AST/ALT-to-platelet ratio (AARPRI) predicts gynaecological cancers: a 8-years follow-up study in 653 women

Abstract

Non-alcoholic fatty liver disease (NAFLD), specifically liver steatosis and fibrosis with steatohepatitis (NASH), is often associated with visceral adiposopathy, whose pathogenetic features have been proposed as tumorigenic triggers. We performed a prospective analysis in 653 metabolic women to reveal any conditions that may predict and concur to cancer development during a 8-years period of follow-up. Among clinical and biochemical variables, only AST and non-invasive liver fibrosis scores (AARPRI, APRI, FIB-4, mFIB4) significantly distinguished cancer-developer women (n = 62, 9.5%) from those who did not develop cancer (p < 0.001). In ROC analysis, these scores also showed good sensitivity and specificity in differentiating women who developed cancer (all p < 0.001). We then calculated OR for these indexes finding that increased AARPRI was associated with the highest risk (OR = 6, p < 0.001) of gynaecological cancers development. We further validated these cut-off values in women who had developed other types of cancer, confirming that AARPRI is able to identify the risk for cancer development (OR = 5, p < 0.001). Our findings support the hypothesis that NAFLD, more than obesity per se, is directly associated with the clinical and pathogenic metabolic scenario of gynaecological cancers and encourage the use of liver fibrosis indexes to detect risk of cancer onset in women. Preventing adiposopathy and NAFLD through lifestyle and therapies may represent an instrumental strategy for cancer prevention and/or co-treatment in oncology.

Figure 1

New cancer diagnosis during the follow-up period. New cancer cases have been recorded during a follow-up period up to 8 years. Patients first assessment was performed from January 2014 to December 2017. Follow-up was performed every year, by phone or clinical evaluation according to clinical conditions and Institutional policy for patients’ prevalent disease, and concluded in December 2022.

Figure 2

Non-invasive hepatic fibrosis scores comparisons between women who developed cancer and women who did not during the follow-up period. Comparisons between AARPRI (A), APRI (B), FIB-4 (C), mFIB-4 (D) values in patients who developed (n = 62) and did not develop (n = 591) cancer during the follow-up period. Statistical significance was assessed by Mann–Whitney U Test, p < 0.05 were considered significant (***p < 0.001). The box plots show the median (second quartile), first and third quartile, Tukey whiskers represents 1.5 times the interquartile distance or to the highest or lowest point, whichever is shorter. Any data beyond these whiskers are shown as points. AST, aspartate transaminases; AARPRI, (AST to ALT ratio) to Platelet Ratio Index; APRI, AST-platelet ratio index; FIB-4, fibrosis-4 index; mFIB-4, modified FIB-4.

Figure 3

ROC reports for gynaecological (uterus, breast, ovarian) cancer discrimination. Cut-off values with related sensitivity and specificity levels and empirical estimation of area under curve (AUC) are shown under each graph for AARPRI (A), FIB-4 (B), APRI (C), and mFIB-4 (D). YI, Youden’s Index; AARPRI, (AST to ALT ratio) to Platelet Ratio Index; FIB-4, fibrosis-4 index; APRI, AST-platelet ratio index; mFIB-4, modified FIB-4.

Figure 4

Risk for gynaecological (uterus, breast, ovarian) cancers development. For WC, FPG, HDL, and TG we considered cut-off values used for Metabolic Syndrome IDF diagnosis. For AARPRI, APRI, FIB-4, and mFIB-4 we considered cut-off values computed in ROC analysis (see Fig. 3). Each row shows the contingency table to assess the Odds Ratio (OR) and detect the association of single dysmetabolic conditions with gynaecological cancers development. For each variable, OR representation with 95% confidence interval is provided. (***) represents p < 0.001. BMI, body mass index; WC, waist circumference; FPG, fasting plasma glucose; TG, triglycerides; AARPRI, (AST to ALT ratio) to platelet ratio index; APRI, AST-platelet ratio index; FIB-4, fibrosis-4 index; mFIB-4, modified FIB-4.

Figure 5

Risk for not gynaecological cancers development. For WC, FPG, HDL, and TG we considered cut-off values used for IDF Metabolic Syndrome diagnosis. For AARPRI, APRI, FIB-4, and mFIB-4 we considered cut-off values computed in ROC analysis (see Fig. 3). Each row shows the contingency table to assess the Odds Ratio (OR) and detect the association of single dysmetabolic conditions with not gynaecological cancer development. For each variable, OR representation with 95% confidence interval is provided. (*) represents p < 0.05, (**) p < 0.01, (***) p-value < 0.001. BMI, body mass index; WC, waist circumference; FPG, fasting plasma glucose; TG, triglycerides; AARPRI, (AST to ALT ratio) to platelet ratio index; APRI, AST-platelet ratio index; FIB-4, fibrosis-4 index; mFIB-4, modified FIB-4.