{"id":"3fb15969-0dea-5785-8d1a-37b5767820a0","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-pf-low-dose-null","predicate":"no_significant_reduction_at_low_dose","statement":"The 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"770240d2-54e2-526f-9be9-d44008bb62c6","mechanism_event_label":"The 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.","subject":{"id":"2bddbb8e-14f7-5d4d-a89e-65ed95a2b3da","slug":"pf-06835919","display_name":"PF-06835919","entity_type_key":"drug"},"object":{"id":"c897f9af-e3c8-5626-96a1-71bcdc16cad4","slug":"human-hepatic-lipid-content","display_name":"Human hepatic lipid content measured by imaging","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"770240d2-54e2-526f-9be9-d44008bb62c6","stable_key":"c8c7aa13-14c6-5f5c-9afc-9217d0f2f736:hfcs-pf-low-dose-null-event","event_type":"observed_relationship","label":"The 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.","description":"The 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2bddbb8e-14f7-5d4d-a89e-65ed95a2b3da","slug":"pf-06835919","display_name":"PF-06835919","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c897f9af-e3c8-5626-96a1-71bcdc16cad4","slug":"human-hepatic-lipid-content","display_name":"Human hepatic lipid content measured by imaging","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"599b478d-692a-5baa-a176-ea5f55769e74","slug":"khk","display_name":"Human ketohexokinase / KHK","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"dose","value_text":"PF-06835919 75 or 300 mg once daily versus placebo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"duration","value_text":"6 weeks","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary abstract/metadata; unrecovered methods explicitly retained.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_scope","value_text":"literature_reviewed; source-specific curation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"53 randomized adults with NAFLD; 48 completed phase 2a trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure_scope","value_text":"Fructose-pathway intervention, not an HFCS challenge","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Small Pfizer-sponsored trial; 300 mg change was relative liver fat, not 18.73 percentage points. Not evidence of an approved drug or proof that HFCS caused each participant's disease.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished.","comparator":null,"unit":null,"notes":"","entity":{"slug":"high-fructose-corn-syrup","display_name":"High-Fructose Corn Syrup / HFCS","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"53 randomized adults with NAFLD; 48 completed phase 2a trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial. (2021). https://pubmed.ncbi.nlm.nih.gov/35590219/ DOI: 10.1016/j.medj.2021.04.007","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral drug; no controlled HFCS exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"MRI proton-density liver fat","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"af263d2b-2e66-5173-8275-498b23948ace","evidence_kind":"source_excerpt","locator":"Lines 605-615","start_line":605,"end_line":615,"excerpt":"## hfcs-pf-low-dose-null\nThe 75 mg/day PF-06835919 arm did not show a significant liver-fat reduction versus placebo.\nModel/species: 53 randomized adults with NAFLD; 48 completed phase 2a trial\nTissue: MRI proton-density liver fat\nExposure: PF-06835919 75 or 300 mg once daily versus placebo\nRoute: Oral drug; no controlled HFCS exposure\nDuration: 6 weeks\nExposure scope: Fructose-pathway intervention, not an HFCS challenge\nLimits: Small Pfizer-sponsored trial; 300 mg change was relative liver fat, not 18.73 percentage points. Not evidence of an approved drug or proof that HFCS caused each participant's disease.\nReference: Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial. (2021). https://pubmed.ncbi.nlm.nih.gov/35590219/ DOI: 10.1016/j.medj.2021.04.007\nAccess: Primary abstract/metadata; unrecovered methods explicitly retained.","model_system":"53 randomized adults with NAFLD; 48 completed phase 2a trial","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Exact original curation span, not a publisher quotation; provenance retained.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"e863ddf6-7c1e-5a70-8335-7f3ac3eeee92","stable_key":"import-c8c7aa13-14c6-5f5c-9afc-9217d0f2f736","title":"High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. 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