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Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r ‫؍‬ 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P ‫؍‬ 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. Conclusion: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.

Liver transplantation (LT) is the only therapeutic option for end-stage primary sclerosing cholangitis (PSC), but PSC can recur (rPSC) in some patients after LT. The aim of our study was to evaluate the risk factors associated with rPSC. Between 1989 and 2004, 69 patients receiving transplantation for PSC (42 male, mean age 41.9 yr). Clinical and laboratory data, activity/extension and treatment of ulcerative colitis (UC), post-LT cytomegalovirus (CMV) infection, and immunosuppression were evaluated. Determination of rPSC was made by radiological and histological findings. Exclusion criteria were ABO blood group incompatibility, hepatic artery stenosis, and biliary strictures occurring in Ͻ3 months post-LT. A total of 48 (70%) patients had PSC and UC pre-LT. rPSC occurred in 7 of 53 (13.5%, 2 patients with de novo UC) who were alive 1 yr after LT and/or met inclusion/exclusion criteria: median 60 (4-120) months. No patient without post-LT UC had rPSC: 0 of 20 vs. 7 of 26 with post-LT UC (P ϭ 0.027). The multivariate logistic regression analysis showed that maintenance steroids for UC (Ͼ3 months) post-LT was the only risk factor significantly associated with rPSC (P ϭ 0.025). In conclusion, the presence of UC post-LT, and the need for maintenance steroids post-LT, which is an independent factor, are associated with rPSC. These findings could help elucidate a possible mechanism of PSC pathogenesis.