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MASH exerts sex differences in those with HIV, according a recent study focused on sex-based differences in trends of MASH with liver fibrosis.

“The influence of sex on the pathogenesis and progression of MASH in people with HIV remains poorly understood, yet may hold profound implications for personalized healthcare delivery,” Dana Kablawi, MD, and colleagues wrote. “In the specific context of HIV infection, sex-related factors may exert differential effects on hepatic lipid metabolism, insulin resistance, and immune-inflammatory responses, thereby modulating disease susceptibility and progression.”

Dr. Kablawi and colleagues noted that sociocultural factors, healthcare-related behavior, and variance in medication adherence can also impact MASH in people with HIV across diverse gender identities. Further, menopause is likely to occur earlier among women with versus without HIV, which could result in a shorter duration of exposure to the protective benefits of estrogens on the liver.

For a study published in HIV Medicine, the researchers conducted a cross-sectional retrospective analysis of four cohorts of people with HIV from international healthcare centers from January 2015 to December 2022. Participants were adults with HIV taking antiretroviral therapy (ART) who underwent screening for MASLD using transient elastography. Exclusion criteria were applied to rule out other liver diseases, significant alcohol intake, and unreliable elastography measurements.

The study focused on examining sex-based differences in trends of MASH with liver fibrosis, using the FibroScan-AST (FAST) score as the primary outcome measure.

Differences in Women With MASH & HIV

The final sample comprised 1,472 people with HIV (25% women; mean age, 51.8). Most patients (83.1%) had undetectable HIV viral loads. The overall prevalence of MASLD was 25%, while 8.1% of participants had MASH with significant liver fibrosis, as determined by the FAST score.

Women with HIV showed distinct clinical profiles compared with men, including higher levels of certain cholesterol types, hormone levels, and liver fat measures, but no difference in liver stiffness measurements (Figure).

While FAST scores were generally higher in men, according to the study results, FAST scores rose in women “during the critical biological age of presumed perimenopause to menopause (between 40 and 50 years),” reaching levels similar to those seen in men by 55.

Further, as these trends plateaued among men, women experienced similar levels of MASH with fibrosis.

“Indeed, the prevalence of MASH with fibrosis was not significantly different after the age of 55 years,” Dr. Kablawi and colleagues wrote. “In the subgroup of 105 women (representing 28.2% of the women in the study) with available hormonal measurements, those who had MASH with fibrosis presented with higher levels of total testosterone than did women without MASH with fibrosis (0.40 ±0.27 nmol/L vs 0.23 ±0.18; P=0.048).”

The researchers saw no difference in follicle-stimulating hormone, luteinizing hormone, or estradiol.

Implications for Clinicians & Future Research

One of the study’s limitations included significant constraints in sample size, which meant that the research could not include non-binary and transgender people. Dr. Kablawi and colleagues wrote that future research “should specifically target these populations to ensure comprehensive understanding.”

Overall, the finding that MASH exhibits sex differences in people with HIV indicates that clinicians should use targeted diagnostic interventions tailored to age and menopause status for women with both conditions.

Further, the findings “emphasize the importance of considering gender-specific factors in the management and treatment of MASH in people with HIV to improve outcomes and reduce disparities in liver disease progression between men and women,” Dr. Kablawi and colleagues wrote.