MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival.

MicroRNAs (miRNAs) have remarkable potential as diagnostic and prognostic markers because of their roles in disease pathogenesis. miRNAs can be released into the bloodstream, where they are sufficiently stable to be detected noninvasively. Here, we prospectively evaluated serum levels of miR-21, miR-34a, miR-122, miR-181b, and miR-885-5p in patients with stable cirrhosis. Total RNA was extracted from the sera of patients with cirrhosis and healthy individuals, and the expression levels of the target miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction. Serum miRNAs levels were correlated with liver function parameters, etiology, and complications of cirrhosis. Circulating miR-34a, miR-122, and miR-885-5p levels were higher in patients with cirrhosis than in healthy individuals. These miRNAs were positively correlated with alanine aminotransferase and aspartate aminotransferase levels, and the relative expression levels were higher in hepatitis C virus-infected patients and lower in patients with Child-Pugh C cirrhosis. miR-122 and miR-885-5p levels were also positively correlated with γ-glutamyl transpeptidase concentrations. miR-21 was associated with transplant-free survival in univariate Cox regression analysis and remained independently associated with survival after adjustment for age, Child-Pugh classification, Model for End-stage Liver Disease score, and history of previous decompensation in multivariate Cox regression analysis. These data suggested that miR-34a, miR-122, and miR-885-5p levels may be more related to the inflammatory process and ongoing hepatocyte damage in patients with cirrhosis. Moreover, miR-21 levels were independently associated with shorter transplant-free survival and may be used as a prognostic tool in outpatients with stable cirrhosis.

From stable disease to acute-on-chronic liver failure: Circulating cytokines are related to prognosis in different stages of cirrhosis.

INTRODUCTION: Although both pro- and anti-inflammatory circulating cytokines are known to be elevated in liver cirrhosis, its clinical significance is not completely recognized. Our aim was to evaluate the prognostic significance of circulating cytokines interleukin (IL)-6, IL-17 and IL-10 in different stages of cirrhosis. METHODS: This prospective study included two cohorts: (1) stable cirrhosis attended in the Outpatient Clinic (n=118), and (2) subjects hospitalized for acute decompensation (AD) (n=130). Thirty healthy subjects served as control group. RESULTS: Patients with cirrhosis exhibited higher levels of cytokines as compared to controls. In stable cirrhosis, during a median follow-up of 17months, liver-related events occurred in 26 patients. Higher IL-10 levels and Child-Pugh B/C were independently associated with reduced event-free survival. In AD cohort, death after 90days of follow-up occurred in 39 patients and was independently associated with ascites, higher IL-6 and model for end-stage liver disease. IL-6 levels also showed higher AUROC than CRP for predicting bacterial infection in the AD cohort (0.831±0.043vs. 0.763±0.048, respectively). IL-17 decreased at third day of hospitalization only in patients who progressed to death. Higher IL-6 levels were observed in acute-on-chronic liver failure (ACLF) patients even in the absence of bacterial infection whereas IL-10 was higher only in subjects with infection-related ACLF. Higher IL-10 and IL-17 levels were associated with progression to death in ACLF. CONCLUSIONS: The pattern of immune response seems to vary according to the phase of cirrhosis and is related to prognosis, from stable disease to ACLF.

Prognostic significance of insulin-like growth factor-I serum levels in acute decompensation of cirrhosis.

CONTEXT: IGF-I serum levels are suppressed in cirrhosis, but its prognostic significance is unknown. OBJECTIVES: To investigate the prognostic value of IGF-I in patients admitted for acute decompensation of cirrhosis. MATERIALS AND METHODS: Cohort study that included 103 patients. IGF-I was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Ninety-day mortality was 26.2% and it was independently associated with MELD, age and IGF-I. The Kaplan-Meier survival probability at 90 days was 94.3% in patients with IGF-I ≥13 ng/mL and 63.2% for patients with IGF-I <13 ng/mL (p = .001). DISCUSSION AND CONCLUSION: IGF-I levels are independently associated with mortality in acute decompensation of cirrhosis.

Enterococcus casseliflavus and Enterococcus gallinarum as causative agents of spontaneous bacterial peritonitis.

Infection by multidrug resistant bacteria is arousing as a relevant issue among hospitalized subjects and is of particular interest in patients with cirrhosis given the frequent use of broad spectrum antibiotics and their altered immune response. We report the first case report of spontaneous bacterial peritonitis (SBP) caused by Enterococcus casseliflavus and the sixth case of SBP caused by Enterococcus gallinarum.

The performance of prognostic models as predictors of mortality in patients with acute decompensation of cirrhosis.

BACKGROUND: Although several prognostic models have been proposed for cirrhotic patients listed for transplantation, the performance of these scores as predictors of mortality in patients admitted for acute decompensation of cirrhosis has not been satisfactorily investigated. AIMS: To study MELD, MELD-Na, MESO, iMELD, Refit-MELD and Refit MELD-Na models as prognostic predictors in cirrhotic patients admitted for acute decompensation, and to compare their performance between admission and 48 hours of hospitalization to predict in-hospital mortality. MATERIAL AND METHODS: This cohort study included cirrhotic patients admitted to hospital due to complications of the disease. Individuals were evaluated on admission and after 48 h of hospitalization, and mortality was evaluated during the present admission. RESULTS: One hundred and twenty-three subjects with a mean age of 54.26 ± 10.79 years were included; 76.4% were male. Mean MELD score was 16.43 ± 7.08 and 52.0% of patients were Child-Pugh C. Twenty-seven patients (22.0%) died during hospitalization. Similar areas under the curve (AUROCs) for prognosis of mortality were observed when different models were compared on admission (P > 0.05) and after 48 h of hospitalization (P > 0.05). When models executed after 48 h of hospitalization were compared to their corresponding model calculated on admission, significantly higher AUROCs were obtained for all models (P < 0.05), except for MELD-Na (P = 0.075) and iMELD (P = 0.119). CONCLUSION: The studied models showed similar accuracy as predictors of in-hospital mortality in cirrhotic patients admitted for acute decompensation. However, the performance of these models was significantly better when applied 48 h after admission when compared to their calculation on admission.

Factors associated with 25-hydroxyvitamin D levels in patients with liver cirrhosis.

INTRODUCTION: Lower 25-hydroxyvitamin D [25(OH)D] levels have been observed in cirrhotic patients and have been related to disease severity. However, most previous studies included patients with very advanced disease, lacking an adequate control for other variables that could interfere with vitamin D levels. We sought to investigate the prevalence of hypovitaminosis D and the factors related to its occurrence. MATERIAL AND METHODS: This cross-sectional study included 133 cirrhotic patients and 30 healthy controls. Bivariate and multivariate analyses were performed to determine factors associated with 25(OH)D levels below the lower tertile. Thirty patients who had been recently hospitalized were compared in two time points. RESULTS: Mean 25(OH)D levels were 32.34 ± 11.38 in controls and 27.03 ± 6.22 ng/mL in patients (P = 0.018). 25(OH)D levels were < 30 ng/mL in 69.9% and < 20 ng/mL in 14.3% of the sample. Levels of 25(OH)D below the lower tertile (< 24 ng/mL) were independently associated with higher triceps skinfold and non-Caucasian race. Parathyroid hormone above the reference value (65 pg/mL) was found in 24.6% of patients without association with 25(OH)D or severity of liver disease. Significantly lower levels of 25(OH)D were found at the time of acute decompensation of cirrhosis. CONCLUSIONS: In conclusion, hypovitaminosis D was prevalent in cirrhotics and it was associated with adiposity and non-Caucasian race in stable patients with relatively well preserved liver function. However, significantly lower levels were observed during admission for acute decompensation suggesting an impact of systemic inflammation or liver dysfunction on 25(OH)D levels.

Acute abdominal perforation as a clinical presentation of coeliac disease.

Intestinal perforation is described in coeliac disease in the setting of refractoriness or Enteropathy-Associated T-cell Lymphoma (EATL). We report the case of a man with untreated coeliac disease who presented intestinal perforation and was diagnosed with EATL over one year later.

Clinical Characteristics of Genuine Acute Autoimmune Hepatitis.

Introduction: Autoimmune hepatitis (AIH) has a spectrum of symptoms ranging from asymptomatic disease to acute severe hepatitis, chronic hepatitis, and decompensated cirrhosis. The acute presentation is not rare and could represent genuine acute AIH (GAAIH) or acute exacerbation of chronic autoimmune hepatitis. We aimed to identify the prevalence, clinical features, and prognostic factors associated with GAAIH and compare these cases with acute exacerbation of chronic AIH. Methods: This cross-sectional observational study evaluated patients with acute AIH presentation, defined as total bilirubin >5 times the upper limit of normality (xULN) and/or alanine aminotransferase >10 xULN, and no prior history of liver disease. Histology findings of acute disease defined GAAIH. Bivariate analyses were performed to identify factors associated with the GAAIH, when compared with acute exacerbation of chronic AIH. Results: Seventy-two patients with acute presentation of AIH were included and six (8.3%) of them presented GAAIH. Comparative analysis between patients with GAAIH and patients with acute exacerbation of chronic AIH revealed that prothrombin activity (96% [74-100] vs. 61% [10-100]; p = 0.003) and albumin levels (3.9 ± 0.2 g/dL vs. 3.4 ± 0.5 g/dL; p < 0.001) were higher in patients with GAAIH. The International Autoimmune Hepatitis Group score was higher in patients with acute exacerbation of chronic AIH (18.5 [8-23] vs. 16.5 [15-17]; p = 0.010). Compared to 15.2% of acute exacerbation of chronic AIH, complete therapeutic response to treatment was achieved in 67.7% of cases with GAAIH (p = 0.018). Conclusions: GAAIH was rare (8.3%), and patients with this presentation exhibited more preserved liver function tests, suggesting that most cases presenting with loss of function are acute exacerbation of chronic AIH. Additionally, patients with GAAIH had a better complete therapeutic response, suggesting a more preserved liver function at presentation, and early diagnosis has a positive therapeutic implication.

Introdução: A hepatite autoimune (HAI) apresenta um espectro de sintomas que varia de doença assintomática a hepatite aguda grave, hepatite crónica e cirrose descompensada. A apresentação aguda não é rara e pode representar hepatite autoimune aguda genuína (HAIAG) ou exacerbação aguda de hepatite autoimune crónica (EAHAIC). O nosso objetivo foi identificar a prevalência, caraterísticas clínicas e fatores prognósticos associados à HAIAG, e comparar esses casos com EAHAIC. Métodos: Estudo observacional, transversal, incluindo doentes com apresentação aguda de HAI, definida como bilirrubina total > 5 vezes o limite superior da normalidade (xLSN) e/ou ALT > 10 xLSN, e sem história prévia de doença hepática. HAIAG foi definida pela presença de achados histológicos de doença aguda. Análises bivariadas foram realizadas para identificar fatores associados à HAIAG, quando comparado com o EAHAIC. Resultados: Foram incluídos setenta e dois doentes com apresentação aguda de HAI, dos quais seis (8.3%) com HAIAG. A análise comparativa entre doentes com HAIAG e doentes com EAHAIC mostrou que a atividade de protrombina (96% (74-100) versus 61% (10-100; p=0.003) e os níveis de albumina (3,9 ± 0,2 g/dL vs. 3,4 ± 0,5 g/dL; p < 0,001) foram significativamente mais elevados em pacientes com HAIAG. O score do Grupo Internacional de Hepatite Autoimune foi mais elevado em doentes com EAHAIC (18.5 (8-23) versus 16.5 (15-17); p=0.010). A resposta terapêutica completa ao tratamento foi alcançada em 66.7% dos casos de HAIAG (vs. 15,2% na EAHAIC, p=0,018). Conclusões: A HAIAG é rara (8.3%), e os doentes com esta apresentação mostraram testes de função hepática mais preservados, sugerindo que a maioria dos casos com perda de função são EAHAIC. Além disso, os doentes com HAIAG tiveram maior taxa de resposta terapêutica completa, sugerindo que uma função hepática mais preservada na apresentação e o diagnóstico precoce tem uma implicação terapêutica positiva.

Acute phase proteins for the diagnosis of bacterial infection and prediction of mortality in acute complications of cirrhosis.

INTRODUCTION: Bacterial infection is a frequent complication in patients with decompensated liver cirrhosis and is related to high mortality rates during follow-up of these individuals. We sought to evaluate the diagnostic value of C-reactive protein (CRP) and procalcitonin (PCT) in diagnosing infection and to investigate the relationship between these biomarkers and mortality after hospital admission. MATERIAL AND METHODS: Prospective study that included cirrhotic patients admitted to the hospital due to complications of the disease. The diagnostic accuracy of CRP and PCT for the diagnosis of infection was evaluated by estimating the sensitivity and specificity and by measuring the area under the receiver operating characteristics curve (AUROC). RESULTS: A total of 64 patients and 81 hospitalizations were analyzed during the study. The mean age was 54.31 ± 11.87 years with male predominance (68.8%). Significantly higher median CRP and PCT levels were observed among infected patients (P < 0.001). The AUROC of CRP and PCT for the diagnosis of infection were 0.835 ± 0.052 and 0.860 ± 0.047, respectively (P = 0.273). CRP levels > 29.5 exhibited sensitivity of 82% and specificity of 81% for the diagnosis of bacterial infection. Similarly, PCT levels > 1.10 showed sensitivity of 67% and specificity of 90%. Significantly higher levels of CRP (P = 0.026) and PCT (P = 0.001) were observed among those who died within three months after admission. CONCLUSION: CRP and PCT were reliable markers of bacterial infection in subjects admitted due to complications of liver cirrhosis and higher levels of these tests are related to short-term mortality in those patients.

IGF-I and IGFBP-3 serum levels in patients hospitalized for complications of liver cirrhosis.

BACKGROUND: IGF-I and IGFBP-3 are part of IGF system and, due to their predominantly hepatic synthesis, they seem to correlate with hepatic dysfunction intensity. AIMS: To investigate the significance of IGF-I and IGFBP-3 in patients with decompensated liver disease. MATERIAL AND METHODS: Cross-sectional study that included cirrhotic patients admitted to hospital due to complications of the disease, in whom IGF-I and IGFBP-3 serum levels were measured by chemiluminescence. RESULTS: Seventy-four subjects with a mean age of 53.1 ± 11.6 years were included in the study, 73% were males. IGF-I levels were positively correlated with IGFBP-3 and albumin, and negatively correlated with Child-Pugh, MELD, creatinine, INR and aPTT ratio. IGFBP-3 levels were positively correlated with IGF-I and albumin, and negatively correlated with Child-Pugh, MELD, creatinine, INR, total bilirubin and aPTT ratio. Significantly lower scores of IGF-I and IGFBP-3 were observed in patients with higher MELD values and higher Child-Pugh classes (P < 0.05). CONCLUSIONS: In cirrhotic patients admitted to hospital due to complications of the disease, IGF-I and IGFBP-3 serum levels were associated with variables related to liver dysfunction and to more advanced liver disease. The levels of these markers seem to undergo little influence from other clinical and laboratory variables, therefore mainly reflecting hepatic functional status.

Fatty liver and celiac disease: Why worry?

Celiac disease (CD) is a chronic inflammatory intestinal disorder mediated by the ingestion of gluten in genetically susceptible individuals. Liver involvement in CD has been widely described, and active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, fatty liver in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. Non-alcoholic fatty liver disease is estimated to affect approximately 25% of the world's adult population and is the world's leading cause of chronic liver disease. In view of both diseases' global significance, and to their correlation, this study reviews the available literature on fatty liver and CD and verifies particularities of the clinical setting.

Celiac disease screening in patients with cryptogenic cirrhosis.

We write a letter to the editor commenting the article "Who to screen and how to screen for celiac disease". We discuss the present literature on cirrhosis and celiac disease (CD) and recommend screening and treating CD in individuals with cryptogenic cirrhosis.

Validation and comparison of simple noninvasive models for the prediction of liver fibrosis in chronic hepatitis C.

INTRODUCTION: Although it is standard procedure in the evaluation of liver diseases, biopsy is an invasive method subject to sampling error and intra or inter-observer variability. Thus, surrogate markers of liver fibrosis have been proposed, with variable availability and accuracy. AIM: Validate and compare the performance of APRI and FIB-4 as predictors of liver fibrosis in HCV patients. MATERIAL AND METHODS: Cross-sectional study including patients with HCV-RNA (+) who underwent liver biopsy. Significant fibrosis was defined as METAVIR stage ≥ 2. The diagnostic performance of the models in predicting significant fibrosis were evaluated and compared by ROC curves. RESULTS: The study included 119 patients, mean age 43.7 ± 10.6 years and 62% males. Significant fibrosis was identified in 41 patients. The AUROCs observed were: APRI = 0.793 ± 0.047, FIB-4 = 0.811 ± 0.045 and AST/ALT = 0.661 ± 0.055 (P = 0.054 for APRI vs. AST/ALT, and P = 0.014 for FIB-4 vs. AST/ALT). Considering classic cutoffs, the PPV and NPV for APRI and FIB-4 were, respectively, 77% and 92% and 83% and 81%. Thirteen (19%) patients were misdiagnosed by APRI and 16 (18%) by FIB-4. By restricting the indication of liver biopsy to patients with intermediate values, it could have been correctly avoided in 47% and 63% of the patients with APRI and FIB-4, respectively. CONCLUSION: The models APRI and FIB-4 were superior to AST/ALT ratio in the diagnosis of significant fibrosis in chronic HCV infection. Even though the overall performance of APRI and FIB-4 was similar, a higher proportion of patients may be correctly classified by FIB-4.

Late-onset systemic lupus erythematosus-associated liver disease.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease, which predominantly affects women under 50 years old. Although liver disease is not included in the diagnostic criteria, abnormal liver tests are common among patients with SLE and, in a significant proportion of those patients, no other underlying condition can be identified. We described a case of liver involvement in late-onset SLE presenting with a predominantly cholestatic pattern. Other conditions associated with abnormal liver tests were excluded, and the patient showed a prompt response to steroid therapy. The spectrum of the liver involvement in SLE is discussed, with emphasis on the differential diagnosis with autoimmune hepatitis.

Elevated calprotectin levels are associated with mortality in patients with acute decompensation of liver cirrhosis.

BACKGROUND: Acute decompensation (AD) of cirrhosis is related to systemic inflammation and elevated circulating cytokines. In this context, biomarkers of inflammation, such as calprotectin, may be of prognostic value. AIM: To evaluate serum calprotectin levels in patients hospitalized for complications of cirrhosis. METHODS: This is a prospective cohort study that included 200 subjects hospitalized for complications of cirrhosis, 20 outpatients with stable cirrhosis, and 20 healthy controls. Serum calprotectin was measured by enzyme-linked immunosorbant assay. RESULTS: Calprotectin levels were higher among groups with cirrhosis when compared to healthy controls. Higher median calprotectin was related to Child-Pugh C, ascites, and hepatic encephalopathy. Higher calprotectin was related to acute-on-chronic liver failure (ACLF) and infection in the bivariate, but not in multivariate analysis. Calprotectin was not associated with survival among patients with ACLF; however, in patients with AD without ACLF, higher calprotectin was associated with a lower 30-d survival, even after adjustment for chronic liver failure-consortium (CLIF-C) AD score. A high-risk group (CLIF-C AD score ≥ 60 and calprotectin ≥ 580 ng/mL) was identified, which had a 30-d survival (27.3%) similar to that of patients with grade 3 ACLF (23.3%). CONCLUSION: Serum calprotectin is associated with prognosis in patients with AD without ACLF and may be useful in clinical practice to early identify patients with a very low short-term survival.

[Epidemiology of hepatitis C virus infection]. / Epidemiologia da infecção pelo vírus da hepatite C.

Hepatitis C is a major cause of chronic liver disease worldwide. There is a significant variation in the prevalence of hepatitis C virus (HCV) infection according to the geographic region studied. These discrepancies reflect not only distinct epidemiological characteristics among the populations, but also differences in the methodologies used for the estimates. Despite scarce data, estimates indicate that Brazil is a country with an intermediate prevalence of HCV infection, ranging from 1% to 2%. The most important risk factors for HCV acquisition include injection drug use, blood product transfusion, organ transplantation, hemodialysis, occupational injury, sexual transmission and vertical transmission. Because there is no vaccine and no post-exposure prophylaxis for HCV, the focus of primary prevention efforts should be identification and removal of the risk factors. In this article we review literature regarding the prevalence of HCV infection, particularly in Brazil. In addition, we discuss the pattern of HCV infection according to the age groups and risk factors for HCV acquisition.

NEUTROPHIL-LYMPHOCYTE RATIO PREDICTS SHORT-TERM MORTALITY IN PATIENTS HOSPITALIZED FOR ACUTE DECOMPENSATION OF CIRRHOSIS.

BACKGROUND: Individuals with cirrhosis have a chronic systemic inflammation associated with an immune dysfunction, affecting the progression of the liver disease. The neutrophil-lymphocyte ratio (NLR) was proposed as a marker of systemic inflammatory response and survival in patients with cirrhosis. OBJECTIVE: Evaluate the prognostic role of NLR in cirrhotic patients and its relation with inflammatory cytokines(IL-6, IL-10 and IL-17). METHODS: In this prospective study two groups were evaluated: 1) Stable cirrhotic in outpatient follow-up (n=193); 2) Hospitalized cirrhotic for acute decompensation for at least 48 hours (n=334) with admission and 48 hours tests evaluation. Circulating inflammatory cytokines were available for 130 hospitalized patients. RESULTS: In outpatients with stable cirrhosis, NLR correlated with MELD score and other variables associated with severity of disease. However, after a median of 32 months of follow up NLR was not associated with mortality (HR 1.058, 95%CI 0.900-1.243; P=0.495). In hospitalized patients, NLR at 48-hour after admission was independently associated with 90-day survival (HR 1.061, 95%CI 1.020-1.103; P=0.003) in multivariate Cox-regression analysis. The 90-day Kaplan-Meier survival probability was 87% for patients with a 48-hour NLR <3.6 and 62% for NLR ≥3.6 (P<0.001). Elevation of NLR in the first 48 hours was also independently associated with mortality (HR 2.038, 95%CI 1295-3207; P=0.002). The 90-day Kaplan-Meier survival probability was 83% when NLR did not increase and 62% when NLR increased (P<0.001). IL-6, IL-10 and IL-17 at admission were positively correlated with both admission and 48-hour NLR. Lower levels of baseline IL-10 were associated with NLR increase during first 48-hour. CONCLUSION: NLR evaluated at 48 hours of hospitalization and its early increase after admission were independently associated with short-term mortality in patients hospitalized for acute decompensation of cirrhosis.

Low sodium to potassium ratio in spot urine sample is associated with progression to acute kidney injury and mortality in hospitalized patients with cirrhosis.

BACKGROUND: sodium to potassium ratio in spot urine sample (Na/Kur) is a surrogate marker of sodium excretion that is recommended for the management of patients with ascites due to cirrhosis. AIMS: to investigate Na/Kur ratio and fractional excretion of sodium (FENa) in patients admitted with decompensated cirrhosis, evaluating its relationship with acute kidney injury (AKI) and prognosis. METHODS: prospective cohort study included 225 adult subjects. Urine samples were obtained within 48 h of hospitalization. RESULTS: AKI at admission was observed in 32.9% of patients and was associated with lower Na/Kur ratio, but not FENa. Among 151 subjects initially without kidney dysfunction, AKI at some point during hospitalization occurred in 26.2% and was independently associated with low Na/Kur ratio at admission. AKI was observed in 44% of the patients with Na/Kur ratio < 1 and only in 8% when values ≥ 2. Na/Kur ratio at admission was independently associated with 30-day mortality, with Kaplan-Meier survival probability of 78.8% for Na/Kur ratio < 1 and 93.6% for values ≥ 1. CONCLUSIONS: low Na/Kur ratio in spot urine sample is associated with progression to AKI and lower short-term survival in patients hospitalized for decompensated cirrhosis.

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis.

BACKGROUND: Macrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF). AIMS: This study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis. METHODS: This prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls. RESULTS: Circulating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002-1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000-1.004, p = 0.041), Child-Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan-Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001). CONCLUSIONS: Higher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.