Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience.

BACKGROUND: During the last decades, several risk factors for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) have been investigated. However, the impact of two important drivers of oncogenesis, namely the immunosuppression and the treatment of acute cellular rejection (ACR) have been marginally addressed. This study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT population. METHODS: Seven hundred and eighty-one adult patients transplanted between February 1, 1985 and June 30, 2016 were retrospectively analyzed. After propensity score match, 116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ACR. RESULTS: Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients (16.4% vs. 0.9%; P<0.0001). At multivariate Cox regression analysis, steroid boluses used to treat ACR were an independent risk factor for HCC recurrence (HR=14.2; 95% CI: 1.8-110.4; P = 0.010). CONCLUSIONS: The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented results. Prospective studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.

Transferrin as a predictor of survival in cirrhosis.

Patients with cirrhosis frequently present with high serum ferritin and low transferrin concentrations, reflecting impaired liver function and inflammation. Recent studies have shown that transferrin and its saturation with iron are Model for End-Stage Liver Disease-independent predictors of mortality in patients with acute-on-chronic liver failure or decompensated cirrhosis. The aim of this study was to evaluate the prognostic utility of serum iron parameters in relation to markers of liver function and immune activation. Clinical, demographic, and biochemical data were retrospectively analyzed from a cohort of 1255 consecutive patients with cirrhosis (age ≥ 18 years) who presented from August 1, 2004 until December 31, 2014 at the University Hospital of Innsbruck. Patients with malignancies at diagnosis including hepatocellular carcinoma were excluded. Survival analysis was carried out by Cox regression by using baseline laboratory parameters, and findings were validated in an independent patient cohort. During a median follow-up of 2.4 years, 193 deaths occurred and 254 patients underwent liver transplantation. In patients with transferrin < 180 mg/dL, 3-month, 1-year, and 5-year transplant-free survival estimates were significantly lower (91.7%, 79.0%, and 30.5%) when compared with the group of patients with transferrin ≥ 180 mg/dL (98.9%, 95.5%, and 68.0%, P < 0.001). Transferrin predicted transplant-free survival independently of Model for End-Stage Liver Disease-sodium (MELD-Na) and C-reactive protein (CRP) in multivariate regression analysis including all patients. When patients with alcoholic or nonalcoholic fatty liver disease were excluded, transferrin was in addition an albumin-independent predictor of transplant-free survival. In conclusion, the association of transferrin with transplant-free survival is independent of MELD-Na score and CRP. In patients without fatty liver disease, transferrin also predicts survival independently of albumin. Liver Transplantation 24 343-351 2018 AASLD.