Liver fibrosis is associated with clinical and economic burden of cardiovascular disease in MASH

Background & Aims: The clinical and economic burden of cardiovascular (CV) disease (CVD) in patients with metabolic dysfunction-associated steatohepatitis (MASH) is incompletely understood. The unCoVer–MASH cohort study aimed to assess the association of CVD-related burden with fibrosis (Fibrosis-4 index [FIB-4]) in patients with MASH in a real-world US database. Methods: Adult patients with an ICD code for non-alcoholic steatohepatitis (NASH; October 2015–June 2022) were included if they had ≥1 FIB-4 measurement calculated from data obtained within 180 days before or 30 days after the NASH diagnosis (index date), ≥12 months of data prior to the index date (baseline period), and no diagnostic evidence of cirrhosis at baseline. FIB-4 categories were low (<1.30), intermediate (1.30–2.67), and high (>2.67). Risk of CV events was assessed during follow-up, and hazard ratios (HRs) were calculated using Cox proportional hazards models. CVD-related economic burden and resource utilization were also assessed. Results: Of 715 patients included at baseline,102 had high, 201 had intermediate, and 412 had low FIB-4 scores. The risk of any CV event was significantly greater in the high (HR 3.44; 95% CI 2.22–5.34; p <0.001) and intermediate (HR 1.53; 95% CI 1.02–2.31; p = 0.040) FIB-4 groups compared with the low group. The risk remained significant after adjustment for CV risk factors in patients with high vs. low FIB-4 (HR 2.026; 95% CI 1.215–3.380; p = 0.007). Additionally, CV-related healthcare resource utilization and CV-related costs increased with higher FIB-4 scores. Conclusions: Patients with MASH and high baseline FIB-4 scores were at an increased risk of CV events and had higher CV-related healthcare costs and resource utilization. Impact and implications: Studies specifically evaluating the clinical and economic burden of CVD in patients with MASH, without diagnostic evidence of cirrhosis, are lacking. In the current study, the clinical and economic burden of CVD in such patients was associated with baseline liver fibrosis severity, as assessed using baseline FIB-4 score, indicating a higher CV burden among patients with higher fibrosis severity. These results are important for both clinicians and payers, as they illustrate that tackling the CV-related burden in MASH is likely to have an appreciable impact on both clinical and economic outcomes.