Chenodiol (Chenodeoxycholic Acid)

Publication Details



Chenodeoxycholic acid (chenodiol) is a primary bile acid, synthesized in the liver and present in high concentrations in bile that is used therapeutically to dissolve cholesterol gallstones. Chronic therapy is associated with transient elevations in serum aminotransferase levels in up to 30% of patients, but chenodiol has been linked to only rare instances of clinically apparent liver injury with jaundice.


Chenodeoxycholic acid or chenodiol (kee" noe dye' ol) is a naturally occurring bile acid that is used therapeutically to dissolve cholesterol gallstone in patients with a functioning gall bladder who have contraindications to cholecystectomy or refuse surgery. Chenodiol is the major bile acid synthesized by the liver and is usually the bile acid in highest concentration in serum, hepatocytes and bile. When given orally, chenodiol is passively absorbed from the small intestine and taken up by the liver via anion transport proteins. High concentrations of chenodiol in liver decrease the hepatic synthesis of both cholesterol and other bile acids, thereby increasing the cholic acid and decreasing cholesterol concentration in bile. This combination of events results in a decrease in cholesterol saturation of bile, the major impetus to the formation of cholesterol gallstones. When given for 2 years or more, chenodeoxycholic acid can dissolve cholesterol gallstones in 15% to 30% of patients. Chenodiol is most effective on small “floating” gallstones. It is not effective for calcified gallstones or in patients with a non-functioning gallbladder. Even with successful therapy, however, gallstone recurrence is as high as 50% within a few years of stopping chenodiol. Chenodiol was approved for use in patients with radiolucent gallstones in 1983 and remains available, although it has largely been replaced by ursodiol which appears to be more effective and is better tolerated. In addition, the introduction of laparoscopic cholecystectomy has markedly decreased the need for medical therapy of gallstones. Chenodiol is available as tablets of 250 mg generically and under the commercial names Chenix and Chenodal. The recommended dose is 13 to 16 mg/kg daily in two divided doses for up to 2 years. Side effects include gastrointestinal upset with diarrhea, bloating, cramps, dyspepsia, nausea and vomiting.


In multiple clinical trials of chenodiol therapy for dissolution of gallstones, serum aminotransferase elevations occurred in up to 30% of patients. The elevations generally arose within 2 months of starting therapy and were typically mild, transient and not accompanied by symptoms or jaundice. Liver biopsies done during chenodiol therapy generally showed mild, nonspecific changes. Clinically apparent liver injury with jaundice was not reported. The liver enzyme elevations were generally dose related and usually did not recur on restarting chenodiol at lower doses. While the serum enzyme abnormalities that occurred on chenodiol therapy generated considerable concern, they appeared to be relatively benign. Since the approval of chenodiol and its more widespread use, at least four instances of liver injury with jaundice have been reported to the sponsor, but the clinical features and outcomes of these cases have not been published. Nevertheless, the product label for chenodiol includes a boxed warning about hepatotoxicity although it does not provide advice on the frequency or how to respond to abnormalities. Thus, the reliability of reports of clinically apparent liver injury with chenodiol therapy remains unclear. Once ursodiol was found to be equally as effective as chenodiol, even at lower doses, and was rarely associated with serum enzyme elevations, it rapidly replaced chenodiol as medical therapy for gallstones.

Likelihood score: E* (Suspected but unproven cause of clinically apparent liver injury).

Mechanism of Liver Injury

Chenodiol is thought to cause serum aminotransferase elevations because of conversion to lithocholic acid which has intrinsic, proven hepatotoxicity. In animal models, chenodiol is less hepatotoxic than lithocholic acid, but is more injurious than ursodiol. The more marked hepatotoxicity of chenodiol and lithocholic acid in rodent and primate models compared to humans has been attributed to a more effective sulfation of lithocholic acid in humans that renders it more water soluble, less toxic and more readily excreted.

Outcome and Management

Patients on chenodiol should be monitored with liver tests, including serum bilirubin, ALT, AST and alkaline phosphatase at periodic intervals. Chenodiol should be discontinued for persistent increases in liver test abnormalities, ALT elevations above 8 times the upper limit of normal, elevations of bilirubin more than twice normal or any symptom or sign of liver injury. Replacing chenodiol with ursodiol is probably appropriate in that there does not appear to be cross sensitivity to liver injury or adverse events between chenodiol and other therapeutic bile acids.

Other bile acids used in digestive diseases include cholic acid, obeticholic acid and ursodeoxycholic acid (ursodiol).

Drug Class: Gastrointestinal Agents, Bile Acids



Chenodiol – Generic, Chenodal®


Gastrointestinal Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 09 September 2016

Abbreviations used: FXR, farnesoid X receptor; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; OCA, obeticholic acid; PBC, primary biliary cirrhosis (cholangitis).

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