Sex- and Age-Related Differences Among Liver Transplant Patients: A Narrative Review

Introduction

Liver transplantation (LT) is the definitive therapy for end-stage liver disease, acute liver failure (ALF), and selected cases of hepatocellular carcinoma (HCC). Although the Model for End-Stage Liver Disease (MELD) and its subsequent revisions—MELD-Na and MELD 3.0—were introduced to allocate organs according to medical urgency, accumulating real-world data indicate that biological and social attributes, most notably sex and age, continue to modulate access to and outcomes after LT.

As the population ages, demand for LT among older patients is rising, and donor age tends to increase in parallel.^1–3 Consequently, debates over allocating scarce resources to senior candidates and over the extent to which recipient age influences post-transplant outcomes remain contentious. Sex- and gender-related disparities in access have likewise been documented repeatedly. The United Network for Organ Sharing (UNOS) reports that women accounted for only 39.4% of all adult candidates listed for LT and 38.8% of those transplanted, even though these proportions have improved relative to previous decades.^1,4 Recent large-scale European registry analyses also confirm that women have a significantly lower probability of receiving LT compared with men, even after adjustment for disease severity and listing characteristics.^5–7 Once listed, women are more likely than men to be removed for being “too sick” and experience longer waiting times and higher wait-list mortality.^4,8–10 These findings suggest that sex- and gender-related disparities in access persist across allocation systems and geographic regions, indicating that structural factors beyond biological severity may contribute to inequity.

Beyond access, age- and sex-related disparities exist in patient and graft survival, especially when donor and recipient sex or age are mismatched.^11–14 Differences in disease etiology between sexes or across age groups explain only part of these gaps; the very structure of the disease-evaluation and allocation systems likely contributes as well. Moreover, the interplay between sex and age suggests hormonal and immunological mechanisms underlying these differences.^10,15–17

In this narrative review, we focus on adult patients and chart an updated landscape of how sex and age jointly shape every stage of LT—from waitlist placement to long-term survival—considering both donor and recipient perspectives. The result is a contemporaneous framework that clinicians and policymakers can use to advance precise LT.

Methods

A scoping literature search was conducted in PubMed to identify studies examining sex-, gender-, and age-related differences in LT. Both Medical Subject Headings (MeSH) and free-text terms were employed to ensure comprehensive retrieval.

The MeSH strategy included (“Liver Transplantation”[Mesh]) AND (“Sex Factors”[Mesh] OR “Sex”[Mesh]) AND (“Age Factors”[Mesh] OR “Aged”[Mesh] OR “Young Adult”[Mesh]). Free-text terms included (liver transplant* OR hepatic transplant*) AND (sex difference* OR gender difference* OR sex disparity*) AND (age difference* OR elderly OR “young adult” OR age disparit*).

Eligible studies reported sex-, gender-, or age-related differences as primary or secondary outcomes in adult LT populations, encompassing both living donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT). Studies published through December 2025 were considered; pediatric populations were excluded.

As this narrative review is informed by a scoping search strategy, no formal systematic review protocol or risk-of-bias assessment was applied. Study selection was guided by relevance to the research question and by the inclusion of representative, high-quality evidence across the transplantation continuum.

This review adheres to the Sex and Gender Equity in Research guidelines. The term “sex” denotes biological attributes, including chromosomal composition, hormonal profiles, and physiological characteristics. Conversely, “gender” refers to sociocultural constructs encompassing roles, behaviors, and structural determinants that influence healthcare access, clinical decision-making, and health outcomes (eg, referral patterns, allocation practices, and lifestyle exposures such as alcohol consumption). These terms are applied consistently throughout to distinguish biological mechanisms from socially and structurally mediated contributors to disparities. While conceptually distinct, sex and gender frequently intersect in shaping health outcomes; this intersection is considered throughout the review.

Discussion

Sex- and age-related differences permeate every stage of LT, from waitlist access to long-term survival. While many disparities have traditionally been attributed to biological mechanisms—such as hormonal modulation, immune regulation, and body size—emerging evidence suggests that part of the observed inequity may also be embedded in allocation structures and clinical decision-making frameworks.

Numerous studies have investigated sex- and age-related disparities in LT; key findings from representative studies cited in this review are summarized in Table 1.

OPEN IN VIEWER

Table 1.

Studies of Sex- and Age-Related Differences in LT.

Outcomes	Influencing Factors	Primary Results	References
Waitlist mortality and delist rate	Sex	- Women are more likely to be removed from the waiting list due to clinical deterioration or death.	Cron et al 4 , Cullaro et al 8 , Locke et al 9 , Lai et al 18 , Nephew et al 23 , Nephew et al 24 , Myers et al 26
	Age	- Patients aged 18−24 years demonstrate higher waitlist dropout rates compared with both pediatric (0-17 years) and older adult (25-34 years) cohorts.	Ebel et al 41
		- Increasing age is an independent risk factor for waitlist mortality.	Su et al 39 , Egbert et al 80
		- Patients older than 65 years are more frequently declined due to comorbidities; however, once listed, their waitlist mortality does not differ from that of younger candidates.	Montalti et al 74
Transplant rate	Sex	- Women have lower access to LT than men.	Cron et al 4 , Lai et al 18 , Darden et al 20 , Nephew et al 23 , Loy et al 25 , Mindikoglu et al 32 , Tanaka et al 33
	Age	- The absolute number and proportion of elderly recipients undergoing LT have increased substantially.	Kwong et al 1 , Di Maira et al 5 , Bittermann et al 13 , Okumura et al 70
Patient or graft survival	Sex	- Survival rates are comparable between sexes or slightly favor men within the first postoperative year.	Nagesh et al 28 , Germani et al 40 , Bruns et al 46 , Lee et al 47 , Serrano et al 54
		- Long-term overall survival is significantly higher in women.	Di Maira et al 5 , Nephew et al 23 , Jain et al 48 , Hong et al 49 , Germani et al 50 , Schoening et al 51 , Tejada et al 53 , Serrano et al 54
	Sex matching	- Female-to-male donor-recipient pairing demonstrates the poorest outcomes.	Chedid et al 12 , Croome et al 14 , Germani et al 40 , Lai et al 55 , Rustgi et al 59 , Schoening et al 61
		- Female-to-male matching shows inferior survival in North American centers, whereas this disparity is not observed in European cohorts.	Zeier et al 60
		- Female-to-male combinations show no impact on survival.	Lehner et al 62
	Age	- Patients over 70 years have higher in-hospital mortality risk.	Gil et al 69
		- Patients aged 18–24 years exhibit the highest post-transplant mortality across all age groups.	Ebel et al 41
		- With strict selection, short-term survival in elderly patients is comparable to that in younger recipients.	Wilson et al 71 , Aduen et al 73 , Montalti et al 74 , Oezcelik et al 76
		- With strict selection, long-term survival in elderly patients is comparable to that in younger recipients.	Bittermann et al 13 , Okumura et al 70 , Akdur et al 79 , Egbert et al 80
		- If first-year postoperative mortality is excluded, long-term survival in recipients over 55 years aligns with the natural life expectancy of the general population.	Schoening et al 51
		- Recipients older than 60 years have lower long-term survival than younger patients, even though their short-term survival is comparable.	Su et al 39 , Jain et al 48 , Garcia et al 63 , Herrero et al 64 , Keswani et al 65 , Malinis et al 66 , Chen et al 67 , Xing et al 68 , Gil et al 69 , Okumura et al 70 , Wilson et al 71
	Age matching	- Graft survival is poorest when recipients under 40 receive organs from donors ≥60 years; conversely, for any recipient age, graft failure rates are uniformly high with donor organs ≥60 and no longer vary by recipient age.	Bittermann et al 13
		- The donor–recipient age gap determines graft survival: survival is highest when the donor is younger, intermediate when 0–9 years older, and poorest when exceeding the recipient's age by >20 years.	Snyder et al 11

Sex and Gender Disparities in Access: Biology and Allocation

Sex and gender disparities have persisted at every stage of care—both before and after LT—since the first transplants were performed decades ago, and evidence suggests they have become even more pronounced in the MELD era, especially for MELD scores ≥ 15.^1,18–20 Multiple reports show that women represent less than 40% of waitlisted candidates, even though this proportion has risen over time and varies by region.^1,3,5,7 Moreover, women are less likely to be listed than men,^21,22 but more likely to be removed from the waitlist,^9,23,24 to endure longer waiting times, and—unsurprisingly—to experience higher waitlist mortality.^{7,9,18,20,25,26} Ultimately, women are less likely to receive a transplant,^{7,9,20,21,24–26} even after adjustment for disease severity and listing characteristics.^6,27 The proportion of women who undergo LT remains virtually identical to their already diminished representation on the waitlist.^1,23,28,29

Several hypotheses have been advanced to explain these disparities. One is simply that men develop end-stage liver disease more often and therefore need LT more frequently; for example, as one of the most important causes for LT, the incidence rate of HCC in men is three to four times higher than that in women. ²⁹

Systematic bias embedded in the evaluation tools is the most frequently cited and extensively studied. Emerging observations reframe allocation inequity not solely as a physiological inevitability but as a potentially modifiable feature of scoring design. The MELD score, adopted in 2002 to underpin the regional allocation system for LT, is increasingly regarded as a main driver of sex disparity. Although the revised MELD-Na score outperforms MELD, it still leaves this inequity uncorrected. ²⁶ Beyond biological differences, gender-related factors—including referral bias, caregiving responsibilities, socioeconomic constraints, and differential health-seeking behaviors—may substantially influence access to transplantation and post-transplant outcomes. These determinants remain inadequately captured by current allocation algorithms, indicating that observed inequities partly reflect structural and systemic factors rather than purely biological variation. The prolonged waiting time experienced by women can likewise be traced to MELD-related bias, as they typically present lower scores than men at comparable physiologic severity.^8,26 This bias arises from women's lower muscle mass, leading to underestimated creatinine and consequently lower MELD scores that underrepresent organ dysfunction.^10,26 Therefore, offers almost invariably flow to males with higher MELD scores, whereas women—whose scores rise as their condition deteriorates—often lose the chance of transplantation. Addressing this inequity, MELD 3.0 was proposed and implemented in July 2023, and it newly includes variables such as sex, albumin, and interactions among multiple variables. A two-center study indicates that MELD 3.0 improves waitlist mortality predictive for female candidates without compromising male patient benefits. ³⁰ Similarly, the Gender-Equity Model for Liver Allocation Sodium (GEMA-Na) has also been proposed in the United Kingdom to target sex-based disparities. Rodríguez-Perálvarez et al demonstrate that female sex, an independent predictor of waitlist mortality under MELD/MELD-Na, loses statistical significance with GEMA-Na and MELD 3.0. ²⁷ Both models show superior prediction of death and delisting compared to MELD/MELD-Na. ³¹ Although requiring further validation, MELD 3.0 and GEMA-Na offer promise for narrowing sex-based disparities in LT allocation.

Beyond scoring systems, size mismatch is equally pivotal. Women possess significantly lower body surface area, height, weight, and liver volume and mass than men.^9,32 Height primarily drives this sex gap ¹⁸ : taller women achieve transplant rates and waitlist outcomes comparable to men, whereas women shorter than 166 cm face higher refusal rates than even shorter men. ⁴ Consequently, despite MELD 3.0, height-mediated disparities persist. ³³ Nonetheless, weight remains relevant, as the heaviest women hold a 2.4% transplant advantage over the lightest men. ²⁰ Ultimately, females are declined more frequently due to inherently smaller liver volumes and intra-abdominal spaces, ⁴ a disadvantage exacerbated by the predominance of male donors in DDLT.^1,3,29,34,35 Furthermore, the limited pool of smaller grafts is often diverted to adolescent patients, leaving adult women to languish on the lists without allocation preferences.^10,18 These findings underscore the necessity to continuously recalibrate allocation systems with sex-specific variables, minimizing structural inequities to accurately reflect true disease severity across diverse patient groups.

Structural and Socioeconomic Determinants

Social and financial supports act as silent gatekeepers for transplantation evaluation. McElroy et al report that higher female unemployment (77% vs 65%, p = 0.001) exacerbates listing inequity, making tertiary education and stable income crucial for women's listing chance. ²¹ Similarly, Zhang et al demonstrate that financial hardship and traditional values pressure Chinese women to forgo LT evaluation. ³⁶

Consequently, sex or gender disparities may arise from multilevel determinants— including referral patterns, evaluation thresholds, and resource distribution—necessitating allocation reforms to avoid perpetuating systemic disadvantage. Additionally, initiatives like the International Women in Intensive and Critical Care Network is expected to narrow the gender gap in critical care.^37,38 Importantly, sex- and age-related disparities do not occur in isolation but intersect with socioeconomic status, education, and healthcare access, forming a multidimensional framework of inequity. Adopting this intersectional perspective is crucial for comprehensively understanding disparities in LT and designing more equitable allocation policies.

Population and Donor Characteristics: Age and Sex Patterns

Over the past three decades, the mean age of LT candidates and recipients has risen to 50–55 years due to aging populations and expanded transplant indications.^{1–3,28,39,40} The increase has been most pronounced among the elderly: the proportion of candidates aged ≥ 60 has more than doubled, now exceeding one-fifth, as reported according to the 2023 Organ Procurement and Transplantation Network /Scientific Registry of Transplant Recipients annual report.^1,2,39 Transplant rates, however, fall with advancing age; patients older than 70 face a 10% higher delisting and death rate than younger candidates.^2,39 Older patients also tend to be listed with lower MELD scores, implying poorer tolerance to severe conditions and lower evaluation and survive for those with high scores.^2,39

Conversely, youngest adults (18-24 years, non-Status 1A) also face higher delisting rates than those younger than 17 or aged 25–34, especially with MELD scores < 20. ⁴¹ One explanation is that few 18- to 24-year-olds with low MELD scores qualify for exception points, while the limited, size-matched grafts suitable for them are frequently allocated to pediatric recipients, leaving this age group with neither pediatric priority nor the accruing advantage of older adults. ⁴¹

In DDLT, male donors (mostly brain-dead) predominate and are markedly younger than female.^1,34,35 Yet, men yield fewer transplanted organs per donor: their higher rates of alcohol or drug abuse and fatal trauma suggest a risk-laden lifestyle drives excess early mortality and leaves usable organs unrecovered.^35,42

In contrast, while recipients remain predominantly male, LDLT donors show a female majority in Poland, several regions in Asia, and the United States.^1,29,43 The aggregate male-to-female LDLT donor ratio approaches 1:1, with the majority of grafts given to blood relatives and spouses.^29,34,43 It is reasonable to conclude that cultural narratives idealizing women's selfless dedication to family carry decisive weight, steering their healthcare decisions toward donation.

Rising demand has widened the graft supply gap, but advances in perfusion, preservation, and peri-operative care now allow the transplantation of marginal organs, pushing the acceptable donor age ever higher worldwide. From 1990 to 2013, the mean donor age has risen by nearly 10 years in the United States, ³ with donors older than 50 surging (exceeding 60% in Mediterranean countries).^5,44 Although grafts from donors older than 55 are still face refusal rates than those younger than 18 (12.4% vs 3.2%), the expansion of the donor age has shortened waiting times and lifted overall transplant rates.^1,5,45

The Impact of Sex and Age on Post-Transplant Outcomes

Biological Mechanisms and Clinical Implications

Sex or age alone is insufficient to predict post-transplant survival. Emerging data from the MELD 3.0 era demonstrate that recipient age and sex interact in shaping long-term survival trajectories. Rather than acting as isolated demographic variables, sex and age appear to function as intersecting biological axes influencing immune competence, frailty, and regenerative capacity. Several mechanisms have been proposed to explain how sex, age, and their interplay influence post-transplant survival (Figure 1).

OPEN IN VIEWER

Figure 1.

Sex-Specific Hormonal and Biochemical Pathways in LT. A. Hepatocellular lipid metabolism and HBV infection. Androgen-androgen receptor (AR) aggregation binds nuclear androgen response elements (AREs) to enhance lipogenesis and induce liver pyruvate kinase (LPK) overexpression, causing mitochondrial dysfunction, causing metabolic dysfunction-associated steatotic liver disease (MASLD); they also bind HBV episome—HBV cccDNA-AREs to promote viral replication, contributing to viral hepatitis (D). Estrogens, conversely, inhibit lipid synthesis through estrogen response elements and suppress HBV replication via competitive antagonism with hepatocyte nuclear factor-4α (HNF-4α). B. Alcohol-induced gut-liver axis injury. Alcohol disrupts intestinal barrier integrity, permitting lipopolysaccharide (LPS) translocation to portal circulation and Toll-like receptor 4 (TLR4) activation on Kupffer cells, triggering nuclear factor-kappa B (NF-κB)-mediated interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release, hepatic stellate cell activation, and M1 macrophage polarization, ultimately causing alcoholic liver disease (ALD), fibrosis, and hepatocellular carcinoma (HCC) (D). Androgens amplify TLR4 expression, whereas estrogens inhibit NF-κB nuclear translocation; however, alcohol paradoxically increases intestinal permeability and TLR4 sensitivity in females, heightening their vulnerability to alcohol-induced injury. C. Postmenopausal metabolic shift. Estrogen withdrawal precipitates visceral adiposity, mitochondrial dysfunction, and oxidative stress, accelerating progression of MASLD, fibrosis, and HCC. E–G. Post-transplant sex-specific outcomes. E. Sustained IL-6 and TNF-α elevation in males promotes HCC recurrence. F. Reduced cytochrome P450 3A4 (CYP3A4) expression in males, postmenopausal women, and elderly recipients impairs calcineurin inhibitor (CNI) clearance, causing over-immunosuppression and nephrotoxicity; immunosenescence additionally contributes to sarcopenia and frailty. G. In fertile women, estrogen-induced CYP3A4 upregulation accelerates CNI metabolism, resulting in under-immunosuppression and acute rejection risk; excessive estrogen also impairs regulatory T cell function (Treg), predisposing to autoimmune hepatitis recurrence.

One of the most frequently cited is hormonal disparity. Encompassing shifts with menopause, hormonal disparities significantly shapes transplant outcomes across age and sex strata. Estrogen protects premenopausal women by inhibiting hepatic fibrogenesis, modulating mitochondrial metabolism, retarding cellular aging, ⁹⁰ regulating lipid and glucose metabolism, safeguarding against metabolic dysfunction-associated steatotic liver disease (MASLD),^90–93 and suppressing multiple pro-inflammatory factors (such as nuclear factor-kappa B and interleukin-6) to prevent HCC.^94,95 Collectively, these mechanisms contribute to superior female recipient survival post-LT.

However, post-menopause, women forfeit the protective advantages conferred by estrogen, and their liver disease trajectory converges with that of men. In women with hepatitis C virus (HCV) infection, liver fibrosis accelerates markedly after menopause, even exceeding rates in age-matched men.^96,97 Similarly, menopause brings a rising incidence of metabolic syndrome, MASLD, and HCC. This hormonal decline may partly explain inferior outcomes from female donor grafts, often older and peri-menopausal. Conflicting evidence exists regarding ischemia-reperfusion injury (IRI) in female grafts: Croome et al suggest estrogen deprivation from IRI may inflict greater damage on female livers, ¹⁴ while Han et al demonstrate better IRI tolerance. ⁹⁸ To date, the mechanism underlying sex-mismatch outcomes remains unclear.

Beyond isolated hormonal effects, transplant outcomes are more profoundly modulated by a broader biological context encompassing immunosenescence, systemic inflammation, and metabolic reserve. These interacting factors likely modulate than isolated hormonal effects alone. Sex differences in immune responses are well-characterized, driven by hormonal milieu and X-linked genes expression in females, ⁹⁹ with premenopausal women exhibiting stronger innate and cellular immune responses than men. ⁹⁰ Immunosenescence, the age-related weakening of the immune response, presents a “double-edged sword”: while allowing lower immunosuppressive doses, it elevates the risk of infection and neoplasia recurrence, with sepsis and malignancy being leading causes of death after LT.^{64–66,72,90}

Liver size and functional reserve also matter. Adult women are, on average, shorter and lighter, yielding livers with smaller volume and mass. ⁹ A “female-sized” liver is usually adequate for another woman but may provide insufficient functional reserve for the typical larger male recipient.^14,55 On the other hand, liver size tends to shrink and metabolic reserve declines with advancing donor age, more markedly in women, potentially compromising recipient survival—particularly when a young, high-demand man receives an older female graft. ² Collectively, both sex and age matching contribute to optimal transplant outcomes.

Introducing age and sex together appears to shed clearer insight through which to uncover how these factors jointly shape survival outcomes; however, such analyses remain scarce.

Whether sex influences post-LT thrombotic risk remains contentious: some cohorts record more vascular thromboses when a female graft is implanted in a male recipient,^14,61 whereas Ikegami et al attribute the excess risk to female recipients themselves. ¹⁰⁰ Likewise, age effects are inconsistent. Immunosenescence would predict higher sepsis rates in older patients, ⁷² yet multiple series detect no sex- or age-linked differences in either surgical complications or infection,^{48,54,64,74–76,79,80} and one study even reports fewer biliary complications among the elderly. ¹⁰¹

Females experience both acute and chronic rejection more often than males, ⁶¹ whereas elderly women have a lower rejection burden. ⁷² Across almost all studies, younger age remains the strongest demographic risk factor for post-LT rejection.^{64,72,75,78,102}

Viral recurrence patterns are sex-skewed: hepatitis B virus (HBV) and HCV relapse are consistently more frequent in men,^14,54,61 although Serrano et al noted that non-malignant HCV recurrence was slightly more common in women.

HCC recurrence is markedly male-predominant, especially when a male graft is used^{10,14,15,54,61,67,103–105}; de novo solid tumors also arise more often in male recipients^15,54; This male excess is abolished, however, when donor age exceeds 40 years, ¹⁰⁴ implying that donor-derived estrogenic signaling—acting via hepatic sex hormone receptors rather than circulating levels—confers protection, whereas androgen signaling fosters HCC cell proliferation.^103–105 Chronological age remains an independent risk factor for both de novo and recurrent malignancy, with incidence rising steadily after the sixth decade.^64,72 Collectively, these observations align with the dual influences of sex hormone milieu and immunosenescence detailed above.

In contrast, among patients transplanted for alcoholic liver disease (ALD), women are more likely to resume drinking after LT and consequently develop allograft dysfunction ¹⁰⁶ ; likewise, younger heavy drinkers maintain abstinence less successfully than older ones. ¹⁰⁶

New-onset chronic kidney disease (CKD) is associated with poorer survival and occurs frequently after LT.^107,108 Fussner et al demonstrate that female sex and advanced age are independent risk factors for CKD. ¹⁰⁸ This excess risk probably reflects (i) women's higher fat mass and lower cytochrome P450 expression, which raise circulating calcineurin inhibitors (CNI) levels and nephrotoxic exposure ¹⁰⁹ ; (ii) immunosenescence that blunts renal repair and magnifies subclinical CNI injury ¹¹⁰ ; and (iii) the steeper age-related decline in female donor liver volume, which amplifies reperfusion-induced systemic inflammation. ¹¹⁰ These mechanisms act in concert to promote post-transplant CKD in older female recipients.

Sex and Age-Related Differences in the Etiology of LT

The HBV and HCV epidemics peaked four to five decades ago; those infected are now elderly. Potent antiviral therapies have slashed the share of viral hepatitis among LT indications, removing it from the top of the list^1,65,111; nevertheless, hepatitis B and HBV cirrhosis still predominate in certain regions, such as eastern Europe and China.^5,112,113 Chronic HBV is male-predominant,^112,114 whereas fulminant HBV is more common in women ¹¹⁴ ; HCV prevalence does not show a consistent trend between the sexes.^112,114 Estrogen appears to curb viral replication ¹¹⁵ and slow fibrosis progression, but this protective edge fades rapidly after menopause, as outlined earlier. Given that many women requiring LT are present in the peri- or post-menopausal period, early initiation of antiviral therapy is especially critical for female patients. ¹⁶

ALD is now the leading indication for adult LT, accounting for > 40% of all transplants. ¹ Although men still outnumber women with alcohol-use disorder, the gender gap is narrowing as female drinking rises.^17,116 While men exhibit a higher absolute prevalence of alcohol-use disorder, women demonstrate heightened biological vulnerability to ALD. Clinically, women progress from heavy drinking to end-stage liver disease and require transplantation at significantly lower cumulative alcohol doses and shorter durations of exposure than men.^117,118

Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, renamed MASLD /metabolic dysfunction-associated steatohepatitis in 2023, is the fastest-growing indication for LT worldwide.^1,5 Its incidence climbs with age and shows clear sex dimorphism^{16,112,119,120}: in the US, MASLD has become the leading cause of LT in women. ¹¹¹ Premenopausal women, potentially due to hormonal and metabolic differences, develop MASLD less often than men, but after menopause their risk rapidly converges to that of age-matched men.^119,120 In addition, gender-related lifestyle differences—such as dietary patterns, physical activity levels, and rates of central obesity—further widen the MASLD incidence gap between sexes. ¹¹⁹

Autoimmune liver disease is also on the rise and has even become the primary cause of LT in certain areas. ¹²¹ Autoimmune hepatitis predominantly affects women and is increasingly diagnosed in the elderly.^10,122 Primary biliary cirrhosis remains overwhelmingly a disease of women, with its incidence peaking in the middle-aged and older population， though male cases are now creeping upward.^10,65,123 In contrast, primary sclerosing cholangitis shows a male predominance and peaks in middle age.^124–126

These disorders collectively account for 10% ∼ 30% of all LTs via HCC.^1,5,113 HCC develops predominantly in men and older patients, a pattern attributable to sex-hormone and immunologic drivers.^10,112,116 Because HCC occurs more frequently in men, they more often receive MELD exception points^24,25 and undergo transplantation at higher rates. ⁴

Conclusion

Sex- and age-related differences profoundly influence every stage of LT, permeating access, allocation, and post-transplant outcomes. Accurate characterization of sex-specific biological variables—including hormonal milieu, immune function, body size, and the impact of postmenopausal estrogen decline—is indispensable for optimizing donor-recipient matching and enhancing transplant success. While chronological age is no longer an absolute contraindication, stringent physiological selection remains paramount for achieving favorable results in older recipients.

Beyond recipient characteristics, donor sex and age exert a significant—yet often underappreciated—influence on graft performance and long-term trajectories. This highlights the imperative for more granular analyses within large, high-quality datasets to refine allocation strategies. Emerging sex-adjusted allocation models demonstrate superior predictive performance compared with traditional scoring systems, thereby supporting the integration of sex-specific variables into clinical decision-making.

Collectively, these findings underscore the urgent need to transcend assumptions of neutrality within current allocation systems. Future frameworks should explicitly integrate sex- and age-sensitive variables, ensuring that access to transplantation authentically reflects both clinical urgency and crucial equity considerations. Ultimately, advancing equity in LT demands not only biological precision but also a keen recognition of the structural and systemic factors that shape disparities, bridging clinical science with health policy and the broader social determinants of health.