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Non-alcoholic fatty liver disease
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 and 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.
NASH was first described in 1980 in a series of patients of the Mayo Clinic. Its relevance and high prevalence were recognized mainly in the 1990s.
Additional recommended knowledge
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 may, rarely, be noticed. More commonly NAFLD is diagnosed following abnormal liver function tests during routine blood tests. By definition, alcohol consumption of over 20 g/day (about 25ml/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).
NAFLD can also be caused by the following medications (termed secondary NAFLD):
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 test which is widely accepted as definitively distinguishing NASH from other forms of liver disease, and can be used to assess the severity of the inflammation and resultant fibrosis.
Other tests are often carried out. Relevant blood tests include erythrocyte sedimentation rate, glucose, albumin, and renal function etc. As the liver is important in coagulation, some coagulation studies are often carried out, especially the INR (international normalized ratio). Blood tests (serology) are usually carried out to rule out viral hepatitis (hepatitis A, B, C, EBV, CMV and herpes viruses), rubella, and autoimmune causes. TSH is warranted, as hypothyroidism is more prevalent in NASH patients.
NAFLD is considered to cover a spectrum of disease activity. This spectrum begins as fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty without disturbing liver function, but by varying mechanisms and possible insults to the liver may also progress to outright inflammation of the liver. When inflammation occurs in this setting, the condition is then called NASH. Over time up to 20 percent of patients with NASH may develop cirrhosis. Cigarette smoking is not associated with an increased risk of developing NASH.
The exact cause of NAFLD is still unknown. However, both obesity and insulin resistance probably play a strong role in the disease process. The exact reasons and mechanisms by which the disease progresses from one stage to the next are the subject of much research and debate.
One debated mechanism proposes a "second hit", or further injury, enough to cause change that leads from hepatic steatosis to hepatic inflammation. Oxidative stress, hormonal imbalances and mitochondrial abnormalities are potential causes for this "second hit" phenomenon.
Trials to optimise treatment of NASH are being conducted (2007), and no treatment has yet emerged as the "gold standard". General recommendations include improving metabolic risk factors and reducing alcohol intake.
A large number of treatments for NAFLD have been studied. While many appear to improve biochemical markers such as alanine transaminase levels, most have not been shown to reverse histological abnormalities or reduce clinical endpoints:.
Categories: Gastroenterology | Hepatitis
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Non-alcoholic_fatty_liver_disease". A list of authors is available in Wikipedia.|