Abstract: OBJECTIVE: To find the survival and the predictors of death of HIV-infected patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD). DESIGN AND METHODS: A prospective cohort study set in the infectious diseases units of four tertiary care public hospitals in AndalucÃa, Spain. From a multicentric cohort of 2664 HIV/HCV-co-infected patients, all consecutive patients with HCV-related cirrhosis who presented with the first hepatic decompensation from January 1997 to June 2004 were followed-up and 153 patients were included. The survival and the demographic, HIV-related and liver-related factors associated with death were evaluated. RESULTS: Ninety-five (62%) patients died during the follow-up. In 79 (85%) individuals, the cause of death was liver related. The median survival time was 13 months. Independent predictors of survival were Child score [hazard ratio (HR), 1.2; 95% confidence interval (CI), 1.08-1.37; P = 0.001], CD4+ cell count at decompensation lower than 100 cells/microl (HR, 2.48; 95% CI, 1.52-4.06; P < 0.001) and hepatic encephalopathy as the first hepatic decompensation (HR, 2.45; 95% CI, 1.41-4.27; P = 0.001). HAART was prescribed to 101 (66%) patients. The cumulative probability of survival in patients under HAART was 60% at 1 year and 40% at 3 years, versus 38 and 18%, respectively, in patients not treated with HAART (P < 0.0001). The HR (95% CI) of death in patients on HAART was 0.5 (0.3-0.9), (P = 0.03). CONCLUSIONS The survival of HIV/HCV-co-infected patients with ESLD is extremely poor. Immunosuppression and markers of severe liver disease predict liver-related mortality in these patients. HAART seems to be associated with a reduced liver-related mortality.
Abstract: OBJECTIVE: Endothelial activation plays an active role in modifications of the circulatory status of cirrhotic patients. Soluble endothelial adhesion molecules, induced by pro-inflammatory cytokines, could be considered markers of endothelial activation. Their role in the natural history of cirrhosis and portal hypertension has not been reported. Our objective was to analyze the prognostic value of soluble adhesion molecules in cirrhotic patients. MATERIAL AND METHODS: Serum concentrations of soluble CD14, soluble receptors of tumor necrosis factor alpha and adhesion molecules ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule 1) as well as mean blood pressure, plasma renin activity, aldosterone, vasopressin and norepinephrine concentrations were determined in 64 cirrhotic patients (Child-Pugh class: A 48.4%, B 34.4%, C 17.2%), without any evidence of infection, and in 25 healthy controls. Patients were followed-up for a mean of 36.4 (range 6-60) months. RESULTS: Increased concentrations of soluble CD14, tumor necrosis factor receptors and ICAM-1 and VCAM-1 were detected in cirrhotic patients when compared with healthy controls. Tumor necrosis factor receptors and adhesion molecule concentrations were both significantly higher in advanced phases of cirrhosis (Child Pugh class C and B versus A). Fifteen patients died as a related consequence of liver cirrhosis. Multivariate analysis demonstrated that Child-Pugh score and serum levels of tumor necrosis factor receptor I and ICAM-1 were associated with mortality. CONCLUSIONS: In addition to the classic factor implicated in mortality (Child-Pugh class), alterations in inflammation-related components and soluble adhesion molecules, as representatives of hemodynamic alterations, are of prognostic significance in cirrhotic patients.
Abstract: BACKGROUND/AIMS: Increased serum concentrations of pro-inflammatory cytokines have been detected in patients with liver cirrhosis. However, their role in the natural history of cirrhosis and portal hypertension, in the absence of infection, and the prognostic significance of inflammation-related cytokines have not been reported. Our objective was the analysis of the prognostic value of inflammation-related cytokines in cirrhotic patients. PATIENTS AND METHODS: Serum concentrations of tumor necrosis factor (TNF-alpha) and its soluble receptors I and II and interleukin 6 (IL-6), as well as mean blood pressure, plasma renin activity, aldosterone, vasopressin and norepinephrine concentrations were determined in 72 cirrhotic patients (Child-Pugh score: A 50%, B 33.3%, C 16.7%), without any evidence of infection, and in 25 healthy controls. Patients were followed up for a median of 35.9 (range 6-60) months. RESULTS: Increased concentrations of soluble TNF receptors were detected in cirrhotic patients when compared with healthy controls. TNF receptors and IL-6 concentrations were both significantly more elevated in advanced phases of cirrhosis (Child-Pugh score C vs B and vs A). Sixteen patients died as a related consequence of liver cirrhosis. Multivariant analysis demonstrated that Child-Pugh score, mean blood pressure and serum levels of TNF receptor I were associated with mortality. CONCLUSIONS: In addition to the classic factors implicated in mortality (Child-Pugh score and hemodynamic parameters), alterations in inflammation-related components are of prognostic significance in cirrhotic patients.
Abstract: To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.
Abstract: BACKGROUND: To relate the renal hemodynamic changes, as assessed by Doppler ultrasonography,with the development of ascites, renal function, and endogenous vasoactive systems in patients with liver cirrhosis. PATIENTS AND METHODS: 60 cirrhotic patients were studied prospectively, 31 of these compensated and 29 with ascites. The renal resistive index, renal function and plasmatic levels of renin, aldosterone, noradrenaline and ADH activity were determined. RESULTS: The renal resistive index was significantly higher in the cirrhotic patients with ascites (0.68) than in the compensated cirrhotics (0.63) and was significantly correlated with the serum levels of creatinine,urinary excretion of sodium, plasmatic renin activity and plasmatic concentration of aldosterone. CONCLUSIONS: The renal resistive index, study by means of Doppler ultrasonography, shows progressively increased levels with the evolution of the disease, with the deterioration of the renal function and with the activation of the endogenous vasoactive systems.
Abstract: AIM: To assess renal hemodynamics by Doppler analysis of resistive index (RI) in small intrarenal arteries in patients with chronic liver diseases at different stages, and to analyze renal RI in patients with cirrhosis as a function of the absence or presence of ascites and the response to diuretic therapy. METHODS: Prospective cross-sectional study of 24 patients with chronic hepatitis, 39 with compensated cirrhosis, and 34 with ascites. The last group was divided into two subgroups: 1) responders to sodium restriction and a low dose of diuretics, and 2) patients with refractory ascites or those requiring high-dose therapy. RESULTS: Renal RI was increased in patients with cirrhosis and ascites (0.68 +/- 0.06) in comparison with patients with compensated cirrhosis (0.63 +/- 0.03, p < 0.01). Renal RI in the latter group was higher than in patients without cirrhosis (0.61 +/- 0.04, p < 0.05). Renal RI in patients with ascites was lower in subgroup 1 than in subgroup 2 (0.65 +/- 0.05 vs 0.72 +/- 0.06, p < 0.01). CONCLUSIONS: Renal RI increases as liver disease progresses. Patients with cirrhosis and ascites and increased RI require high-dose treatment or do not respond. Further studies are needed to demonstrate the predictive value of renal RI in assessing the effectiveness of diuretic therapy.
Abstract: OBJECTIVE: The aim of this study was to identify factors related with mortality in patients with cirrhosis in the absence of habitual biochemical markers of liver dysfunction. METHODS: Seventy-five cirrhotic patients in Child-Pugh stage A, without hepatocellular carcinoma, were followed until death or the end of the study period. We analyzed the association between cumulative survival and 15 variables determined at the moment of inclusion: age, sex, time from diagnosis of cirrhosis, alcohol abuse, history of variceal bleeding, hepatitis B and C virus infection, Child-Pugh score, plasma albumin and bilirubin levels, prothrombin activity, and four sonographic parameters (size of liver, portal vein diameter, size of spleen, and presence of collateral circulation). RESULTS: Mean follow-up was 38.7+/-10 months. Eighteen patients died. Four-year cumulative survival was 77.4+/-5%. Only five variables had a significant influence on survival according to log-rank test: sex, previous variceal bleeding, hepatitis B virus infection, portal vein diameter, and size of the spleen. Multivariate Cox's model showed male sex (relative risk 4.6; 95% confidence interval 1.2-16.8) and diameter of the portal vein > 13 mm, splenomegaly > 145 mm, or both together (relative risk 6.0; 95% confidence interval 1.3-27.2) as independent predictors of the risk of death. CONCLUSIONS: Child-Pugh stage A cirrhotic patients have substantial variability in mid-term survival. Ultrasonography is a useful aid in establishing their prognosis. Men with dilation of the portal vein, splenomegaly, or both, form a group with a significantly higher risk of death.
