Liver transplantation for HCV cirrhosis: Improved survival in recent years and increased severity of recurrent disease in female recipients: Results of a long term retrospective study

Abstract

In recent years, a worsening outcome of hepatitis C virus (HCV)-positive recipients and a faster progression of recurrent disease to overt cirrhosis have been reported. Our aims were to 1) assess patient survival and development of severe recurrent disease (Ishak fibrosis score Ͼ 3) in different transplant years; and 2) model the effects of pre-and post-liver transplantation (LT) variables on the severity of recurrent disease. A multicenter retrospective analysis was conducted on 502 consecutive HCV-positive transplant recipients between January 1990 and December 2002. Protocol liver biopsies were obtained at 1, 3, 5, 7, and 10 yr post-LT in almost 90% of the patients. All 502 patients were included in the overall survival analysis, while only the 354 patients with a follow-up longer than 1 yr were considered for the analysis of predictors of disease progression. The overall Kaplan-Meier survival rates were 78.7%, 66.3%, and 58.6%, at 12, 60, and 120 months, respectively, and a trend for a better patient survival over the years emerged from all 3 centers. The cumulative probability of developing HCV-related recurrent severe fibrosis (Ishak score 4-6) in the cohort of 354 patients who survived at least 1 yr remained unchanged over the years. Multivariate analysis indicated that older donors (P ϭ 0.0001) and female gender of recipient (P ϭ 0.02) were the 2 major risk factors for the development of severe recurrent disease, while the adoption of antilymphocytic preparations was associated with a less aggressive course (P ϭ 0.03). Two of these prognostic factors, donor age and recipient gender, are easily available before LT and their combination showed an important synergy, such that a female recipient not only had a much higher probability of severe recurrent disease than a male recipient but her risk increased with the increasing age of the donor, reaching almost 100% when the age of the donor was 60 or older. In conclusion, a trend for a better patient survival was observed in more recent years but the cumulative probability of developing severe recurrent disease remained unchanged. The combination of a female recipient receiving an older graft emerged as a strong risk factor for a severe recurrence. Liver Transpl 13:733-740, 2007.

Azathioprine in Liver Transplantation: A Reevaluation of Its Use and a Comparison with Mycophenolate Mofetil

“…study (4 (18)(19)(20)(21)(22)(23)(24)(25)(26). AZA was associated with reduced severity of HCV recurrence in five studies (56%) (18,19,22,23,25), evaluated in a univariate analysis in one, multivariate in three, and with chi-square test in one, whereas in four studies (44%) (20,21,24,26) (5,19,23,24,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), only two studies (12%) (31,33) found decreased severity of HCV recurrence, and in one (31) there was no multivariate analysis.…”

“…AZA was associated with reduced severity of HCV recurrence in five studies (56%) (18,19,22,23,25), evaluated in a univariate analysis in one, multivariate in three, and with chi-square test in one, whereas in four studies (44%) (20,21,24,26) (5,19,23,24,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), only two studies (12%) (31,33) found decreased severity of HCV recurrence, and in one (31) there was no multivariate analysis. Nine studies (53%) (5,19,24,(26)(27)(28)(29)(30)32) documented similar severity of HCV recurrence, but six (35%) (23,(34)(35)(36)(37)(38) showed increased severity of HCV recurrence (Tables 2 and 3 …”

Improving Outcomes of Liver Retransplantation: An Analysis of Trends and the Impact of Hepatitis C Infection

“…In this study, donor age was a risk factor for mortality and graft failure only in HCV recipients, as it was not found to be significant factor in the non-HCV patients. The reason for the disproportionate risk with older donors in HCV patients is not known, but HCV recurrence is universal and is known to progress more rapidly in older grafts (23,26,27). Similar to non-HCV patients, HCV patients bare the risks of early graft failure related to advanced donor age, but in addition have longer term risks related to accelerated progression of recurrent HCV.…”

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“…2 Recurrent HCV has an accelerated natural history with 20% to 54% of patients developing allograft cirrhosis within 5 years and reduced allograft and recipient survival. [3][4][5][6][7][8][9][10][11][12] Historically, recurrent HCV has been treated with peginterferon (PEG) and ribavirin (RBV) with rates of sustained virologic response (SVR) (undetectable HCV RNA at 6 months after end of treatment) of 28% to 45%. [13][14][15][16][17][18][19] Contributing to this relatively low SVR is a high prevalence of patients with HCV genotype 1 and the presence of cytopenias limiting the use of maximal dosing of PEG and RBV.…”