Cholestatic course

Fig. 22.4 Feathery degeneration (arrows) of ballooned hepatocytes, massive liver cell oedema and bihrubinostasis in the cana-hculi. Clinically cholestatic course of acute viral hepatitis B...

The cholestatic course of disease (W. Siede, 1942) is largely identical to the periacinal form of icterus catarrhalis (H. Eppinger, 1937), cholangiolitic hepatitis (C.J. Watson et al., 1946), hepatitis with intrahepatic obstruction (I. Magyar, 1953) and hepatitis with a cholestatic element (H. Kalk, 1957). 

Those forms of acute viral hepatitis that have a normal clinical course also present discrete quantities of bile to be found as intraepithelial drops and intercellular cylinders or deposits in the stellate cells. These findings cannot be confirmed biochemically. A cholestatic course of disease is occasionally witnessed with a marked increase in alkaline phosphatase, particularly in older patients and in women. It is mostly accompanied by jaundice. The... 

Cholestyramine may prove necessary for severe pruritus due to a cholestatic course of disease (4-8 g prior to breakfast) - if antihistamines were unsuccessful. With such a cholestatic course of disease, the application of ursodeoxycholic acid (2-3 x 250 mg) is most suitable. (166) In some cases with a fulminant course, interferon alpha has been successfully used. Special diets , glucocorticoids or other medication are not necessary. 

Cholestyramine may be advisable in cases of pronounced pruritus as a result of a cholestatic course of disease (4-8 g before breakfast). 

Ursodeoxycholic acid was used to treat acute viral hepatitis B without cholestasis for the first time by our working group in 1988. (166) At the time, we attributed the markedly positive effect of treatment in 9 out of 10 patients to the potential immunomodulatory effect of UDCA. (149, 154, 216) In 1993 reports were also published by A. D. Jorge on the good results achieved in 22 patients suffering from acute viral hepatitis and cholestasis. Administration in acute viral hepatitis is therefore recommended in controlled studies, since side effects are not to be expected and the current level of knowledge on the pharmacological effects of UDCA can be deepened. The beneficial effects of UDCA as reported so far in the cholestatic course of acute viral hepatitis are evidence of the success of this treatment. 

The use of ursodeoxycholic acid is advisable in cases involving a cholestatic course of NAFLD or NASH. With a dosage of 13-15 mg/kg BW/day, it was possible to achieve an improvement in the transaminase values and the fat content of the liver. An increase in dosage to 20-25 mg/kg BW/day might be advisable. (57)... 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

Most of the synthetic androgens and anabolic agents are 17-alkyl-substituted steroids. Administration of drugs with this structure is often associated with evidence of hepatic dysfunction. Hepatic dysfunction usually occurs early in the course of treatment, and the degree is proportionate to the dose. Bilirubin levels may increase until clinical jaundice is apparent. The cholestatic jaundice is reversible upon cessation of therapy, and permanent changes do not occur. In older males, prostatic hyperplasia may develop, causing urinary retention. 

This virus species derived its name from the town of Coxsackie in the state of New York, where virological evidence thereof was successfully obtained for the first time. Coxsackie viruses are assigned to the picornavirus group, consisting at present of 23 A and 6 B types. Coxsackie hepatitis with mesenchymal reactions, portal infiltration and focal hepatocellular necrosis sometimes occurs, especially in infants. Cholestatic, predominantly centrolobular forms of the disease, can develop in adults. A lethal course is extremely rare. (66-68) The course of infection with the Coxsackie type B4 or B5 virus may give rise to the Fitz-Hugh-Curtis syndrome with the development of the typical violin string-like adhesive strands. (65) (s. fig. 24.2)... 

Shigella Infections with shigella are rarely accompanied by hepatitis. Direct involvement of the liver in the course of shigellosis is, however, to be feared, as first demonstrated by positive shigella identification from liver biopsy as early as 1910 (J.H.N. Knox Jr. et al.). Shigella-induced cholestatic hepatitis with jaundice and marked histological changes has likewise been reported. (21)... 

Fatal cholestatic hver failure occurred in a 45-year-old woman with metastatic breast cancer who was given gemcitabine and carboplatin and pre-existing liver damage. After four courses of gemcitabine -I- carboplatin she developed severe decompensated cholestatic hepatitis (9). Liver biopsy showed marked cholestasis and hepatocellular injury consistent with drug-induced hepatotoxicity. 

W14. Wollheim, F. A., Immunoglobulins in the course of viral hepatitis and in cholestatic and obstructive jaundice. Acta. Med. Scand. 183, 473-479 (1968). 

Cholestatic hepatitis was reported in a 35-year-old woman who had been taking celandine for 4 months. The woman had been taking thyroxine for 5 years and took a course of roxithromycine in the month prior to the hepatitis (Greving et al. 1998). Severe cholestatic hepatitis was reported in a 39-year-old woman, with both incidences temporally related to the use of celandine. In both cases, the woman was taking or had recently finished taking either sulfamethoxazole or penicillin (Stickel et al. 2003). 

Hepatitis and jaundice caused by the combination of amoxicillin and clavulanic acid were first identified in 1988. The combination of the two drugs is associated with a higher incidence of liver injury than the administration of amoxicillin alone. The risk of this drug-induced liver injury, mostly cholestatic in nature, increases with age and by about a factor of 3 after 2 or more consecutive courses of drug. 

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