Abstract
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.
Highlights
Alcoholic cirrhosis is the end-stage serious liver disease with high morbidity and mortality and is the leading cause of liver transplantation [1,2,3]
Our results showed that RIPK3mediated necroptosis and neutrophil-mediated alcoholic liver inflammatory response are highly correlated with poor prognosis in end-stage alcoholic cirrhotic patients
To confirm whether neutrophil infiltration contributes to this process, hematoxylin and eosin (H&E) staining and IHC staining for MPO were performed
Summary
Alcoholic cirrhosis is the end-stage serious liver disease with high morbidity and mortality and is the leading cause of liver transplantation [1,2,3]. Prognostic models can be used to assess the severity and survival of the disease and can be useful as a medical decision-making tool to guide patient care. The early detection and evaluation of this severe disease have not been fully elucidated. The most widely used noninvasive predictor of poor prognosis in alcoholic liver cirrhosis is the model for endstage liver disease (MELD) scoring systems [4]. While for specific predictors, histologic scoring system is the main method [5, 6]. The ALD grading and staging schema were
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