Non-invasive Assessment of Liver Fibrosis in Patients with Hepatitis C

By Liz Highleyman

Liver biopsies are the “gold standard” for assessing the extent of liver fibrosis, which is used to help guide decisions about which patients require treatment for hepatitis C.

Because liver biopsy is uncomfortable, expensive, and associated with a small risk of complications such as excessive bleeding, researchers have expended considerable effort on developing non-invasive techniques for assessing liver disease progression using plasma biochemical markers, imaging, and other methods.

Two articles and an editorial in the July 2006 Journal of Clinical Gastroenterology were devoted to studies of non-invasive fibrosis assessment methods in patients with chronic hepatitis C.

Study 1

In the first study, researchers from the University of Genoa in Italy evaluated the performance of the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and platelet count in diagnosing the presence or absence of significant fibrosis.

The study population was a large cohort of chronic hepatitis C patients seen at two tertiary referral centers. Liver biopsies from 409 patients were evaluated. Fibrosis staging was based on Ishak and METAVIR scores.

Receiver operating characteristic (ROC) curves were used to identify AST/ALT ratio and platelet count cut-offs with the highest accuracy for diagnosing significant fibrosis. These cut-offs were then used to devise an algorithm the researchers hoped could be used to diagnose or rule out significant fibrosis, ultimately reducing the need for biopsies.

Results

• Significant fibrosis was detected in 43% of patients
• AST/ALT ratios increased and platelet counts decreased as liver fibrosis worsened
• Both AST/ALT ratio and platelet count were highly accurate for diagnosing of significant fibrosis (C-index = 0.747 and 0.733, respectively).
• The use of AST/ALT ratio and platelet count cut-offs in a diagnostic algorithm would have avoided liver biopsy in 68.9% of the patients.
• Such an algorithm would have correctly identified the absence or presence of significant fibrosis in 80.5% of these cases.

Conclusion

In conclusion, the authors wrote, “In clinical practice, the use of simple, reproducible, and inexpensive parameters such as the AST/ALT ratio and platelet count can reduce the need for liver biopsy in a substantial proportion of patients with chronic hepatitis C.”

Study 2

In the second study, researchers from the University of Texas Medical Branch evaluated a different biochemical measure, the AST to platelet ratio index (APRI), as a predictor of significant fibrosis.

The authors retrospectively reviewed the medical records of 339 chronic hepatitis C patients who received liver biopsies between January 2000 and March 2003. They later prospectively evaluated 151 patients receiving pretreatment liver biopsies. Biopsy samples were staged using the Batts-Ludwig criteria.

Results

• The area under the ROC curve of the calculated APRI compared with liver biopsy demonstrated that the fibrosis score was 0.790 in the retrospective group and 0.889 in the prospective group.
• To achieve predictive values of approximately 90%, useful upper and lower cut-offs were 0.40 and 1.5 in the retrospective study, and 0.42 and 1.2 in the prospective study.
• These cut-offs left intermediate zones of 58.9% in the retrospective study and 41.1% in the prospective study.
• In the prospective group, 34 of 36 patients (94%) with values less 0.42 were accurately diagnosed as having minimal or mild fibrosis, while 50 of 54 patients (93%) with values greater than 1.2 were accurately diagnosed as having significant fibrosis.

Conclusion

The authors concluded that, “APRI is a good estimator of hepatic fibrosis and was more accurate in a prospective group than a retrospective one. It potentially could be used to decrease the number of liver biopsies.

”While both studies demonstrate progress in the use of non-invasive methods for predicting fibrosis, more research is needed to refine these methods. Today’s techniques --- both biochemical indices and imaging methods -- are useful for determining which patients have advanced fibrosis and which have little or no liver damage. However, they are not as good at distinguishing intermediate fibrosis stages, which is precisely what is needed in many cases to aid treatment decision-making.

8/15/06 

References

E G Giannini, A Zaman, P Ceppa, and others. A Simple Approach to Noninvasively Identifying Significant Fibrosis in Chronic Hepatitis C Patients in Clinical Practice. Journal of Clinical Gastroenterology 40(6): 521-527. July 2006.

N Snyder, L Gajula, S Y Xiao, and others. APRI: An Easy and Validated Predictor of Hepatic Fibrosis in Chronic Hepatitis C. Journal of Clinical Gastroenterology 40(6): 535-542. July 2006.

P J Pockros. Noninvasive Markers of Fibrosis in Chronic Hepatitis Patients. Journal of Clinical Gastroenterology 40(6): 461-463. July 2006.