Vol. 1 Issue 4
On the cover: Official Journal of the Mexican Association of Hepatology
Drug-induced hepatotoxicity is a significant and still unresolved clinical problem. The limitation in current knowledge regarding mechanisms of hepatic toxicity renders most of the preclinical review process failing and most of drug-induced hepatic injury remains unpredictable. Current knowledge on the mechanisms of drug-induced liver cell death is reviewed here. The intervention of both intra- and extracellular factors in determining the appearance of drug-induced cell apoptosis or necrosis is also discussed. Finally, the role of both mitochondria and non parenchymal cells are reviewed with respect to approaches useful to manage drug-induced liver injury.
Genomic medicine represents a powerful armamentarium to tackle down most of chronic diseases which have not, so far, defeated. Thus, this new and powerful biotechnologic set of weapons enable us to make use of molecular diagnostic to detect silent diseases, otherwise undetectable by conventional analysis. Moreover, elucidation of the complete and final draft of the human genome code will allow, although not in this decade, the design of specific farmaco-genetic treatments for patients on basis of their individual genetic code. Regarding new medical treatments, gene therapy as emerged as a true hope for treatment of many chronic diseases. 636 FDA-.approved clinical protocols are currently undergoing and sooner than later we´ll be witness of the results.
Portal hypertension surgery has evolved widely in the last decades. Since the first surgical shunt was done in 1945 for the treatment of recurrent hemorrhage, many surgical options have been developed including selective shunts, low diameter shunts and extensive devascularization procedures. Many of them have been studied and compared showing their advantages and disadvantages, evolving also their role in the therapeutic armamentarium. Surgery is nowadays a second line treatment option (after β blockers and endoscopic therapy), and it's main indication is for patients whose main and only problem is history of bleeding, with good liver function (Child-Pugh A). For emergency situations it has a very limited role and for primary prophylaxis virtually has also no role. Patients with good liver function, electively operated with portal blood flow preserving procedures are the patients that benefit from surgical treatment. Patients with a bad liver function are better candidates for a liver transplant.
Viral hepatitis has been shown to be associated with various extrahepatic manifestations. These can be seen in both acute and chronic liver disease, may precede or follow overt liver disease. Aims and objects: To study the prevalence of extrahepatic manifestations of viral hepatitis and follow the course of the disease in response to antiviral therapy whenever indicated. Methods: Prospectively 448 patients of viral hepatitis were evaluated for extrahepatic manifestations and patients of glomerulonephritis (GN), polyarteritis nodosa (PAN) and cryoglobulinemia were tested for viral markers. All patients were investigated for liver and kidney function tests, hematological workup and viral markers such as HBsAg, HBeAg, Anti HBeAg, HCV RNA, IgM anti HAV and IgM anti HEV. Serum electrophoresis and kidney biopsies were done whenever indicated. In 10 cases of hepatitis B glomerulonephritis immunohistochemistry was done on kidney biopsies for demonstration of hepatitis B surface and core antigen. Results: Of total 448 cases 181 (40.4%) had hepatitis B infection, 142 (31.6%) had hepatitis C infection, 86 (19.1%) hepatitis E and 39 (8.7%) had hepatitis A infection. Extrahepatic manifestations were seen in 29 (6.4%) cases and these were cases of GN, PAN, cryoglobulinemia, thrombocytopenia, agranulocytosis, aplastic anemia and pancreatitis. Patients with hepatitis A with extrahepatic manifestations showed complete recovery in both hepatitis and extrahepatic manifestations. Six patients with PAN were treated with interferon of which 4 showed excellent response. Three patients of hepatitis B and hepatitis C related GN were given interferon and 4/6 responded well to treatment. Conclusion: Prevalence of extrahepatic manifestations with viral hepatitis was found to be 6.4%. These manifestations recover completely with recovery from viral hepatitis.
The most practical screening test for hepatitis C virus antibodies are second and third- generation enzyme immunoassays. We evaluated the usefulness of the third generation microparticle enzyme immunoassay (MEIA) in predicting HCV viraemia in anti-HCV positive patients. Serum samples from 106 patients with positive anti-HCV were obtained. To evaluate the diagnostic value of the MEIA test in predicting HCV viraemia, anti-HCV positive patients were categorized in two groups according to the presence or absence of serum HCV-RNA. Among the 106 patients, 26 had non detectable serum HCV-RNA and 80 had detectable HCV-RNA by PCR. The assay automatically calculates a result based on the ratio of sample rate to the cut-of rate for each sample and control (S/CO). When the means of S/CO values for patients with detectable and non detectable HCV-RNA were analyzed, a statistically significant difference was found, (79.3 SD 22.2 vs. 8.2 SD 6.4, respectively) (p 0.0001). We further analyzed the best cut-off value of the S/CO in differentiating viremic from non viremic patients. The S/CO value of 26 showed a sensitivity of 99% and a specificity off 96% in discriminating both categories of HCV infected patients. In conclusion, our data demonstrate that viremic HCV patients had higher S/CO values in the MEIA test in comparison with non viremic patients. Hence, this assay may be used to predict HCV viraemia in anti-HCV positive individuals.
Livers cold preserved in University of Wisconsin (UW) solution followed by reperfusion suffer ischemia/reperfusion injuries. Microcirculation is the primary target of damage, characterized by sinusoidal perfusion failure due, mainly, to morphological changes of sinusoidal endothelial cells. Here, we demonstrated that the addition of S-nitrosoglutathione (GSNO) to the UW solution before cold storage, as a nitric oxide (NO) donor, attenuated hepatic injuries. Wistar adult rat livers were stored in UW solution (0ºC – 48 hs) and then reperfused during 60 minutes using the Isolated Perfused Rat Model (IPRL). We assayed four GSNO concentration (50, 100, 250 and 500 μM). NO concentration was estimated calculating the amount of nitrite (NO2 -) generated in the UW solution. Injuries during cold preservation were established measuring lactate dehydrogenase (LDH) released to the UW solution. Meanwhile, intrahepatic resistance (IR), LDH released to the perfusate, the effluent/perfusate ratio for K+, bile flow, liver glycogen content and sinusoidal endothelial cell morphology were studied after 1 hour of reperfusion in the IPRL system. In cold preserved livers without GSNO, glycogen content was dramatically reduced, IR increased markedly, LDH released was high, bile flow diminished and sinusoidal endothelial cells appeared rounded and detached from perisinusoidal matrix after reperfusion. The presence of 100 μM GSNO prevented the IR rise and LDH release, improved bile production and partially reduced endothelial cells damages. In conclusion, the addition of 100 μM GSNO to UW solution improved hemodynamic and function capacity of cold preserved/reperfused livers.
This is a twenty two years old male patient with weight loss, abdominal pain, hepatomegaly and elevated liver function tests. The serological markers for viral B, C hepatitis and tumoral markers were normal. The CT scan demonstrated a hipodense, nodular lesion in the liver and the histological examination was reported as a typical fibrolamellar hepatocarcinoma.