Association Of Serum Apolipoprotein B Level With Non-alcoholic Fatty Liver Disease

OBJECTIVE:Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases. As the prevalence of NAFLD increased rapidly in recent years, it has become a significant public health concern worldwide. NAFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidaemia and is regarded as the liver manifestation of metabolic syndrome. Cardiovascular disease (CVD) represents the most common cause of death in patients with NAFLD. NAFLD is a well-established risk factor for CVD, but they also share common risk factors, in particular disturbed lipid homeostasis accompanied by dyslipidemia. Abnormalities in lipid and lipoprotein metabolism accompanied by chronic inflammation are considered to be the central pathway for the development of several obesity-related co-morbidities such as NAFLD and CVD. We performed population-based studies to expolore the association between serum apolipoprotein B(ApoB) level and NAFLD.METHODS:To expolore the association between serum ApoB level and NAFLD, a cross-sectional study and a subsequent prospective study were performed among the adults who took their annual healthy examination at Zhenhai Lianhua Hospital, Ningbo. The questionnaires, physical examinations.laboratory tests and liver ultrasonography were performed. The diagnosis of NAFLD was based on the criteria suggested by the Chinese Liver Disease Association. The diagnosis of metabolic syndrome was based on the criteria suggested by the new International Diabetes Federation definition, including five metabolic disorder criteria.RESULTS:PartⅠ:A cross-sectional study was performed among 8553 participants. A total of 1476 (17.26%) fulfilled the diagnostic criteria of NAFLD. Participants with NAFLD were older, male predominant, and had higher BMI, waist circumference, systolic and diastolic blood pressure than those without NAFLD. The NAFLD patients also had higher serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, LDL cholesterol, fasting plasma glucose, and serum uric acid, while lower serum HDL cholesterol levels than NAFLD-free participants (all with P<0.001).We divided all the participants into quintiles according to their serum ApoB levels:<0.73,0.73-0.86,0.87-1.00,1.01-1.17, and> 1.17 g/L. We observed a linear correlation between serum ApoB quintiles and prevalence of NAFLD, metabolic syndrome and its parameters. The prevalence of NAFLD was 5.39% among the subjects with serum ApoB in the first quintile, and increased to 9.33%,16.30%, 23.34% and 32.71% in quintiles 2,3,4, and 5, respectively (P for trend< 0.001). Also we found that serum ApoB quintiles were positively correlated with prevalence of metabolic syndrome and its parametersWe performed stepwise multiple regression analysis to investigate factors associated with NAFLD. We found that ten variables were closely associated with risk for NAFLD. A noticeable finding was that serum ApoB was significantly associated with risk for NAFLD (OR=3.118,95% CI:2.230-4.360, P< 0.001).Part II:The 7077 subjects (4548 men and 2529 women) who were free of NAFLD at baseline were included for the prospective study. Of 7077 subjects,129 (100 men and 29 women) did not complete any follow-up during 7-year period. Comparisons among baseline clinical characteristics showed that age, gender, BMI,or waist circumference was not statistically different between the subjects who completed the follow-up and those lost to follow-up.Of 6948 subjects complete the follow-up study during 7-year period,1139 developed NAFLD during the 7 year study. In contrast to participants without incident NAFLD, those with incident NAFLD were relatively predominantly male, had higher baceline BMI, waist circumference, systolic and diastolic blood pressure, and higher serum levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, total cholesterol, LDL cholesterol, fasting plasma glucose, and serum uric acid than those without NAFLD (all with P< 0.001).We observed that baseline ApoB quintiles predicted the incidence of NAFLD in a graded and dose-responsive manner. The overall incidence of NAFLD was 27.41 per 1000 person-year follow-up, ranging from 16.69 in quintile 1 to 22.63,24.73,37.51, and 42.77 in quintile 2, quintile 3, quintile 4, and quintile 5, respectively (P for trend< 0.001).Cox proportional hazards regression analyses (both univariate and multivariable models) were applied. Certain variables were correlated with incident NAFLD in the univariate models:higher ApoB level, male gender, higher BMI, higher waist circumference, higher blood pressure, higher serum liver enzymes, higher serum lipids (including TC, TQ and LDL-C), higher uric acid, and lower HDL-C. In multivariable models, serum ApoB level was an independent factor related with incident NAFLD (P=0.001).CONCLUSION:Our cross-sectional results showed a significant association between higher serum ApoB levels and NAFLD. Our prospective study provided evidence that serum ApoB levels is a significant factor associated with NAFLD development.