Recent literature has shown that women have a lower risk for non-alcoholic fatty liver disease (NAFLD) but a higher risk for advanced fibrosis once NAFLD is established.1 We explored the relationship of common NAFLD biomarkers in assessing disease progression risk in women vs. men with NAFLD.
Medical records for 651 patients from 10 US centers (referred for NAFLD screening with transient elastography, TE) were reviewed. There were 417 women and 234 men. Average age was 55.9. BMI range: 32% < 30, 49% 30 to 40, and 17% > 40. We analyzed TE liver stiffness (kPa), ALT, AST, age and gender. F-Score was defined as follows: F0-1: kPa< 7, F2: kPa 7–10, F3: kPa 10–14 and F4: kPa >14. These lab thresholds were used when comparing risk ratios between populations: ALT >40, AST >48, AST/ALT >1. Binomial logistic regression was used to quantify likelihood of lab values above thresholds across genders and F-Score stages (F1, F2 compared to F3, F4). Risk ratios allow us to quantify population disparities. We evaluate them with P-values, sensitivity (SEN), specificity (SPE), NPV and PPV.
We replicated previous findings that women have lower AST and ALT compared to men but higher AST/ALT ratios. Men were 1.78x more likely to have an ALT greater than 40 (P = 0.0000001) and 1.62x more likely to have an AST greater than 48 (P = 0.005). Women were 1.56x more likely to have an AST/ALT>1 (P = 0.0003). Women had more significant and consistent increases in AST/ALT compared to men as F-stage progressed. In the (F3, F4) group, women were 1.4x more likely to have AST/ALT ratios >1 compared to women in (F1, F2) group (P = 0.003). This relationship was not observed amongst males (P = 0.319). By optimizing for the sum of SEN and SPE in classifying a patient with kPa > 10 (TE advanced fibrosis category), we arrived at an AST/ALT threshold of 1.2 for women. Women with AST/ALT ratios above this threshold are 1.94x more likely to have kPa > 10 (P = 0.001). If we perform TE on all women above this threshold, 37% are expected to have kPa >10.
AST/ALT ratio increased more in women compared to men with NAFLD as TE liver stiffness F-scores increased. This could indicate a greater inflammatory response in women as NAFLD progresses. AST/ALT threshold of > 1.2 may hold promise as a proxy for disease advancement and indicate the need for additional diagnostic and/or therapeutic intervention.
1. Kanwal, et al. Clinical Gastro and Hep 2020: In Press.