Zhu-Jun Cao1, Jing Li2, Yun Wang1, Rebecca Bao3, Yu-Han Liu1, Xiao-Gang Xiang1, Lan-Yi Lin1, Fu-Xiang Ye4, Jie Lu1, Qing Xie5, Shi-San Bao6, Hui Wang7. 1. Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. 2. Department of Infectious Diseases, Huai-An Fourth People's Hospital, Jiangsu 223002, China. 3. Discipline of Anatomy and Histology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. 4. Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. 5. Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: xieqingrjh@163.com. 6. Discipline of Pathology, School of Medical Sciences and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: bob.bao@sydney.edu.au. 7. Department of Infectious Diseases, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wanghuirj@163.com.
Abstract
BACKGROUND: Hepatocyte death, either apoptosis or necrosis, is closely associated with hepatic inflammation and fibrosis. AIMS: To investigate the potential values of hepatocytes death biomarker, M30 (apoptosis) and M65 (total death) in predicting histological lesions in chronic hepatitis B virus (HBV) infection. METHODS: Total 201 treatment-naïve patients were prospectively recruited. Liver biopsies were performed prior to antiviral treatments for treatments starting evaluation. Sera were collected on the day of liver biopsy for biomarker measurements. Sera from 200 age-matched healthy volunteers served as healthy controls (HCs). RESULTS: Significant histological lesions (SHL, i.e. significant inflammation and/or significant fibrosis) were confirmed in 150 (74.63%) patients. There were significantly higher serum M30 and M65 in patients with SHL than those without SHL (p<0.001) or than HCs (p<0.001). Serum M30, but not M65, independently predicted SHL [odds ratio:3.4 (95% CI, 1.8-6.2) per increase of 50U/L, p<0.001] after adjusting other potential confounding factors. A novel model based on M30 provided good diagnostic performance in predicting SHL [AUC, 0.87 (0.81-0.92)]. Cut-off value of >0 to confirm or ≤-0.5 to exclude SHL has ∼12% misclassification rate. CONCLUSION: Hepatocyte apoptosis biomarker, M30 is a promising non-invasive alternative to liver biopsy in chronic HBV infection upon treatment evaluation.
BACKGROUND: Hepatocyte death, either apoptosis or necrosis, is closely associated with hepatic inflammation and fibrosis. AIMS: To investigate the potential values of hepatocytes death biomarker, M30 (apoptosis) and M65 (total death) in predicting histological lesions in chronic hepatitis B virus (HBV) infection. METHODS: Total 201 treatment-naïve patients were prospectively recruited. Liver biopsies were performed prior to antiviral treatments for treatments starting evaluation. Sera were collected on the day of liver biopsy for biomarker measurements. Sera from 200 age-matched healthy volunteers served as healthy controls (HCs). RESULTS: Significant histological lesions (SHL, i.e. significant inflammation and/or significant fibrosis) were confirmed in 150 (74.63%) patients. There were significantly higher serum M30 and M65 in patients with SHL than those without SHL (p<0.001) or than HCs (p<0.001). Serum M30, but not M65, independently predicted SHL [odds ratio:3.4 (95% CI, 1.8-6.2) per increase of 50U/L, p<0.001] after adjusting other potential confounding factors. A novel model based on M30 provided good diagnostic performance in predicting SHL [AUC, 0.87 (0.81-0.92)]. Cut-off value of >0 to confirm or ≤-0.5 to exclude SHL has ∼12% misclassification rate. CONCLUSION: Hepatocyte apoptosis biomarker, M30 is a promising non-invasive alternative to liver biopsy in chronic HBV infection upon treatment evaluation.
Authors: Guadalupe Garcia-Tsao; Michael Fuchs; Mitchell Shiffman; Brian B Borg; Nikolaos Pyrsopoulos; Kirti Shetty; Juan F Gallegos-Orozco; K Rajender Reddy; Eyob Feyssa; Jean L Chan; Mason Yamashita; James M Robinson; Alfred P Spada; David T Hagerty; Jaime Bosch Journal: Hepatology Date: 2018-11-26 Impact factor: 17.425