代谢相关脂肪性肝病患者发生糖代谢异常的相关因素分析

Analysis of factor associated with the occurence of abnormal glucose metabolism in patients with metabolic associated fatty liver disease

目的探讨代谢相关脂肪性肝病(MAFLD)患者发生糖代谢异常的相关因素。方法本研究为横断面研究。纳入自2010年1月至2022年12月于浙江省人民医院和杭州师范大学附属医院就诊的404例MAFLD活检患者作为研究对象。收集患者的一般资料和实验室指标。根据血糖状况,将研究对象分为糖代谢正常组和糖代谢异常组。采用单因素、多因素logistic回归分析法分析与MAFLD患者糖代谢异常相关的临床因素。采用逐步logistic回归分析法分析MAFLD患者糖代谢异常与不同病理组织严重程度之间的相关性。结果在404例患者中,32.7%(132/404)出现糖代谢异常,49.2%(65/132)的单纯性脂肪肝(NAFL)患者和50.8%(67/132)的疑似或确诊为代谢相关脂肪性肝炎(MASH)患者出现糖代谢异常(P<0.001)。与糖代谢正常组相比,糖代谢异常组的肝脏脂肪变性、气球样变、小叶内炎症显著上升(均P<0.05)。多因素logistic回归分析显示,年龄(OR=1.037,95%CI 1.007~1.068)、体重指数(OR=1.090,95%CI 1.035~1.148)和乙型肝炎病毒表面抗原(HBsAg)阳性(OR=0.561,95%CI 0.327~0.962)与MAFLD患者的糖代谢异常相关(均P<0.05)。根据病理分层结果显示,MASH患者发生糖代谢异常的风险是NAFL患者的1.235倍(OR=2.235,95%CI 1.342~3.722,P<0.05),但小叶内炎症或纤维化与MAFLD患者糖代谢异常之间无关(P>0.05)。与MAFLD组相比,MAFLD伴慢性乙型肝炎病毒(HBV)感染者的脂肪变性、MASH程度相对较轻,而显著肝纤维化较重(P<0.05)。对病理相关的混杂因素进行校正后发现,相比于MAFLD患者,合并慢性HBV感染的MAFLD患者糖代谢异常风险仍较低(OR=0.523,95%CI 0.318~0.858,P=0.010)。进一步对MAFLD合并慢性HBV感染患者的肝纤维化严重程度进行分层发现,与F0阶段相比,F1、F2阶段患者糖代谢异常风险较低(OR=0.200,95%CI 0.044~0.915,P=0.038;OR=0.190,95%CI 0.038~0.959,P=0.044)。但当肝纤维化进入F3、F4阶段时,其与糖代谢异常的风险无关(P>0.05)。结论MAFLD患者发生糖代谢异常可能与年龄、体重指数、HBsAg阳性有关。其中,慢性HBV感染与MAFLD患者糖代谢异常风险呈负相关。

Objective To investigate the factors associated with the occurrence of abnormal glucose metabolism in patients with metabolic associated fatty liver disease(MAFLD).Methods This was a cross-sectional study.A total of 404 patients with MAFLD biopsies who attended Zhejiang Provincial People′s Hospital and Affiliated Hospital of Hangzhou Normal University from January 2010 to December 2022 were included.General information and laboratory indices.According to the blood glucose status,the group was divided into normal glucose metabolism group and abnormal glucose metabolism group.Clinical factors associated with abnormal glucose metabolism in patients with MAFLD were determined using single-factor and multifactor logistic regression analysis.Stepwise logistic regression analysis was used to determine the independent correlation between abnormal glucose metabolism and the severity of different pathological tissues in MAFLD patients.Results A total of 132 of 404 patients(32.7%)had abnormal glucose metabolism.Abnormal glucose metabolism was present in 49.2%(65/132)of patients with nonalcoholic fatty liver(NAFL)and 50.8%(67/132)of patients with suspected or confirmed metabolic dysfunction-associated steatohepatitis(MASH)(P<0.001).Hepatic steatosis,ballooning,and intralobular inflammation were significantly higher in the abnormal glucose metabolism group compared with the normal glucose metabolism group(all P<0.05).Multifactorial logistic regression analysis showed that age(OR=1.037,95%CI 1.009-1.068),body mass index(OR=1.090,95%CI 1.035-1.148)and hepatitis B surface antigen(HbsAg)positivity(OR=0.561,95%CI 0.327-0.912)were associated with abnormal glucose metabolism in patients with MAFLD associated(all P<0.05).According to the results of pathological stratification,the risk of abnormal glucose metabolism in MASH patients was 1.235 times higher than that in patients with NAFL(OR=2.235,95%CI 1.342-3.722,P<0.05),but there was no association between intralobular inflammation or fibrosis and abnormal glucose metabolism in MAFLD patients(P>0.05).Compared with the MAFLD group,those with MAFLD with chronic hepatitis B virus(HBV)infection had relatively less steatosis,less MASH,and more significant liver fibrosis(P<0.05).After correction for pathology-related confounders,the risk of abnormal glucose metabolism remained lower in patients with MAFLD with chronic HBV infection compared with those with MAFLD(OR=0.523,95%CI 0.318-0.858,P=0.010).Further stratification of the severity of liver fibrosis in patients with MAFLD combined with chronic HBV infection revealed that patients in the stage F1 and F2 had a lower risk of abnormal glucose metabolism compared to the stage F0(OR=0.200,95%CI 0.044-0.915,P=0.038;OR=0.190,95%CI 0.038-0.959,P=0.044).However,it was not associated with the risk of abnormal glucose metabolism when liver fibrosis reached stages F3 and F4(P>0.05).Conclusion The occurrence of abnormal glucose metabolism in MAFLD patients may be related to age,body mass index,and HBsAg positivity.Among these,chronic HBV infection was negatively associated with the risk of abnormal glucose metabolism in patients with MAFLD.