SAN FRANCISCO — The liver biopsy remains the preferred method for diagnosing nonalcoholic fatty liver disease, but biopsy candidates should be chosen with care. Not all patients with signs of the disease will require a biopsy, Dr. Nathan M. Bass said at the Third World Congress on Insulin Resistance Syndrome.
Patients who are eventually diagnosed with nonalcoholic fatty liver disease (NAFLD) present initially in a variety of ways, said Dr. Bass of the University of California, San Francisco.
For example, an insurance exam can turn up an incidental aminotransferase elevation or an enlarged liver. An abdominal imaging study may reveal a fatty liver. A patient may have a complication of cirrhosis. Or NAFLD patients may be identified by screening high-risk populations with liver enzyme tests or liver ultrasound. In addition, an increasing number of NAFLD patients are being identified by liver biopsy during weight-reduction surgery, Dr. Bass said.
But it's not practical or desirable to screen all at-risk patients with a biopsy, and there are some good reasons not to do so. (See box.) About 25% of patients will experience significant pain during the biopsy. In addition, 1%–3.5% of patients will have morbidities such as hypotension, pneumothorax, hemoperitoneum, hemobilia, and gall bladder penetration. About 0.1% of patients will die from the procedure.
There are five situations in which a liver biopsy is essential: when a patient's liver enzymes show an unusual pattern or are 3–5 times normal; when other liver disease can't be excluded; when the patient doesn't have metabolic syndrome; to confirm a clinical suspicion of cirrhosis; and for qualifying a patient for entry into a clinical trial.
Although a definitive diagnosis still requires a biopsy, there are several alternatives for assessing the liver, Dr. Bass said.
Elevated liver enzymes can be very suggestive of NAFLD, but in a phenomenon Dr. Bass called “The Silence of the Labs,” some patients with NAFLD have normal liver enzymes. He pointed to one study of patients undergoing gastric bypass in which 68% had normal ALT and AST, but only 52% had a normal liver biopsy. Among the remaining 48% with abnormal biopsy results, about 27% were found to have nonalcoholic fatty liver, and the others had nonalcoholic steatohepatitis.
The diagnosis of NAFLD is often made by exclusion. After the physician excludes alcoholic liver disease, drug-induced liver injury, iron overload, hepatitis B and C, and autoimmune hepatitis, NAFLD is the diagnosis that remains.
It can be difficult, however, to exclude a significant contribution from alcohol, especially since patients are not always truthful. For the purposes of inclusion in clinical trials, NIH defines “nonalcoholic” as less than 14 units of alcohol per week for men or less than 7 units per week for women. A unit is one can of beer, one glass of wine, or one shot of hard liquor, but there's considerable variation in the alcoholic content of drinks within each class.
The combination of ultrasound evidence of fatty liver plus liver enzyme elevation without markers for hepatitis C or B yields a 96% positive predictive value for NAFLD, according to one study. The problem is that although ultrasound is sensitive, it's not very specific.
Pros
▸ Grade and stage of NAFLD are determined.
▸ Confidence in the diagnosis is 100%.
▸ Patients are motivated to lose weight.
▸ Biopsy is essential for enrollment inclinical trials of treatments.
Cons
▸ Risk of morbidity is increased with biopsy.
▸ Noninvasive diagnosis is quite accurate.
▸ Natural history of NAFLD is benign in most patients.
▸ NAFLD is a common disorder.
▸ There is no proven, specific treatment for NAFLD.
Source: Dr. Bass
CT imaging is somewhat more specific. In CT, a normal liver has about the same density as the spleen, whereas in NAFLD, the spleen will be quite a bit brighter than the liver. Unfortunately, CT is too expensive for routine screening.
At least three serological tests for hepatic fibrosis are under development, Dr. Bass said. In addition, transient elastography—a combination of 5 MHz ultrasound and 50 Hz elastic waves—may make the diagnosis simpler in the near future.