Interobserver Agreement in Hepatitis C Grading and Staging and in the Banff Grading Schema for Acute Cellular Rejection: The “Hepatitis C 3” Multi-Institutional Trial Experience

Abstract

Abstract Context.—Establishing adequate interobserver agreement is crucial not only for standardization of patient care but also to ensure validity of findings in multi-institutional trials. Objective.—To evaluate interobserver agreement in assessing chronic hepatitis C (HCV) and acute cellular rejection (ACR) among 17 hepatopathologists involved in the “Hepatitis C 3” trial. Design.—The trial is a randomized multicenter (17 institutions) study involving 312 patients undergoing transplantation for HCV. Patients are randomized to 3 treatment arms. For final data analysis, all biopsy specimens are reviewed by a central pathologist (G.J.N.). Recurrence of HCV is evaluated according to the Batts and Ludwig schema. The 1997 Banff schema is used to evaluate ACR. To assess interobserver agreement, hematoxylin-eosin–stained sections from 11 liver biopsy specimens (6 HCV and 5 ACR) were sent by the central pathologist to 16 local pathologists from 13 institutions. Statistical analysis was performed on raw ACR/HCV data as well as data grouped according to clinically significant primary endpoint cutoffs. Results.—Statistically significant agreement was found among all participating pathologists (P < .001). On κ analysis, the degree of agreement was rated “moderate” for HCV grade and stage and ACR global grading (κ = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (κ = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (κ = 0.76 “almost perfect” for HCV and 0.62 “substantial” for ACR). Conclusions.—An overall statistically significant interobserver agreement was found among 17 pathologists using the 1997 Banff schema and the Batts and Ludwig schema.