Risk Factors and Histologic Pathways of Fibrosis Progression and Architectural Distortion in Chronic Hepatitis C Virus Infection after Liver Transplantation
EO Ochoa, G Alarcon, Z Gao, DT Tran, AJ Demetris. University of Pittsburgh Medical Center, Pittsburgh, PA; Hospital Universitario de la UANL, Monterrey, Nuevo Leon, Mexico; University of Calgary, Calgary, AB, Canada
Background: Chronic hepatitis C virus (HCV)-induced cirrhosis is the leading indication for liver transplantation (OLT) and recurrent disease is universal. The rate of fibrosis progression is variable, but significantly accelerated compared to native livers, which enables pathologists to closely monitor histologic pathways responsible for liver injury and architectural distortion.
Design: 67 highly selected HCV+ OLT recipients were divided into two groups based on the presence or absence of bridging fibrosis year 3. Those with co-existent conditions that might accelerate fibrosis progression were excluded. Donor and recipient demographic, clinical and laboratory parameters were evaluated for an association with fibrosis progression. A subset of 23 patients had early (1-12 months) and late (2-5 yrs) biopsies available for comparison.
Results: Demographic and clinical factor analysis (n=67) showed that older donor age (> 40 yrs; p=0.048) and older recipient age (p=0.0269) were associated with rapid fibrosis progression, which more often led to graft failure (p=0.0005), re-transplantation (p=0.007) and death (p=0.014). Histologic findings in early biopsies (n=23) of rapid progressors showed more severe interface hepatitis (> 2 Ishak scale; p=0.025); portal inflammation (>2; p=0.025); total mHAI score > 5 (p=0.010); lymphoid aggregates (p=0.004) and hepatocyte ballooning (p=0.025). Late biopsies of rapid progressors showed more severe interface hepatitis (>2; p=0.0195); lobular necro-inflammatory activity (p=0.0545); portal inflammation (p=0.0245); total mHAI score (>6; p=0.0195); and prominent ductular reactions (p=0.0195), which caused stellate portal tract expansion (p=0.0001) and was responsible for the architectural distortion.
Conclusions: The combination of more severe necro-inflammatory activity/injury in older donor livers in early biopsies predicts the development in later biopsies of a more prominent ductular reaction, stellate portal expansion, and recurrent cirrhosis followed by allograft failure. These observations are consistent with default activation of the ductular reaction as an important mechanistic contributor to architectural distortion in allografts and identifies at risk patients early after transplantation for therapeutic intervention.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 183, Tuesday Morning