Noninvasive Models Underestimate CSPH in MASH Cirrhosis vs HVPG

Two noninvasive models for detecting clinically significant portal hypertension (CSPH), the Baveno VII criteria and the ANTICIPATE-NASH model, showed only moderate agreement with hepatic venous pressure gradient (HVPG) in patients with compensated metabolic dysfunction-associated steatohepatitis (MASH) cirrhosis. Both models identified fewer patients with CSPH than HVPG did, according to a baseline analysis of the phase 2b GT-026 trial of belapectin.¹

Naim Alkhouri, MD, and colleagues presented the findings as a poster at The Liver Meeting 2026 in Denver, Colorado. The investigators concluded that both algorithms may underestimate the true burden of CSPH in this population.¹

HVPG measurement is the reference standard for assessing portal hypertension, and an HVPG of at least 10 mm Hg defines CSPH, a threshold that identifies patients with compensated cirrhosis at high risk of decompensation.¹,⁶ Because HVPG is invasive and requires specialized expertise, the 2022 Baveno VII consensus endorsed noninvasive tests (NITs) for risk stratification. Under Baveno VII, liver stiffness measurement (LSM) of at least 25 kPa rules in CSPH, and LSM of 15 kPa or less with a platelet count of at least 150 × 10⁹/L rules it out.⁴

Performance of these criteria has been less consistent in patients with obesity and MASH. In the international cohort study that developed ANTICIPATE-NASH, portal hypertension was less prevalent in patients with NASH than in other etiologies (60.9% overall and 53.3% among those with obesity). The LSM rule-in cutoff had a positive predictive value of only 62.8% in patients with NASH and obesity. To address this, the investigators built the ANTICIPATE-NASH model, which adds body mass index to LSM and platelet count.⁵ The ANTICIPATE models were later externally validated in compensated NASH cirrhosis, with areas under the curve above 0.8.⁶ A 2026 individual patient data meta-analysis found the Baveno VII rule-in threshold performed well across etiologies, except in MASLD with obesity.⁷

How Well Did Noninvasive Models Agree With HVPG?

All patients in GT-026 had compensated MASH cirrhosis and underwent HVPG assessment at baseline. Investigators defined portal hypertension as HVPG of 6 to less than 10 mm Hg and CSPH as HVPG of at least 10 mm Hg. Baveno VII categories were based on LSM and platelet count.¹

ANTICIPATE-NASH estimated CSPH probability from LSM, platelet count, and body mass index¹:

• A probability of at least 75% was considered rule-in for CSPH.
• A probability of at least 50% was considered an enrichment threshold for clinical trials.

Agreement with HVPG was assessed using κ statistics.

Of 161 patients with HVPG data, HVPG identified CSPH in 67.1% (n = 108). The remaining 32.9% (n = 53) had portal hypertension without CSPH. Laboratory data needed to apply the noninvasive models were available for 131 patients.¹

By Baveno VII criteria¹:

• 51.1% (n = 67) met CSPH criteria
• 23.7% (n = 31) were classified as probable CSPH
• 25.2% (n = 33) were at low or no risk

Agreement with HVPG-defined CSPH yielded a κ of 0.44 (95% CI, 0.24–0.58; P < .001).¹

Using ANTICIPATE-NASH, CSPH probability was¹:

• 0% to 25% in 13.0% of patients (n = 17)
• 25% to 50% in 22.1% (n = 29)
• 50% to 75% in 26.7% (n = 35)
• At least 75% in 38.2% (n = 50)

Agreement between the 75% or greater probability threshold and HVPG-defined CSPH yielded a κ of 0.41 (95% CI, 0.28–0.61; P < .001).¹

Among patients with HVPG-confirmed CSPH, 62.6% met Baveno VII CSPH criteria and 48.4% met the ANTICIPATE-NASH threshold of 75% or greater.¹

Where Does Belapectin Stand in MASH Cirrhosis?

Belapectin is an intravenous galectin-3 inhibitor. In the primary GT-026 analysis of 162 patients, 1 year of biweekly infusions did not significantly reduce HVPG or fibrosis compared with placebo. In a subgroup of 81 patients without esophageal varices at baseline, however, belapectin 2 mg/kg was associated with reduced HVPG (P = .02) and fewer new varices (P = .03).²

The subsequent phase 2b/3 NAVIGATE trial tested belapectin for varices prevention in MASH cirrhosis. In topline results reported in December 2024, the incidence of varices was 43.2% lower with belapectin 2 mg/kg than with placebo in the intention-to-treat population, but the composite primary endpoint did not reach statistical significance. In the per-protocol population, varices incidence was 48.9% lower with belapectin.³

What Do the Findings Mean for CSPH Assessment in MASH?

The investigators reported that Baveno VII showed slightly greater concordance with HVPG and broader clinical stratification than ANTICIPATE-NASH. They suggested ANTICIPATE-NASH may need revisiting to better identify CSPH in MASH cirrhosis.¹

The authors concluded that noninvasive risk stratification tools can help identify patients with CSPH to enrich clinical trial populations in MASH cirrhosis.¹ Both models missed a substantial share of HVPG-confirmed CSPH in this cohort, so the findings also highlight the limits of relying on NITs alone in this population.

The analysis was conducted in a clinical trial population, and not all patients with HVPG data could be evaluated with both models. The investigators did not report how many patients were classified as false positives by either model.

*Editor’s Note: Coauthor Khurram Jamil, MD, is chief medical officer of Galectin Therapeutics, which developed belapectin.*³

References

1. Alkhouri N, Chalasani N, Lawitz E, et al. Correlation of Baveno VII and ANTICIPATE-NASH noninvasive models with HVPG in patients with MASH cirrhosis: findings from a phase 2b belapectin trial. Poster presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Chalasani N, Abdelmalek MF, Garcia-Tsao G, et al. Effects of belapectin, an inhibitor of galectin-3, in patients with nonalcoholic steatohepatitis with cirrhosis and portal hypertension. Gastroenterology. 2020;158(5):1334-1345.e5. doi:10.1053/j.gastro.2019.11.296
3. Galectin Therapeutics. Galectin Therapeutics announces top-line results of NAVIGATE clinical trial evaluating belapectin in patients with cirrhotic portal hypertension caused by MASH. Published December 20, 2024. Accessed November 5, 2026. https://investor.galectintherapeutics.com/node/18321/pdf
4. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C; Baveno VII Faculty. Baveno VII – renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959-974. doi:10.1016/j.jhep.2021.12.022
5. Pons M, Augustin S, Scheiner B, et al. Noninvasive diagnosis of portal hypertension in patients with compensated advanced chronic liver disease. Am J Gastroenterol. 2021;116(4):723-732. doi:10.14309/ajg.0000000000000994
6. Rabiee A, Deng Y, Ciarleglio M, et al. Noninvasive predictors of clinically significant portal hypertension in NASH cirrhosis: validation of ANTICIPATE models and development of a lab-based model. Hepatol Commun. 2022;6(12):3324-3334. doi:10.1002/hep4.2091
7. Bañares J, Pons M, Reiberger T, et al. Refining the Baveno VII criteria for clinically significant portal hypertension: an individual patient data meta-analysis. J Hepatol. 2026;84(3):543-553. doi:10.1016/j.jhep.2025.10.014