Search

The hepatoprotective mechanisms of N-acetylcysteine (NAC) in non-acetaminophen-induced liver injury have not been studied in detail. We investigated the possibility that NAC could affect key pathways of hepatocellular metabolism with or without changes in glutathione (GSH) synthesis. Hepatocellular metabolites and high-energy phosphates were quantified from mouse liver extracts by 1H- and 31P-NMR (nuclear magnetic resonance) spectroscopy. 13C-NMR-isotopomer analysis was used to measure [U-13C]glucose metabolism through pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC). NAC (150-1,200 mg/kg) increased liver concentrations of GSH from 8.60 +/- 0.48 to a maximum of 12.95 +/- 1.03 micromol/g ww, whereas hypotaurine (HTau) concentrations increased from 0.05 +/- 0.02 to 9.95 +/- 1.12 micromol/g ww. The limited capacity of NAC to increase GSH synthesis was attributed to impaired glucose metabolism through PC. However, 300 mg/kg NAC significantly increased the fractional 13C-enrichment in Glu (from 2.08% +/- 0.26% to 4.00% +/- 0.44%) synthesized through PDH, a key enzyme for mitochondrial energy metabolism. This effect could be uncoupled from GSH synthesis and was associated with the prevention of liver injury induced by tert-butylhydroperoxide and 3-nitropropionic acid. In conclusion, NAC (1) has a limited capacity to elevate GSH synthesis; (2) increases HTau formation linearly; and (3) improves mitochondrial tricarboxylic acid (TCA) cycle metabolism by stimulation of carbon flux through PDH. This latter effect is independent of the capacity of NAC to replete GSH stores. These metabolic actions, among other yet unknown effects, are critical for NAC's therapeutic value and should be taken into account when deciding on a wider use of NAC.

Background: Bleeding is a recognized complication of abdominal paracentesis. Special concern has been raised when it is performed in patients with liver failure because of coagulation disorders and collaterals in the abdominal wall., Aim: To assess the clinical characteristics of patients who developed haemorrhagic complications after paracentesis., Methods: We reviewed all cases of severe haemorrhage occurring after paracentesis in patients admitted to the Liver Unit of our institution between 1994 and 2004., Results: Nine cases were identified among 4729 procedures. The occurrence of severe haemorrhage represented 0.19% of all procedures with a death rate of 0.016%. Bleeding was not related to operator experience, elevated international normalized ratio or low platelets. It occurred in patients with high model for end-stage liver disease and Child-Pugh scores. Furthermore, some degree of renal failure was present in all but one patient., Conclusion: Severe haemorrhage after abdominal paracentesis in patients with liver disease occurs in 0.2% of cases. It occurs in patients with severe liver failure and is often associated with significant pre-existing renal dysfunction.

Hepatocyte cell death is a cardinal feature of almost every liver disease. Apoptosis is a mode of cell death characterized by specific morphological and biochemical features. Over the past decade, the importance of apoptosis has been appreciated, and it is now thought to be the main mode of cell death in liver diseases. The recognition that apoptosis can be modulated by the cell itself or by the extracellular environment has given hope that treatments can be designed to modify the evolution of disease. This article presents an overview of this important phenomenon, as well as models of hepatocyte apoptosis and goals of current research. The significance of apoptosis to the pathophysiology of liver disease is discussed.

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level. [ABSTRACT FROM AUTHOR]

The number of hepatitis C virus ( HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical. [ABSTRACT FROM AUTHOR]

The disease burden of hepatitis C virus ( HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing. [ABSTRACT FROM AUTHOR]

Variceal bleeding in cirrhotic patients with severe liver failure that is not controllable by endoscupic sclerotherapy is a life-threatening situation. We report the case of a patient with decompensated cirrhosis (Pugh class C) who bled repeatedly from gastric varices despite multiple sessions of sclerotherapy. The portal vein vias catheterized by a transjugular approach. A tract between a hepatic vein and the portal vein was created after balloon dilatation, and this opening was stented with an expandable stainless steel Palmaz stent. The portal vein pressure decreased from 35 mm Hg to 19 mm Hg after shunting. Gastric varices also were embolized. Two months later, bleeding had not recurred; the shunt remained opened and the marked decrease in portal pressure still persisted. Endoscopy showed the disappearance of gastric varices. This procedures could become a life-saving therapeutic option for such critically ill cirrhotic patients. [ABSTRACT FROM AUTHOR]