Steatotic liver disease (SLD), which includes metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD), and alcohol-associated liver disease (ALD), affects up to 40% of the global population. Advanced fibrosis in SLD is more common in patients with type 2 diabetes (T2D) and is associated with a poorer prognosis. SLD is associated with other ectopic fat depositions and cardiac remodelling. Although MASLD is the most common chronic liver disease worldwide, evidence from Swedish primary care remains limited. 

The relationship between MASLD and microvascular complications of T2D remains uncertain. Activin A has been linked to fibrogenesis, but its value as a biomarker for advanced fibrosis is unclear. Although interest in SLD screening among patients with T2D is increasing, its optimal design and cost-effectiveness remain unresolved. 

This thesis examines the prevalence, clinical correlates, and management of MASLD, with or without advanced fibrosis, among patients with T2D in primary care. It also evaluates activin A as a biomarker for advanced fibrosis and assesses the cost-effectiveness of a screening and management algorithm for SLD. 

Paper I was a retrospective primary care cohort study of patients with T2D, using medical record review and non-invasive algorithms to assess steatosis and advanced fibrosis risk. Papers II and IV analysed baseline data from a prospective primary care cohort in which patients with T2D underwent magnetic resonance imaging/spectroscopy and transient elastography to assess MASLD, with or without advanced fibrosis; Paper II also included medical record review of microvascular complications. Paper III used follow-up data from a cohort of participants with biopsy-proven MASLD to assess activin A levels and PNPLA3 I148M genotype. Paper V used a lifetime microsimulation model to evaluate the costs and health outcomes of a SLD screening and management algorithm in primary care for patients with T2D. 

In Paper I, 350 participants were included. Most had increased steatosis risk, 29–65% had increased risk of advanced fibrosis, and few had known steatosis. In Paper II, which included 308 participants with T2D, MASLD was not associated with a higher overall prevalence of microvascular complications. In Paper III, 41 participants were included; higher activin A levels were associated with advanced fibrosis and the PNPLA3 I148M G/G genotype. In Paper IV, 59% of 308 participants had MASLD and 7% had suspected advanced fibrosis. MASLD was associated with obesity, ectopic fat deposition and distinct left ventricular characteristics. In Paper V, the ICER for screening and management compared with standard of care was EUR 128,072/QALY overall, ranging from EUR 5,168/QALY for ALD to EUR 157,489/QALY for MASLD. 

In conclusion, MASLD is common among patients with T2D in Swedish primary care, although advanced disease appears uncommon and awareness of MASLD has historically been low. MASLD was not associated with an overall increase in microvascular complications, whereas obesity was associated with both MASLD and advanced fibrosis. Activin A showed potential as a biomarker for advanced fibrosis. The SLD screening and management algorithm were unlikely to be cost-effective overall, despite substantial variation between SLD subtypes.