不同Child-Pugh分级慢性乙型肝炎肝硬化患者糖代谢、胰岛素分泌情况及其与炎症反应的相关性分析

目的 探讨不同Child-Pugh分级的慢性乙型肝炎(CHB)合并肝硬化患者糖代谢和胰岛素分泌情况及与炎症反应相关性。方法 选取2013年1月-2018年1月广州市红十字会医院收治的CHB合并肝硬化患者147例,另纳入同期65例体检正常的人群作为对照组。收集患者入院12 h内资料,包括年龄、性别、BMI、收缩压、舒张压、HBV DNA载量、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、ALT、AST、TNFα、IL-6、中性粒细胞与淋巴细胞比值(NLR)、空腹血糖、血浆胰岛素、C肽水平、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌功能。记录口服葡萄糖耐量试验(OGTT)后2 h血糖、胰岛素及C肽水平,并计算患者此时的NLR。计数资料2组间比较采用χ2检验。计量资料2组间比较采用t检验。等级资料多组间比较和进一步两两比较均采用Kruskal-Wallis H秩和检验。相关性检验采用Pearson分析。结果 CHB合并肝硬化患者的TNFα、IL-6、NLR、胰岛素水平、HOMA-IR明显高于对照组,而胰岛素分泌功能明显低于对照组(P值均<0.05);根据Child-Pugh分级将147例CHB合并肝硬化患者分为3组(Child-Pugh A、B、C),3组间TNFα、IL-6、NLR、胰岛素水平、HOMA-IR、胰岛素分泌功能比较,差异均有统计学意义(P值均<0.05)。CHB合并肝硬化患者OGTT后2 h血糖、胰岛素、C肽水平及NLR、TNFα、IL-6均显著高于对照组(P值均<0.05);3组不同Child-Pugh分级患者OGTT后2 h血糖、胰岛素、NLR、TNFα、IL-6比较,差异均有统计学意义(P值均<0.05)。Child-Pugh评分与OGTT后2 h NLR、血糖、胰岛素水平均呈正相关(r值分别为0.678、0.451、0.644,P值均<0.001);OGTT后2 h NLR与血糖、胰岛素水平均呈正相关(r值分别为0.408、0.795,P值均<0.001)。结论 CHB合并肝硬化患者存在一定程度糖代谢异常和胰岛素抵抗,肝损伤越严重,糖代谢异常和胰岛素抵抗越明显,而炎症反应可能介导上述二者之间的联系。

Glucose metabolism and insulin secretion in patients with chronic hepatitis B cirrhosis of different Child-Pugh grades and their association with inflammatory response

Objective To investigate glucose metabolism and insulin secretion in patients with chronic hepatitis B (CHB) of different Child-Pugh grades and liver cirrhosis and their association with inflammatory response. Methods A total of 147 patients with CHB and liver cirrhosis who were admitted to Guangzhou Red Cross Hospital from January 2013 to January 2018 were enrolled, and 65 healthy individuals who underwent physical examination in our hospital during the same period of time were enrolled as control group. The clinical data within 12 hours after admission were collected, including age, sex, body mass index, systolic pressure, diastolic pressure, HBV DNA load, total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor α (TNFα), neutrophil-lymphocyte ratio (NLR), fasting blood glucose, plasma insulin, C-peptide level, homeostasis model assessment of insulin resistance (HOMA-IR), and insulin secretion function. Blood glucose, insulin, and C-peptide were recorded at 2 hours after oral glucose tolerance test (OGTT). The chi-square test was used for comparison of categorical data between two groups;the t-test was used for comparison of continuous data between two groups;the Kruskal-Wallis H test was used for comparison of ranked data between multiple groups and further comparison between two groups. A Pearson correlation analysis was used to investigate correlation. Results Compared with the control group, the patients with CHB and liver cirrhosis had significantly higher TNFα, interleukin-6 (IL-6), NLR, insulin, and HOMA-IR (all P<0.05) and significantly lower insulin secretion function (P<0.05). The 147 patients with CHB and liver cirrhosis were divided into Child-Pugh A, B, and C groups according to Child-Pugh grade, and there were significant differences in TNFα, IL-6, NLR, insulin, HOMA-IR, and insulin secretion function between these three groups (all P<0.05). Compared with the control group, the patients with CHB and liver cirrhosis had significantly higher blood glucose, insulin, C-peptide, NLR, TNFα, and IL-6 at 2 hours after OGTT (all P<0.05);there were significant differences in blood glucose, insulin, NLR, TNFα, and IL-6 at 2 hours after OGTT between the three groups with different Child-Pugh grades (all P<0.05). Child-Pugh score was positively correlated with NLR and blood glucose and insulin at 2 hours after OGTT (r=0.678, 0.451, and 0.644, all P<0.001), and NLR was positively correlated with blood glucose and insulin at 2 hours after OGTT (r=0.408 and 0.795, both P<0.001). Conclusion There is a certain degree of abnormal glucose metabolism and insulin resistance in CHB patients with liver cirrhosis, and the severities of abnormal glucose metabolism and insulin resistance increase with the increase in liver injury, while inflammation may mediate the association between them.