Background and Aims Coronavirus disease 2019 (COVID‐19), the illness caused by the SARS‐CoV‐2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID‐19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID‐19 pandemic on liver patients and healthcare providers. Approach and Results This article discusses what is known about COVID‐19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID‐19 pandemic on their patients’ care. Conclusions The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID‐19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver.

COVID-19 coronavirus disease 2019 SARS-CoV-2 severe acute respiratory syndrome coronavirus 2 CLD chronic liver disease EUA emergency use authorization FDA Food and Drug Administration VE vaccine efficacy BNT162b2 Pfizer-BioNTech mRNA vaccine mRNA-1273 Moderna mRNA vaccine VAERS Vaccine Adverse Event Reporting System CDC Centers for Disease Control and Prevention SOT solid organ transplant ACR acute cellular rejection

Vitamin D is a secosteroid with known effects on calcium homeostasis that has recently been shown to have other significant functions regarding immune modulation, cell differentiation and proliferation, and the inflammatory response. As our understanding of the many functions of vitamin D has grown, the presence of vitamin D deficiency (VDD) has become more evident in Western populations. Concomitantly, nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease. NAFLD and VDD are often found together, and while this is not unexpected, given their similar associations with obesity and sedentary lifestyle, a growing body of evidence points to a closely linked and potentially causative relationship between VDD and NAFLD. The epidemiologic association between VDD and NAFLD as well as the role of VDD in the pathogenesis of NAFLD and the available evidence on the clinical utility of vitamin D replacement in NAFLD populations are discussed. (HEPATOLOGY 2013;58:1166-1174 I n the last decade, the importance of vitamin D beyond its effects on calcium homeostasis has become more evident and its functions in immune modulation, cell differentiation and proliferation, and the inflammatory response have all been well described. However, an interesting paradox has developed: while our understanding of the physiological functions of vitamin D have become better known, vitamin D deficiency (VDD) has silently become increasingly more common in Western populations. Concomitantly, the last decade has seen nonalcoholic fatty liver disease (NAFLD) rise to become the most common cause of chronic liver disease in Western nations. Given that VDD and NAFLD have both indirect and direct associations with obesity and sedentary lifestyle, it is not unexpected that VDD would coexist with NAFLD. A growing body of evidence points to a linked and potentially causative relationship between VDD and NAFLD. This review will assess the role of VDD in the pathogenesis of NAFLD, identify trends in the epidemiology of VDD and NAFLD, and evaluate available evidence on the clinical utility of vitamin D replacement in NAFLD populations. Vitamin D MetabolismVitamin D is a secosteroid that is obtained both exogenously (Vitamin D2) and endogenously (Vitamin D3). Since dietary vitamin D (D2) is naturally contained in very few foods, dietary supplementation and dermal synthesis (D3) are the primary sources of vitamin D. Previtamin D3 is synthesized in skin by UV sunlight from 7-dehydrocholesterol which is then converted to vitamin D3 or cholecalciferol 1 (Fig. 1)

Comorbid primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) represent a unique disease phenotype with a different risk profile than PSC or IBD alone. While the pathogenetic mechanisms behind both diseases remain unclear, recent studies have targeted several immune-mediated pathways in an attempt to find a potential therapeutic target. Patients with PSC-associated IBD typically exhibit pancolitis with a right-to-left intestinal inflammatory gradient associated with a greater incidence of backwash ileitis and rectal sparing. Although there is an increased incidence of pancolitis in this population, bowel symptoms tend to be less significant than in IBD alone. Likewise, the degree of inflammation and symptoms of PSC-associated IBD are characteristically less clinically significant. Despite the relatively quiescent clinical presentation of PSC-associated IBD, there is an increased risk for colorectal and hepatobiliary malignancy making vigilance for malignancy essential.

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is associated with worse outcomes. The combination of ledipasvir (LDV) and sofosbuvir (SOF) has been approved for HCV treatment after LT, but there are limited data on the effectiveness and safety of LDV/SOF in the "real-world" setting. This multicenter study is the largest report to date on the effectiveness and safety of LDV/SOF in the post-LT setting. A total of 204 patients (72% male, 68% Caucasian, 66% genotype [GT] 1a, 21% METAVIR F3-F4, 49% treatment-experienced) were treated with LDV/SOF. The mean duration from LT to treatment initiation was 4.8 years. The overall sustained virological response rate 12 weeks after completion of therapy (SVR12) was 96%. Patients treated with 8 or 12 weeks of LDV/SOF without RBV experienced an SVR12 rate of 100% and 96%, respectively. Calcineurin inhibitors were used in 89% of patients, and 32% of patients underwent adjustment in immunosuppression during treatment. One episode of mild rejection, responsive to an increase in immunosuppression dosage, was observed. There was no graft loss attributed to HCV treatment. Four deaths occurred unrelated to HCV treatment, and no significant serious adverse events were documented. In conclusion, SOF and LDV with or without RBV for 8, 12, or 24 weeks in post-LT patients was effective and safe with a high SVR12 rate across a spectrum of GTs and stages of fibrosis. Liver Transplantation 22 1536-1543 2016 AASLD.