Dataset Information

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

ABSTRACT:

Background and aims

Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America.

Methods

The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively from 32 North American academic centres. The primary outcome was a composite of 21-day all-cause mortality or requirement for liver transplantation (death/LT).

Results

Patients with hypochloremia (<98 mEq/L) had a significantly higher 21-day mortality rate (42.1%) compared with those with normal (27.5%) or high (>107 mEq/L) chloride (28.0%) (p < .001). There was lower transplant-free cumulative survival in the hypochloremic group than in the normo- or hyper-chloremic groups (log-rank, χ² 24.2, p < .001). Serum chloride was inversely associated with the hazard of 21-day death/LT with multivariable adjustment for known prognostic factors (adjusted hazard ratio [aHR]: 0.977; 95% CI: 0.969-0.985; p < .001). Adding chloride to the ALFSG Prognostic Index more accurately predicted risk of death/LT in 19% of patients (net reclassification improvement [NRI] = 0.19, 95% CI: 0.13-0.25) but underestimated the probability of transplant-free survival in 34% of patients (NRI = -0.34, 95% CI: -0.39 to -0.28).

Conclusions

Hypochloremia is a novel independent adverse prognostic factor in ALF. A new ALFSG-Cl Prognostic Index may improve the sensitivity to identify patients at risk for death without LT.

SUBMITTER: Wang J

PROVIDER: S-EPMC10668517 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

Wang Jiexin J Liu Po-Hong PH Xu Pin P Sumarsono Andrew A Rule Jody A JA Hedayati S Susan SS Lee William M WM

Liver international : official journal of the International Association for the Study of the Liver 20221017 12

<h4>Background and aims</h4>Emerging evidence has identified hypochloremia as an independent predictor for mortality in multiple conditions including cirrhosis. Acute liver failure (ALF) is frequently complicated by electrolyte abnormalities. We investigated the prognostic value of hypochloremia in a large cohort of ALF patients from North America.<h4>Methods</h4>The Acute Liver Failure Study Group (ALFSG) registry is a longitudinal cohort study involving 2588 ALF patients enrolled prospectively ...[more]

PMID: 36203349

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Project description:BackgroundIn patients with heart failure (HF), multiple electrolyte disorders are common, and recent studies have shown that chloride disorders play a significant role in the prognosis of HF. Data about the prevalence and prognostic role of hypochloremia in patients with acute HF (AHF) are scarce in African nations, including Ethiopia. Hence, this study aimed to assess the prevalence, associated factors, and prognostic role of hypochloremia in patients with AHF in Ethiopia.MethodsThis was a single-center retrospective analysis of AHF patients, aged ≥15 years, with chloride determination upon admission to the medical wards and medical ICU of Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia, from July 1, 2022, to July 1, 2023. Statistical Package for Social Sciences, version 26, was used to enter and analyze the data. Descriptive analysis was used to summarize clinical profiles, laboratory data, and outcomes of AHF patients stratified by the presence and absence of hypochloremia. Logistic regression analysis was used to determine the factors associated with hypochloremia and to assess the association of hypochloremia and other factors with in-hospital mortality in patients with AHF. A two-tailed P value <0.05 was regarded as statistically significant.ResultsA total of 267 AHF patients who had chloride determination on admission were included in this study; the mean age was 56.7 years (standard deviation: 18.6), and the gender-based distribution of the patients was nearly equal. The prevalence of hypochloremia was 36.7%. Diastolic blood pressure <60 mm Hg [adjusted odds ratio (AOR) = 3.63, 95% confidence interval (CI), 1.04, 12.72] and hyponatremia (AOR = 29.20, 95% CI, 13.21, 64.56) were significantly associated with hypochloremia. The in-hospital mortality rate was higher in AHF patients with hypochloremia (16.3%) compared to those without hypochloremia (4.7%). The odds of in-hospital mortality among AHF patients with hypochloremia were 2.8 times higher compared to patients without hypochloremia (AOR = 2.82, 95% CI: 1.08, 7.04) after adjusting for ICU admission, systolic blood pressure < 120 mm Hg and diastolic blood pressure < 60 mm Hg.ConclusionsThis study revealed a high prevalence of hypochloremia among patients with AHF. Low diastolic blood pressure and hyponatremia were significantly associated with the development of hypochloremia. Most importantly, AHF patients with hypochloremia had a higher in-hospital mortality rate compared to those without hypochloremia. Hence, hypochloremia on admission should be considered a potential prognostic factor in patients with AHF, and further research with a larger sample size is needed to support the findings of this study.

Project description:Background & aimsAcetaminophen (APAP)-induced acute liver failure (ALF) remains the most common cause of ALF in the Western world. Conventional prognostic models, utilising markers of liver injury and organ failure, lack sensitivity for mortality prediction. We previously identified a microRNA signature that is associated with successful regeneration post-auxiliary liver transplant and with recovery from APAP-ALF. Herein, we aimed to use this microRNA signature to develop outcome prediction models for APAP-ALF.MethodsWe undertook a nested, case-control study using serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. A microRNA qPCR panel of 22 microRNAs was utilised to assess microRNA expression at both time-points. Multiple logistic regression was used to develop models which were compared to conventional prognostic models using the DeLong method.ResultsIndividual microRNAs confer limited prognostic value when utilised in isolation. However, incorporating them within microRNA-based outcome prediction models increases their clinical utility. Our early time-point model (AUC = 0.78, 95% CI 0.71-0.84) contained a microRNA signature associated with liver regeneration and our late time-point model (AUC = 0.83, 95% CI 0.76-0.89) contained a microRNA signature associated with cell-death. Both models were enhanced when combined with model for end-stage liver disease (MELD) score and vasopressor use and both outperformed the King's College criteria. The early time-point model combined with clinical parameters outperformed the ALF Study Group prognostic index and the MELD score.ConclusionsOur findings demonstrate that a regeneration-linked microRNA signature combined with readily available clinical parameters can outperform existing prognostic models for ALF in identifying patients with poor prognosis who may benefit from transplantation.Lay summaryWhile acute liver failure can be reversible, some patients will die without a liver transplant. We show that blood test markers that measure the potential for liver recovery may help improve identification of patients unlikely to survive acute liver failure who may benefit from a liver transplant.

Project description:Purpose: Neutrophils and cytokines play a major role in the pathogenesis of acute-on-chronic liver failure (ACLF). We aimed to determine whether chemokine (CXC) ligand 1 (CXCL1), a key marker of neutrophil recruitment and activation, could predict the severity and prognosis of hepatitis B virus-related ACLF (HBV-ACLF). Methods: Hospitalized patients with HBV-ACLF were enrolled in a prospective study and stratified as survivors (alive at 28 days) and nonsurvivors (deceased at 28 days). Serum CXCL1 levels were measured in healthy controls, patients with chronic HBV, patients with HBV-related compensated cirrhosis, and patients with HBV-ACLF. Univariate and multivariable logistic analyses, Pearson correlation analysis, area under the receiver operating characteristic curve (AUROC), and Z tests were used to evaluate the performance of CXCL1 as a marker in HBV-ACLF. Results: Patients with HBV-ACLF had significantly higher serum levels of CXCL1 and neutrophil count than healthy controls and patients with chronic HBV or HBV-related compensated cirrhosis (P < 0.01, respectively). Among patients with HBV-ACLF, survivors had lower serum CXCL1 levels and neutrophil count than those of nonsurvivors (P < 0.001, P < 0.05, respectively). Serum CXCL1 level was positively correlated with neutrophil count (r = 0.256, P = 0.001), ACLF grade (r = 0.295, P < 0.001) and organ failure, including coagulation (r = 0.21, P = 0.005) and brain failure (r = 0.198, P = 0.008). Multivariable logistic analyses showed serum CXCL1 [OR (95% CI) = 1.017 (1.009-1.025), P < 0.001] was an independent risk factor for 28-day mortality in HBV-ACLF. Meanwhile, the AUROC analysis demonstrated that serum CXCL1 [0.741 (0.669-0.804)] might be a reliable prognostic biomarker for patients with HBV-ACLF. Conclusions: Overall, serum CXCL1 can serve as a biomarker indicating the severity of disease and prognosis for patients with HBV-ACLF. CXCL1 might also be a therapeutic target in this disease.

Project description:Recent epidemiological studies have implicated chloride, rather than sodium, as the driver of poor survival previously attributed to hyponatremia in heart failure. Accumulating basic science evidence has identified chloride as a critical factor in renal salt sensing. Our goal was to probe the physiology bridging this basic and epidemiological literature. Two heart failure cohorts were included: (1) observational: patients receiving loop diuretics at the Yale Transitional Care Center (N=162) and (2) interventional pilot: stable outpatients receiving ≥80 mg furosemide equivalents were studied before and after 3 days of 115 mmol/d supplemental lysine chloride (N=10). At the Yale Transitional Care Center, 31.5% of patients had hypochloremia (chloride ≤96 mmol/L). Plasma renin concentration correlated with serum chloride (r=-0.46; P<0.001) with no incremental contribution from serum sodium (P=0.49). Hypochloremic versus nonhypochloremic patients exhibited renal wasting of chloride (P=0.04) and of chloride relative to sodium (P=0.01), despite better renal free water excretion (urine osmolality 343±101 mOsm/kg versus 475±136; P<0.001). Hypochloremia was associated with poor diuretic response (odds ratio, 7.3; 95% confidence interval, 3.3-16.1; P<0.001). In the interventional pilot, lysine chloride supplementation was associated with an increase in serum chloride levels of 2.2±2.3 mmol/L, and the majority of participants experienced findings such as hemoconcentration, weight loss, reduction in amino terminal, pro B-type natriuretic peptide, increased plasma renin activity, and increased blood urea nitrogen to creatinine ratio. Hypochloremia is associated with neurohormonal activation and diuretic resistance with chloride depletion as a candidate mechanism. Sodium-free chloride supplementation was associated with increases in serum chloride and changes in several cardiorenal parameters. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02031354.

Dataset Information

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

Background and aims

Methods

Results

Conclusions

Publications

Hypochloremia as a novel adverse prognostic factor in acute liver failure.

Similar Datasets

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