Temporal Patterns Of Liver Injury And Disease Outcome Of In-patients With COVID-19

Background: 2019 novel coronavirus pneumonia(Coronavirus disease 2019,COVID-19)is a newly discovered respiratory disease with high mortality and high infectious rate.At present,COVID-19 has spread all over the world,and it has shown a pandemic level,seriously endangering human health.Many studies have reported that liver is an important organ involved in patients with COVID-19.However,the clinical characteristics of liver injury in patients with COVID-19 and its effect on prognosis are not clear.Objective: It is urgent to explore the relationship between the liver function indexes of patients with COVID-19 and its effects of prognosis,including the distribution and change trend of clinical characteristics of liver injury in patients with COVID-19,the relationship between liver function indexes and all-cause mortality in patients with COVID-19,and the related factors of liver function indexes in patients with COVID-19.It is helpful to guide clinicians to monitor the change trend of liver function indexes in patients with COVID-19,and to intervene and treat the liver injury caused by COVID-19 in the early stage.Methods: The basic information,medical history,clinical characteristics,laboratory examination,imaging examination,treatment intervention and outcome of7029 patients with COVID-19 who were treated in 10 hospitals in Hubei Province from December 20,2019 to March 8,2020 were collected.After strict inclusion exclusion criteria and quality control,5771 COVID-19 patients were included.The change trend of related indicators of COVID-19 induced liver injury and its influence on prognosis were analyzed by multicenter,retrospective and multivariate analysis.It is mainly to show the baseline characteristics of patients with COVID-19 by frequency(percentage)of categorical variables and median(interquartile range(IQR))of continuous variables.To show the peak distribution of liver function index and its change trend with the course of disease by Gauss kernel density and local weighted regression.To study the liver function index and death of patients with covid-19 by Cox risk proportion regression model of mixed effect.Logistic regression model was used to analyze the correlation between the liver function indexes of COVID-19 patients and clinical characteristics,clinical medication and other factors.Results: A total of 5771 patients with covid-19 were included in the analysis.According to the severity of the disease,4585 patients(79.4%)were non severe patients with COVID-19,1186 patients(20.6%)were severe patients,the median age of the patients was 56 years old(IQR,43-65 years old),2724 patients(47.2%)were male patients,4119 patients(71.4%)had fever,1008 patients(17.5%)had dyspnea,etc.The top five basic diseases in patients with COVID-19 were diabetes,coronary heart disease,cerebrovascular disease,chronic kidney disease and chronic liver disease.In the imaging examination of patients with COVID-19,4405 patients(83.1%)had bilateral accumulated lesions.In the laboratory examination,the level of C-reactive protein increased(51.5%),the level of D-dimer increased(38.5%),the number of lymphocyte decreased(37.1%),the number of red blood cells decreased(31.5%),the median of albumin level was 37.5 g/L(IQR,34.2-40.7),and the median of ALT level was 24.0 U/L(IQR,17.0-35.0),AST median level was 24.0 U/L(IQR,15.1-39.0),ALP median level was 64.0 U/L(IQR,51.0-83.0),globulin level was27.2 g/L(IQR,24.2-30.4)and TBIL median level was 10.4 μmol/L(IQR,7.9-14.1),The difference of the above results is statistically significant(P < 0.05).In the treatment of COVID-19 patients during hospitalization,more than 50% of the patients used traditional Chinese medicine,antiviral drugs and antibiotic drugs.The incidence of acute liver injury(ALI)was 6.2% in patients with COVID-19.The median day of days of acute liver injury was on the 17 th day after symptom onset(IQR,13-23days).During hospitalization,the dynamic changes of ALT,AST,ALP and TBIL in patients with COVID-19 were different,compared with patients without severe disease,the levels of AST and ALT in patients with severe disease were increased to different degrees,the range of AST increased was more significant,the level of ALT exceeded the normal line;the level of ALP slightly increased,basically kept in the normal range during hospitalization;the level of TBIL fluctuated in patients lighter.The increased levels of ALT,AST,ALP and TBIL increased the risk of death in COVID-19 patients,and the HR of all-cause mortality with AST > 120u/L was 14.87(95%CI: 9.65 ～ 22.93),P < 0.05,compared with patients with normal AST level.The positive correlation factors with the increase of liver injury index were male,neutrophil count increase,lymphocyte count decrease,OR > 1,P < 0.05,with statistical significance.Conclusions: The change trend of liver function related indexes and potential risk factors in the course of COVID-19 provide important clinical evidence for the prevention,treatment and prognosis of COVID-19 combined with liver injury.Because the abnormal liver function index of patients with COVID-19 is related to the increased risk of death,especially AST is closely related to the risk of death,continuous monitoring of the liver function index of patients with COVID-19 should be carried out during hospitalization,which is helpful for patients with COVID-19 to carry out preventive treatment in the early stage of liver injury,so as to avoid the occurrence of liver injury,or more serious liver failure,or even death.