The pathogenesis of metabolic dysfunction-associated steatotic liver disease and nucleoside reverse transcriptase inhibitors (NRTIs) -based HIV-antiretroviral regimens: A comprehensive narrative review.

Metabolically-dysfunction-associated steatotic liver disease (MASLD) is the result of fat accumulation in > 5 % of hepatocytes, given the absence of excessive alcohol consumption. The metabolic conditions, such as obesity with ectopic fat accumulation, serve as one of the risk factors of MASLD. The pathogenesis of MASLD may be attributed to the impaired systemic lipid metabolism as well as activation of de novo lipogenesis transcription factors, such as ChREBP and SREBP-1C, in the liver. The combined effects of both systemic dyslipidaemia and hyperactive hepatic de novo lipogenesis have been widely associated with the onset and progression of MASLD from steatosis to metabolic dysfunction-associated steatosis hepatitis (MASH). Moreover, systemic insulin resistance and impaired hepatic insulin function also correlate with the onset of MASLD. People living with HIV (PLWHIV) have been reported to be more susceptible to the development of MASLD. However, whether this could be attributed to the chronic use of antiretroviral therapy treatments (ART) or the detrimental effects of the virus remains the subject of research. Over the past decades, different regimens of ART, including highly active antiretroviral therapy (HAART), have been introduced. However, some of the HAART regimen drugs are continually being discontinued citing a variety of side effects, including metabolic derangements. Furthermore, the recent developments on GLP-1 agonists showing the cardioprotective and antidiabetic effects have elicited increasing interest in their potential repurposing for the treatment of MASLD. The preventative measures for MASLD will be imperative in the future, and this may include constant monitoring of hepatic de novo lipogenesis markers in individuals on chronic medications such as ART.