Risk of cardio-nephro-metabolic disease from NAFLD to MAFLD: fact or fiction?

Abstract

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common etiology for chronic liver disease. Despite this, our understanding of this illness is lacking. The previous paradigm is that central adiposity, hyperlipidemia, hypertension, and insulin resistance, also known as metabolic syndrome, lead to NAFLD, and this relationship is unidirectional. However, recent evidence clearly shows that the clinical burden of this illness extends well beyond liver-related morbidity and mortality and is associated with multiple extrahepatic complications, particularly metabolic consequences. Due to this, the professional consensus has proposed using the term metabolic associated fatty liver disease (MAFLD) to more accurately reflect pathogenesis and help in patient stratification for management. This review discusses the shared pathophysiological mechanisms that link these diseases and how this can be leveraged to prevent these complications in individuals with NAFLD/MAFLD.

Cardiovascular disease in patients with metabolic dysfunction-associated steatohepatitis compared with metabolic dysfunction-associated steatotic liver disease and other liver diseases: A systematic review

“…Many patients included in the identified studies had other CV risk factors in addition to MASH. In particular, MASH was often comorbid with T2D, which is commonly the case as the 2 conditions share several risk factors, notably insulin resistance and obesity [ 32 ], and the presence of both increases the risk of CV events [ 33 ]. The relationship between T2D and MASLD is thought to be bidirectional, in that T2D promotes the progression of MASLD to MASH and cirrhosis, and increases all-cause and liver-related mortality, while MASLD leads to insulin resistance and poor glycemic control [ 32 ].…”

“…In particular, MASH was often comorbid with T2D, which is commonly the case as the 2 conditions share several risk factors, notably insulin resistance and obesity [ 32 ], and the presence of both increases the risk of CV events [ 33 ]. The relationship between T2D and MASLD is thought to be bidirectional, in that T2D promotes the progression of MASLD to MASH and cirrhosis, and increases all-cause and liver-related mortality, while MASLD leads to insulin resistance and poor glycemic control [ 32 ]. Other comorbidities, such as overweight/obesity and lipid imbalances, also likely mediate the relationship between MASH and CVD risk, and indeed MASH is considered as the liver manifestation of the metabolic syndrome [ 2 , 34 ].…”