Correspondence

Idiopathic Biliary Ductopenia

N Engl J Med 1997; 337:280-281July 24, 1997

Article

To the Editor:

Moreno et al. (March 20 issue)1 describe a mild form of idiopathic biliary intrahepatic ductopenia in 24 asymptomatic adults who had persistently abnormal results on liver-function tests for at least one year. The authors state that liver injury from drugs or toxic agents was ruled out after comprehensive and careful interviews with the patients. The histopathological features shown, however, raise the question of long-term drug use. Pericanalicular lipofuscinosis is reported in all the patients, with ground-glass hepatocytes in 18. These findings are characteristic and highly suggestive of the long-term use of medications metabolized by hepatocytes.2 Ground-glass hepatocytes of the type shown in Figure 1B of the article develop with long-term use of widely available drugs, including analgesics, barbiturates, chlorpromazine, steroids, and antiepileptic drugs.2,3 Likewise, the presence of hepatic lipofuscinosis is associated with the long-term use of analgesics such as phenacetin, and also with chlorpromazine and other less commonly used drugs.2 Drug toxicity is an established cause of the vanishing-bile-duct syndrome.4

Moreno et al. state that the histopathological features, other than the ductopenia, found in the liver-biopsy specimens were of unknown importance. I believe that the authors should have discussed the known association between these features and the long-term use of drugs, some of which are available over the counter. It is surprising that in a group of 24 adults, the majority of whom were middle-aged women, there was no reported exposure to such commonly used drugs.

Antonio R. Perez-Atayde, M.D.
Children's Hospital, Boston, MA 02115

4 References

1. 1

   Moreno A, Carreno V, Cano A, Gonzalez C. Idiopathic biliary ductopenia in adults without symptoms of liver disease. N Engl J Med 1997;336:835-838
   Full Text | Web of Science | Medline

2. 2

   Zimmerman HJ, Ishak KG. Hepatic injury due to drugs and toxins. In: MacSween RNM, Anthony PP, Scheuer PJ, Burt AD, Portmann BC, eds. Pathology of the liver. New York: Churchill Livingstone, 1994:563-633.
   

3. 3

   Klinge O, Bannasch P. Zur Vermehrung des glatten endoplasmatischen Retikulum in Hepatocyten menschlicher Leberpunktate. Verhandl Dtsch Gesell Pathol 1968;52:568-573
   Medline

4. 4

   Degott C, Feldmann G, Larrey D, et al. Drug-induced prolonged cholestasis in adults: a histological semiquantitative study demonstrating progressive ductopenia. Hepatology 1992;15:244-251
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Carreño and a colleague reply:

To the Editor: Patients with long-term use of drugs (whether or not they were hepatotoxic), including women taking oral contraceptives, were excluded from our study. All 24 patients were healthy and asymptomatic, and their liver-enzyme abnormalities were detected during a routine analysis. All the patients were carefully interviewed (in most cases, a family member was present) to exclude the possibility of drug-induced liver disease. None had a history of jaundice. In contrast, cases of drug-induced ductopenia described in the literature involved an acute episode of jaundice and pruritus (coinciding with the drug intake).1,2 For example, in the report by Degott et al.,3 prolonged cholestasis was preceded by an acute icteric phase in all the patients, and all but two had pruritus.

The histologic features of drug-induced ductopenia (ductal injury, inflammatory portal infiltrate, fibrosis, and so forth) were not present in the liver-biopsy specimens from our patients. Lipofuscinosis and ground-glass hepatocytes are nonspecific histologic features and may be observed in several liver diseases not related to long-term drug use (e.g., Wilson's disease, hemochromatosis, and chronic hepatitis B).4 Thus, our patients did not meet the international criteria for a drug-induced liver disorder.5

Javier Bartolomé, Ph.D.
Vicente Carreño, M.D.
Fundación Jiménez Díaz, 28040 Madrid, Spain

5 References

1. 1

   Glober GA, Wilkerson JA. Biliary cirrhosis following the administration of methyltestosterone. JAMA 1968;204:170-173
   CrossRef | Web of Science | Medline

2. 2

   Kowdley KV, Keeffe EB, Fawaz KA. Prolonged cholestasis due to trimethoprim sulfamethoxazole. Gastroenterology 1992;102:2148-2150
   Web of Science | Medline

3. 3

   Degott C, Feldmann G, Larrey D, et al. Drug-induced prolonged cholestasis in adults: a histological semiquantitative study demonstrating progressive ductopenia. Hepatology 1992;15:244-251
   CrossRef | Web of Science | Medline

4. 4

   Scheuer PJ, Lefkowitch JH. Liver biopsy interpretation. 5th ed. Vol. 31 of Major problems in pathology. London: Saunders, 1994.
   

5. 5

   Benichou C. Criteria of drug-induced liver disorders: report of an international consensus meeting. J Hepatol 1990;11:272-276
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Yasuni Nakanuma, Yoh Zen, Bernard C. Portmann. 2012. Diseases of the bile ducts. , 491-562.
   CrossRef