Vol. 3 Issue 3
On the cover: Official Journal of the Mexican Association of Hepatology
Oxidative stress is a major pathogenetic event occurring in several liver disorders ranging from metabolic to proliferative ones, and is a major cause of liver damage due to Ischemia/Reperfusion (I/R) during liver transplantation. The main sources of ROS are represented by mitochondria and cytocrome P450 enzymes in the hepatocyte, by Kupffer cells and by neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. A cellular oxidative stress condition is determined by an imbalance between the generation of ROS and the antioxidant defense capacity of the cell and can affect major cellular components including lipids, proteins and DNA. Proteins are very important signposts of cellular redox status and through their structure/function modulation, ROS can also influence gene expression profile by affecting intracellular signal transduction pathways. While several enzymatic (such as superoxide dismutase, catalase, glutathione peroxidase) and non enzymatic (such as 4-hydroxynonenal, decrease of glutathione, vitamin E, vitamin C, malondialdehyde) markers of chronic oxidative stress in liver are well known, early protein targets of oxidative injury are yet not well defined. Identification of these markers will enable early detection of liver diseases and will allow monitoring the degree of liver damage, the response to pharmacological therapies and the development of new therapeutic approaches. In the new era of molecular medicine, new proteomics methodologies promise to establish a relationship between pathological hallmarks of disease and protein structural and functional abnormalities in liver disease, thus allowing a better understanding and a more rational therapy on these disorders.
Nonalcoholic fatty liver disease is a clinicopathologic syndrome that encompasses several clinical entities. The spectrum of conditions ranges from simple steatosis to steatohepatitis, fibrosis and end stage liver disease. The condition was originally described in obese, diabetic, middle-aged females without a history of significant alcohol use with liver histology consistent with alcoholic hepatitis.1,2 It is known that this entity occurs without any particular sex predilection, in lean individuals,3 as well as an increasing number of obese children.4 Other terms have been used to describe this clinical entity such as alcohol-like hepatitis, pseudo-alcoholic hepatitis, diabetic hepatitis and steatonecrosis. Ludwig and colleagues introduced the term nonalcoholic steatohepatitis (NASH) to describe patients fitting the picture of alcoholic hepatitis but without a history of significant alcohol abuse.2 The term nonalcoholic fatty liver disease (NAFLD) is used more frequently to include the spectrum of conditions that range from steatosis through steatohepatitis, fibrosis and cirrhosis. NASH is reserved for patients with steatohepatitis and fibrosis. NAFLD is now being recognized as the most common cause of elevated liver enzymes in the United States. Although the exact etiology of NAFLD is not known, it may be caused by insulin resistance coupled with increased oxidative stress to the hepatocytes. No specific therapy has been approved for this condition and the mainstay of management is weight loss.
Transjugular liver biopsy was first reported in 1967. Since then, this technique has been broadly performed in many medical centers around the world. The number of its indications has increased, and by modifying the needles, the quality of the liver tissue sample has improved. The advantage of transjugular biopsy is that it can be performed in patients in whom the use of percutaneous biopsy is contraindicated Indications for transjugular liver biopsy are, precisely, most of the contraindications for percutaneous liver biopsy. This fact increases the number of patients that can benefit from this procedure. In most cases, the procedure is successfully performed. . Minor complications may occur in 1% to 15% and major complications (perforation of the hepatic capsule, cholangitis, and intra-peritoneal bleeding) are observed in 1-3% of the cases. Mortality related to the procedure varies form 0.2 to 0.3%. It has been reported that diagnosis yielded by transjugular liver biopsy induced changes of treatment in 50% of patients with an acute hepatic illness, in 62% of the patients with a chronic hepatic illness, and in 87% of the patients with liver transplants. In conclusion, transjugular liver biopsy is a useful procedure in the diagnosis of hepatic diseases. Its success rate is high; it is a very safe procedure because complications and mortality are rare; and it is well tolerated by patients.
Objetive: Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to endstage liver disease. We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease. Research methods and procedures: A double-blind, placebo- controlled trial. Twenty-seven women with a body mass index of >30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups (ursodeoxycholic acid, n = 14: placebo n = 13). Both groups received a normal diet (1,200 kcal/d) plus 1200 mg/d of ursodeoxycholic acid or placebo. Hepatic steatosis, was assessed by abdominal ultrasound. Fasting glucose, cholesterol, triglycerides, and aminotransferases levels were determined before and after treatment. Results: Body mass index decreases significantly from 34.2 ± 4.2 kg/m2 and 33.3 ± 1.6 kg/m2 to 31.8 ± 4.5 kg/ m2 and 30.6 ± 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups, p < 0.001. The hepatic steatosis index decreased from 2.3 ± 0.7 to 1.0 ± 0.6 and 2.2 ± 0.7 to 1.1 ± 0.7 in the ursodeoxycholic acid and placebo groups, p<0.003. Serum AST decreased significantly from 41.2 ± 5.6 to 34.5 ± 3.4 in the ursodeoxycholic acid group, p <0.001, and from 43.6 ± 4.2 to 35.3 ± 2.9 in the placebo group, p <0.001. Serum ALT decreased from 62.9 ± 6.5 to 44.0 ± 3.5 in the ursodeoxycholic acid group, p <0.001, and from 63.5 ± 4.5 to 44.0 ± 3.5 in the placebo group. We did not find any differences in all variables studied between groups. Conclusions: The present study shows beneficial effect of weight reduction, producing improvements in biochemical and imaging markers of liver disease.
Aim: To evaluate the effects of ribavirin on cytokine production of recall antigen and PHA-stimulated PBMC obtained from healthy individuals. Materials and methods: PBMC were challenged with tetanus toxoid (5μg/ mL) and PHA (10 μg/mL) in absence or presence of ribavirin at different concentrations (1, 10 and 100 (μM). Parallel sets of wells containing PBMC exposed to medium alone were used as negative controls. On day 3 after initiation of the cultures, IL-2, IFN-γ, IL-4, IL-10, TNF-α content were determined in supernatants of PBMC from the different individuals. Results: The effects of ribavirin on cytokine released by human PBMC in response to PHA and TT showed a great variation among individuals. No significant changes were observed between 1-10μ M concentrations in the production of TNF-α, IFN-γ and IL-10 by both PHA and TT-stimulated PBMC. Ribavirin inhibited TNF-α, IFN-γ, and IL-10 in both PHA and TTstimulated PBMC at 100 μM (p <0.05). At this concentration, ribavirin induced an increase of 124% in the production of IL-2 by PHA-stimulated PBMC (p <0.05). Conclusions: The present data suggest that ribavirin may cause diverse effects on immunoregulatory cytokine secretion with changes in the Th1/Th2 balance.
Aims: To report a case of polysplenia syndrome (PSS) in an adult patient. Background: The PSS is a form of situs ambiguos with multiple spleen, cardiac anomalies, abdominal heterotaxia, short pancreas, major venous system and bronquial malformations. It is a rare syndrome, more often found in childhood, and only the 10% of the patients that do not have cardiac anomalies can reach adulthood. Results: A 56 y/o male with obstructive jaundice and intestinal obstruction who was submitted to an abdominal laparotomy suspecting cholangiocarcinoma. He had choledocolithiasis, duodenal kinking by a preduodenal portal vein, intestinal levorotation, hypoplasic vena cava with a prominent acigos vein, short pancreas and polysplenia. A cholecistectomy, biliodigestive and gastroyeyunal bypasses were performed without any complications and with a succesful evolution. Conclusions: In conclusion, PSS is a rare hereditary syndrome that often occurs in childhood and its discovery in an adult is frequently fortuitus. Surgical treatment is an excellent therapeutic option, however is reserved just for complications. The outcome is good and the final evolution depends on the degree of the cardiac anomalies.
We describe the case of a 36-years-old male patient, originating from India, who presented with enlarged cervical lymph nodes and elevated liver chemistry tests. Histologically necrosing granulomas were observed in the lymph nodes, and PCR revealed DNA from mycobacterium tuberculosis. However, in the liver biopsy granulomatous hepatitis without central necrosis was seen. With a positive PCR for mycobacteria from liver tissue and no evidence for other hepatic diseases we started drug treatment with standard quadruple regimen consisting of isoniazid, rifampicin, ethambutol, and pyrazinamide. Five days after onset of therapy, liver chemistry tests rose 10-fold, forcing us to interrupt treatment. Gradual step-wise re-exposition with the same medication after return of liver chemistry tests to baseline was well tolerated without any further side effects. Liver involvement of tuberculosis can have many facets and may be treated by gradual dosing of standard drugs.