Probability of liver cancer and survival in HCV-related or alcoholic-decompensated cirrhosis. A study of 377 patients.

BACKGROUND: Although chronic alcohol intake and chronic hepatitis C may progress to cirrhosis and hepatocellular carcinoma (HCC), few data are available about survival and probability of developing HCC in decompensated cirrhosis of both aetiologies. METHODS: This study identified factors related with probability of developing HCC and survival in a cohort of 377 consecutive patients with decompensated HCV-related cirrhosis (200 cases) or alcoholic cirrhosis (177 cases) without known HCC, hospitalized for their first hepatic decompensation, as well as to evaluate differences between both aetiologies. Patients were followed for a mean period of 39 +/- 2 months. RESULTS: During follow-up, 42 patients (11.1%) developed HCC (16.5% vs 5.1%) in groups HCV and alcohol, respectively; p = 0.0008), and 131 patients (34.7%) died (42% vs 26.6% in groups HCV and alcohol, respectively; p = 0.002). Age and HCV-cirrhosis were independently related to HCC development, while baseline age and Child-Turcotte-Pugh score were independently correlated with survival. CONCLUSION: Survival in decompensated HCV-related or alcoholic cirrhosis is influenced by age and baseline Child-Turcotte-Pugh score, without differences in cirrhosis aetiology. The risk of developing HCC is greater in HCV-related cirrhosis than in alcoholic cirrhosis.     

Sterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice

BACKGROUND & AIMS: Sterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo. METHODS: Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice. RESULTS: SCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed. CONCLUSIONS: These results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism, and intestinal cholesterol absorption.     

Idiopathic chronic pancreatitis (with diffuse stenosis of Wirsung's duct) in ulcerative colitis

We describe a case of chronic idiopathic pancreatitis associated with ulcerative colitis. Pancreatitis is a rare extra-intestinal manifestations of inflammatory bowel disease. Chronic idiopathic pancreatitis associated with ulcerative colitis are usually painless, without calcification, with stricture of the main pancreatic duct and with severe exocrine pancreatic insufficiency.     

Hepatitis C virus kinetics during and immediately after liver transplantation

The study of hepatitis C virus (HCV) kinetics after liver transplantation (LT) might be important to design strategies to prevent HCV infection of the graft. We analyzed HCV kinetics during and immediately after LT in 20 consecutive patients undergoing LT for HCV-related cirrhosis. HCV RNA was quantified in blood samples obtained at regular intervals before, during, and after transplantation. HCV-RNA concentrations decreased in 18 of 20 patients during the anhepatic phase (mean decay slope -0.92, mean HCV elimination half-life 2.2 hours). We found a significant correlation between the HCV viral load decay and the blood loss during the anhepatic phase, indicating that the observed HCV clearance rates are maximum estimates. In fact, in 1 patient with an unusually long anhepatic phase of 20 hours and with minimum blood loss, the HCV elimination half-life was 10.3 hours. Eight to 24 hours after graft reperfusion a sharp decrease in HCV viral load occurred in 19 patients (mean decay slope -0.34, mean HCV elimination half-life 3.44 hours). HCV RNA became undetectable in only 1 patient. During the following days, HCV-RNA concentrations increased rapidly in 10 patients (mean HCV doubling time 13.8 hours), remained at similar levels in 4, and continued to decrease in 6. The only variable associated with a second-phase viral load decay was the absence of corticosteroids as part of the immunosuppressive regimen. In conclusion, a sharp decrease in HCV viral load occurs during the anhepatic phase and immediately after graft reperfusion, most likely owing to a lack of virion production and hepatic viral clearance. HCV infection of the graft, however, is an extremely dynamic process and viral replication begins a few hours after LT.     

Is pre-operative anaemia a risk marker for in-hospital mortality and morbidity after valve replacement?

AIMS: To assess the level of pre-operative haemoglobin (HB) as a risk marker for morbidity and mortality in the early post-operative period of patients who underwent elective valve replacement. METHODS AND RESULTS: Between January 1998 and March 2004, clinical and outcomes data were collected for the 201 patients who had elective valve replacement. For each gender, the criterion to choose the best cut-off point was that which achieved the maximum likelihood after several General Additive Model models performed in a Bootstrap procedure. The best cut-off point obtained for pre-operative HB was 12 g/dL. Overall peri-operative mortality (deaths occurring during hospital period or within 30 days) was 9.5%. After adjusting well-known independent pre-operative risk factors for operative mortality, pre-operative HB <12 g/dL was identified as an independent predictor for in-hospital mortality (OR, 3.23; 95% CI, 1.09-9.55; P = 0.03). Also adjusting for EuroScore, pre-operative HB remained significant (OR, 3.64; 95% CI, 1.32-10.06; P = 0.01). The same model was applied to post-operative morbidity, and pre-operative HB <12 g/dL was identified as an independent predictor with and without EuroScore (OR, 4.67; 95% CI, 2.03-10.71; P < 0.001), (OR, 5.18; 95% CI, 2.18-12.3; P < 0.001), respectively. CONCLUSION: In patients undergoing elective valve replacement pre-operative HB <12 g/dL is a risk marker of in-hospital mortality and serious adverse outcomes.     

Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease

OBJECTIVES: Increased homocysteine contributes to the pathophysiology of several chronic inflammatory diseases. Whether homocysteine could participate in mucosal inflammation in inflammatory bowel disease (IBD) has not been explored yet. Our aims were to study the levels of plasma and mucosal homocysteine in IBD patients and to assess whether homocysteine can trigger an inflammatory reaction on human intestinal microvascular endothelial cells (HIMECs). METHODS: Homocysteine was measured in the plasma, mucosal biopsy, and lamina propria mononuclear cell (LPMC) supernatants from normal and IBD subjects. HIMEC were cultured in presence of homocysteine, TNF-alpha, or folic acid, alone or in combination. Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 was measured by flow cytometry and monocyte chemoattractant protein-1 (MCP-1) production by ELISA. Phosphorylation of p38 and p42/44 was assessed by immunoblot in HIMEC extracts. T-cell- and monocyte-HIMEC adhesion assays were used to evaluate the impact of homocysteine on leukocyte adhesion to intestinal endothelial cells. RESULTS: Patients with IBD displayed significantly higher homocysteine plasma and mucosal levels than control subjects. IBD-derived LPMC released higher homocysteine than control-derived LPMC. Treatment of HIMEC with homocysteine, and synergistically with the combination of TNF-alpha and homocysteine, triggered HIMEC inflammation, resulting in VCAM-1 up-regulation, MCP-1 production, and p38 phosphorylation. These events lead to an increased capacity of HIMEC to adhere T- and monocyte cells and were blocked by folic acid treatment. CONCLUSIONS: Homocysteine is increased in both the mucosa and plasma of patients with Crohn's disease and ulcerative colitis and contributes to the inflammatory state of the mucosal IBD endothelium. Therefore, homocysteine could play a proinflammatory role in IBD, which can be efficiently targeted by folic acid supplementation.     

Efectividad de una intervención educativa y de ejercicio físico sobre la capacidad funcional de los pacientes en hemodiálisis

Objective

To describe the impact of a standard hospital educational intervention including active physical exercises on personal well-being, functional capacity and knowledge of the benefits of prescribed physical activity for patients undergoing haemodialysis.