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Acute Hepatitis Associated with the Chinese Herbal Product Jin Bu Huan

Graham M. Woolf, MD; Lidija M. Petrovic, MD; Sergio E. Rojter, MD; Sherrilyn Wainwright, DVM, MPH; Federico G. Villamil, MD; William N. Katkov, MD; Pina Michieletti, MD; Ian R. Wanless, MD; Frank R. Stermitz, PhD; John J. Beck, BS; and John M. Vierling, MD
[+] Article and Author Information

From Cedars-Sinai Medical Center, Los Angeles, California; Centers for Disease Control and Prevention, Atlanta, Georgia; St. John's Hospital, Santa Monica, California; The Toronto Hospital, Toronto, Ontario, Canada; and Colorado State University, Fort Collins, Colorado. Requests for Reprints: Graham M. Woolf, MD, Hepatology and Liver Transplantation Programs, Cedars-Sinai Medical Center, Los Angeles, 8700 Beverly Boulevard, Suite #7511, Los Angeles, CA 90048. Acknowledgments: The authors thank Angela Hutzenbuhler, MD; Rick Perrie, MD; and Ronald Fishbach, MD, Andrew Lewin, MD, and Jerome Goldwasser, MD, for patient referral.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1994;121(10):729-735. doi:10.7326/0003-4819-121-10-199411150-00001
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Objective: To describe the hepatotoxicity associated with ingestion of the Chinese herbal product Jin Bu Huan Anodyne Tablets (Lycopodium serratum) and to propose possible mechanisms of injury.

Design: Retrospective analysis.

Setting: Academic hepatology units and private practice facilities.

Patients: Seven previously healthy patients.

Measurements: Clinical, laboratory, radiologic, and histologic studies.

Results: Acute hepatitis occurred after a mean of 20 weeks (range, 7 to 52 weeks) of Jin Bu Huan ingestion and resolved in six patients within a mean of 8 weeks (range, 2 to 30 weeks); another patient is currently improving. Hepatitis was associated with symptoms of fever, fatigue, nausea, pruritus, and abdominal pain and with signs of jaundice and hepatomegaly. Biopsy specimens showed that one patient had hepatitis with eosinophils (consistent with a drug reaction) and the other had mild hepatitis, moderate fibrosis, and microvesicular steatosis. Decreasing the Jin Bu Huan dose in one patient improved liver test results. Reusing Jin Bu Huan in two other patients caused abrupt recrudescence of hepatitis.

Conclusion: Jin Bu Huan can cause liver injury. Although the hepatotoxic mechanisms are not defined, they may include hypersensitive or idiosyncratic reactions or direct toxicity to active metabolites. Hepatotoxicity caused by herbal products underscores the importance of national surveillance programs and quality control of the manufacture of these products.

Figures

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Figure 1.
Effect of Jin Bu Huan Anodyne Tablets on aminotransferase levels.

A. Patient 1. The first episode of increased aminotransferase levels occurred after the use of Jin Bu Huan for a 12-week period. Jin Bu Huan use was discontinued, and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were near normal 3 weeks later. At this time, the patient resumed use of Jin Bu Huan for 1 week with recurrent increases in levels of AST and ALT. Levels of aminotransferase normalized completely within 3 weeks of discontinuation of Jin Bu Huan use. B. Patient 5. The first episode of increased aminotransferase levels occurred after intermittent use of Jin Bu Huan for 24 weeks. Jin Bu Huan use was discontinued, and the AST and ALT levels decreased during the next 5 weeks. The patient resumed use of Jin Bu Huan for 4 weeks, and aminotransferase levels increased. The AST and ALT levels became normal 4 weeks after Jin Bu Huan use was discontined. C. Patient 7. During the first 12 months of Jin Bu Huan use (3 tablets per day), aminotransferase levels increased. During the last 18 months, dosage reduction to 1 tablet per day resulted in a decrease in aminotransferase levels. When Jin Bu Huan use was discontinued, aminotransferase levels returned to normal.

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Figure 2.
Liver biopsy specimen from patient 2.arrowarrowsarrowsarrows

A. Focal hepatocellular necrosis, sinusoidal lymphocytic inflammation, and portal tract with mixed cellular infiltrate ( ). B. Numerous acidophilic bodies ( ) with focal hepatocellular necrosis. C. Hepatocytes with various degrees of degeneration, some undergoing apoptotic necrosis ( ). D. Eosinophils ( ) in portal tract. (Hematoxylin and eosin; original magnification, × 400.).

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Figure 3.
Liver biopsy specimen from patient 7.Top left.arrowsTop right.arrowsBottom.arrows

Moderate fibrous portal expansion ( ) (Masson trichrome; original magnification, × 170). Numerous clusters of pigmented macrophages ( ) near a hepatic vein (hv), indicating ingestion of necrotic hepatocytes. (periodic acid-Schiff with diastase; original magnification, × 325). Mild focal hepatocellular necrosis with lymphocytic inflammation ( ) and microvesicular steatosis (arrowheads). (Hematoxylin and eosin; original magnification, × 520).

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The clinical spectrum of Jin Bu Huan toxicity. Arch Intern Med 1996;156(8):899-903.
Chronic hepatitis induced by Jin Bu Huan. J Hepatol 1998;28(1):165-7.
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