Stable Decompensated Cirrhosis Research Articles

The Clinical Courses and Prognosis of Cirrhotic Patients after First Acute Decompensation: Prospective Cohort Study.

The European Foundation for the Study of Chronic Liver Failure (EF-CLIF) consortium suggested that the clinical courses after acute decompensation (AD) stratify the long-term prognosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre acute-on-chronic liver failure (pre ACLF), and ACLF. However, previous studies included patients with a history of previous AD and had limitations associated with identifying the clinical factors related to prognosis after the first AD. The prospective Korean Acute-on-Chronic Liver Failure (KACLiF) cohort included cirrhotic patients who were hospitalised with first AD between July 2015 and August 2018. We analysed the factors associated with readmission after the first AD and compared the characteristics and prognosis among each subgroup to evaluate the risk factors for the occurrence of pre ACLF after AD. A total of 746 cirrhotic patients who were hospitalised with first AD were enrolled. The subgroups consisted of SDC (n = 565), UDC (n = 29), pre ACLF (n = 28), and ACLF (n = 124). Of note, pre ACLF showed a poorer prognosis than ACLF. The risk factors associated with readmission within 3 months of first AD were non-variceal gastrointestinal (GI) bleeding, hepatic encephalopathy (HE), and high MELD score. Viral aetiology was associated with the occurrence of pre ACLF compared with alcohol aetiology regardless of baseline liver function status. Cirrhotic patients with first AD who present as non-variceal GI bleeding and HE can easily relapse. Interestingly, the occurrence of AD with organ failure within 3 months of first AD (pre ACLF) has worse prognosis compared with the occurrence of organ failure at first AD (ACLF). In particular, cirrhotic patients with viral hepatitis with/without alcohol consumption showed poor prognosis compared to other aetiologies. Therefore, patients with ACLF after AD within 3 months should be treated more carefully and definitive treatment through LT should be considered.

Predictors of clinical trajectories of patients with acutely decompensated cirrhosis. An external validation of the PREDICT study.

The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre-ACLF, developing acute-on-chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re-admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory. Baseline data, 3-month ACLF and readmission incidence and 1-year survival were analysed in a prospective cohort of patients admitted for AD. A multinomial multivariable model was used to evaluate the association between baseline features and clinical trajectories. Of the 311 patients enrolled, 55% met the criteria for SDC, 18% for UDC and 27% for pre-ACLF, presenting a significantly different 1-year mortality: pre-ACLF 65%, UDC 46%, SDC 21% (p < .001). The presence of hepatic encephalopathy (HE) was associated with UDC (p = .043), while the absence of ascites to SDC (p = .017). Among laboratory parameters, an increase in MELD-Na (p = .001) and C-reactive protein (p = .009) and a decrease in haemoglobin (p = .004) and albumin (p = .008) levels were associated with pre-ACLF. The present study confirms that AD patients have three different clinical trajectories with different mortality rates. Besides the severity of cirrhosis, the association with C-reactive protein supports the predominant role of systemic inflammation in ACLF pathophysiology. Finally, HE is associated with the UDC phenotype highlighting the need for better management of this complication after discharge.

Prognostic assessment of liver cirrhosis and its complications: current concepts and future perspectives.

Liver cirrhosis is an irreversible stage of chronic liver disease with varying clinical course. Acute decompensation of liver cirrhosis represents a watershed in prognosis and is characterized by the occurrence of clinical complications such as ascites, jaundice, hepatic encephalopathy, infections, or portal-hypertensive hemorrhages. Emergent data indicate that an acute decompensation can be subdivided into stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre-acute-on chronic liver failure (pre-ACLF) and acute-on chronic liver failure (ACLF), while the mortality risk varies greatly between the respective subgroups. ACLF is the most severe form of acutely decompensated cirrhosis and characterized by the development of organ failure(s) and a high short-term mortality. Due to the dynamic disease course of acute decompensation, it is paramount to detect patients at particular risk for severe complications those at high risk for developing ACLF as early as possible in order to initiate optimal management. This review describes new concepts and perspectives in the definition and classification of decompensated cirrhosis and provides on overview on emerging predictive scoring systems, non-invasive measurement methods and new biomarkers, which allow an early identification of patients with acute decompensation at risk.

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

Role of precipitants in transition of acute decompensation to acute-on-chronic liver failure in patients with HBV-related cirrhosis

Background & AimsPre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis.MethodsIn total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected.ResultsAmong 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95.ConclusionsThree distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant–systemic inflammation–organ injury framework could be a useful tool for predicting ACLF occurrence.Clinical trial numberNCT02457637 and NCT03641872.Lay summaryIt was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).

Cardiac reserve and response to terlipressin in decompensated cirrhosis patients for prediction of development of AKI and mortality: A prospective cohort study

Background and Aim: Cirrhosis patients have limited cardiac reserve. Terlipressin alters the cardiac function and hyperdynamic circulation in cirrhosis patients. We investigated cardiac reserve, influence of terlipressin and its impact on clinical outcomes on patients with acute decompensated (AD) as compared to stable decompensated (SD) cirrhosis.

An exploratory study of ascitic fluid lactate as prognostic factor of mortality in cirrhotic patients with spontaneous bacterial peritonitis.

The diagnostic value of ascitic fluid lactate (AF lactate) was previously evaluated in spontaneous bacterial peritonitis (SBP) but its prognostic value was not established. To assess the prognostic value of AF lactate in SBP. We prospectively studied 63 consecutive patients with SBP. Fifty patients with acute-on-chronic liver failure (ACLF) or acute decompensation (AD) (ACLF/AD group) without SBP and 30 with stable decompensated cirrhosis (DC) were included as controls. In SBP, mortality was recorded at 30, 90 and 180 days. Arterial and AF lactate were significantly higher in SBP compared to other groups. Analyzing the SBP group alone, AF lactate accurately differentiated survivors from nonsurvivors in all time points. The prognostic performance of AF lactate was improved over time, with the area under the receiver operating characteristic computed at 0.894, 0.927 and 0.934 at 30, 90 and 180 days, respectively. The cutoff level of 2 mmol/L was associated with 100, 100 and 94.7% sensitivity, 57.9, 73.3 and 80% specificity, 61, 80.5 and 87.8% positive predictive value and 100, 100 and 90.9% negative predictive value, respectively. Arterial lactate, neutrophil-to-lymphocyte ratio (NLR) and Model for End-Stage Liver Disease (MELD) score predicted outcomes less accurately than AF lactate. Patients with AF lactate >2 mmol/L had a worse prognosis compared to patients with ≤2 mmol/L (log-rank P < 0.001). No case with AF lactate ≤2 mmol/L died within 90 days postSBP diagnosis. In Cox multivariate analysis at all time points, only AF lactate and NLR were independent predictors of mortality. An AF lactate level of 2 mmol/L has a high ability to differentiate survivors from nonsurvivors in the first 180 days postSBP. Its prognostic value outperformed arterial-lactate, NLR and MELD.

Decreasing von Willebrand Factor Levels Upon Nonselective Beta Blocker Therapy Indicate a Decreased Risk of Further Decompensation, Acute-on-chronic Liver Failure, and Death

Nonselective beta blockers (NSBBs) exert beneficial effects beyond lowering hepatic venous pressure gradient (HVPG), which may be particularly relevant in patients with decompensated cirrhosis (DC), in whom bacterial translocation and bacterial-induced systemic inflammation drive the development of complications such as acute-on-chronic liver failure (ACLF). We evaluated whether NSBB-related changes in von Willebrand factor (VWF) may serve as a biomarker for these effects. In this retrospective analysis, 159 prospectively characterized patients with clinically stable DC (ie, without acute decompensation) who underwent paired HVPG/VWF assessments before/on NSBB therapy were classified as 'VWF-responders' (as defined by a ≥5% decrease in VWF) versus 'VWF-non-responders.' There were no major differences in baseline characteristics between VWF-responders (61%) and VWF-non-responders. VWF-responders showed more pronounced decreases in inflammation (procalcitonin), whereas rates of HVPG-response were similar. In line, NSBB-related changes in VWF correlated with the dynamics of bacterial translocation/inflammation (lipopolysaccharide-binding protein, C-reactive protein, and procalcitonin), rather than those of HVPG. Interestingly, VWF-responders also showed less pronounced NSBB-related decreases in mean arterial pressure, suggesting an amelioration of systemic vasodilatation. Finally, VWF-response was associated with decreased risks of further decompensation (adjusted hazard ratio [aHR], 0.555; 95% confidence interval [CI], 0.337-0.912; P= .020), ACLF (aHR, 0.302; 95% CI, 0.126-0.721; P= .007), and liver-related death (aHR, 0.332; 95% CI, 0.179-0.616; P < .001) in Cox regression models adjusted for prognostic factors including changes in HVPG. Decreases in VWF upon NSBB therapy reflect their anti-inflammatory activity, are accompanied by less pronounced adverse effects on systemic hemodynamics, and are independently associated with a decreased risk of further decompensation, ACLF, and death. VWF-response may discriminate between decompensated patients who benefit from NSBB treatment and have a favorable prognosis versus patients with poor outcomes.

Assessment of biventricular function in patients with hepatopulmonary syndrome.

Cardiac function impairment in the setting of hepatopulmonary syndrome (HPS) in patients with end stage liver disease remains an issue of debate. The current study evaluated possible correlations between HPS and biventricular systolic function in patients with decompensated cirrhosis. Consecutive liver transplantation candidates with stable decompensated cirrhosis were prospectively evaluated. HPS was defined as the presence of an elevated alveolar-arterial oxygen gradient and intrapulmonary vasodilatation, detected by contrast enhanced echocardiography. HPS severity was determined based on arterial blood oxygen pressure values, while shunt size was assessed with a semi-quantitative method. Demographic, clinical and laboratory parameters were also prospectively collected. In total, 130 patients (mean age 56.5, M/F: 94/36, MELD score 14.6 ± 5.6) were enrolled, of whom 45 (34.6%) fulfilled the criteria for HPS diagnosis (mild: 57.7%, moderate: 33.3%, severe 4.4% and very severe 4.4%). Significantly lower absolute left ventricular (LV) global longitudinal strain (GLS) values (- 21.6 ± 2.3 vs. - 22.6 ± 2.5%, p = 0.041) were measured in patients with HPS compared to cirrhotic patients without HPS, while there was no statistically significant difference regarding right ventricular GLS (- 22.1 ± 3.3 vs. - 23.2 ± 3.5%, p = 0.061) between the two groups. Lower LV ejection fraction values were also recorded in the HPS group (53.9 ± 3.5 vs. 56.3 ± 4.5%, p < 0.01). No other echocardiographic parameter was correlated to HPS. Intrapulmonary shunt grading was correlated to HPS classification (χ2 = 19.8, p < 0.01), with lower arterial oxygen values being recorded in higher stages of intrapulmonary shunt. In patients with cirrhosis, the presence of HPS is associated with worse LV contractile performance.

Patterns of acute decompensation in hospitalized patients with cirrhosis and course of acute‐on‐chronic liver failure

IntroductionRecently, based on data from the PREDICT study, the European Foundation for the Study of Chronic Liver Failure (EF‐CLIF) consortium proposed pathophysiological/prognostic groups in hospitalized patients with cirrhosis: stable decompensated cirrhosis (SDC), unstable decompensated cirrhosis (UDC), pre‐acute‐on‐chronic liver failure (pre‐ACLF), and ACLF. We evaluated the outcomes of these subgroups in a real‐life cohort of hospitalized patients with cirrhosis.MethodsPatients with cirrhosis developing first AD between 09/2010 and 12/2017 at the Vienna General Hospital were evaluated for this retrospective analysis.ResultsTwo hundred and ten patients with cirrhosis (aged 57.6 ± 11.8 years) including n = 45 (21.4%) SDC, n = 100 (47.6%) UDC, n = 28 (13.3%) pre‐ACLF, and n = 37 (17.6%) with ACLF were considered. The proposed AD subgroups discriminated between patients with favorable (1‐year mortality: SDC: 6.7% and UDC: 19.6%) and dismal prognosis (90‐day mortality: pre‐ACLF: 42.9%). Interestingly, systemic inflammation gradually increased (e.g., C‐reactive protein, SDC: 0.9 mg/dl, vs. UDC: 2.0 mg/dl vs. pre‐ACLF: 3.2 mg/dl, p < 0.001) while renal function was progressively deteriorating (creatinine levels, SDC: 0.8 mg/dl vs. UDC: 0.9 mg/dl vs. pre‐ACLF: 1.2 mg/dl, p < 0.001) across prognostic subgroups in patients with cirrhosis.DiscussionThe recently proposed pathophysiological/prognostic EF‐CLIF subgroups are also reproduceable in a real‐life cohort of cirrhotic patients. As ACLF is a common and important complication, patients at risk of pre‐ACLF at index AD should be evaluated and if disease proceeds, been treated early and aggressively to avoid excessive mortality.

New prognostic score based on galectin-3 has similar performance to model for end-stage liver disease and sodium score in patients with stable decompensated cirrhosis.

BackgroundGalectin-3 (gal-3) has been proposed as a marker of established renal impairment, with predictive value in stable decompensated cirrhosis.Methods150 stable decompensated patients were assessed in 2 transplant centers. Patients’ renal function was assessed using 51Chromium-EDTA (“true” glomerular filtration rate). We measured basic laboratory variables and gal-3 in serum samples. Factors associated with patients’ outcomes were determined.ResultsOur patients were followed up for 12 months (range 1-48, interquartile range [IQR] 6, 95% confidence interval [CI] 10-13.5) and their mean prognostic scores were Child-Turcotte-Pugh (CTP) 7±2 and model for end-stage liver disease and sodium (MELD-Na) 15±6. Median gal-3 levels were 22 ng/mL. In a multivariate analysis of 94 patients (training group), gal-3 (hazard ratio [HR] 1.026, 95% confidence interval [CI] 1.011-1.041; P=0.003) and serum sodium (HR 1.032, 95%CI 1.006-1.062; P=0.05) were the only factors independently associated with patients’ outcomes. Kaplan-Meier analysis using the median gal-3 values revealed different times of survival (log-rank P=0.006). We derived a new prognostic score, (0.026) × serum gal-3+ (-0.079) × serum sodium, with very good discriminative accuracy for the outcome (area under the curve [AUC] 0.71, 95%CI 0.63-0.88), similar to that of the MELD-Na score (AUC 0.69, 95%CI 0.67-0.89; P=0.73), while its diagnostic accuracy was validated in the remaining 56 decompensated patients (AUC 0.81, 95%CI 0.65-0.97).ConclusionsGal-3 proved to be an accurate and plausible biomarker of renal dysfunction in patients with decompensated cirrhosis. A new prognostic model incorporating gal-3 and sodium was derived, with very good discriminative accuracy for the outcome.

From the Editor's Desk...

In the PREDICT study, a European, prospective, observational study, Trebicka et al. aim to characterize the clinical course of acute decompensation (AD) of cirrhosis in 1,071 patients. Three groups of patients were identified: patients with pre-acute-on-chronic liver failure (ACLF), who developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively; patients with unstable decompensated cirrhosis who did not develop ACLF but required ≥1 hospital readmission, and had mortality rates of 21.0% and 35.6%, respectively; patients with stable decompensated cirrhosis who neither developed ACLF nor were readmitted, and had a 1-year mortality rate of only 9.5%.

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n= 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n= 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n= 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. CLINICALTRIALS. NCT03056612. Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk.

The significance of C-reactive protein to albumin ratio in patients with decompensated cirrhosis.

BackgroundPrognostic indicators in patients with decompensated cirrhosis are vital for the estimation of death risk. The ratio of C-reactive protein to albumin (CAR) has been verified as a prognostic marker in patients with hepatocellular carcinoma and decompensated cirrhosis related to hepatitis B virus. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and gamma globulins have been separately studied in cirrhosis. We evaluated the predictive role of CAR and other inflammatory markers in decompensated patients.MethodsWe prospectively studied 159 patients with stable decompensated cirrhosis, calculating the following indexes: CAR, NLR, LMR, Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD).ResultsMELD (area under the curve [AUC] 0.814) and CTP score (AUC 0.752) were superior to the other markers above in predicting patients’ mortality (P<0.05). Patients with CAR<2.17 (median value) presented better times of survival: 20 months (12-27) vs. 14 months (10-17) (log rank P=0.015). NLR and LMR barely discriminated patients’ prognosis. In multivariate analysis, only MELD and CTP scores were significant risk factors, whether using the proposed cutoff of 1.3 (hazard ratio [HR] 1.17 [1.106-2.44], P<0.001) or the median 2.17 CAR categorical variable (HR 1.17 [1.104-1.243], P<0.001). When patients who underwent liver transplantation were excluded, apart from the MELD and CTP scores CAR 2.17 was the only significant factor associated with the outcome (HR 3.61 [0.96-13.6], P=0.05) and detected different survival times: 10 (1-48) vs. 11 (2-38) months, log rank P=0.003. Patients with LMR≥1.9 presented significantly better renal function, in terms of true glomerular filtration rate (80±34 vs. 64±33 mL/min, P=0.004) and creatinine levels: 0.84 (0.1-1.8) vs. 0.98 (0.59-3.3) mg/dL (P=0.001).ConclusionOur findings demonstrate the significance of CAR and LMR in the outcome and renal function of decompensated patients.

Galectin-3 is associated with glomerular filtration rate and outcome in patients with stable decompensated cirrhosis

BackgroundNewly introduced galectin-3 (gal-3) has been associated to impaired renal function. Gal-3 may become prognostic biomarker in hepatic diseases. AimTo investigate the association of gal-3 with prognosis and renal function in patients with stable decompensated cirrhosis. MethodWe studied prospectively 100 stable decompensated patients in our Department between 2010 and 2017. We measured gal-3 in serum samples. Patients’ renal function was assessed using 51Chromium-EDTA (“true GFR”). ResultsSeventy patients (70%) survived and 30 died (n = 16) or underwent LT (n = 14). Twenty nine patients (29%) had normal gal-3, 71 (71%) had ≥11.7 ng/mL; they differed significantly regarding mean “true”-GFR: 90 ± 20 mL/min vs. 76 ± 26 mL/min, p = 0.03 and mean creatinine: 0.83 ± 0.14 mg/dL vs. 0.97 ± 0.4 mg/dL, p = 0.05. Median gal-3 levels were 17.5 ng/mL (range 4.9–76.5 ng/mL); 49 patients with gal-3 ≥17.5 ng/mL had significantly higher MELD score, (15 ± 5 vs. 13 ± 4, p = 0.02) and worse “true” GFR (74 vs. 85 mL/min, p = 0.04). Gal-3 had good performance in predicting “true”-GFR < 60 mL/min; AUC: 0.71, 95%CI [0.58–0.85], best cut off value 17.5 ng/mL. Kaplan–Meier analysis, using median gal-3 (17.5 ng/mL) revealed different survival time for our patients (log-rank p = 0.04). ConclusionGal-3 proved trustworthy marker of established chronic kidney disease, with predictive ability in stable decompensated cirrhosis. Gal-3 came also a significant factor for our patients’ outcome.

ALBI and PALBI Grades Are Associated with the Outcome of Patients with Stable Decompensated Cirrhosis

Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC.Aim. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality / liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases.Material and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome.Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p < 0.001 and HR: 2.06, 95%CI [1.47, 2.9], p < 0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621,0.744], respectively). ALBI and PALBI performed better than CTP score (p = 0.0044 and p = 0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complicationsConclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosis

ALBI and PALBI Grades Are Associated with the Outcome of Patients with Stable Decompensated Cirrhosis

Introduction and aim. Studies carried out mainly in patients with hepatocellular carcinoma (HCC), have shown the prognostic significance of albumin-bilirubin (ALBI) grade. Recently, another predictive score incorporating platelet count into ALBI, PALBI grade, was introduced in patients with HCC. Aim of the study. We evaluated the ability of ALBI and PALBI grades in predicting the outcome (mortality/ liver transplantation) of patients with stable decompensated cirrhosis with various etiology of liver diseases. Materials and methods. We prospectively studied 325 patients with stable decompensated cirrhosis awaiting liver transplantation. Their clinical and laboratory characteristics were recorded including albumin, bilirubin levels, platelets. We estimated ALBI and PALBI grades for every patient. Conventional prognostic scores were also evaluated; Child-Pugh (CTP), Model for End stage Liver Disease (MELD). We followed them up and recorded their outcome. Results. Beyond MELD and CTP, ALBI and PALBI grades proved significant factors associated with the outcome (HR: 2.13, 95%CI [1.59, 2.85], p&lt;0.001 and HR: 2.06, 95%CI [1.47, 2.9], p&lt;0.001, respectively), and their predictive capability was established (ROC analysis; AUC: 0.695, 95% CI [0.634, 0.755] and AUC: 0.683, 95% CI [0.621, 0.744], respectively). ALBI and PALBI performed better than CTP score (p=0.0044 and p=0.014, respectively). Categorization of our patients into three ALBI groups detected statistically different survival times. Accordingly, PALBI grade 3 compared to those with PALBI grade 1 and 2 patients, had worse outcome and significantly higher frequency of cirrhosis-related complications. Conclusions. ALBI and PALBI grades were validated and can be used to predict the outcome in patients with stable decompensated cirrhosis.

Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis

BackgroundThe clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. AimExplore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. Material and methodsPatients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFa) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 |ig corticotropin. Results113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 ng/dL and 22.7 ng/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/ L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] ConclusionsThe presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

High serum ferritin is associated with worse outcome of patients with decompensated cirrhosis.

BackgroundStudies in patients with decompensated cirrhosis showed a correlation between serum ferritin levels and patients’ prognosis. Besides, red blood cell distribution width (RDW) and mean platelet volume (MPV) have been associated with the severity of hepatic function. The aim of this study was to evaluate the prognostic impact of serum ferritin and RDW/MPV in the outcome [survival, death, or liver transplantation (LT)] of patients with stable decompensated cirrhosis.MethodsConsecutive adult patients with stable decompensated cirrhosis admitted to our department between September 2010 and February 2016 were included. Serum ferritin, RDW and MPV were recorded in every patient. They were followed up and their outcome (alive, death, or LT) was evaluated.Results192 consecutive patients with stable decompensated cirrhosis (142 men, age 54.2±12 years); at the end of follow up [12 (range: 1-64) months] 62 patients remained alive and 130 died or underwent LT. In multivariate analysis, serum ferritin (HR 1.001, 95%CI 1.00-1.002, P=0.005) and GFR (HR 0.96, 95%CI 0.92-0.99, P=0.035) were the only independent factors significantly associated with the outcome. Ferritin had low discriminative ability (AUC: 0.61) to the outcome yielding a sensitivity and specificity of 85.3% and 44.2%, respectively, at the best cut-off point (>55 ng/mL), while patients with ferritin >55 ng/mL (n=145) had a worse outcome compared to those with ferritin ≤55 ng/mL (n=47) (log rank P=0.001). RDW and MPV were not associated with the outcome.ConclusionHigh serum ferritin, but not RDW/MPV, is associated with worse outcome in patients with established decompensated cirrhosis. However, further studies are needed to elucidate better this issue.

Hepatopulmonary syndrome is associated with the presence of hepatocellular carcinoma in patients with decompensated cirrhosis.

BackgroundHepatopulmonary syndrome (HPS) is a relatively common complication in patients with decompensated cirrhosis. Our aim was to evaluate the prevalence of HPS, its clinical impact, and the possible association between HPS and characteristics of patients with decompensated cirrhosis.MethodsPatients with stable decompensated cirrhosis admitted to our department and assessed for HPS were included. For each patient, several clinical, laboratory and echocardiographic parameters as well as renal function were recorded. The severity of liver disease was evaluated according to the Model for End-stage Liver Disease and Child-Pugh scores, and renal function was assessed using 51chromium complexed with ethylene diamine tetracetic acid. In addition, the short synacthen test was performed in each patient to evaluate the adrenal function.ResultsSixty-three patients were enrolled, 26 (41.3%) of whom diagnosed with HPS. In multivariate analysis, the presence of hepatocellular carcinoma [odds ratio (OR) 8.1, 95% confidence interval (CI) 5.3-27.9, P=0.045] and salivary cortisol at T60 (60 min after the intravenous injection of 250 μg corticotropin) (OR 0.88, 95%CI 0.71-0.98, P=0.045) were the factors independently associated with HPS. T60 salivary cortisol had relatively good discriminative ability for the presence of HPS (area under the curve=0.73). The presence of HPS was not associated with the outcome (P=0.22).ConclusionIn our cohort of patients with decompensated cirrhosis, the presence of hepatocellular carcinoma and T60 salivary cortisol were the only factors independently associated with HPS.