Noninvasive Tests

While liver biopsy is considered the “gold standard” for assessing the severity of liver disease, it is not always accurate and has several shortcomings. Liver biopsy can under- or over-estimate the severity of hepatitis C, particularly if the biopsy is small and if it is not read by a knowledgeable expert. In addition, 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. Rare complications include puncture of another organ, infection, and bleeding. Significant bleeding after liver biopsy occurs in one out of 100 to one out of 1,000 cases, and deaths are reported in one out of 5,000 to one out of 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 inflammation and liver cell injury on liver biopsy. Furthermore, patients who maintain ALT levels above five times the upper limit of normal usually have marked inflammatory 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 and measure fibrosis 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 decrease in platelet count (which is perhaps the earliest change), elevations in serum 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 completely reliable, their presence should raise the suspicion of significant fibrosis and lead to evaluation for treatment sooner rather than later.
Recently, x-ray and imaging studies have been developed that may be able to separate different degrees of fibrosis in the liver. At present, these techniques are experimental and of unproven accuracy, particularly in detecting early stages of fibrosis. The most promising technique is “elastrography,” in which sound or magnetic waves are passed through the liver and the speed with which they return is measured, which provides an index of the elasticity and stiffness of the liver. Liver stiffness is used as an indirect measure of liver fibrosis. Most importantly, measuring the relative stiffness of the liver over time may provide a noninvasive way to monitor the development of fibrosis and help guide recommendations for when therapy should be recommended. Ultrasound elastrography is currently under evaluation for its reliability in measuring the degree of fibrosis in the liver in patients with hepatitis C. Ultimately, elastrography may be able to replace liver biopsy as a way of monitoring the progression of disease in chronic hepatitis C.