Association Between Liver Fibrosis and Serum Prostate Specific Antigen (PSA) Among US Men: Findings from National Health and Nutrition Examination Survey (NHANES) 2001–2010
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Importance Some studies have observed that men with liver cirrhosis have lower serum prostate specific antigen (PSA) concentration, which could delay the detection of an occult prostate cancer. Yet, no previous study has examined the association of liver function and advanced fibrosis with serum PSA level in a US nationally representative sample of men. Objective To evaluate the association of liver fibrosis scores with PSA level among men aged older than 40 years in the overall US population and among non-Hispanic White, non- Hispanic Black, and Mexican-American or other Hispanic men. Design, Setting and Participants Data from the 2001 to 2010 continuous National Health and Nutrition Examination Survey (NHANES) were used. Males aged 40 years and over without a diagnosis of prostate cancer and who had serum PSA, liver enzymes (aspartate transaminase [AST], alanine aminotransferase [ALT]), and albumin concentrations, and platelet counts measured as part of the NHANES protocol were included in this cross- sectional analysis. Exposures Liver fibrosis was measured using three established, non-invasive fibrosis scores: AST to platelet ratio index (APRI), fibrosis 4 index (FIB-4) and NAFLD fibrosis score (NFS). Main Outcomes and Measures We assessed the overall and race-stratified geometric mean PSA concentrations by categories of the liver fibrosis scores using predictive margins by multivariable linear regression, and the association of abnormal liver fibrosis scores (APRI>1, FIB-4 >2.67, NFS>0.676) and elevated PSA levels (>2ng/mL, >4ng/mL) by multivariable logistic regression. We adjusted for age, race/ethnicity, body mass index, diabetes status, alcohol drinking, and smoking. Results Overall, 6,774 men were included in this study (mean age 55.1 years). Men with higher liver fibrosis scores had lower geometric mean PSA: APRI (p trend<0.001), FIB-4 (p trend=0.007) and NFS (p trend<0.001). After stratifying by race, this pattern remained among each race/ethnicity, though not statistically significant among non-Hispanic Black and Mexican-American/Other Hispanic men (both p trend>0.05). Men with abnormal liver fibrosis scores had a lower PSA compared with those without advanced liver fibrosis, which was also observed in each race/ethnicity group p <0.05). Moreover, regardless of the race/ethnicity men with abnormal liver fibrosis scores had a lower odds of an elevated PSA level (e.g., defined by APRI: OR of PSA >2 ng/mL=0.67; OR of PSA >4 ng/mL=0.33). Conclusions and Relevance In this US nationally representative study, men of all race/ethnicities with higher liver fibrosis scores had lower serum PSA concentration and men with advanced fibrosis scores had a lower odds of an elevated PSA, which could lower the probability of detecting asymptomatic prostate cancer. Given that early detection may be beneficial for prostate cancer treatment and survival and given that Black men are more likely to develop aggressive prostate cancer, a delayed diagnosis could contribute to the higher prostate cancer mortality among US Black men. As for any man, the risk and benefits of prostate cancer screening for men with diagnosed liver disease should be considered in decision-making.