Diabetes and hepatic oxidative damage are associated with hepatitis C progression after liver transplantation.
BACKGROUND
Posttransplant diabetes mellitus (PTDM) is common after liver transplantation and was recently identified as a risk factor for hepatitis C progression. Increased levels of oxidative stress have been identified in diabetes and hepatitis C. The aim of this study was to evaluate the relationship among PTDM, oxidative damage in liver biopsy specimens, and fibrosis progression posttransplant.


METHODS
Subjects consisted of 27 hepatitis C-infected liver transplant recipients who had liver biopsy specimens available from 49 protocol liver biopsies. Paraffin embedded liver tissue sections were stained for 8-hydroxy-2' deoxyguanosine (8-OHdG), an indicator of hydroxyl radical mediated tissue damage. The percentage of cells staining for 8-OHdG in a histologic section was categorized as high (>66%) versus low score (< or =66%). Fibrosis index was calculated as fibrosis score (0-4)/ years posttransplant. Time to bridging fibrosis or cirrhosis (F3-4) was compared as a function of PTDM and 8-OHdG score.


RESULTS
Considering all 49 biopsies, fibrosis index was higher in cases with PTDM (P<0.001) and high 8-OHdG score (P=0.004). High 8-OHdG score was associated with PTDM (P=0.012). In time to event analyses, time to F3-4 was more rapid in patients with PTDM (P=0.02) and in those with high 8-OHdG scores (P<0.001).


CONCLUSIONS
This study confirmed a relationship between PTDM and hepatitis C fibrosis progression and found that oxidative damage in liver biopsy specimens was associated with PTDM and more rapid development of advanced fibrosis.
Cotler
Scott J
SJ
Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA. scotler@uic.edu
Kallwitz
Eric
E
TenCate
Veronica
V
Bhushan
Anita
A
Berkes
Jamie
J
Benedetti
Enrico
E
Layden-Almer
Jennifer
J
Layden
Thomas J
TJ
Valyi-Nagy
Tibor
T
Guzman
Grace
G
D000080242:8-Hydroxy-2'-Deoxyguanosine; D001706:Biopsy; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003920:Diabetes Mellitus / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000473:pathology / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D015996:Survival Rate; D013997:Time Factors
D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine