Metabolic comorbidity in metabolic dysfunction associated steatotic liver disease

MASLD encompasses a broad spectrum of pathologies ranging from fat accumulation alone (isolated steatosis) to fat accumulation with associated inflammation and liver cell damage (hepatocyte ballooning), collectively referred to as metabolic dysfunction-associated steatohepatitis (MASH; formerly known as nonalcoholic steatohepatitis [NASH]), and increasing degrees of fibrosis up to cirrhosis (F0–F4). Stages of worsening disease, from isolated steatosis to MASH with fibrosis or cirrhosis, are associated with progressively higher risks of adverse clinical outcomes. The progression of steatosis to MASH, fibrosis, and liver carcinoma is heterogeneous, occurring over several years or decades, and is influenced by both nonmodifiable factors (such as age, sex, race/ethnicity, heredity) and modifiable factors (such as diet, lifestyle, and medications). Since MASLD is the hepatic manifestation of metabolic syndrome, it is part of a complex multiorgan disease, with a bidirectional relationship, including overlapping risk factors. Regarding the genetic factors of MASLD and cardiovascular disease, several associated genetic variants have been reported, such as TM6SF2E16K and PNPLA3I148M. In MASLD, there are cardiometabolic risk factors such as high blood pressure, type 2 diabetes, obesity, and dyslipidemia that influence its diagnosis, prevalence, and prognosis. This chapter will discuss each of these factors.