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February 10, 2012

Fatty Liver (cont.)

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What are the difficulties in evaluating NAFLD and NASH?

To make the diagnosis of NAFLD or NASH, the doctor must fully consider the possible role of alcohol in the patient's liver disease. This consideration requires detailed interviewing of the patient. The patient must also be honest in reporting alcohol use to the doctor. Unfortunately, this is not always the case. Moreover, the quantity of alcohol required to cause liver disease is debated. In fact, the amount varies from one study to another and from one country to another, and also varies widely according to individual rates of processing (metabolizing) the alcohol.

One unit of an alcoholic beverage contains 10 grams of alcohol (ethanol). A unit is roughly equivalent to one 12-ounce bottle of beer (5% alcohol), one 4-ounce glass of wine (12% alcohol), or one 1-ounce shot of hard liquor (40% alcohol). Most specialists would agree that at or above a consumption of 4 units/day in women and 6 units/day in men for at least a year, liver disease (due to alcohol) is highly likely to occur. However, there are reports that as little as 2 units/day in women and 4 units/day in men may be sufficient to promote liver disease, including fatty liver. The issue is further complicated by the possibility that in the setting of insulin resistance, even small quantities of alcohol could promote liver disease.

Studies have shown conclusively that NASH is associated with increased liver enzymes (transaminases). The importance of these elevations, however, can be somewhat overestimated because of what is referred to in statistics as an inclusion bias. That is, in most studies as well as in most clinical practice, only patients with persistently elevated transaminases are selected (included) for liver biopsies.

Some studies, however, have included patients for liver biopsies based on other criteria than elevated liver enzymes. These studies showed that NASH can be present on a liver biopsy in individuals with normal liver tests in up to 30% of cases of NASH. Furthermore, the degree of liver damage in NASH does not relate to (correlate with) the level of the liver enzymes. (Chronic HCV infection is another situation in which liver enzyme levels do not correlate with the severity of disease.) Moreover, a fatty liver alone can produce increased liver enzymes, even high elevations.

Among healthy individuals, liver enzyme levels are significantly higher in those with a BMI greater than 23kg/m2 as compared to those with a BMI less than 23kg/m2. This difference suggests that the upper limit of normal for liver enzymes should be adjusted according to the BMI.

All factors considered, NASH certainly cannot be diagnosed based just on a finding of abnormal liver enzymes and signs of a fatty liver on ultrasound. Furthermore, the exclusion of patients for liver biopsy on the basis of normal liver enzymes will invariably exclude potential cases of NASH.


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