Tong Xin, Wan Yawen, Yin Shengxia, Shao Li, Yao Renling, Ma Xiaoyan, Rui Fajuan, Shi Junping, Wu Chao, Li Jie
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Clin Proteomics. 2025 May 13;22(1):19. doi: 10.1186/s12014-024-09523-3.
In recent years, the prevalence of non-alcoholic fatty liver disease (NAFLD) has risen among patients with chronic hepatitis B (CHB), coinciding with the increasing rates of obesity and metabolic syndrome. Both conditions can contribute to liver fibrosis and even hepatocellular carcinoma; however, the pathogenesis of each disease, as well as CHB concurrent with NAFLD, remains incompletely understood.
We comprehensively analyzed protein levels in liver tissues from four distinct groups: healthy controls, patients with CHB, patients with NAFLD, and those with CHB and NAFLD using proteomic profiling. Subsequently, we performed bioinformatics analyses based on the results of differentially expressed proteins (DEPs). We also verified the levels of select DEPs in both patient liver samples and a murine model.
Our investigation revealed that enhanced viral clearance in patients with hepatitis B virus (HBV) with concurrent NAFLD might be associated with an inflammatory response and the activation of numerous metabolic pathways within the body. Meanwhile, the degree of hepatic steatosis was associated with anomalies in fatty acid degradation, glycolysis/gluconeogenesis, and other metabolic processes. However, the prognosis for patients with CHB and concurrent NAFLD may be severe, and this may be connected to the altered levels of proteins such as ACAT1, ACY1, SERPINB3, MTCH2, ALDH2, ECHS1, S100A7, and LRP6.
In comparison to CHB and NAFLD alone, the prognosis for CHB complicated by NAFLD appears less favorable. This disparity is closely correlated with distinct protein level patterns in the liver following the onset of both diseases. Our study provides novel insights into the disease progression and clinical mechanisms underlying CHB and NAFLD.
近年来，慢性乙型肝炎（CHB）患者中非酒精性脂肪性肝病（NAFLD）的患病率有所上升，这与肥胖和代谢综合征发病率的增加相吻合。这两种情况都可能导致肝纤维化甚至肝细胞癌；然而，每种疾病以及合并NAFLD的CHB的发病机制仍未完全明了。
我们使用蛋白质组分析全面分析了四个不同组的肝组织蛋白质水平：健康对照、CHB患者、NAFLD患者以及CHB合并NAFLD患者。随后，我们根据差异表达蛋白（DEP）的结果进行了生物信息学分析。我们还在患者肝样本和小鼠模型中验证了所选DEP的水平。
我们的研究表明，合并NAFLD的乙型肝炎病毒（HBV）患者病毒清除增强可能与炎症反应以及体内多种代谢途径的激活有关。同时，肝脂肪变性程度与脂肪酸降解、糖酵解/糖异生及其他代谢过程的异常有关。然而，CHB合并NAFLD患者的预后可能较差，这可能与ACAT1、ACY1、SERPINB3、MTCH2、ALDH2、ECHS1、S100A7和LRP6等蛋白质水平的改变有关。
与单独的CHB和NAFLD相比，合并NAFLD的CHB预后似乎较差。这种差异与两种疾病发病后肝脏中不同的蛋白质水平模式密切相关。我们的研究为CHB和NAFLD的疾病进展和临床机制提供了新的见解。
