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.

Extensively drug-resistant bacteria are an independent predictive factor of mortality in 130 patients with spontaneous bacterial peritonitis or spontaneous bacteremia.

AIM: To evaluate the epidemiology and outcomes of culture-positive spontaneous bacterial peritonitis (SBP) and spontaneous bacteremia (SB) in decompensated cirrhosis. METHODS: We prospectively collected clinical, laboratory characteristics, type of administered antibiotic, susceptibility and resistance of bacteria to antibiotics in one hundred thirty cases (68.5% males) with positive ascitic fluid and/or blood cultures during the period from January 1, 2012 to May 30, 2014. All patients with SBP had polymorphonuclear cell count in ascitic fluid > 250/mm(3). In patients with SB a thorough study did not reveal any other cause of bacteremia. The patients were followed-up for a 30-d period following diagnosis of the infection. The final outcome of the patients was recorded in the end of follow-up and comparison among 3 groups of patients according to the pattern of drug resistance was performed. RESULTS: Gram-positive-cocci (GPC) were found in half of the cases. The most prevalent organisms in a descending order were Escherichia coli (33), Enterococcus spp (30), Streptococcus spp (25), Klebsiella pneumonia (16), S. aureus (8), Pseudomanas aeruginosa (5), other Gram-negative-bacteria (GNB) (11) and anaerobes (2). Overall, 20.8% of isolates were multidrug-resistant (MDR) and 10% extensively drug-resistant (XDR). Health-care-associated (HCA) and/or nosocomial infections were present in 100% of MDR/XDR and in 65.5% of non-DR cases. Meropenem was the empirically prescribed antibiotic in HCA/nosocomial infections showing a drug-resistance rate of 30.7% while third generation cephalosporins of 43.8%. Meropenem was ineffective on both XDR bacteria and Enterococcus faecium (E. faecium). All but one XDR were susceptible to colistin while all GPC (including E. faecium) and the 86% of GNB to tigecycline. Overall 30-d mortality was 37.7% (69.2% for XDR and 34.2% for the rest of the patients) (log rank, P = 0.015). In multivariate analysis, factors adversely affecting outcome included XDR infection (HR = 2.263, 95%CI: 1.005-5.095, P = 0.049), creatinine (HR = 1.125, 95%CI: 1.024-1.236, P = 0.015) and INR (HR =1.553, 95%CI: 1.106-2.180, P = 0.011). CONCLUSION: XDR bacteria are an independent life-threatening factor in SBP/SB. Strategies aiming at restricting antibiotic overuse and rapid identification of the responsible bacteria could help improve survival.

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.

Diastolic myocardial dysfunction does not affect survival in patients with cirrhosis.

Left ventricular diastolic dysfunction (DDF) has been considered as a component of cirrhotic cardiomyopathy. The clinical significance of DDF in cirrhotics has not been clarified. We prospectively evaluated the echocardiographic-Doppler, tissue-Doppler (TDI) findings of left ventricular function and survival in cirrhotics with or without DDF. Seventy-six cirrhotics without endogenous heart disease were included. DDF was diagnosed by mitral inflow Doppler parameters and diastolic myocardial velocities. Assessments of demographics, liver dysfunction, laboratory, echocardiographic systolic/diastolic indices, TDI of mitral annular motion and M-mode echocardiography were recorded. Patients were followed-up for a median of 25 months (15-40). DDF was diagnosed in 51 (67%) patients. Patients with compared with those without DDF had significantly older age and higher pulse rate as well as more frequently severe ascites, greater aortic root diameter and interventricular septal thickness. There was no difference in systolic myocardial function between two groups. Patients with DDF had a trend for worse survival (long rank, P = 0.094). A multivariate analysis showed that age, MELD and sodium but no DDF were predictive of death. DDF is prevalent in advanced cirrhosis and is associated with severe ascites. Systolic myocardial function and mortality do not seem to be strongly affected by the presence of DDF.

Left ventricle enlargement and increased systolic velocity in the mitral valve are indirect markers of the hepatopulmonary syndrome.

BACKGROUND AND AIMS: Hepatopulmonary syndrome (HPS) has been associated with left atrial enlargement, but the presence of other markers of left and right diastolic and/or systolic cardiac dysfunction has not been clarified. We prospectively evaluated the possible associations between echocardiographical-Doppler findings and HPS. METHODS: Seventy-nine cirrhotic patients without endogenous heart or pulmonary disease were included. HPS was diagnosed by the presence of increased arterial-alveolar-difference and intrapulmonary right-to-left shunt at contrast-enhanced transthoracic echocardiography. Echocardiographical systolic and diastolic indices, tissue Doppler imaging (TDI) of mitral and tricuspid annular motion and M-mode echocardiography measurements were recorded. RESULTS: Hepatopulmonary syndrome was diagnosed in 12 (15.2%) patients. Patients with compared with those without HPS had significantly younger age, albumin levels and saturation of oxygen (SaO(2)) in an erect position, but higher left ventricular end diastolic diameter (LVEDD), ejection fraction, E-wave peak velocity of tricuspid valve, left atrial volume, TDI E wave (early diastolic period) at the right free wall/tricuspid annulus (cm/s) and TDI S wave (systolic) at the left lateral wall/mitral annulus (TDI Smv). In multivariate analysis, the presence of HPS was found to be independently associated with younger age (P=0.027), lower SaO(2) in an erect position (P=0.023), higher LVEDD (P=0.019) and higher TDI Smv (P=0.026). LVEDD and TDI Smv offered good diagnostic accuracy for HPS diagnosis (AUROC/c-statistic: 0.724 and 0.736 respectively). CONCLUSIONS: We confirmed that in patients with cirrhosis, the development of HPS is associated with higher cardiac output and hyperdynamic circulation. Left ventricle enlargement and higher systolic velocity in the mitral valve represent satisfactory indirect markers of HPS.