A Meta-Epidemiological Analysis of Sex Disparities in Hepatology Clinical Trials

Study Overview

Clinical trials have historically enrolled disproportionately fewer women, yet the extent of this disparity in hepatology had not been systematically characterized. In this meta-epidemiological study, Dr. Anna Goebel and colleagues searched PubMed to identify 1,593 randomized controlled trials (RCTs) in adult liver disease published between 2013 and 2024. Studies were grouped into four disease domains: non-MASLD chronic liver disease (CLD), metabolic dysfunction-associated steatotic liver disease (MASLD), liver cancer, and cirrhosis/liver transplantation.

To benchmark female representation meaningfully, the team linked trial enrollment data to national registries—NHANES for liver disease prevalence and UNOS for transplant waitlist demographics—allowing them to calculate participation-to-prevalence ratios (PPRs) for each domain over time. This approach situates trial enrollment within the real-world burden of disease carried by women.

Key Findings

• Women were consistently underrepresented in non-MASLD CLD trials, with PPRs as low as 0.61 in 2016, and a statistically significant decline in female enrollment over the study period (β = −0.004; P = .006).
• In contrast, MASLD trials showed adequate representation (PPRs 0.8–1.2 throughout) and a significant increase in female enrollment over time (β = 0.006; P = .025).
• Women were intermittently underrepresented in cirrhosis/transplant and liver cancer trials, with no statistically significant secular trend in either domain.
• There was a significant interaction between trial region and disease domain (P = .012): women were underrepresented in non-MASLD CLD trials conducted in the United States but not in other regions, while MASLD representation was adequate across all regions.
• Most included trials were conducted in Asia (36.3%), followed by Europe (19.5%) and the United States (16.0%).

Clinical Significance

Persistent sex-based enrollment gaps in hepatology trials risk producing evidence that does not fully generalize to women—a population that may face distinct disease biology, treatment responses, and barriers to care. The domain-specific pattern identified here suggests that disparities are not uniform: structural features of MASLD trials (primary care recruitment, high disease prevalence) may naturally facilitate enrollment equity, while non-MASLD CLD trials may be shaped by referral patterns and specialty clinic dynamics that disadvantage women.

Practical solutions include expanding eligibility criteria, offering logistical support (transportation, flexible scheduling, caregiver assistance), and increasing female investigator leadership—which correlates with higher female enrollment. At a policy level, enforcing sex-stratified enrollment targets and incorporating sex-specific subgroup analyses into trial design are essential steps toward closing these gaps.