Unrecognized hepatic steatosis and non-alcoholic steatohepatitis in adjuvant tamoxifen for breast cancer patients.
Adjuvant tamoxifen has become the treatment of choice against estrogen receptor-positive breast cancer. Adverse effects are rarely observed and since symptoms of hepatic steatosis, non-alcoholic steatohepatitis and cirrhosis are usually negligible, such effects are not well characterized despite large cohort studies of adjuvant tamoxifen. This issue remains to be systematically studied. The present study consisted of 136 breast cancer patients treated with or without tamoxifen. Patients had laboratory tests once each month and underwent abdominal computed tomography (CT) annually for 5 years. The extent of hepatic steatosis was assessed by CT as the liver/spleen ratio. While receiving adjuvant tamoxifen, 40 of 105 patients developed hepatic steatosis (liver/spleen ratio <0.9) without obvious changes in body mass index. Twenty-one had a liver spleen ratio of <0.5, whereas none of the 31 patients treated without tamoxifen had a ratio <0.9 or <0.5 (p<0.0001 and p<0.0001, respectively). Hepatic steatosis was recognized in 35 of the 40 patients within the first 2 years of receiving adjuvant tamoxifen and 21 of the 40 had increased transaminase levels. Liver biopsy revealed NASH in 6 of 7 patients among the 21 with a liver/spleen ratio of <0.5. A subset of individuals given adjuvant tamoxifen developed progressive hepatic steatosis without significant changes in the body mass index. We suggest a liver/spleen ratio of <0.5 as a criterion upon which liver biopsy should be recommended since NASH frequently occurred in such patients.
Murata
Y
Y
Department of Radiology, Kochi Medical School, Oko-cho, Nankoku 783-8505, Japan. muratay@kochi-ms.ac.jp
Ogawa
Y
Y
Saibara
T
T
Nishioka
A
A
Fujiwara
Y
Y
Fukumoto
M
M
Inomata
T
T
Enzan
H
H
Onishi
S
S
Yoshida
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D018567:Breast Neoplasms, Male / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology*; D002784:Cholesterol / Q000097:blood; D003520:Cyclophosphamide / Q000008:administration & dosage; D003937:Diagnosis, Differential; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D005234:Fatty Liver / Q000139:chemically induced* / Q000175:diagnosis / Q000201:enzymology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D013629:Tamoxifen / Q000009:adverse effects*; D014280:Triglycerides / Q000097:blood
D018931:Antineoplastic Agents, Hormonal; D014280:Triglycerides; D013629:Tamoxifen; D004317:Doxorubicin; D003520:Cyclophosphamide; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005472:Fluorouracil