Factors influencing renal function after liver transplantation. Results from the MOST, an international observational study.

INTRODUCTION: Renal failure, both acute and chronic, is a common complication after liver transplantation and can seriously jeopardise long-term outcome. Given organ shortage it should be essential to determine which patients will experience progressive and severe renal dysfunction after liver transplantation (LT). AIM: To correlate pre-transplant renal function and risk factors for renal failure after liver transplantation with occurrence of renal failure at 1 and 5 years after LT, with particular attention to hepatitis C virus (HCV) infection. METHODS: Data from patients enrolled in the liver section of Neoral MOST (Multinational Observational Study in Transplantation) study were used for the analysis. HCV status, pre-transplant serum creatinine level, recipient gender, recipient age, pre-transplant arterial hypertension, pre-transplant diabetes mellitus, pre-transplant antiviral therapy, the time of the transplant (before or after 2000) and immunosuppressive regimen were collected for each patient. Post-transplant occurrence of renal failure at 1 and 5 years was defined as a GFR<60 mL/min/1.73 m(2) (Stage III of the National Kidney Foundation). RESULTS: Data from 1948 patients enrolled in the study were considered. Glomerular filtration rate (GFR) was evaluated in 406 patients at 1 year and in 233 patients at 5 years after LT. The prevalence of HCV infection was 35% in the former and 37% in the latter. The median GFR was 70 mL/min/1.73 m(2) after 1 year and 69 mL/min after 5 years, significantly lower in HCV-positive (HCV+) than in HCV-negative (HCV-) patients both 1 and 5 years after LT (p<0.001). GFR before transplant correlated with GFR at 1 month, 1 and 3 years (p<0.0001 for all correlations). Multivariate analysis confirmed HCV status, pre-LT serum creatinine levels and recipient gender as significant predictors of 1-year GFR (p<0.001 for all three). Further analysis of the effect of recipient gender indicated that the only significant risk factor observed in both male and female patients was HCV positivity. Only 1-year GFR was an independent predictor of 5-year GFR (p<0.001). HCV+ status, cyclosporine (CsA) exposure, antiviral therapy and diabetes mellitus had no significant influence on 5-year GFR. CONCLUSIONS: HCV status and pre-LT serum creatinine levels were independent predictors of renal function a year after LT, together with GFR before transplant. The negative impact of HCV positivity on renal function was not confirmed in the long term, whereas the prognostic influence of an abnormal renal function in the early post-transplant period was more persistent

HCV infection in haemodialysed patients: A role for serum IL-10 and TGF-beta(1) in liver damage?

Abstract BACKGROUND: Hepatitis C virus (HCV) infection is often clinically silent in haemodialysed (HD) patients and their immune response may modulate liver damage in HCV infection. IL-10 and TGF-beta1 could play a role in this setting as, IL-10 down-regulates hepatic fibrosis, while TGF-beta1 is a pro-fibrotic cytokine. AIM: To evaluate the role of IL-10 and TGF-beta1 in HD/HCV+ patients. PATIENTS: 71 HD/HCV+ patients (58 with normal [HD/HCV-N] and 13 with high serum transaminases [HD/HCV-H]), 40 non-uremic patients with chronic hepatitis C (HCV+), 56 HD anti-HCV- patients and 20 healthy volunteers (H). METHODS: IL-10 and TGF-beta1 serum levels were assessed using ELISA tests. Liver histology was assessed by Ishak's score. RESULTS: IL-10 serum levels were significantly higher in HD patients, both HCV+ (3.7+/-0.4 pg/ml; p<0.01) and HCV- (3.8+/-0.8 pg/ml; p<0.05) than in non-uremic HCV patients (2.3+/-0.4 pg/ml). Among the HD/HCV+ patients, IL-10 serum levels were similar in HD/HCV-N and in HD/HCV-H patients. Among the HD/HCV+ patients, IL-10 serum levels were similar in those with moderate histological damage compared to those with mild damage. TGF-beta1 serum levels were significantly lower in HD patients, both HCV+ (4.6+/-0.9 ng/ml) and HCV- (6.0+/-0.9 ng/ml) than in non-uremic HCV+ patients (8.1+/-1.1 ng/ml; p<0.001 and p<0.01, respectively), but similar to the values found in H (5.3+/-0.9 ng/ml; p=n.s.). No correlation was seen between IL-10 and TGF-beta1 serum levels in any of the groups considered. CONCLUSIONS: Patients on haemodialysis treatment to have high levels of IL-10, which remain high even when patients are anti-HCV+, whereas the opposite is true of TGF-beta1. The cytokine pattern observed in HD patients is compatible with the hypothesis explaining the relatively benign evolution of HCV-related liver disease in HD patients, and has a pathophysiological role

Accident proneness and impulsiveness in an Italian group of burn patients.

There is controversy about the existence of a predisposition to burn incidents (accident proneness). Our objective was to examine, in a group of burn patients, the conditions or "unconscious" subjective predisposition, the presence of impulsiveness that may have contributed to bringing about the "burn" event, and to assess the presence of psychiatric diagnoses and specific characteristics of temperament. 25 consecutive burn patients were interviewed by using specific psychometric tests. The sample was divided into two groups: "control" group (N=10), composed of subjects who had accidentally been involved in the incident and "case" group (N=15) composed of subjects who had very likely and more or less "knowingly" put themselves at risk of injury. We observed a marked statistically significant difference with case group subjects appearing to be more impulsive than the ones in control group. Higher levels of impulsiveness may predispose case group patients to a greater risk of burn. Our survey also seems to reveal a relationship between impulsiveness and the proneness of some subjects to burns

HCV infection in haemodialysed patients: a role for serum IL-10 and TGF-beta1 in liver damage?

BACKGROUND: Hepatitis C virus (HCV) infection is often clinically silent in haemodialysed (HD) patients and their immune response may modulate liver damage in HCV infection. IL-10 and TGF-beta1 could play a role in this setting as, IL-10 down-regulates hepatic fibrosis, while TGF-beta1 is a pro-fibrotic cytokine. AIM: To evaluate the role of IL-10 and TGF-beta1 in HD/HCV+ patients. PATIENTS: 71 HD/HCV+ patients (58 with normal [HD/HCV-N] and 13 with high serum transaminases [HD/HCV-H]), 40 non-uremic patients with chronic hepatitis C (HCV+), 56 HD anti-HCV- patients and 20 healthy volunteers (H). METHODS: IL-10 and TGF-beta1 serum levels were assessed using ELISA tests. Liver histology was assessed by Ishak's score. RESULTS: IL-10 serum levels were significantly higher in HD patients, both HCV+ (3.7+/-0.4 pg/ml; p<0.01) and HCV- (3.8+/-0.8 pg/ml; p<0.05) than in non-uremic HCV patients (2.3+/-0.4 pg/ml). Among the HD/HCV+ patients, IL-10 serum levels were similar in HD/HCV-N and in HD/HCV-H patients. Among the HD/HCV+ patients, IL-10 serum levels were similar in those with moderate histological damage compared to those with mild damage. TGF-beta1 serum levels were significantly lower in HD patients, both HCV+ (4.6+/-0.9 ng/ml) and HCV- (6.0+/-0.9 ng/ml) than in non-uremic HCV+ patients (8.1+/-1.1 ng/ml; p<0.001 and p<0.01, respectively), but similar to the values found in H (5.3+/-0.9 ng/ml; p=n.s.). No correlation was seen between IL-10 and TGF-beta1 serum levels in any of the groups considered. CONCLUSIONS: Patients on haemodialysis treatment to have high levels of IL-10, which remain high even when patients are anti-HCV+, whereas the opposite is true of TGF-beta1. The cytokine pattern observed in HD patients is compatible with the hypothesis explaining the relatively benign evolution of HCV-related liver disease in HD patients, and has a pathophysiological role

Torque Teno virus: any pathological role in liver transplanted patients?

Few studies have been performed on the prevalence of Torque Teno Virus (TTV) infection in liver transplant (LT) recipients. The aim of this study was to assess the prevalence, viremia and genogroup pattern of TTV among LT patients and to ascertain whether TTV causes liver damage in liver transplanted patients with biochemical and histological changes of unknown origin. Twenty-five patients were evaluated before and after LT; 80 healthy subjects were considered as controls. Serum samples were serially obtained from all the patients before LT and thereafter at 3, 6 and 12 months post-transplant. Serum TTV-DNA and genogroups were assessed by PCR. Patients underwent protocol serial liver biopsies at 6 and 12 months after LT. Results were compared using the Chi-squared tests, McNemar's and Student's t-tests. TTV-DNA was found in 25/25 patients before LT and in 60/80 blood donors (P < 0.01). The TTV-DNA load increased significantly after LT (P < 0.001). TTV-DNA was significantly higher in patients on calcineurin inhibitors (CNI) and azathioprine or mycophenolate mofetil than in patients on CNI alone (P = 0.04) at 3 months after LT. Genogroup analysis showed a significant increase in genogroup 5 positivity after LT. No differences were seen in the viremia of patients compared according to their viral versus other etiologies of their liver disease before transplantation. Viremia and TTV genotype patterns did not correlate with the presence of hypertransaminasemia or histological liver damage of unknown etiology. The prevalence of TTV-DNA was significantly higher in patients with liver cirrhosis than in controls and the viral load was significantly higher after LT than beforehand. On the basis of our data, TTV does not seem to cause liver damage following LT, although larger studies with a long-term follow up are needed to confirm these findings