Thursday, 17 April 2008

What is non-alcoholic fatty liver disease?

Non-alcoholic fatty liver disease (NAFLD) is a fairly recently-recognised entity that incorporates a range of liver disease all characterised by a fatty liver not caused by alcohol.

It can be subdivided into three elements. In each case, there can be progression to the next stage, but most people don't progress there. The stages are:
  • Steatosis (fatty liver) - simple fat accumulation within the hepatocytes (note, not the adipocytes). It is generally believed to be a harmless condition.

  • Non-alcoholic steatohepatitis (NASH) - fatty accumulation as above plus associated surrounding inflammation and hepatocyte necrosis. Eventually, this process can progress to include fibrosis, which leads smoothly towards...

  • Cirrhosis - obviously not limited to the NAFLD spectrum (it can be caused, and far more commonly is, by other things), but a definite potential outcome of long-standing NASH.
It is ultimately unclear what causes NAFLD. From what I can gather, the number one cause is insulin resistance. Insulin resistance refers to a disruption of the signalling pathways between insulin and the body's cells, and tends to cause alterations in the cellular handling of both carbohydrates and lipids. Of particular relevance, it appears to stimulate uptake of triglycerides by the liver, where they are subsequently stored in vesicles within the hepatocytes.

Although some authorities prefer to limit the definition of NAFLD to that caused by insulin resistance, most centres recognise insulin resistance as only the most common cause of NAFLD. The list of other causes is extensive, and includes drugs, toxins, malnutrition, total parenteral malnutrition, dyslipidaemias, etc.

Albeit controversially, it is also hypothesised that a second-hit is required to transform steatosis into NASH. Oxidative stress [Wiki defn: imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage], hormonal imbalances and mitochondrial abnormalities (secondary to fat accumulation) are potential suspects.

Diagnosis is primarily one of exclusion, but is suggested by:
  • unexplained raised transaminases (AST, ALT) - things like viral hepatitis must be excluded

  • in associated with an enlarged fatty liver - this can be presumptively shown on ultrasound (hyperechoic/bright liver), CT or even MRI. Only a liver biopsy is definitive, but this is usually not necessary.

  • if a significant alcohol history can be excluded

Treatment is again controversial, and much more research is required before any sort of consensus can be reached. Currently, if the cause is insulin resistance, many authorities recommend treating the 'metabolic syndrome' aspects of the condition; specifically, weight loss, and (diabetic) drugs that reduce insulin resistance (metformin and the thiazolidinediones) are promising.

As you can probably tell, the entity of NAFLD is one in evolution. Much of the above will change, and most of the above would already be criticised by numerous people in the field. Be that as it may, it may perhaps still prove useful.


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  3. Many people who are overweight or who have diabetes, prediabetes, or high cholesterol may also have liver damage without knowing it. Nonalcoholic steatohepatitis (NASH) is a liver disease that occurs when a buildup of fat in the liver causes irritation (inflammation) and damage that may interfere with how the liver works. Many people with NASH feel fine and do not even know they have the condition.

    If you have been told that you have or may have either NASH or a fatty liver, and diet and exercise haven’t worked, you may want to consider participation in the VIA clinical research study.

    What is the purpose of the VIA clinical research study?
    The VIA study is evaluating whether a once-daily, oral investigational medication called volixibat, is tolerable, safe, and effective in reducing liver damage in people with NASH. The study will evaluate the effects (if any) of three different doses of volixibat in patients with NASH.

    For more details click here