liver. Over time this may lead to cirrhosis. The exact reasons and mechanisims by which this disease progresses from one entity to the next is a subject of much research and debate.

The main cause is still unknown. However both obesity and insulin resistance likely play a strong role in this disease process.

Treatment

Trials are presently being conducted to optimise treatment of NASH. Generally, treatment of underlying diabetes mellitus will be undertaken, including weight loss and insulin sensitising drugs (metformin, pioglitazone or rosiglitazone).

History

NASH was described in 1980 in a series of patients of the Mayo Clinic. Its relevance and high prevalence were recognized mainly in the 1990s.

External links

• Medscape article on NASH.
• MEDICINENET article on Steatosis.
• NIH page on Nonalcoholic Steatohepatitis