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Tamoxifen in treatment of primary biliary cirrhosis

2004; Lippincott Williams & Wilkins; Volume: 39; Issue: 4 Linguagem: Inglês

10.1002/hep.20164

1527-3350

Pietro Invernizzi, Domenico Alvaro, Andrea Crosignani, Eugenio Gaudio, Mauro Podda,

Liver Disease Diagnosis and Treatment

Although ursodeoxycholic acid may improve liver biochemistry and slow disease progression, primary biliary cirrhosis (PBC) remains without a definite cure, and the search for additional medications continues.1 Cholangiocytes are the primary target of damage in PBC, and the balance between proliferation and death of these cells may condition the progression of the disease.2-4 We have recently found that estrogen receptors (ER) are expressed in cholangiocytes of rats with bile duct ligation (an animal model of cholestasis) and that selective modulators of ER influences cholangiocyte proliferation and death.2, 3. Furthermore, the cholangiocytes of PBC patients but not normal subjects expressed ER, and the degree of expression was shown to correlate with cell proliferation and with disease progression.4 On the basis of these findings, we hypothesize that selective ER modulators might have an impact on the biochemical and clinical expression of PBC. We searched the database of the entire patient population who had been on regular follow-up in our Liver Unit for at least 18 months since 1974. Of 488 women with PBC, 3 had been treated for at least 18 months with tamoxifen (TMX), a selective ER modulator,5 for breast cancer. They received TMX (20 mg/day) for 18 months (case A), 60 months (case B), and 30 months (case C) Fig. 1 shows the effect of TMX on liver enzymes related with cholestasis in these patients. At the beginning of the observation period, the patients were 58, 49, and 49 years old, respectively. Case B had liver cirrhosis. Case C received TMX while on ursodeoxycholic acid (15 mg/kg/day). Biochemical effect of tamoxifen (TMX) alone or in association with ursodeoxycholic acid (UDCA) in 3 patients with primary biliary cirrhosis. Normal values: alkaline phosphatase <279 IU/L; γ-glutamyltransferase <32 IU/L. Serum bilirubin levels were normal and did not change throughout the observation period in all the three cases. In cases A and B there was a marked decrease of alkaline phosphatase (about 70% and 85%, respectively) levels and of γ-glutamyltransferase (about 60% and 75%, respectively) levels during the TMX therapy, with a complete reversal in case A after TMX withdrawal. A reduction of the liver enzymes was observed also in case C, who had concomitant treatment with ursodeoxycholic acid. During the observation period, none of these patients developed any complications of liver cirrhosis. In conclusion, this retrospective survey shows a biochemical benefit of TMX, a selective ER-β antagonist and mixed agonist/antagonist ER-α modulator, in patients with PBC. TMX could affect PBC progression by regulating cholangiocyte proliferation and death. Further studies are warranted to assess the safety andefficacy of TMX (alone or in combination with ursodeoxycholic acid) in the treatment of PBC.