Early cirrhosis and a preserved bone marrow niche favor regenerative response to growth factors in decompensated cirrhosis
Lovkesh Anand
Chhagan Bihari
Chandan Kumar Kedarisetty
Sheetalnath B Rooge
Dhananjay Kumar
Smriti Shubham
Guresh Kumar
Amrish Sahney
Manoj Kumar Sharma
… See all authors
First published: 01 July 2018 https://doi.org/10.1111/liv.13923
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/liv.13923
ePDFPDF
Tools
Share
Abstract
Background
Exogenous growth factor mobilized Bone Marrow (BM) stem cells has shown a differential response in the management of decompensated cirrhosis (DC). This study was designed to evaluate potential clinical benefit of adding Erythropoietin (EPO) in Granulocyte colony stimulating factor (G‐CSF) mobilized stem cell therapy, possible mechanisms of regeneration and predictive factors of regenerative response.
Methods
60 consecutive DC patients received either G‐CSF with EPO (Group A; n=30) or G‐CSF and placebo (Group B; n=30) for 2 months and were carefully followed for one year. Baseline and post‐treatment liver biopsy, BM biopsy, and BM aspirate were analyzed for fibro‐inflammatory and regenerative response and BM hematopoietic reservoir.
Results
Addition of EPO to G‐CSF showed a significant improvement in Child‐Pugh score (p=0.03) and MELD score(p=0.003) as compared to G‐CSF alone, with reduction in mortality (16.6% vs. 36.7%, p=0.09). The combination arm also demonstrated adecreased incidence of acute kidney injury (p<0.001), encephalopathy (p=0.005) and refilling of ascites(p=0.03). Compared to monotherapy, it increased CD163+ macrophages (p=0.013), Ki67+ index(p<0.001) with decrease in α‐SMA levels(p<0.001) in liver tissue. The response was better with grade 1 and 2 than with grade 3 ascites; Child B cirrhosis and MELD<16.Non‐responders had lower hematopoietic stem cells(HSCs) at baseline. On multivariate analysis, the liver disease severity (MELD<16) and a relatively preserved BM (BM‐HSCs>0.4) predicted therapeutic response(AUROC=0.82).
Conclusions
Early decompensated cirrhosis (MELD<16) patients with mild‐moderate ascites and those with a healthy cellular baseline BM respond better to growth factor therapy. Addition of EPO to G‐CSF provides better regenerative response than G‐CSF monotherapy.
This article is protected by copyright. All rights reserved. 作者: StephenW 时间: 2018-7-4 18:02