Gut Microbes and Hepatic Encephalopathy: From the Old Concepts to New Perspectives

Hepatic encephalopathy (HE) is a severe complication of advanced liver disease and acute liver failure. The clinical spectrum ranges from minor cognitive dysfunctions to lethargy, depressed consciousness, and coma and significantly impact the quality of life, morbidity, and mortality of the patients. It is commonly accepted that the gut milieu is essential for the development of HE; however, despite intensive research efforts, the pathogenesis of HE is still not fully elucidated. As our knowledge of gut microbiota moves from the pioneering era of culture-dependent studies, the connection between microbes, inflammation, and metabolic pathways in the pathogenesis of HE is becoming increasingly clear, providing exciting therapeutic perspectives. This review will critically examine the latest research findings on the role of gut microbes in the pathophysiological pathways underlying HE. Moreover, currently available therapeutic options and novel treatment strategies are discussed.

Burden, Quality of Life, and Palliative Care for Family Caregivers of Individuals with Advanced Liver Disease: a Systematic Literature Review

Purpose of Review Identify and describe prior studies of family caregiver quality of life, health, and burden experienced while caring for patients with advanced liver disease and the possible role of palliative care. Recent Findings Thirty-six articles were identified that met inclusion criteria. Studies identified included cross-sectional, longitudinal, and prospective intervention studies, with a high proportion of qualitative and descriptive research. Resulting studies addressed type of family caregiver burden, including physical, psychological, and financial causes of burden, including HE, lack of information and communication, and unpredictability of the disease course. Few prospective studies were identified. The interventions described included nurse-led palliative care, mindfulness-based stress reduction, and coping interventions. Summary Little has been published on the nature of family caregiving, burden, quality of life, or the role of palliative care for family caregivers of people with advanced liver disease. Prospective studies that address unmet family caregiver needs, including palliative care interventions, are lacking.

487. Experience with Remdesivir for Treatment of SARS-CoV-2 in Patients with Liver Cirrhosis

Background Remdesivir is a nucleotide analogue antiviral that was FDA approved for the treatment of hospitalized patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Remdesivir has been associated with elevations in serum aminotransferase levels but most cases being mild to moderate and reversible upon discontinuation. Although national COVID-19 guidelines and the American Association for the Study of Liver Diseases (AASLD) currently recommend remdesivir for use in hospitalized patients requiring supplemental oxygen, data is limited using remdesivir in patients with chronic liver disease. Here, we describe our experience with remdesivir in patients with liver cirrhosis. Methods Patients with liver cirrhosis who received remdesivir were identified either prospectively or retrospectively by primary or secondary ICD-10 codes indicating liver disease. Data collected included patient demographics, underlying cause of cirrhosis, co-morbidities, Child-Pugh score, laboratory values (serum aminotransferase levels, serum creatinine) during and following remdesivir, adverse reactions attributed to remdesivir, and mortality (in-hospital, 30-day, and 90-day). Results A total of 4 patients with underlying liver cirrhosis completed a 5-day course of remdesivir treatment. On admission, Child-Pugh class was A for 1 patient, B for 2 patients, and C for 1 patient. Causes for cirrhosis were nonalcoholic steatohepatitis (NASH), hepatic amyloidosis, and chronic hepatitis B. There were no acute elevations in aminotransferase levels or adverse events attributed to remdesivir therapy. Mortality was high with 50% in-hospital mortality. Of the 2 other patients who survived to discharge, one was discharged to home hospice and the other was readmitted within 30 days and expired during that admission. Conclusion Since there is limited data available using remdesivir in patients with advanced liver disease, we did not identify any safety concerns related to remdesivir in our cirrhotic patients. Mortality was high illustrating the poor outcomes of patients with advanced liver disease and COVID-19. Patients with cirrhosis should be offered remdesivir if clinically appropriate. Disclosures All Authors: No reported disclosures

A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.