Vol. 2 Issue 2
On the cover: Official Journal of the Mexican Association of Hepatology
Reactive oxygen species (ROS) act as signaling intermediates regulting multiple cellular processes. The fate and disposal of the signaling species are determined by the actions of antioxidants, particularly glutathione (GSH). The mitochondrial pool of GSH (mGSH) arises from the transport of cytosol GSH by a specific mitochondrial carrier and is responsible for the maintenance of a healthy competent organelle. The depletion of mGSH upon impairment of the mitochondrial transport activity leaves mitochondria unprotected from damaging effects of ROS overgeneration within the mitochondrial electron transport chain. Tumor necrosis factor-α (TNF-α) has emerged as a key player in the progression of the alcohol-induced liver disease (ALD), and is known to target mitochondria. Key components of TNF signaling include sphingolipids, particularly ceramide generated from acidic sphingomyelinase activation serving as a source for gangliosides. In experimental models alcohol consumption enhances cholesterol levels and subsequent deposition into mitochondria resulting in selective decrease in the mGSH stores which is sufficient by itself to sensitize hepatocytes to TNF-α-mediated cell death. Thus, the combination of TNF-α overproduction, enhanced glycosphingolipid generation and selective mGSH depletion by alcohol intake cooperate making the liver sensitive to alcohol.
The prevalence of HCV infection is very diversified according to geographical areas and ranges from 1% in the Northern regions of the world to more than 20% as we move South. Due to the presence of HCVassociated liver diseases and the development of effective treatments, the diagnosis of HCV infection is a growing medical need. Several tests are available, from simple screening to identify the presence of anti- HCV antibodies to the more sophisticated quantification of viral load and genotyping. However, these tests are to be used in a logical, consequential and cost-effective manner. This review article will report on the protocol in use in the North-Eastern part of Italy for the screening and diagnosis of HCV infection. The protocol is based on a consensus among several experts and may be the basis for a more rational approach in this rapidly growing field.
Alcohol metabolism is a complex process with large individual variations related to absorption, distribution and elimination. Among the multiple factors which influence these variations, genetic factors especially those related to the different alleles of ADH2 and ALDH2, are the most well known and are related to the development of alcohol dependence, particularly in some populations such as those of Asian origin. The importance of new polymorphisms such as those in the ALDH promotor region requires further study. Furthermore, the importance of other factors such as nutrition and gastric metabolism should be taken into account to explain the variations in ethanol metabolism. The metabolic alterations produced by alcohol in the liver are responsible for liver damage. The individual variations in the metabolism of alcohol are responsible for the different toxicity of alcohol in both the liver and other organs.
Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and extra cellular matrix. In this study we analyzed the benefit of adding either 500 μM Sodium Nitroprusside (NPNa) or 100 μM S-nitrosoglutathione (GSNO) as Nitric Oxide (NO) donors to the UW solution to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (0ºC) for 48Hs and reperfused (60 minutes) in the isolated perfused rat liver model (IPRL). Untreated livers were used as normal controls. Livers perfused but not preserved were used as controls of reperfusion. Parenchyma damages were evaluated by Hematoxylin-Eosin stain. Picrosirius Red and Gordon-Sweets stains were used for collagen and reticulin networks, respectively. An inmunohistochemistry assay for albumin was used as functional test. Cold preservation step was followed by swollen hepatocytes with "light empty halos" surrounding the nucleus, conserved hepatocyte cords and many rounded endothelial cells. The addition of NPNa or GSNO into UW solution, avoid these alterations. Livers preserved for 48 Hs and then reperfused showed extended areas of vacuolation around central veins, and many endothelial cells were rounded and located inside sinusoidal lumens. The collagen network was disorganized while the reticulin one was less altered. Albumin was distributed preferentially in pericentral areas. On the contrary, livers preserved in presence of NPNa or GSNO did not show vacuolation and both collagen and reticulin networks were unchanged. Albumin was more homogeneously distributed in both groups. In conclusion, the addition of 500 μM NPNa or 100 μM GSNO as a NO donor, improves UW solution properties to preserve rat livers by maintaining the hepatic morphology and avoiding hepatic injury post-cold preservation/reperfusion.
Introduction: The course of HBV infection and the outcome of interferon alpha (IFNα) therapy of patients with chronic hepatitis B, is determined by the antiviral immune response of the host. The aim of the study was to investigate 1) the correlation between IL-6 and IL-12 serum levels and biochemical and histopathological changes in children with chronic hepatitis B, 2) predictive value of pre-treatment serum levels of these cytokines in patients treated with interferon alpha and 3) changes in serum levels of these cytokines after interferon alpha treatment. Methods: Serum levels of IL-6, IL-12 (heterodimer p70) and IL-12 (heterodimer p70 & p40 subunit) were determined by specific ELISA in 39 children with chronic hepatitis B on the first and the last day of IFNα therapy. Results: Serum levels of IL-6, IL-12 (p70) and IL-12 (p70&p40) were respectively within the following ranges of values: 0-1.7 pg/mL, 3.0-85.1pg/mL, 93.7-442.7 pg/mL and they showed no correlation with biochemical and histopathological changes. The pre-treatment cytokines levels in patients who responded and those who did not respond to IFNa therapy did not differ statistically. There was no statistical difference between the end and pre-treatment cytokines levels in both groups. Conclusions: Serum levels of IL-6 and IL-12 do not reflect the inflammatory activity of hepatitis and have no predictive value of positive response to the IFNα therapy in children with chronic hepatitis B. Serum IL-6 and IL-12 levels at the end of INFα treatment do not inform of their role in immunological changes which take place while inhibition of HBV replication or virus clearance.
A 32-year-old woman was admitted to hospital complaining of right upper quadrant and epigastrium abdominal pain, and nausea. On routine physical examination an abdominal mass was discovered on the right upper quadrant. Liver tests were normal. Magnetic resonance imaging of the abdomen revealed a lowdensity cystic mass. A cystectomy was performed. Hydatid sand containing a protoscolex of Echinococcus granulosus was seen on microscopical examination. Specific antiparasitic treatment was given and after two months the patient is asymptomatic.