Effect of hypertension on long-term adverse clinical outcomes and liver fibrosis progression in MASLD

Abstract

Background & aims: hypertension is common in metabolic dysfunction-associated steatotic liver disease (MASLD), but its impact on long-term clinical outcomes and disease progression remains unclear. This study investigated the association of hypertension and risk of adverse clinical outcomes and progression of liver stiffness/fibrosis in MASLD.Methods: three multicenter prospective cohorts were analyzed: the UK BioBank (UKBB) cohort to assess the risk of adverse clinical outcomes, the VCTE-Prognosis cohort to assess liver stiffness/fibrosis progression, and the Paired Liver Biopsy cohort to assess histologic liver fibrosis progression. Adverse clinical outcomes were defined as all-cause mortality, cardiovascular events, and/or liver-related events. Liver stiffness progression was defined as an increase in liver stiffness measurement (LSM) from <10 kPa to ≥10 kPa or an increase of ≥20% for baseline LSM ≥10 kPa. Liver fibrosis progression was defined as a 1-stage fibrosis stage increase. Cox regression and Kaplan-Meier analyses were used to evaluate the impact of baseline hypertension on the outcomes.Results: 107,316 adults from the UKBB cohort, 8,169 from the VCTE-Prognosis cohort, and 1,670 from the Paired Liver Biopsy cohort were included. Hypertension rates were 37.1%, 33.4%, and 48.9%, respectively. In the UKBB cohort, hypertension was associated with long-term adverse clinical outcomes (adjusted HR=1.30, 95%CI 1.26-1.33, P<0.001). In the VCTE-Prognosis cohort, hypertension was associated with a higher risk of liver stiffness progression (adjusted HR=1.57, 95%CI 1.30-1.90, P<0.001), while in the Paired Liver Biopsy cohort, hypertension was associated with a greater risk of histologic liver fibrosis progression (adjusted HR=1.41, 95%CI 1.12-1.78, P=0.004). Subgroup and sensitivity analyses supported these findings.Conclusions: hypertension is a modifiable risk factor and increases risk of adverse clinical outcomes and progression of liver stiffness/fibrosis