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Background: Several tests have been developed to screen varices needing treatment (VNT) in different screening settings. We aimed to develop simple estimators to quantify VNT risk and spare endoscopy while missing <5% of VNT, adapted to different screenings in the main etiologies., Methods: 2,368 patients with chronic liver disease were included. The main VNT predictors were platelets, prothrombin index (PI) and LSM. Their interactions led to score construction, LIP: (LSM*45)/(PI*platelets), and BLIP: BMI-adjusted LIP in NAFLD. Scores were categorized either for population (VNT sensitivity ≥95%) or individual (negative predictive value ≥95%) VNT screening., Results: 1) Scores diagnosing VNT. AUROCs were, PLER: 0.767 Anticipate: 0.773 (p=0.059 vs previous), LIP: 0.779 (p=0.136), PLEASE: 0.789 (p=0.196). 2) Population screening performance was in increasing order (with missed VNT rate), Baveno 6 criteria: 23.9% (2.5%), Anticipate: 24.5%, p=0.367 vs previous (3.3%), PLER: 27.3%, p<0.001 (3.6%), LIP: 33.4%, p<0.001 (4.2%), PLEASE: 35.2%, p=0.006 (3.6%). In NAFLD, LIP: 38.6%, BLIP: 40.8%, p=0.038. 3) Individual screening performance was, expanded Baveno 6 criteria: 42.7%, LIP: 54.1%, p<0.001. In NAFLD, performance was, NAFLD-cirrhosis criteria: 66.7%, BLIP: 74.6%, p<0.001., Conclusion: LIP combined simplicity, performance and safety in each etiology. In NAFLD, BMI-adjusted LIP outperformed other tests., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background and Aims: We aimed to improve non-invasive screening of varices needing treatment (VNT) and compare different screening strategies., Methods: 2,290 patients with chronic liver disease were included in a retrospective study. Etiologies were: virus: 50.0%, NAFLD: 29.5%, alcohol: 20.5%, VNT: 14.9%. Test descriptors were performance (spared endoscopy) and safety (missed VNT). VNT tests were evaluated according to their safety levels either for individual screening (95% negative predictive value (NPV)), population screening (95% sensitivity) or undifferentiated screening (100% sensitivity/NPV) without missed VNT. The tests provided three categories: missed VNT <5%, VNT 100% specificity (new category), both sparing endoscopies, and intermediate (endoscopy required)., Results: Independent VNT predictors (etiology, sex, age, platelets, prothrombin index, albumin, ALT, liver stiffness) were included in two tests: VNT virus alcohol NAFLD test (VANT) and varice risk score (VARS). We report results of the whole population. Considering population screening, performances were, Baveno VI criteria: 24.1%, Anticipate: 24.7%, VariScreen: 35.3%, VANT: 40.2% (p<0.001 vs other tests). VANT spared 58.0% more endoscopies in the whole population than Baveno criteria in compensated advanced chronic liver diseases. Considering individual screening, VARS performance was, in all patients: 62.0% vs 42.9% for the expanded Baveno VI criteria (p<0.001), and, in NAFLD: 72.8% vs 65.1% for the NAFLD cirrhosis criteria (p<0.001). Considering undifferentiated screening, VARS performance was 12%. The VARS score estimated VNT probability from 0 to 100% (AUROC: 0.826)., Conclusion: VANT and VARS spared from 12% (undifferentiated screening) to 40% (population screening) or 62% (individual screening) of endoscopies in main-etiology patients without ascites., Competing Interests: Declaration of Conflict of Interest None related to the topic., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background & Aims: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Patients with compensated advanced chronic liver disease (cACLD) can safely avoid screening endoscopy with a platelet count >150 × 10 9 cells/L and a liver stiffness measurement (LSM) <20 kPa (Baveno VI criteria). However, the total number of avoided endoscopies using this rule is relatively low. We aimed at expanding the Baveno VI criteria and validating them in additional cohorts. Patients from the Anticipate cohort (499 patients with cACLD of different etiologies) were used to study the performance of different thresholds of platelets and LSM for the identification of patients at very low risk (<5%) of having varices needing treatment (VNT). The new criteria (Expanded-Baveno VI) were validated in two additional cohorts from London (309 patients) and Barcelona (117 patients). The performance of the new criteria by etiology of cACLD was also assessed. The best new expanded classification rule was platelet count >110 × 10 9 cells/L and LSM <25 kPa. This was validated in the two additional cohorts. Overall, the Expanded-Baveno VI criteria would potentially spare 367 (40%) endoscopies (21% with Baveno VI criteria) with a risk of missing VNT of 1.6% (95% confidence interval, 0.7%-3.5%) in patients within the criteria and 0.6% (95% confidence interval, 0.3%-1.4%) in the overall population of 925 patients evaluated. The Expanded-Baveno VI criteria performed well in patients with cACLD with hepatitis C virus and alcoholic and nonalcoholic steatohepatitis., Conclusion: The new Expanded-Baveno VI criteria spare more endoscopies than the original criteria with a minimal risk of missing VNT in most of the main etiologies of cACLD. (Hepatology 2017;66:1980-1988)., (© 2017 by the American Association for the Study of Liver Diseases.)

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., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aims: Non-invasive methods are required to diagnose presence and grading of esophageal varices in patients with hepatic cirrhosis and in this respect we have evaluated the role of transient elastography and abdominal ultrasound parameters., Material and Methods: Cirrhotic patients were prospectively evaluated by transient elastography and Doppler ultrasound for diagnosis of presence and grading of esophageal varices, the results being compared with the findings of the esophagogastroduodenoscopy., Results: Sixty patients with hepatic cirrhosis were analysed. The parameters that reached statistical significance for diagnosis of esophageal varices were: liver stiffness (LSM) > 15 kPa, hemodynamic liver index (PVr1) >/= 0.66, portal vascular resistance (PVR) > 17.66 and splenoportal index (SPI) > 4.77. The only parameter that reached statistical power for the diagnosis of large esophageal varices was LSM at a cut-off value of 28.8 kPa., Conclusions: Assessment of LSM in patients with liver cirrhosis can predict both the presence of esophageal varices and of large esophageal varices. The PVr1, PVR and SPI Doppler indexes can be used to diagnose the presence of esophageal varices but have no role in the prediction of large esophageal varices. Further studies are required to confirm these results and offer a stronger clinical significance.

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., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

Background and Aim: 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., Patients and Methods: 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., Results: 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., Conclusion: 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., (© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)