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Background & Aims Significant liver fibrosis (F ⩾2) and portal hypertension (hepatic venous pressure gradient [HVPG] ⩾6mmHg) 1year after liver transplantation (LT) are predictors of severe hepatitis C recurrence. Periportal sinusoidal fibrosis (SF) is an early expression of the fibrogenic process in response to liver injury. We aimed to evaluate whether SF in early liver biopsies represents an early and accurate marker for identifying patients with severe HCV recurrence after LT. Methods A total of 101 HCV LT patients with early biopsy (<6months), and HVPG measurement and/or liver biopsy one year after LT were included. Early biopsies were stained with Sirius Red and SF was graded semi-quantitatively. Results were compared between groups (significant SF vs. non-significant SF) and correlated with the development of severe HCV recurrence one year after LT. Results Patients with early significant SF had older donor age and higher necroinflammatory activity (NIA). The presence of early significant SF enabled identification of 78.9% and 90.6% of patients with F ⩾2 and HVPG ⩾6mmHg, respectively, one year after LT. Donor age and NIA were independent predictors of significant fibrosis (F ⩾2) one year after LT, whereas donor age, ALT (3months), NIA, and SF grade were independent predictors of portal hypertension (HVPG ⩾6). Conclusions Significant SF in early biopsies is a good predictor of severe hepatitis C recurrence. This histological finding, when combined with simple variables, may be useful to select the best candidates for early antiviral therapy after LT. [ABSTRACT FROM AUTHOR]

Alcohol-related liver disease (ALD) is the primary cause of liver-related mortality and morbidity. Liver fibrosis remains the best validated surrogate marker for patient prognosis and is usually assessed in liver biopsies using histochemical stains detecting collagen as the major extracellular matrix (ECM) component in ALD. Distinction of collagen subtypes is of clinical interest, as they, including their cleavage products, have different functions. Changes in production, distribution, and composition of specific collagen subtypes and other extracellular matrix (ECM) components as well as markers for their main cellular source (activated hepatic stellate cells (aHSCs) and myofibroblasts (MFBs)) have not been fully elucidated in ALD. Our aims were to investigate the stage-dependent expression of collagen subtypes and markers for aHSCs and MFBs in ALD. We included liver biopsies from 49 ALD patients with fibrosis stages F0–F4. Biopsies were classified according to the semi-quantitative non‐alcoholic fatty liver disease (NAFLD) activity score (NAS‐CRN). Slides were stained with H&E, Sirius Red, and immunohistochemically with antibodies against collagen types I, III, IV and VI, and aHSC/MFB markers α-SMA, osteonectin, and CD271. Expression was examined using automated digital imaging analysis (DIA), by calculating the positive area relative to the total liver biopsy area (proportionate area). Likewise, collagen-proportionate area (CPA) was assessed using DIA of Sirius Red stained slides. CPA correlated highly with fibrosis stage (r s = 0.88, P = 5.9E-17) and moderately with activity score (r s = 0.58, P = 0.00001). Collagen type I proportionate area increased from 0.3% (± 0.1) at F1 to 10.2% (± 1.6) at F4 (P < 0.001). Collagen type III proportionate area increased from 0.6% (± 0.2) at F0 to 11.9% (± 1.7) at F4 (P < 0.001). Collagen type IV proportionate area increased from 17.0% (± 2.5) at F0 to 27.0% (± 3.9) at F4 (P = 0.079). Collagen type VI proportionate area increased from 14.8% (± 1.4) at F0 to 31.4% (± 2.4) at F4 (P < 0.001). Proportionate areas for α-SMA and CD271 increased from 10.7% (± 1.6) and 6.5% (± 1.0) at F0 to 29.5% (± 3.4) and 22.1% (± 2.2) at F4 (P < 0.001). Proportionate area for osteonectin increased from 1.4–1.8% at F0–F2 to 3.1% (± 0.5) at F3 and 3.2% (± 0.6) at F4 (P < 0.05). In conclusion, our data indicate that collagen types I, III and VI and the aHSC/MFB markers α-SMA and CD271 show a stage-dependent increase in ALD. In early ALD, collagen types IV and VI are important components of the perisinusoidal and pericellular fibrosis. Immunohistochemistry is a valuable additional tool to characterize the ECM changes in ALD. Further research is needed to explore the functional role of CD271 and the stage-dependent expression of other collagen subtypes in ALD. [ABSTRACT FROM AUTHOR]