Clinical Study On Acute Kidney Injury In Patients With Hepatitis B-related Acute-on-chronic Liver Failure And Decompensated Cirrhosis

[Background and aims]Acute kidney injury(AKI)is a common and serious complication of hepatitis B virus(HBV)-related acute-on-chronic liver failure(HBV-ACLF)and decompensated cirrhosis(HBV-DC).Previous studies have been clearly established that the acute-on-chronic liver failure and decompensated liver cirrhosis are two different diseases.However,the differences in acute kidney injury among patients with these two diseases are rarely studied.Recently,studies had found that some novel renal tubular biomarkers in urine are usefulness in distinguishing the cause of renal injury.In current study,we detected the levels of five extensively studied renal tubular injury biomarker((neutrophil gelatinase-associated lipocalin(NGAL),interleukin-18(IL-18),kidney injury molecule-1(KIM-1),liver-type fatty acid binding protein(L-FABP),and cystatin C(Cys C))in blood and urine to define the major causes of AKI in HBV-ACLF and HBV-DC patients,and compared the incidence and natural course of AKI,patient’s response to terlipressin as well as patient’s outcomes among patients with these diseases,aimed at evaluating the differences in AKI between these two diseases.[Methods]All patients with HBV-ACLF or HBV-DC consecutively addmitted to the department of infectious disease of Tongji Hospital between December 1,2015 and July 31,2017 were included in a prospective study.Ten milliliter blood and/or urine specimens were collected at admission or during hospital within two days after AKI diagnosed.Blood and urine specimens of 24 chronic hepatitis B patients(CHB)and 20 healthy individuals(HC)were also collected as control groups at the same time.All renal tubular biomarkers in blood and urine were measured using ELISA method.The AKI incidence,natural history,response to terlipressin treatment in different groups were also recorded,and all patients were followed up for 3 months or until death.[Results]A total of 280 patients with HBV-ACLF and 132 with HBV-DC were enrolled in this study,AKI were occurred in 71 and 28 patients with HBV-ACLF and HBV-DC,respectively(25.4% vs.21.2%,p=0.358).Four of the five biomarker levels(NGAL,Cys C,L-FABP,IL-18)in urine were markedly elevated in patients with HBV-ACLF and AKI(ACLF-AKI)but not in patients with HBV-DC and AKI(DC-AKI).Forty-three ACLF-AKI patients and nineteen DC-AKI patients who were volume non-responsive had received terlipressin treatment,the response rate was significantly lower in ACLF-AKI patients than in DC-AKI patients [14/43(32.6%)vs 11/19(57.9%),p=0.018].There also a higher proportion of patients with AKI progression in ACLF-AKI group than in DC-AKI group(54.9% vs 17.9%,p=0.002).The 28-day and 90-day survival rates of patients with AKI were significantly lower than those without AKI,and patients with ACLF-AKI had the lowest survival rate among all patients(p<0.001).[Conclusions]AKI in patients with HBV-ACLF is distinctly different from in HBV-DC patients.In HBV-ACLF patients,AKI is more likely to be caused by structural damages and tends to be more progressive,with a poorer response to terlipressin and a worse prognosis than in HBV-DC patients.[Background and aims]Previous studies have found that some biomarkers of renal tubular injury in urine can be used not only for the early diagnosis of acute kidney injury(AKI),but also as a predictor of AKI progression and death in several clinical settings.However,their prognostic utility in patients with AKI in end-stage liver disease has not been well studied.This study was aimed to evaluating the prediction performance of five widely studied urinary tubular injury biomarkers[neutrophil gelatinase-associated protein(NGAL),interleukin 18(IL-18),cysteine Caspase inhibitor C(Cys C),liver-type fatty acid-binding protein(L-FABP),and renal injury molecule 1(KIM-1)] in patients with AKI with end-stage liver disease.[Methods]This study prospectively enrollment all the patients with end-stage liver disease(including 280 with HBV-related acute liver failure and 132 with HBV-related decompensated cirrhosis)who were consecutively admitted to the Department of Infectious Diseases of Tongji Hospital Affiliated to Huazhong University of Science and Technology between December 1,2015 and July 31,2017.Patients with stage1 or 2 AKI at the time of AKI diagnosed at admission or during hospitalization were selected for this part research.Urine specimens were collected from these patients at the time of acute kidney injury diagnosed,and levels of these renal tubular injury biomarker were detected by ELISA.The area under the receiver operating characteristic curves(AUC-ROC)was used to evaluate the prognostic ability of each renal tubular injury biomarker.In addition,In addition,calculate the category-free net reclassification improvement(cf NRI)and the integrated discrimination improvement(IDI)after these kidney injury markers are respectively combined with the clinical model to quantify the role of each marker in improving the predictive power of the clinical model.The primary outcome of this study were patients with AKI progression(progression from grade 1 to grade 2 or 3 and progression from grade2 to grade 3)or death within 30 days.[Results]A total of 85 patients had a stage 1 or 2 AKI at the time of AKI diagnosed were eligible for this section study.of which patients,56 had experienced the primary outcome((9 patients with AKI progression,26 with AKI progression and died within30 days,and 21 patients died prior to AKI progression).All biomarkers levels except KIM-1were significantly higher in patients who experienced the primary outcome than those who did not.Multivariate analysis showed that only the MELD score was an independent risk factor for poor outcomes among the clinical datas.The category-free net reclassification inprovement(cf NRI)and integrated discrimination index(IDI)analysis futher demonstrated that these biomarkers markedly improved the prognositic prediction ability of the clinical model(all p <0.05).There was a significant correlation between these biomarkers in correlation analysis,and multivariate logistics regression analysis showed that only L-FABP could predict the prognosis independent from other biomarkers,and the AUC-ROC of clinical model could be increased from 0.76 to 0.82.[Conclusions]Multiple urinary renal tubular injury biomarkers(NGAL,Cys C,L-FABP and IL-18)can be used as early markers of poor prognosis in patients with end-stage liver disease and AKI.A combination of these biomarkers does not improve the predictive ability.More researches are needed to confirm these findings.