1) Hepatitis C virus (HCV) liver transplant (LT) recipients receiving perioperative transfusions have increased fibrosis and decreased 1- and 5-year survival when compared to their non-transfused counterparts.
2) Negative impact of transfusion may be due to early immune modulation leading to suppression of HCV-specific IFN-gamma and activation of IL-17.
Evidence rating: 2 (Good)
Study Rundown: HCV infects 170-200 million people worldwide, and is frequently complicated by liver cirrhosis, failure, and hepatocellular carcinoma. These HCV-mediated diseases are the leading indications for LT in the USA. This study found that adult patients transplanted for HCV-related liver disease who received perioperative packed red blood cell (PRBC) transfusions experienced worse post-operative outcomes than their non-transfused counterparts. Transfused patients also had serum markers favoring HCV replication. This study is limited primarily by its small sample size, retrospective nature, and by difficulty standardizing the time-points of blood and tissue samples. Additionally, the multivariate analysis may not account for confounding variables related to the decision to transfuse. Nevertheless, this study demonstrates the negative effect of transfusion on outcomes and provides a convincing immunological explanation.
In-Depth [retrospective study]: This study included 257 adult patients transplanted for HCV-related liver disease between January 2003 and December 2010 at a single institution. Blood samples were obtained pre-transplant and at 1, 6, and 12 months, post-transplant; liver biopsy was performed 10-14 months post-transplant. An ELISpot assay was used to determine HCV-specific immune responses, and multiplex bead immunoassays were used to measure serum cytokines.
Transfused patients were younger, had a higher pre-transplant MELD score, higher INR, lower hemoglobin, and higher bilirubin. Increasing donor age, PRBC transfusion, and platelet administration were associated with worse survival. While pre-LT HCV viral load was not significantly different between transfused and non-transfused patients, post-LT viral load was higher in those transfused (10.3 vs. 5.6 106 copies/ml, p=0.032). One-year survival was 95% in the non-transfused and 88% in the transfused (p=0.02); five-year survival was 77% and 66%, respectively (p=0.05). Incidence of advanced fibrosis at one year was higher in the transfused group (p=0.04). After transplant, transfused patients had increased IL-10, IL-17, IL-1beta, and decreased IFN-gamma, with a significantly increased rate of HCV IL-17 production.
By Mariya Samoylova and Chaz Carrier
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