Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis, National Clinical Research Center of Digestive Diseases, Beijing, China.
Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
J Med Virol. 2023 Oct;95(10):e29156. doi: 10.1002/jmv.29156.
Despite the increasing prevalence of steatosis in patients with chronic hepatitis B (CHB), whether the changes in steatosis impact fibrosis regression during antiviral therapy remain unclear. We aimed to identify the association between histological changes of steatosis and fibrosis in patients undergone antiviral treatment. Patients with paired liver biopsies before and after 78 weeks of antiviral therapy were enrolled in this study. Liver fibrosis was assessed by the Ishak score combined with Beijing Classification predominantly progressive, indeterminate, and predominately regressive score. Steatosis was evaluated by the nonalcoholic fatty liver disease activity score. Collagen in each site was quantitated by second harmonic generation/two photon excitation fluorescence technology. Serum proteomic changes after treatment were characterized by mass-based spectrometry. A total of 239 CHB patients were included and divided into four groups according to the changes in steatosis: 162 (67.8%) had no steatosis throughout, 24 (10.0%) developed new-onset steatosis, 21 (8.8%) had initial steatosis which disappeared, and 32 (13.4%) had persistent steatosis. The persistent steatosis group showed the lowest rate of fibrosis regression (14/32, 43.8%). Persistent steatosis correlated with decreased fibrosis regression significantly after adjusting for age, sex, fibrosis stage, and metabolic factors at baseline, as well as the viral response (adjusted odds ratio = 0.380, 95% confidence interval 0.145-0.996, p = 0.049). This decreased fibrosis regression was associated with accumulated collagen in the perisinusoidal area. Patients with persistent steatosis showed unique changes in glycolipid metabolism according to the serum proteomic atlas. Persistent steatosis correlated with decreased fibrosis regression during antiviral therapy in patients with CHB.
尽管慢性乙型肝炎(CHB)患者的脂肪变性患病率不断增加,但脂肪变性的变化是否会影响抗病毒治疗期间的纤维化消退尚不清楚。我们旨在确定接受抗病毒治疗的患者肝组织脂肪变性和纤维化变化之间的关联。本研究纳入了接受抗病毒治疗 78 周前后有配对肝活检的患者。肝纤维化采用 Ishak 评分结合北京分类(主要进展型、不确定型和主要消退型)进行评估。脂肪变性采用非酒精性脂肪性肝病活动评分进行评估。通过二次谐波产生/双光子激发荧光技术定量每个部位的胶原。采用基于质谱的方法描述治疗后血清蛋白质组的变化。共纳入 239 例 CHB 患者,根据脂肪变性的变化分为四组:162 例(67.8%)始终无脂肪变性,24 例(10.0%)新发脂肪变性,21 例(8.8%)初始脂肪变性消失,32 例(13.4%)持续脂肪变性。持续脂肪变性组的纤维化消退率最低(32/32,43.8%)。调整基线时的年龄、性别、纤维化分期和代谢因素以及病毒应答后,持续脂肪变性与纤维化消退显著相关(调整后的比值比=0.380,95%置信区间 0.145-0.996,p=0.049)。这种纤维化消退减少与窦周区胶原积累有关。根据血清蛋白质组图谱,持续脂肪变性患者的糖脂代谢显示出独特的变化。在 CHB 患者的抗病毒治疗期间,持续脂肪变性与纤维化消退减少相关。