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Hepatic Met-enkephalin immunoreactivity is enhanced in primary biliary cirrhosis


Nora V. Bergasa, MD, Columbia University, College of Physicians and Surgeons, 630 W 168th St., P & S 10–508, New York, New York 10032. Tel: (212) 305–8156, Fax: (212) 305–6443, e-mail:


Abstract:  Background/aims: In contrast to the normal adult liver, the fetal human and rat livers, and the liver of rats with cholestasis secondary to bile duct resection (BDR) express the preproenkephalin (ppENK) mRNA, which codes for the endogenous opioid peptide Met-enkephalin. In addition, Met-enkephalin immunoreactivity (MEIR) is detected in hepatocytes and in proliferating bile ductules in the cholestatic rat liver. These data suggest that cholestasis is associated with the resurgence of cells that produce Met-enkephalin. To explore further the status of opioids in cholestasis, we studied the expression of MEIR in liver tissue.

Methods: The MEIR was sought in paraffin-preserved liver tissues from patients with primary biliary cirrhosis (PBC) (n = 10).

Results: The MEIR was detected in all the PBC livers. Its intensity varied from weak to strong on hepatocytes and bile ducts and the strongest expression appeared as coarse granules. The MEIR was either absent or only faintly expressed by some hepatocytes from disease and nondisease control biopsies, but absent from bile ducts.

Conclusion: These results suggest that the human liver in cholestasis may be a source of endogenous opioids.