Tsuji Yuki, Namisaki Tadashi, Kaji Kosuke, Takaya Hiroaki, Nakanishi Keisuke, Sato Shinya, Saikawa Soichiro, Sawada Yasuhiko, Kitagawa Kou, Shimozato Naotaka, Kawaratani Hideto, Moriya Kei, Noguchi Ryuichi, Akahane Takemi, Mitoro Akira, Yoshiji Hitoshi
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Exp Ther Med. 2020 Aug;20(2):985-995. doi: 10.3892/etm.2020.8798. Epub 2020 May 27.
Chronic hepatitis B (CHB) virus continues to be a leading cause of morbidity and mortality worldwide. The diagnosis of liver fibrosis has a key role in selecting patients with CHB for antiviral treatment. However, serum biomarkers demonstrate limited diagnostic utility. The present study aimed to compare the performances of fibrosis biomarkers for diagnosing significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB and to identify the most appropriate biomarker for these patients. The current study included 96 antiviral-naïve patients with CHB who underwent liver biopsy. METAVIR scoring system was used to assess liver fibrosis and necroinflammation. The diagnostic performances were evaluated of the platelet (PLT) count; the levels of hyaluronan, serum 7S domain of type 4 collagen, procollagen type III N-terminal peptide, tissue inhibitor of metalloproteinases 1, Mac-2 binding protein glycosylation isomer (M2BPGi) and N-terminal type III collagen propeptide (Pro-C3); the fibrosis index based on four factors; the aspartate aminotransferase-to-platelet ratio index; and enhanced liver fibrosis score for identifying significant liver fibrosis [≥fibrosis stage 2 (F2)]. All fibrosis biomarkers, except the Pro-C3 level, correlated with the fibrosis stage. M2BPGi was better than other biomarkers for diagnosing ≥F2, with the highest area under the curve of 0.902. M2BPGi demonstrated a higher diagnostic accuracy for significant fibrosis than mild/severe fibrosis or cirrhosis. However, no significant correlation was observed between the M2BPGi level and fibrosis stage in patients with CHB having significant liver necroinflammation defined as ≥ necroinflammatory activity 2. The M2BPGi level and PLT count were exclusively correlated with the fibrosis stage in 73 patients without significant liver necroinflammation. M2BPGi demonstrated the highest diagnostic performance for significant fibrosis in patients having significant liver fibrosis with no significant liver necroinflammation. In conclusion, the M2BPGi level can accurately diagnose significant liver fibrosis that indicates the need for antiviral therapy in patients with CHB.
慢性乙型肝炎（CHB）病毒仍然是全球发病和死亡的主要原因。肝纤维化的诊断在选择CHB患者进行抗病毒治疗方面起着关键作用。然而，血清生物标志物的诊断效用有限。本研究旨在比较用于诊断显著肝纤维化（表明CHB患者需要抗病毒治疗）的纤维化生物标志物的性能，并为这些患者确定最合适的生物标志物。本研究纳入了96例未接受过抗病毒治疗的CHB患者，这些患者均接受了肝活检。采用METAVIR评分系统评估肝纤维化和坏死性炎症。评估了血小板（PLT）计数、透明质酸、血清4型胶原7S结构域、III型前胶原N端肽、金属蛋白酶组织抑制剂1、Mac-2结合蛋白糖基化异构体（M2BPGi）和III型胶原前肽N端（Pro-C3）的水平；基于四个因素的纤维化指数；天冬氨酸转氨酶与血小板比值指数；以及用于识别显著肝纤维化[≥纤维化2期（F2）]的增强肝纤维化评分的诊断性能。除Pro-C3水平外，所有纤维化生物标志物均与纤维化分期相关。M2BPGi在诊断≥F2方面优于其他生物标志物，曲线下面积最高为0.902。M2BPGi对显著纤维化的诊断准确性高于轻度/重度纤维化或肝硬化。然而，在定义为≥坏死性炎症活动度2的有显著肝坏死性炎症的CHB患者中，未观察到M2BPGi水平与纤维化分期之间存在显著相关性。在73例无显著肝坏死性炎症的患者中，M2BPGi水平和PLT计数仅与纤维化分期相关。M2BPGi在无显著肝坏死性炎症的显著肝纤维化患者中对显著纤维化的诊断性能最高。总之，M2BPGi水平可以准确诊断表明CHB患者需要抗病毒治疗的显著肝纤维化。
