Serum troponin is elevated in acute decompensation and acute-on-chronic liver failure and is associated with severity of liver disease and short-term mortality.

BACKGROUND: The role of high sensitive cardiac Troponin (hs-cTn) in patients with liver cirrhosis (LC) and liver-related acute events is not well established. AIM: To assess the prognostic performance of hs-cTn I in acute decompensation (AD) and acute-on-chronic liver failure (ACLF). METHODS: Two cohorts of consecutive patients, a derivation (retrospective) and a validation (prospective), were evaluated and 30-day-mortality was recorded. Hs-cTnI values were measured. Very low hs-cTnΙ (4 ng/L) was considered the cutoff-level. RESULTS: A total of 296 patients with LC [69.3% male, median age 57 (IQR 51-68) years, MELD score 19 (13-25), ACLF (29.4%), AD (48.3%), and without liver-related acute events (22.3%)] were included in the derivation cohort. The 66.2% of total patients had hs-cTnI ≥4 ng/L. Patients with hs-cTnI ≥4 ng/L were older and had more severe LC compared to those with <4ng/L. The multivariate analysis demonstrated that age (p < 0.001) and MELD (p = 0.001) were independent variables associated with elevated hs-cTnI after adjustment for age, sex and hepatic encephalopathy in total patients.When ACLF and AD were analyzed separately, the mortality was higher in patients with hs-cTnI ≥ 4 ng/L compared to lower values (log-rank p = 0.036 and p = 0.019, respectively). In multivariate analysis, MELD (p < 0.001) and hs-cTnI ≥4 ng/L (p = 0.032) were independent prognostic factors of mortality in ACLF/AD groups, after adjustment for age and sex. Similar results were obtained from the validation cohort (N = 148). CONCLUSIONS: hs-cTnI levels were higher in patients with severe liver disease. The low cutoff-point of 4 ng/L is accurate in ruling out non-survivors mainly in AD group.

Myostatin in combination with creatine phosphokinase or albumin may differentiate patients with cirrhosis and sarcopenia.

In patients with liver cirrhosis (LC), sarcopenia is correlated with frequent complications and increased mortality. Myostatin, a myokine, is a potential biomarker of skeletal mass and/or sarcopenia. The aim of this study was to examine the association between myostatin and muscle mass and evaluate myostatin as a biomarker of sarcopenia in LC. Skeletal muscle index (SMI) and myosteatosis were evaluated by computed tomography scan. Muscle quantity and quality along with muscle strength and function were used to diagnose sarcopenia. Serum myostatin was measured by ELISA. One hundred and fifteen consecutive patients with LC [72.2% male, median age 59 yr (IQR 52-67), MELD 12 (8-16), 28.7% with compensated LC] were included. Low SMI was diagnosed in 49.6% and sarcopenia in 34.8% (21.7% severe). Myostatin levels were lower in low (P < 0.001) compared with patients with normal SMI and were strongly correlated with SMI in MELD score ≥ 15 (r = 0.571, P < 0.001). Myostatin was also lower in patients with sarcopenia compared with those without (P < 0.001) and even lower in severe sarcopenia (P < 0.001). In multivariate analysis, myostatin, age, and albumin remained significant predictors of low SMI after adjustment for sex, MELD, and creatine phosphokinase (CPK). Similarly, myostatin and age predicted sarcopenia after adjustment for sex, MELD, CPK, and albumin. The ratios log10myostatin-to-CPK or albumin-to-myostatin were found to have acceptable diagnostic accuracy in ruling out sarcopenia in total patients. However, the best diagnostic performance was shown in MELD ≥ 15 (AUROC 0.829 or 0.801, respectively). Myostatin is independently associated with both skeletal muscle mass and sarcopenia. Myostatin in combination with CPK or albumin are good surrogate markers in excluding sarcopenia.NEW & NOTEWORTHY Serum levels of myostatin were significantly lower in cirrhotic patients with impaired skeletal mass index (SMI) and sarcopenia than those without. Serum levels of myostatin have a positive correlation with SMI. Myostatin levels are independently associated with sarcopenia, diagnosed according to the latest criteria, in patients with cirrhosis. Myostatin in combination with creatine phosphokinase or albumin have good accuracy excluding sarcopenia in patients with cirrhosis.

Human beta-defensin-1 is a highly predictive marker of mortality in patients with acute-on-chronic liver failure.

BACKGROUND & AIM: Human beta-defensin-1 (hBD-1) is a natural antimicrobial peptide expressed in the epithelia of multiple tissues including the digestive tract. In the current study, hBD-1 levels were determined in different subsets of patients with decompensated cirrhosis including acute-on-chronic liver failure (ACLF). In addition, the association with mortality of hBD-1, C-reactive protein (CRP) and procalcitonin (PCT) was assessed. METHODS: A total of 125 patients were divided into three groups: 39 with ACLF (derivation cohort), 46 with acute decompensation without ACLF (AD) and 40 with decompensated cirrhosis without an acute event (DC). The data from 24 different ACLF patients were used for validation and 15 healthy individuals as control group. RESULTS: Serum hBD-1, CRP and PCT levels were higher in ACLF compared to both AD and DC groups (P < 0.001). Healthy controls demonstrated similar hBD-1 and PCT values compared to DC group. In ROC curve, the performance of hBD-1 to predict 60-day mortality in ACLF group was similar in derivation and validation cohorts (c-statistic 0.834 and 0.879, respectively). CRP was a poor predictor of mortality. In ACLF group, patients with high hBD-1 (>36.625 ng/mL) had a poor prognosis at 60 days compared to those with lower values (log-rank P = 0.001). In Cox multivariate regression analysis, only hBD-1 (HR 1.020, 95%CI 1.006-1.035, P = 0.006) emerged as an independent predictor of death in ACLF group. In AD group, neither hBD-1 nor PCT or CRP variables were associated with mortality. CONCLUSIONS: High hBD-1 was detected at presentation in patients with ACLF who died during follow-up period. hBD-1 is an accurate predictor of short-term mortality in patients with ACLF.

Evaluation of noninvasive markers for the diagnosis of cystic fibrosis liver disease.

OBJECTIVES: In cystic fibrosis (CF), liver disease (LD) is the third leading cause of mortality. As liver biopsy was considered inconsistent in CFLD diagnosis, a combination of modalities were utilized in the conventional Debray criteria (DC). More recently, noninvasive liver fibrosis biomarkers were applied by Koh et al (New criteria-NC). In the current study, we aimed to evaluate noninvasive biomarkers for the CFLD diagnosis. METHODS: Longitudinal data were collected from a cohort of genetically confirmed CF patients. CFLD was diagnosed by both DC and NC. Apart from transient elastography (TE) > 6.8 kPa, biomarkers incorporated in the NC included AST/ALT-ratio (AAR) ≥ 1, FIB-4 index ≥3.25 and APRI >0.50. RESULTS: 62 patients with CF, [56.5% male, age at enrollment 25 (22-31) years], were prospectively followed-up for 33 (28-36) months. Sixteen (25.8%) and 27 (43.5%) patients met DC and NC, respectively. Twenty-four fulfilling NC had at least one positive biomarker (6 TE, 7 AAR, 6 both TE and AAR, 2 both APRI and AAR and 3 both APRI and TE). Thirteen (48.1%) had diffuse LD/cirrhosis by the NC and all had at least one additional parameter classifying them as CFLD. From the 14 (51.8%) with no-diffuse-LD, 64.3%, 14.3% and 21.4% had 2, 3 and 4 of the necessary modalities incorporated in NC, respectively, confirming their classification as CFLD. TE was 100% specific to rule in CFLD but had a moderate sensitivity. CONCLUSIONS: NC were able to identify 17.7% more CFLD patients compared to DC. The multiple biomarkers incorporated in NC may enhance the ability to detect CFLD.

High serum lipopolysaccharide binding protein is associated with increased mortality in patients with decompensated cirrhosis.

BACKGROUND & AIMS: Lipopolysaccharide-binding-protein (LBP) is an acute-phase-protein produced by hepatocytes. Changes in LBP are associated with the dynamics of bacterial translocation and intestinal permeability in decompensated cirrhosis (DC). We assessed serum and ascitic-fluid (AF) LBP and examined their association with mortality in patients with DC. METHODS: Eighty-eight consecutive patients (73.9% males) underwent thorough diagnostic investigations for infection. LBP (ng/mL) was assessed in serum (N=88) and AF (n=49) by enzyme-linked-immunosorbent-assay and expressed in natural logarithm (ln). RESULTS: Serum lnLBP was higher in 18 patients with overt infection compared to those without (P<.001). Serum and AF lnLBP 13.49 and 12.11 displayed a very good-negative-predictive value of 90% and 95.1% to rule out infection and spontaneous-bacterial-peritonitis (SBP), respectively. LBP was higher in serum than in AF (P<.001). Serum and AF LBP levels showed a positive correlation with surrogate markers of inflammation. Patients without overt infection were prospectively followed up. The 90-day-mortality rate was 48% and 24.4% in patients with high (≥13.49) and low (<13.49) lnLBP, respectively, (log rank P=0.045). In univariate Cox regression analysis, neutrophils, LBP, MELD score and CRP were predictive of mortality. However, only high LBP (HR 8.1 95%CI 2.0-31.5, P=0.003) and MELD (HR 1.1 95%CI 1.0-1.2, P=0.002) were predictive of mortality in multivariate analysis. CONCLUSIONS: Serum and AF LBP concentrations showed a high negative-predictive-value to exclude infection and SBP, respectively. High serum LBP was detected in patients without infection at presentation who died during the 90-day-follow-up period. Elevated serum LBP is a marker of short-term mortality in patients without overt bacterial infection.

Single center validation of mortality scores in patients with acute decompensation of cirrhosis with and without acute-on-chronic liver failure.

OBJECTIVES: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD. METHODS: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter. RESULTS: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p = .974) but a worse, yet adequate, in the ACLF-group at 28 days (p = .08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel's concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh. CONCLUSIONS: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.

Evaluation of neutrophil/leukocyte ratio and organ failure score as predictors of reversibility and survival following an acute-on-chronic liver failure event.

AIM: Acute-on-chronic liver failure (ACLF) is defined as an acute deterioration of liver disease with high mortality in patients with cirrhosis. The early mortality in ACLF is associated with organ failure and high leukocyte count. The time needed to reverse this condition and the factors affecting mortality after the early 30-day-period were evaluated. METHODS: One hundred and ninety-seven consecutive patients with cirrhosis were included. Patients were prospectively followed up for 180 days. RESULTS: ACLF was diagnosed in 54.8% of the patients. Infection was the most common precipitating event in patients with ACLF. On multivariate analysis, only the neutrophil/leukocyte ratio and Chronic Liver Failure Consortium Organ Failure (CLIF-C OF) score were associated with mortality. Hazard ratios for mortality of patients with ACLF compared with those without at different time end-points post-enrollment revealed that the relative risk of death in the ACLF group was 8.54 during the first 30-day period and declined to 1.94 during the second period of observation. The time varying effect of neutrophil/leukocyte ratio and CLIF-C score was negative (1% and 18% decline in the hazard ratio per month) while that of Model for End-Stage Liver Disease (MELD) was positive (3% increase in the hazard ratio per month). CONCLUSION: The condition of ACLF was reversible in patients who survived. During the 30-180-day period following the acute event, the probability of death in ACLF became gradually similar to the non-ACLF group. The impact of inflammatory response and organ failure on survival is powerful during the first 30-day period and weakens thereafter while that of MELD increases.

Soluble CD146, a novel endothelial marker, is related to the severity of liver disease.

OBJECTIVES: Angiogenesis and inflammation have been involved in the progression of fibrosis in patients with chronic liver disease (CLD). Soluble CD146 (sCD146), a biomarker that was recently characterized as a novel component of the endothelial junction is implicated in endothelial proliferation. Our study evaluates the performance of sCD146 in assessing liver fibrosis and cirrhosis, and determines if its levels are related to the severity of liver disease in patients with cirrhosis. MATERIAL AND METHODS: sCD146 levels were determined by a commercially available immunoenzymatic technique in 62 consecutive patients with cirrhosis, 43 patients with CLD and 27 healthy controls. RESULTS: Patients with cirrhosis compared to non-cirrhotics with CLD had a higher median sCD146 concentration (639 vs. 317 ng/ml). In receiver operating characteristic (ROC) curve analysis, the cut-off of 412 ng/ml showed a sensitivity of 78% and a specificity of 75% for diagnosis of cirrhosis, offering good diagnostic accuracy (area under the ROC curve [AUROC: 0.838]). Patients with compensated compared to those with decompensated cirrhosis had a lower median sCD146 concentration (399 vs. 848 ng/ml, respectively). A cut-off of 534 ng/ml offered a sensitivity of 83% and a specificity of 78% for differentiating compensated from decompensated cirrhosis (AUROC: 0.866). Furthermore, in cirrhotics, sCD146 correlated positively with AST, bilirubin levels and most importantly with international normalized ratio and model for end-stage liver disease (r = 0.648, p < 0.001 and r = 0.567, p < 0.001, respectively). CONCLUSION: sCD146 can be used as a surrogate, inexpensive biomarker for the diagnosis of cirrhosis. It is also well correlated with severity of liver disease in cirrhotic patients. Further studies are needed to define its role in clinical practice.

Presence of spur cells as a highly predictive factor of mortality in patients with cirrhosis.

BACKGROUND AND AIM: The presence of spur-cell anemia (SCA) is due to lipid disturbances of the erythrocyte membrane and may develop in patients with advanced liver cirrhosis. The accurate predicting value of SC for survival has not been clarified. The aim of this study was to evaluate SCA as a prognostic indicator in patients with cirrhosis. METHODS: We prospectively evaluated clinical, laboratory parameters, and survival in patients with cirrhosis, with or without SCA, during the period 2008-2011. Patients who had at admission renal failure, other causes of hemolytic anemia, hepatocellular carcinoma, sepsis, and/or active bleeding, were excluded. One hundred sixteen patients with cirrhosis were included. The presence of SCA (SC rate higher or equal to 5% [≥ 5%]) was diagnosed in 36 (31%) patients. RESULTS: Patients with SCA compared to those without had more advanced liver disease (higher Model for End-Stage Liver Disease [MELD], P < 0.001), higher total bilirubin (P < 0.001), and International Normalized Ratio (P < 0.001). Patients with SCA had worse survival (log rank P < 0.001). Survival of patients with SCA at the first, second, and third month of follow-up was 77%, 45%, and 33%, respectively. In multivariate Cox's regression analysis, the presence of SCA was an independent predictor of mortality (hazard ratio = 3.17 [95% CI 1.55-6.48]). CONCLUSIONS: The presence of spur-cell anemia is not uncommon in cirrhosis and seems to be strongly associated with mortality. SCA can be used in combination with MELD as an additional predictor of early mortality.

Evaluation of Five Screening Tools in Detecting Physical Frailty in Cirrhosis and Their Prognostic Role.

Background: Physical frailty (PF) is a syndrome of decreased physical function and reserves, preventing patients from coping with stressful events. PF screening tools in patients with liver cirrhosis (LC) can help evaluate the risk of complications and death. The aim of this study was to assess the performance of five screening tools in detecting PF and their ability to predict 18-month mortality in LC. Methods: The Short Physical Performance Battery (SPPB), Fried frailty phenotype (FFP), Clinical Frailty Scale (CFS) and 6-Minute Walk Test (6MWT) were compared with the Liver Frailty Index (LFI) as the method of reference. Patients with an LFI ≥ 4.5, SPPB ≤ 8, FFP ≥ 3, CFS ≥ 6 points, and those walking <250 m, were considered frail. Results: A total of 109 consecutive patients with stable LC were included [63.3% male, median age 62 years, (IQR 52-70), MELD 9 (7-14.5), 46.8% with decompensated LC (DC)]. PF was present in 23.9%, 27.5%, 41.3%, 13.8%, and 28.4% as assessed by the LFI, SPPB, FFP, CFS, and 6MWT, respectively. Cohen's kappa measurement of agreement of four of the tools with LFI was 0.568, 0.334, 0.439, and 0.502, respectively (p < 0.001 for each). Kaplan-Meier survival curves at 18 months showed higher mortality in frail patients compared to non-frail patients by any method (log rank p < 0.05). In the multivariate models, PF defined by any method emerged as an independent prognostic factor of 18-month mortality after adjustment for age, gender, and MELD-score. Conclusions: Patients characterized as frail by five screening tools were not identical. However, PF defined by either method was proven to be an independent poor prognostic factor for long-term mortality after adjustment for covariates.

Evaluation of parameters influencing the quality of colon preparation with a split-dose regimen of sulfate salts.

Background: Bowel cleansing is an important factor for the quality of colonoscopy. We aimed to evaluate the efficacy of split-dose oral sulfate salts on bowel preparation and to determine parameters influencing the quality of bowel cleaning. Method: Consecutive adults who completed their preparation for colonoscopy with a regimen of sulfate salts were enrolled. Results: Of the 446 patients, 11 were excluded from the analysis. Among the 435 patients, 257 (59.1%) were female, mean age was 62.0±11.6 years and median body mass index (BMI) 26.1 kg/m2 (interquartile range [IQR] 23.8-29.4). Indications for colonoscopy were screening 155 (35.6%), surveillance 102 (23.5%), or other 178 (40.9%). The median time between the end of second dose of the preparation regimen and colonoscopy initiation was 5:15 h (IQR 4:30-6:00, min: 2:20, max: 12:20). Minor adverse events were reported in 62 (14.3%) patients. BBPS=9 was observed in 279 (64.14%) patients. Segmental BBPS=3 was achieved in 387 (88.97%), 346 (79.54%) and 289 (66.44%) patients (P<0.001) in the descending, transverse and ascending colon, respectively. Multivariate analysis revealed that BMI (odds ratio [OR] 1.05, 95% confidence interval [CI] 1-1.1) and time between the end of the second laxative dose and colonoscopy initiation (OR 1.25, 95%CI 1.08-1.45) were associated with poorer bowel preparation. Conclusions: A split dose of oral sulfate salts is an efficacious and well tolerated regimen. Obesity and a longer time interval between the end of the second dose and colonoscopy initiation negatively influence bowel cleanliness.

Serial rotational thromboelastometry measurements show worsening hypocoagulability in acute-on-chronic liver failure and are associated with the severity of liver disease.

Background: Viscoelastic tests are used to better understand the complex picture of hemostasis in cirrhosis. Limited data exist regarding the clinical relevance of rotational thromboelastometry (ROTEM) in acute-on-chronic liver failure (ACLF) or acute decompensation (AD). We examined the pattern and role of sequential observations of 9 ROTEM components in both ACLF and AD groups. Method: ROTEM measurements were compared within and between groups at 3 time points: on admission (T1), at 24 h (T2) and 48 h post-admission (T3). Results: Forty-two consecutive patients (22 ACLF, 20 AD) were included. ROTEM determinants exhibited significant hypocoagulable deterioration in ACLF but not in AD over the 3 time points in clot formation time (CFT)EXTEM (P=0.01), maximum clot firmnessEXTEM (P=0.014), CFTINTEM (P<0.001), and alphaINTEM (P=0.028). The sum of hypocoagulable determinants increased from T1 to T3 in ACLF (P=0.029), but remained stable in AD. Five ROTEM variables showed significant differences towards hypocoagulability in ACLF compared to AD at T3. A "hypocoagulable" profile was associated with more severe liver disease (P<0.001 for model for end-stage liver disease [MELD] or Child-Pugh scores) and higher 30- and 90-day mortality (log-rank P=0.001 and P=0.013, respectively) but no more bleeding episodes or transfusions. Two ROTEM variables displayed strong correlations with MELD at T1 and 7 at T3 (|r coefficient|>0.5). Conclusions: ROTEM measurements indicated worsening hypocoagulability shortly post-admission compared to baseline in ACLF, but remained stable in AD. The hypocoagulable derangement was mostly correlated with the severity of liver disease and higher short-term mortality, but not more bleeding episodes.

A combination of clot formation abnormalities in thromboelastometry has a high prognostic value in patients with acute-on-chronic liver failure.

BACKGROUND: Global coagulation tests offer a better tool to assess procoagulant and anticoagulant pathways, fibrinolysis and clot firmness and evaluate more accurately coagulation defects compared to conventional coagulation tests. Their prognostic role in acute-on-chronic liver disease (ACLF) or acute decompensation (AD) has not been well established. AIMS: To assess the properties and prognostic value of the coagulation profile measured by rotational thromboelastometry (ROTEM) in ACLF and AD. METHODS: 84 consecutive patients (35 ACLF and 49 AD) were prospectively studied. Twenty healthy persons matched for age and gender were used as controls. 'Hypocoagulable' or 'hypercoagulable' profiles on admission were assessed based on nine ROTEM parameters and mortality was recorded at 30 and 90 days. RESULTS: Individual ROTEM parameters denoted significantly more hypocoagulability in patients compared to controls. 'Hypocoagulable' profile (defined as a composite of 4 or more ROTEM parameters outside the range) was associated with more severe liver disease assessed either as MELD or Child-Pugh scores ( P  < 0.001 for both) and higher 30-day mortality (Log-rank P  = 0.012). 'Hypocoagulable' profile (HR 3.160, 95% CI 1.003-9.957, P  = 0.049) and ACLF status (HR 23.786, 95% CI 3.115-181.614, P  = 0.002) were independent predictors of 30-day mortality, in multivariate model. A higher early mortality rate was shown in ACLF patients with 'hypocoagulable' phenotype compared to those without (Log-rank P  = 0.017). 'Hypocoagulable' profile was not associated with mortality in AD. CONCLUSION: 'Hypocoagulable' profile was associated with more advanced liver disease and higher short-term mortality in patients with ACLF.

Mechanisms of sarcopenia in liver cirrhosis and the role of myokines.

Sarcopenia is a syndrome characterized by a decline in skeletal muscle quantity and/or quality, strength and performance, leading to unfortunate events, such as injurious falls or even death. It is not identical to frailty and malnutrition, even though there is a significant overlap among these syndromes. In patients with liver cirrhosis (LC), sarcopenia is classified as secondary and has been associated with increased morbidity and mortality during the pre- and post-transplantation period. It can be a result of malnutrition, hyperammonemia, low physical activity, endocrine abnormalities, accelerated starvation, metabolic disturbances, altered gut function leading to chronic inflammation, and alcohol abuse. Myokines are peptides mainly synthesized by contracting muscle and adipose tissue cells and may play a key role in the pathophysiology of sarcopenia. More than a hundred myokines have been recognized, but only a few have been investigated. They can be classified as negative regulators, such as myostatin, tumor growth factor-ß, activins, growth differentiation factor-11, and positive regulators of muscle growth including follistatin, bone morphogenic proteins, and irisin. So far, only myostatin, follistatin, irisin and decorin have been studied in LC-associated sarcopenia. In this review, we focused on the mechanisms of cirrhosis-related sarcopenia and the role of myokines that have already been studied in the literature, either as markers helping in the diagnostic evaluation of sarcopenia, or as prognostic factors of survival. Standard therapeutic options to prevent or treat sarcopenia in LC are also being reported, as well as the possible therapeutic implication of myokines.

HFA-PEFF score as an independent predictor of 2-year mortality in liver cirrhosis patients.

BACKGROUND AND AIMS: Cardiovascular complications of liver cirrhosis include high cardiac output heart failure with reduced afterload and diastolic dysfunction. Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) (values 0-6) is a diagnostic tool for heart failure. It is a cluster of echocardiographic and biochemical parameters. The purpose of this prospective study was to assess if HFA-PEFF score is associated with the severity of liver disease and to determine its prognostic significance in patients with cirrhosis. METHODS: Patients with cirrhosis without an acute event were enrolled. A comprehensive echocardiography study was conducted, brain natriuretic peptide and N-terminal-pro-B-type Natriuretic Peptide levels were measured and HFA-PEFF score was calculated. All patients were prospectively followed up after enrollment. The study end-point was defined as the composite of all-cause death. RESULTS: Seventy-two consecutive patients [median age 59 years (inter-quartile range: 52-65), 72.2% males, Model for End-stage Liver Disease (MELD) 12.9 (8.5-16.3)] were included. The 52.8% had a high HFA-PEFF score (5 or 6) and the 47.2% intermediate/low score (0-4). HFA-PEFF score was correlated with MELD score (rho = 0.566, P < 0.001), but not with age, SBP and heart rate. The median follow-up was 24.2 (9.5-38.8) months. The 1- and 2-year cumulative mortality was higher in patients with high HFA-PEFF compared to those with intermediate/low (log-rank P < 0.001 for both). The predicted 2-year probability of survival in high vs intermediate/low HFA-PEFF was found to be a prognostic factor of death even when adjusted for age, gender and MELD score [hazard ratio = 3.539 (1.134-11.046), P = 0.029]. CONCLUSION: HFA-PEFF score is high among patients with liver cirrhosis, especially those with advanced liver disease. HFA-PEFF score is associated with survival even when adjusting for cirrhosis severity.

The Presence of Myosteatosis Is Associated with Age, Severity of Liver Disease and Poor Outcome and May Represent a Prodromal Phase of Sarcopenia in Patients with Liver Cirrhosis.

BACKGROUND/AIMS: Myosteatosis implies impaired muscle quality. The aim of the study was to investigate the association of myosteatosis with other muscle abnormalities and its role in the prognosis of liver cirrhosis (LC). METHOD: Skeletal muscle index (SMI) and myosteatosis were measured by computed tomography. Myosteatosis was defined as muscle radiodensity and evaluated according to dry body mass index (BMI). Median values and interquartile range were used for continuous and count (percentage) for categorical variables. RESULTS: A total of 197 consecutive patients were included (age 61 (IQR 52-68); 67% male; MELD score 11 (interquartile range 7.5-16)). Myosteatosis was identified in 73.6% and sarcopenia in 44.6% of patients. Myosteatosis was positively associated with age (p = 0.024) and Child-Pugh (p = 0.017) and inversely associated with SMI (p = 0.026). Patients with myosteatosis exhibited lower 360-day survival (log-rank p = 0.001) compared to those without it. MELD (p < 0.001) and myosteatosis (p = 0.048) emerged as negative prognostic factors of survival in multivariate model. Individuals combining low muscle strength and impaired muscle quality and quantity displayed more advanced LC, impaired muscle performance, lower BMI (p < 0.001 each) and a three times higher mortality rate compared to those with low muscle quality alone. CONCLUSIONS: The presence of myosteatosis was associated with advanced age, low skeletal mass and more severe LC. Myosteatosis was associated with poor prognosis and may represent a prodromal phase of muscle degeneration before the development of sarcopenia.

Modern diagnostic approaches to cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a very aggressive tumor with poor survival. Therefore, early diagnosis and surgical resection are of paramount importance. Its diagnosis is difficult because access to the tumor is not easy. Biopsy is possible only for intrahepatic cholangiocarcinoma, which accounts for 10% of cases. Routine brush cytology from endoscopic retrograde cholangiopancreatography (ERCP) has a high specificity of 100% but unfortunately a low sensitivity of 30%. In this review we briefly describe new diagnostic techniques applicable to ERCP brush cytology specimens and targeting the genetic background of the disease, in particular fluorescence in situ hybridization (FISH) and digital image analysis (DIA). DATA SOURCES: The PubMed database up to 2011 was used for the retrieval of relevant articles. The search terms FISH, fluorescence in situ hybridization, DIA, digital image analysis and cholangiocarcinoma were used. Both original and review articles were used. RESULTS: FISH identifies cells with chromosomal abnormalities, mainly numerical aberrations, using a mixture of fluorescence-labeled probes. FISH offers a higher sensitivity than routine cytology, retaining a high level of specificity. The DIA criterion for malignancy is demonstration of aneuploidy. This technique increases the sensitivity to 40%, but the specificity remains low. Preliminary data from application to other tumors suggest that combination of FISH and DIA may be of further benefit. CONCLUSIONS: The new techniques offer a significantly enhanced diagnostic efficacy in the evaluation of ERCP brush specimens. Apart from contributing to a more timely diagnosis, their wider application to cholangiocarcinoma may also facilitate the genetic study of the disease and add to our understanding of oncogenesis at the molecular level, with the prospect of identifying targets for novel therapeutic interventions.