Background: The assessment of liver fibrosis in chronic hepatitis C patients is important for prognosis and making decisions regarding antiviral treatment. Although liver biopsy is considered the reference standard for assessing hepatic fibrosis in patients with chronic hepatitis C, it is invasive and associated with sampling and interobserver variability. Serum fibrosis markers have been utilized as surrogates for a liver biopsy.
Methods: We completed a prospective study of 191 patients in which blood draws and liver biopsies were performed on the same visit. Using liver biopsies the sensitivity, specificity, and negative and positive predictive values for both aspartate aminotransferase/platelet ratio index (APRI) and enhanced liver fibrosis (ELF) were determined. The patients were divided into training and validation patient sets to develop and validate a clinically useful algorithm for differentiating mild and significant fibrosis.
Results: The area under the ROC curve for the APRI and ELF tests for the training set was 0.865 and 0.880, respectively. The clinical sensitivity in separating mild (F0-F1) from significant fibrosis (F2-F4) was 80% and 86.0% with a clinical specificity of 86.7% and 77.8%, respectively. For the validation sets the area under the ROC curve for the APRI and ELF tests was, 0.855 and 0.780, respectively. The clinical sensitivity of the APRI and ELF tests in separating mild (F0-F1) from significant (F2-F4) fibrosis for the validation set was 90.0% and 70.0% with a clinical specificity of 73.3% and 86.7%, respectively. There were no differences between the APRI and ELF tests in distinguishing mild from significant fibrosis for either the training or validation sets (P=0.61 and 0.20, respectively). Using APRI as the primary test followed by ELF for patients in the intermediate zone, would have decreased the number of liver biopsies needed by 40% for the validation set. Overall, use of our algorithm would have decreased the number of patients who needed a liver biopsy from 95 to 24—a 74.7% reduction.
Conclusions: This study has shown that the APRI and ELF tests are equally accurate in distinguishing mild from significant liver fibrosis, and combining them into a validated algorithm improves their performance in distinguishing mild from significant fibrosis.
*Department of Pathology, University of Texas Medical Branch, Galveston
**Internal Medicine, Division of Gastroenterology, Kelsey-Seybold Clinic, Houston, TX
†Hernando Gastroenterology Associates, Brooksville, FL
‡Riverside Health System, 805 Progress Court, Newport News, VA
§Public Health and Medical Statistics, University of Southampton, Southampton
¶Division of Medicine, The Institute for Liver and Digestive Health, University College London, London, UK
#Department of Pathology, University of Chicago, Chicago, IL
The studies at the University of Texas Medical Branch were supported by Grant M01 RR 00073 from the National Center for Research Services, NIH, USPHS.
W.M.R. has financial relationships with the following companies: Siemens, Roche Pharma, Gilead, MSD, and iQur Limited.
The content of this paper includes discussions of a product (ELF) developed through an academic collaboration between Bayer Healthcare and the European Liver Fibrosis Group and licensed to Siemens in which there was a financial interest (W.M.R) or a paid employee (R.C.).
iQur Limited provided the ELF test studies on the patients. The samples were collected while patients were in the General Clinical Research Center at the University of Texas Medical Branch at Galveston.
The authors declare that they have nothing to disclose.
Reprints: John R. Petersen, PhD, Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0551 (e-mail: email@example.com).
Received February 27, 2013
Accepted July 29, 2013