Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, 13-1 Takara-Machi, Kanazawa, Ishikawa, 920-8641, Japan.
J Gastroenterol. 2019 Jun;54(6):549-557. doi: 10.1007/s00535-019-01551-3. Epub 2019 Feb 1.
Nonalcoholic steatohepatitis (NASH) is associated with liver inflammation in patients with nonalcoholic fatty liver disease, and it can progress to liver fibrosis at an advanced stage, as well as hepatocellular carcinoma (HCC) and portal hypertension. Although liver fibrosis is accurately diagnosed via biopsy, noninvasive methods are preferable. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with HCC and is secreted into the blood by liver cells via a lysosome-mediated nonclassical pathway. Accordingly, we analyzed whether secretion of AKR1B10 protein is associated with advanced NASH.
We performed histological staging in 85 Matteoni classification type III and IV NASH patients and evaluated the incidence of HCC, formation of gastroesophageal varices, and prognosis according to serum AKR1B10 and Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA(+)-M2BP)(M2BPGi) and by comparison with conventional markers of fibrosis.
A positive correlation was found between the Brunt classification and serum AKR1B10 level. In Brunt stage 4 patients, AKR1B10 levels were higher than those of other liver fibrosis markers, with higher specificity. The cutoff values for AKR1B10 and WFA(+)-M2BP for stage 4 fibrosis were 1.03 and 3.11, respectively. The rates of stage 4 fibrosis, HCC incidence, and gastroesophageal varix formation were significantly different between the two groups subdivided according to these cutoff levels. Moreover, the patients in the higher value group had significantly worse prognosis after NASH diagnosis CONCLUSION: AKR1B10 is a useful serum biomarker for advanced liver fibrosis in NASH and, combined with serum WFA(+)-M2BP, can predict HCC development, gastroesophageal varix formation, and poor prognosis.
非酒精性脂肪性肝炎（NASH）与非酒精性脂肪性肝病患者的肝脏炎症有关，在晚期可进展为肝纤维化，以及肝细胞癌（HCC）和门静脉高压。虽然肝纤维化可以通过活检准确诊断，但非侵入性方法更可取。醛酮还原酶家族 1 成员 B10（AKR1B10）与 HCC 相关，并通过溶酶体介导的非经典途径由肝细胞分泌到血液中。因此，我们分析了 AKR1B10 蛋白的分泌是否与晚期 NASH 有关。
我们对 85 例 Matteoni 分类 III 型和 IV 型 NASH 患者进行组织学分期，并根据血清 AKR1B10 和槐凝集素阳性 Mac-2 结合蛋白（WFA(+)-M2BP）（M2BPGi）评估 HCC、胃食管静脉曲张形成和预后的发生率，并与纤维化的常规标志物进行比较。
Brunt 分类与血清 AKR1B10 水平呈正相关。在 Brunt 分期 4 期患者中，AKR1B10 水平高于其他肝纤维化标志物，特异性更高。AKR1B10 和 WFA(+)-M2BP 分期 4 纤维化的截断值分别为 1.03 和 3.11。根据这两个截断值分组，分期 4 纤维化、HCC 发生率和胃食管静脉曲张形成的发生率在两组之间存在显著差异。此外，在 NASH 诊断后，更高值组的患者预后明显较差。
AKR1B10 是 NASH 晚期肝纤维化的有用血清生物标志物，与血清 WFA(+)-M2BP 联合使用，可预测 HCC 发生、胃食管静脉曲张形成和不良预后。
