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Lonardo. Metab Target Organ Damage 2024;4:7 https://dx.doi.org/10.20517/mtod.2023.56 Page 3 of 7

factors, MAFLD was found to be moderately associated with the cancers of the female genital tract: labium,
uterus, cervix, and ovary [hazard ratio (HR) 2.24; 95%CI: 1.09-4.60].

A recent study conducted by Yuan et al. among 151,391 Chinese participants in the Kailuan cohort reported
a substantially increased risk of breast cancer in MAFLD associated with excessive alcohol consumption
(HR = 7.27, 95%CI: 2.33-22.69) and, to a lower extent, in MAFLD with metabolic dysregulation, (HR = 1.99,
95%CI: 1.01-3.92); and in MAFLD with overweight and metabolic dysregulation (HR = 1.33, 95%CI: 1.02-
1.74) . Interestingly, these authors also found that liver fibrosis was associated with increased odds of
[14]
[14]
overall incident cancer and various site-specific cancer incidence and mortality among MAFLD patients .
The importance of hepatic fibrosis as a determinant of cancer risk is also pinpointed by the study by Chung
[15]
et al. . These authors leveraged the Korean National Health Insurance Service database to categorize the
9,718,182 participants into three groups: (A) single-etiology MAFLD (= 29%) (SMAFLD); (B) mixed-
etiology MAFLD (M-MAFLD) (e.g., concurrent liver diseases and/or heavy alcohol consumption = 7%);
and (C) MAFLD-free controls. During the median 8.3-year follow-up, it was the M-MAFLD with fibrosis
group (defined with BARD score ≥ 2) that suffered the highest odds of all-cancer incidence [adjusted HR
(aHR) = 1.38, 95%CI = 1.36-1.39], followed by the M-MAFLD without fibrosis group (aHR = 1.09, 95%CI =
1.06-1.11) . Cancer-related mortality exhibited similar trends .
[15]
[15]
THE STUDY BY CRUDELE ET AL. [16]
With this intriguing backset highlighting the potential risk of cancer of the female genital tract among those
individuals with fibrotic liver disease, Crudele et al. utilized the aspartate transaminase/alanine transaminase
(AST/ALT)-to-platelet ratio (AARPRI), a surrogate index of hepatic fibrosis, to ascertain whether NAFLD,
more than obesity per se, is a risk factor for the development of cancer of the female genital system . To
[16]
this end, 653 women with metabolic dysfunction were followed up for 8 years. Data have shown that a set of
surrogate indices of liver fibrosis AARPRI, AST to Platelet Ratio Index (APRI), Fibrosis-4 index (FIB-4),
modified FIB-4 (mFIB-4) could significantly differentiate those women who developed cancer from those
who did not (P < 0.001). Receiver-operating curve (ROC) analysis showed that these non-invasive indices
had good sensitivity, and specificity in identifying those cancer-developing women (P < 0.001). Moreover,
increased AARPRI had the highest odds of development of genital cancer among women
[16]
[odds ratio (OR) = 6, (P < 0.001)] . The authors conclude that their study supports the notion that it is
NAFLD, more than obesity, that is linked with the milieu of gynecological cancers .
[16]

The findings from this study are closely reminiscent of the seminal study by Allen et al. . These authors, by
[17]
comparing to 441 age and sex-matched controls 4,722 USA NAFLD patients, found that NAFLD was
associated with an approximately 2-fold increased risk of developing cancers [IRR = 1.9 (95%CI: 1.3-2.7)]
during a median follow-up of 8 years (range, 1-21). Interestingly, the uterus was among the most often
affected organs. Additionally, this study also found that the increased risk of cancer was more strongly
associated with NAFLD than with obesity, identified through body mass index .
[17]

Collectively, the above studies would support the utilization of scores of hepatic fibrosis to triage those
individuals at risk of developing cancer . However, given the common occurrence of NAFLD/MAFLD in
[18]
the general population, additional studies are needed to confirm these findings and evaluate the cost/benefit
ratio of extensive screening practices aimed at early diagnosis of female genital tract among asymptomatic
women with fibrosing NAFLD/MAFLD.