早期肝硬化和保留的骨髓龛有利于失代偿性肝硬化对生长因

StephenW

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

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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.

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StephenW

早期肝硬化和保留的骨髓龛有利于失代偿性肝硬化对生长因子的再生反应
洛夫克斯阿南德
Chhagan Bihari
Chandan Kumar Kedarisetty
Sheetalnath B Rooge
Dhananjay Kumar
Smriti Shubham
Guresh Kumar
阿米什·萨尼
Manoj Kumar Sharma
......见所有作者
首次发布：2018年7月1日
https://doi.org/10.1111/liv.13923

本文已被接受发布并经过完整的同行评审，但尚未通过编辑，排版，分页和校对过程，这可能导致此版本与记录版本之间存在差异。请引用本文为doi：10.1111 / liv.13923

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抽象
背景

动员的外源性生长因子骨髓（BM）干细胞在失代偿性肝硬化（DC）的治疗中表现出不同的反应。本研究旨在评估添加促红细胞生成素（EPO）在粒细胞集落刺激因子（G-CSF）动员的干细胞治疗，可能的再生机制和再生反应的预测因素方面的潜在临床益处。
方法

60名连续DC患者接受G-CSF与EPO（A组; n = 30）或G-CSF和安慰剂（B组; n = 30）2个月，并仔细跟踪一年。分析基线和治疗后肝活检，BM活检和BM抽吸物的纤维 - 炎症和再生反应以及BM造血库。
结果

与单独使用G-CSF相比，向G-CSF添加EPO显示Child-Pugh评分（p = 0.03）和MELD评分（p = 0.003）显着改善，死亡率降低（16.6％对36.7％，p = 0.09）。联合组还证实了急性肾损伤（p <0.001），脑病（p = 0.005）和腹水再灌注（p = 0.03）的发病率增加。与单一疗法相比，它增加了CD163 +巨噬细胞（p = 0.013），Ki67 +指数（p <0.001），肝组织中α-SMA水平降低（p <0.001）。 1级和2级的反应优于3级腹水; Child B肝硬化和MELD <16。非应答者在基线时具有较低的造血干细胞（HSC）。在多变量分析中，肝病严重程度（MELD <16）和相对保留的BM（BM-HSC> 0.4）预测治疗反应（AUROC = 0.82）。
结论

早期失代偿期肝硬化（MELD <16）轻度 - 中度腹水患者和健康细胞基线BM患者对生长因子治疗反应更好。向G-CSF添加EPO比G-CSF单一疗法提供更好的再生反应。

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kkklovearsenal

利用骨髓里的生长因子，白血病倒是这种思路