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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]

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.

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]

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]

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]

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]

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]

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.