A Decreased Response to Resistin in Mononuclear Leukocytes Contributes to Oxidative Stress in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Deregulation of immune response and oxidative stress contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Resistin is a physiological modulator of inflammation and redox homeostasis of different cell types. Increased resistin serum concentration and the direct association between resistin hepatic expression and NAFLD severity suggest that resistin participates in NAFLD pathogenesis. AIMS: To evaluate resistin-induced regulation of redox homeostasis in mononuclear leukocytes from NAFLD patients and controls. METHODS: We evaluated basal and resistin-mediated modulation of reactive oxygen species (ROS) and glutathione content by flow cytometry, and antioxidant enzyme activities by spectrophotometry. RESULTS: Peripheral blood mononuclear cells (PBMC) from NAFLD patients showed higher ROS content and glutathione peroxidase activity and lower glutathione content, superoxide dismutase and glutathione reductase activities than control PBMC. Resistin decreased ROS levels and superoxide dismutase activity and increased glutathione reductase and catalase activities in PBMC from controls but not from patients. Resistin decreased glutathione content in PBMC from control and NAFLD patients, with greater effect on patient cells. Basal and resistin-modulated ROS levels were directly associated with obesity-related risk factors for NAFLD. Hepatic myeloid cells and T-lymphocytes from NAFLD patients showed higher basal ROS content than cells from controls. Resistin decreased ROS levels in hepatic T-lymphocytes from controls but not from patients. CONCLUSIONS: Resistin regulates redox homeostasis in mononuclear leukocytes. A decreased response to resistin in leukocytes from NAFLD patients is associated with an impaired redox homeostasis.

Fibrosis progression in maintenance liver transplant patients with hepatitis C recurrence: a randomised study of everolimus vs. calcineurin inhibitors.

BACKGROUND & AIMS: Robust clinical data evaluating fibrosis progression in hepatitis C virus (HCV) liver transplant patients receiving an mTOR inhibitor vs. calcineurin inhibitor (CNI) are lacking. To evaluate fibrosis progression in maintenance liver transplant patients receiving everolimus- or CNI-based immunosuppression. METHODS: In a randomised, multicentre, open-label study, 43 maintenance liver transplant patients with recurrent HCV infection were randomised to continue CNI-based immunosuppression or switch to everolimus. RESULTS: For patients with biopsy data at month 12, mean Ishak-Knodell fibrosis score at baseline was 2.6 ± 0.9 (n = 14) with everolimus vs. 1.9 ± 1.1 (n = 18) with CNI (P = 0.043), and 1.9 ± 1.2 vs. 2.2 ± 1.3 at month 12. Ishak-Knodell fibrosis score decreased from baseline to month 12 by a mean of -0.7 ± 1.1 with everolimus, but increased by 0.2 ± 1.2 with CNI (P = 0.046). No acute rejection or graft losses occurred up to month 12. Estimated GFR at month 12 was 65.6 ml/min/1.73 m² with everolimus and 62.2 ml/min/1.73 m² with CNI [mean difference 3.4 ml/min/1.73 m² compared to CNI control group, 95% CI -4.9, 11.8 ml/min/1.73 m², P = 0.411 (analysis of covariance adjusting for baseline GFR)]. Adverse events occurred in 95.5% of everolimus patients and 71.4% of CNI patients (serious adverse events 31.8% and 0.0%, respectively). Adverse events led to everolimus discontinuation in five patients (22.7%). CONCLUSIONS: This exploratory study suggests that conversion from CNI to everolimus reduces progression of liver fibrosis, and preserves renal function without jeopardising efficacy in liver transplant recipients with recurrent HCV, but is associated with a higher incidence of adverse events and serious adverse events. These preliminary findings merit examination in a larger trial.

[Hepatocellular carcinoma within Milan criteria and beyond: outcomes of liver transplantation in a single Argentinian institution]. / Hepatocarcinoma dentro y fuera de los criterios de Milán: resultados de un centro de trasplante hepático en la Argentina.

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67% and non-Milan (NM) 33%. Global recurrence rate, and M-group and NM-group recurrence rates were 19%; 12% and 32%, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86% and 91% (NS), 77% and 88% (NS), and 67% and 86% (P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86% and 71%; 82% and 61%, and 78% and 58%, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.

Hepatitis E: un virus infrecuente o un agente infrecuentemente pensado? / [Hepatitis E: an infrequent virus or an unfrecuently investigated agent?].

Two cases of hepatitis E that were assisted in our Unit of Hepatology and Liver Transplantation are described in this article. The first patient had prior hepatic involvement and therefore a more severe course, whereas the second case, with normal liver function, only developed a self-limited acute hepatitis.

Hepatocarcinoma dentro y fuera de los criterios de Milán: resultados de un centro de trasplante hepático en la Argentina / [Hepatocellular carcinoma within Milan criteria and beyond: outcomes of liver transplantation in a single Argentinian institution].

Hepatocellular carcinoma (HCC) recurrence following liver transplantation is associated to bad prognosis. We retrospectively analyzed the data of 95 patients who underwent liver transplantation for HCC. Recurrence rate and variables associated with recurrence were reviewed. According to the findings on the explanted livers they were divided in two groups: Milan (M) 67

. Global recurrence rate, and M-group and NM-group recurrence rates were 19

, respectively (P = 0.001). Although in the univariate analysis we found some factors associated to recurrence (hemocromathosis, year of transplant, bilobar distribution, vascular invasion and previous chemoembolization), they were not independent predictors of recurrence in the multivariate analysis. Actuarial survival in cirrhotic patients with and without HCC at 1, 3 and 5 years was 86

(NS), and 67

(P = 0.002), respectively; whereas actuarial survival of the M and NM groups was 86

, and 78

, respectively (P = 0.02). We had a satisfactory five-year global survival in our series even though one third of our patients grafted for HCC were outside Milan criteria.