Introduction

Aims & Methods

Results

Conclusion

References

Introduction

Prediction of early mortality is crucial in patients with Acute on Chronic Liver Failure (ACLF), a highly fatal syndrome characterized by intense systemic inflammation and organ failure. Performance of the Model of End-stage Liver Disease (MELD) appears to be suboptimal in ACLF, although the prognostic potential of combining MELD with inflammatory indexes remains uncertain.

Aims & Methods

The aim of the study was to evaluate a combination of MELD with neutrophil-to-lymphocyte ratio (NLR) for in-hospital mortality prediction in patients with ACLF.
A retrospective cohort study was conducted evaluating consecutive ACLF patients followed till hospital discharge. The predictive ability and optimal cut-points of MELD and NLR calculated on admission were determined by ROC analyses. Four prognostic groups, determined by score combinations below or above the optimal cut-points, were analyzed with respect to in-hospital mortality.

Results

A total of 122 patients (50.8% males, mean age 61.8±12.1) were hospitalized with ACLF between April 2021 and February 2023. The etiology of pre-existing liver disease was alcoholic in 44.3% and in-hospital mortality was 31.1%. The areas under ROC were 0.79 for MELD and 0.68 for NLR, with optimal cut-off points 20 (sensitivity/specificity: 0.89/0.57) and 5.1 (sensitivity/specificity: 0.84/0.60), respectively. Compared to patients with low MELD and NLR scores, patients with high scores displayed significantly higher in-hospital mortality (73.7% vs 6.7%; adjusted OR=13.96, p=0.007), whereas those with a single elevated score did not (high-MELD/low-NLR: 15.4%; adjusted OR=1.98, p=0.49; low-MELD/high NLR: 14.2%; adjusted OR=1.30, p=0.79).

Conclusion

In patients hospitalized with ACLF, a combination of high baseline MELD and NLR appears to delineate poor prognosis, correlating with a high risk of in-hospital death.

Introduction

Acute-on-chronic liver failure ( ACLF) is a severe form of acute decompensation of chronic liver disease with a high short-term mortality rate. It is characterized by excessive systemic inflammatory response and extrahepatic multiorgan failures (1). Previously published data have shown that therapeutic plasma exchange (TPE) decreases mortality rate in patients with ACLF reducing cytokine levels, serum bilirubin, and coagulopathy (2,3).

Aims & Methods

This retrospective study was conducted at the University Clinical Center of Serbia. All patients diagnosed with ACLF according to the EASL criteria and treated with TPE from January 2021 to January 2024 were included. (1) The main indication for providing TPE was serum bilirubin level >12 mg/dl with no improvement to standard medical treatment (SMT). The following scores were calculated at the hospital admission: Model for end-stage liver disease (MELD), Model for end-stage liver disease-Sodium (MELD-Na), Chronic Liver Failure Consortium- acute-on-chronic liver failure (CLIF-C ACLF). All patients were followed for 90 days. MELD and MELD-Na scores were calculated as well on the day 28.
The aims of this study were: assessment of 28-day and 90-day survival in patients with ACLF, the impact of TPE on MELD, and MELD-Na score.

Results

The study included 40 patients in whom SMT did not lead to improvement, of which 32 (80%) were male and 8 (20%) were female with a median age of 45.5 ( 39.75-58.5) years. The most frequent cause of liver cirrhosis was alcohol ( n=28; 70%), followed by Wilson disease (n=4; 10%), metabolic dysfunction-associated fatty liver disease ( MAFLD) (n=3; 7,5%), autoimmune hepatitis ( n=2; 5%), primary biliary cholangitis ( n=2; %%), AIH/ PSC syndrome overlap (n=1; 2.5%). Eighteen patients (45%) were previously diagnosed with acute decompensation ( Table 1). The average number of performed TPEs was 6±12.73. In alcohol-related liver disease (ALD) cirrhosis, alcoholic hepatitis was the main cause of ACLF in 22 (78.5%) patients. Twenty-two patients (55%) were diagnosed with Community-acquired infections. At admission, the average MELD and MELD-Na scores were 28.5±6.43 and 31±6.21. The mean MELD and MELD-Na scores in surviving patients after 28 days were 24.3 ±7.78 and 25.52±7.58, respectively. The average CLIF C-ACLF score at admission was 47±8.07. ACLF grade 1 was observed in 20 patients (50%), ACLF grade 2 in 18, (45%), and ACLF grade 3 in 2 (5%). The 28-day mortality in this study group was 37.5% (n=15), with 25% (n=5) in ACLF grade 1, 44.4%(n=8) in ACLF grade 2, and 100% (n=2) in ACLF grade 3. Ninety-day mortality was 62.5% (n=25). Regarding the ACLF grade, the following 90-day mortality was observed: grade 1-45%( n=9), grade 2-77.8%( n=14), and grade 3-100 (n=2). With the use of TPE in addition to SMT, a statistically significant decrease in MELD and MELD-Na as well was observed after 28 days (p <0.01).

Conclusion

TPE may be a beneficial treatment option for patients who do not respond to SMT, but in our study, short-term mortality is still high. New prospective randomized studies with a larger number of subjects are needed to examine this therapeutic modality accurately.

References

1. European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on acute-on-chronic liver failure. Journal of Hepatology, 79(2), 461–491.
2. Mao WL, Chen Y, Chen YM, Li LJ. Changes of serum cytokine levels in patients with acute on chronic liver failure treated by plasma exchange. J Clin Gastroenterol. 2011;45:551–555.
3. Chris-Olaiya A, Kapoor A, Ricci KS, Lindenmeyer CC. Therapeutic plasma exchange in liver failure. World J Hepatol. 2021;13(8):904-915.

Disclosure

There is no conflict of interest.

Introduction

Patients with acute-on-chronic liver failure (ACLF) have traditionally been considered with a tendecy for bleeding however, they frequently display a paradoxical prothrombotic state. ACLF is characterized systemic inflammation and an increased risk of both bleeding and thrombosis. Bleeding arises from decreased pro-coagulation factors and platelet sequestration due to portal hypertension, while thrombosis is exacerbated by endothelial dysfunction and elevated heparinoids, thrombomodulin, or von Willebrand factor.

Aims & Methods

The aim of this study was to evaluate platelet aggregation pattern in patients with ACLF compared to acute decompensated (AD) liver cirrhosis.
The study took place in between the 1^st of July 2024- 31^st of January 2025 and we prospectively included cirrhotic patients, divided in two groups: ACLF group and AD group. The exclusion criteria were people with compensated liver cirrhosis, antiaggregant or anticoagulant treatment and patients with hepatocellular carcinoma or other malignancies. We investigated platelet aggregability in whole blood, by using multiplate aggregometry. For analysis, platelet aggregometry was performed induced by: adenosine diphosphate (ADP), arachidonic acid (ASPI), prostaglandin E2 (PGE2) and thrombin receptor-activated peptide (TRAP-6) as agonist were determined. TRAP‑6 is a peptide that stimulates protease-activated receptor 1 (PAR1) on platelet membrane.

Results

In this study we included 52 patients – 25 patients with ACLF and 27 patients with AD. There were no differences regarding demographic parameters and liver disease etiology between the two study groups. Compared to AD group, patients with ACLF showed an enhanced maximal platelet aggregation with TRAP-6 (AUC 85±12 U vs 45±10 U, p<0.0001). In contrast, we did not detect any differences in platelet aggregation between the two groups after ADP, ASPI or PGE2 activations. We observe that PAR-1 stimulation induces the highest aggregation curve and area under the curve in patients with ACLF and AD, but ACLF patients show the strongest response, highlighting that the degree of liver decompensation influences aggregation results. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

Conclusion

Our results indirectly indicate that platelet reactivity is higher in patients with ACLF likely due to enhanced PAR-1 receptor activity. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

References

1. EASL Clinical Practice Guidelines on acute on liver failure; J. Hepatol. 2023
2. Napolitano et al. European Journal of Internal Medicine 2017
3. Tripodi et al. Hepatology 2006
4. Lisman et al. Hepatology 2006
5. Nassar et al. BIOMEDICINES 2023
6. Rogalski et al. Scandinavian Journal of Gastroenterology 2019
7. Zanetto et al. Liver International 2022
8. Vecerzan et al. Cureus 2024
​