Serum Interleukin-4 and Ascitic CD206 Predict Mortality in Acute Cirrhosis Decompensation and Acute-on-Chronic Liver Failure

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Lashen, Berihan Salem, Esraa Ibrahim, Dalia Abd Elmoaty, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7049789/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background & Aim : Acute-on-chronic liver failure (ACLF) is the most severe form of acute decompensation (AD) with intense systemic inflammation and immune dysfunction. IL-4 polarizes macrophages toward the M2 phenotype. CD206 can identify inflammatory peritoneal macrophages in cirrhotic patients and could be linked to prognosis in ACLF. We investigated the predictive value of serum IL-4 and ascitic sCD206 in patients with AD and ACLF and their relation to morbidity and early mortality. Patients and Methods : We included 60 patients with ACLF and AD as well as 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 3 months. Blood samples were analyzed at admission for liver and renal function tests as well as serum IL-4 and ascitic soluble CD206 levels. Correlation with liver function indicators and prognosis was assessed. Results : IL-4 and CD206 were significantly higher in AD and ACLF patients compared to control and were positively correlated with each other’s Child-Pugh score, MELD-Na, and ACLF severity scores. Multivariate regression showed that baseline Child-Pugh score, ascitic sCD206, and serum IL-4 level are the only independent predictors of one-month as well as 3-month mortality. Conclusions : Serum IL-4 and ascitic sCD206 (macrophage markers) could predict early mortality in AD and ACLF. Incorporation of these markers into the traditional liver disease scores can improve their prognostic/predictive performance. Liver cirrhosis CD206 Interleukin-4 Acute decompensation Acute on chronic liver failure (ACLF) Figures Figure 1 Figure 2 Introduction and aim During the course of liver cirrhosis (LC), acute decompensation (AD) represents the typical complication, with the acute-on-chronic liver failure (ACLF) represents the most severe phenotype. ACLF is marked by organ failures, significant systemic inflammation (SI), and increased 28-day mortality. (1, 2) Peritoneal macrophages (PM) make up most of the immune cells residing in the peritoneum. They produce and regulate hepatic and SI by identifying damage-associated and pathogen-associated molecular patterns. (3) Macrophages are typically categorized into M1 (pro-inflammatory) or M2 (anti-inflammatory) types as they adapt to the local environment during liver injury. (4) Recent evidence indicates a link between immune activation in the peritoneum, SI, complications, and outcomes in decompensated cirrhosis. (5) Interleukin-4 (IL-4) directs macrophages to adopt the M2 phenotype. Depending on the type of cell, IL-4 may trigger regulatory, suppressive, or pro-inflammatory reactions. (6) CD206, previously utilized for identifying activated (M2) macrophages, is a membrane-bound C-type lectin that acts as a pattern recognition scavenger receptor. (7) CD206 facilitates endocytosis, enhances antigen presentation, and activates T-cells. Soluble variants of CD206 are released peripherally following proteolytic cleavage from the surface of macrophages and can modify both adaptive and innate immune responses. (8) Markers of macrophages have been used as surrogate parameters to predict disease severity and outcomes in a wide range of disorders. (9) In this context, the present study aimed to evaluate serum levels of IL-4 and ascitic levels of soluble CD206 (sCD206) in cirrhotic patients with AD and ACLF and their relation to the severity of liver disease and patient survival. Materials and Methods In a prospective case-control design, we included LC patients who presented to our hospital with AD or ACLF, whose symptoms started within 2 weeks before admission. The sample size was calculated assuming a power of 95%, an α-error of 0.05, a between-groups variance of 0.2 and a prevalence of 30% for ACLF in Egyptian tertiary hospitals. (10) Among 130 patients who were screened, 70 patients were excluded due to non-eligibility [patients with hepatocellular carcinoma or other malignancies, chronic heart failure, chronic pulmonary, renal, or rheumatological diseases, severe alcoholic hepatitis, and patients with incomplete records]. Finally, 60 participants were included. We also included 30 patients as a control group. Cohort definition : The total 90 patients were assigned into three groups as following ( Supplementary Fig. 1 ): Group -A (AD patients): patients with liver cirrhosis who are presenting with AD, defined as jaundice, coagulopathy [international normalized ratio (INR) ≥ 1.5], and presence of large ascites (grade 2 or 3) within < 2 weeks of presentation, those with acute hepatic encephalopathy (HE), and with gastrointestinal bleeding; Group -B (ACLF patients): patients with acute hepatic insult plus organ failure: liver failure as defined by a serum bilirubin level > 5 mg/dl, renal failure as defined by a serum creatinine ≥ 2 mg/dl, cerebral failure as defined by HE grade III or IV, coagulation failure (INR ≥ 2.5 and/or platelet count of less than 20 x10 9 /L), circulatory failure as defined by the use of vasopressors, and respiratory failure as defined by a peripheral capillary oxygen saturation (SpO2) to FiO2 ratio of ≤ 200, within the last 4 weeks (11) ; Group - C (control group): patients with cirrhotic ascites who don't fulfill the criteria of patients in Group A or Group B. All patients were followed for a minimum of 90 days through outpatient systems and by telephone to assess survival. The endpoint of the study was the occurrence of death or end of follow up, whichever comes first. All patients received a clinical evaluation. Blood samples were collected at the time of admission for complete blood cell count, and blood chemistry including liver profile, renal function tests, and electrolytes. Serum IL-4 levels were measured using a commercially available ELISA kit (Finetest, Wuhan, China; cat.# EH0199). Ascitic fluid analysis was done with ascitic sCD206 quantification using a commercially available ELISA kit (Finetest, Wuhan, China; cat.# EH1802). The severity of liver disease was graded according to Child-Turcotte-Pugh (CTP), and the Model for End-Stage Liver Disease (MELD-Na) scores. CLIF-C AD score was used for AD patients while ACLF was assessed by the CLIF-SOFA score. (12) Severity was stratified by considering the number of organs failed (OF): grade 1 (1 OF), grade 2 (2 OFs), and grade 3 (3 to 6 OFs). Survival rates were assessed for 1, and 3 months. Ethics The study was approved by the institutional ethical committee board (IRB number 0107126), and conducted following the provisions of the Declaration of Helsinki of 1975, as revised in 2008. Informed consent was obtained from all subjects (or their legal guardians when applicable) included in the study. We have no financial support. Statistical analysis The IBM SPSS software package version 26.0 (Armonk, NY; IBM Corp) was used for statistical analysis. The sample size was calculated using STATA 15.1 package (StataCorp, USA). Data were presented as (minimum-maximum), median, Mean ± SD, or number (per cent). Categorical variables were compared using the Chi-square test or Fisher's exact test. Means were compared by Kruskal Wallis or Mann–Whitney U tests. ROC analysis was done on MELD-NA, serum IL-4, and ascitic sCD206. Kaplan-Meier analysis for 1-, and 3-month mortality as well as Cox regression analysis were used to evaluate the effect of baseline parameters on mortality risk. Results Demographic data : The baseline data of the study groups are shown in Table 1 . Precipitating factors for acute presentation included acute HCV infection, variceal bleeding, and recent infections other than viral hepatitis [pneumonia (38%), soft tissue infections (21%), and urinary tract (17%)]. SBP was met in 7 (22.6%) patients (2 patients in the AD group and 5 patients in the ACLF group). Table 1 Baseline demographic data of study population at admission: Acute decompensation ( n = 30) Acute-on-chronic liver failure ( n = 30) Cirrhotic control ( n = 30) P b Age 56.62 ± 16.45 59.41 ± 14.90 56.10 ± 8.78 0.60 Gender (male, n, %) 13 (43.30) 15 (50.00) 17 (56.70) 0.58 f Etiology of chronic liver disease : Viral hepatitis: (n, %) 21 (70) 21 (70) 14 (46.66) 0.08 − Post DAAs for HCV 12 (40.00) 8 (26.66) 7 (23.33) 0.22 e − Active chronic HCV 4 (13.33) 8 (26.66) 4 (13.33) − HCV/HBV co-infection 2 (6.66) 1 (3.33) 0 (0.00) − Chronic hepatitis B 3 (10) 4 (13.3) 3 (10.00) Alcoholic liver disease 2(6.66) 2 (6.66) 3 (10.00) 0.94 e MASLD 4 (13.33) 5 (16.66) 3 (10.00) 0.91 e Autoimmune hepatitis 1 (3.33) 2 (6.66) 2 (6.66) 0.99 e Budd-Chiari syndrome 1 (3.33) 0 (0.00) 1 (3.33) 0.99 e Unknown 1 (13.33) 0 (0.00) 7 (23.3) 0.34 e Precipitating factors of acute presentation − Acute HCV infection 0 (0.00) 2 (6.66) 0 (0.00) - − Recent infection Σ 12 (40.00) 17 (56.66) 2 (6.66) < 0.001 f − Variceal bleeding 18 (60.00) 16 (53.33) 0 (0.00) 0.001 Clinical examination MBP (mmHg) 83.84 ± 12.21 82.12 ± 12.73 80.54 ± 8.52 0.53 Hepatic encephalopathy : − Absent 11(36.67) 7 (23.33) 30 (100) < 0.001 e − Grade 1 6 (20.00) 00 (0) 0 (0) − Grade 2 11 (36.67) 00 (0) 0 (0) − Grade 3 2 (6.66) 6 (20.0) 0 (0) − Grade 4 0 (0.00) 17 (56.70) 0 (0) Ascites grades : − Mild 1 (3.33) 5 (16.67) 4 (13.33) 0.03 e − Moderate 13 (43.33) 17 (56.66) 8 (26.67) − Marked/tense 16 (53.34) 8 (26.67) 18 (60.00) Baseline Laboratory parameters : Hemoglobin (g/dl) 9.01 ± 2.23 cd 10.23 ± 2.30 d 10.30 ± 1.78 0.033 Platelets (x 10 3 ) c/cmm a 32.00–551.00 (104.00) 14.00–478. (87.00) 26.00–516.00 (101) 0.125 g TLC (x 10 3 ) c/cmm a 2.70–18.57 (6.54) 1.88–23.60 (9.48) 2.09–10.4 (5.24) < 0.001 g ALT (IU/L) a 12.00–450.00 (31.50) 14.00–2031.00 (43.50) 13.00–103.00 (30.50) 0.047 g AST (IU/L) a 18.00–1760.00 (66.00) 23.00–4397.00 (104.0) 20.00–200.00 (47.00) 0.001 g Albumen (g/dl) 2.73 ± 0.57 2.55 ± 0.50 2.67 ± 0.31 0.30 Bilirubin (mg/dl) a 0.60–12.00 (3.10) 2.10–35.10 (11.90) 0.72–4.80 (1.90) < 0.001 g INR 1.67 ± 0.30 cd 2.28 ± 0.87 d 1.33 ± 0.17 < 0.001 Blood Urea (mg/dl) 74.14 ± 44.57 cd 152.56 ± 73.50 d 42.69 ± 14.61 < 0.001 Creatinine (mg/dl) 1.26 ± 0.54 c 4.10 ± 2.24 d 0.98 ± 0.24 < 0.001 Serum Na (meq/l) 130.46 ± 7.23 131.53 ± 6.30 132.30 ± 4.76 0.51 Serum Potassium (meq/l) 4.11 ± 0.63 4.28 ± 0.90 4.17 ± 0.64 0.65 Serum IL-4 (pg/ml) a 0.21–11.28 (1.03) cd 1.03–16.82 (12.08) d 0.06–2.14 (0.22) < 0.001 g Ascitic CD206 (ng/ml) a 1.40–49.77 (13.95) cd 4.23–59.70 (35.59) d 0.20–17.12 (5.00) < 0.001 g Severity of liver disease : CTP score 10.53 ± 1.33 cd 11.97 ± 1.44 d 9.23 ± 1.33 < 0.001 CTP class − A 0 (0.00) 0 (0.00) 0 (0.00) < 0.001 f − B 8 (26.67) 0 (0.00) 19 (63.30) − C 22 (73.33) 30 (100) 11 (36.70) MELD Na score 22.8 ± 6.44 cd 35.83 ± 6.60 d 16.80 ± 4.70 < 0.001 ACLF grade − I - 1 (3.33) - - − II - 8 (26.67) - - − III - 21 (70.00) - - CLIF-C AD 58.97 ± 8.64 - - - CLIF-C ACLF - 58.73 ± 11.24 - - CLIF-OF - 12.16 ± 2.46 - - CLIF SOFA-ACLF - 12.16 ± 2.46 - - ACLF: Acute on chronic liver failure; AD: Acute decompensation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CTP: Child-Pugh-Turcotte; DAAs: Direct-acting antiviral drugs; HBV: Hepatitis B virus; HCV: Hepatitis C virus; IL: Interleukin; INR: International normalization ratio; MASLD: Metabolic Dysfunction-Associated Steatotic Liver Disease; MBP: Mean blood pressure; MELD: Model of End-stage Liver Disease; TLC: Total leucocyte count . a : Data is expressed as minimum-maximum (median). b : One-way ANOVA test. c : significant difference from the ACLF group (Mann-Whitney U test). d : significant difference from the control group (Mann-Whitney U test). e : Fisher’s Exact test. f : Chi-square test. g : Kruskal Wallis test. Comparison between groups as regards the serum IL4 and levels of ascitic sCD206 : The serum levels of IL-4 (pg/ml) ranged between (0.21–11.28 pg/ml), (1.03–16.82 pg/ml), and (0.06–2.14 pg/ml) in AD, ACLF patients, and the control group, respectively. The median level of serum IL-4 was significantly higher in AD and ACLF patients when compared to the control group, and in ACLF patients compared to AD patients (P < 0.001). The level of sCD206 in ascitic fluid ranged between (1.40–49.77 ng/ml), (4.23–59.70 ng/ml) and (0.20–17.12 ng/ml ) in AD, ACLF patients, and the control group, respectively. The median level of ascitic sCD206 was significantly higher in AD and ACLF groups compared to the control group, and in ACLF patients compared to AD patients (P < 0.001), (Table 1 ). In a subgroup analysis, patients with clinical sepsis were compared to patients with no sepsis as regards the mean levels of serum IL-4 and ascitic sCD206. There was no statistically significant difference between subgroups (P > 0.05), ( Supplementary table 1 ) . ROC analysis for serum IL4 and levels of ascitic sCD206 and its relation to cumulative mortality at one-month mortality : ROC analysis was performed for the serum IL4 and ascitic level of sCD206 to investigate their performance in predicting one-month mortality among patients with AD and ACLF. At a cut-off value 3.60 pg/ml for serum IL4 and 19.30 ng/ml for sCD206 both could predict mortality at one month with a sensitivity of 92.9%, 89.3%, and specificity of 75% and 90.5% respectively (AUC = 0.91 and AUC = 0.94, P = 0.001 and 0.002, respectively), compared to sensitivity and specificity of 82.1% and 62.5% respectively for MELD-Na (Fig. 1 ). When we applied the rule of having both IL-4 ≥ 3.6 pg/ml and CD206 ≥ 19.3 ng/ml, at the same time, the sensitivity and specificity, PPV, and NPV of this combination in the prediction of 1-month mortality were 85.7%,95.2%, 88.9%, and 93.7%, respectively. When we applied the rule of having both MELD-NA ≥ 26.5 together with ascitic sCD206 ≥ 19.3 ng/ml, at the same time, the sensitivity and specificity, PPV, and NPV of this combination in the prediction of 1-month mortality were 78.6%, 93.4%, 91.6% and 83.3% respectively. Correlation between serum IL-4 and ascitic sCD206 and different parameters : Serum IL-4 and ascitic level of sCD206 were positively correlated with history of recent infection, WBCs count, absolute neutrophil count, CRP, ascitic fluid PMN, CTP score, MELD-Na in all patients, CLIF-AD in AD patients; and CLIF-C ACLF, and CLIF-OF scores in ACLF patients. Serum IL-4 showed a significant correlation to ascitic sCD206 in all patients. (Table 2 ) Table 2 Correlations between serum IL-4, ascitic sCD206, and clinico-laboratory parameters: Parameter* IL-4 sCD206 r p r p History of infection # 0.48 < 0.001 0.47 < 0.001 WBCs 0.36 < 0.001 0.46 < 0.001 ANC 0.43 < 0.001 0.53 < 0.001 CRP 0.38 < 0.001 0.33 0.002 IL-4 - - 0.87 < 0.001 Ascitic PMN 0.63 < 0.001 0.74 < 0.001 CTP score 0.67 < 0.001 0.68 < 0.001 MELD-Na 0.79 < 0.001 0.75 < 0.001 CLIF-AD** 0.49 0.006 0.41 0.027 CLIF-C-ACLF*** 0.48 0.007 0.65 < 0.001 CLIF-OF*** 0.57 0.001 0.59 0.001 ACLF: Acute-on-Chronic Liver Failure; AD: Acute decompensation; ANC: Absolute Neutrophilic Count; CLIF: Chronic Liver Failure; CRP: C-reactive protein; CTP: Child-Turcotte-Pugh; MELD-Na: The Model for End-Stage Liver Disease-Sodium; PMN: Polymorph nuclear Leucocytes. #Pearson correlation. * Analysis for the three groups (n = 90) ** AD patients (n = 30) *** ACLF patients (n = 30) Mortality/Survival assessment and Kaplan-Meier analysis : The cumulative 1-, and 3-month mortality rates were significantly different between groups. At one month, 8 (26.7%) patients in the AD group, 20 (66.7%) patients in the ACLF group and none of the control group died (p < 0.001, χ2 = 31.5). At 3 months, 12 (40%) patients in the AD group, 24 (80%) patients in the ACLF group, and 5 (16.7%) patients in the control group died (p < 0.001, χ 2 = 24.81). Patients with serum IL-4 levels ≥ 3.6 pg/ml had higher mortality rates than patients with IL-4 levels < 3.6 pg/ml at 1-, and 3 months, respectively (P < 0.001). Similarly, patients with ascitic sCD206 levels ≥ 19.30 ng/ml had higher mortality rates than patients with sCD206 levels < 19.30 ng/ml at 1-, 3-months respectively (P < 0.001), (Table 3 ) Table 3 Comparison of cumulative one-, three-months mortality according to IL-4 and sCD206 cut-off values among patients with AD and ACLF (n = 60) IL-4 IL-4 ≥ 3.60 pg/ml (n = 34 ) IL-4 < 3.60 pg/ml (n = 26) Mortality Yes No Yes No χ 2 P − At 1 month 26 (76.50) 8 (23.50) 2 (7.70) 24 (92.30) 28.0 < 0.001 − At 3 month 32 (94.10) 2 (5.90) 4 (15.4) 22 (84.6) 38.10 < 0.001 CD206 sCD206 ≥ 19.30 ng/ml (n = 28) sCD206 < 19.30 ng/ml (n = 32) Mortality Yes No Yes No χ 2 P − At 1 month 25(89.30) 3(10.70) 3 (9.40) 29 (90.60) 38.30 < 0.001 − At 3 month 28 (100) 0 (0.0) 8 (25.0) 24 (75.0) 35.00 < 0.001 ACLF: Acute-on-Chronic Liver Failure; AD: Acute decompensation The overall survival rate was significantly different among the three study groups. Patients in the ACLF group had a median of 8 days of survival (95% CI: 2–9.99), patients in the AD group had a median of 30 days of survival (95% CI: 24.56–35.44), while the control group had a median of 88 days, (log-rank test χ 2 = 43.5, P < 0.001; 95% CI: 16.15–159.86) ( Supplementary Fig. 2 ). Kaplan-Meier analysis was done only for the serum IL4 and ascitic CD206 to stratify cases, and the analysis was done for the AD and ACLF groups (n = 60). At 1 month, patients with serum IL4 ≥ 3.6 pg/ml had a significantly shorter median overall survival compared to patients with IL4 < 3.6 pg/ml (15 vs. 29 days) ( Log-rank test χ 2 = 44.21, P < 0.001; 95% CI: 11.2–19.2, and 95%CI: 28.1–30.7, respectively ), (Fig. 2 -a). Similarly, at 1- month, patients with ascitic CD206 ≥ 19.3 ng/ml had a significantly shorter median overall survival compared to patients with ascitic CD206 < 19.3 ng/ml (8 vs. 28 days) ( Log-rank test χ 2 = 44.80, P < 0.001; 95% CI: 5.6–17.1, and 95% CI: 27.4–30.1, respectively ) (Fig. 2 -b). At 3-months, patients with serum IL-4 ≥ 3.6 pg/ml had significantly shorter median survival compared to patients with IL-4 < 3.6 pg/ml (18 vs. 81 days) ( Log-rank test χ 2 = 52.51, P < 0.001; 95% CI: 12.7–24.9, and 95%CI: 72.4–90.2, respectively), (Fig. 2 -c). Similarly, at 3- months, patients with ascitic sCD206 ≥ 19.3 ng/ml had a significantly shorter median overall survival compared to patients with ascitic sCD206 < 19.3 ng/ml (14 vs. 76 days) ( Log-rank test χ 2 = 57.20 , P < 0.001;95% CI: 9.0–18.9, and 95%CI: 67.5–85.0, respectively), (Fig. 2 -d). Cox regression analysis for predictors of mortality : The univariate analysis identified baseline parameters (CTP score, MELD-Na, serum creatinine, serum bilirubin, INR, ascitic sCD206, and serum IL-4 ) as significant for the prediction of 1- and 3-month mortality ( Supplementary table 3 ). However, cox regression analysis showed that baseline CTP score, ascitic sCD206, and serum IL-4 level are the only independent predictors of 1- and 3-month mortality (P < 0.001) (Table 4 ). Table 4 Cox-regression for predictors of in-hospital as well as 3 months mortality among acute decompensation and acute-on-chronic liver failure patients ( n = 60) One month mortality three months mortality Parameter P OR 95% CI P OR 95% CI CTP score 0.01 0.59 0.39–0.89 0.018 0.64 0.45–0.93 MELD-Na 0.40 - - 0.66 - - Cr 0.22 - - 0.52 - - Bilirubin 0.95 - - 0.65 - - INR 0.08 - - 0.18 - - Serum IL-4 < 0.001 1.3 1.12–1.47 <0.001 1.27 1.14–1.42 Ascitic CD206 0.001 1.1 1.03–1.13 <0.001 1.08 1.04–1.14 CI: Confidence interval; CTP: Child-Turcotte-Pugh; Cr: Creatinine; INR: International normalization ratio; IL-4: Interleukin − 4; MELD: Model of end-stage liver disease; OR: Odd’s ratio. Discussion Immune dysregulation is the cornerstone for the progression of ACLF. As portal hypertension (PHTN) progresses, immune dysfunction intensifies and ultimately leads to total immune exhaustion. (13) CD206 is regarded as a marker of M2 macrophage phenotype, and can be released into the bloodstream as a soluble form. (14) While numerous scores have been developed to estimate mortality in ACLF and AD, these metrics fall short of incorporating indicators that reflect disease progression or pathogenesis. Thus, it is essential to identify novel promising markers that accurately forecast prognosis. In this research, we measured the serum concentration of IL-4 and ascitic sCD206 in cirrhotic individuals with ACLF or AD, and analyzed their association with liver disease severity and patient survival. Our study's initial finding reveals that both ascitic sCD206 and serum IL-4 levels were notably elevated in patients with AD and ACLF, showing a positive correlation with liver disease severity scores; additionally, these markers effectively categorized patients with increased risks of mortality at 1 and 3 months. Simultaneously, patients exhibiting IL-4 levels ≥ 3.6 pg/ml and sCD206 levels ≥ 19.3 ng/mL experienced increased mortality rates and reduced survival times. Typically, CD206 functions in recognizing and internalizing pathogens. Although sCD206 is consistently found in the plasma of healthy individuals, its concentration rises across various diseases when triggered by activation from fungi and lipopolysaccharide both in vivo and in vitro. (8) CD206 associated with macrophage-derived extracellular vesicles can influence the immune response by modifying the phenotype of endothelial cells and T cells, leading to enhanced recruitment and activation of leukocytes. (15) Patients with liver diseases, severe illness, sepsis, and organ failure exhibited notably elevated sCD206 levels. (16) sCD206 is not specific to any disease; instead, it reflects the overall status of the immune system. It shows a strong association with indicators of significant immune activation, such as tumor necrosis factor. (9) sCD206 levels show a relationship with inflammation and fibrosis in MASLD, chronic HCV, and PBC patients. In LC, elevated serum sCD206 levels were observed compared to healthy individuals and were linked to liver decompensation. (17) Additionally, levels of CD206 were reduced following antiviral therapy. (18) Patients with acute alcoholic hepatitis, acute liver failure, and ACLF exhibit the highest concentrations of sCD206. (8, 19) A connection exists between sCD206 and changes in metabolic pathways associated with mitochondrial energy production, contributing to the advancement of organ failure in ACLF. Activation of macrophages in cirrhosis might indicate a persistent inflammatory upregulation, which may be further intensified by an overall systemic inflammatory condition, resulting in immune activation. (20) Due to its large molecular size, the renal clearance of sCD206 protein is improbable. In addition, decreased hepatic metabolism, and shunting of portal blood may also explain the elevated levels of sCD206 in our study. All participants in our research experienced PHTN, which, along with the impaired gut-blood barrier, facilitates the translocation of intestinal bacteria and PAMPs. These can stimulate the toll-like receptors of resident hepatic macrophages inside the liver. sCD206 showed a correlation with gut permeability indicators. sCD206 also has been assessed in predictive scores for clinically significant PHTN. (21, 22) In our research, ascitic sCD206 and serum IL-4 emerged as independent predictors for mortality at 1 and 3 months. Incorporating sCD206 into MELD-Na enhanced its effectiveness in predicting patient survival. Serum sCD206 was linked to mortality at 28 and 90 days in ACLF. (18, 21) Integrating sCD206 with the CLIF-C AD-score significantly enhances the accuracy of predicting mortality at 90 and 180 days for patients with AD. (19, 23) ACLF patients exhibiting elevated sCD206 levels exhibited more severe liver, coagulation, cardiovascular, or cerebral failures and encountered bacterial infections and sepsis. Additionally, sCD206 influenced the prognosis in cirrhotic patients without ALCF, suggesting a role that is separate from severe inflammation. (19) In ACLF patients, the level of sCD206 was related to the severity of the disease. (24) sCD206 has the ability to bind with CD45 on macrophages, resulting in cellular reprogramming towards an inflammatory phenotype driven by Src/Akt/NF-κB pathway. Moreover, sCD206 is involved in removing glycoproteins through the breakdown of endogenous glycoproteins like β-glucuronidase and procollagen, which increase during inflammation. (25) Only a single prior study examined ascitic sCD206 in individuals with SBP. At concentrations greater than 0.53 mg/L, sCD206 indicated poorer survival at 3 months. The disparity in the outcomes between our findings and those of Stengel et al., might be attributed to the greater number of patients with SBP in their research, unlike ours. (5) Live bacteria and toll-like receptor (TLRs) agonists can stimulate PM, resulting in alterations to their CD206 expression, triggering the release of sCD206. (5) Comparing sCD206 levels across studies is difficult because there is no standardized assay available for detecting sCD206. The peritoneal concentration of sCD206 correlates with an inflammatory macrophage phenotype and activation of macrophages. PM expressing sCD206 showed notably elevated levels of TLRs and chemokines when stimulated. Additionally, sCD206 is involved in the capture of antigens and their transport to cells that participate in the humoral immune response. This contradicts the earlier thought that CD206 + macrophages have anti-inflammatory properties, indicating their plasticity. (26) In our study, we found a correlation between IL-4 and sCD206. Previous research has demonstrated that IL-4 enhances the expression of CD206. (27) IL-4 prompts monocytes and macrophages to differentiate into M2 phenotypes. The transcription factors STAT6, IRF4, and PPARγ, responsible for regulating genes associated with M2a macrophages such as CD206, are activated and relocated by IL-4. In M2a macrophages, the mRNA expression of the mannose receptor CD206 reached its highest level 72 hours following IL-4 stimulation. (28) Macrophages primed with IL-4 exhibit a strong proinflammatory capacity when compared to naive and M1 macrophages. IL-4Rα on macrophages facilitates hepatic inflammation and fibrosis, and blocking it reverses these effects. (29) IL-4 also triggers hepatocyte apoptosis via a pathway that is independent of Fas. Other research suggested encouraging reparative and fibrotic function of IL-4 in hepatocytes. (6) Furthermore, IL-4 serves as an indicator of the TH2 response in ACLF. (30) We acknowledge that the limited sample size in our study poses a restriction, yet a significant advantage of this study is that it represents the first assessment of ascitic sCD206 as a potential marker for predicting mortality risk in patients with AD and ACLF, regardless of SBP existence. However, future research is suggested to investigate the influence of SBP on sCD206 levels using a larger group. In addition, our research is one of few studies that investigate IL-4 in ACLF patients and its relation to sCD206 in vivo. In summary , the link between ascitic sCD206 and serum IL-4 levels with AD and ACLF severity, as well as mortality, indicates the crucial role of PM in the progression and outcomes of ACLF. Incorporating macrophage biomarkers [ascitic sCD206 and serum IL-4] into the ACLF and AD scores is proposed to enhance the prognostic and predictive capabilities beyond those of conventional scores. Declarations Author Contribution Sameh A lashen: Methodology; Project administration; review & editing; Software; Supervision.Perihan Salem: Validation; Visualization; Roles/Writing .Esraa Ibrahim: Methodology; Project administration; Resources .Dalia Abd El-Moety: Investigation; Methodology.Walid I. Yousif: Roles/Writing - original draft; and Writing - review &editing and Conceptualization. References Schierwagen R, Gu W, Brieger A, et al. Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure. Am J Physiol Physiol 2023; 325: C129–40. Wong F. Innovative approaches to the management of ascites in cirrhosis. JHEP Rep 2023; 5: 100749. Wen Y, Lambrecht J, Ju C, et al. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol Immunol 2021; 18: 45–56. Wang C, Ma C, Gong L, et al. Macrophage Polarization and Its Role in Liver Disease. Front Immunol 2021; 12: 803037. Stengel S, Quickert S, Lutz P, et al. Peritoneal Level of CD206 Associates With Mortality and an Inflammatory Macrophage Phenotype in Patients With Decompensated Cirrhosis and Spontaneous Bacterial Peritonitis. Gastroenterol 2020; 158: 1745–61. Lynch R, Hawley C, Bain C, et al. Role of exogenous interleukin 4 in the dynamics of acute liver injury. Lancet 2017; 389: S64. Tsuchiya K, Suzuki Y, Yoshimura K, et al. Author Correction: Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia. Sci Rep 2020; 10: 3324. Nielsen MC, Hvidbjerg Gantzel R, Clària J, et al. Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 2020; 9: 1175. Ossen L, Vesterhus M, Hov JR, et al. Circulating Macrophage Activation Markers Predict Transplant-Free Survival in Patients With Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2021;12 :e00315. El Ray A, Fouad R, ElMakhzangy H, et al. Characterizing a cohort of Egyptian patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2021;33:1023-28. Zaccherini G, Weiss E, Moreau R. Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment. JHEP Rep 2020; 3:100176. Rashed E, Soldera J. CLIF-SOFA and CLIF-C scores for the prognostication of acute-on-chronic liver failure and acute decompensation of cirrhosis: A systematic review. World J Hepatol 2022 ;14 :2025–43. Martin-Mateos R, Alvarez-Mon M, Albillos A. Dysfunctional Immune Response in Acute-on-Chronic Liver Failure: It Takes Two to Tango. Front Immunol 2019; 10: 973. Chen S, Saeed AFUH, Liu Q, et al. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 2023;8:1–35. Li L, Cheng Y, Emrich S, et al. Activation of endothelial cells by extracellular vesicles derived from Mycobacterium tuberculosis-infected macrophages or mice. PLoS One 2018; 13: e0198337. Rødgaard-Hansen S, Rafique A, Christensen PA, et al. A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness. Clin Chem Lab Med 2014; 52: 453–61. Grønbæk H, Gantzel RH, Laursen TL, et al. Macrophage markers and innate immunity in cirrhosis. J Hepatol 2020; 73:1586–8. Grønbæk H, Rødgaard-Hansen S, Aagaard NK, et al. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF). J Hepatol 2016; 64: 813–22. Khorami SHH, Nejatollahi F, Davarpanah MA. Serum Levels of Interleukin-4, Interleukin-10 and Interferon-γ in Patients with Chronic Hepatitis B Infection. Hepat Mon 2018; 18: e60377. Rainer F, Horvath A, Sandahl TD, et al. Soluble CD163 and soluble mannose receptors predict survival and decompensation in patients with liver cirrhosis and correlate with gut permeability and bacterial translocation. Aliment Pharmacol Ther 2018; 47: 657–64. Orntoft NW, Blé M, Baiges A, et al. Divergences in Macrophage Activation Markers Soluble CD163 and Mannose Receptor in Patients With Non-cirrhotic and Cirrhotic Portal Hypertension. Front Physiol 2021; 12:649668. Li TP, Guan SH, Wang Q, et al. Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2019;25:5667–75. van der Zande HJP, Nitsche D, Schlautmann L, et al. The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation. Front Immunol 2021; 12: 765034. Nielsen MC, Hvidbjerg Gantzel R, Clària J, et al. Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 2020; 9: 1175. Ahmed AMM, Kadaru AGY, Omer I, et al. Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor. J Clin Exp Hepatol 2014; 4: 279. Tan-Garcia A, Lai F, Sheng Yeong JP, et al. Liver fibrosis and CD206 + macrophage accumulation are suppressed by anti-GM-CSF therapy. JHEP Reports 2020;2 :100062. Dang B, Gao Q, Zhang L, et al. The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages. Cell Rep 2023; 42: 112471. Li L, Chen L, Lin F, et al. Study of the Expression of Inflammatory Factors IL-4, IL-6, IL-10, and IL-17 in Liver Failure Complicated by Coagulation Dysfunction and Sepsis. J Inflamm Res 2021 ;14:1447. Cheng Y, Tian Y, Xia J, et al. The role of PTEN in the regulation of hepatic macrophage activation and function in the progression and reversal of liver fibrosis. Toxicol Appl Pharmacol 2017; 317: 51–62. Weiss E, de la Grange P, Defaye M, et al. Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF. Front Immunol 2021; 11:619039. Additional Declarations No competing interests reported. Supplementary Files 09Supplemetarytablesandfigures.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7049789","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485566311,"identity":"8f891915-fff3-43c0-8519-d0648c2b8122","order_by":0,"name":"Sameh A. Lashen","email":"","orcid":"","institution":"Faculty of Medicine, University of Alexandria","correspondingAuthor":false,"prefix":"","firstName":"Sameh","middleName":"A.","lastName":"Lashen","suffix":""},{"id":485566312,"identity":"a1621ac4-b3ca-471b-ac63-2eab3674a6b5","order_by":1,"name":"Berihan Salem","email":"","orcid":"","institution":"Faculty of Medicine, University of Alexandria","correspondingAuthor":false,"prefix":"","firstName":"Berihan","middleName":"","lastName":"Salem","suffix":""},{"id":485566313,"identity":"6994840e-ea21-4715-b69e-95b300c28b23","order_by":2,"name":"Esraa Ibrahim","email":"","orcid":"","institution":"Faculty of Medicine, University of Alexandria","correspondingAuthor":false,"prefix":"","firstName":"Esraa","middleName":"","lastName":"Ibrahim","suffix":""},{"id":485566314,"identity":"3086a503-ea66-432e-9efa-4dab5a13b829","order_by":3,"name":"Dalia Abd Elmoaty","email":"","orcid":"","institution":"Faculty of Medicine, Alexandria University","correspondingAuthor":false,"prefix":"","firstName":"Dalia","middleName":"Abd","lastName":"Elmoaty","suffix":""},{"id":485566315,"identity":"1a893480-fd94-40d8-a12a-f91b8ef0a5d3","order_by":4,"name":"walid .i yousif","email":"data:image/png;base64,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","orcid":"","institution":"Faculty of Medicine, University of Alexandria","correspondingAuthor":true,"prefix":"","firstName":"walid","middleName":".i","lastName":"yousif","suffix":""}],"badges":[],"createdAt":"2025-07-05 00:23:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7049789/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7049789/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87265721,"identity":"e4bb83f4-a4e8-43f8-b191-c8eb5affb1b3","added_by":"auto","created_at":"2025-07-22 07:57:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":40794,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan Meier analysis for serum IL4 and levels of ascitic \u0026nbsp;sCD206 as regards one- and three-months mortality (a) mortality at one month for serum IL4, (b) mortality at one month for ascitic \u0026nbsp;sCD206, (c) mortality at three months for serum IL4, (d) mortality at three months for ascitic sCD206.\u003c/p\u003e","description":"","filename":"figure1cd206.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7049789/v1/dfb7c03e0abb5d798805b03f.jpg"},{"id":87265722,"identity":"48ea0ad0-3d3b-40a4-9d3f-df28e72c439b","added_by":"auto","created_at":"2025-07-22 07:57:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":106759,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis for serum IL-4 , levels of ascitic \u0026nbsp;sCD206 and MELD-Na to find cut-off value for risk of mortality at one month.\u003c/p\u003e","description":"","filename":"figure2cd206.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7049789/v1/6970f1e3b6193956d2180712.jpg"},{"id":88840450,"identity":"474ab806-0402-4d33-a052-417bf281261a","added_by":"auto","created_at":"2025-08-12 02:23:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1746547,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7049789/v1/198fd493-2ed1-4330-8f8a-8808e69e43b0.pdf"},{"id":87265736,"identity":"3a6da366-d85c-4bb4-943d-a7b1e683b6d7","added_by":"auto","created_at":"2025-07-22 07:57:23","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":149925,"visible":true,"origin":"","legend":"","description":"","filename":"09Supplemetarytablesandfigures.docx","url":"https://assets-eu.researchsquare.com/files/rs-7049789/v1/455a6a8433a125d7175f0ea2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Serum Interleukin-4 and Ascitic CD206 Predict Mortality in Acute Cirrhosis Decompensation and Acute-on-Chronic Liver Failure","fulltext":[{"header":"Introduction and aim","content":"\u003cp\u003eDuring the course of liver cirrhosis (LC), acute decompensation (AD) represents the typical complication, with the acute-on-chronic liver failure (ACLF) represents the most severe phenotype. ACLF is marked by organ failures, significant systemic inflammation (SI), and increased 28-day mortality. \u003csup\u003e(1, 2)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePeritoneal macrophages (PM) make up most of the immune cells residing in the peritoneum. They produce and regulate hepatic and SI by identifying damage-associated and pathogen-associated molecular patterns. \u003csup\u003e(3)\u003c/sup\u003e Macrophages are typically categorized into M1 (pro-inflammatory) or M2 (anti-inflammatory) types as they adapt to the local environment during liver injury. \u003csup\u003e(4)\u003c/sup\u003e Recent evidence indicates a link between immune activation in the peritoneum, SI, complications, and outcomes in decompensated cirrhosis. \u003csup\u003e(5)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eInterleukin-4 (IL-4) directs macrophages to adopt the M2 phenotype. Depending on the type of cell, IL-4 may trigger regulatory, suppressive, or pro-inflammatory reactions. \u003csup\u003e(6)\u003c/sup\u003e CD206, previously utilized for identifying activated (M2) macrophages, is a membrane-bound C-type lectin that acts as a pattern recognition scavenger receptor. \u003csup\u003e(7)\u003c/sup\u003e CD206 facilitates endocytosis, enhances antigen presentation, and activates T-cells. Soluble variants of CD206 are released peripherally following proteolytic cleavage from the surface of macrophages and can modify both adaptive and innate immune responses. \u003csup\u003e(8)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eMarkers of macrophages have been used as surrogate parameters to predict disease severity and outcomes in a wide range of disorders. \u003csup\u003e(9)\u003c/sup\u003e In this context, the present study aimed to evaluate serum levels of IL-4 and ascitic levels of soluble CD206 (sCD206) in cirrhotic patients with AD and ACLF and their relation to the severity of liver disease and patient survival.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eIn a prospective case-control design, we included LC patients who presented to our hospital with AD or ACLF, whose symptoms started within 2 weeks before admission. The sample size was calculated assuming a power of 95%, an α-error of 0.05, a between-groups variance of 0.2 and a prevalence of 30% for ACLF in Egyptian tertiary hospitals. \u003csup\u003e(10)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAmong 130 patients who were screened, 70 patients were excluded due to non-eligibility [patients with hepatocellular carcinoma or other malignancies, chronic heart failure, chronic pulmonary, renal, or rheumatological diseases, severe alcoholic hepatitis, and patients with incomplete records]. Finally, 60 participants were included. We also included 30 patients as a control group.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCohort definition\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe total 90 patients were assigned into three groups as following (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e): \u003cb\u003eGroup -A\u003c/b\u003e (AD patients): patients with liver cirrhosis who are presenting with AD, defined as jaundice, coagulopathy [international normalized ratio (INR)\u0026thinsp;\u0026ge;\u0026thinsp;1.5], and presence of large ascites (grade 2 or 3) within \u0026lt;\u0026thinsp;2 weeks of presentation, those with acute hepatic encephalopathy (HE), and with gastrointestinal bleeding; \u003cb\u003eGroup -B\u003c/b\u003e (ACLF patients): patients with acute hepatic insult plus organ failure: liver failure as defined by a serum bilirubin level\u0026thinsp;\u0026gt;\u0026thinsp;5 mg/dl, renal failure as defined by a serum creatinine\u0026thinsp;\u0026ge;\u0026thinsp;2 mg/dl, cerebral failure as defined by HE grade III or IV, coagulation failure (INR\u0026thinsp;\u0026ge;\u0026thinsp;2.5 and/or platelet count of less than 20 x10\u003csup\u003e9\u003c/sup\u003e/L), circulatory failure as defined by the use of vasopressors, and respiratory failure as defined by a peripheral capillary oxygen saturation (SpO2) to FiO2 ratio of \u0026le;\u0026thinsp;200, within the last 4 weeks \u003csup\u003e(11)\u003c/sup\u003e; \u003cb\u003eGroup - C\u003c/b\u003e (control group): patients with cirrhotic ascites who don't fulfill the criteria of patients in Group A or Group B. All patients were followed for a minimum of 90 days through outpatient systems and by telephone to assess survival. The endpoint of the study was the occurrence of death or end of follow up, whichever comes first.\u003c/p\u003e\u003cp\u003eAll patients received a clinical evaluation. Blood samples were collected at the time of admission for complete blood cell count, and blood chemistry including liver profile, renal function tests, and electrolytes. Serum IL-4 levels were measured using a commercially available ELISA kit (Finetest, Wuhan, China; cat.# EH0199). Ascitic fluid analysis was done with ascitic sCD206 quantification using a commercially available ELISA kit (Finetest, Wuhan, China; cat.# EH1802).\u003c/p\u003e\u003cp\u003eThe severity of liver disease was graded according to Child-Turcotte-Pugh (CTP), and the Model for End-Stage Liver Disease (MELD-Na) scores. CLIF-C AD score was used for AD patients while ACLF was assessed by the CLIF-SOFA score.\u003csup\u003e(12)\u003c/sup\u003e Severity was stratified by considering the number of organs failed (OF): grade 1 (1 OF), grade 2 (2 OFs), and grade 3 (3 to 6 OFs). Survival rates were assessed for 1, and 3 months.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEthics\u003c/b\u003e\u003c/p\u003e\u003cp\u003e The study was approved by the institutional ethical committee board (IRB number 0107126), and conducted following the provisions of the Declaration of Helsinki of 1975, as revised in 2008. Informed consent was obtained from all subjects (or their legal guardians when applicable) included in the study. We have no financial support.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe IBM SPSS software package version 26.0 (Armonk, NY; IBM Corp) was used for statistical analysis. The sample size was calculated using STATA 15.1 package (StataCorp, USA). Data were presented as (minimum-maximum), median, Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, or number (per cent). Categorical variables were compared using the Chi-square test or Fisher's exact test. Means were compared by Kruskal Wallis or Mann\u0026ndash;Whitney U tests. ROC analysis was done on MELD-NA, serum IL-4, and ascitic sCD206. Kaplan-Meier analysis for 1-, and 3-month mortality as well as Cox regression analysis were used to evaluate the effect of baseline parameters on mortality risk.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eDemographic data\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe baseline data of the study groups are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Precipitating factors for acute presentation included acute HCV infection, variceal bleeding, and recent infections other than viral hepatitis [pneumonia (38%), soft tissue infections (21%), and urinary tract (17%)]. SBP was met in 7 (22.6%) patients (2 patients in the AD group and 5 patients in the ACLF group).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline demographic data of study population at admission:\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute decompensation\u003c/p\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAcute-on-chronic liver failure (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCirrhotic control\u003c/p\u003e\u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56.62\u0026thinsp;\u0026plusmn;\u0026thinsp;16.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59.41\u0026thinsp;\u0026plusmn;\u0026thinsp;14.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56.10\u0026thinsp;\u0026plusmn;\u0026thinsp;8.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.60\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender (male, n, %)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (43.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (50.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17 (56.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.58 \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEtiology of chronic liver disease\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eViral hepatitis: (n, %)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14 (46.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003ePost DAAs for HCV\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (26.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (23.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e0.22\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eActive chronic HCV\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (26.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (13.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eHCV/HBV co-infection\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eChronic hepatitis B\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (13.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAlcoholic liver disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2(6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.94 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMASLD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (13.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (16.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.91 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAutoimmune hepatitis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.99 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBudd-Chiari syndrome\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.99 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUnknown\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (13.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7 (23.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.34 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePrecipitating factors of acute presentation\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAcute HCV infection\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eRecent infection\u003c/b\u003e \u003csup\u003e\u003cb\u003eΣ\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (56.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eVariceal bleeding\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (60.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (53.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical examination\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMBP (mmHg)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.84\u0026thinsp;\u0026plusmn;\u0026thinsp;12.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e82.12\u0026thinsp;\u0026plusmn;\u0026thinsp;12.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80.54\u0026thinsp;\u0026plusmn;\u0026thinsp;8.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHepatic encephalopathy\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAbsent\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11(36.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (23.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eGrade 1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e00 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eGrade 2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (36.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e00 (0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eGrade 3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (20.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eGrade 4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (56.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAscites grades\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eMild\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (16.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (13.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e0.03 \u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eModerate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (43.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (56.66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (26.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eMarked/tense\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (53.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (26.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (60.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBaseline Laboratory parameters\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHemoglobin (g/dl)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.23\u0026thinsp;\u0026plusmn;\u0026thinsp;2.30\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.30\u0026thinsp;\u0026plusmn;\u0026thinsp;1.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePlatelets (x 10\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e) c/cmm\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.00\u0026ndash;551.00 (104.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.00\u0026ndash;478. (87.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26.00\u0026ndash;516.00 (101)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.125\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTLC (x 10\u003c/b\u003e\u003csup\u003e\u003cb\u003e3\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e) c/cmm\u003c/b\u003e\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.70\u0026ndash;18.57 (6.54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.88\u0026ndash;23.60 (9.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.09\u0026ndash;10.4 (5.24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALT (IU/L)\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.00\u0026ndash;450.00 (31.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.00\u0026ndash;2031.00 (43.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e13.00\u0026ndash;103.00 (30.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.047 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAST (IU/L)\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18.00\u0026ndash;1760.00 (66.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.00\u0026ndash;4397.00 (104.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.00\u0026ndash;200.00 (47.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAlbumen (g/dl)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBilirubin (mg/dl)\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.60\u0026ndash;12.00 (3.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.10\u0026ndash;35.10 (11.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.72\u0026ndash;4.80 (1.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eINR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30 \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.87 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBlood Urea (mg/dl)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74.14\u0026thinsp;\u0026plusmn;\u0026thinsp;44.57 \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e152.56\u0026thinsp;\u0026plusmn;\u0026thinsp;73.50 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e42.69\u0026thinsp;\u0026plusmn;\u0026thinsp;14.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCreatinine (mg/dl)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.26\u0026thinsp;\u0026plusmn;\u0026thinsp;0.54 \u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.24 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Na (meq/l)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130.46\u0026thinsp;\u0026plusmn;\u0026thinsp;7.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e131.53\u0026thinsp;\u0026plusmn;\u0026thinsp;6.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e132.30\u0026thinsp;\u0026plusmn;\u0026thinsp;4.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Potassium (meq/l)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.28\u0026thinsp;\u0026plusmn;\u0026thinsp;0.90\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum IL-4 (pg/ml)\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.21\u0026ndash;11.28 (1.03) \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.03\u0026ndash;16.82 (12.08) \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.06\u0026ndash;2.14 (0.22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAscitic CD206 (ng/ml)\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.40\u0026ndash;49.77 (13.95) \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.23\u0026ndash;59.70 (35.59) \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.20\u0026ndash;17.12 (5.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSeverity of liver disease\u003c/b\u003e:\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCTP score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33 \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.44 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.23\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCTP class\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eA\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001 \u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eB\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (26.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (63.30)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22 (73.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (36.70)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMELD Na score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.44 \u003csup\u003ecd\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.83\u0026thinsp;\u0026plusmn;\u0026thinsp;6.60 \u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16.80\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eACLF grade\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eI\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eII\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (26.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eIII\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (70.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-C AD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58.97\u0026thinsp;\u0026plusmn;\u0026thinsp;8.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-C ACLF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.73\u0026thinsp;\u0026plusmn;\u0026thinsp;11.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-OF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF SOFA-ACLF\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.16\u0026thinsp;\u0026plusmn;\u0026thinsp;2.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eACLF: Acute on chronic liver failure; AD: Acute decompensation; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CTP: Child-Pugh-Turcotte; DAAs: Direct-acting antiviral drugs; HBV: Hepatitis B virus; HCV: Hepatitis C virus; IL: Interleukin; INR: International normalization ratio; MASLD: Metabolic Dysfunction-Associated Steatotic Liver Disease; MBP: Mean blood pressure; MELD: Model of End-stage Liver Disease; TLC: Total leucocyte count .\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e: Data is expressed as minimum-maximum (median).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eb\u003c/sup\u003e : One-way ANOVA test.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ec\u003c/sup\u003e : significant difference from the ACLF group (Mann-Whitney \u003cem\u003eU\u003c/em\u003e test).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ed\u003c/sup\u003e : significant difference from the control group (Mann-Whitney \u003cem\u003eU\u003c/em\u003e test).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ee\u003c/sup\u003e : Fisher\u0026rsquo;s Exact test.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ef\u003c/sup\u003e : Chi-square test.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003eg\u003c/sup\u003e : Kruskal Wallis test.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eComparison between groups as regards the serum IL4 and levels of ascitic sCD206\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe serum levels of IL-4 (pg/ml) ranged between (0.21\u0026ndash;11.28 pg/ml), (1.03\u0026ndash;16.82 pg/ml), and (0.06\u0026ndash;2.14 pg/ml) in AD, ACLF patients, and the control group, respectively. The median level of serum IL-4 was significantly higher in AD and ACLF patients when compared to the control group, and in ACLF patients compared to AD patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003eThe level of sCD206 in ascitic fluid ranged between (1.40\u0026ndash;49.77 ng/ml), (4.23\u0026ndash;59.70 ng/ml) and (0.20\u0026ndash;17.12 ng/ml ) in AD, ACLF patients, and the control group, respectively. The median level of ascitic sCD206 was significantly higher in AD and ACLF groups compared to the control group, and in ACLF patients compared to AD patients (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn a subgroup analysis, patients with clinical sepsis were compared to patients with no sepsis as regards the mean levels of serum IL-4 and ascitic sCD206. There was no statistically significant difference between subgroups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), (\u003cb\u003eSupplementary table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eROC analysis for serum IL4 and levels of ascitic sCD206 and its relation to cumulative mortality at one-month mortality\u003c/b\u003e :\u003c/p\u003e\u003cp\u003eROC analysis was performed for the serum IL4 and ascitic level of sCD206 to investigate their performance in predicting one-month mortality among patients with AD and ACLF. At a cut-off value 3.60 pg/ml for serum IL4 and 19.30 ng/ml for sCD206 both could predict mortality at one month with a sensitivity of 92.9%, 89.3%, and specificity of 75% and 90.5% respectively (AUC\u0026thinsp;=\u0026thinsp;0.91 and AUC\u0026thinsp;=\u0026thinsp;0.94, P\u0026thinsp;=\u0026thinsp;0.001 and 0.002, respectively), compared to sensitivity and specificity of 82.1% and 62.5% respectively for MELD-Na (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWhen we applied the rule of having both IL-4\u0026thinsp;\u0026ge;\u0026thinsp;3.6 pg/ml and CD206\u0026thinsp;\u0026ge;\u0026thinsp;19.3 ng/ml, at the same time, the sensitivity and specificity, PPV, and NPV of this combination in the prediction of 1-month mortality were 85.7%,95.2%, 88.9%, and 93.7%, respectively. When we applied the rule of having both MELD-NA\u0026thinsp;\u0026ge;\u0026thinsp;26.5 together with ascitic sCD206\u0026thinsp;\u0026ge;\u0026thinsp;19.3 ng/ml, at the same time, the sensitivity and specificity, PPV, and NPV of this combination in the prediction of 1-month mortality were 78.6%, 93.4%, 91.6% and 83.3% respectively.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCorrelation between serum IL-4 and ascitic sCD206 and different parameters\u003c/b\u003e :\u003c/p\u003e\u003cp\u003eSerum IL-4 and ascitic level of sCD206 were positively correlated with history of recent infection, WBCs count, absolute neutrophil count, CRP, ascitic fluid PMN, CTP score, MELD-Na in all patients, CLIF-AD in AD patients; and CLIF-C ACLF, and CLIF-OF scores in ACLF patients. Serum IL-4 showed a significant correlation to ascitic sCD206 in all patients. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCorrelations between serum IL-4, ascitic sCD206, and clinico-laboratory parameters:\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eParameter*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eIL-4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003esCD206\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003er\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHistory of infection\u003c/b\u003e\u003csup\u003e\u003cb\u003e#\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eWBCs\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eANC\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCRP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIL-4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAscitic PMN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCTP score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMELD-Na\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-AD**\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-C-ACLF***\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCLIF-OF***\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eACLF: Acute-on-Chronic Liver Failure; AD: Acute decompensation; ANC: Absolute Neutrophilic Count; CLIF: Chronic Liver Failure; CRP: C-reactive protein; CTP: Child-Turcotte-Pugh; MELD-Na: The Model for End-Stage Liver Disease-Sodium; PMN: Polymorph nuclear Leucocytes.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e#Pearson correlation.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003e*\u003c/b\u003eAnalysis for the three groups (n\u0026thinsp;=\u0026thinsp;90)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003e**\u003c/b\u003e AD patients (n\u0026thinsp;=\u0026thinsp;30)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cb\u003e***\u003c/b\u003e ACLF patients (n\u0026thinsp;=\u0026thinsp;30)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMortality/Survival assessment and Kaplan-Meier analysis\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe cumulative 1-, and 3-month mortality rates were significantly different between groups. At one month, 8 (26.7%) patients in the AD group, 20 (66.7%) patients in the ACLF group and none of the control group died (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, χ2\u0026thinsp;=\u0026thinsp;31.5). At 3 months, 12 (40%) patients in the AD group, 24 (80%) patients in the ACLF group, and 5 (16.7%) patients in the control group died (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;24.81).\u003c/p\u003e\u003cp\u003ePatients with serum IL-4 levels\u0026thinsp;\u003cb\u003e\u0026ge;\u003c/b\u003e\u0026thinsp;3.6 pg/ml had higher mortality rates than patients with IL-4 levels\u0026thinsp;\u0026lt;\u0026thinsp;3.6 pg/ml at 1-, and 3 months, respectively (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, patients with ascitic sCD206 levels\u0026thinsp;\u0026ge;\u0026thinsp;19.30 ng/ml had higher mortality rates than patients with sCD206 levels\u0026thinsp;\u0026lt;\u0026thinsp;19.30 ng/ml at 1-, 3-months respectively (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of cumulative one-, three-months mortality according to IL-4 and sCD206 cut-off values among patients with AD and ACLF (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIL-4\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eIL-4 \u0026ge; 3.60 pg/ml (n\u0026thinsp;=\u0026thinsp;34 )\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eIL-4 \u0026lt; 3.60 pg/ml (n = 26)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMortality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eχ\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAt 1 month\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (76.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (23.50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (7.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24 (92.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e28.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAt 3 month\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (94.10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (15.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e22 (84.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCD206\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003esCD206 \u0026ge; 19.30 ng/ml (n\u0026thinsp;=\u0026thinsp;28)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003e\u003cb\u003esCD206 \u0026lt; 19.30 ng/ml (n\u0026thinsp;=\u0026thinsp;32)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMortality\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eχ\u003c/b\u003e \u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAt 1 month\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25(89.30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(10.70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (9.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e29 (90.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026minus; \u003cb\u003eAt 3 month\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (100)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e24 (75.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eACLF: Acute-on-Chronic Liver Failure; AD: Acute decompensation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe overall survival rate was significantly different among the three study groups. Patients in the ACLF group had a median of 8 days of survival (95% CI: 2\u0026ndash;9.99), patients in the AD group had a median of 30 days of survival (95% CI: 24.56\u0026ndash;35.44), while the control group had a median of 88 days, (log-rank test χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;43.5, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI: 16.15\u0026ndash;159.86) ( \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e).\u003c/p\u003e\u003cp\u003eKaplan-Meier analysis was done only for the serum IL4 and ascitic CD206 to stratify cases, and the analysis was done for the AD and ACLF groups (n\u0026thinsp;=\u0026thinsp;60). At 1 month, patients with serum IL4\u0026thinsp;\u0026ge;\u0026thinsp;3.6 pg/ml had a significantly shorter median overall survival compared to patients with IL4\u0026thinsp;\u0026lt;\u0026thinsp;3.6 pg/ml (15 vs. 29 days) (\u003cem\u003eLog-rank test\u003c/em\u003e χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;44.21, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; \u003cem\u003e95% CI: 11.2\u0026ndash;19.2, and 95%CI: 28.1\u0026ndash;30.7, respectively\u003c/em\u003e), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e-a). Similarly, at 1- month, patients with ascitic CD206\u0026thinsp;\u0026ge;\u0026thinsp;19.3 ng/ml had a significantly shorter median overall survival compared to patients with ascitic CD206\u0026thinsp;\u0026lt;\u0026thinsp;19.3 ng/ml (8 vs. 28 days) (\u003cem\u003eLog-rank test\u003c/em\u003e χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u003cem\u003e=\u0026thinsp;44.80, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI: 5.6\u0026ndash;17.1, and 95% CI: 27.4\u0026ndash;30.1, respectively\u003c/em\u003e) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e-b).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAt 3-months, patients with serum IL-4\u0026thinsp;\u0026ge;\u0026thinsp;3.6 pg/ml had significantly shorter median survival compared to patients with IL-4\u0026thinsp;\u0026lt;\u0026thinsp;3.6 pg/ml (18 vs. 81 days) (\u003cem\u003eLog-rank test\u003c/em\u003e χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;52.51, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; 95% CI: 12.7\u0026ndash;24.9, and 95%CI: 72.4\u0026ndash;90.2, respectively), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e-c). Similarly, at 3- months, patients with ascitic sCD206\u0026thinsp;\u0026ge;\u0026thinsp;19.3 ng/ml had a significantly shorter median overall survival compared to patients with ascitic sCD206\u0026thinsp;\u0026lt;\u0026thinsp;19.3 ng/ml (14 vs. 76 days) (\u003cem\u003eLog-rank test\u003c/em\u003e χ\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;\u003cem\u003e=\u0026thinsp;57.20\u003c/em\u003e, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001;95% CI: 9.0\u0026ndash;18.9, and 95%CI: 67.5\u0026ndash;85.0, respectively), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e-d).\u003c/p\u003e\u003cp\u003e\u003cb\u003eCox regression analysis for predictors of mortality\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe univariate analysis identified baseline parameters (CTP score, MELD-Na, serum creatinine, serum bilirubin, INR, ascitic sCD206, and serum IL-4 ) as significant for the prediction of 1- and 3-month mortality (\u003cb\u003eSupplementary table 3\u003c/b\u003e). However, cox regression analysis showed that baseline CTP score, ascitic sCD206, and serum IL-4 level are the only independent predictors of 1- and 3-month mortality (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCox-regression for predictors of in-hospital as well as 3 months mortality among acute decompensation and acute-on-chronic liver failure patients (\u003cem\u003en\u0026thinsp;=\u003c/em\u003e\u0026thinsp;60)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eOne month mortality\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003ethree months mortality\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCTP score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.59\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.39\u0026ndash;0.89\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.64\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.45\u0026ndash;0.93\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMELD-Na\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eCr\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBilirubin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eINR\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum IL-4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1.3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e1.12\u0026ndash;1.47\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e1.27\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e1.14\u0026ndash;1.42\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAscitic CD206\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1.1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e1.03\u0026ndash;1.13\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e1.08\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e1.04\u0026ndash;1.14\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eCI: Confidence interval; CTP: Child-Turcotte-Pugh; Cr: Creatinine; INR: International normalization ratio; IL-4: Interleukin \u0026minus;\u0026thinsp;4; MELD: Model of end-stage liver disease; OR: Odd\u0026rsquo;s ratio.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eImmune dysregulation is the cornerstone for the progression of ACLF. As portal hypertension (PHTN) progresses, immune dysfunction intensifies and ultimately leads to total immune exhaustion.\u003csup\u003e(13)\u003c/sup\u003e CD206 is regarded as a marker of M2 macrophage phenotype, and can be released into the bloodstream as a soluble form.\u003csup\u003e(14)\u003c/sup\u003e While numerous scores have been developed to estimate mortality in ACLF and AD, these metrics fall short of incorporating indicators that reflect disease progression or pathogenesis. Thus, it is essential to identify novel promising markers that accurately forecast prognosis. In this research, we measured the serum concentration of IL-4 and ascitic sCD206 in cirrhotic individuals with ACLF or AD, and analyzed their association with liver disease severity and patient survival.\u003c/p\u003e\u003cp\u003eOur study's initial finding reveals that both ascitic sCD206 and serum IL-4 levels were notably elevated in patients with AD and ACLF, showing a positive correlation with liver disease severity scores; additionally, these markers effectively categorized patients with increased risks of mortality at 1 and 3 months. Simultaneously, patients exhibiting IL-4 levels\u0026thinsp;\u0026ge;\u0026thinsp;3.6 pg/ml and sCD206 levels\u0026thinsp;\u0026ge;\u0026thinsp;19.3 ng/mL experienced increased mortality rates and reduced survival times.\u003c/p\u003e\u003cp\u003eTypically, CD206 functions in recognizing and internalizing pathogens. Although sCD206 is consistently found in the plasma of healthy individuals, its concentration rises across various diseases when triggered by activation from fungi and lipopolysaccharide both in vivo and in vitro.\u003csup\u003e(8)\u003c/sup\u003e CD206 associated with macrophage-derived extracellular vesicles can influence the immune response by modifying the phenotype of endothelial cells and T cells, leading to enhanced recruitment and activation of leukocytes. \u003csup\u003e(15)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePatients with liver diseases, severe illness, sepsis, and organ failure exhibited notably elevated sCD206 levels. \u003csup\u003e(16)\u003c/sup\u003e sCD206 is not specific to any disease; instead, it reflects the overall status of the immune system. It shows a strong association with indicators of significant immune activation, such as tumor necrosis factor.\u003csup\u003e(9)\u003c/sup\u003e sCD206 levels show a relationship with inflammation and fibrosis in MASLD, chronic HCV, and PBC patients. In LC, elevated serum sCD206 levels were observed compared to healthy individuals and were linked to liver decompensation. \u003csup\u003e(17)\u003c/sup\u003e Additionally, levels of CD206 were reduced following antiviral therapy.\u003csup\u003e(18)\u003c/sup\u003e Patients with acute alcoholic hepatitis, acute liver failure, and ACLF exhibit the highest concentrations of sCD206. \u003csup\u003e(8, 19)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA connection exists between sCD206 and changes in metabolic pathways associated with mitochondrial energy production, contributing to the advancement of organ failure in ACLF. Activation of macrophages in cirrhosis might indicate a persistent inflammatory upregulation, which may be further intensified by an overall systemic inflammatory condition, resulting in immune activation. \u003csup\u003e(20)\u003c/sup\u003e Due to its large molecular size, the renal clearance of sCD206 protein is improbable. In addition, decreased hepatic metabolism, and shunting of portal blood may also explain the elevated levels of sCD206 in our study.\u003c/p\u003e\u003cp\u003e All participants in our research experienced PHTN, which, along with the impaired gut-blood barrier, facilitates the translocation of intestinal bacteria and PAMPs. These can stimulate the toll-like receptors of resident hepatic macrophages inside the liver. sCD206 showed a correlation with gut permeability indicators. sCD206 also has been assessed in predictive scores for clinically significant PHTN. \u003csup\u003e(21, 22)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn our research, ascitic sCD206 and serum IL-4 emerged as independent predictors for mortality at 1 and 3 months. Incorporating sCD206 into MELD-Na enhanced its effectiveness in predicting patient survival. Serum sCD206 was linked to mortality at 28 and 90 days in ACLF. \u003csup\u003e(18, 21)\u003c/sup\u003e Integrating sCD206 with the CLIF-C AD-score significantly enhances the accuracy of predicting mortality at 90 and 180 days for patients with AD.\u003csup\u003e(19, 23)\u003c/sup\u003e ACLF patients exhibiting elevated sCD206 levels exhibited more severe liver, coagulation, cardiovascular, or cerebral failures and encountered bacterial infections and sepsis. Additionally, sCD206 influenced the prognosis in cirrhotic patients without ALCF, suggesting a role that is separate from severe inflammation. \u003csup\u003e(19)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn ACLF patients, the level of sCD206 was related to the severity of the disease.\u003csup\u003e(24)\u003c/sup\u003e sCD206 has the ability to bind with CD45 on macrophages, resulting in cellular reprogramming towards an inflammatory phenotype driven by Src/Akt/NF-κB pathway. Moreover, sCD206 is involved in removing glycoproteins through the breakdown of endogenous glycoproteins like β-glucuronidase and procollagen, which increase during inflammation.\u003csup\u003e(25)\u003c/sup\u003e Only a single prior study examined ascitic sCD206 in individuals with SBP. At concentrations greater than 0.53 mg/L, sCD206 indicated poorer survival at 3 months. The disparity in the outcomes between our findings and those of Stengel et al., might be attributed to the greater number of patients with SBP in their research, unlike ours. \u003csup\u003e(5)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eLive bacteria and toll-like receptor (TLRs) agonists can stimulate PM, resulting in alterations to their CD206 expression, triggering the release of sCD206.\u003csup\u003e(5)\u003c/sup\u003e Comparing sCD206 levels across studies is difficult because there is no standardized assay available for detecting sCD206. The peritoneal concentration of sCD206 correlates with an inflammatory macrophage phenotype and activation of macrophages. PM expressing sCD206 showed notably elevated levels of TLRs and chemokines when stimulated. Additionally, sCD206 is involved in the capture of antigens and their transport to cells that participate in the humoral immune response. This contradicts the earlier thought that CD206\u0026thinsp;+\u0026thinsp;macrophages have anti-inflammatory properties, indicating their plasticity.\u003csup\u003e(26)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn our study, we found a correlation between IL-4 and sCD206. Previous research has demonstrated that IL-4 enhances the expression of CD206. \u003csup\u003e(27)\u003c/sup\u003e IL-4 prompts monocytes and macrophages to differentiate into M2 phenotypes. The transcription factors STAT6, IRF4, and PPARγ, responsible for regulating genes associated with M2a macrophages such as CD206, are activated and relocated by IL-4. In M2a macrophages, the mRNA expression of the mannose receptor CD206 reached its highest level 72 hours following IL-4 stimulation. \u003csup\u003e(28)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eMacrophages primed with IL-4 exhibit a strong proinflammatory capacity when compared to naive and M1 macrophages. IL-4Rα on macrophages facilitates hepatic inflammation and fibrosis, and blocking it reverses these effects. \u003csup\u003e(29)\u003c/sup\u003e IL-4 also triggers hepatocyte apoptosis via a pathway that is independent of Fas. Other research suggested encouraging reparative and fibrotic function of IL-4 in hepatocytes. \u003csup\u003e(6)\u003c/sup\u003e Furthermore, IL-4 serves as an indicator of the TH2 response in ACLF. \u003csup\u003e(30)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWe acknowledge that the limited sample size in our study poses a restriction, yet a significant advantage of this study is that it represents the first assessment of ascitic sCD206 as a potential marker for predicting mortality risk in patients with AD and ACLF, regardless of SBP existence. However, future research is suggested to investigate the influence of SBP on sCD206 levels using a larger group. In addition, our research is one of few studies that investigate IL-4 in ACLF patients and its relation to sCD206 in vivo.\u003c/p\u003e\u003cp\u003e\u003cb\u003eIn summary\u003c/b\u003e, the link between ascitic sCD206 and serum IL-4 levels with AD and ACLF severity, as well as mortality, indicates the crucial role of PM in the progression and outcomes of ACLF. Incorporating macrophage biomarkers [ascitic sCD206 and serum IL-4] into the ACLF and AD scores is proposed to enhance the prognostic and predictive capabilities beyond those of conventional scores.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eSameh A lashen: Methodology; Project administration; review \u0026amp; editing; Software; Supervision.Perihan Salem: Validation; Visualization; Roles/Writing .Esraa Ibrahim: Methodology; Project administration; Resources .Dalia Abd El-Moety: Investigation; Methodology.Walid I. Yousif: Roles/Writing - original draft; and Writing - review \u0026amp;editing and Conceptualization.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSchierwagen R, Gu W, Brieger A, et al. Pathogenetic mechanisms and therapeutic approaches of acute-to-chronic liver failure. Am J Physiol Physiol 2023; 325: C129–40.\u003c/li\u003e\n\u003cli\u003eWong F. Innovative approaches to the management of ascites in cirrhosis. JHEP Rep 2023; 5: 100749.\u003c/li\u003e\n\u003cli\u003eWen Y, Lambrecht J, Ju C, et al. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol Immunol 2021; 18: 45–56.\u003c/li\u003e\n\u003cli\u003eWang C, Ma C, Gong L, et al. Macrophage Polarization and Its Role in Liver Disease. Front Immunol 2021; 12: 803037.\u003c/li\u003e\n\u003cli\u003eStengel S, Quickert S, Lutz P, et al. Peritoneal Level of CD206 Associates With Mortality and an Inflammatory Macrophage Phenotype in Patients With Decompensated Cirrhosis and Spontaneous Bacterial Peritonitis. Gastroenterol 2020; 158: 1745–61.\u003c/li\u003e\n\u003cli\u003eLynch R, Hawley C, Bain C, et al. Role of exogenous interleukin 4 in the dynamics of acute liver injury. Lancet 2017; 389: S64.\u003c/li\u003e\n\u003cli\u003eTsuchiya K, Suzuki Y, Yoshimura K, et al. Author Correction: Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-acquired Pneumonia. Sci Rep 2020; 10: 3324.\u003c/li\u003e\n\u003cli\u003eNielsen MC, Hvidbjerg Gantzel R, Clària J, et al. Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 2020; 9: 1175.\u003c/li\u003e\n\u003cli\u003eOssen L, Vesterhus M, Hov JR, et al. Circulating Macrophage Activation Markers Predict Transplant-Free Survival in Patients With Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2021;12 :e00315.\u003c/li\u003e\n\u003cli\u003eEl Ray A, Fouad R, ElMakhzangy H, et al. Characterizing a cohort of Egyptian patients with acute-on-chronic liver failure. Eur J Gastroenterol Hepatol 2021;33:1023-28.\u003c/li\u003e\n\u003cli\u003eZaccherini G, Weiss E, Moreau R. Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment. JHEP Rep 2020; 3:100176.\u003c/li\u003e\n\u003cli\u003eRashed E, Soldera J. CLIF-SOFA and CLIF-C scores for the prognostication of acute-on-chronic liver failure and acute decompensation of cirrhosis: A systematic review. World J Hepatol 2022 ;14 :2025–43.\u003c/li\u003e\n\u003cli\u003eMartin-Mateos R, Alvarez-Mon M, Albillos A. Dysfunctional Immune Response in Acute-on-Chronic Liver Failure: It Takes Two to Tango. Front Immunol 2019; 10: 973.\u003c/li\u003e\n\u003cli\u003eChen S, Saeed AFUH, Liu Q, et al. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 2023;8:1–35.\u003c/li\u003e\n\u003cli\u003eLi L, Cheng Y, Emrich S, et al. Activation of endothelial cells by extracellular vesicles derived from Mycobacterium tuberculosis-infected macrophages or mice. PLoS One 2018; 13: e0198337.\u003c/li\u003e\n\u003cli\u003eRødgaard-Hansen S, Rafique A, Christensen PA, et al. A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness. Clin Chem Lab Med 2014; 52: 453–61.\u003c/li\u003e\n\u003cli\u003eGrønbæk H, Gantzel RH, Laursen TL, et al. Macrophage markers and innate immunity in cirrhosis. J Hepatol 2020; 73:1586–8.\u003c/li\u003e\n\u003cli\u003eGrønbæk H, Rødgaard-Hansen S, Aagaard NK, et al. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute-on-chronic liver failure (ACLF). J Hepatol 2016; 64: 813–22.\u003c/li\u003e\n\u003cli\u003eKhorami SHH, Nejatollahi F, Davarpanah MA. Serum Levels of Interleukin-4, Interleukin-10 and Interferon-γ in Patients with Chronic Hepatitis B Infection. Hepat Mon 2018; 18: e60377.\u003c/li\u003e\n\u003cli\u003eRainer F, Horvath A, Sandahl TD, et al. Soluble CD163 and soluble mannose receptors predict survival and decompensation in patients with liver cirrhosis and correlate with gut permeability and bacterial translocation. Aliment Pharmacol Ther 2018; 47: 657–64.\u003c/li\u003e\n\u003cli\u003eOrntoft NW, Blé M, Baiges A, et al. Divergences in Macrophage Activation Markers Soluble CD163 and Mannose Receptor in Patients With Non-cirrhotic and Cirrhotic Portal Hypertension. Front Physiol 2021; 12:649668.\u003c/li\u003e\n\u003cli\u003eLi TP, Guan SH, Wang Q, et al. Soluble mannose receptor as a predictor of prognosis of hepatitis B virus-related acute-on-chronic liver failure. World J Gastroenterol 2019;25:5667–75.\u003c/li\u003e\n\u003cli\u003evan der Zande HJP, Nitsche D, Schlautmann L, et al. The Mannose Receptor: From Endocytic Receptor and Biomarker to Regulator of (Meta)Inflammation. Front Immunol 2021; 12: 765034.\u003c/li\u003e\n\u003cli\u003eNielsen MC, Hvidbjerg Gantzel R, Clària J, et al. Macrophage Activation Markers, CD163 and CD206, in Acute-on-Chronic Liver Failure. Cells 2020; 9: 1175.\u003c/li\u003e\n\u003cli\u003eAhmed AMM, Kadaru AGY, Omer I, et al. Macrophages from Patients with Cirrhotic Ascites Showed Function Alteration of Host Defense Receptor. J Clin Exp Hepatol 2014; 4: 279.\u003c/li\u003e\n\u003cli\u003eTan-Garcia A, Lai F, Sheng Yeong JP, et al. Liver fibrosis and CD206 + macrophage accumulation are suppressed by anti-GM-CSF therapy. JHEP Reports 2020;2 :100062.\u003c/li\u003e\n\u003cli\u003eDang B, Gao Q, Zhang L, et al. The glycolysis/HIF-1α axis defines the inflammatory role of IL-4-primed macrophages. Cell Rep 2023; 42: 112471.\u003c/li\u003e\n\u003cli\u003eLi L, Chen L, Lin F, et al. Study of the Expression of Inflammatory Factors IL-4, IL-6, IL-10, and IL-17 in Liver Failure Complicated by Coagulation Dysfunction and Sepsis. J Inflamm Res 2021 ;14:1447.\u003c/li\u003e\n\u003cli\u003eCheng Y, Tian Y, Xia J, et al. The role of PTEN in the regulation of hepatic macrophage activation and function in the progression and reversal of liver fibrosis. Toxicol Appl Pharmacol 2017; 317: 51–62.\u003c/li\u003e\n\u003cli\u003eWeiss E, de la Grange P, Defaye M, et al. Characterization of Blood Immune Cells in Patients With Decompensated Cirrhosis Including ACLF. Front Immunol 2021; 11:619039.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Liver cirrhosis, CD206, Interleukin-4, Acute decompensation, Acute on chronic liver failure (ACLF)","lastPublishedDoi":"10.21203/rs.3.rs-7049789/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7049789/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u0026amp; Aim\u003c/strong\u003e: Acute-on-chronic liver failure (ACLF) is the most severe form of acute decompensation (AD) with intense systemic inflammation and immune dysfunction. IL-4 polarizes macrophages toward the M2 phenotype. CD206 can identify inflammatory peritoneal macrophages in cirrhotic patients and could be linked to prognosis in ACLF. We investigated the predictive value of serum IL-4 and ascitic sCD206 in patients with AD and ACLF and their relation to morbidity and early mortality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and Methods\u003c/strong\u003e: We included 60 patients with ACLF and AD as well as 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 3 months. Blood samples were analyzed at admission for liver and renal function tests as well as serum IL-4 and ascitic soluble CD206 levels. Correlation with liver function indicators and prognosis was assessed.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: IL-4 and CD206 were significantly higher in AD and ACLF patients compared to control and were positively correlated with each other’s Child-Pugh score, MELD-Na, and ACLF severity scores. Multivariate regression showed that baseline Child-Pugh score, ascitic sCD206, and serum IL-4 level are the only independent predictors of one-month as well as 3-month mortality.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Serum IL-4 and ascitic sCD206 (macrophage markers) could predict early mortality in AD and ACLF. Incorporation of these markers into the traditional liver disease scores can improve their prognostic/predictive performance.\u003c/p\u003e","manuscriptTitle":"Serum Interleukin-4 and Ascitic CD206 Predict Mortality in Acute Cirrhosis Decompensation and Acute-on-Chronic Liver Failure","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 07:57:18","doi":"10.21203/rs.3.rs-7049789/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e8c78aab-6b9f-484e-a3c8-2b4e010be2c1","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-12T02:23:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 07:57:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7049789","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7049789","identity":"rs-7049789","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}