Prognostic Risk Factors Of Patients With Hepatitis B Virus-related Acute-on-chronic Liver Failure And Its Combined Acute Renal Injury

Background and ObjectiveAcute-on-chronic liver failure(ACLF)is a result of acute or sub-acute hepatic decompensation occurring in a short time with underlying chronic liver disease,which is often accompanied by failure of multiple organs or systems,and followed by poor prognosis.Although the East and the West side of the ACLF diagnostic criteria have not yet reached a consensus,but it is undeniable that ACLF is still the most common in all of the liver failure.According to epidemiological data,etiologies of ACLF is mostly alcoholic liver diseases in western countries,when compared to chronic hepatitis B virus(HBV)-related liver diseases in China.Acute kidney injury(AKI),previously defined as acute renal failure(ARF),is one of the most common complications of end-stage liver diseases.AKI is usually associated with poor outcome,and almost all patients with stage-3 AKI need renal replacement therapy(RRT)once AKI progress occurs.Impairment of renal function is significantly associated with poor outcome in patients with ACLF.In the past,the concept of hepatorenal syndrome(HRS)was primarily used to evaluate the renal injury in ACLF.However,it is difficult to establish the diagnosis of HRS due to the narrow range of diagnostic performance particularly the long determination time and low prevalence in liver diseases.Fortunately,introduction of AKI,may better to solve these dilemmas,which is practicability superior than HRS in terms of serum creatinine(s Cr)determination,staging criteria,treatment guidance and prognosis.Currently,available studies on liver disease-related AKI abroad concentrate mostly on decompensated cirrhosis without ACLF.HBV infection is the foremost cause of ACLF among Chinese population.However,clinical characteristics and prognosis of HBV-related ACLF patients with AKI onset have scarcely been studied.Therefore,we conducted a follow-up study on the clinical characteristics and outcome of HBV-related ACLF patients with AKI,in order to provide more references for clinical diagnosis and treatment.MethodsA total of 1,167 patients with HBV-related ACLF from January 2010 to January 2015 were enrolled and the clinical,laboratory and imaging data of all ACLF patients were collected.All patients received follow-up after discharge for a median duration of one year with death or loss to follow-up as the endpoint.OS and severe complications of patients were recorded.All patients were followed up to investigate clinical characteristics,long-term overall survival(OS)and risk factors.Results1.A total of 600 patients died within the 1-year follow-up period,and the mortality rate was 55.2%.2.A total of 308(26.4%)ACLF patients experienced onset of AKI,in which 256(83.1%)patients with prerenal AKI,50(16.2%)patients with intrarenal AKI and 2(0.7%)patients with postrenal AKI.Patients with intrarenal AKI are on an upward trend.3.The death group showed the higher level of age,alanine aminotransferase(ALT),total bilirubin(TBIL),internatonal normalized ratio(INR),urea nitrogen(BUN),serum creatinine(s Cr),white blood cell(WBC),percentage of neutrophils,HBV DNA load,Child score and Model for End-Stage Liver Disease(MELD)score than the survival group(P<0.01).But its mean arterial pressure(MAP),platelet(PLT)and serum Na+ is lower than survival group(all P<0.01).TBIL,INR,s Cr and MELD scores were higher in AKI group than in non-AKI group.4.The time of AKI occurred from HBV activation was longer than the time from infection(or blood volume insufficiency).5.There were significantly higher incidences of severe complications like ascites,spontaneous bacterial peritonitis(SBP),upper gastrointestinal bleeding,pulmonary infection,sepsis,electrolyte imbalance,hepatic encephalopathy(HE)and acute kidney injure(AKI)in death group than in survival group(all P<0.01).6.Median duration of hospitalization in AKI group was shorter than in non-AKI group.There were significantly higher incidences of severe complications like ascites,SBP,upper gastrointestinal bleeding,pulmonary infection,sepsis,electrolyte imbalance and HE in AKI group than in non-AKI group(all P<0.01).7.The patients in AKI group and non-AKI group had 30-day OS of 44.8% and 70.3%;90-day OS of 17.9% and 55.4%;and 1-year OS of 15.6% and 51.2%,respectively(all P<0.01).8.Significant differences were observed in 30-day,90-day and 1-year OS between subgroups with different AKI stages(P<0.01).There was no significant difference in 30-day,90-day and 360-day OS between pre-renal AKI group and renal AKI group.9.The Cox regression analysis showed that age,WBC,MELD score,HE,electrolyte disturbance,AKI and PLT were the risk factors for the 1-year mortality in HBV-ACLF patients(all P<0.05).10.It was found that high WBC,neutrophil,ALT and MELD score were risk factors for 30-day mortality in AKI group,whereas HE,high MELD score and low PLT were risk factors for 90-day mortality in AKI group.11.Two criteria,KDIGO and AKIN criteria showed parallel in staging AKI in patients with HBV-related ACLF(Kappa=0.807,P<0.001).12.Among the four commonly used e GFR calculation formula,MDRD calculation formula owed the highest diagnostic efficiency.Conclusions1.Our findings show that HBV-ACLF has a high mortality rate and is often accompanied by serious complications.2.AKI is closely associated with increased short-term mortality in Chinese HBV-related ACLF patients,particularly those with infection and high MELD score.3.The major risk factors affecting the 1-year mortality in HBV-ACLF patients are age,WBC,MELD score,hepatic encephalopathy,electrolyte disturbance,AKI and PLT.4.Both KDIGO and AKIN criteria can be used for staging AKI in patients with HBV-related ACLF.