Liver transplant failure risk: Females with HCV

Posted on June 14, 2015

Prospective Liver Match study unequivocally shows that female gender is a risk factor for graft loss after liver transplantation for hepatitis C virus (HCV)-related cirrhosis. Women lose their graft more frequently than men, secondary to more aggressive recurrent HCV infection. This study also confirms that the use of elderly donors is a strong predictor of poor graft outcome in HCV-infected lung transplant recipients. The prospective Liver Match observational cohort includes 1530 consecutive first transplants performed in adult recipients in Italy between June 2007 and May 2009 for which detailed baseline and follow-up information regarding both donors and recipients have been prospectively recorded.

Natural history studies of HCV infection show that women experience a slower rate of fibrosis progression per year and a lower incidence of end-stage liver disease compared with men. However, retrospective liver transplant studies surprisingly suggest that the risk for graft loss is increased in anti-HCV-positive female versus male recipients. While there are a number of well-established risk factors that influence the outcome of liver transplantation in HCV-infected individuals, such as donor age and Model for End-stage Liver Disease (MELD) score, the role of gender as a risk factor for graft loss after liver transplantation remains unclear. More definitive answers from a prospective assessment of the role of gender and other donor/recipient covariates on graft outcome, were recently published online in the journal Digestive and Liver Disease. (Belli LS et al. Dig Liver Dis. 2015 Apr 16. [Epub ahead of print])

  • Baseline and follow up data for 1530 consecutive adult recipients of first liver transplants performed between June 1, 2007 and May 31, 2009 were prospectively recorded and analyzed (the Italian Liver Match prospective observational cohort).
    • Twenty transplant centers, representing approximately 90% of the whole adult liver transplantation activity performed in Italy, agreed to participate in the data collection.
    • Follow-up data was prospectively recorded until December 31, 2013, with a median follow-up after liver transplantation of 51 months for surviving grafts.
    • Patients transplanted for fulminant hepatic failure (FHF, n = 45, 2.9%), infected with human immunodeficiency virus (HIV, n = 34, 2.3%), or non-viremic anti-HCV positive patients (n = 44) were excluded from the analysis. FHF patients are transplanted in a situation of urgency, which virtually precludes the possibility of donor/recipient matching.
    • 648 adult recipients were anti-HCV positive at the time of liver transplantation.
    • After a median follow-up of 51 months, 194 graft losses occurred in 604 HCV-RNA positive recipients (32%), and 181 among the 790 HCV-all-negative recipients (22.9%). Five-year graft survival was significantly reduced in HCV-positive patients (64% vs 76%, P = 0.0002).

Of the 194 graft losses observed among HCV-RNA positive recipients, 147 were observed in male recipients (29.8%) and 47 were observed in female recipients (42.3%). Analyses showed that the higher rate of graft loss observed among female recipients was almost exclusively attributable to severe HCV recurrence.

  • Characteristics more frequently found to be significantly associated with graft failure among HCV-RNA positive liver transplant recipients:
    • Recipient female gender (P = 0.0107) and presence of complete portal vein thrombosis (P = 0.0325).
    • Increasing donor age (P = 0.0007), increasing donor risk index (P = 0.0018), and donor anti-HBc positivity (P = 0.0459).
    • Recipient gender was significantly associated with a worse graft survival in HCV-RNA positive recipients, but not in HCV-all-negative ones.

HCV-RNA positive female recipients differed significantly from HCV-RNA positive male counterparts. HCV-RNA positive female recipients were older, had less hepatocellular carcinoma, their donors had a higher age and a lower BMI, and their grafts were more frequently split livers. All these variables were considered in the multivariate analysis.

  • Cox analysis identified recipient female gender (HR = 1.44, 95% CI 1.03–2.00, P = 0.0319), MELD score (every 10 units, HR = 1.25, 95% CI 1.03–1.50; P = 0.022), portal thrombosis (HR = 2.40, 95% CI 1.20–4.79, P = 0.0134) and donor age (every 10 years, HR = 1.14, 95% CI 1.05–1.24, P = 0.0024) as independent determinants of graft loss.

Study authors note that these results unequivocally show that women lose their graft more frequently than men secondary to more aggressive recurrent HCV infection, and suggest that women may need to be monitored more closely for disease progression and possibly treated earlier with the new direct acting antiviral therapies. The authors conclude the following:

  • “This study based on a large Italian population of lung transplant recipients, demonstrates that females with recurrent HCV infection have a worse outcome and the use of elderly donors is once again confirmed to be a strong predictor of poor graft outcome in HCV-infected lung transplant recipients of both genders. The results of the prospective Liver Match cohort represent an ideal benchmark to evaluate what will be the impact of new DAAs on lung transplantation outcomes.”

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