Context:

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a liver disease characterized by fat accumulation and inflammation in the liver. Genetic factors, such as variants in the PNPLA3, TM6SF2, GCKR, and MBOAT7 genes, play a significant role in increasing the risk and progression of MASH. Family history and ethnicity also contribute to the likelihood of developing MASH, with higher prevalence observed in individuals of Hispanic and European descent. Additional risk factors include certain lifestyle choices, such as high-fat diets, sedentary habits, smoking, and exposure to air pollution, as well as underlying health conditions like obesity and diabetes. The disease is more common in older adults and can lead to severe complications, including liver fibrosis and cancer, significantly reducing life expectancy compared to the general population.

Dive Deeper:

• MASH is an advanced form of fatty liver disease involving both fat build-up and inflammation, which distinguishes it from simpler forms of fatty liver disease.

• Genetic variants such as PNPLA3 p.I148M and TM6SF2 E167K are linked to increased fat accumulation and inflammation in the liver, contributing to the onset and progression of MASH.

• First-degree relatives of individuals with MASH have a higher risk of developing the condition, indicating a strong genetic component in its transmission within families.

• The prevalence of MASH varies among ethnic groups, with Hispanic and European populations in the United States exhibiting the highest rates, while African Americans have the lowest.

• Lifestyle factors, including high-fat diets, lack of physical activity, smoking, and long-term exposure to air pollution, exacerbate the risk of developing MASH.

• Metabolic conditions such as obesity and diabetes significantly heighten the risk of MASH by promoting liver fat accumulation and disrupting lipid metabolism.

• The progression of MASH is associated with aging, as older adults are more prone to liver fat accumulation, fibrosis, and potential liver cancer, impacting their overall life expectancy.