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Multidrug-resistant organisms are an increasing concern in patients with decompensated cirrhosis. We aimed to evaluate the prevalence of infections with carbapenem-resistant Enterobacteriaceae in patients with decompensated cirrhosis. Patients with decompensated cirrhosis admitted to ICU were included. The isolated Enterobacteriaceae strains were tested for carbapenemase-producing genes using the Roche LightMix® Modular VIM/IMP/NDM/GES/KPC/OXA48 -carbapenemase detection kit. 48 culture-positive infections were registered in 75 patients with acutely decompensated cirrhosis. Thirty patients contracted a second infection. 46% of bacteria isolated at admission and 60% of bacteria responsible for infections identified during ICU-stay were multiresistant. ESBL+ Enterobacteriaceae were predominant at admission, while carbapenem-resistance was dominant in both Enterobacteriaceae and Non-Fermenting-Gram-Negative Bacteria responsible for infections diagnosed during hospitalisation. OXA 48 or KPC type carbapenemases were present in 30% of the analyzed Enterobacteriaceae and in 40% of the phenotypically carbapenem-resistant Klebsiella pneumoniae strains. The length of ICU stay was a risk-factor for a second infection (p=0.04). Previous carbapenem usage was associated with occurence of infections with carbapenem-resistant Gram-negative bacteria during hospitalization (p=0.03). The prevalence of infections with carbapenem-resistant Enterobacteriaceae is high in patients with decompensated cirrhosis admitted to ICU. Carbapenemase-producing genes in Enterobacteriaceae in our center are bla OXA-48 and bla KPC. [ABSTRACT FROM AUTHOR]

Bacterial infections impair prognosis in patients with cirrhosis. Presepsin and, more recently, resistin are promising markers of infection and sepsis in patients without cirrhosis. The aim of our study was to assess the performance of presepsin and resistin as early markers of infection compared with C reactive protein (CRP) and procalcitonin (PCT), and their prognostic relevance in patients with decompensated cirrhosis. One hundred and fourteen consecutive patients with decompensated cirrhosis were enrolled and followed-up for 28 days. Diagnostic performances of CRP, PCT, presepsin and resistin were assessed. Fifty-three (46.5%) patients had bacterial infections of which 30 (56%) had sepsis. Presepsin and resistin had similar performance as CRP and PCT for the diagnosis of infection (best cut-off of 1444 pg/ml and 20 ng/ml, respectively) and sepsis. Presepsin (HR = 5.5; 95%CI: 2.36–13.21, p < 0.0001) and the ≥500 pg/ml increase of presepsin at 48 h (HR = 9.24; 95%CI: 3.66–23.27, p < 0.008) were independently associated with 28-day mortality. Presepsin and resistin have similar diagnostic performances to CRP and PCT for bacterial infection in decompensated cirrhosis. Presepsin and Δ presepsin ≥500 pg/ml have also a prognostic relevance for 28-day mortality. [ABSTRACT FROM AUTHOR]

Portal hypertension is the strongest predictor of hepatic decompensation and death in patients with cirrhosis. However, its discriminatory accuracy in patients with nonalcoholic fatty liver disease (NAFLD) has been challenged because hepatic vein catheterization may not reflect the real portal vein pressure as accurately as in patients with other etiologies. We aimed to evaluate the relationship between hepatic venous pressure gradient (HVPG) and presence of portal hypertension–related decompensation in patients with advanced NAFLD (aNAFLD). Multicenter cross-sectional study included 548 patients with aNAFLD and 444 with advanced RNA-positive hepatitis C (aHCV) who had detailed portal hypertension evaluation (HVPG measurement, gastroscopy, and abdominal imaging). We examined the relationship between etiology, HVPG, and decompensation by logistic regression models. We also compared the proportions of compensated/decompensated patients at different HVPG levels. Both cohorts, aNAFLD and aHVC, had similar baseline age, gender, Child-Pugh score, and Model for End-Stage Liver Disease score. Median HVPG was lower in the aNAFLD cohort (13 vs 15 mmHg) despite similar liver function and higher rates of decompensation in aNAFLD group (32% vs 25%; P =.019) than in the aHCV group. For any of the HVPG cutoff analyzed (<10, 10–12, or 12 mmHg) the prevalence of decompensation was higher in the aNAFLD group than in the aHCV group. Patients with aNAFLD have higher prevalence of portal hypertension–related decompensation at any value of HVPG as compared with aHCV patients. Longitudinal studies aiming to identify HVPG thresholds able to predict decompensation and long-term outcomes in aNAFLD population are strongly needed. [ABSTRACT FROM AUTHOR]

Background The diagnostic performance of biochemical scores and artificial neural network models for portal hypertension and cirrhosis is not well established. Aims To assess diagnostic accuracy of six serum scores, artificial neural networks and liver stiffness measured by transient elastography, for diagnosing cirrhosis, clinically significant portal hypertension and oesophageal varices. Methods 202 consecutive compensated patients requiring liver biopsy and hepatic venous pressure gradient measurement were included. Several serum tests (alone and combined into scores) and liver stiffness were measured. Artificial neural networks containing or not liver stiffness as input variable were also created. Results The best non-invasive method for diagnosing cirrhosis, portal hypertension and oesophageal varices was liver stiffness ( C -statistics = 0.93, 0.94, and 0.90, respectively). Among serum tests/scores the best for diagnosing cirrhosis and portal hypertension and oesophageal varices were, respectively, Fibrosis-4, and Lok score. Artificial neural networks including liver stiffness had high diagnostic performance for cirrhosis, portal hypertension and oesophageal varices (accuracy > 80%), but were not statistically superior to liver stiffness alone. Conclusions Liver stiffness was the best non-invasive method to assess the presence of cirrhosis, portal hypertension and oesophageal varices. The use of artificial neural networks integrating different non-invasive tests did not increase the diagnostic accuracy of liver stiffness alone. [ABSTRACT FROM AUTHOR]

Based on platelets and liver stiffness measurements, the Baveno VI criteria (B6C), the expanded B6C (EB6C), and the ANTICIPATE score can be used to rule out varices needing treatment (VNT) in patients with compensated chronic liver disease. We aimed to improve these tests by including data on the ratio of platelets to liver stiffness. In a retrospective analysis of data from 10 study populations, collected from 2004 through 2018, we randomly assigned data from 2368 patients with chronic liver disease of different etiologies to a derivation population (n = 1579; 15.1% with VNT, 50.2% with viral hepatitis, 28.9% with nonalcoholic fatty liver disease, 20.8% with alcohol-associated liver disease, with model for end-stage liver disease scores of 9.5 ± 3.0, and 93.0% with liver stiffness measurements ≥10 kPa) or a validation population (n = 789). Test results were compared with results from a sequential algorithm (VariScreen). VariScreen incorporated data on platelets or liver stiffness measurements and then the ratio of platelets to liver stiffness measurement, adjusted for etiology, patient sex, and international normalized ratio. In the derivation population, endoscopies were spared for 23.9% of patients using the B6C (VNT missed in 2.9%), 24.3% of patients using the ANTICIPATE score (VNT missed in 4.6%), 34.5% of patients using VariScreen (VNT missed in 2.9%), and 41.9% of patients using the EB6C (VNT missed in 10.9%). Differences in spared endoscopy rates were significant (P ≤.001), except for B6C vs ANTICIPATE and in missed VNT only for EB6C vs the others (P ≤.009). VariScreen was the only safe test regardless of sex or etiology (missed VNT ≤5%). Moreover, VariScreen secured screening without missed VNT in patients with model for end-stage liver disease scores higher than 10. This overall strategy performed better than a selective strategy restricted to patients with compensated liver disease. Test performance and safety did not differ significantly among populations. In a retrospective study of data from 2368 patients with chronic liver disease, we found that the B6C are safe whereas the EB6C are unsafe, based on missed VNT. The VariScreen algorithm performed well in patients with chronic liver disease of any etiology or severity. It is the only test that safely rules out VNT and can be used in clinical practice. [Display omitted] [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]

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]

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]

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]