Cognitive impairment is epidemic in Veterans with cirrhosis, which poses a major psychosocial, financial, and clinical burden. While it is assumed that hepatic encephalopathy (HE, both minimal, MHE or overt forms) is the major cause of this impairment, recent work by our group has shown the frequent other causes/contributors in up to half of Veterans with cognitive complaints referred to our VAs specialized testing clinic had a non-HE related cause. The differential diagnosis for non-HE cognitive complaints includes mild cognitive impairment (MCI) and dementia, mood disorders, post-traumatic stress disorder (PTSD), obstructive sleep apnea (OSA), and Parkinson’s. A major issue is the lack of confirmatory test(s) for HE and the often-flawed current mode of clinical diagnosis. As a result, most clinicians treat every Veteran with cirrhosis with cognitive complaints for HE which results in therapies that are either poorly tolerated (lactulose), or expensive (rifaximin), while ignoring underlying causes of cognitive complaints. Specialized cognitive testing clinics, detailed inquiry of symptoms, co-morbid conditions, and interpretation are ideal but not practical without training, expertise, and significant financial investment. Therefore, we need better strategies to reliably diagnose/exclude HE, which will minimize unnecessary poorly tolerated and expensive therapy, avoid misdiagnosis in roughly half of patients, and guide clinicians taking care of Veterans with cirrhosis. Microbiome composition is altered in patients with HE (both MHE and overt) and predicts clinically relevant outcomes. Our recent research showed that the gut microbial analysis accurately differentiates between microbial profiles due to addiction disorders, PTSD, MCI/dementia, and rules out MHE-related cognitive impairment. Specificity of a clinical HE diagnosis was 50% versus >90% for microbiome profiling when both were compared to the detailed neuropsychological evaluation. As a result, reliable mi