Drug-induced cholestatic injury can manifest clinically with jaundice, pruritus, dark urine and pale stools.
Liver enzyme studies typically reveal elevation of alkaline phosphatase and -glutamyl transferase.
Transaminases can be variably elevated. A Danish study of 1100 cases of drug-associated injury reported 16% with the acute cholestatic pattern.
The histological patterns of injury can be divided into two forms.
(1) Pure (bland) cholestasis in which bile plugs are seen in hepatocytes or canaliculi and are most prominent in zone 3.
Inflammation and hepatocellular injury are not observed. This pattern is typically observed with anabolic steroids and oral contraceptives.
Other drugs that have been incriminated include prochlorperazine, thiabendazole and warfarin.
(2) Cholestatic hepatitis in which the cholestasis is accompanied by inflammation and hepatocellular injury.
Bile ductular reaction may be present. This pattern also has been referred to as cholangiolitic or hypersensitivity cholestasis.
This pattern manifests as mixed-type injury on liver biochemical tests.
Cholestatic hepatitis can result from a wide variety of drugs; it is the classic pattern seen with toxicity due to macrolide antibiotics such as erythromycin and the antipsychotic agent chlorpromazine.
See also
anabolic-steroid-induced pure cholestasis
erythromycin-induced cholestatic hepatitis
Differential diagnosis
Drug-induced cholestatic injury can be histologically indistinguishable from obstructive biliary disease.
While the latter typically results in portal tract oedema and ductular reaction with inflammation, cholestasis may be the only significant feature in early stages.
Drug-induced cholestatic hepatitis also needs to be distinguished from autoimmune hepatitis and acute viral hepatitis.
Bland cholestasis can occur in several systemic disorders such as sepsis, cardiac failure and shock, and hence clinical information is necessary to establish the aetiology.
In the appropriate clinical setting, benign recurrent intrahepatic cholestasis, postoperative cholestasis and intrahepatic cholestasis of pregnancy have to be considered. Benign recurrent intrahepatic cholestasis is a mild, non-progressive variant of bile transporter disorder characterised by intermittent episodes of cholestasis.
Intrahepatic cholestasis of pregnancy also is due to bile transporter gene variation, although it additionally appears affected by hormonal status, as twin pregnancies and patients on oral contraceptives are reported to be more susceptible to intrahepatic cholestasis of pregnancy.
Chronic biliary diseases such as primary biliary cirrhosis and primary sclerosing cholangitis do not show cholestasis on biopsy early in the course of the disease; serological tests such as antimitochondrial antibodies and cholangiography, respectively, can more definitely rule out these diagnoses.