Daño hepático inducido por drogas

Drug induced liver disease is responsible of 5 percent of hospital admissions for jaundice in USA, and 10 percent of acute hepatitis in France and North Europe. In addition, 20 to 50 percent of the cases of fulminant hepatic failure in USA are due to drugs. Tradicionally drug induced liver disease has been divided in two groups : 1. Non predictable toxicity (idiosyncratic reaction). 2. Predictable toxicity (Intrinsec toxicity). From the clinical point of view, most of the patients present jaundice associated with elevation of aminotransferases and alkaline phosphatase. However, some patients presents acute liver failure and death. Te duration of illness permit another classification in two groups : acute, frequently characterized by microvesicular steatosis; a picture similar to acute viral hepatitis or biliary obstruction (cholestasic jaundice) with elevated alkaline phosphatase and pruritus. Chronic, manifested by different presentations such as acute hepatitis, chronic hepatitis, (autoimmune), sclerosing cholangitis, phospholipidosis and non cirrhotic or cirrhotic portal hypertension. Histologically drug toxicity can induce the following morphologic changes : a) Pure cholestasis more frequently seen with estrogens. b) Viral hepatitis like. c) Fulminant hepatic failure more commonly seen with halotane, acetaminophen, phenytoin and methyldopa shows multilobular necrosis frequently asssociated with hypersensitivity features (fever, pruritus, eosinofilia)...

Enfermedad alcohólica del hígado (EHA)

Alcohol consumption with all its severe organic complications has become one of the leading causes of morbidity and mortality in United States. In the metropolitan areas, alcohol consumption is the third cause of death between people aged 30 to 64. Latest estimates have shown that 20 percent of the total cost of health care is related to alcohol. Liver disease secondary to alcohol has been studied extensively and all its clinico-pathological consequences described. Alcoholic hepatitis characterized by anorexia, jaundice, hepatomegaly, fever, mental changes, leukocytosis and neutrophilia has been described associated to elevated bilirubin, low albumin, high AST levels and prolonged prothrombin time; histologically the picture has the following microscopic findings: degenerative changes of liver cells such as "ballooning" mainly around the terminal hepatic veins, acute and chronic inflammatory infiltrates and latest, pericellular fibrosis in the centrolobular area. Some patients develop sclerosing hyaline necrosis consistent in collapse of hepatocytes, alcoholic hyaline accumulation, neutrophilic inflammation and severe fibrosis leading to a functional obstruction of the hepatic veins, portal hypertension, ascitis and liver failure. A characteristic cytosqueletic abnormality is the Mallory Body that for many authorities constitutes the hallmark of alcoholic hepatitis. Recently the role of megamitochondrias in this entity has been unveiled showing that patients with increased number have better prognosis that the group with few megamitochondrias. Finally a significant role for cellular immunity, cytoquines, histocompatibility antigens and malnutrition has been found determinant in order to explain progression of disease after alcohol discontinuation, and prognosis after nutritional therapy.

Malignidad primaria del hígado

The most common liver tumor in USA and most of the western world is metastasic. Primary hepatic tumors can derive from hepatocytes (hepatocarcinoma), biliary ducts (cholangiocarcinoma) and Kupffer's cells (hemangiosarcoma). The most common primary liver tumor in the world is the hepatocarcinoma, this is due to the high prevalence of the lesion in many areas of Africa and Asia, although it is unusual in the western hemisphere. Risk factors for hepatocarcinoma include: HBsAg carrier state, hepatitis C infection, cirrhosis of the liver, alcoholic liver disease, aflatoxin exposure, thorium dioxide, pesticides, anabolic steroids and hemochromatosis. The regenerative nodule can be considered as a preneoplastic lesion. Several tumoral markers have been found helpful in the diagnosis of this tumor: the classic one AFP is present only in 43 percent of the cases, HBsAg in studies in Taiwan in 58 percent of non neoplastic hepatocytes, AAT in 70 percent of the patients. These marquers are expressed in the liver cell in several forms: granulofibrilar occupying most of the cytoplasm and diffuse granular mainly in malignant hepatocytes. Immunoperoxidase stain shows a thick expression of the granular antigen in regenerating cells: this is true for AFP, AAT and HBsAg. The morphology of the tumor is multicentric in cirrhotic livers or focal in normal ones. Characteristically has a notorius tendency to invade the venous system and generally can appear as: a) nodular, b) massive, c) diffuse. The most common histologic pattern is the trabecular-pseudoglandular. The OMS classification of this lesion described 12 different types. In general the prognosis is very poor with the exception of the fibrolamelar type seen in young people that frequently can be resected...