Liver defect

The patient may have two liver defects—fatty liver and multilobular cirrhosis. Fatty liver results from malnutrition multilobular cirrhosis results from the occlusion of the intrahepatic bile ducts, followed by atrophy and necrosis of the hepatic cells with regeneration and fibrosis. When cirrhosis is severe, hepatic insufficiency and portal hypertension (hypersplenism, esophageal varices, ascites) develop. 

These dru are contraindicated in patients with known hypersensitivity. Hydroxychloroquine is contraindicated in patients with porphyria (a group of serious inherited disorders affecting the bone marrow or the liver), psoriasis (chronic skin disorder), and retinal disease (may cause irreversible retinal damage). MTX is contraindicated during pregnancy because it is a Pregnancy Category X dmg and may cause birth defects... 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor approach. They are below levels that might cause adverse health effects in the people most sensitive to such chemical-induced effects. MRLs are derived for acute (1-14 days), intermediate (15-364 days), and chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not mean that adverse health effects will occur. 

HBV-based vectors efficiently target quiescent hepatocytes and HBV-specific promoter and enhancer elements allow hepatocyte specific gene expression (Protzer et al. 1999). In addition, a very favorable ratio of infectious to defective particles renders HBV-based vectors good candidates for liver-directed gene transfer. Improved HBV vectors, in which HBV gene expression was abolished (Untergasser and Protzer 2004), were used in chimpanzees to treat chronic HCV infection and did not show any toxicity (Shin et al. 2005). 

Inherited defects in the enzymes of (3-oxidation and ketogenesis also lead to nonketotic hypoglycemia, coma, and fatty hver. Defects are known in long- and short-chain 3-hydroxyacyl-CoA dehydrogenase (deficiency of the long-chain enzyme may be a cause of acute fetty liver of pr nancy). 3-Ketoacyl-CoA thiolase and HMG-CoA lyase deficiency also affect the degradation of leucine, a ketogenic amino acid (Chapter 30). 

Hypolipoproteinemias Abetaiipoproteinemia No chylomicrons, VLDL, or LDL are formed because of defect in the loading of apo B with lipid. Rare blood acylglycerols low intestine and liver accumulate acylglycerols. Intestinal malabsorption. Early death avoidable by administration of large doses of fat-soluble vitamins, particularly vitamin E. 

The probable metabohc defect in type I tyrosine-mia (tyrosinosis) is at himarylacetoacetate hydrolase (reaction 4, Figure 30-12). Therapy employs a diet low in tyrosine and phenylalanine. Untreated acute and chronic tyrosinosis leads to death from liver failure. Alternate metabolites of tyrosine are also excreted in type II tyrosinemia (Richner-Hanhart syndrome), a defect in tyrosine aminotransferase (reaction 1, Figure 30-12), and in neonatal tyrosinemia, due to lowered y>-hydroxyphenylpyruvate hydroxylase activity (reaction 2, Figure 30-12). Therapy employs a diet low in protein. 

Hypouricemia and increased excretion of hypoxanthine and xanthine are associated with xanthine oxidase deficiency due to a genetic defect or to severe liver damage. Patients with a severe enzyme deficiency may exhibit xanthinuria and xanthine lithiasis. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

A protease-specific model has also been reported in which a replication-defective adenovirus encoding an NS3 protease-SEAP fusion protein is injected into mouse tail veins, resulting in expression of the fusion protein in the liver [82, 83]. Protease activity can be detected both by measuring activity of liberated SEAP or by protease-induced liver damage. Protease activity was found to be reduced by administration of protease inhibitors. This model can be used to show that candidate inhibitors have adequate pharmacokinetic properties in mice to function in the intended target organ, but it is not a true disease model. 

Drinking large amounts of diisopropyl methylphosphonate kills animals. The amount needed to cause death in humans is not known for sure. Animal studies have shown no evidence that drinking or eating diisopropyl methylphosphonate causes fertility problems or birth defects. Animal studies have shown that eating diisopropyl methylphosphonate can affect some liver enzymes (indicating a response by the liver). However, test animals showed no liver disease. While most animal studies have shown only minimal toxic effects below a certain level of... 

---