Introduction

Bacterial infections are common and difficult to diagnose in decompensated chronic liver disease (DCLD) patients (1). Early diagnosis and treatment of infection in DCLD can improve the outcome. Studies show that neutrophilic cluster of differentiation 64 (nCD64) is more accurate than procalcitonin (PCT) and C-reactive protein for identifying bacterial infections (2,3). nCD64 is rapidly upregulated to >10-fold higher in an immune response to infection. Pediatric studies on the role of nCD64 in liver disease are lacking.

Aims & Methods

We prospectively studied the role of nCD64 as a biomarker of bacterial infection in children with DCLD. We also compared the accuracy of nCD64 with PCT and total leucocyte count (TLC) for diagnosis, severity, and post-treatment persistence or resolution of infection.
Consecutive children admitted with DCLD were enrolled. Neutrophils were gated according to CD64 activity by flow-cytometry and expressed as percentage of neutrophil expressing CD64 positivity. nCD64, PCT and hemogram were measured at admission and 7-14 days after treatment in those with infection. Appropriate tests like urine microscopy, ascitic fluid analysis, chest x-ray and cultures (blood, urine, ascitic fluid) were done. Presence of infection, site and severity were classified as per standard guidelines (4,5).

Results

107 children [64 boys, median age 97 (18-168) months] were studied. Autoimmune hepatitis was the commonest etiology.72.9% (78/107) cases had infection, 24.2% had severe sepsis and 56% had SIRS at admission. Ascitic fluid (n-37) was the commonest site of infection, followed by pneumonia (n-24), urinary tract (n-15), bacteremia (n-10), cholangitis (n-8) and cellulitis (n-3). For nCD64 we derived a cut-off of 51% to diagnose infection and for PCT the best cut-off was > 0.58 ng/mL. Table 1 shows the sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic accuracy of the biomarkers. nCD64 performed better than PCT alone. Elevated nCD64, PCT and TLC had a specificity of 100%, suggesting that infection is always present if all tests are elevated.
nCD64 and PCT correlated well with infection severity. The levels of nCD64 and PCT were highest in severe sepsis [88 (70.73-96.5) % and 1.98 (0.83-10.36) ng/mL], than infection alone [71.8 (45.07-84.37) % and 1.09 (0.45-2.07) ng/mL], and no-infection [36 (20.2-47.7) % and 0.42 (0.19-1.08) ng/mL] respectively. There was no difference in PCT or nCD64 with regards to site of infection, both were elevated almost equally in systemic infections except cellulitis (local infection). Subjects with resolved infection (n-64), showed a significant decline in proportion of cases with elevated nCD64 and PCT in follow-up. However, the biomarkers continued to be positive in those with persistent infection (n-14). Only, 10% of children with clinically resolved infection had elevated nCD64, as compared to 43% with elevated PCT, suggesting that nCD64 shows a faster decline with resolving infection than PCT.

Table 1: Comparison of biomarkers of infection in children with chronic liver disease

Conclusion

nCD64 can identify infection better than PCT and correlates well with infection severity in children with DCLD. Combination of nCD64, PCT and TLC can identify infection with 100% specificity.

References

1. Bolia R, Srivastava A, Marak R, Yachha SK, Poddar U. Prevalence and Impact of Bacterial Infections in Children With Liver Disease—A Prospective Study. J Clin Exp Hepatol. 2018;8:35–41.
2. Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar AN, Gmeiner-Stopar T, Derganc M. Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med. 2009;35:1950–8.
3. García-Salido A, de Azagra-Garde AM, García-Teresa MA et al. Accuracy of CD64 expression on neutrophils and monocytes in bacterial infection diagnosis at pediatric intensive care admission. Eur J Clin Microbiol Infect Dis. 2019;38:1079–85.
4. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005;6:2-8.
5. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections, 1988. Am J Infect Control. 1988;16:128–40.

Introduction

Ammonia is a known biomarker for hepatic encephalopathy and has also been suggested as a prognostic marker in compensated advanced chronic liver disease (ACLD), showing an association with increased risk of hospitalization and 1-year mortality, with superior performance compared to the Child-Pugh (CP) and MELDNa+ scores. However, its prognostic role in decompensated ACLD (D-ACLD) remains debated.

Aims & Methods

This study aimed to assess the prognostic performance of ammonia in D-ACLD.
​A prospective, single-center cohort study including patients hospitalized for D-ACLD from 12/01/2022 to 12/01/2023, with a 1-year follow-up post-discharge. Daily clinical, laboratory, and imaging assessments were conducted during hospitalization, with ammonia levels measured at admission (D0) and on day 3 (D3). D-ACLD characterization included infection, hepatocellular carcinoma, portal vein thrombosis, rehospitalization, and mortality (in-hospital, 6-month, and 12-month).

Results

A total of 82 patients were included (mean age: 61.5 years), mostly with alcohol-related ACLD (53.7%). On average, each patient presented with 1.8 decompensations at D0, primarily hepatic encephalopathy (53.7%; n=44) and ascites (45.1%; n=37). Mean ammonia levels were 85.1 µmol/L (±67.0) at D0 and 64.8 µmol/L (±35.6) at D3. The in-hospital mortality rate was 19.5% (n=16). In univariate and multivariate analysis, ammonia-D0 correlated with MELDNa+-D0 and in-hospital infection (p<0.05). Ammonia-D3 correlated with infection and in-hospital mortality (p<0.05). ROC curve analysis for in-hospital infection prediction at D0 showed an AUC of 0.649 for ammonia, 0.648 for CP, and 0.59 for MELDNa+. ROC analysis for 6-month mortality prediction at D3 showed an AUC of 0.622 for ammonia, 0.468 for CP, and 0.351 for MELDNa+.

Conclusion

Ammonia has prognostic significance in D-ACLD, particularly in predicting in-hospital infection and 6-month mortality. However, its performance remains inferior to classical prognostic scores (CP, MELDNa+) for predicting other outcomes.

References

Shalimar, M. F. Sheikh, R. P. Mookerjee, B. Agarwal, S. K. Acharya, and R. Jalan, “Prognostic Role of Ammonia in Patients With Cirrhosis,” Hepatology, vol. 70, no. 3, pp. 982–994, Sep. 2019, doi: 10.1002/hep.30534.
M. Faisal Sheikh, R. P. Mookerjee, B. Agarwal, S. Kumar Acharya, and R. Jalan, “Prognostic Role of Ammonia in Patients With Cirrhosis,” Hepatology, vol. 70, no. 3, 2019, doi: 10.1002/hep.30534/suppinfo
T. H. Tranah et al., “Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis,” J Hepatol, vol. 77, no. 6, pp. 1554–1563, Dec. 2022, doi: 10.1016/j.jhep.2022.07.014

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been associated with a variety of complications, including liver damage. However, its impact on chronic liver disease (CLD) and its association with cholestasis remains unclear. This retrospective cohort study aimed to investigate the incidence of cholestasis and its impact in patients with CLD after SARS-CoV-2 infection.

Aims & Methods

We retrospectively analyzed medical records of 428 patients followed in a tertiary center Liver Unit who were diagnosed with SARS-CoV-2 infection between March 2020 and September 2022. Patients were stratified as having no CLD, non-advanced CLD (NACLD) or advanced CLD (ACLD). Liver chemistries before and several times after SARS-CoV-2 infection were registered. The incidence of cholestasis and its associated risk factors were analyzed using multivariate logistic regression.

Results

A total of 428 patients were included, 357 (66.1% males) with CLD (NACLD in 198 and ACLD in 159 patients). Alcohol-associated liver disease (ALD) was the main etiology (30.8%), closely followed by metabolic-associated fatty liver disease (MAFLD) (24.6%). SARS-CoV-2 infection-related cholestasis was higher in patients with ACLD than in patients with NACLD (39.6% vs. 5.6%, p<0.001). No patient without CLD developed cholestasis. The incidence of decompensation episodes, such as ascites, hepatic encephalopathy and variceal bleeding was significantly higher in patients with cholestasis (32.4%, 32.4% and 17.6% vs. 0.3%, 0.3% and 0%, respectively; p<0.001). Additionally, patients with cholestasis had a longer hospital stay (median/IQR 17/12 vs. 10.5/9 days, p=0.483) and a significantly higher mortality rate (23.0% vs. 0.6%, p<0.001) than those without cholestasis. Patients with ACLD (vs. NACLD) presented higher global mortality (10.7% vs. 0%, p<0.001) and liver-related mortality (10.1% vs. 0%, p<0.001). Multivariate logistic regression analysis showed that ACLD and decompensated disease were independent risk factors for cholestasis in patients with SARS-CoV-2 infection (p=0.031 and p<0.001, respectively).

Conclusion

Our study suggests that SARS-CoV-2 infection is a risk factor for cholestasis in patients with CLD, especially in those with ACLD or decompensated disease. Clinicians should be aware of the potential for cholestasis in these patients with underlying liver disease and closely monitor liver function tests. Further studies are needed to investigate the underlying mechanisms of SARS-CoV-2-induced cholestasis and develop appropriate management strategies for these patients.