Chalasani, NagaAbdelmalek, Manal F.Garcia-Tsao, GuadalupeVuppalanchi, RajAlkhouri, NaimRinella, MaryNoureddin, MazenPyko, MaxmillanShiffman, MitchellSanyal, ArunAllgood, AdamShlevin, HaroldHorton, RexZomer, EliezerIrish, WilliamGoodman, ZacharyHarrison, Stephen A.Traber, Peter G.2021-09-102021-09-102020-04Chalasani, N., Abdelmalek, M. F., Garcia-Tsao, G., Vuppalanchi, R., Alkhouri, N., Rinella, M., Noureddin, M., Pyko, M., Shiffman, M., Sanyal, A., Allgood, A., Shlevin, H., Horton, R., Zomer, E., Irish, W., Goodman, Z., Harrison, S. A., Traber, P. G., & Belapectin (GR-MD-02) Study Investigators. (2020). Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension. Gastroenterology, 158(5), 1334-1345.e5. https://doi.org/10.1053/j.gastro.2019.11.296https://hdl.handle.net/1805/26624Background & Aims Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies. We performed a phase 2b, randomized trial of the safety and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension. Methods Patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) from 36 centers were randomly assigned, in a double-blind manner, to groups that received biweekly infusions of belapectin 2 mg/kg (n = 54), 8 mg/kg (n = 54), or placebo (n = 54) for 52 weeks. The primary endpoint was change in HVPG (Δ HVPG) at the end of the 52-week period compared with baseline. Secondary endpoints included changes in liver histology and development of liver-related outcomes. Results We found no significant difference in ΔHVPG between the 2 mg/kg belapectin group and placebo group (–0.28 mm HG vs 0.10 mm HG, P = 1.0) or between the 8 mg/kg belapectin and placebo group (–0.25 mm HG vs 0.10 mm HG, P = 1.0). Belapectin had no significant effect on fibrosis or nonalcoholic fatty liver disease activity score, and liver-related outcomes did not differ significantly among groups. In an analysis of a subgroup of patients without esophageal varices at baseline (n = 81), 2 mg/kg belapectin was associated with a reduction in HVPG at 52 weeks compared with baseline (P = .02) and reduced development of new varices (P = .03). Belapectin (2 mg/kg) was well tolerated and produced no safety signals. Conclusions In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with significant reduction in HVPG or fibrosis compared with placebo. However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce HVPG and development of varices.enAttribution-NonCommercial-NoDerivatives 4.0 InternationalNAFLDcarbohydrate-binding proteininflammationArticle