Nonalcoholic fatty liver disease (NAFLD) and hepatitis C virus (HCV)-related liver disease are common in the general population, but their concurrence is 2- to 3-fold higher than would be expected by chance alone. In patients with chronic HCV infection, steatosis is attributable to a variable combination of the mechanisms considered to play a role in the pathogenesis of NAFLD--insulin resistance in the obese and in the lean subject--along with a direct effect of HCV on hepatic lipid metabolism that leads to triglyceride accumulation through inhibition of export proteins that are required for very low density lipoprotein (VLDL) assembly and secretion. Accumulating evidence suggests that steatosis contributes to the progression of fibrosis in HCV-related disease in a pattern similar to that observed in NAFLD. Potential mechanisms of this effect include the increased sensitivity of steatotic livers to oxidative stress and cytokine-mediated injury. Steatosis-related hepatic insulin resistance may also play a role through the profibrogenic effects of the compensatory hyperinsulinemia and provides a potential explanation for the association between HCV and type 2 diabetes mellitus. Indeed, an appreciation of the importance of fat in HCV has recently led to trials of adjuvant therapy for HCV directed at steatosis-associated disease mechanisms, with encouraging results reported for various modalities, including weight loss and antioxidants. Future therapy should be aimed at exploiting the interactions of HCV with host insulin and lipid metabolism, particularly in nonresponders to standard antiviral schedules.

Endoscopic therapy reduces the rebleeding rate, the need for surgery, and the mortality in patients with peptic ulcer and active bleeding or visible vessel. Injection of epinephrine is the most popular therapeutic method. Guidelines disagree on the need for a second hemostatic procedure immediately after epinephrine; although it seems to reduce further bleeding, its effects on morbidity, surgery rates, and mortality remain unclear. The aim of this study was to perform a systematic review and meta-analysis to determine whether the addition of a second procedure improves hemostatic efficacy and/or patient outcomes after epinephrine injection.

The aim of our study was to conduct a systematic review of studies evaluating prevalence of hepatitis C virus (HCV) infection in B-cell non-Hodgkin's lymphoma (B-NHL) and to perform a meta-analysis of case-control studies comparing this prevalence with that of a reference group.

Reports in the literature regarding the relationship of infection with cagA -positive strains of Helicobacter pylori to gastric cancer over and above H. pylori infection alone are conflicting. The aim of this study was to estimate the magnitude of the risk for gastric cancer associated with cagA seropositivity and to identify any sources of heterogeneity between studies.

The vectorial transport of bile salts from blood into bile is essential for the generation of bile flow, solubilization of cholesterol in bile, and emulsification of lipids in the intestine. Major transport proteins involved in the enterohepatic circulation of bile salts include the hepatocellular bile salt export pump (BSEP, ABCB11), the apical sodium-dependent bile salt transporter (ASBT, SLC10A2) in cholangiocytes and enterocytes, the sodium-dependent hepatocyte bile salt uptake system NTCP (SLC10A1), the organic anion transporting polypeptides OATP-C (SLC21A6), OATP8 (SLC21A8) and OATP-A (SLC21A3), and the multidrug resistance protein MRP3 (ABCC3). Synthesis and transport of bile salts are intricately linked processes that undergo extensive feedback and feed-forward regulation by transcriptional and posttranscriptional mechanisms. A key regulator of hepatocellular bile salt homeostasis is the bile acid receptor/farnesoid X receptor FXR, which activates transcription of the BSEP and OATP8 genes and of the small heterodimer partner 1 (SHP). SHP is a transcriptional repressor that mediates bile acid-induced repression of the bile salt uptake systems rat Ntcp and human OATP-C. A nuclear receptor that activates rodent Oatp2 (Slc21a5) and human MRP2 (ABCC2) is the pregnane X receptor/steroid X receptor PXR/SXR. Intracellular trafficking and membrane insertion of bile salt transporters is regulated by lipid, protein, and extracellular signal-related kinases in response to physiologic stimuli such as cyclic adenosine monophosphate or taurocholate. Finally, dysfunction of individual bile salt transporters such as BSEP, on account of genetic mutations, steric inhibition, suppression of gene expression, or disturbed signaling, is an important cause of cholestatic liver disease.

Ghrelin, a novel 28-amino acid orexigenic peptide discovered in 1999, has given us further insights into the control of energy homeostasis and growth hormone secretion. As a natural endogenous ligand of the growth hormone secretagogue receptor, it potently stimulates growth hormone release but is also implicated in many other homeostatic mechanisms. Released from the stomach, it stimulates lactotroph and corticotroph secretion, increases appetite and adiposity, has beneficial hemodynamic effects, has prokinetic and gastric acid secretory functions in the stomach, and may even be implicated in sleep. As advances in the understanding of appetite and obesity are made, it is timely to review the possibly central role of ghrelin in these physiological and pathophysiological states. This review will discuss the recent literature concerning this exciting novel neuropeptide and discuss the possible therapeutic possibilities it may open up to us.

Ischemia/reperfusion is the main cause of hepatic damage consequent to temporary clamping of the hepatoduodenal ligament during liver surgery as well as graft failure after liver transplantation. In recent years, a number of animal studies have shown that pre-exposure of the liver to transient ischemia, hyperthermia, or mild oxidative stress increases the tolerance to reperfusion injury, a phenomenon known as hepatic preconditioning. The development of hepatic preconditioning can be differentiated into 2 phases. An immediate phase (early preconditioning) occurs within minutes and involves the direct modulation of energy supplies, pH regulation, Na(+) and Ca(2+) homeostasis, and caspase activation. The subsequent phase (late preconditioning) begins 12-24 hours after the stimulus and requires the synthesis of multiple stress-response proteins, including heat shock proteins HSP70, HSP27, and HSP32/heme oxygenase 1. Hepatic preconditioning is not limited to parenchymal cells but ameliorates sinusoidal perfusion, prevents postischemic neutrophil infiltration, and decreases the production of proinflammatory cytokines by Kupffer cells. This latter effect is important in improving systemic disorders associated with hepatic ischemia/reperfusion. The signals triggering hepatic preconditioning have been partially characterized, showing that adenosine, nitric oxide, and reactive oxygen species can activate multiple protein kinase cascades involving, among others, protein kinase C and p38 mitogen-activated protein kinase. These observations, along with preliminary studies in humans, give a rationale to perform clinical trials aimed at verifying the possible application of hepatic preconditioning in preventing ischemia/reperfusion injury during liver surgery.