Hepatocellular damage

Primary biliary cirrhosis is characterized by progressive inflammatory destruction of the bile ducts. Immune-mediated inflammation of intrahepatic bile ducts results in remodeling and scarring, causing retention of bile within the liver and subsequent hepatocellular damage and cirrhosis. The number of patients affected with primary biliary cirrhosis is difficult to estimate because many people are asymptomatic and incidental diagnosis during routine health care visits is common. 

Hepatocellular damage manifests as elevated serum aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)]. The degree of transaminase elevation does not correlate with the remaining functional metabolic capacity of the liver. An AST level two-fold higher than ALT is indicative of alcoholic liver damage. 

Chelators of iron, which are now widely applied for the treatment of patients with thalassemia and other pathologies associated with iron overload, are the intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI) (Figure 19.23, see also Chapter 31). Desferrioxamine (DFO) belongs to a class of natural compounds called siderophores produced by microorganisms. The antioxidant activity of DFO has been studied and compared with that of synthetic hydroxypyrid-4-nones (LI) and classic antioxidants (vitamin E). It is known that chronic iron overload in humans is associated with hepatocellular damage. Therefore, Morel et al. [370] studied the antioxidant effects of DFO, another siderophore pyoverdin, and hydroxypyrid-4-ones on lipid peroxidation in primary hepatocyte culture. These authors found that the efficacy of chelators to inhibit iron-stimulated lipid peroxidation in hepatocytes decreased in the range of DFO > hydroxypyrid-4-ones > pyoverdin. It seems that other siderophores are also less effective inhibitors of lipid peroxidation than DFO [371],... 

This pattern of results is typical of hepatocellular damage (necrosis). The high activity of AST and ALT are due to leakage from damaged cells the normal albumin value indicates that this is an acute (recent) condition. The modest rise in bilirubin concentration in plasma is not itself diagnostic at this stage. 

Hepatic function impairment Patients started on pyrazinamide should have baseline liver function determinations. Closely follow those patients with pre-existing liver disease or those at increased risk for drug-related hepatitis. Discontinue pyrazinamide and do not resume if signs of hepatocellular damage appear. 

Hepatitis/hepatocellular damage Agranulocytosis Erythemas Arrhythmias... 

The mercury ion is capable of causing local or systemic toxicity. For local irritation, they are combined with theophylline in an attempt to diminish the irritative toxicity at the site of injection. IV administration may lead to ventricular arrhythmias. They cause hepatocellular damage and even precipitate hepatic failure. They can also lead to low salt syndrome, hypochloraemic alkalosis and potassium depletion. 

Hepatocellular damage has occasionally been attributed to pioglitazone. 

The mechanisms underlying hepatotoxicity from halothane remain unclear, but studies in animals have implicated the formation of reactive metabolites that either cause direct hepatocellular damage (eg, free radical intermediates) or initiate immune-mediated responses. With regard to the latter mechanism, serum from patients with halothane hepatitis contains a variety of autoantibodies against hepatic proteins, many of which are in a trifluoroacetylated form. These trifluoroacetylated proteins could be formed in the hepatocyte during the biotransformation of halothane by liver drug-metabolizing enzymes. However, TFA proteins have also been identified in the sera of patients who did not develop hepatitis after halothane anesthesia. 

Barr virus confirmed that he had infectious mononucleosis. He was kept in bed for 2 weeks, by which time the signs of inflammation and hepatocellular damage entirely disappeared. However, mild anemia (hemoglobin 110-120 g/L) with reticulocytosis (50%-6.0%), increased serum unconjugated bilirubin, and splenomegaly still remained, suggesting the presence of persistent hemolysis. The physician therefore performed further examinations to confirm the diagnosis of hemolytic anemia. 

Alanine aminotransferase (ALT) is present in high concentrations in the liver and the enzyme is released during hepatocellular damage and a modestly raised level like Mrs MW s is indicative of chronic liver disease. 

ALT gives an early signal of hepatocellular damage but with a peak-to-baseline ratio of less than 4, it falls slower than bilirubin. 

ALP rises relatively early and settles very late but the peak-to-baseline ratio is less than 2. This is because it shows sludging of the bile duct as a secondary event to the hepatocellular damage. 

Amineptine has a seven-membered carbon side-chain and is reported to have more stimulant and fewer sedative effects than other tricyclic compounds, possibly owing to differential actions on dopaminergic rather than serotonergic mechanisms. Amineptine appears to have an unusual propensity for causing hepatocellular damage, which may limit its clinical use (2). 

The adverse effects of the MAO inhibitors include hepatocellular damage, similar to that which led to the withdrawal of the earlier hydrazine derivatives, hypotension, often a pronounced adverse effect (possibly due to... 

Rashes have been reported, but their relation to drug ingestion is poorly substantiated. The hepatocellular damage caused by hydrazine derivatives is probably mediated by an immunological mechanism. 

A 23-year-old man became unresponsive and had a seizure after taking cocaine and alcohol (201). Severe liver necrosis developed and hepatocellular damage was documented with "mTc-PYP imaging. 

GGT is fouud particularly iu hepatocytes aud biliary epithelial cells. GGT serum levels may be high iu liver disease, but it is particularly a feature of biliary outflow obstruction more so than hepatocellular damage. GGT serum measuremeut provides a very sensitive indicator of the presence or absence of hepatobiliary disease. However, raised GGT levels have also been reported in a variety of other clinical conditions, including pancreatic disease, myocardial infarction, chronic obstructive pulmonary disease, renal failure, diabetes, obesity and alcoholism. It is also a sensitive indicator of liver damage through alcohol iugestion. 

Injury to the hepatocytes, for example by hepatotoxins or viruses, will result in hepatocellular damage. This generally manifests itself as fatty infiltration (steatosis), inflammation (hepatitis) or cell death (necrosis). If the assault is mild and remits, the liver will recover and overall liver function will remain normal. Snstained injnry causing hepatocyte cell death will, however, nltimately lead to fibrosis and cirrhosis and potentially severe liver dysfimction. 

O Connor N, Dargan PI, Jones AL (2003) Hepatocellular damage from nonsteroidal anti-inflammatory drugs. QJ Med 96 787-791. 

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