A novel predictive score for citrate accumulation among patients receiving artificial liver support system therapy with regional citrate anticoagulation

Abstract

Patients with liver failure may suffer citrate accumulation when using regional citrate anticoagulation for artificial liver support system therapy (RCA-ALSS therapy). This study aimed to develop a predictive scoring system to stratify the risk of citrate accumulation. A total of 338 patients treated with RCA-ALSS therapy were retrospectively enrolled and randomly divided into derivation and validation cohorts. Longer duration of citrate accumulation (LDCA) was defined as the presence of citrate accumulation 2 h after RCA-ALSS therapy. Four baseline variables were found to be independently associated with LDCA: gender, international normalized ratio of prothrombin time, serum creatinine, and serum chloride. A predictive R-CA model and its simplified R-CA score were developed. The R-CA model (AUROC = 0.848) was found to be superior to the MELD score (AUROC = 0.725; p = 0.022) and other univariate predictors (AUROCs < 0.700; all p ≤ 0.001) in predicting LDCA. The R-CA score (AUROC = 0.803) was as capable as the R-CA model (p = 0.369) and the MELD score (p = 0.174), and was superior to other univariate predictors (all p < 0.05) in predicting LDCA. An R-CA score of 0-2 had a negative predictive value of 90.2% for LDCA. Our R-CA score reliably predicts LDCA in patients with RCA-ALSS therapy, and it is easy to use. Patients with R-CA score of 0-2 can safely receive RCA-ALSS therapy, while others should be carefully evaluated before treatment. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000029179. Registered 17 January 2020, https ://www.chict r.org.cn/showp roj.aspx?proj=48084. Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical deterioration and high mortality. Artificial liver support system (ALSS) therapy is an available treatment for patients with ACLF and is a bridge to liver transplantation 1. However, the optimal extracorporeal anticoagulation regimen for ALSS therapy remains uncertain. Regional citrate anticoagulation (RCA) is now the preferred anticoagulation method for patients underwent continuous renal replacement therapy (CRRT) 2,3. RCA seems also safe and feasible for patients with liver failure, and citrate accumulation is well tolerated by them 4-14. The blood purification techniques used in these patients include a dialysis technique that can remove citrate directly. Our previous study suggests that RCA is relatively safe and effective in patients with ACLF receiving double plasma molecular adsorption system plus plasma exchange (DPMAS plus PE) therapy that does not include dialysis and filtration techniques 15. However, transient citrate accumulation was found in all patients due to PE therapy in both groups and RCA in RCA group, and it remained much higher in RCA group than that in heparin anticoagulation group 2 h after the conclusion of the ALSS therapy (34.0% vs. 7.4%, p = 0.000) 15. Citrate accumulation is a feared and potentially lethal complication of RCA manifesting as an increased ratio of total calcium (Ca tot) to ionized calcium (Ca ...

Development of a Multivariable Prediction Model for Citrate Accumulation in Liver Transplant Patients Undergoing Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

“…Boer et al [15] performed a multivariate analysis using mixed-effects models for elevation of total/ionized calcium in patients with nonhepatic dysfunction who underwent CRRT. Another recent study about the risk assessment of CA in patients receiving artificial liver support system therapy also developed a multivariable prediction model [16]. We referenced the methodologies of these articles and used generalized linear mixed-effect models to analyze our data to develop a predictive model for the risk of CA in liver transplant patients undergoing CRRT with RCA.…”

“…Other studies [8, 14] also confirmed that lactate was critical for the prediction of CA. Many studies have evaluated a single predictor for CA; however, studies of multivariate analyses for CA have been published recently [15, 16]. We believe that CA is multifactorial, and before administering RCA to liver transplant patients with liver dysfunction, a clinician should consider the risk of CA to make appropriate anticoagulation decisions.…”

Association between longer duration of citrate accumulation and 90-day mortality of acute-on-chronic liver failure

“…Regional citrate anticoagulation (RCA) is an optional anticoagulant for plasma adsorption (PA) plus plasma exchange (PE) therapy in patients with acute-on-chronic liver failure (ACLF), but with risk of transient citrate accumulation due to plasma and citrate [ 1 ]. Regardless of the anticoagulants: heparin or citrate, some patients would suffer from longer duration of citrate accumulation (LDCA), defined as the presence of citrate accumulation 2 h after PA plus PE therapy with RCA [ 1 , 2 ]. However, whether citrate accumulation itself would lead to poor prognosis remains uncertain.…”

“…We conducted a retrospective study based on medical records to assess the association between LDCA and prognosis of hepatitis B virus (HBV)-related ACLF. Methods and some data from this cohort have been published already [ 2 ]. We kept to follow-up these patients for another 90 days after acquiring further ethical approval and registered this study with ChiCTR-OON-17013631.…”

“…HBV-ACLF was diagnosed according to COSSH ACLF criteria [ 3 ]. Citrate accumulation was defined as the ratio of total calcium (Ca tot ) to ionized calcium (Ca ion ), (Ca tot /Ca ion ), over or equal to 2.5 (Ca tot /Ca ion ≥ 2.5) [ 1 , 2 ]. Cox proportional hazards models were applied to evaluate the association of LDCA with outcome.…”