Cholestasis liver function tests

As this patient has cholestasis they may be at a higher risk of HRT causing a further increase in bilirubin levels and worsening cholestasis. Liver function tests should be measured before treatment is started, and be monitored closely during treatment. Treatment should be stopped if a significant change occurs. 

Late adverse effects include hepatic dysfunction, with altered liver function tests and hyperbilirubinemia. After prolonged use of nicotinic acid and nicotinyl alcohol, histological changes, for example parenchymal cell injury, portal fibrosis, cholangitis, cholestasis, biliary casts, and lymphocytic infiltrations around the bile ducts, have occasionally been seen. 

Cholestasis occurred in a woman with alpha-1 antitrypsin deficiency (phenotype PiZZ) who had taken prochlorperazine 5-10 mg qds for 27 months (3). She developed jaundice and ascites. Liver biopsy confirmed diffuse advanced chronic cholestasis, moderate portal and periportal inflammation, and bridging necrosis. Her liver function tests normalized within days of withdrawal of prochlorperazine. 

Two small studies have examined the effect of HRT on liver function tests in healthy women. The women had regular assessment of their liver function tests during therapy. Hepatotoxicity and cholestasis were not observed [10, 11]. 

There have been several reports of hepatotoxicity of iodipamide, variously characterized by epigastric pain, nausea and vomiting, jaundice, pyrexia, and tenderness over the liver, with abnormal liver function tests. Biopsy has shown centrilobular necrosis (154). The incidence of abnormal liver function tests may be as high as 18% after a dose of 40 ml, and the quantity given should be as small as possible. Prior administration of glucocorticoids or sulfonylureas impairs hepatic excretion of ioglycamide. Both iodoxamate and iotroxate can affect liver function tests in a small series of cases, the degree of intrahepatic cholestasis appeared to be relatively more marked after iodoxamate than after iotroxate (SED-12, 1168) (155). 

Changes in liver function tests, resolving on withdrawal, have been reported (34). In one case there was histological evidence of cholestasis. 

Six cases of acute hepatitis occurred in four patients during the first 10 weeks of treatment, and in two after 15 weeks of therapy (3). They were represented by jaundice (n = 5), itching (n = 2), weakness (n = 3), and anorexia, nausea, and vomiting (n = 2). Increases in liver enzymes varied from 1.5 to over 30 times the upper limit of the reference range. Liver biopsy showed centrilobular or panlobular bridging necrosis in the four women and intra-hepatic cholestasis in the two men. Complete recovery of normal liver function tests ensued at follow-up after interruption of nimesulide therapy. 

A 50-year-old woman taking spironolactone for androgenic alopecia developed hepatitis with minimal cholestasis 6 weeks after starting therapy (9). After withdrawal of spironolactone, her symptoms resolved and liver function tests improved. She was not rechallenged. 

Liver There are a small number of reported cases of ajmaline-induced hepatitis or cholestasis associated witii chronic use of the drug. In all reports, patients had a similar clinical picture and recovered after conservative therapy. However, there are no other reports of hepatotoxicity occurring after the administration of low doses in diagnostic challenges. The mechanism of this side effect may be related to polymorphism of CYP 2D6 which is the main enzyme responsible for ajmaline metabolism. Routine liver function testing is recommended before an ajmaline challenge [10]. 

A 41-year-old man developed severe hepatic dysfunction following a 3.5-week course of terbinafine (250 mg/ day) (40). He had marked pruritus, jaundice, malaise, anorexia, and loin pain. His serum bilirubin rose to a peak of 718 pmol/l with alkahne phosphatase 569 U/1, alanine transaminase 90 U/1, aspartate transaminase 63 U/1, and a prolonged prothrombin time of 21 seconds, unresponsive to vitamin K. Liver biopsy showed canalicular cholestasis consistent with a drug reaction. His symptoms resolved 11 months after drug withdrawal, and his hver function tests normalized after 15 months. 

Two infants with intestinal failure and parenteral nutrition-associated liver disease were given an intravenous fat emulsion containing primarily omega-3 fatty acids instead of the conventional emulsion [30 ]. Biochemical tests of liver function improved significantly. One child was removed from the liver transplantation list because of improved hepatic function, and the second child had complete resolution of cholestasis while solely on parenteral nutrition. 

Strictly speaking these are tests which measure the specific functions of the liver, e.g. its excretory functions (bilirubin, BSP etc.) or its synthetic function (as reflected by serum albumin levels). In practice the term is also used to include tests for liver cell damage (e.g. aminotransferases released from damaged cells), tests for cholestasis (e.g. alkaline phosphatase and 5 -nucleo-tidase) and possibly a number of other miscellaneous tests (e.g. a-fetoprotein for primary hepatoma). 

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