Leapin' liver enzymes

Upper limit of liver enzyme levels leave 'normal' behind.
Time to adjust testing for chubby Canadians?

By Katherine Addleman

Mohammed Shad, a 40-year -old professor of engineering, recently had a liver function test (LFT) to see if the antivirals he was taking were keeping his hepatitis C virus (HCV) under control and to make sure his liver wasn't heading for trouble. As he waited anxiously, his doctor reviewed the lab results which told him Mr Shad's liver enzyme levels registered in the normal range ? albeit in the upper limit. So nothing to worry about, right? Wrong. A recent study cautions against jumping to this conclusion when LFTs come back 'normal.' Mr Shad and his liver may not actually be in the clear just yet.

According to Dr Hyeon Chang Kim of Yonsei University College of Medicine in Seoul, doctors may be a little too complacent when it comes to patients' seemingly normal LFTs. Dr Kim published his results in the April 24 issue of the British Medical Journal from a huge, eight-year prospective study that questions the so-called 'normal' serum ranges for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the most common of the LFTs.

Enzymes that leak out into the bloodstream act as indicators that all's not well and LFTs can give physicians a heads up on potential disease. By themselves, LFT results aren't conclusive, but they indicate that further testing and maybe even a biopsy are a good idea.

However, many factors complicate the interpretation of these tests. For example, ALT may rise in response to problems that have nothing at all to do with liver function. Bone disease is one such culprit. And both ALT and AST are found in skeletal muscle, so serum concentrations can spike surprisingly when a muscle is injured, when myositis occurs or even after strenuous exercise. Obese patients also tend to have higher liver enzymes, as they cultivate their own personal foie gras.

To complicate things further, quite a high proportion of patients with chronic liver diseases like cirrhosis or hepatitis may have ALT and AST levels within normal ranges. "When tested monthly for six months or every other month for a year, 80% of patients with chronic HCV will have abnormal aminotransferase values," says Dr Morris Sherman, Assistant Professor of Medicine at the University of Toronto and an expert on HCV. In diseases like HCV, the liver cells die, producing less and less AST and ALT as they succumb. In fact, HCV patients can have safe serum ALTs, even when biopsies show inflammation.

WHAT'S NORMAL ANYWAY?
The results from Dr Kim's study showed that even liver enzymes within the 'normal' range (35-40IU/L) can indicate an increased risk of liver disease. He and his colleagues analyzed data from the medical records of over 94,000 men and 47,000 women aged 35-59 collected by the Korea Medical Insurance Corporation, in an area of the country heavily affected by liver disease ? chronic liver disease is common in many Asian countries due to endemically high hepatitis levels. They found that, as expected, the mortality rate from liver disease was proportional to liver enzyme levels. The high LFTs were also positively linked to hypertension, high cholesterol, diabetes, cigarette smoking, alcohol consumption and a family history of liver disease.

What was surprising was that the positive association with death from liver disease started to show up even when the AST and ALT were within normal ranges. When they calculated the relative risk of death for men with an AST of 20-29IU/L and of 30-39IU/L ? considered high normal ? they found the relative risk had jumped to 2.5, and 8.0, respectively. Results were even worse for women in these AST ranges. ALT figures were similar.

Dr Kim and his colleagues suggested that so-called 'normal' ranges may be better divided into 'optimum' levels (<30IU/L) and higher 'borderline' levels (30-39IU/L). In Canada chronic liver diseases are on the rise due to lifestyle changes such as obesity and alcoholism. Adjusting the upper normal limit could help clinicians detect liver disease earlier, and initiate secondary prevention strategies. Dr Arni Sekar, gastroenterologist at Ottawa Hospital, says that "these findings aren't surprising because a change in enzyme levels isn't the whole story in liver diseases." Given this study's results, he cautions that "enzymes alone shouldn't be guiding us. The clinical picture and other studies, such as imaging ultrasounds and CT scans are very important." As killer diseases go, liver disease ranks fourth in Canada and earlier detection could bring down the high number of fatalities in this country.