Liver injury paracetamol

McLean, A. and Nuttal, L. (1978). An in vitro model of liver injury using paracetamol treatment of liver slices and prevention of injury by some antioxidants. Biochem. Pharmacol. 27, 425-430. 

Despite this theory, the evidence that therapeutic doses of paracetamol can produce liver injury in alcoholics is scanty (98,99). There has been only one study of the... 

A 32-year-old woman, who had been taking paracetamol 2-4 g/day for several weeks, was given rifampicin 600 mg bd, and 2 days later developed agitation, confusion, and laboratory abnormalities indicative of severe liver injury. Both rifampicin and paracetamol were withdrawn and she was given acetylcysteine. Her liver dysfunction resolved. 

Ricinis communis was shown to be effective in treatment of experimental liver injury [212]. Ricinine was not found to have hepatoprotective activity [213]. /V-Demethylricinine, however, displayed dose-dependent choleretic activity, and anticholestatic and hepatoprotective activity against hepatic damage induced with paracetamol [213]. 

Hepatotoxicity does not occur at recommended doses of acetaminophen. Administration of 2 g, or twice the recommended dose, of intravenous paracetamol in healthy subjects has been shown to stay far below the threshold of hepatotoxicity. When ingested at high doses, acetaminophen is metabolized to JV-acetyl-p-benzoquinone-imine (NAPQI). NAPQI is rapidly conjugated with glutathione to a nontoxic compound. The depletion of glutathione results in the accumulation of NAPQI that is responsible for liver injury. Acetaminophen has a narrow therapeutic window and even minor overdoses may cause severe hepatic injury. Liver necrosis occurs at 7.5-10 g of acetaminophen. 

Liver Nimesulide-induced hepatotoxidty can occur, with serious and potentially fatal outcomes. Three cases of liver failure related to nimesulide have been reported 77, 78 ]. In a retrospective analysis from the Irish national liver transplant unit all recipients of a liver transplant for fulminant hepatic failure of unknown cause (1994-2007) were evaluated [79 ]. There were 32 patients with seronegative, non-paracetamol-induced liver failure. Nimesulide had been started within 6 months in six patients and was assessed as probably associated with liver injury in all of these cases. 

In an acute hepatocellular injury, such as following a paracetamol overdose, there may he significant damage over a short period. This results in a marked increase in the AST and ALT levels (which can be in the thousands) due to massive hepatocyte damage or death. The converse can occur with chronic severe disease, where the hepatocyte mass has reduced to such an extent that the AST and ALT levels have returned to normal owing to the reduction in hepatocyte numbers able to release the enzyme (i.e. a false normal result). In fatty liver, ALT and AST levels are likely to be up to three times ULN, whereas in hepatitis ALT and AST levels can range from nearly normal to in the hundreds, depending on how acute the condition is. 

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