Serum Markers of Hepatic Fibrosis

Liver biopsy is an invasive procedure that is expensive and not without complications. At least 20 percent of patients have pain requiring medications after liver biopsy. More uncommon complications include puncture of another organ, infection, and bleeding. Significant bleeding after liver biopsy occurs in 1/100 to 1/1,000 cases, and deaths are reported in 1/5,000 to 1/10,000 cases. Obviously, noninvasive means of grading and staging liver disease would be very helpful.

ALT levels, particularly if tested over an extended period, are reasonably accurate reflections of disease activity. Thus, patients with repeatedly normal ALT levels usually have mild necroinflammatory activity on liver biopsy. Furthermore, patients who maintain ALT levels above 5 times the upper limit of normal usually have marked necroinflammatory activity. But for the majority of patients with mild-to-moderate ALT elevations, the actual level is not very predictive of liver biopsy findings.

More important is a means to stage liver disease short of liver biopsy. Unfortunately, serum tests are not reliable in predicting fibrosis, particularly earlier stages (0, 1, and 2). When patients develop bridging (stage 3) fibrosis and cirrhosis (stage 4), serum tests may be helpful. The "danger signals" that suggest the presence of advanced fibrosis include an aspartate aminotransferase (AST) that is higher than ALT (reversal of the ALT/AST ratio), a high gamma glutamyl transpeptidase or alkaline phosphatase, a low platelet count (which is perhaps the earliest change), rheumatoid factor, elevations in globulins, and, of course, abnormal bilirubin, albumin or prothrombin time. Physical findings of a firm liver, or enlarged spleen or prominent spider angionata or palmar erythema, are also danger signals. While none of these findings are perfect, their presence should raise the suspicion of significant fibrosis and lead to evaluation for treatment earlier rather than later.

source: http://digestive.niddk.nih.gov/ddiseases/pubs/chronichepc/index.htm