Impact of the donor liver with steatosis in patients with hepatitis C virus: Not so FAst

Abstract

It is currently estimated that 20% to 25% of the adult population has nonalcoholic fatty liver disease. Hepatic steatosis is one of the features of metabolic syndrome, which includes diabetes mellitus, hypercholesterolemia, and hypertension. These features are significant risk factors leading to cardiovascular and cerebrovascular mortality. Hepatic steatosis is therefore present in many older donors. Impairment in cognitive function associated with acute alcohol intoxication is a major factor contributing to mortality from motor vehicle and other accidents. Approximately 12% to 20% of organ donations stem from injuries precipitated by alcohol use, andmany of these individuals are found to have hepatic steatosis. As a result, hepatic steatosis is found in about 15% to 25% of potential organ donors. The negative impact of severe hepatic steatosis on graft dysfunction during the immediate posttransplant period has long been recognized. Donor livers containing greater than 30% to 50% steatosis are at increased risk of developing primary nonfunction and delayed function and are associated with reduced graft and patient survival. Historically, these livers were not routinely used for liver transplantation (LT) unless the potential recipient was critically ill and/or the transplant team was willing to accept these risks. Persons with significant hepatic steatosis have also been excluded as candidates for living liver donation because of similar concerns. Over the past decade, the number of patients on the LT waiting list, the waiting time to receive a donor liver, and pre–LT mortality have all increased. In an effort to blunt this trend, the use of so-called marginal donor livers, including those with significant steatosis, has increased substantially. Chronic hepatitis C virus (HCV) is the most common indication for LT. Nearly half of all LT recipients in North and South America, Europe, and Australia develop cirrhosis and/or hepatocellular carcinoma secondary to chronic HCV. The recurrence of chronic HCV following LT is universal, and progression to advanced bridging fibrosis or cirrhosis occurs in approximately 30% of these patients within 5 years and in approximately 40% within 10 years of LT. Numerous studies have attempted to define those factors that are associated with progressive fibrosis in LT recipients with recurrent HCV. Many different factors have been implicated in various studies. However, the one consistent finding in nearly all of these studies has been allograft rejection and its subsequent treatment with either high-dose steroids and/or monoclonal antibody preparations. Hepatic steatosis is known to lead to more rapid fibrosis progression in patients with chronic HCV, and a recent study has demonstrated that this also contributes to progressive fibrosis of the LT allograft in patients with recurrent HCV. Several studies have examined the impact of steatosis within the donor graft on the severity of recurrent HCV and/or survival following LT. The most recent of these studies by Briceno and colleagues from Reina Sofia University Hospital (Cordoba, Spain) appears in this issue of Liver Transplantation. The study by Briceno et al. suggests that severe steatosis of the donor graft is associated with earlier recurrence of chronic HCV, more rapid fibrosis progression, and a reduction in graft survival. An extensive list of donor and recipient factors were evaluated with univariate analysis and then multivariate analysis to identify those factors associated with decreased graft survival in this study. Donor graft steatosis greater than 30%, donor age greater than 55 years, and a cold ischemic time greater