Severity And Risk Factors Of Adverse Outcomes In Decompensated Cirrhotic Patients With COVID-19

Chapter 1 Cirrhosis and COVID-19:a Meta-analysisObjects:Meta-analysis was conducted to explore the differences on risk factors and clinical outcomes of cirrhotic patients with COVID-19.Methods:Before December 6th,2021,publications were searched from seven well-known databases(including Pubmed,Web of Science,Embase,Cochrane Library,China National Knowledge Internet,Wanfang Data and VIP Data).Searched terms were ’COVID-19’,’SARS-COV-2’,’2019-NCOV’,’2019 Novel Coronavirus’,’Coronavirus Disease-19’,’SARS-Coronavirus2’,’Liver’,’Hepatic’,’Fibrosis’,and ’Fibroses’.Relevant literature was screened according to inclusion and exclusion criteria.NOS scale was used to evaluate the literature,and articles of high quality were reserved as the final included articles.Associated data were extracted for Meta-analysis in R(version 3.6.2)and R Studio(version 1.1.463).Results:17 researches were included,involving a total of 115,170 participants.1.In the case of COVID-19 infection,leukocyte count,neutrophil count,platelet count,hemoglobin,albumin decreased significantly in patients with cirrhosis compared with ones without cirrhosis(P<0.05);total bilirubin,aspartate aminotransferase,alkaline phosphatase and the international standardized ratios of prothrombin time increased significantly(P<0.05);2.Cirrhotic patients combined with COVID-19 had significantly lower platelet counts,alkaline phosphatase and total bilirubin,in addition to significantly higher aspartate aminotransferase than those without COVID-19 infection(P<0.05);3.Cirrhotic patients with COVID-19 were 1.77 folds(95%CI,1.32～2.38)more likely to have mortality risk than those without COVID19;4.COVID-19 patients with cirrhosis increased the risk of death to 2.55 folds(95%CI,1.54～4.23)that of those without cirrhosis;5.The mortality was 28.1%(95%CI,20.32%～36.57%)in cirrhotic patients with COVID-19;The mortality was 41.96%(95%CI,26.76%～57.17%)in decompensated cirrhotic patients with COVID-19;The risk of death in patients with decompensated cirrhosis was 2.04 folds(95%CI,1.59～2.60)higher than that in patients with compensatory cirrhosis;6.Alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,prothrombin time,the international standardized ratio of prothrombin time,serum creatinine,total bilirubin and albumin decrease were closely related to the adverse outcomes in cirrhotic patients with COVID-19;Patients with Child-Pugh scores B/C and higher MELD scores had a higher risk of death in cirrhotic patients with COVID-19(P<0.05).Conclusion:Compared with the control groups,cirrhotic patients combined with COVID-19 showed changes in blood routine,liver function,coagulation function and other laboratory test results,as well as an increased risk of mortality,some of which may be related to the occurrence of adverse outcomes.In addition,cirrhotic patients with COVID-19 had a high mortality rate,especially among patients with decompensated cirrhosis.Chapter 2 Risk factors associated with severity and adverse outcomes in decompensated cirrhotic patients with COVID-19:a multicenter cohort studyObjects:To investigate possible associated risk factors in a multicenter cohort study among decompensated cirrhotic patients with COVID-19.Methods:This study was a multicenter retrospective cohort study of hospitalized COVID-19 patients admitted from 24 hospitals in central China between January and March,2020.The diagnosis of decompensated cirrhosis and COVID-19 were examined by two or more professional physicians.Patients with decompensated cirrhosis and age-and sexmatched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.The information and data of the subjects were collected from electronic medical records.The information recorded included:demographic data,comorbidities,clinical manifestations,laboratory examinations,treatments,and clinical outcomes.Categorical variables were described as frequency and percentage,while continuous variables were illustrated by average,median,and quartile spacing(IQR).Student’s t test would be applied to compare the mean value of continuous variables if normally distributed;otherwise,Mann-Whitney U test would be utilized.Categorical variables were analyzed using chi-square tests or Fisher’s exact test.Univariate and multivariate logistic regression was used to explore risk factors that predict the severity and outcomes.Results:A total of 66 patients with decompensated cirrhosis and COVID-19 comorbidity were included as the positive group,including 38 patients with severe COVID-19 and 28 patients with non-severe COVID19.264 COVID-19 patients without liver disease were regarded as the control group.Our results demonstrated that:1.Decompensated cirrhotic patients with COVID-19 had significantly higher Charleson’s comorbidity index with more hypertension,diabetes,chronic lung disease,and malignant tumors than patients without liver disease(P<0.05).The proportion of hyperpyrexia,bleeding,ascites,jaundice,diarrhea and shortness of breath was higher(P<0.05),while the proportion of cough was lower(P<0.05).There were plenty of abnormal laboratory test indicators,including abnormal blood routine,liver function,liver function and kidney function(P<0.05).2.Decompensated cirrhotic patients with COVID-19 had less bleeding(P<0.001)and more shortness of breath(P<0.001)than decompensated cirrhotic patients with other pathogens.Erythrocyte count,hemoglobin,alanine aminotransferase,aspartate aminotransferase and serum creatinine were significantly increased(P<0.05),while lymphocyte count was significantly decreased(P<0.05).3.The proportion of severe COVID-19(P<0.01),and mortality rate(P<0.001)were significantly higher among decompensated cirrhotic patients with COVID-19 than the control groups;4.In patients with decompensated cirrhosis,more ascites,jaundice,higher mortality and the abnormal degree of liver function were companied with the increasing severity of COVID-19(P<0.05).Multivariate logistic regression analysis suggested that patients with lower albumin level,higher MELD score and CURB-65 score were more likely to develop severe type of COVID-19(P<0.05);5.Decompensated cirrhotic patients with COVID-19 had a higher proportion of patients with death associated with cardiovascular disease(P<0.05),fewer Child-Pugh scores of class A and more class C(P<0.05)than those survivors.Child-pugh score,MELD score and CURB-65 score were higher in death group(P<0.05).Among laboratory indicators,white blood cell count,neutrophil count,activated partial thrombin time and creatinine level were significantly increased(P<0.05),while lymphocyte count was significantly decreased(P<0.05)in death group.Multivariate logistic regression analysis suggested that Child-Pugh and CURB-65 scores were correlated with the risk of death in this group of patients(P<0.05).ROC curve showed that Child-pugh class greater than A and CURB-65 score greater than 2 made patients more prone to adverse clinical manifestations.Conclusion:Patients with decompensated cirrhosis had a higher proportion of mortality and exposing severe COVID-19 than patients without liver disease.Low level of albumin,high MELD and CURB-65 scores at the beginning of the disease may be risk factors for severe COVID-19 syndrome,while Child-Pugh class and CURB-65 scores may be associated with the risk of death in this group of patients.