Identification of Plasma Biomarkers for Non-Invasive Diagnosis of Hepatitis B Cirrhosis

Hepatitis B virus (HBV) infection represents a major public health challenge due to its potential progression to liver cirrhosis and hepatocellular carcinoma, underscoring the importance of early diagnosis for effective management. This study aimed to identify plasma biomarkers for the non-invasive diagnosis of hepatitis B cirrhosis (HBC). We employed quantitative proteomic analysis via liquid chromatography-tandem mass spectrometry on plasma samples from 27 individuals, including 13 patients with HBC and 14 with chronic hepatitis B (CHB). Bioinformatics analysis of 963 identified proteins revealed 234 differential expressed proteins, comprising 115 upregulated and 119 downregulated proteins. Four candidate biomarkers—CHI3L1, IGFBP1, SHBG, and TIMP2—were subsequently selected and validated using ELISA in a cohort of 158 patients, all demonstrating elevated levels in HBC patients. The four-biomarker panel (4MP) demonstrated superior diagnostic performance, achieving an area under the curve (AUC) of 0.902 for distinguishing HBC from CHB. For differentiating decompensated HBC from CHB, the 4MP achieved an AUC of 0.993, with a sensitivity of 93.75% and specificity of 98.73%. Mostly, the 4MP also performed well in identifying severe HBC from non-severe HBC, achieving an AUC of 0.911, with a sensitivity of 93.75% and specificity of 98.73%. In conclusion, this study identifies four novel plasma biomarkers for HBC, highlighting their potential to enhance non-invasive diagnostic strategies for monitoring HBC progression.