Dinesh Ganapathy

Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis

Cognitive difficulties manifested by the growing elderly population with cirrhosis could be amnestic (memory-related) or non-amnestic (memory-unrelated). The underlying neuro-biological and gut-brain changes are unclear in this population. We aimed to define gut-brain axis alterations in elderly cirrhotics compared to non-cirrhotic individuals based on presence of cirrhosis and on neuropsychological performance. Age-matched outpatients with/without cirrhosis underwent cognitive testing (amnestic/non-amnestic domains), quality of life (HRQOL), multi-modal MRI (fMRI go/no-go task, volumetry and MR spectroscopy), blood (inflammatory cytokines) and stool collection (for microbiota). Groups were studied based on cirrhosis/not and also based on neuropsychological performance (amnestic-type, amnestic/non-amnestic-type and unimpaired). Cirrhotics were impaired on non-amnestic and selected amnestic tests, HRQOL and systemic inflammation compared to non-cirrhotics. Cirrhotics demonstrated significant changes on MR spectroscopy but not on fMRI or volumetry. Correlation networks showed that Lactobacillales members were positively while Enterobacteriaceae and Porphyromonadaceae were negatively linked with cognition. Using the neuropsychological classification amnestic/non-amnestic-type individuals were majority cirrhosis and had worse HRQOL, higher inflammation and decreased autochthonous taxa relative abundance compared to the rest. This classification also predicted fMRI, MR spectroscopy and volumetry changes between groups. We conclude that gut-brain axis alterations may be associated with the type of neurobehavioral decline or inflamm-aging in elderly cirrhotic subjects.

Liver Transplantation Significantly Improves Global Functioning and Cerebral Processing.

The functional basis of cognitive and quality of life changes after liver transplant is unclear. We aimed to evaluate the neurometabolic and functional brain changes as modulators of cognition and quality of life after transplant in patients with cirrhosis who were with/without pretransplant cognitive impairment and hepatic encephalopathy (HE). Patients with cirrhosis underwent detailed cognitive and quality of life assessment at enrollment and 6 months after transplant. A subset underwent brain magnetic resonance imaging (functional magnetic resonance imaging [fMRI], diffusion tensor imaging [DTI], and magnetic resonance spectroscopy [MRS]) before and after transplant. Changes before and after transplant were analyzed in all patients and by dividing groups in those with/without pretransplant cognitive impairment or with/without pretransplant HE. MRS evaluated ammonia‐related metabolites; fMRI studied brain activation for correct lure inhibition on the inhibitory control test; and DTI studied white matter integrity. Sixty‐six patients (mean Model for End‐Stage Liver Disease score, 21.8; 38 HE patients and 24 cognitively impaired [CI] patients) were enrolled. Quality of life was significantly worse in CI and HE groups before transplant, which improved to a lesser extent in those with prior cognitive impairment. In the entire group after transplant, there was (1) significantly lower brain activation needed for lure inhibition (shown on fMRI); (2) reversal of pretransplant ammonia‐associated changes (shown on MRS); and (3) improved white matter integrity (shown on DTI). Importantly, study findings suggest that pretransplant cognitive impairment serves as a marker for clinical outcomes. Regardless of pretransplant history of HE, it was the pretransplant cognitive impairment that was predictive of both posttransplant cognitive and psychosocial outcomes. Therefore, when working with patients and their families, a clinician may rely on the pretransplant cognitive profile to develop expectations regarding posttransplant neurobehavioral recovery. We conclude that functional brain changes after liver transplant depend on pretransplant cognitive impairment and are ultimately linked with posttransplant cognition and quality of life in cirrhosis. Liver Transplantation 22 1379–1390 2016 AASLD.

HCV eradication does not impact gut dysbiosis or systemic inflammation in cirrhotic patients.

Eradication of hepatitis C virus (HCV) is increasing but its residual impact on the pro‐inflammatory milieu in cirrhosis, which is associated with gut dysbiosis, is unclear.

The Patient Buddy App Can Potentially Prevent Hepatic Encephalopathy-Related Readmissions

Readmissions are a major burden in cirrhosis. A proportion of readmissions in cirrhosis, especially because of hepatic encephalopathy (HE) could be avoided through patient and caregiver engagement. We aimed to define the feasibility of using the Patient Buddy App and its impact on 30‐day readmissions by engaging and educating cirrhotic inpatients and caregivers in a pilot study.

Overt hepatic encephalopathy impairs learning on the EncephalApp stroop which is reversible after liver transplantation

After an initial exposure, patients can develop test‐taking/learning strategies called the “test sophistication effect.” Patients with cirrhosis with prior overt hepatic encephalopathy (OHE) could have persistent learning impairments. The aim was to define learning/test sophistication on EncephalApp (downloadable application) in OHE patients compared with patients without prior overt hepatic encephalopathy (no‐OHE) patients and controls cross‐sectionally and longitudinally. The EncephalApp Stroop App consists of 2 sections: the easier “Off” run assesses psychomotor speed while the difficult “On” run assesses cognitive flexibility. For the cross‐sectional analysis, outpatients with cirrhosis with/without controlled OHE and healthy controls underwent EncephalApp testing, which requires 5 Off and 5 On runs. We studied the difference in time required between completing trial 1 compared with trial 5 (delta 1‐5) in both the On and Off runs in controls, all patients with cirrhosis, and between prior OHE/no‐OHE patients with cirrhosis. For the longitudinal analyses, 2 groups of patients with cirrhosis were studied; 1 was administered the EncephalApp ≥ 2 weeks apart, and the second was administered before and 6 months after liver transplantation. The study included 89 controls and 230 patients with cirrhosis (85 prior OHE; Model for End‐Stage Liver Disease, 11) with similar age (64 versus 61 years; P = 0.92). Patients with cirrhosis had impaired EncephalApp total times and impaired learning on the On runs compared with controls. OHE patients had worse EncephalApp times and learning with the On runs compared with no‐OHE patients, which persisted in the longitudinal cohort. No differences in learning were seen in the Off runs. After transplant, there was restoration of learning capability with the On runs in the OHE patients. In conclusion, cognitive flexibility tested by the EncephalApp On runs improves over time in healthy controls and no‐OHE but not prior OHE. Psychomotor speed remains similar over time. The learning impairment manifested by patients with cirrhosis with OHE is restored after transplant. Liver Transplantation 23 1396–1403 2017 AASLD.

Patient Acceptance of Lactulose Varies Between Indian and American Cohorts: Implications for Comparing and Designing Global Hepatic Encephalopathy Trials

Background Lactulose is the first-line drug for hepatic encephalopathy (HE), but its acceptance widely differs between Western and Eastern studies. Patient preference for lactulose between different parts of the world has not been examined systematically. Aim To define the preferences and reasons behind acceptance of lactulose in patients from USA and India. Methods A discrete-choice questionnaire with six hypothetical scenarios was constructed. Situations 1-3 studied preference for lactulose vs no-lactulose, while 4-6 studied preference for high-dose vs low-dose lactulose varying the overt HE prevention at 6 months and adverse event rates in each situation. This was administered to outpatient cirrhotics without prior/current experience with lactulose after dedicated education. Results 100 patients (50 Indian, 50 USA) with similar MELD scores were included. A significantly higher proportion of Indian respondents agreed to lactulose in all situations compared to Americans. While their acceptance of lactulose decreased in the situation with the least difference in overt HE prevention, it was consistently higher than Americans. In the high-dose vs low-dose scenario, the relative proportion of American respondents accepting high-dose increased with the higher presented protection against overt HE. On the other hand, Indian respondents remained largely consistent with low-dose lactulose option. Conclusions There are significant variations in the acceptance of lactulose in Indian and American populations. The acceptance increases with a more favorable perceived benefit/risk profile, which is strongly influenced by socio-cultural factors. These results have important implications when designing, comparing and interpreting HE trials from different parts of the world.

No Association Between Quick Sequential Organ Failure Assessment and Outcomes of Patients With Cirrhosis and Infections

No Association Between Quick Sequential Organ Failure Assessment and Outcomes of Patients With Cirrhosis and Infections Kavish R. Patidar,* Jawaid Shaw, Chathur Acharya, Leroy R. Thacker,k,¶ Melanie B. White,* Dinesh Ganapathy,* Andrew Fagan, Edith A. Gavis, and Jasmohan S. Bajaj* *Division of Gastroenterology, Hepatology and Nutrition, Division of General Internal Medicine, kDepartment of Biostatistics and Family and Community Health Nursing, Virginia Commonwealth University, Richmond, Virginia; Division of Gastroenterology and Hepatology, McGuire VA Medical Center, Richmond, Virginia

Neurological examination: Neurological Examination

A typical neurological examination in any patient broadly consists of: (1) higher mental function testing, (2) cranial nerve examination, (3) deep tendon reflexes, (4) gait and coordination, (5) muscle bulk and tone, and (6) sensation (sharp, soft, proprioception, temperature, and vibratory). Prior studies demonstrate that a detailed neurological examination and cognitive testing can unearth signs of persistent hepatic encephalopathy (HE) and neurological deficits in patients who were considered otherwise controlled on current therapy. A thorough neurological examination can potentially help differentiate between liver disease–related and coexistent conditions such as Wernicke encephalopathy, alcoholic withdrawal, obstructive sleep apnea, and dementia.