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Liver Update: Obesity and nonalcoholic fatty liver disease: From pathophysiology to therapeutics

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eMediNexus    05 December 2021

The sudden emergence of the epidemic of obesity has also increased the prevalence and severity of nonalcoholic fatty liver disease (NAFLD). Obesity is associated not only with simple steatosis (SS) but also with advanced diseases, like nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma. 

Thus obesity has not only increased all-cause mortality but also liver-specific mortality in NAFLD patients. Since there are no approved pharmacological interventions for NAFLD, targeting obesity can be of great value in its management. Lifestyle modification (diet and exercise) remains the cornerstone of the management, however, it may be difficult to achieve and sustain. Adding pharmacotherapy is recommended in case the primary step fails. 

Several anti-obesity medications like orlistat, glucagon-like peptide-1 analogs have been investigated for use in NAFLD. While other anti-obesity medications like lorcaserin, phentermine hydrochloric, phentermine/topiramate and naltrexone/bupropion still demand an investigation. Some medications like sodium-glucose cotransporter-2 inhibitors, farnesoid X receptor ligands, having weight-lowering efficacy are not approved to be used for obesity. 

In case of failure of lifestyle modification and pharmacotherapy combination, bariatric surgery should be considered in selected morbidly obese individuals. 

Source: Metabolism, 2019;92:82-97. https://doi.org/10.1016/j.metabol.2018.11.014.

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