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This book presents topical research in the study of liver cirrhosis, including etiologic types of end stage chronic liver disease; hepatocellular carcinoma screening in the cirrhotic patient; hepatic myofibroblasts and their role in liver fibrogenesis; the role of trace elements in the pathogenesis of liver cirrhosis and cell-based therapy for liver cirrhosis.
Chapter 1 – Thalidomide is currently used for treating erythema nodosum leprosum,multiple myeloma, angiogenesis, rheumatoid arthritis, graft-versus-host disease, among others. Thalidomide effects are related to its capacity to inhibit the proinflammatory cytokine tumor necrosis factor-α (TNF-α) and, in consequence, causes immunomodulation on other cytokines. During the establishment of some diseases the balance between proinflammatory and antiinflammatory cytokines is disrupted, promoting a pathological state; thus, elevated levels of proinflammatory cytokines mediate several deleterious processes such as inflammation, necrosis, apoptosis and fibrosis. These events are present in acute and chronic degenerative liver diseases such as hepatitis, cholangitis, cirrhosis and hepatocellular carcinoma (HCC). Therefore, the regulation of immunity to cytokines by drugs appears. Medicinal purpose to improve liver damage and cirrhosis. In fact, nothing Sufficient medicines to relieve or treat cirrhosis are currently some of the most expensive, It can be unstable and calm or cause side effects. The new analog was thalidomide Synthesized with improved stability and strength as a TNF-α inhibitor and safety regulator
There are few or no agents, and teratogen. Thalidomide and its experimental evaluation Analogs of animal models of liver injury show very promising results. thalidomide And the two analogs showed anticholestasis, antinecrosis and antifibrotic activity in bile. Biliary cirrhosis due to tube closure. Another analog protected D-galactosamine/endotoxintreated mice from liver damage. Thalidomide ameliorated the alcoholic hepatic injury and prevented necrosis, cholestasis and fibrosis induced by CCl4 in rats. Moreover, this drug salvaged from lethal hepatic necroinflammation and accelerated the recovery from established
thioacetamide-provoked cirrhosis in rats. The antiinflammatory, antinecrotic and antifibrotic effects elicited by thalidomide and its analogs are mainly mediated by the inhibition on TNF- through two different routes, as well as the down-regulation of nuclear factor-B (NF-B) signaling pathway and by diminishing adhesion molecules to prevent the progression of liver fibrosis and cirrhosis. Furthermore, thalidomide showed beneficial effects on HCC by decreasing angiogenesis and metastasis in murine models; therefore, diverse clinical phase
I/II studies were carried out to evaluate its antitumoral or disease control outcomes. However, thalidomide as a single drug therapy yields very modest benefits, although in most cases this from hepatocytes and cholangiocytes through a process of epithelial to mesenchymal transition. Hepatic myofibroblasts have been reported to play additional crucial roles, including modulation of immune responses in the chronically injured liver and the cross talk with hepatic progenitor (stem) cells as well as with malignant cells of either primary hepatocellular carcinomas or of metastatic cancers.
Chapter 6 – Liver cirrhosis (LC) is not a single disease. It is the outcome of different diseases that are associated with chronic loss of hepatocytes and its replacement by fibrosis and formation of regenerative nodules. The process distorts the architecture of liver parenchyma resulting in development of porto-systemic shunting of blood and impairment of hepatic function. Chronic alcohol abuse, chronic hepatitis B virus (HBV) and chronic Hepatitis C virus (HCV) infection is the leading cause of liver cirrhosis worldwide. There is minor causes of LC. The LC type is common in any country or community:
Determined by geocultural factors. While HBV infection is the main cause of cirrhosis HCV infection is a major cause in Asia and Africa, Japan. Wine and now
Emerging HCV infection in the West is the leading cause of cirrhosis. Among minor causes of cirrhosis hepatic vena cava disease (HVD) is reported only from developing countries. The reported incidence of LC in HVD varied from 71 to 100%.
Chapter 7 – This chapter will present the critical interplay between liver cirrhosis and surgery. First, the question of patients with cirrhosis needing to undergo a surgical procedure will be explored. Specifically, the different ways that the level and severity of cirrhosis can be estimated will be examined, and how these could determine the safety of proceeding with a surgery, as well as the prognosis of these patients, according to the different surgical procedures. The second question to consider is the role of surgery as a portal therapy High blood pressure, one of the deadliest complications of cirrhosis. it will be Verified by pathophysiological analysis of portal hypertension in cirrhosis and presentation
Different surgical procedures for the treatment of portal hypertension and its complications Particular emphasis on the indications and contraindications for each. Finally a file has been created The risk of cirrhosis is the development of hepatocellular carcinoma. This chapter will present: The pathophysiology leading to this progression, as well as the site of surgery as a treatment Hepatocellular carcinoma in cirrhotic patients with two main alternatives Surgical resection versus transplantation. The aim is to identify groups of patients It is best served by any alternative.
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