Introduction The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. Methods and analysis This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. Ethics and dissemination The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. Trial registration number NCT05499949.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease linked with metabolic dysfunction-associated steatotic liver disease (MASLD), which may increase cardiovascular (CV) risk. This study explores the association between liver fibrosis, assessed by the Fibrosis-4 (FIB-4) index, and CV risk factors in RA patients. Methods: Cross-sectional data from the Franciscus Rheumatoid Arthritis and Cardiovascular Intervention Study (FRANCIS), a randomized, cardiovascular single center, intervention study involving RA patients without cardiovascular disease (CVD) or type 2 diabetes (T2DM), were analyzed. Liver fibrosis was assessed using FIB-4, with a cut-off point of ≥ 1.3 to define high fibrosis risk, and its relationship with CV risk factors, medication use, and subclinical atherosclerosis, measured by carotid intima-media thickness (cIMT), was evaluated. Results: Among 326 patients (68.4% female, age 53 ± 11 years, BMI 26.5 ± 4.5 kg/m²), those with high FIB-4 (n = 49) had higher cIMT (p = 0.002), apolipoprotein B48 (p = 0.04), systolic blood pressure (p = 0.007), alkaline phosphatase (p = 0.002), and anti-CCP levels (p = 0.02). High FIB-4 was associated with lower leukocyte count and complement component 3. Statin use was linked to higher FIB-4 (OR = 4.49, p = 0.014), while hydroxychloroquine use was associated with lower FIB-4 (OR = 0.11, p = 0.004). Disease activity scores did not differ between low and high FIB-4 groups. Conclusions: Elevated FIB-4 in RA patients is associated with increased cIMT, higher blood pressure, and elevated atherogenic remnants. Incorporating FIB-4 measurements into routine clinical care for RA populations could effectively identify individuals at the highest CV risk, enabling the implementation of more intensive CV risk management strategies. Key Points • RA patients with liver fibrosis have higher cIMT, indicating greater risk of atherosclerosis. • RA patients with liver fibrosis show accumulation of circulating atherogenic chylomicron remnants, contributing to atherogenesis. • HCQ may provide a protective effect against liver fibrosis in RA patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD), especially the progressive stages accompanied by liver fibrosis, are associated with liver-related and cardiovascular (CV) complications in middle-aged cohorts. We evaluated whether liver fibrosis is associated with increased mortality and cause-specific endpoints in an elderly population, and whether statin treatment could reduce these risks. PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a double-blind randomized clinical trial comparing pravastatin to placebo in an elderly Caucasian population of 5,804 patients (>70 years of age) at increased risk of CV disease. Endpoints were composite and single (CV) endpoints and all-cause mortality. The Fibrosis-4 index (FIB-4) score was classified as: low risk of liver fibrosis (FIB-4 70 years of age) with an indication of liver fibrosis.

Background: Liver fibrosis progression is influenced by older age and cardiometabolic risk factors such as obesity and is associated with an increased risk of cardiovascular events. While statins may protect against cardiovascular complications, their effects in elderly individuals with obesity and liver fibrosis are unclear.Method: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) database was used to evaluate the effect of pravastatin on major adverse cardiovascular events in an elderly population (>70 years). Subjects were categorized by BMI: lean (<25 kg/m²), overweight (25–29.9 kg/m²) and obese (≥30 kg/m²). Liver fibrosis was assessed using the FIB‐4 index: low risk (<2.0), intermediate risk (2.0–2.66) and high risk (≥2.67). Time‐to‐event data were analysed using the Cox proportional hazards model, adjusted for confounders and compared the placebo and pravastatin groups.Results: A total of 5.804 subjects were included. In the placebo group, the highest risk group (high FIB‐4 and obesity) had a significantly higher hazard ratio for (non‐)fatal stroke (HR 2.74; 95% CI 1.19–6.29) compared to the low FIB‐4, lean BMI group. This risk disappeared in the same pravastatin group. Pravastatin did not affect other cardiovascular endpoints. All‐cause mortality was significantly higher in subjects with lean weight and high FIB‐4 on placebo (HR 1.88; 95% CI 1.14–3.11), but not on pravastatin (HR .58; 95% CI .28–1.20).Conclusion: Elderly individuals with obesity and liver fibrosis are at higher risk for (non‐)fatal stroke, which is reduced with pravastatin. Pravastatin also potentially lowers all‐cause mortality in subjects with lean weight and liver fibrosis.