VariScreen secures the screening of high-risk varices in patients with hepatitis B virus-related cirrhosis beyond Baveno VI criteria.

We aimed to validate the performance of the ratio of the platelet count (PLT) to liver stiffness measurement (LSM) in excluding high-risk varices (HRVs) in patients with hepatitis B virus (HBV)-related compensated cirrhosis beyond Baveno VI criteria. A total of 310 patients were assessed. The performances of the PLT:LSM ratio (PLER), PLER adjusted for the international normalized ratio, etiology, age, and sex (PLEASE), and the sequential algorithm for HRV screening (VariScreen) in excluding HRVs were evaluated and compared with those of expanded Baveno VI criteria (LSM <25 kPa and PLT >110×109/L, EB6C); PLT >150×109/L and model for end-stage liver disease score = 6 (P150M6 criterion); PLT >120×109/L and albumin >36 g/L (P120A36 criterion); and albumin-bilirubin (ALBI) grade and PLT score (ALBI-PLT score). Among the enrolled patients, 43 (13.9%) had HRVs. The area under the receiver operating characteristic curve of PLER for predicting HRVs (0.771, 95% confidence interval, 0.720-0.817) was significantly higher than that for PLT and LSM (p < 0.01). PLER was an independent risk factor for HRVs. VariScreen, PLEASE, and PLER could spare 20 (6.5%), 91 (29.4%), and 60 (19.4%) endoscopies, with 0, 3 (3.3%), and 1 (1.7%) HRVs missed, respectively. The EB6C and P120A36 criteria could spare 45 (14.5%) and 36 (11.6%) endoscopies, with 1 (2.2%) and 1 (2.8%) HRVs missed, respectively. The P150M6 criterion and ALBI-PLT score missed 6.8% and 10.3% of HRVs, respectively. We found that PLER performed better than other non-invasive tests. VariScreen secured the screening of HRVs in patients with HBV-related cirrhosis beyond Baveno VI criteria.

ABC: a novel algorithm to stratify decompensation risk in patients with compensated advanced chronic liver disease (CHESS2108): an international, multicenter cohort study.

BACKGROUND: Liver-related death is preceded by clinical decompensation; therefore, the risk stratification of decompensation in compensated advanced chronic liver disease (cACLD) is extraordinary significant. METHODS: The international, multicenter study included three cohorts from January 2009 to August 2021. In training cohort, the unfavorable Baveno VI criteria patients were used to develop the novel CHESS criteria to stratify decompensation risk. The Algorithm based on Baveno VI criteria plus CHESS criteria (ABC model) was validated in validation cohort, and used to diagnose clinically significant portal hypertension (CSPH) in hepatic venous pressure gradient (HVPG)-performed cohort. RESULTS: A total of 1377 cACLD patients were enrolled. In training cohort, multivariate analysis revealed that liver stiffness measurement (LSM), platelet count (PLT), albumin, alanine aminotransferase (ALT) and varices were the independent risk factors for hepatic decompensation. The novel CHESS criteria was produced (0.036 × LSM [kPa]) + (- 0.013 × PLT [109/L]) + (- 0.068 × Albumin [g/L])) + (- 0.016 × ALT [U/L]) + (0.651 × Varices [present: 1, absent: 0]), and < - 4.4, - 4.4 to - 3.1 and > - 3.1 indicated the low risk, medium risk, and high risk of decompensation, with a 3 year-time-dependent area under the curve (tAUC) of 0.851 (0.800-0.901). In validation cohort, the 3 year-tAUC of ABC model was 0.843 (0.742-0.943). Notably, in HVPG cohort, the high risk group was used to rule in CSPH with a positive predictive value of 93.0%. CONCLUSIONS: The ABC model can stratify the risk of decompensation in cACLD. HVPG evaluation can be waived in both low risk and high risk cACLD patients as they can be managed by Baveno VI criteria and non-selective ß-blockers intervention, respectively, and the remaining medium risk patients need further HVPG evaluation.

Ultrasonic spleen thickness-based indexes surpass Baveno VI criteria in high-risk gastroesophageal varices detection.

AIMS: To evaluate the efficiency of ultrasonic spleen thickness (UST), routine variables and (expanded) Baveno VI criteria for high-risk gastroesophageal varices (HRGOV) detection in cirrhotic patients. METHODS: In total, 305 cirrhotic patients were retrospectively enrolled in the deriving cohort and 328 cirrhotic patients with hepatitis B sustained viral response were prospectively enrolled in the validation cohort. HRGOV was defined as medium and severe gastroesophageal varices (GOV), mild GOV with red signs or Child-Pugh C. The cut-offs for HRGOV were determined by likelihood ratio indicating strong evidences. Algorithms of Spleen thickness-Age-Liver stiffness measurement (LSM, by Fibroscan®)-Albumin (SALA) and Spleen thickness-Platelet-Albumin (SPA) were derived by multivariate analyses. RESULTS: The area under receiver operating characteristics curve of SALA, SPA, UST, platelet, and LSM were 0.849, 0.835, 0.808, 0.746, and 0.655 in the deriving cohort, and improved to 0.901, 0.904, 0.858, 0.876, and 0.811 in the validation cohort, respectively. While SALA, SPA, UST, platelet, Baveno VI criteria (BVI), and expanded BVI spared 46.6%, 38.0%, 29.2%, 21.0%, 12.1%, and 23.6% esophagogastroduodenoscopy in the deriving cohort, these numbers were improved to 68.1%, 66.8%, 27.1%, 37.8%, 36.0%, and 61.0% in the validating cohort, respectively; however, the negative likelihood ratio of expanded BVI was up to 0.16. SPA spared less esophagogastroduodenoscopy than SALA, which can be supplemented by stepwise applying UST and SPA. Sequentially combining UST and SALA, BVI and SALA exempted additional 10-5% endoscopies. CONCLUSIONS: SPA, without LSM, improves HRGOV detection comparing with BVI. UST based algorithms combination can achieve the best efficiency especially in sustained virus response hepatitis B.

Validation of the EVendo score for the prediction of varices in cirrhotic patients.

Background: Screening endoscopy for varices may be deferred when the calculated EVendo score is ≤3.90. This novel score has not been validated in an external cohort. This study aimed to assess the performance of the EVendo score and compare it with the Baveno VI criteria. Methods: We identified and calculated this score in all cirrhotic patients who underwent screening endoscopy for the first time with laboratory tests and liver stiffness measurements within 6 months of the endoscopy date. Results: In total, 103 patients were included. An EVendo score of ≤3.90 identified patients with no gastroesophageal varices (GEV) and varices needing treatment (VNT) with sensitivities of 82% and 83% and specificities of 57% and 34%, respectively. The negative predictive value for VNT was 94%. A comparison with the Baveno VI criteria in Child-Turcotte-Pugh-A patients showed spared endoscopy and missed VNT rates with EVendo score cutoffs of ≤3.9 and ≤4.5 and the Baveno VI criteria of 25%, 33%, and 16.6% and 1.7%, 1.7%, and 0%, respectively. Conclusions: EVendo score is reliable in clinical practice for predicting GEV and VNT. The number of spared endoscopies was higher than that with the Baveno VI criteria; however, there were more missed VNT cases.

Liver stiffness can predict decompensation and need for beta-blockers in compensated cirrhosis: a step beyond Baveno-VI criteria.

BACKGROUND AND AIMS: Liver stiffness measurement (LSM) alone or its combination with platelet counts [Baveno-VI criteria (B6C)] is an important non-invasive tool to predict risk of clinical decompensation in patients with advanced compensated cirrhosis. We compared its utility to decide need for beta-blockers in this regard compared with hepatic venous pressure gradient (HVPG) estimation. METHODS: Patients with compensated cirrhosis with available baseline HVPG and LSM were followed up over a median follow-up of 26 (IQR 7-55) months to determine onset of clinical decompensations. Optimal cut-off for LSM for predicting decompensations was identified and compared with HVPG of 10 mmHg and B6C. Feasibility of initiating beta-blockers based on these strategies was assessed using decision curve analysis (DCA) at different threshold probabilities of rates of clinical decompensation. RESULTS: 626 patients (mean age: 50.8 ± 12.4 years, 72.4% males) related to alcohol (30.3%), non-alcoholic steatohepatitis (26.4%), hepatitis C (16.6%), hepatitis B (10.2%) were included. Altogether, 132 (21.0%) patients developed clinical decompensation. The time-dependant area under curve over 5 years for HVPG and LSM for predicting clinical decompensation was 0.716-0.742 and 0.709-0.784, respectively. A LSM of 22 kPa (Sensitivity-88.6%/Specificity-51.8%) had a similar negative predictive value but a higher positive predictive value [37.9% (LSM) vs.30.9% (HVPG)vs.30.6% (B6C), p = 0.026 at 3 years] for incident decompensations. On DCA, LSM-based strategy emerged superior for deciding beta-blocker initiation with 150, 47, and 18 additional patients meriting treatment identified over and above B6C and HVPG based strategy at 5%, 10%, 20% annual rates of clinical decompensation, respectively. CONCLUSION: Measurement of liver stiffness alone can be a useful alternative to B6C and HVPG in deciding need for beta-blockers to prevent decompensations in compensated cirrhosis.

Including Ratio of Platelets to Liver Stiffness Improves Accuracy of Screening for Esophageal Varices That Require Treatment.

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.

Baveno VI criteria and spleen stiffness measurement rule out high-risk varices in virally suppressed HBV-related cirrhosis.

BACKGROUND & AIMS: There are no data validating the performance of spleen stiffness measurement in ruling out high-risk varices in patients with HBV-related cirrhosis under maintained viral suppression. Thus, we aimed to prospectively validate the performance of spleen stiffness measurement (cut-off 46 kPa) combined with Baveno VI criteria in ruling out high-risk varices in these patients. METHODS: Patients with cirrhosis were enrolled from April to December 2019 at the hepatology unit of the Nanfang Hospital, China. Liver and spleen transient elastography and esophagogastroduodenoscopy were performed at enrollment. Antiviral regimen(s) and virological responses, evaluated every 3-6 months, were recorded. RESULTS: Overall 341 patients with HBV-related cirrhosis under maintained viral suppression were enrolled, and the prevalence of high-risk varices was 20.5% (70/341). Baveno VI criteria spared 37.0% (126/341) esophagogastroduodenoscopies and no high-risk varices were missed (0/70). Eight cases of high-risk varices (8/70, 11.4%) were misclassified in patients (208/341, 61.0%) within the expanded Baveno VI criteria. The spleen stiffness measurement cut-off (≤46.0 kPa) was shown to safely rule out high-risk varices in these patients (the percentage of missed high-risk varices was 4.3%). Over half (61.6%, 210/341) of patients met the combined model (Baveno VI criteria and spleen stiffness measurement cut-off ≤46 kPa) and 4.3% (3/70) of high-risk varices cases were misclassified. This combined model exhibited a sensitivity of 95.71%, specificity of 76.38%, negative predictive value of 98.57%, and negative likelihood ratio of 0.06 for ruling out high-risk varices. CONCLUSIONS: We validated the excellent performance of Baveno VI criteria combined with spleen stiffness measurement (cut-off 46 kPa) for safely ruling out high-risk varices in patients with HBV-related cirrhosis under viral suppression; more than half of esophagogastroduodenoscopy procedures were spared using this combination. CLINICAL TRIAL NUMBER: NCT04123509 LAY SUMMARY: Esophageal varices have important prognostic implications in patients with cirrhosis. Thus, their timely identification is important so that treatment can be initiated early. Herein, we validated the excellent performance of the combination of Baveno VI criteria with spleen stiffness measurement (cut-off 46 kPa) for ruling out high-risk esophageal varices in patients with HBV-related cirrhosis under maintained viral suppression (with antiviral treatment). This combined model was able to safely rule out high-risk varices (missed/total <5%) and over half (61.6%) of esophagogastroduodenoscopy procedures were spared.

Application of Baveno Criteria and Modified Baveno Criteria with Shear-wave Elastography in Compensated Advanced Chronic Liver Disease.

BACKGROUND: We aimed to validate Baveno VI and expanded Baveno VI criteria using two dimensional shear-wave elastography (2D-SWE) in compensated advanced chronic liver disease (cACLD) patients with alcohol as the main etiology. METHODS: Clinical data from 305 patients with cACLD who underwent a liver stiffness measurement (LSM) with 2D-SWE and endoscopy were consecutively collected. RESULTS: Among 305 patients, high-risk varix (HRV) was identified in 21.3% (n = 65). The main etiology was alcoholic liver disease (51.8%), followed by hepatitis B virus (29.8%) and hepatitis C virus (9.1%). Baveno VI criteria spared endoscopy in 118 of the 305 (38.7%) patients, and 7 (5.9%) were missed with HRV. Expanded Baveno VI criteria spared more endoscopies (60.0%), but missed more HRV (9.8%) compared with Baveno VI criteria. The other classification described as the modified Baveno VI criteria were LSM < 25 kPa and PLT ≥ 150 × 10³/mm³. In total, 131 of the 305 (43.0%) patients were within the modified Baveno VI criteria, of whom seven (5.3%) had missed HRV. After adding spleen diameter < 12 cm to the modified Baveno VI criteria, the number of spared endoscopies increased by 106/305 (34.8%), with three (2.8%) presenting with HRV, indicating a risk of missing HRV. CONCLUSION: Baveno VI and expanded Baveno VI criteria with 2D-SWE were insufficient with an HRV miss rate of over 5%. The modified Baveno VI criteria with spleen diameters < 12 cm with 2D-SWE spared more endoscopies with a minimal risk of missing HRV in cACLD patients with alcohol as the main etiology.

A novel spleen-dedicated stiffness measurement by FibroScan® improves the screening of high-risk oesophageal varices.

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.

Prediction of Esophageal Varices by Liver Stiffness and Platelets in Persons With Human Immunodeficiency Virus Infection and Compensated Advanced Chronic Liver Disease.

BACKGROUND: People living with human immunodeficiency virus (PLWH) are at increased risk of cirrhosis and esophageal varices. Baveno VI criteria, based on liver stiffness measurement (LSM) and platelet count, have been proposed to avoid unnecessary esophagogastroduodenoscopy (EGD) screening for esophageal varices needing treatment (EVNT). This approach has not been validated in PLWH. METHODS: PLWH from 8 prospective cohorts were included if they fulfilled the following criteria: (1) compensated advanced chronic liver disease (LSM >10 kPa); (2) availability of EGD within 6 months of reliable LSM. Baveno VI (LSM <20 kPa and platelets >150 000/µL), expanded Baveno VI (LSM <25 kPa and platelets >110 000/µL), and Estudio de las Hepatitis Víricas (HEPAVIR) criteria (LSM <21 kPa) were applied to identify patients not requiring EGD screening. Criteria optimization was based on the percentage of EGDs spared, while keeping the risk of missing EVNT <5%. RESULTS: Five hundred seven PLWH were divided into a training (n = 318) and a validation set (n = 189). EVNT were found in 7.5%. In the training set, Baveno VI, expanded Baveno VI, and HEPAVIR criteria spared 10.1%, 25.5%, and 28% of EGDs, while missing 0%, 1.2%, and 2.2% of EVNT, respectively. The best thresholds to rule out EVNT were platelets >110 000/µL and LSM <30 kPa (HIV cirrhosis criteria), with 34.6% of EGDs spared and 0% EVNT missed. In the validation set, HEPAVIR and HIV cirrhosis criteria spared 54% and 48.7% of EGDs, while missing 4.9% and 2.2% EVNT, respectively. CONCLUSIONS: Baveno VI criteria can be extended to HEPAVIR and HIV cirrhosis criteria while sparing a significant number of EGDs, thus improving resource utilization for PLWH with compensated advanced chronic liver disease.

How to clarify the Baveno VI criteria for ruling out varices needing treatment by noninvasive tests.

BACKGROUND & AIMS: Baveno VI criteria enabled the screening of varices needing treatment (VNT) without endoscopy but created confusion by not stating the method used to calculate the 5% missed VNT limit, resulting in different calculations across validation studies. We analysed those calculations to clarify their diagnostic meaning. METHODS: (a) Literature review and recalculation of the missed VNT rates according to the three definitions encountered. (b) Contingency table comparison of these latter to determine their diagnostic meanings. (c) Real case analysis. 4/Simulation of variations in the three main statistical descriptors (VNT, missed VNT or spared endoscopies). RESULTS: Missed VNT rates in the three definitions varied five- to 10-fold across 7 papers. The contingency table showed that the definitions based on VNT prevalence and spared endoscopy as reference corresponded, respectively, to sensitivity and negative predictive value (NPV). The whole population-based definition corresponded to diagnostic accuracy (not pertinent in that setting). Real case analysis showed that concerning liver stiffness, the 95% sensitivity and NPV cut-offs for VNT were, respectively, 14.1 and 26.5 kPa. The VNT-based definition offered a more statistically powerful paired comparison between diagnostic tests, whereas the definition based on spared endoscopies was hampered by an unpaired comparison. Case simulation showed that the VNT-based definition was the most sensitive to descriptor variations. CONCLUSION: The definitions of missed VNT rate placing VNT or spared endoscopy as the denominator are appropriate, providing, respectively, sensitivity and NPV for VNT. We privilege the first since it corresponds to the true proportion of missed VNT.

Validation of the Baveno VI and the expanded Baveno VI criteria to identify patients who could avoid screening endoscopy.

BACKGROUND & AIMS: The Baveno VI and the expanded Baveno VI criteria were proposed to help identify patients who could safely avoid screening endoscopies for clinically significant varices among patients with compensated advanced chronic liver disease. However, these criteria require cross-validation, especially in Asian populations where the aetiologies of liver disease are different. METHODS: A total of 1035 patients, including 282 patients with compensated advanced chronic liver disease of different aetiology, were analysed. The compensated advanced chronic liver disease was defined by liver stiffness measurement ≥10 kPa, Child-Pugh class A and absence of prior liver decompensation. High-risk varix was defined as a grade ≥2 oesophageal varix, any varix with a red colour sign or gastric varices. RESULTS: High-risk varixs were present in 19.5% (55/282 patients) with compensated advanced chronic liver disease. Among compensated advanced chronic liver disease patients, the expanded criteria could spare more endoscopies (51.7%) than the original criteria (27.6%). However, the expanded criteria missed a greater number of high-risk varixs (6.8%) than the original criteria (3.8%). When stratified according to liver disease aetiology, the negative predictive values for the original Baveno VI criteria were 0.92, 1.00, 1.00 and 1.00, and the negative predictive values for the expanded criteria were 0.92, 0.96, 0.92 and 0.93 for hepatitis B, hepatitis C, alcohol and non-alcoholic fatty liver disease, respectively. High-risk varixs were rarely detected in patients without compensated advanced chronic liver disease (1.1%, 8/753 patients). CONCLUSIONS: In this Asian cohort study, the Baveno VI criteria were able to identify who could safely avoid screening endoscopy. The expanded Baveno VI criteria could spare more endoscopies but also could increase the odds of missing a high-risk varix.

Invasive and non-invasive assessment of portal hypertension.

Portal hypertension is the central driver of complications in patients with chronic liver diseases and cirrhosis. The diagnosis of portal hypertension has important prognostic and clinical implications. In particular, screening for varices in patients with portal hypertension can effectively reduce the morbidity and mortality of variceal bleeding. In this article, we review the invasive and non-invasive methods to assess portal hypertension. Hepatic venous pressure gradient remains the gold standard to measure portal pressure but is invasive and seldom performed outside expert centers and research settings. In recent years, a number of non-invasive tests of fibrosis have shown good correlation with liver histology. They also show promise in identifying patients with portal hypertension and large varices. As a result, the latest Baveno VI consensus guidelines endorse the use of liver stiffness measurement by transient elastography and platelet count as initial assessment to select patients for varices screening. On the other hand, the performance of non-invasive tests in assessing the response to non-selective beta-blockers or transjugular intrahepatic portosystemic shunting is either suboptimal or unclear.