Since 1990, the prevalence of obesity has more than doubled. In 2022, nearly one billion people were living with obesity. ⁱ The health risks of being obese or overweight are well understood and include higher mortality and morbidity due to cardiovascular disease, diabetes, cancer, neurological disorders, chronic respiratory disease, and gastrointestinal disease. Here we discuss the hepatic complications of obesity and the value of treatment for obesity for those liver complications.   

Metabolic-dysfunction associated steatotic liver disease (‘MASLD’) is found in the majority of obese patients and the prevalence correlates with the degree of obesity (i.e., the higher the grade of obesity the greater the likelihood of finding MASLD). Of patients with MASLD, 20-30% will have an inflammatory, fibrotic form of steatotic liver disease called Metabolic-dysfunction Associated SteatoHepatitis (‘MASH’) and 10-15% of MASH patients will progress to cirrhosis.ⁱⁱⁱ Among patients with co-existing type 2 diabetes and obesity of all degrees, the prevalence of MASLD, MASH, and cirrhosis has been found to be 55.5%, 37.3%, and 17%. ^iv As well, obesity worsens the prognosis of patients with compensated cirrhosis due to other causes.^v Obesity is an independent risk factor for the development of hepatocellular carcinoma (‘HCC’) and is associated with a 2-3 fold increased risk for the development of HCC, a 4-fold increase in HCC-related mortality, and a 2-fold increase in serious surgical complications following HCC resection.^vi  

Obesity results in multiple metabolic derangements that contribute to the development of steatotic liver disease and HCC. Insulin resistance and resulting hyperinsulinemia lead to diminished insulin responsiveness and failure of target organs to dispose of blood glucose. Subsequently, there is hyperglycemia, loss of inhibition of lipolysis, increased circulating free fatty acids and increased intra cellular free fatty acid intermediaries (lipotoxicity), decreased glycogen synthesis, and liver production of glucose.^vii Lipid accumulation and lipotoxicity results from excessive lipid influx and impaired lipid export, and lipid accumulation in the liver is directly related to hepatic toxicity, oxidative stress, and endoplasmic reticulum stress. These stressors activate an inflammatory cascade that can recruit and activate inflammatory cells and trigger hepatic stellate cells ushering the transition from bland steatosis (MASLD) to MASH and increasing risk of HCC.^viii  

Weight loss is the cornerstone of effective management of hepatic complications of obesity and is associated with improvement in all-cause mortality, MASLD, MASH, complications of cirrhosis, and HCC. A sustained weight loss of 5-7% of total body weight is required to achieve improvements in hepatic steatosis and hepatic steatohepatitis. Greater weight loss is required to show improvement in liver disease activity and fibrosis. Dietary modification and lifestyle interventions have been shown to achieve weight loss and improvement in MASLD, but sustained weight loss is rarely achieved with lifestyle interventions alone.^ix