Sex and ethnic disparities in hepatitis B evaluation and treatment across the world.

BACKGROUND & AIMS: Oral antiviral therapy with nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB) is well-tolerated and lifesaving, but real-world data on utilization are limited. We examined rates of evaluation and treatment in patients from the REAL-B consortium. METHODS: This was a cross-sectional study nested within our retrospective multinational clinical consortium (2000-2021). We determined the proportions of patients receiving adequate evaluation, meeting AASLD treatment criteria, and initiating treatment at any time during the study period. We also identified factors associated with receiving adequate evaluation and treatment using multivariable logistic regression analyses. RESULTS: We analyzed 12,566 adult treatment-naïve patients with CHB from 25 centers in 9 countries (mean age 47.1 years, 41.7% female, 96.1% Asian, 49.6% Western region, 8.7% cirrhosis). Overall, 73.3% (9,206 patients) received adequate evaluation. Among the adequately evaluated, 32.6% (3,001 patients) were treatment eligible by AASLD criteria, 83.3% (2,500 patients) of whom were initiated on NAs, with consistent findings in analyses using EASL criteria. On multivariable logistic regression adjusting for age, sex, cirrhosis, and ethnicity plus region, female sex was associated with adequate evaluation (adjusted odds ratio [aOR] 1.13, p = 0.004), but female treatment-eligible patients were about 50% less likely to initiate NAs (aOR 0.54, p <0.001). Additionally, the lowest evaluation and treatment rates were among Asian patients from the West, but no difference was observed between non-Asian patients and Asian patients from the East. Asian patients from the West (vs. East) were about 40-50% less likely to undergo adequate evaluation (aOR 0.60) and initiate NAs (aOR 0.54) (both p <0.001). CONCLUSIONS: Evaluation and treatment rates were suboptimal for patients with CHB in both the East and West, with significant sex and ethnic disparities. Improved linkage to care with linguistically competent and culturally sensitive approaches is needed. IMPACT AND IMPLICATIONS: Significant sex and ethnic disparities exist in hepatitis B evaluation and treatment, with female treatment-eligible patients about 50% less likely to receive antiviral treatment and Asian patients from Western regions also about 50% less likely to receive adequate evaluation or treatment compared to Asians from the East (there was no significant difference between Asian patients from the East and non-Asian patients). Improved linkage to care with linguistically competent and culturally sensitive approaches is needed.

Quantitative HBeAg is a strong predictor of HBeAg loss among patients receiving pegylated interferon.

BACKGROUND: HBeAg loss is an important endpoint for antiviral therapy in chronic hepatitis B (CHB), however there are no reliable biomarkers to identify patients who will respond to the addition of pegylated interferon to nucleos(t)ide analogue (NA) therapy. AIM: To evaluate the use of serum biomarkers to predict HBeAg loss. METHODS: HBeAg positive CHB participants on NAs who switched-to or added-on 48 weeks pegylated interferon alpha2b (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBeAg loss. The predictive ability of qHBeAg, qHBsAg, HBV RNA and clinical variables for HBeAg loss were investigated. RESULTS: HBeAg loss occurred in 15/55 (27.3%) participants who completed 48 weeks of pegylated interferon. There was a lower baseline qHBeAg (1.18 IU/mL [2.27] versus 10.04 IU/mL [24.87], P = 0.007) among participants who lost HBeAg. Baseline qHBeAg (OR = 0.15, 95% CI 0.03-0.66, P = 0.01) and detectable HBV DNA at baseline (OR = 25.00, 95% CI 1.67-374.70, P = 0.02) were independent predictors of HBeAg loss. In addition, on-treatment qHBeAg was also a strong predictor of HBeAg loss (OR = 0.39, 95% CI 0.18-0.81, P = 0.012). The models combining detectable baseline HBV DNA with baseline (C-statistic 0.82) and on-treatment (C-statistic 0.83) had good accuracy for predicting HBeAg loss. A rise in qHBeAg ≥ 10 IU/ml was a predictor of flare (ALT ≥ 120 U/ml) on univariable analysis but not after adjustment for treatment arm. CONCLUSIONS: Baseline and on-treatment qHBeAg is a useful biomarker that can identify participants on NA therapy who may benefit from adding or switching to pegylated interferon.

Single-cell landscape of functionally cured chronic hepatitis B patients reveals activation of innate and altered CD4-CTL-driven adaptive immunity.

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) loss or functional cure (FC) is considered the optimal therapeutic outcome for patients with chronic hepatitis B (CHB). However, the immune-pathological biomarkers and underlying mechanisms of FC remain unclear. In this study we comprehensively interrogate disease-associated cell states identified within intrahepatic tissue and matched PBMCs (peripheral blood mononuclear cells) from patients with CHB or after FC, at the resolution of single cells, to provide novel insights into putative mechanisms underlying FC. METHODS: We combined single-cell transcriptomics (single-cell RNA sequencing) with multiparametric flow cytometry-based immune phenotyping, and multiplexed immunofluorescence to elucidate the immunopathological cell states associated with CHB vs. FC. RESULTS: We found that the intrahepatic environment in CHB and FC displays specific cell identities and molecular signatures that are distinct from those found in matched PBMCs. FC is associated with the emergence of an altered adaptive immune response marked by CD4 cytotoxic T lymphocytes, and an activated innate response represented by liver-resident natural killer cells, specific Kupffer cell subtypes and marginated neutrophils. Surprisingly, we found MHC class II-expressing hepatocytes in patients achieving FC, as well as low but persistent levels of covalently closed circular DNA and pregenomic RNA, which may play an important role in FC. CONCLUSIONS: Our study provides conceptually novel insights into the immuno-pathological control of HBV cure, and opens exciting new avenues for clinical management, biomarker discovery and therapeutic development. We believe that the discoveries from this study, as it relates to the activation of an innate and altered immune response that may facilitate sustained, low-grade inflammation, may have broader implications in the resolution of chronic viral hepatitis. IMPACT AND IMPLICATIONS: This study dissects the immuno-pathological cell states associated with functionally cured chronic hepatitis B (defined by the loss of HBV surface antigen or HBsAg). We identified the sustained presence of very low viral load, accessory antigen-presenting hepatocytes, adaptive-memory-like natural killer cells, and the emergence of helper CD4 T cells with cytotoxic or effector-like signatures associated with functional cure, suggesting previously unsuspected alterations in the adaptive immune response, as well as a key role for the innate immune response in achieving or maintaining functional cure. Overall, the insights generated from this study may provide new avenues for the development of alternative therapies as well as patient surveillance for better clinical management of chronic hepatitis B.

Antiviral therapy substantially reduces HCC risk in patients with chronic hepatitis B infection in the indeterminate phase.

BACKGROUND AND AIMS: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. APPROACH AND RESULTS: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminase

An Uncommon Case of Weight Loss in a Nonagenarian.

Weight loss in older adults can be due to multiple causes. A systematic approach is required to pinpoint the etiology. Dysphagia is an important symptom associated with weight loss. In the absence of anatomical abnormalities, functional swallowing disorders such as achalasia can be mistaken for an aging esophagus or oropharynx. The incidence of achalasia in older adults is rare, with most cases presenting between 30 to 60 years of age. Here, we present an uncommon case of achalasia in a 93-year-old Chinese woman. A barium swallow and high-resolution manometry confirmed the diagnosis of achalasia. Botulinum toxin injection was administered. She did well, achieving weight gain and resolution of her symptoms. In conclusion, early recognition and appropriate management of uncommon causes of weight loss can greatly improve the quality of life of older adults.

Switching to or Add-on Peginterferon in Patients on Nucleos(t)ide Analogues for Chronic Hepatitis B: The SWAP RCT.

BACKGROUND & AIMS: The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA. METHODS: We conducted a randomized controlled trial of CHB patients on NA >12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 µg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg) >1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg <200 IU/mL, qHBsAg <100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT). RESULTS: A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P < .0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P < .001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P < .0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy). CONCLUSIONS: ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.

Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study.

BACKGROUND AND AIMS: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). METHODS: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan-Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). RESULTS: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11-1.43) was associated with higher risk of worsening renal function. CONCLUSION: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

Comparative biomarkers for HBsAg loss with antiviral therapy shows dominant influence of quantitative HBsAg (qHBsAg).

BACKGROUND: Biomarkers such as quantitative HBsAg (qHBsAg), quantitative hepatitis B virus (HBV) core-related antigen (qHBcrAg) and HBV RNA may be useful in predicting HBsAg loss in patients with chronic hepatitis B (CHB) undergoing antiviral therapy. AIM(S): Our study evaluated qHBsAg, HBV RNA and qHBcrAg as a posthoc analysis of a randomized clinical trial of peginterferon±NA to determine their utility in predicting HBsAg loss. METHODS: CHB patients who completed therapy with 48weeks peginterferon alpha2b ± nucleoside analogue therapy (clinicaltrial.gov NCT01928511) were evaluated at week 72 for HBsAg loss. The predictive ability of qHBsAg, qHBcrAg, HBV RNA and other variables were investigated by univariate and multivariate logistic models for HBeAg-negative patients by odds ratios, area under the curve (AUC), sensitivity, specificity, and positive and negative likelihood ratios (LR). RESULTS: HBsAg loss occurred in 15/114(13%) HBeAg-negative CHB patients who completed 48 weeks of peginterferon. At baseline, qHBsAg was superior to HBcrAg and HBV RNA with AUC 0.916, 0.649 and 0.542, respectively. Using multivariate analysis, the model comprising treatmentarm, age, gender, baseline qHBsAg, HBcrAg and HBV RNA, weeks 4 & 8 qHBsAg had the highest AUC(0.98), but the univariate model with week 8 qHBsAg <70 IU/mL had AUC 0.96. Hence, the contributions of variables other than qHBsAg were marginal. HBV RNA and qHBcrAg were weak predictors of HBsAg loss. Kinetics of the novel markers showed only qHBsAg had a good relationship with HBsAg loss while HBV RNA had a marginal relationship and HBcrAg did not change at all, and none had a good relationship with viral rebound. CONCLUSIONS: On-treatment biomarker predictors were better than baseline ones, and the best predictor of HBsAg loss at 72 weeks was week 8 qHBsAg <70 IU/mL.

Effects of Prolonged Spaceflight on Atrial Size, Atrial Electrophysiology, and Risk of Atrial Fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) in active astronauts is ≈5%, similar to the general population but at a younger age. Risk factors for AF include left atrial enlargement, increased number of premature atrial complexes, and certain parameters on signal-averaged electrocardiography, such as P-wave duration, root mean square voltage for the terminal 20 ms of the signal-averaged P wave, and P-wave amplitude. We aimed to evaluate changes in atrial structure, supraventricular beats, and atrial electrophysiology to determine whether spaceflight could increase the risk of AF. METHODS: Thirteen astronauts underwent cardiac magnetic resonance imaging to assess atrial structure and function before and after 6 months in space and high-resolution Holter monitoring for multiple 48-hour time periods before flight, during flight, and on landing day. RESULTS: Left atrial volume transiently increased after 6 months in space (12±18 mL; P=0.03) without changing atrial function. Right atrial size remained unchanged. No changes in supraventricular beats were noted. One astronaut had a large increase in supraventricular ectopic beats but none developed AF. Filtered P-wave duration did not change over time, but root mean square voltage for the terminal 20 ms decreased on all fight days except landing day. No changes in P-wave amplitude were seen in leads II or V1 except landing day for lead V1. CONCLUSIONS: Six months of spaceflight may be sufficient to cause transient changes in left atrial structure and atrial electrophysiology that increase the risk of AF. However, there was no definite evidence of increased supraventricular arrhythmias and no identified episodes of AF.

Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study.

BACKGROUND AND AIMS: Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. METHODS: Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. RESULTS: Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12-2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27-2.85). CONCLUSIONS: Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

Statin-associated muscle symptoms and SLCO1B1 rs4149056 genotype in patients with familial hypercholesterolemia.

UNLABELLED: Patients with familial hypercholesterolemia (FH) may be at increased risk for statin-associated muscle symptoms because they require long-term treatment with high-intensity statin therapy. We sought to determine (1) whether other predisposing factors, including the well-known genetic variant associated with statin-associated muscle symptoms-solute carrier organic anion transporter family, member 1B1 (SLCO1B1) rs4149056-also increase the risk of statin-associated muscle symptoms in FH patients, and (2) the natural history and management for FH patients with statin-associated muscle symptoms. METHODS: We queried electronic records (2004-2014) of 278 genetically screened FH patients (113 men, 165 women; mean [SD] pretreatment low-density lipoprotein cholesterol [LDL-C] 259 [72] mg/dL) recruited from lipid clinics in the Dallas, TX, area from 2004 to 2014. Statin-associated muscle symptoms were defined as muscle symptoms arising while taking a statin and interrupting therapy. RESULTS: The risk of muscle symptoms was associated with age (odds ratio 1.6 [95% CI 1.2-2.2]), body mass index in non-African Americans (0.90 [0.83-0.97]), and hypertension (0.4 [0.2-0.9]). Simvastatin was the most commonly used statin, and it was the statin most associated with muscle symptoms. Among FH patients with muscle symptoms, 41% (n = 40) reestablished statin therapy ("eventually tolerant") and 29% (n = 28) never reestablished statin therapy ("never tolerant"). Rosuvastatin (43%) and pravastatin (30%) were the most common eventually tolerated statins, and eventually tolerant patients achieved lower treated LDL-C levels (eventually tolerant 127 vs never tolerant 192 mg/dL, P < .001). Never tolerant patients also developed muscle symptoms on nonstatins (16% vs 50%, P = .003). SLCO1B1 rs4149056 genotyping revealed 224 wild-type patients (TT) and 49 heterozygotes (TC). SLCO1B1 genotype was not associated with the risk of statin-associated muscle symptoms (odds ratio 1.40 [95% CI 0.74-2.64]). CONCLUSION: Age, not SLCO1B1 rs4149056 genotype, was the strongest risk factor for statin-associated muscle symptoms in FH patients. After developing muscle symptoms, many patients reestablished statin therapy and achieved significant LDL-C reductions. Overall, 10% of all FH patients had statin-associated muscle symptoms and never reestablished statin therapy. Such patients developed muscle symptoms even on nonstatin lipid-lowering drugs and continued to have elevations in LDL-C. Further insight is needed into the relationship between FH and statin-associated muscle symptoms so all FH patients can be adequately treated.

Polymerase II promoter strength determines efficacy of microRNA adapted shRNAs.

Since the discovery of RNAi and microRNAs more than 10 years ago, much research has focused on the development of systems that usurp microRNA pathways to downregulate gene expression in mammalian cells. One of these systems makes use of endogenous microRNA pri-cursors that are expressed from polymerase II promoters where the mature microRNA sequence is replaced by gene specific duplexes that guide RNAi (shRNA-miRs). Although shRNA-miRs are effective in directing target mRNA knockdown and hence reducing protein expression in many cell types, variability of RNAi efficacy in cell lines has been an issue. Here we show that the choice of the polymerase II promoter used to drive shRNA expression is of critical importance to allow effective mRNA target knockdown. We tested the abundance of shRNA-miRs expressed from five different polymerase II promoters in 6 human cell lines and measured their ability to drive target knockdown. We observed a clear positive correlation between promoter strength, siRNA expression levels, and protein target knockdown. Differences in RNAi from the shRNA-miRs expressed from the various promoters were particularly pronounced in immune cells. Our findings have direct implications for the design of shRNA-directed RNAi experiments and the preferred RNAi system to use for each cell type.

MassCode liquid arrays as a tool for multiplexed high-throughput genetic profiling.

Multiplexed detection assays that analyze a modest number of nucleic acid targets over large sample sets are emerging as the preferred testing approach in such applications as routine pathogen typing, outbreak monitoring, and diagnostics. However, very few DNA testing platforms have proven to offer a solution for mid-plexed analysis that is high-throughput, sensitive, and with a low cost per test. In this work, an enhanced genotyping method based on MassCode technology was devised and integrated as part of a high-throughput mid-plexing analytical system that facilitates robust qualitative differential detection of DNA targets. Samples are first analyzed using MassCode PCR (MC-PCR) performed with an array of primer sets encoded with unique mass tags. Lambda exonuclease and an array of MassCode probes are then contacted with MC-PCR products for further interrogation and target sequences are specifically identified. Primer and probe hybridizations occur in homogeneous solution, a clear advantage over micro- or nanoparticle suspension arrays. The two cognate tags coupled to resultant MassCode hybrids are detected in an automated process using a benchtop single quadrupole mass spectrometer. The prospective value of using MassCode probe arrays for multiplexed bioanalysis was demonstrated after developing a 14plex proof of concept assay designed to subtype a select panel of Salmonella enterica serogroups and serovars. This MassCode system is very flexible and test panels can be customized to include more, less, or different markers.

The significance of monoamine oxidase-A expression in high grade prostate cancer.

PURPOSE: Gleason grade 4/5 prostate cancer is a determinant for recurrence following radical prostatectomy. Monoamine oxidase-A is over expressed in grade 4/5 compared to grade 3 cancer. Monoamine oxidase-A is also expressed by normal basal cells and in vitro studies suggest that its function is to repress secretory differentiation. Therefore, monoamine oxidase-A in grade 4/5 cancer might reflect dedifferentiation to a basal cell-like phenotype. We investigated whether monoamine oxidase-A expression correlates with another basal cell protein, CD44, in high grade cancer and whether either is associated with an aggressive phenotype. MATERIALS AND METHODS: A total of 133 grade 4/5 archival cancers from a cohort previously used to evaluate the prognostic significance of histomorphological variables were scored for monoamine oxidase-A and CD44 immunohistochemical labeling. Spearman rank correlations of the proteins, and histomorphological and clinical variables were determined. The univariate and multivariate value of each variable as a determinant of biochemical recurrence was assessed by logistic regression. RESULTS: Monoamine oxidase-A expression correlated with CD44. Neither was prognostic for biochemical recurrence. However, monoamine oxidase-A expression positively correlated with preoperative serum prostate specific antigen and the percent of grade 4/5 cancer. CONCLUSIONS: Concurrent expression of monoamine oxidase-A and CD44 suggests that grade 4/5 cancer may be basal cell-like in nature, despite the absence of other classic basal cell biomarkers such as cytokeratins 5 and 14, and p63. The correlation of monoamine oxidase-A expression with prostate specific antigen and the percent of grade 4/5 cancer suggests that monoamine oxidase-A may contribute to growth of high grade cancer and that antidepressant drugs that target monoamine oxidase-A may have applications in treating prostate cancer.