The effect of donor race on the survival of Black Americans undergoing liver transplantation for chronic hepatitis C: Is racial mismatch a predictor of graft survival?

Abstract

Chronic liver diseases are the 12th leading cause of death in the United States, and the burden of disease has been projected to increase substantially in the next several decades. Hepatitis C virus (HCV) is the most common disorder leading to liver transplantation, and its late-stage complications are expected to result in increased hospitalizations and morbidity. The epidemiology of chronic hepatitis C, the natural history of the disease, and its response to therapy are greatly influenced by racial and ethnic differences. African Americans exhibit a higher prevalence of hepatitis C–positive viral serology, and in comparison with nonHispanic whites, they are twice as likely to get infected with genotype 1, which reduces the probability of sustained virological clearance when they are treated. The dissimilarity in viral clearance has been speculated to be a function of racial variation in immunological reactivity. A study of HCV-specific CD41 cell response indicated that even though African Americans have a significantly greater proliferative response to HCV NS3NS5 antigens than non-Hispanic whites, the HCV-specific CD41 T-cell proliferative response is dysfunctional, and the production of gamma interferon, a cytokine that inhibits protein synthesis and RNA replication of subgenomic and genomic HCV replicons, is reduced in this population. The speculated dysfunctional immunological reactivity would explain partially why African Americans progress more often to cirrhosis than nonHispanic whites. Nevertheless, more recently, the National Institutes of Health–sponsored Viral Resistance to Antiviral Therapy of Chronic Hepatitis C (VIRAHEP-C) study, with all of its substudies, has failed to show any racial difference in viral genetics or immunological variability to which the lack of response to antiviral treatment could be attributed. Race also seems to play an important role in access to liver transplantation and in graft survival post–orthotopic liver transplantation (OLT). Prior to the introduction of the Model for End-Stage Liver Disease (MELD), liver organ allocation was based on subjective parameters such as severity of ascites and grade of hepatic encephalopathy. Several studies performed during the pre-MELD era illustrated that African American were underrepresented on the transplant waiting list and among recipients of transplantation. African Americans were also more likely to be referred for liver transplantation at a later stage of their disease in comparison with white patients and had a higher probability of becoming too ill or dying while waiting for liver transplantation. The use of the MELD scoring system has provided a more objective method for the assessment of severity of liver disease and eliminated race as a predictor of organ allocation and as a risk factor for death on the waiting list. The effect of race and ethnicity on post–liver transplantation outcomes has also been extensively reviewed; the most common findings are the reduced 2and 5-year patient survival observed in African Americans after liver transplantation and the in-