Dr Bruno and colleagues from Italy assessed the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women.
The investigators designed a prospective, randomized, double blind, placebo controlled trial.
The research team included 5408 healthy women who had had hysterectomies, recruited into the Italian tamoxifen chemoprevention trial from 58 centers in Italy.
The team randomly assigned the women to receive 20 mg daily tamoxifen or placebo for 5 years.
|34 of 52 patients potentially developed non-alcoholic fatty liver disease and these had received tamoxifen|
|British Medical Journal|
The researchers’ main outcome measure was the development of non-alcoholic fatty liver disease in all women with normal baseline liver function.
The main outcome measure was based on all women who showed at least 2 elevations of alanine aminotransferase of 1.5 times upper limit of normal levels over a 6 month period.
The investigators reported that during follow up, 64 women met the predefined criteria.
The researchers noted that 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease with 34 patients in the tamoxifen group and 18 with placebo.
In all 52 women ultrasonography confirmed the presence of fatty liver.
The team found that other factors associated with the development of non-alcoholic fatty liver disease included overweight, obesity, hypercholesterolemia and arterial hypertension.
The researchers reported that 22 women had liver biopsies of which 15 were diagnosed as having mild to moderate steatohepatitis with 12 patients in the tamoxifen group and 3 with placebo.
5 patients had fatty liver alone of which 1 patient received tamoxifen and 4 placebo.
The research team observed no clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 9 years.
Dr Bruno concludes, “Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome."
“Non-alcoholic steatohepatitis seems to be indolent in both the tamoxifen and the placebo group after 10 years of follow up.”