Autotaxin准确，无创生物标志物慢性HBV纤维化

StephenW

Autotaxin accurate, noninvasive biomarker for fibrosis in chronic HBV

Joshita S, et al. Heptaol Res. 2017;doi:10.1111/hepr.12997.
November 30, 2017

Serum autotaxin was an accurate, noninvasive biomarker for liver fibrosis among patients with chronic hepatitis B in a recently published study.

“Serum autotaxin (ATX) has recently been reported as a novel marker candidate to assess liver fibrosis. ATX was originally isolated from the conditioned medium of A2058 human melanoma cells as a potent cell motility-stimulating factor,” Satoru Joshita, MD, from the division of gastroenterology and hepatology at Shinshu University of Medicine, Japan, and colleagues wrote. “As the clinical features of ATX in patients with hepatitis B remain unknown, this study evaluated the performance of serum ATX in predicting histological fibrosis in chronic HBV infection.”


The researchers enrolled 101 patients with chronic HBV who were nucleos(t)ide analogue treatment-naive and 160 age- and sex-matched controls. Patients had undergone liver biopsy and did not have concomitant hepatitis C, HIV or other liver disease, and had no history of organ transplantation.

Based on histology, patients included in the study had fibrosis stage 0 (n = 4), stage 1 (n = 33), stage 2 (n = 25), stage 3 (n = 22) or stage 4 (n = 17).

To evaluate the association between ATX and liver fibrosis stage, the researchers followed the patients for a median of 154 weeks. Additionally, the researchers enrolled 15 treatment-naive patients with chronic HBC for a longitudinal analysis of ATX during nucleos(t)ide analogue therapy.

Compared with controls, patients with HBV had significantly higher levels of ATX (P < .0001). Women had significantly higher levels of ATX compared with both men in the control cohort (P = .038) and men in the HBV cohort (P < .0001).

ATX levels correlated significantly with fibrosis stage among all patients (r = 0.46; P < .0001) and among male (r = 0.55; P < .0001) and female (r = 0.52; P < .0006) groupings. While ATX levels also correlated significantly with histological activity grade in all patients (r = 0.27; P < .007) and men (r = 0.43; P < .001), the association was not significant in women.

ATX vs. other noninvasive markers

Regarding other noninvasive biomarkers, ATX correlated significantly among all patients with Wisteria floribunda agglutinin-positive Mac-2 binding protein (r = 0.51; P < .001), hyaluronic acid (r = 0.58; P < .001), type IV collagen 7S (r = 0.47; P < .001), aspartate aminotransferase-to-platelet ratio index (r = 0.31; P = .002; APRI) and Fibrosis-4 index (r = 0.54; P < .001).

ATX remained significantly correlated with the other noninvasive fibrosis markers in both men and women except for type IV collagen 7S in women.

ATX demonstrated a high diagnostic ability among patients with fibrosis stage 2 or higher (AUROC = 0.761), those with stage 3 or higher (AUROC = 0.691) and those with fibrosis stage 4 (AUROC = 0.758), which remained high for both men and women.


Among the 15 treatment-naive patients with chronic HBV in the longitudinal study, treatment with nucleos(t)ide analogue therapy for 12 months significantly decreased alanine aminotransferase levels (P < .001), HBV-DNA (P < .001), hepatitis B core-related antigen (P < .01) and APRI (P < .01), but the researchers observed no significant differences in ATX levels in all patients, men or women.

“An earlier report showed that ATX was a prognostic factor for overall survival in patients with cirrhosis, suggesting that it played an important role in disease progression involving such complications as [hepatocellular carcinoma] and hepatic failure,” the researchers concluded. “However, no significant association was detected between serum ATX and the incidence of HCC development in our cohort ... and thus requires additional study.” – by Talitha Bennett

Disclosure: Healio.com/Hepatology was unable to determine relevant financial disclosures of the authors at the time of publication.

StephenW

Autotaxin准确，无创生物标志物慢性HBV纤维化

Joshita S等人Heptaol Res。 2017; DOI：10.1111 / hepr.12997。
2017年11月30日

在最近发表的一项研究中，血清autotaxin是慢性乙型肝炎患者肝纤维化的准确无创生物标志物。

“血清autotaxin（ATX）最近已被报道为评估肝纤维化的新型候选标记物。 ATX最初是从A2058人类黑色素瘤细胞的条件培养基中分离出来的，它是一种有效的细胞运动刺激因子，日本信州医科大学消化病与肝病学系的Satoru Joshita博士及其同事写道。 “由于ATX在乙型肝炎患者中的临床特征仍然未知，本研究评估了血清ATX在预测慢性HBV感染组织学纤维化中的表现。


研究人员招募了101名慢性乙肝患者，这些患者是核苷（酸）类似物治疗初治者，160名年龄和性别匹配的对照者。病人经过肝活检，没有伴随丙型肝炎，HIV或其他肝脏疾病，也没有器官移植史。

根据组织学，包括在研究中的患者具有纤维化阶段0（n = 4），阶段1（n = 33），阶段2（n = 25），阶段3（n = 22）或阶段4（n = 17） 。

为了评估ATX与肝纤维化分期之间的关系，研究人员随访患者的中位数为154周。此外，研究人员招募了15名未接受治疗的慢性HBC患者进行核苷（酸）类似物治疗期间的ATX纵向分析。

与对照组相比，HBV患者ATX水平显着升高（P <.0001）。与对照队列（P = .038）和HBV队列中男性相比，女性的ATX水平显着更高（P <.0001）。

ATX水平与纤维化分期显着相关（r = 0.46; P <.0001），男性（r = 0.55; P <.0001）和女性（r = 0.52; P <.0006）尽管ATX水平也与所有患者（r = 0.27; P <.007）和男性（r = 0.43; P <.001）的组织学活动度显着相关，但这种关联在女性中并不显着。

ATX与其他无创标记物

对于其他非侵袭性生物标志物，ATX与所有紫藤凝集素阳性Mac-2结合蛋白（r = 0.51; P <0.001），透明质酸（r = 0.58; P <0.001），IV型胶原蛋白7S （r = 0.47; P <0.001），天冬氨酸转氨酶 - 血小板比值指数（r = 0.31; P = 0.002; APRI）和纤维化-4指数（r = 0.54; P <0.001）。
除了IV型胶原蛋白7S以外，ATX在男性和女性中都与其他非侵入性纤维化标记物保持显着相关。

ATX对2级以上纤维化患者（AUROC = 0.761），3级以上患者（AUROC = 0.691）和4级纤维化患者（AUROC = 0.758）的诊断能力较高，妇女。


在纵向研究的15例慢性乙型肝炎患者中，核苷类似物治疗12个月后，丙氨酸转氨酶水平（P <0.001），HBV-DNA（P <0.001），肝炎B核心相关抗原（P <0.01）和APRI（P <0.01），但研究人员观察到所有患者（男性或女性）ATX水平无显着差异。

“一项较早的报告显示，ATX是肝硬化患者总生存的预后因子，表明它在包括[肝细胞癌]和肝功能衰竭等并发症在内的疾病进展中发挥重要作用，”研究人员总结说。 “然而，血清ATX和我们队列中HCC发生率之间没有显着的相关性，因此需要进一步研究。” - Talitha Bennett

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