title: Endotheliitis in chronic viral hepatitis: a comparison with acute cellular rejection and non-alcoholic steatohepatitis.
abstract: Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (<or=1, n=35), Ishak scores were 1.66 and 1.37, respectively (P=0.00001 for portal inflammation and P=0.00001 for periportal injury, respectively). Our results suggest that minimal to mild subendotheliitis is common in portal veins in chronic hepatitis C and B, but is significantly less intense than that seen in ACR. The degree of endotheliitis correlates with inflammatory activity. These observations may help minimize the risk of overdiagnosing ACR when the patient has recurrent viral hepatitis, and may help clinicians avoid exposing patients to unnecessary immunosuppressive regimens when patients do not have cellular rejection.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195-6100, USA. myeh@u.washington.edu
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.forename: Anne M
authors.initials: AM
authors.lastname: Larson
authors.forename: Bruce Y
authors.initials: BY
authors.lastname: Tung
authors.forename: Paul E
authors.initials: PE
authors.lastname: Swanson
authors.forename: Melissa P
authors.initials: MP
authors.lastname: Upton
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000473:pathology*; D005234:Fatty Liver / Q000473:pathology*; D005260:Female; D006084:Graft Rejection / Q000473:pathology*; D006521:Hepatitis, Chronic / Q000473:pathology*; D006525:Hepatitis, Viral, Human / Q000473:pathology; D006801:Humans; D008099:Liver / Q000098:blood supply / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D011168:Portal System / Q000473:pathology*; D012189:Retrospective Studies