The full content of Annals is available to subscribers

Subscribe/Learn More  >
Original Research |

Mixed Hepatocellular–Cholestatic Liver Injury after Pioglitazone Therapy

Louis D. May, MD; Jay H. Lefkowitch, MD; Michael T. Kram, MD; and David E. Rubin, MD
[+] Article, Author, and Disclosure Information

From Good Samaritan Hospital, Suffern, and Columbia Presbyterian Medical Center, New York, New York.

Requests for Single Reprints: Louis D. May, MD, Gastrointestinal Associates of Rockland, 500 New Hempstead Road, New City, NY 10956.

Current Author Addresses: Drs. May and Kram: Gastrointestinal Associates of Rockland, 500 New Hempstead Road, New City, NY 10956.

Dr. Lefkowitch: Columbia Presbyterian Medical Center, 630 West 168th Street, New York, NY 10032.

Dr. Rubin: Good Samaritan Hospital, Route 59, Suffern, NY 10901.

Author Contributions: Conception and design: L.D. May, J.H. Lefkowitch, M.T. Kram.

Analysis and interpretation of the data: L.D. May, J.H. Lefkowitch, D.E. Rubin.

Drafting of the article: L.D. May, J.H. Lefkowitch, M.T. Kram.

Critical revision of the article for important intellectual content: L.D. May, J.H. Lefkowitch, D.E. Rubin.

Final approval of the article: L.D. May, J.H. Lefkowitch, M.T. Kram, D.E. Rubin.

Provision of study materials or patients: L.D. May, M.T. Kram, D.E. Rubin.

Administrative, technical, or logistic support: D.E. Rubin.

Collection and assembly of data: L.D. May, D.E. Rubin.

Ann Intern Med. 2002;136(6):449-452. doi:10.7326/0003-4819-136-6-200203190-00008
Text Size: A A A

Background: Pioglitazone is an oral hypoglycemic agent in the thiazolidinedione class. Only one case of hepatotoxicity related to this agent has previously been reported.

Objective: To report the clinical course of a patient with hepatitis after therapy with pioglitazone.

Design: Case report.

Setting: A community hospital.

Patient: A 49-year-old diabetic man taking pioglitazone, 30 mg/d.

Intervention: Discontinuation of pioglitazone therapy.

Measurements: Serum aminotransferase and bilirubin levels, standard blood tests for causes of hepatitis and cirrhosis other than drug toxicity, and liver biopsy.

Results: After 6 months of pioglitazone therapy, significant hepatic dysfunction developed. Blood tests excluded viral, metabolic, and autoimmune disorders. Liver biopsy showed mixed hepatocellular–cholestatic injury compatible with drug toxicity. After treatment with pioglitazone was discontinued, liver enzyme values returned to normal.

Conclusion: Patients receiving pioglitazone may develop serious liver injury and should be observed for evidence of hepatitis.


Grahic Jump Location
Figure 1.
Liver biopsy specimen showing mild portal lymphocytic inflammation.curved arrowstraight arrow

Several profiles of the bile duct are seen in this portal tract, showing mildly altered nuclear polarity ( ) and intraepithelial lymphocytes ( ). The lymphocyte is at 3 o'clock in the duct. (Hematoxylin–eosin; original magnification, ×325).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Serum liver enzyme value associated with pioglitazone administration.

ALT = alanine aminotransferase. To convert µkat/L to U/L, divide by 0.01667; to convert µkat/L to nkat/L, multiply by 1000; to convert µmol/L to mg/dL, divide by 17.104.

Grahic Jump Location




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).


Submit a Comment/Letter
Submit a Comment/Letter

Summary for Patients

Liver Damage in a Person Taking the Diabetes Drug Pioglitazone

The summary below is from the full report titled “Mixed Hepatocellular–Cholestatic Liver Injury after Pioglitazone Therapy.” It is in the 19 March 2002 issue of Annals of Internal Medicine (volume 136, pages 449-452). The authors are LD May, JH Lefkowitch, MT Kram, and DE Rubin. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians–American Society of Internal Medicine.


Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.


Buy Now for $32.00

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Related Articles
Topic Collections
PubMed Articles
Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.