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Aim: Differentiating alcoholic hepatitis (AH) from acute decompensation of alcoholic cirrhosis (DC) is challenging, as the presentation and biochemistry are similar. We aimed to identify potential metabolomic biomarkers to differentiate between AH and DC, and to predict short-term mortality. Methods: We included consecutive biopsy proven AH and DC patients, which were managed according to current guidelines and followed up until the end of the study. Untargeted metabolomics was assessed in all patients at baseline. Specific analyses were successively performed to identify potential biomarkers, which were further semi-quantitatively analysed against relevant clinical endpoints. Results: Thirty-four patients with AH and 37 with DC were included. UHPLC-MS analysis identified 83 molecules potentially differentiating between AH and DC. C16-Sphinganine-1P (S1P) was the most increased, whereas Prostaglandin E2 (PGE2) was the most decreased. The PGE2/S1P ratio < 1.03 excellently discriminates between AH and DC: AUC 0.965 (p < 0.001), Se 90%, Sp 100%, PPV 0.91, NPV 1, and diagnostic accuracy 95%. This ratio is not influenced by the presence of infection (AUC 0.967 vs. 0.962), correlates with the Lille score at 7 days (r  = −0.60; P  = 0.022) and tends to be lower in corticosteroid non-responders as compared with patients who responded [0.85(±0.02) vs. 0.89(±0.05), P  = 0.069]. Additionally, decreased ursodeoxycholic acid levels are correlated with MELD and Maddrey scores and predict mortality with a 77.27% accuracy (NPV = 100%). Conclusion: This study suggests the PGE2 (decreased)/S1P (increased) ratio as a biomarker to differentiate AH from DC. The study also finds that low levels of ursodeoxycholic acid could predict increased mortality in AH. [ABSTRACT FROM AUTHOR]

Background and aims. Non-cirrhotic portal hypertension (NCPHT) represents an entity that is still incompletely studied as a whole. The aim of the present study is to obtain information on the prevalence, etiology, clinical and biological features of the NCPHT. Methods. This is a prospective cross-sectional study of a population of 105 consecutive patients with NCPHT admitted in the Third Medical Clinic in Cluj-Napoca, Romania from October 2004 to October 2006. As control group, 105 consecutive cirrhotic patients admitted in the same clinic from September 2006 to October 2006 were studied. In this two-year period a total of 1474 patients with portal hypertension (PHT) were admitted. Results. Non-cirrhotic PHT was present in 105/1474 (7.12%) of the patients with PHT. Solid cancers had represented the dominant etiology of PHT (58%). Venous thrombosis (35.2%), extrinsic compression (31.4%) and vascular tumor invasion (28.5%) were almost equally responsible for the NCPHT. Prehepatic PHT was dominant (83.8%) and 33.3% of the patients had segmental PHT in the NCPHT group. The gastric varices (12/69 patients v. 0/100 patients) and the associated esophageal + gastric varices (10/69 patients v. 5/100 patients) were significant more frequent in NCPHT than in cirrhosis (p<0.05). The mean value of platelet count (249,904±13,281/mm3) was normal in the NCPHT group while in the cirrhotic group thrombocytopenia (108,215±65,069/mm3) was noticed. A significant difference was found between the platelet count in NCPHT group and cirrhosis group in patients with spleen diameter over 120 mm (243,240±126,328 v. 106,175±66,470) (p<0.001) as well as a diameter less than 120 mm (214,333±75,191 v. 128,306±54,663) (p<0.001). A negative correlation was found between the platelets count and spleen size in the cirrhosis group (r=-0.292; p=0.002), but not in the NCPHT group (r=0.016; p=0.871). Conclusion. Patients with NCPHT represented 7.12% from the patients with PHT. Thrombosis, tumor invasion and extrinsic compression were equally responsible for the NCPHT. One third of the patients with PHT had segmental PHT. The patients with NCPHT had normal platelets value. In contrast, thrombocytopenia was found in those with cirrhosis, which was negatively correlated with spleen size (might not be caused by PHT but by advanced hepatic fibrosis). [ABSTRACT FROM AUTHOR]

(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients—32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0–0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine. [ABSTRACT FROM AUTHOR]

Background: Hepatic hydrothorax (HH) is an understudied complication of decompensated cirrhosis. We aimed to evaluate the long-term prognosis of patients with HH by comparing them with a matched non-HH group. Methods: This retrospective study included 763 consecutive patients hospitalized for decompensated cirrhosis and ascites. Ninety-seven patients with HH were matched for survival analysis with non-HH patients based on liver disease severity. Results: The prevalence of HH was 13.1%. Patients with HH had significantly worse overall liver function. Upon matching, patients with HH had a lower long-term survival (15.4% vs. 30.9% at 5 years) with a mean overall survival of 22.2 ± 2.2 months for the HH group vs. 27.1 ± 2.6 months for the non-HH group (Log Rank–0.05). On multivariate survival analysis using Cox regression, the MELD-Na score, ALBI grade, hepato-renal syndrome, and grade III ascites had a significant impact on mortality in patients with HH. In patients with HH, a MELD-Na score ≥ 16, ALBI grade III, hepato-renal syndrome, or severe ascites delineated high-mortality risk groups. Conclusions: HH is consistently associated with more advanced liver disease. Patients with HH have worse long-term survival, their prognosis being closely intertwined with overlapping decompensating events. [ABSTRACT FROM AUTHOR]

Background: The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility. Objectives: The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment. Patients and Method: A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard. Results: Significant fibrosis (F . 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F . 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis. Conclusions: The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage. [ABSTRACT FROM AUTHOR]

Background and aims: The current study aims to evaluate the performance of a new elastographic method (ARFI) in noninvasive fibrosis assessment and to compare it to another validated technology (transient elastography, TE). Method: 112 consecutive chronic hepatitis C patients (histologically proven according to the Metavir scoring system: 12.5% F0, 26.6% F1, 16.1% F2, 7.1% F3, 37.5% F4) were prospectively included in this study. They were examined on the same day, using both ARFI (with shear wave velocity - SWV- quantification) and TE (with liver stiffness quantification). Results: SWV is correlated only with fibrosis (r=0.717, p<0.0001) and necroinfiammatory activity (r=0.328, p=0.014), but not with steatosis (r=0.122, p=0.121). There is a significant increase of SWV in parallel with the increase in the fibrosis stage: 1.079±0.150 (F0-F1), 1.504±0.895 (F2), 1.520±0.575 (F3), 2.552±0.782 (F4), p<0.0001, but there is a certain degree of overlap between the consecutive stages F1-F2 (p=0.072), F2-F3 (p=0.965). SWV cut-off values (m/s) that were predictive for each fibrosis stage were: 1.19 (F≥1), 1.34 (F≥2), 1.61 (F≥3) and 2.00 (F4). AUROC for ARFI vs TE were: 0.709 vs 0.902, p=0.006 (F≥1), 0.851 vs 0.941, p=0.022 (F≥2), 0.869 vs 0.926, p=0.153 (F≥3) and 0.911 vs 0.945, p=0.331 (F4). Conclusions: ARFI allows SWV quantification, in strong correlation with the fibrosis stage. Steatosis does not influence SWV. The maximal performance of the method consists of the prediction in severe fibrosis and cirrhosis. The diagnostic accuracy is strongly comparable to TE only for the prediction of severe fibrosis and cirrhosis, whereas for earlier stages, TE performs better. [ABSTRACT FROM AUTHOR]