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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]

(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 & Aims. The current study aimed to establish the liver stiffness (LS) cut-off values and their performance in the prediction of the fibrosis stage in chronic hepatitis C (CHC) patients, to find the anthropometric and biochemical factors leading to overestimation of the fibrosis stage and to analyze the factors leading to the technique failure. Methods. 1,202 consecutive CHC patients were prospectively included in the study. All of them underwent percutaneous liver biopsy for grading and staging the disease (METAVIR) and were referred to LS measurement 1 day prior to biopsy. Results. LS values varied between 2.8-75 kPa. Transient elastography success rate (SR) ranged between 0-100% (84.82±24.46%). In 27 patients (2.2%), no valid measurement was obtained; high BMI influenced independently the measurement failure. In 11.2% of cases, the SR was <60%, but 10 valid measurements were nevertheless recorded; the female sex and high BMI were the only factors independently leading to a SR<60%. AUROCs for the diagnosis of fibrosis F≥1, F≥2, F≥3, and F=4 were 0.879,0.889,0.941 and 0.970, for the cut-off values of 5.3 kPa, 7.4 kPa, 9.1 kPa and 13.2 kPa respectively, and they did not significantly differ from the adjusted AUROC values. The patients with false positive results were younger and had significantly higher serum aminotransferase (ALT, AST) and gamma glutamyl-transpeptidase levels than the patients with concordant results. The multivariate analysis showed that only high ALT levels influenced independently the occurrence of false positive results. Conclusion. Transient elastography is a useful non-invasive method for the assessment of fibrosis in CHC patients. However, it must be interpreted in the clinical and biochemical context, in order to insure high-quality results. [ABSTRACT FROM AUTHOR]

Splenomegaly in a common finding in liver cirrhosis that should determine changes in the spleen's density because of portal and splenic congestion and/or because of tissue hyperplasia and fibrosis. These changes might be quantified by elastography, so the aim of the study was to investigate whether spleen stiffness measured by transient elastography varies as liver disease progresses and whether this would be a suitable method for the noninvasive evaluation of the presence of esophageal varices. One hundred and ninety-one patients (135 liver cirrhosis, 39 chronic hepatitis and 17 healthy controls) were evaluated by transient elastography for measurements of spleen and liver stiffness. Cirrhotic patients also underwent upper endoscopy for the diagnosis of esophageal varices. Spleen stiffness showed higher values in liver cirrhosis patients as compared with chronic hepatitis and with controls: 60.96 vs 34.49 vs 22.01 KPa ( P < 0.0001). In the case of liver cirrhosis, spleen stiffness was significantly higher in patients with varices as compared with those without (63.69 vs 47.78 KPa, P < 0.0001), 52.5 KPa being the best cut-off value, with an area under the receiver operating characteristic of 0.74. Using both liver and spleen stiffness measurement we correctly predicted the presence of esophageal varices with 89.95% diagnostic accuracy. Spleen stiffness can be assessed using transient elastography, its value increasing as the liver disease progresses. In liver cirrhosis patients spleen stiffness can predict the presence, but not the grade of esophageal varices. Esophageal varices' presence can be better predicted if both spleen and liver stiffness measurements are used. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "Spleen stiffness in patients with cirrhosis in predicting esophageal varices" by P. Sharma and colleagues in a 2013 issue is presented.

Corticosteroids are the only effective therapy for severe alcohol-associated hepatitis (AH), defined by a model for end-stage liver disease (MELD) score >20. However, there are patients who may be too sick to benefit from therapy. Herein, we aimed to identify the range of MELD scores within which steroids are effective for AH. We performed a retrospective, international multicenter cohort study across 4 continents, including 3,380 adults with a clinical and/or histological diagnosis of AH. The main outcome was mortality at 30 days. We used a discrete-time survival analysis model, and MELD cut-offs were established using the transform-the-endpoints method. In our cohort, median age was 49 (40–56) years, 76.5% were male, and 79% had underlying cirrhosis. Median MELD at admission was 24 (19–29). Survival was 88% (87–89) at 30 days, 77% (76–78) at 90 days, and 72% (72–74) at 180 days. A total of 1,225 patients received corticosteroids. In an adjusted-survival-model, corticosteroid use decreased 30-day mortality by 41% (hazard ratio [HR] 0.59; 0.47–0.74; p < 0.001). Steroids only improved survival in patients with MELD scores between 21 (HR 0.61; 0.39–0.95; p = 0.027) and 51 (HR 0.72; 0.52–0.99; p = 0.041). The maximum effect of corticosteroid treatment (21–30% survival benefit) was observed with MELD scores between 25 (HR 0.58; 0.42–0.77; p < 0.001) and 39 (HR 0.57; 0.41–0.79; p < 0.001). No corticosteroid benefit was seen in patients with MELD >51. The type of corticosteroids used (prednisone, prednisolone, or methylprednisolone) was not associated with survival benefit (p = 0.247). Corticosteroids improve 30-day survival only among patients with severe AH, especially with MELD scores between 25 and 39. Alcohol-associated hepatitis is a condition where the liver is severely inflamed as a result of excess alcohol use. It is associated with high mortality and it is not clear whether the most commonly used treatments (corticosteroids) are effective, particularly in patients with very severe liver disease. In this worldwide study, the use of corticosteroids was associated with increased 30-day, but not 90- or 180-day, survival. The maximal benefit was observed in patients with an MELD score (a marker of severity of liver disease; higher scores signify worse disease) between 25-39. However, this benefit was lost in patients with the most severe liver disease (MELD score higher than 51). [Display omitted] • We validated the use of corticosteroids for patients with severe alcohol-associated hepatitis defined by an MELD score >20. • The use of corticosteroids was associated with increased 30-day survival. • The maximum benefit of corticosteroids was seen in patients with MELD scores between 25-39. • A MELD score >51 can be used to define futility of corticosteroid treatment in patients with severe AH. • The survival benefit was not sustained at 90 or 180 days. [ABSTRACT FROM AUTHOR]

Esophageal varices (EVs) are among the most severe complications of cirrhosis, with a prevalence of 50% to 60% among cirrhotic patients. International guidelines therefore recommend that cirrhotic patients should be screened for the presence of EVs. The main objective of this study was to introduce a new spleen-dedicated FibroScan (Echosens, Paris, France) examination and to assess its performance in detecting large EVs (grade 2 and 3). This novel examination has been validated in simulation and phantom studies and has been used in a population of patients with chronic liver disease. The study described here suggests that the novel spleen-dedicated FibroScan examination performs better than the standard FibroScan for the detection of large EVs (area under the curve = 0.70 for the standard examination and 0.79 [p <0.01] for the spleen examination), but further clinical studies are needed to investigate the role of spleen stiffness in the management of cirrhotic patients. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents an automatic tool capable to learn from a patients data set with 24 medical indicators characterizing each sample and to subsequently use the acquired knowledge to differentiate between five degrees of liver fibrosis. The indicators represent clinical observations and the liver stiffness provided by the new, non-invasive procedure of Fibroscan. The proposed technique combines a hill climbing algorithm that selects subsets of important attributes for an accurate classification and a core represented by a cooperative coevolutionary classifier that builds rules for establishing the diagnosis for every new patient. The results of the novel method proved to be superior as compared to the ones obtained by other important classification techniques from the literature. Additionally, the proposed methodology extracts a set of the most meaningful attributes from the available ones. [Copyright &y& Elsevier]