PHILADELPHIA — Liver biopsy is losing its appeal as a diagnostic tool for chronic liver disease, Dr. K. Rajender Reddy said at the annual meeting of the American College of Physicians.
Problems associated with liver biopsy such as sampling error, inadequate specimens, and interobserver variability have become increasingly apparent in recent years, whereas noninvasive markers of fibrosis and inflammation are showing more promise as diagnostic tools.
Overall, liver biopsy is assuming a role more as a prognostic test than as a diagnostic test. At the very least, it should not be used “as a knee-jerk response to hepatic biochemical test abnormalities,” said Dr. Reddy, professor of medicine and surgery and director of hepatology at the University of Pennsylvania, Philadelphia.
Studies published in the past 3–8 years suggest that because liver biopsy samples less than 1/50,000 of the liver, cirrhosis may be missed in up to 20% of patients. Moreover, grades of inflammation and stage of fibrosis may be underscored in short, narrow specimens. Obtaining an adequate specimen—ideally more than 2.5 cm long, more than 1.4 mm wide, and with 11 or more portal triads—is often a challenge.
Panels of noninvasive markers of fibrosis and inflammation are not quite “ready for prime time,” but such tests may be validated in the near future. Indirect markers include the aspartate transaminase:alanine transaminase (AST:ALT) ratio, AST-platelet ratio index, the Fibro Test, and ActiTest. Direct markers such as hyaluronic acid and YKL-40 may prove useful as well. In addition, an ultrasonographic tool called FibroScan is being evaluated in Europe.
The relative pros and cons of doing a liver biopsy depend on the condition. With hepatitis C, biopsy may help determine the extent of fibrosis and inflammation, which are the best predictors of disease progression. On the other hand, noninvasive markers may also accurately stage and grade disease.
In hepatitis C patients with genotype 1, which carries the lowest treatment response rate, biopsy may help identify patients most in need of treatment. But patients with the more responsive genotypes 2 and 3 may be more motivated for therapy anyway and may forego biopsy.
Biopsy can help determine the need for treatment in patients experiencing side effects or in those who were previously treated and therefore less likely to respond to retreatment. However, “we don't really have effective retreatment strategies,” he said.
With hepatitis B, the decision to treat is generally made with hepatitis B serologies, viral DNA, and ALT, although biopsy might be considered in patients with fluctuating ALT levels. And, although biopsy might prompt screening for varices and hepatocellular carcinoma (HCC) in a patient with hepatitis B, surveillance for HCC is recommended in these patients whether cirrhosis is present or not, he noted.
For patients with elevated ALT levels, a biopsy can help confirm a diagnosis. However, a cause for abnormal hepatic biochemical tests is accurately identified clinically in more than 90% of cases without a biopsy. Similarly, the diagnosis of nonalcoholic fatty liver disease (NAFLD) is also usually made clinically, although not all patients have classic risk factors. Currently, only biopsy can distinguish simple steatosis from steatohepatitis, although noninvasive markers may accomplish this in the future.
Although the presence of steatohepatitis or fibrosis might motivate a patient with NAFLD to undertake risk-factor modification, there is no proven therapy for NAFLD. The absence of steatohepatitis or fibrosis might remove that motivation, Dr. Reddy cautioned.
Overall, he said, “noninvasive markers may be as 'good' or as 'flawed' as a liver biopsy, and may complement a liver biopsy rather than replace it—time will tell.”
Noninvasive markers 'may complement a liver biopsy rather than replace it—time will tell.' DR. REDDY