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.
BACKGROUND
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.


METHODS
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 kappa analysis, the degree of agreement was rated "moderate" for HCV grade and stage and ACR global grading (kappa = 0.30, 0.33, and 0.37, respectively). Interobserver agreement was weaker for rejection activity index scoring of ACR (kappa = 0.15). A stronger degree of agreement was found when scores were grouped based on endpoint cutoffs (kappa = 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.
Netto
George J
GJ
Departments of Pathology, Baylor University Medical Center, Dallas, Tex, USA. gnetto1@jhmi.edu
Watkins
David L
DL
Williams
James W
JW
Colby
Thomas V
TV
dePetris
Giovanni
G
Sharkey
Francis E
FE
Corless
Christopher L
CL
Lewin
David
D
Petrovic
Lydia
L
Sharma
Shobha
S
Kanel
Gary
G
Theise
Neil
N
West
A Brian
AB
Koehler
Alison
A
Jhala
Nirag C
NC
Lefkowitch
Jay
J
Lezzoni
Julia
J
Jennings
Linda W
LW
Tillery
G Weldon
GW
Klintmalm
Goran B
GB
D000208:Acute Disease; D006084:Graft Rejection / Q000145:classification*; D006526:Hepatitis C / Q000145:classification* / Q000175:diagnosis / Q000601:surgery; D006801:Humans; D016031:Liver Transplantation; D015588:Observer Variation; D015203:Reproducibility of Results