Philips Cyriac A, Augustine Philip, Rajesh Sasidharan, Ahamed Rizwan, George Tom, Padsalgi Guruprasad, Paramaguru Rajaguru, Valiathan Gopakumar, John Solomon K
The Liver Unit, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi, Kerala.
Gastroenterology, Cochin Gastroenterology Group, Ernakulam Medical Center, Kochi, Kerala.
J Clin Exp Hepatol. 2020 Mar-Apr;10(2):124-134. doi: 10.1016/j.jceh.2019.05.003. Epub 2019 Jun 1.
Granulocyte colony-stimulating factor (GCSF) has been utilized in decompensated cirrhosis (DC) for improving transplant-free survival (TFS). Data from multiple centers are conflicting with regard to patient outcomes. In this retrospective study, we present our 'real-world experience' of GCSF use in a large group of DC.
From September 2016 to September 2018, 1231 patients with cirrhosis were screened, of which 754 were found to have decompensation(s). Seventy-three patients with active ascites, jaundice, or both completed GCSF treatment (10 mcg/kg per day for 5 days, followed by 5 mcg/kg/day once every third day for total 12 doses). Per-protocol analysis (n = 56) was performed to study clinical events, liver disease severity, and outcomes at 3, 6, and 12 months after treatment. Modified intention-to-treat (mITT, n = 100) analysis was performed to study overall survival at 180 days. Outcomes were compared with a matched historical control (HC) group (n = 24).
Nine (16%, n = 56), 24 (43%, n = 56), and 36 (75%, n = 48) patients died at 3, 6, and 12-month follow-up after GCSF. The commonest cause of death was sepsis (53%) followed by progressive liver failure (33%). Nine percent of patients developed hepatocellular carcinoma on follow-up at the end of 1 year. Acute variceal bleeds, overt hepatic encephalopathy, intensive unit admissions, and liver disease severity scores were higher after treatment at the end of 1 year. The Child-Pugh score >11 and model for end-stage liver disease-sodium score >25 and > 20 predicted worse outcomes at all time points and at 6 and 12 months after GCSF, respectively. Compared to a matched HC group, patients receiving GCSF had higher mortality (75% vs 46%, = 0.04) at one year. mITT analysis revealed poor overall survival at 6 months compared to HCs (48% vs 75%, = 0.04).
Survival in DC was shorter than what was expected in the natural history of the disease after GCSF use.
粒细胞集落刺激因子（GCSF）已被用于失代偿期肝硬化（DC）以提高无移植生存期（TFS）。多个中心的数据在患者预后方面存在冲突。在这项回顾性研究中，我们展示了在一大群DC患者中使用GCSF的“真实世界经验”。
2016年9月至2018年9月，对1231例肝硬化患者进行筛查，其中754例被发现有失代偿情况。73例有活动性腹水、黄疸或两者皆有的患者完成了GCSF治疗（每天10 mcg/kg，共5天，随后每三天一次，每次5 mcg/kg，共12剂）。进行符合方案分析（n = 56）以研究治疗后3、6和12个月的临床事件、肝病严重程度和预后。进行改良意向性治疗（mITT，n = 100）分析以研究180天的总生存期。将结果与匹配的历史对照（HC）组（n = 24）进行比较。
在GCSF治疗后的3、6和12个月随访中，分别有9例（16%，n = 56）、24例（43%，n = 56）和36例（75%，n = 48）患者死亡。最常见的死亡原因是败血症（53%），其次是进行性肝衰竭（33%）。1%的患者在1年随访结束时发生肝细胞癌。1年后治疗结束时，急性静脉曲张出血、显性肝性脑病、重症监护病房入院率和肝病严重程度评分更高。Child-Pugh评分>11以及终末期肝病-钠评分>25和>20分别在所有时间点以及GCSF治疗后的6个月和12个月预测了更差的预后。与匹配的HC组相比，接受GCSF治疗的患者1年时死亡率更高（75%对46%，P = 0.04）。mITT分析显示，与HC组相比，6个月时总生存期较差（48%对75%，P = 0.04）。
使用GCSF后，DC患者的生存期比该疾病自然史中预期的要短。
