Increased MMP‐7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia

Background Validated non-invasive examinations are necessary to monitor liver fibrosis in children with biliary atresia (BA) after the Kasai procedure. Purpose To evaluate the diagnostic accuracy of two-dimensional shear wave elastography (2D-SWE), transient elastography (TE), and the serologic biomarkers of aspartate transaminase-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) score for evaluating native liver fibrosis in children with BA. Material and Methods We retrospectively reviewed same-day 2D-SWE and TE liver stiffness (LS) measurements of 63 patients with BA who underwent the Kasai procedure. The APRI and FIB-4 score were computed. Hepatic fibrosis was categorized into three clinical categories based on the ultrasound (US) hepatic morphology and clinical manifestations of liver cirrhosis: I, pre-cirrhotic liver state (n = 15); II, US and/or clinical signs of liver cirrhosis with compensated liver function (n = 27); and III, liver cirrhosis with decompensated liver function (n = 21). We compared area under the receiver operating characteristic curve (AUC) data among 2D-SWE, TE, APRI, and FIB-4 score. Combined evaluation of serologic fibrosis indices and US elastography was conducted and AUCs of combinations were analyzed. Results 2D-SWE, TE, APRI, and FIB-4 score showed good to excellent diagnostic accuracy for differentiating clinical categories (AUCs 0.779–0.955). AUC values were significantly increased after adding TE to FIB-4 score for detecting liver cirrhosis ( P = 0.02). Conclusion 2D-SWE, TE, APRI, and FIB-4 score are accurate non-invasive markers for monitoring native liver fibrosis in patients with BA. Combined use of serologic markers and US elastography could yield more accurate diagnoses of liver fibrosis than serologic markers alone.

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Diagnosing native liver fibrosis and esophageal varices using liver and spleen stiffness measurements in biliary atresia: a pilot study

Pediatric Radiology ◽

10.1007/s00247-016-3637-4 ◽

2016 ◽

Vol 46 (10) ◽

pp. 1409-1417 ◽

Cited By ~ 14

Author(s):

Hirofumi Tomita ◽

Kiyoshi Ohkuma ◽

Yohei Masugi ◽

Naoki Hosoe ◽

Ken Hoshino ◽

...

Keyword(s):

Pilot Study ◽

Liver Fibrosis ◽

Biliary Atresia ◽

Esophageal Varices ◽

Native Liver ◽

Spleen Stiffness

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EXISTENCE OF BACTERIA IN NATIVE LIVER OF BILIARY ATRESIA PATIENTS IS ASSOCIATED WITH SUBSEQUENT BACTERIAL INFECTIONS POST TRANSPLANTATION

10.26226/morressier.58fa1768d462b80290b50baa ◽

2017 ◽

Author(s):

Kazuhiro Uda

Keyword(s):

Biliary Atresia ◽

Bacterial Infections ◽

Post Transplantation ◽

Native Liver

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Centralization of Biliary Atresia: Has Germany Learned Its Lessons?

European Journal of Pediatric Surgery ◽

10.1055/s-0041-1723994 ◽

2021 ◽

Author(s):

Omid Madadi-Sanjani ◽

David Fortmann ◽

Udo Rolle ◽

Burkhard Rodeck ◽

Ekkehard Sturm ◽

...

Keyword(s):

Biliary Atresia ◽

Data Transfer ◽

Previous Analysis ◽

Outcome Data ◽

Free Survival ◽

Change In Practice ◽

Native Liver ◽

Survival With Native Liver ◽

Pediatric Liver Transplant

Abstract Introduction The majority of pediatric surgeons and hepatologists recommend the centralization of biliary atresia (BA) treatment within experienced liver units. We aimed to investigate whether voluntary self-restriction and acceptance of the need for this change in practice changed the BA referral policy in Germany during the last decade. Materials and Methods In cooperation with pediatric surgeons, gastroenterologists or hepatologists, and pediatric liver transplant units, the 2-year follow-up data of infants with BA born in Germany between 2010 and 2014 were collected using www.bard-online.com or pseudonymized data transfer. Results were compared with our previous analysis of the outcome data of infants with BA born between 2001 and 2005 in Germany. Result Overall, 173 infants with BA were identified, of whom 160 underwent Kasai portoenterostomy (KPE; 92.5%) and 13 (7.5%) underwent primary liver transplantation at 21 German centers. At 2-year follow-up, overall survival was 87.7% (vs. 81.9% in 2001–2005 [p = 0.19]), survival with native liver post-KPE was 29.2% (vs. 22.8% in 2001–2005 [p = 0.24]), and jaundice-free survival with native liver post-KPE was 24.0% (vs. 20.1% in 2001–2005 [p = 0.5]). Compared with the 2001–2005 analysis, all criteria showed improvement but the differences are statistically not significant. Conclusion Our observation shows that KPE management requires improvement in Germany. Centralization of BA patients to German reference liver units is not yet mandatory. However, European and national efforts with regard to the centralization of rare diseases support our common endeavor in this direction.

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Current Concepts of Biliary Atresia and Matrix Metalloproteinase-7: A Review of Literature

Frontiers in Medicine ◽

10.3389/fmed.2020.617261 ◽

2020 ◽

Vol 7 ◽

Author(s):

Mark Nomden ◽

Leonie Beljaars ◽

Henkjan J. Verkade ◽

Jan B. F. Hulscher ◽

Peter Olinga

Keyword(s):

Immune Response ◽

Liver Fibrosis ◽

Pulmonary Fibrosis ◽

Matrix Metalloproteinase ◽

Biliary Atresia ◽

Adaptive Immune Response ◽

Cell Contact ◽

T Helper 1 ◽

Matrix Metalloproteinase 7

Biliary atresia (BA) is a rare cholangiopathy of infancy in which the bile ducts obliterate, leading to profound cholestasis and liver fibrosis. BA is hypothesized to be caused by a viral insult that leads to over-activation of the immune system. Patients with BA are surgically treated with a Kasai portoenterostomy (KPE), which aims to restore bile flow from the liver to the intestines. After KPE, progressive liver fibrosis is often observed in BA patients, even despite surgical success and clearance of their jaundice. The innate immune response is involved during the initial damage to the cholangiocytes and further differentiation of the adaptive immune response into a T-helper 1 cell (Th1) response. Multiple studies have shown that there is continuing elevation of involved cytokines that can lead to the progressive liver fibrosis. However, the mechanism by which the progressive injury occurs is not fully elucidated. Recently, matrix metalloproteinase-7 (MMP-7) has been investigated to be used as a biomarker to diagnose BA. MMPs are involved in extracellular matrix (ECM) turnover, but also have non-ECM related functions. The role of MMP-7 and other MMPs in liver fibrosis is just starting to be elucidated. Multiple studies have shown that serum MMP-7 measurements are able to accurately diagnose BA in a cohort of cholestatic patients while hepatic MMP-7 expression correlated with BA-related liver fibrosis. While the mechanism by which MMP-7 can be involved in the pathophysiology of BA is unclear, MMP-7 has been investigated in other fibrotic pathologies such as renal and idiopathic pulmonary fibrosis. MMP-7 is involved in Wnt/β-catenin signaling, reducing cell-to-cell contact by shedding of E-cadherin, amplifying inflammation and fibrosis via osteopontin (OPN) and TNF-α while it also appears to play a role in induction of angiogenesis This review aims to describe the current understandings of the pathophysiology of BA. Subsequently, we describe how MMP-7 is involved in other pathologies, such as renal and pulmonary fibrosis. Then, we propose how MMP-7 can potentially be involved in BA. By doing this, we aim to describe the putative role of MMP-7 as a prognostic biomarker in BA and to provide possible new therapeutic and research targets that can be investigated in the future.

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