Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease.
Serum Matrix Metalloproteinase 7 Is a Diagnostic Biomarker of Biliary Injury and Fibrosis in Pediatric Autoimmune Liver Disease.
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DOI：
10.1002/hep4.1589
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发表时间：
2020-11
影响因子：
5.1
通讯作者：
Miethke AG
中科院分区：
文献类型：
--
作者：
Lam S;Singh R;Dillman JR;Trout AT;Serai SD;Sharma D;Sheridan R;Su W;Fei L;Karns R;Haramija MM;Ridgway G;Goldfinger M;Squires JE;Denson LA;Hyams JS;Miethke AG
在自身免疫性肝病(AILD)中，包括自身免疫性肝炎(AIH)、原发性硬化性胆管炎(PSC)和AIH和PSC重叠综合征(ASC)，胆道损伤的存在预示着预后较差。我们研究了血清基质金属蛋白酶7(SMMP7)作为儿童硬化性胆管炎(SC)的生物标志物。我们在我们的中心前瞻性地招募了54名患有AILD(AIH，n=26；ASC，n=16；PSC，n=12)的儿童(中位年龄，16岁)。SC患者血清sMMP7浓度高于无胆管病患者(P<0.001)。SMMP7浓度为23.7 ng/mL时，诊断SC的敏感性和特异性分别为79%和96%，优于碱性磷酸酶(ALP)和γ-谷氨酰转移酶(GGT)。血清浓度与肝脏MMP7基因表达水平相关(r=0.70；P<0.001)。免疫荧光显示MMP7主要定位于SC患者的胆管细胞。在46名肝活检患者中，sMMP7浓度升高与淋巴细胞性胆管炎、中性粒细胞胆管炎和导管周围纤维化的存在分离，并与Ishak、Ludwig和Nakanuma评分系统相关。磁共振弹性成像测量的肝脏硬度也与sMMP7浓度相关(r=0.56；P<0.01)。磁共振胆胰管成像(MRCP+)显示34例患者的sMMP7与胆管扩张(r=0.54；P<0.01)和狭窄(r=0.56；P<0.01)相关。MMP7作为胆道损伤的标志在溃疡性结肠炎儿童的独立队列中得到验证。SMMP7浓度升高也与SC相关并发症的病史相关。结论：MMP7是一种有前景的儿童SC的生物标志物，其诊断效果优于ALP和GGT。SMMP7可能直接反映了胆管损伤和纤维化，这是SC疾病进展的主要驱动因素。
In autoimmune liver disease (AILD), including autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and overlap syndrome of AIH and PSC (ASC), the presence of biliary injury portends a worse prognosis. We studied serum matrix metalloproteinase 7 (sMMP7) as a biomarker for pediatric sclerosing cholangitis (SC). We prospectively enrolled 54 children (median age, 16 years) with AILD (AIH, n = 26; ASC, n = 16; and PSC, n = 12) at our center. The sMMP7 concentrations were higher in patients with SC compared to those without cholangiopathy (P < 0.001). An sMMP7 concentration >23.7 ng/mL had a sensitivity and specificity of 79% and 96%, respectively, and outperformed alkaline phosphatase (ALP) and gamma‐glutamyltransferase (GGT) in segregating patients with SC. Serum concentrations correlated with liver gene expression levels for MMP7 (r = 0.70; P < 0.001). Using immunofluorescence, MMP7 was localized primarily to the cholangiocytes of patients with SC. In 46 subjects with liver biopsy available for blinded review, elevation in sMMP7 concentrations segregated with the presence of lymphocytic and neutrophilic cholangitis and periductal fibrosis and correlated with Ishak, Ludwig, and Nakanuma scoring systems. Liver stiffness measured by magnetic resonance elastography also correlated with sMMP7 concentrations (r = 0.56; P < 0.01). Using magnetic resonance cholangiopancreatography plus (MRCP+), sMMP7 in 34 patients correlated with the number of biliary dilatations (r = 0.54; P < 0.01) and strictures (r = 0.56; P < 0.01). MMP7 as a marker of biliary injury was validated in an independent cohort of children with ulcerative colitis. Higher sMMP7 concentrations also correlated with a history of SC‐related complication. Conclusion: MMP7 is a promising biomarker for pediatric SC that diagnostically outperforms ALP and GGT. sMMP7 may directly reflect biliary injury and fibrosis, the main drivers of disease progression in SC.
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影响因子：
12.6
作者：
Miloh, Tamir;Arnon, Ronen;Kerkar, Nanda
通讯作者：
Kerkar, Nanda
影响因子：
13.5
作者：
Loomba, Rohit;Sirlin, Claude B.;Schwimmer, Jeffrey B.;Lavine, Joel E.
通讯作者：
Lavine, Joel E.
DOI：
10.1016/s2468-1253(17)30252-2
发表时间：
2017-12
期刊：
The lancet. Gastroenterology & hepatology
影响因子：
--
作者：
Hyams JS;Davis S;Mack DR;Boyle B;Griffiths AM;LeLeiko NS;Sauer CG;Keljo DJ;Markowitz J;Baker SS;Rosh J;Baldassano RN;Patel A;Pfefferkorn M;Otley A;Heyman M;Noe J;Oliva-Hemker M;Rufo P;Strople J;Ziring D;Guthery SL;Sudel B;Benkov K;Wali P;Moulton D;Evans J;Kappelman MD;Marquis A;Sylvester FA;Collins MH;Venkateswaran S;Dubinsky M;Tangpricha V;Spada KL;Britt A;Saul B;Gotman N;Wang J;Serrano J;Kugathasan S;Walters T;Denson LA
通讯作者：
Denson LA
影响因子：
5.1
作者：
Deneau MR;Mack C;Abdou R;Amin M;Amir A;Auth M;Bazerbachi F;Marie Broderick A;Chan A;DiGuglielmo M;El-Matary W;El-Youssef M;Ferrari F;Furuya KN;Gottrand F;Gupta N;Homan M;Jensen MK;Kamath BM;Mo Kim K;Kolho KL;Konidari A;Koot B;Iorio R;Martinez M;Mohan P;Palle S;Papadopoulou A;Ricciuto A;Saubermann L;Sathya P;Shteyer E;Smolka V;Tanaka A;Valentino PL;Varier R;Venkat V;Vitola B;Vos MB;Woynarowski M;Yap J;Miloh T
通讯作者：
Miloh T
影响因子：
17.1
作者：
Lertudomphonwanit C;Mourya R;Fei L;Zhang Y;Gutta S;Yang L;Bove KE;Shivakumar P;Bezerra JA
通讯作者：
Bezerra JA