RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis

Alcoholic cirrhosis is an end-stage liver disease with impaired survival and often requires liver transplantation. Recent data suggests that receptor-interacting protein kinase-3- (RIPK3-) mediated necroptosis plays an important role in alcoholic cirrhosis. Additionally, neutrophil infiltration is t...

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Main Authors: Zhenzhen Zhang, Guomin Xie, Li Liang, Hui Liu, Jing Pan, Hao Cheng, Hua Wang, Aijuan Qu, Yan Wang
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2018/1509851
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author Zhenzhen Zhang
Guomin Xie
Li Liang
Hui Liu
Jing Pan
Hao Cheng
Hua Wang
Aijuan Qu
Yan Wang
author_facet Zhenzhen Zhang
Guomin Xie
Li Liang
Hui Liu
Jing Pan
Hao Cheng
Hua Wang
Aijuan Qu
Yan Wang
author_sort Zhenzhen Zhang
collection DOAJ
description Alcoholic cirrhosis is an end-stage liver disease with impaired survival and often requires liver transplantation. Recent data suggests that receptor-interacting protein kinase-3- (RIPK3-) mediated necroptosis plays an important role in alcoholic cirrhosis. Additionally, neutrophil infiltration is the most characteristic pathologic hallmark of alcoholic hepatitis. Whether RIPK3 level is correlated with neutrophil infiltration or poor prognosis in alcoholic cirrhotic patients is still unknown. We aimed to determine the correlation of RIPK3 and neutrophil infiltration with the prognosis in the end-stage alcoholic cirrhotic patients. A total of 20 alcoholic cirrhotic patients subjected to liver transplantation and 5 normal liver samples from control patients were retrospectively enrolled in this study. Neutrophil infiltration and necroptosis were assessed by immunohistochemical staining for myeloperoxidase (MPO) and RIPK3, respectively. The noninvasive score system (model for end-stage liver disease (MELD)) and histological score systems (Ishak, Knodell, and ALD grading and ALD stage) were used to evaluate the prognosis. Neutrophil infiltration was aggravated in patients with a high MELD score (≥32) in the liver. The MPO and RIPK3 levels in the liver were positively related to the Ishak score. The RIPK3 was also significantly and positively related to the Knodell score. In conclusion, RIPK3-mediated necroptosis and neutrophil-mediated alcoholic liver inflammatory response are highly correlated with poor prognosis in patients with end-stage alcoholic cirrhosis. RIPK3 and MPO might serve as potential predictors for poor prognosis in alcoholic cirrhotic patients.
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spelling doaj-art-36354f7a42ad4d0d9e959dd2aacb4c7d2025-02-03T06:11:47ZengWileyJournal of Immunology Research2314-88612314-71562018-01-01201810.1155/2018/15098511509851RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic CirrhosisZhenzhen Zhang0Guomin Xie1Li Liang2Hui Liu3Jing Pan4Hao Cheng5Hua Wang6Aijuan Qu7Yan Wang8Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Key Laboratory of Metabolic Disturbance-Related Cardiovascular Disease, Beijing 100069, ChinaDepartment of Pathology, Peking University First Hospital, Beijing 100034, ChinaDepartment of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, ChinaDepartment of Infectious Diseases, Peking University First Hospital, Beijing 100034, ChinaDepartment of Infectious Diseases, Peking University First Hospital, Beijing 100034, ChinaDepartment of Oncology, The First Affiliated Hospital, Institute for Liver Diseases of Anhui Medical University, Hefei 230032, ChinaDepartment of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Key Laboratory of Metabolic Disturbance-Related Cardiovascular Disease, Beijing 100069, ChinaDepartment of Infectious Diseases, Peking University First Hospital, Beijing 100034, ChinaAlcoholic cirrhosis is an end-stage liver disease with impaired survival and often requires liver transplantation. Recent data suggests that receptor-interacting protein kinase-3- (RIPK3-) mediated necroptosis plays an important role in alcoholic cirrhosis. Additionally, neutrophil infiltration is the most characteristic pathologic hallmark of alcoholic hepatitis. Whether RIPK3 level is correlated with neutrophil infiltration or poor prognosis in alcoholic cirrhotic patients is still unknown. We aimed to determine the correlation of RIPK3 and neutrophil infiltration with the prognosis in the end-stage alcoholic cirrhotic patients. A total of 20 alcoholic cirrhotic patients subjected to liver transplantation and 5 normal liver samples from control patients were retrospectively enrolled in this study. Neutrophil infiltration and necroptosis were assessed by immunohistochemical staining for myeloperoxidase (MPO) and RIPK3, respectively. The noninvasive score system (model for end-stage liver disease (MELD)) and histological score systems (Ishak, Knodell, and ALD grading and ALD stage) were used to evaluate the prognosis. Neutrophil infiltration was aggravated in patients with a high MELD score (≥32) in the liver. The MPO and RIPK3 levels in the liver were positively related to the Ishak score. The RIPK3 was also significantly and positively related to the Knodell score. In conclusion, RIPK3-mediated necroptosis and neutrophil-mediated alcoholic liver inflammatory response are highly correlated with poor prognosis in patients with end-stage alcoholic cirrhosis. RIPK3 and MPO might serve as potential predictors for poor prognosis in alcoholic cirrhotic patients.http://dx.doi.org/10.1155/2018/1509851
spellingShingle Zhenzhen Zhang
Guomin Xie
Li Liang
Hui Liu
Jing Pan
Hao Cheng
Hua Wang
Aijuan Qu
Yan Wang
RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
Journal of Immunology Research
title RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
title_full RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
title_fullStr RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
title_full_unstemmed RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
title_short RIPK3-Mediated Necroptosis and Neutrophil Infiltration Are Associated with Poor Prognosis in Patients with Alcoholic Cirrhosis
title_sort ripk3 mediated necroptosis and neutrophil infiltration are associated with poor prognosis in patients with alcoholic cirrhosis
url http://dx.doi.org/10.1155/2018/1509851
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