The Clinical Characteristics And Related Factors Of Non-alcoholic Fatty Liver Associated With Tamoxifen In Patients With Breast Cancer

Background:Breast cancer is the most common cancer with the highest incidence in theworld.Morbidity and mortality are also increasing in our country.With thedevelopment of modem medicine,the treatment of breast cancer has gradually changed into a mode that is dominated by various surgical methods and assisted by comprehensive treatment.Breast cancer is a kind of hormone dependent tumor,70%of breast cancer patients are hormone receptor positive,endocrine therapy is an important part of comprehensive treatment.Tamoxifen is a non-steroidal anti-estrogen drug that is used worldwide as an endocrine adjuvant therapy for women with breast cancer.Tamoxifen is associated with a tripling of the development risk of nonalcoholic fatty liver disease(NAFLD)and nonalcoholic steatohepatitis(NASH),and has been widely reported to cause NAFLD and NASH.Although fatty liver is a benign and reversible liver disease,it can progress to fatty hepatitis,eirrhosis and evendeath.Therefore,the early diagnosis of liver disease is crucial.Currently,studies on the effect of tamoxifen on the liver of breast cancer patients are mostly performed with abdominal ultrasound when NAFLD and NASH are evaluated,and some studies are performed with CT or MRI.Ultrasound,CT and MRI have limitations in the diagnosis of non-alcoholic fatty liver disease and liver fibrosis,so it is necessary to seek a quantitative,reliable and objective method to effectively reflect the disease.Objectives:In this study,the Fibroscan(FS)technique was used to assess the incidence and grade of NAFLD and NASHassociated with tamoxifen treatment in breast cancer patients.Hepatic fatty degeneration(CAP)and hepatic fibrosis(LSM)were used to represent.Meanwhile,the changes of liver enzymes ATL and AST were observed.Relevant factors affecting NAFLD in breast cancer patients after treatment with tamoxifen were analyzed.Methods:In this study,209 breast cancer patients who received tamoxifen treatment from January l,2010 to January 1,2017,were collected in the breast department of Southern Hospital,and 188 of them met the exclusion criteria were analyzed.The grade and incidence of fatty liver and liver fibrosis,liver function,blood lipid and blood glucose,and the duration of medication were statistically analyzed.Independent risk factors for tamoxifen-related hepatic adiposis were analyzed in combination with the patient’s basic data and previous history.Results:1.In this study,the incidence of tamoxifen-related hepatic steatosis was 31.4%,and the proportion of mild,moderate and severe fatty liver in the steatosis group was(16.9%,83.1%).The incidence of liver fibrosis was 5.9%(n=11),and the LSM value of 3 patients was above of 12.2kpa(1.6%),which had reached the diagnostic criteria of liver cirrhosis.2.ALT difference of 14.5±19.5U/L(P<0.001)in the adipogenic group before and after tamoxifen treatment.ALT difference of 5.2 10.0(P<0.001)in the normal group.The follow-up ALT value of 30.8 19.9U/L in the adipogenic group was higher than that of the normal group(18.5 ±11.0U/L,P<0.001).The AST shows the same trend.This indicates that tamoxifen has a certain effect on the liver function of patients.After the treatment with tamoxifen,the liver enzymes increased in the normal range,and the liver enzymes increased more in the steatosis group than in the normal group.3.There was no correlation between serum total cholesterol TC,low-density lipoprotein LDL,fasting glucose GLU and hepatic adiposis in patients treated with trmoxifen(P=0.34,P=0.27 and P=0.10,respectively).High-density lipoprotein(HDL)was associated with hepatic adiposis(P<0.001).4.TAM maintenance treatment time was not correlated with CAP value(r＝-0.033,P)0.65)and LSM value(r＝-0.019,P=0.80).TAM maintenance time did not affect the severity of fatty liver or hepatic fibrosis.5.COX regression multivariate analysis results showed that:BMI(HR 1.17,95%ci 1.08-1.27,P<0.001),baseline ALT(HR 1.05,95%ci 1.003-1.09,P=0’036),hypertension(HR1.9,95%cil.3-2.9,P=0.027),and follow-up TG(HR 1.28,95%ci 1.06-1.6,P=0.01)were independent risk factors for tamoxifen-associated fatty liver disease in breast cancer patients.Conclusion:1.In tamoxifen-related non-alcoholic fatty liver disease,the incidence of severe hepatic steatosis is higher than that of mild to moderate hepatic steatosis,which can develop into cirrhosis in severe cases.2.Liver enzymes were significantly elevated in the normal range after tamoxifen administration;The degree of hepatic enzyme elevation in the patients with fatty change was higher than that in the normal patients.3.Lower HDL may be a risk factor for hepatic fatty degeneration.Higher BMI,hypertension,higher baseline ALT,and higher triglyceride TG were independent risk factors for hepatic steatosis.4.The duration of maintenance treatment with tamoxifen was not correlated with the severity of NAFLD and NASH.5.This study uses a quantitative,reliable and objective method to dynamically monitor the incidence and grade of NAFLD and NASHin breast cancer patients after tamoxifen treatment.the changes of liver enzymes ATL and AST were observed.Relevant factors affecting NAFLD in breast cancer patients after treatment with tamoxifen were analyzed.it provides a reference for clinical diagnosis of fatty liver,it also provides a basis for guiding patients to use medicine.lt has important clinical signifieance for the successful completion of endocrine therapy in breast eancer patients.