Granulocyte Colony-Stimulating Factor Mobilizes CD34+ Cells and Improves Survival of Patients With Acute-on-Chronic Liver Failure

被引:291
作者
Garg, Vishal [2 ]
Garg, Hitendra [1 ]
Khan, Arshi [1 ]
Trehanpati, Nirupama [1 ]
Kumar, Ashish [1 ]
Sharma, Barjesh Chander [2 ]
Sakhuja, Puja [3 ]
Sarin, Shiv Kumar [1 ,2 ]
机构
[1] Inst Liver & Biliary Sci, Dept Hepatol, New Delhi 110070, India
[2] GB Pant Hosp, Dept Gastroenterol, New Delhi, India
[3] GB Pant Hosp, Dept Pathol, New Delhi, India
关键词
Liver Regeneration; Liver Stem Cells; Growth Factor; Cirrhosis; HEMATOPOIETIC STEM-CELLS; CRITICALLY-ILL PATIENTS; SHORT-TERM PROGNOSIS; BONE-MARROW; G-CSF; CIRRHOTIC-PATIENTS; REGENERATION; MORTALITY; DYSFUNCTION; PREDICTORS;
D O I
10.1053/j.gastro.2011.11.027
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) develops in patients with chronic liver disease and has high mortality. Mobilization of bone marrow-derived stem cells with granulocyte colony-stimulating factor (G-CSF) could promote hepatic regeneration. METHODS: Consecutive patients with ACLF were randomly assigned to groups given 5 mu g/kg G-CSF subcutaneously (12 doses; group A, n = 23) or placebo (group B, n = 24) plus standard medical therapy. We assessed survival until day 60; Child-Turcotte-Pugh (CTP), Model for End-Stage Liver Disease (MELD), and Sequential Organ Failure Assessment (SOFA) scores; and the development of other related complications. RESULTS: After 1 week of treatment, group A had higher median leukocyte and neutrophil counts than group B (P < .001). Sixteen patients in group A (69.6%) and 7 in group B (29%) survived; the actuarial probability of survival at day 60 was 66% versus 26%, respectively (P = .001). Treatment with G-CSF also reduced CTP scores in group A by a median of 33.3% compared with an increase of 7.1% in group B (P = .001), along with MELD (median reduction of 15.3% compared with an increase of 11.7% in group B; P = .008) and SOFA scores (median reduction of 50% compared with an increase of 50% in group B; P = .001). The percentages of patients who developed hepatorenal syndrome, hepatic encephalopathy, or sepsis were lower in group A than in group B (19% vs 71% [P = .0002], 19% vs 66% [P = .001], and 14% vs 41% [P = .04], respectively). After 1 month of treatment, G-CSF increased the number of CD34(+) cells in the liver (by 45% compared with 27.5% in group B; P = .01). CONCLUSIONS: G-CSF therapy more than doubles the percentage of patients with ACLF who survive for 2 months; it also significantly reduces CTP, MELD, and SOFA scores and prevents the development of sepsis, hepatorenal syndrome, and hepatic encephalopathy.
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收藏
页码:505 / U156
页数:9
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