Study Of Endocrine Disorders In Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome, which exists as accumulation of lipid within hepotocytes. NAFLD is also a wide spectrum of liver diseases, ranging from simple steatosis through nonalcoholic steatohepatitis (NASH) to cirrhosis.NAFLD is closely associated with features of the metabolic syndrome, including obesity, type2diabetes, hypertension, and dyslipidemia. Therefore, NAFLD is considered as the hepatic manifestation of the metabolic syndrome. In recent years, The prevalence NAFLD increased rapidly. Recent data showed that the prevalence rate reached25-30%in the western countries, and reached about15-20%in China. Some research data even showed the prevalence was up to30-50%.NAFLD is often seen in patients with with endocrine diseases, such as thyroid, pituitary diseases, suggesting that endocrine disorders may be involved in the pathogenesis of NAFLD. However, how the endocrine system participation involved the NAFLD and the exact mechanisms are unclear. We performed cross-sectional and prospective case-control studies, to expolore the association between growth hormone/thyroide hormone and NAFLD. Part I:Association between Serum Growth Hormone Levels and Nonalcoholic Fatty Liver Disease:a Cross-Sectional StudyBackground/Aims:Growth hormone (GH) is an important regulator of metabolism and body composition. GH deficiency is associated with increased visceral body fat and other features of the metabolic syndrome.This study aimed to explore the association of growth hormone with non-alcoholic fatty liver disease (NAFLD) by a population-based study.Methods:A cross-sectional study was performed among7146Chinese who took their annual healthy examination at Zhenhai Lianhua Hospital, Ningbo,China.Results:A total of1667subjects were diagnosed as NAFLD according the diagnostic criteria, and5479subjects were defined as controls. The NAFLD patients had significantly lower serum GH levels than the controls (P<0.01). The lower GH group had higher prevalence of NAFLD and the metabolic syndrome (P<0.01). A stepwise logistic regression analysis showed that GH was significantly associated with risk factor for NAFLD (OR=0.651,95%CI=0.574-0.738, P<0.001).Conclusion:Our results showed a significant association between lower serum GH levels and NAFLD. Part II:Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly ChineseObjective:Thyroid dysfunction commonly occurs in the elderly population and overt thyroid dysfunction is associated with some liver abnormalities. This study aimed to investigate the association of thyroid function with non-alcoholic fatty liver disease (NAFLD) in euthyroid elderly Chinese.Methods:A cross-sectional study was performed among878euthyroid elderly Chinese who took their annual healthy examination at Zhenhai Lianhua Hospital, Ningbo, China.Results:A total of227(25.85%) subjects fulfilled the diagnostic criteria of NAFLD. NAFLD patients had significantly lower levels of serum free thyroxine (FT4) than controls (11.12±1.43vs.11.58±1.47pmol/L; P<0.001). The prevalence rate of NAFLD decreased along with progressively higher serum FT4levels (P for trend<0.001). Age, gender, and smoking status adjusted correlation analysis showed that serum FT4level was negatively correlated with body mass index, waist circumference, triglyceride, and serum uric acid levels (All with P<0.05). Stepwise logistic regression analysis showed that serum FT4level was significantly associated with the risk for NAFLD (odds ratio [OR]:0.847,95%confidence interval [CI]:0.743-0.966; P=0.013).Conclusion:Our findings suggest that thyroid function, even within the reference range, is associated with NAFLD in elderly Chinese. Part III:Impact of subclinical hypothyroidism on the development of non-alcoholic fatty liver disease:a prospective case-control studyObjective:The causal relationship between hypothyroidism and NAFLD could not be identified by our and other cross-sectional studies.This study aimed to evaluate the impact of subclinical hypothyroidism on the development of NAFLD in a Chinese population.Methods:we performed a prospective case-control study. A total of327subclinical hypothyroidism subjects were enrolled. Age, gender,and body mass index (BMI) are three major factors that may influence the development of NAFLD.To reduce the influence of these variables, we randomly selected327age, gender, and BMI matched euthyroid subjects as controls.All the subjects were free of NAFLD at baseline,2006. Subclinical hypothyroidism was defined as a TSH level of4.5mIU/L or greater.Results:A total of63subclinical hypothyroidism subjects and35euthyroid subjects developed NAFLD during a median follow-up of4.92years. Compared to the euthyroid subjects, the incidence of NAFLD for1000person-years of follow-up was significantly higher in the subjects with subclinical hypothyroidism (38.3vs.21.8; P <0.05). The incidence of NAFLD showed an increased trend with increasing TSH levels.The incidence of NAFLD per1000person-years of follow-up was21.8,34.2,48.3and52.5for the euthyroid, mild, moderate and severe elevation subgroup, respectively (P<0.05for trend). Cox proportional hazards regression analyses showed that subclinical hypothyroidism was a risk factor for the development of NAFLD in the unadjusted model, the hazard ratio (95%CI) was1.77(1.17-2.67). After adjusted the indicators of the metabolic syndrome in the Cox proportional hazards regression analysis. The result showed that the relationship of subclinical hypothyroidism with incident NAFLDConclusion:our prospective case-control study provided evidence that subclinical hypothyroidism is a significant factor associated with NAFLD development.