Search

LINKED CONTENT: This article is linked to Hassanein et al papers. To view these articles, visit https://doi.org/10.1111/apt.18054 and https://doi.org/10.1111/apt.18128. [ABSTRACT FROM AUTHOR]

Background & Aims: Several non‐invasive tests (NITs) have been developed to diagnose oesophageal varices (EV), including the recent Baveno VI criteria to rule out high‐risk varices (HRV). Spleen stiffness measurement (SSM) with the standard FibroScan® (SSM@50Hz) has been evaluated. However, the EV grading could be underestimated because of a ceiling threshold (75 kPa) of the SSM@50Hz. The aims were to evaluate SSM by a novel spleen‐dedicated FibroScan® (SSM@100Hz) for EV diagnosis compared with SSM@50Hz, other validated NITs and Baveno VI criteria. Methods: This prospective multicentre study consecutively enrolled patients with chronic liver disease; blood data, endoscopy, liver stiffness measurement (LSM), SSM@50Hz and SSM@100Hz were collected. Results: Two hundred and sixty patients met inclusion criteria. SSM@100Hz success rate was significantly higher than that of SSM@50Hz (92.5% vs 76.0%, P <.001). SSM@100Hz accuracy for the presence of EV (AUC = 0.728) and HRV (AUC = 0.756) was higher than in other NITs. SSM@100Hz AUC for large EV (0.782) was higher than SSM@50Hz (0.720, P =.027). AUC for HRV with SSM@100Hz (0.780) was higher than with LSM (0.615, P <.001). The spared endoscopy rate of Baveno VI criteria (8.1%) was significantly increased by the combination to SSM@50Hz (26.5%) or SSM@100Hz (38.9%, P <.001 vs others). The missed HRV rate was, respectively, 0% and 4.7% for combinations. Conclusions: SSM@100Hz is a new performant non‐invasive marker for EV and HRV providing a higher accuracy than SSM@50Hz and other NITs. The combination of Baveno VI criteria and SSM@100Hz significantly increased the spared endoscopy rate compared to Baveno VI criteria alone or combined with SSM@50Hz. Clinical trial number: NCT02180113. [ABSTRACT FROM AUTHOR]

Background & Aims Liver stiffness ( LS), spleen stiffness ( SS) and serum markers have been proposed to non-invasively assess portal hypertension or oesophageal varices ( EV) in cirrhotic patients. We aimed to evaluate the performance of a stepwise algorithm that combines Lok score with LS and SS for diagnosing high-risk EV ( HREV) and to compare it with other already-validated non-invasive methods. Methods We performed a cross-sectional study including 136 consecutive compensated cirrhotic patients with various aetiologies, divided into training (90) and validation (46) set. Endoscopy was performed within 6 months from inclusion for EV screening. Spleen diameter was assessed by ultrasonography. LS and SS were measured using Fibroscan. Lok score, platelet count/spleen diameter ratio, LSM-spleen diameter to platelet ratio score and oesophageal varices risk score ( EVRS) were calculated and their diagnostic accuracy for HREV was assessed. The algorithm classified patients as having/not-having HREV. Its performance was tested and compared in both groups. Results In the training set, all variables could select patients with HREV with moderate accuracy, the best being LSPS ( AUROC = 0.818; 0.93 sensitivity; 0.63 specificity). EVRS, however, was the only independent predictor of HREV ( OR = 1.521; P = 0.032). The algorithm correctly classified 69 (76.66%) patients in the training set ( P < 0.0001) and 36 (78.26%) in the validation one. In the validation group, the algorithm performed slightly better than LSPS and EVRS, showing 100% sensitivity and negative predicted value. Conclusion The stepwise algorithm combining Lok score, LS and SS could be used to select patients at low risk of having HREV and who may benefit from more distanced endoscopic evaluation. [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]

Background and aim: Noninvasive serum liver fibrosis markers and liver stiffness could be used as predictors of esophageal varices in cirrhotic patients because portal hypertension is related to liver fibrosis. The aim of this study was to compare the performance of common serum fibrosis scores and transient elastography in diagnosing esophageal varices and to propose a new algorithm for predicting large varices. Methods: 231 consecutive cirrhotic patients (58.4% males, mean age 55.9 years) were enrolled. Routine biological tests were performed, so that APRI, FIB-4, Forns Index and Lok Score could be calculated. All patients underwent transient elastography and eso-gastroscopy. The diagnostic performance of the methods was assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, likelihood ratios and receiver operating characteristic curves. Results: The Lok Score was the best among all the serum scores for diagnosing the varices. For a value higher than 0.8, it had a 45.5% positive predictive value, 86.4% negative predictive value and 67.72% diagnostic accuracy for prediction of large varices. For liver stiffness higher than 30.8KPa, the positive predictive value was 47.3%, negative predictive value 81% and diagnostic accuracy 68.32%. Using both tests simultaneously, the presence of large varices was predicted with a diagnostic accuracy of 78.12%, obtaining an increment in NPV and -LR up to 93.67% and 0.21, respectively. Conclusion: The Lok Score is a good predictor for excluding the presence of large varices in cirrhotic patients, similarly with liver stiffness. The two methods can be successfully combined into a noninvasive algorithm for the assessment of esophageal varices in cirrhotic patients. [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]

Simple Summary: Intermittent fasting has the potential to beneficially act upon several pathways that are involved in hepato-cellular carcinoma pathogenesis. Especially among non-alcoholic steatohepatitis patients (NASH), intermittent fasting could effectively reduce the chance of progression to advanced liver disease and hepatocellular carcinoma. Although intermittent fasting activates similar pathways among those without NASH, the altered metabolism in cirrhotic patients may make them exceptionally vulnerable to malnutrition and increase the risk of liver-related adverse events. Hepatocellular carcinoma (HCC), one of the leading causes of cancer-related deaths worldwide, is a multistep process that usually develops in the background of cirrhosis, but also in a non-cirrhotic state in patients with non-alcoholic fatty liver disease (NAFLD) or viral hepatis. Emerging evidence suggests that intermittent fasting can reduce the risk of cancer development and could improve response and tolerance to treatment through the metabolic and hormonal adaptations induced by the low energy availability that finally impairs cancer cells' adaptability, survival and growth. The current review will outline the beneficial effects of fasting in NAFLD/NASH patients and the possible mechanisms that can prevent HCC development, including circadian clock re-synchronization, with a special focus on the possibility of applying this dietary intervention to cirrhotic patients. [ABSTRACT FROM AUTHOR]

Aims: This study assessed the effectiveness of three ultrasound-based techniques (2D-SWE.PLUS, Att.PLUS, Vi.PLUS) for non-invasive evaluation of liver fibrosis, steatosis, and inflammation in chronic liver disease (CLD) patients. Materials and methods: Involving 209 consecutive compensated CLD patients, the study compared these ultrasound methods from Aixplorer with standard Vibration-controlled Transient Elastography (VCTE) and Controlled Attenuation Parameter (CAP) from Fibroscan, alongside non-invasive serological markers. Results: High validity rates were observed in measurements: 99% for VCTE, 89% for 2D-SWE.PLUS/Vi.PLUS, and 96.6% for Att.PLUS. 2D-SWE.PLUS showed a strong correlation with VCTE (R=0.91) and excelled at a lower Stability Index (80%), with optimal cut-offs for moderate and severe fibrosis at 8 kPa and 10 kPa, respectively. 2D-SWE.PLUS was superior to Fib4, eLIFT, APRI, BARD, and NFS in detecting advanced CLD. Att.PLUS moderately correlated with CAP (R=0.47) for steatosis grades, while Viscosity was highly effective in identifying significant fibrosis (AUC=0.87) but less so for inflammation. Conclusions: 2D-SWE.PLUS demonstrated superior diagnostic precision in liver fibrosis, exceeding other non-invasive markers. Att.PLUS was relatively accurate for liver steatosis, and viscosity more effectively indicated fibrosis stages than inflammation in CLD patients. [ABSTRACT FROM AUTHOR]

Background: MASLD is a prevalent chronic liver condition with substantial clinical implications. This study aimed to assess the effectiveness of three new, elastography-based, scoring systems for advanced fibrosis ≥F3 (Agile 3+), cirrhosis F4 (Agile 4), and fibrotic NASH: NASH + NAS ≥4 + F≥2 (FAST score), in a cohort of biopsy-proven NAFLD meeting MASLD criteria. Our secondary aim was to compare their diagnostic performances with those of other fibrosis prediction tools: LSM-VCTE alone, and common, easily available scores (FIB-4 or APRI). Methods: Single-center, retrospective study, on consecutive patients with baseline laboratory tests, liver biopsy, and reliable LSM-VCTE measurements. The discrimination between tests was evaluated by analyzing the AUROCs. Dual cut-off approaches were applied to rule-out and rule-in ≥F3, F4 and fibrotic NASH. We tested previously reported cut-off values and provided our best thresholds to achieve Se ≥85%, Se ≥90%, and Sp ≥90%, Sp ≥95%. Results: Among 246 patients, 113 (45.9%) were women, and 75 (30.5%) presented diabetes. Agile 3+ and Agile 4 demonstrated excellent performance in identifying ≥F3 and F4, achieving AUROCs of 0.909 and 0.968, while the FAST score yielded acceptable results in distinguishing fibrotic NASH. When compared to FIB-4 and LSM-VCTE, both Agile 3+ and Agile 4 performed better than FIB-4 and had a similar performance to LSM-VCTE, but with higher diagnostic accuracy, hence reducing the grey zone. Conclusion: Agile 3+ and Agile 4 are reliable, non-invasive tests for identifying advanced fibrosis or cirrhosis in MASLD patients, while FAST score demonstrates moderate performance in identifying fibrotic NASH. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a societal burden due to the lack of effective treatment and incomplete pathophysiology understanding. This review explores the intricate connections among liver sinusoidal endothelial cells (LSECs), platelets, neutrophil extracellular traps (NETs), and coagulation disruptions in MASLD pathogenesis. In MASLD's early stages, LSECs undergo capillarization and dysfunction due to excessive dietary macronutrients and gut-derived products. Capillarization leads to ischemic changes in hepatocytes, triggering pro-inflammatory responses in Kupffer cells (KCs) and activating hepatic stellate cells (HSCs). Capillarized LSECs show a pro-inflammatory phenotype through adhesion molecule overexpression, autophagy loss, and increased cytokines production. Platelet interaction favors leucocyte recruitment, NETs formation, and liver inflammatory foci. Liver fibrosis is facilitated by reduced nitric oxide, HSC activation, profibrogenic mediators, and increased angiogenesis. Moreover, platelet attachment, activation, α-granule cargo release, and NETs formation contribute to MASLD progression. Platelets foster fibrosis and microthrombosis, leading to parenchymal extinction and fibrotic healing. Additionally, platelets promote tumor growth, epithelial–mesenchymal transition, and tumor cell metastasis. MASLD's prothrombotic features are exacerbated by insulin resistance, diabetes, and obesity, manifesting as increased von Willebrand factor, platelet hyperaggregability, hypo-fibrinolysis, and a prothrombotic fibrin clot structure. Improving LSEC health and using antiplatelet treatment appear promising for preventing MASLD development and progression. [ABSTRACT FROM AUTHOR]

The article presents a study which examines whether spleen stiffness is a pedictor of clinical decompensation in cirrhotic patients. A real life experience using spleen stiffness measurement (SSM) and modified SSM (MSSM) as long-term predictors of clinical decompensation in patients with cirrhosis is discussed. The study found MSSM to be an independent predictor of CD.

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.

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 & Aims: A novel non-invasive tool based on the evaluation of ultrasound attenuation using transient elastography (TE) has been developed, called controlled attenuation parameter (CAP). We aim to establish the histopathological parameters that significantly influence CAP, the cutoff values and their performance in predicting each steatosis grade on a group of biopsied patients with chronic liver diseases (CLD) from Romania. Methods. We prospectively analyzed 201 consecutive CLD patients who underwent CAP measurements using TE. Steatosis, liver fibrosis and necroinflammatory activity were staged and graded during the pathological analysis of bioptic specimens. Univariate and multivariate regression analyses were applied to identify the variables correlated with CAP values. The diagnostic performance of CAP for steatosis prediction was assessed using an AUC analysis. Results. Among the histopathological factors correlating with CAP, the multivariate analysis found steatosis as the only factor independently influencing CAP values (p<0.001). Maximal diagnostic accuracy (DA) was obtained for the prediction of ⩾34-66% (S2) fatty load and of 67-100% (S3) fatty load (82.06%, respectively 81.59%) while, for the prediction of ⩾11-33% (SI) fatty load, DA reached only 76.11%. The negative predictive value for the exclusion of ⩾S2 and S3 was 93.5% and 98.7%, respectively. AUCs calculated between each two steatosis grades were: 0.772 (SO vs SI), 0.874 (SO vs S2), 0.904 (SO vs S3), 0.659 (Slvs S2), 0.777 (SI vs S3), and 0.665 (S2 vs S3). Conclusion. Steatosis is the only histopathological factor independently influencing CAP. Maximal DA could be obtained for the prediction of ⩾S2 and S3 (82.06% and 81.59%), while for the prediction of Si, the accuracy reached only 76.11%. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver stiffness (LS) is increased in liver cirrhosis, higher values being associated with complications, among them the development of hepatocellular carcinoma (HCC). However, LS values alone cannot accurately differentiate patients with HCC. Therefore, our aim was to study the performance of LS measurement data and common biomarkers for the detection of HCC in HCV related liver cirrhosis. Methods: We performed a case matching study comparing HCV cirrhotic patients with and without HCC (72 in each group) that were identical in terms of sex, age, BMI and duration of HCV infection. All patients underwent LS measurement, endoscopy, liver imaging and liver function tests. A multiple regression analysis was performed and a HCC detection model was calculated, which was further validated in another group of 40 HCV infected cirrhotics, of whom 52% had HCC. Results: In the HCC group, LS was significantly higher (42 vs 27 kPa, p<0.0001). In the multivariate analysis higher values of LS, alanine-aminotransferase (ALAT), alpha-fetoprotein (AFP) and interquartile range (IQR) of LS measurements were independently associated with the presence of HCC (p<0.0001 for all parameters; Odds Ratios of 8.27, 1.01, 1.04 and 1.16, respectively). The detection model combining the four variables showed a good diagnostic performance in both training and validation groups, with AUROCs of 0.86 and 0.8, respectively. All variables were also positively correlated with tumor size. Conclusion: In HCV related cirrhosis, HCC is associated with increased LS and IQR values and high ALAT and AFP levels. By combining these four parameters into a regression model, liver cancer may be noninvasively predicted with good accuracy. [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]

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]

INTRODUCTION: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. METHODS: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH. RESULTS: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 x 109/L ruled out CSPH in most etiologies. DISCUSSION: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH. [ABSTRACT FROM AUTHOR]

Background & Aims: Liver stiffness measured with 2‐dimensional shear wave elastography by Supersonic Imagine (2DSWE‐SSI) is well‐established for fibrosis diagnostics, but non‐conclusive for portal hypertension. Methods: We performed an individual patient data meta‐analysis of 2DSWE‐SSI to identify clinically significant portal hypertension (CSPH), severe portal hypertension and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta‐analytical integration of diagnostic accuracies with optimized rule‐out (sensitivity‐90%) and rule‐in (specificity‐90%) cut‐offs. Results: Five studies from seven centres shared data on 519 patients. After exclusion, we included 328 patients. Eighty‐nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE‐SSI < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of patients, with minimal between‐study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE‐SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut‐off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral aetiology or BMI < 25 kg/m2. 2DSWE‐SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. Conclusion: Liver stiffness using 2‐dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE‐SSI cannot predict varices needing treatment. [ABSTRACT FROM AUTHOR]

Background. In patients with cirrhosis, the gold standard for assessment of portal hypertension is the measurement of the hepatic venous pressure gradient (HVPG), a minimally invasive radiological technique that determines indirectly the porto systemic pressure gradient (PPG). However, the technique is available only in referral centres and requires special expertise. Recently, EUS-guided techniques for the measurement of the PPG (EUSPPGm) by directly puncturing the portal vein and the hepatic vein, have shown promising results in terms of feasibility and safety. Nevertheless, the equipment for this procedure uses special devises that require a high purchase cost, and the pressure results are difficult to interpret. The aim of our study was to evaluate the feasibility and safety of EUS-PPGm using a 22 G FNA in a cohort of patients with cirrhosis undergoing TIPS placement for the indication of recurrent variceal bleeding or refractory ascites. Methodology. The patients were included prospectively. Patients with complete portal vein thrombosis were excluded. The EUS-PPGm was performed under general anesthesia, prior to TIPS procedure, by experienced endosonographers, using a linear echoendoscope and a 22-G FNA transgastrically, close to the cardia. After checking the intravascular position of FNA by injecting saline, the pressures were recorded using the same hemodynamic unit as the HVPG, XperFlex Cardio (Philips). The systemic pressure was measured at the level of the median SHV and the portal pressure was measured at the level of the portal trunk. Feasibility was defined as successful PPGm in each patient. Safety was based on adverse events captured during the perioperative period and in a the postprocedural interview. Results. The study included 7 patients (5 male and 2 female), mean age 57 years, mean platelets count 104/mm3, range [52-172]. The indication for TIPS was refractory ascites in 5 patients and variceal bleeding in the other 2 patients. In two patients, the direct puncture of the SHV was not feasible due to poor visualization of portal vein in an obese patient and narrow SHV in a patient with advanced cirrhosis. The mean PPG-EUS was 12.2 mmHg SD 2.68 and mean PPG-TIPS was 15 mmHg, SD 3.317. There were no intraprocedural or post procedural complications recorded. Conclusion. EUS-PPGm using a 22-G FNA is feasible and appears safe. Given the availability of EUS, EUS-PPGm may represent a promising breakthrough for procuring indispensable information in the management of patients with liver disease. [ABSTRACT FROM AUTHOR]

The evaluation of patients with early hepatocellular carcinoma (HCC) referred for liver resection is still a matter of debate. Aims: 1) to compare liver stiffness measurement (LSM) by transient elastography with hepatic venous pressure gradient (HVPG) in the prediction of decompensation after liver resection in patients with cirrhosis and early HCC; 2) to identify which definition for posthepatectomy liver failure is better associated with survival.Material and Methods: Fifty-one patients (MELD score of 10±3) were included. In this group, 34 patients underwent HVPG measurement, of which 13 (38%) had clinically significant portal hypertension (CSPH) and 35 patients underwent LSM (21.8±17.9 kPa). The study's end-points were: posthepatectomy liver failure (PHLF) defined according to International Study Group of Liver Surgery criteria and 3-month decompensation defined as de novo ascites, variceal bleeding, jaundice, hepatic encephalopathy and acute kidney injury. The performance of LSM compared to HVPG in predicting the end-points were assessed by AUROC curves and accuracy.Results: Twenty (39%) patients developed PHLF and 15 (29%) developed decompensationat 3 months. Three-month decompensation tended to be better correlated with survival. LSM performed well in predicting decompensation at 3 months (AUROC=0.78, 95%CI: 0.63-0.94; p=0.01), comparable with HVPG (AUROC=0.89, 95%CI: 0.79-1.00; p<0.01) (DeLong test p=0.21). LSM was not sufficiently accurate to predict PHLF.Conclusion: LSM has a similar performance to HVPG in predicting decompensation at 3 months in patients with early HCC submitted to liver resection. Three-month decompensation is better associated with survival. [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]

Background & Aims: Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD. Methods: 30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept crosssectional study. Baseline assessment consisted in evaluation of Maddrey's Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis. Results: From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV. Conclusion: Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD. [ABSTRACT FROM AUTHOR]

Liver cirrhosis is a diffuse chronic liver disease affecting the entire liver. The fibrosis accumulation and distribution in the liver are known to be heterogeneous. „Localized" or „focal" cirrhosis is only anecdotically reported. Acute hepatitis E virus (HEV) infection is uncommon in western countries, especially in temperate climate areas and is very often missed or underdiagnosed. However, it may be responsible of up to 15% of acute-on-chronic liver failure cases. We present the case of a 35-year-old patient with a very uncommon association of Budd-Chiari syndrome secondary to hepatocellular carcinoma (HCC) developed on a noncirrhotic right liver lobe and secondary biliary cirrhosis of the left liver lobe, that further complicated with acute HEV infection leading to acute-on-chronic liver failure and death. [ABSTRACT FROM AUTHOR]

Multiple biliary hamartomas, also known as von Mayenburg complexes (VMC), are rare, benign malformations of the intrahepatic bile ducts. VMC are frequently incidental imaging findings and may mimic multifocal liver lesions, including metastases. The present case report is aimed to illustrate the distictive imaging and histopatological features of VMC. A 44-year-old male patient with no significant past medical history was admitted to our tertiary referral hospital for unintentional weight loss and fatigability. Laboratory workup evidenced no significant abnormalities and preserved liver function. Autoimmune and viral ethiologies of liver damage were excluded. Abdominal ultrasound revealed multiple hyperechoic liver lesions up to 5 mm each, scattered throughout the prenchyma with no signs of portal hypertension. Liver stiffness measured by 2D-share wave elastography was 5.2 kPa. Contrast-enhanced ultrasonography showed homogenous hepatic enhancement with no wash-out. Magnetic resonance cholangiopancreatography revealed disseminated subcentimetric cystic liver lesions without communication to the normal biliary tree. Percutaneous liver biopsy was performed and histological findings revealed irregular and disorganized dilated bile ducts with single layer cubic epithelium without cytological atypia, sorrounded by collagenous stroma, highly suggestive for the diagnosis of VMC. Here we reported the case of a patient with rare biliary hamartomas, highlighting the role of key imaging aspects combined with histological findings in establishing the diagnosis. biliary hamartoma, von Meyenburg complexes, percutaneous liver biopsy. [ABSTRACT FROM AUTHOR]

Background: The role of ultrasound (US) surveillance for transjugular intrahepatic portosystemic shunt (TIPS) dysfunction has long been a matter of debate, and clear-cut criteria have yet to be conventionally defined. To evaluate the role of US parameters in detecting hemodynamic TIPS dysfunction in the absence of clinical signs of decompensation. We included all the patients treated with TIPS for portal hypertension-related complications who had a scheduled TIPS revision within the first six weeks after the procedure, irrespective of the clinical and US variables. Clinical TIPS dysfunction (CD) was defined as the recurrence of variceal bleeding or inadequate control of ascites. Hemodynamic TIPS dysfunction (HD) was defined by a PPG exceeding ten mmHg at the first revision. Thus, we have comparatively analyzed the US parameters of 86 patients at TIPS placement and first TIPS revision. Recurrent variceal bleeding was the main indication for TIPS in 72 patients (83.7%). While 14 patients (16.3%) had intractable ascites as the main TIPS indication, 51 patients (59.3%) had ascites prior to TIPS. The rate of CD at the first revision was 2.7% (n=2/72) for variceal bleeding and 33% (n=17/51) for inadequate control of ascites. HD occurred in 44 cases (51.2%). Among the patients with CD for inadequate control of ascites, 13 also had HD. Patients with HD had a significantly lower PVV when compared to patients with a revision PPG below ten mmHg (36 ± 14.7 cm/s vs. 45.7 ± 19.2 cm/s, p=0.008). However, the discriminative capabilities of PVV in detecting HD were modest, with an AUROC of 0.655 for a cut-off value of 30.5 cm/s. Patients with HD also had a significant decrease in PVV at the first revision (-5.4 ± 20 cm/s), compared o patients without HD, which more frequently had an increase in PVV (+6.1 ± 20.9 cm/s), p=0.01. Patients with hemodynamic TIPS dysfunction had a significantly lower PVV and have shown a decreasing PVV compared to the baseline value. A low or decreasing PVV might be sufficient to prompt hepatic catheterization in the absence of clinical recurrence, given the substantially higher rate of clinically silent HD. [ABSTRACT FROM AUTHOR]

The multiparametric assessment of liver fibrosis, steatosis and inflammation offers valuable prognostic information in chronic liver disease (CLD) patients (1). The current study aims to evaluate the feasibility and performance of three new ultrasound-based techniques for the noninvasive assessment of liver fibrosis, steatosis and inflammation in CLD patients. 209-consecutive compensated CLD patients were included in the study. Ultrasound-based measurements were performed in all patients, in the same session, using ShearWave Elastography (2D-SWE.PLUS), Attenuation Plane-wave Ultrasound (Att.PLUS), Viscosity Plane-wave Ultrasound (Vi.PLUS) from Aixplorer and Transient Elastography (TE) with Controlled Attenuation Parameter (CAP) from FibroScan as reference method. Valid measurements were obtained in 99% of patients by TE, in 89% of patients by 2D-SWE.PLUS/Vi.PLUS, and in 96.65% of patients by Att.PLUS. Accurate 2D-SWE.PLUS/Vi.PLUS measurements were achieved even at lower levels of Stability index, 80%. 2D-SWE.PLUS values showed excellent correlation with TE values (R=0.913), irrespective of liver fibrosis or steatosis stage. The best cut-off value for moderate fibrosis was 8 kPa (AUC 0.95) and for severe fibrosis 10 kPa (AUC 0.97). CAP values correlated moderately with Att.PLUS (R=0.472). Att.PLUS had moderate performance in predicting different steatosis stages (AUC 0.76->0.77) with the best cut-off values S1-0.45, S2-0.5, S3-0.55 dB/cm/MHz. Viscosity had excellent performance for predicting significant fibrosis (AUC=0.87), with excellent power to predict it as the degree of liver steatosis increased (AUC 0.84->0.89->0.91) but with a less predictive value than 2D-SWE.PLUS (R=0.68 vs R=0.91). Viscosity correlated poorly with GOT level and not at all with GPT. The multiparametric ultrasound evaluation offers valuable prognostic information in a single analysis in CLD patients. 2D-SWE.PLUS has excellent diagnostic accuracy of liver fibrosis while Att.PLUS has a relatively good accuracy of liver steatosis. Viscosity can better reflect liver fibrosis stage than liver inflammation. [ABSTRACT FROM AUTHOR]

Background & Aims: Obesity proved to favor clinical decompensation in patients with cirrhosis. Our aim was to investigate if metabolic syndrome (MS) in cirrhotic patients represents a risk factor for decompensation. Methods: 704 cirrhotics, included in a MS prevalence study were considered for evaluation; 121 patients were excluded because they did not complete the follow-up and 303 because they were decompensated at the start of the study. The remaining 280 were followed-up for a median period of 28.1±18 months. Patients were censored at the end of follow-up or at occurrence of a liver related event (LRE). Liver related events were considered the following: decompensation (ascites, variceal bleeding, hepatorenal syndrome, jaundice, encephalopathy), hepatocellular carcinoma, portal vein thrombosis and infections. Results: All MS criteria except the abdominal circumference were significantly different between decompensated and compensated patients. HDL-cholesterol levels were lower in decompensated patients. Among the 280 patients who completed the follow-up, 85 (30%) presented LREs. Ascites was the most frequent event. In the univariate analysis of the MS criteria we found a trend to significance of an inverse correlation between MS and LREs. There was no significant difference between patients with or without MS regarding survival free of LREs, 76.7% and 66.5%, respectively. None of the MS criteria reached the level of significance in discriminating patients with and without LREs. Conclusions: In short term, presence of MS was not a risk factor for LREs. In short term, liver function and lower nutritional status influenced the prognosis. In decompensated patients, the MS defining criteria are not applicable. [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]

Abstract: Objective: Hepatic fibrosis, the principal pointer to the development of a liver disease within chronic hepatitis C, can be measured through several stages. The correct evaluation of its degree, based on recent different non-invasive procedures, is of current major concern. The latest methodology for assessing it is the Fibroscan and the effect of its employment is impressive. However, the complex interaction between its stiffness indicator and the other biochemical and clinical examinations towards a respective degree of liver fibrosis is hard to be manually discovered. In this respect, the novel, well-performing evolutionary-powered support vector machines are proposed towards an automated learning of the relationship between medical attributes and fibrosis levels. The traditional support vector machines have been an often choice for addressing hepatic fibrosis, while the evolutionary option has been validated on many real-world tasks and proven flexibility and good performance. Methods and materials: The evolutionary approach is simple and direct, resulting from the hybridization of the learning component within support vector machines and the optimization engine of evolutionary algorithms. It discovers the optimal coefficients of surfaces that separate instances of distinct classes. Apart from a detached manner of establishing the fibrosis degree for new cases, a resulting formula also offers insight upon the correspondence between the medical factors and the respective outcome. What is more, a feature selection genetic algorithm can be further embedded into the method structure, in order to dynamically concentrate search only on the most relevant attributes. The data set refers 722 patients with chronic hepatitis C infection and 24 indicators. The five possible degrees of fibrosis range from F0 (no fibrosis) to F4 (cirrhosis). Results: Since the standard support vector machines are among the most frequently used methods in recent artificial intelligence studies for hepatic fibrosis staging, the evolutionary method is viewed in comparison to the traditional one. The multifaceted discrimination into all five degrees of fibrosis and the slightly less difficult common separation into solely three related stages are both investigated. The resulting performance proves the superiority over the standard support vector classification and the attained formula is helpful in providing an immediate calculation of the liver stage for new cases, while establishing the presence/absence and comprehending the weight of each medical factor with respect to a certain fibrosis level. Conclusion: The use of the evolutionary technique for fibrosis degree prediction triggers simplicity and offers a direct expression of the influence of dynamically selected indicators on the corresponding stage. Perhaps most importantly, it significantly surpasses the classical support vector machines, which are both widely used and technically sound. All these therefore confirm the promise of the new methodology towards a dependable support within the medical decision-making. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is probably the epitome of a screening target, with a well-defined high-risk population, accessible screening methods, and multiple curative-intent treatments available for early disease. Per major societies guideline consensus, biannual ultrasound (US) surveillance of the at-risk patients is the current standard of care worldwide. Yet, despite its documented success in the past decades, this standard is far from perfect. While the whole community is working to further tighten the knots, a worrying number of cases still slip through this safety net. Consequently, these patients lose their chance to a curative solution which leads to a high disease burden with disproportionate mortality. While US will probably remain the fundamental staple in the screening strategy, key questions are seeking better answers. How can its caveats be addressed, and the technique be improved? When are further steps needed? How to increase accuracy without giving up on accessibility? This narrative review discusses the place of US surveillance in the bigger HCC picture, trying to navigate through its strengths and limits based on the most recent available evidence. [ABSTRACT FROM AUTHOR]

The article discusses study which investigated the accuracy of liver stiffness measurement (LSM) during direct acting antiviral (DAA) therapy to estimate clinically significant portal hypertension (CSPH) and to predict long-term outcome in compensated advanced chronic liver disease (cACLD) patients after obtaining sustained virologic response (SVR). Topics covered include a reduction of LSM during treatment, and the role of HPV-induced inflammation on hepatic vascular resistance.

The article discusses the role of vitamin D in nonalcoholic fatty liver disease in metabolomics for genomics.