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Our understanding of the hepatic consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resultant coronavirus disease 2019 (COVID-19) has evolved rapidly since the onset of the pandemic. In this Review, we discuss the hepatotropism of SARS-CoV-2, including the differential expression of viral receptors on liver cell types, and we describe the liver histology features present in patients with COVID-19. We also provide an overview of the pattern and relevance of abnormal liver biochemistry during COVID-19 and present the possible underlying direct and indirect mechanisms for liver injury. Furthermore, large international cohorts have been able to characterize the disease course of COVID-19 in patients with pre-existing chronic liver disease. Patients with cirrhosis have particularly high rates of hepatic decompensation and death following SARS-CoV-2 infection and we outline hypotheses to explain these findings, including the possible role of cirrhosis-associated immune dysfunction. This finding contrasts with outcome data in pharmacologically immunosuppressed patients after liver transplantation who seem to have comparatively better outcomes from COVID-19 than those with advanced liver disease. Finally, we discuss the approach to SARS-CoV-2 vaccination in patients with cirrhosis and after liver transplantation and predict how changes in social behaviours and clinical care pathways during the pandemic might lead to increased liver disease incidence and severity. This Review provides mechanistic and clinical insights into COVID-19 in the context of liver disease, discussing the potential underlying biology and clinical features of SARS-CoV-2 infection in patients with pre-existing liver conditions. The management of these patients is also discussed, including SARS-CoV-2 vaccination strategies. Key points Patients with cirrhosis have high rates of hepatic decompensation, acute-on-chronic liver failure and death from respiratory failure following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and should be prioritized for coronavirus disease 2019 (COVID-19) vaccination. The possible pathogenic mechanisms linking cirrhosis with severe COVID-19 lung disease include increased systemic inflammation, cirrhosis-associated immune dysfunction, coagulopathy and intestinal dysbiosis. Abnormal liver biochemistry values are common in patients with COVID-19; both the prognostic significance of these derangements and whether they are directly attributable to hepatic SARS-CoV-2 infection remain uncertain. Expression profiles of SARS-CoV-2 entry receptors vary across different in vitro and in vivo liver models; however, evidence of specific viral hepatotropism is limited. Liver transplant recipients do not appear to have an increased risk of mortality following SARS-CoV-2 infection compared with the matched general population. The pandemic has been associated with increased alcohol consumption, unhealthy eating habits, and interruptions to hepatology services, which might lead to an upward trend in liver disease incidence and severity.

The importance of nutrition is often underrecognized in the routine clinical care of patients with chronic liver disease. Nutrition therapy plays a significant role in the management of alcohol-related liver disease and nonalcoholic fatty liver disease. In patients with cirrhosis from any etiology, malnutrition and sarcopenia are directly related to mortality, and nutritional interventions play an important role in the management of these patients. This review explores the role of nutritional intervention as adjuvant therapy across all chronic liver disease. A narrative, qualitative systematic review was performed via searches of PubMed for nutritional aspects in the care of chronic liver disease. Nutritional therapy plays a critical role in the management of chronic liver disease. In nonalcoholic fatty liver disease, specific macronutrient management can lead to weight loss and improved outcomes in these patients. In patients with alcohol-related liver disease, chronic cholestatic liver disease, and decompensated cirrhosis, caloric and protein intake plays a vital role improving outcomes in these patients. Micronutrient deficencies are also common in these patients and require supplementation to prevent other complications of malnutrition. Assessment and management of nutrition should accompany the typical care plan of patients with chronic liver disease. This review of nutritional therapy in chronic liver disease highlights the current evidence-based and societal recommendations of macronutrient and micronutrient management across the spectrum of all chronic liver disease.

BackgroundDespite concerns that patients with autoimmune hepatitis (AIH) may be at increased risk of adverse outcomes from COVID-19 due to use of immunosuppression, the impact of SARS-CoV-2 infection on this patient group remains unclear.MethodsTwo international reporting registries (COVID-Hep. net and SECURE-cirrhosis) collected data on the clinical course of laboratory-confirmed SARS-CoV-2 infection in patients with chronic liver disease (CLD), including AIH.ResultsBetween 25th March and 30th June 2020, 677 patients with CLD were reported. This included 51 cases of AIH from 13 countries; female (65%), median age 48 yrs, isolated AIH (75%), PBC overlap (14%), PSC overlap (4%), cirrhosis (57%). 80% AIH patients were receiving immunosuppression; prednisolone (53%), azathioprine (41%), mycophenolate (16%), budesonide (12%), tacrolimus (8%). Hospitalisation was lower in AIH compared to other causes of CLD (75% v. 91%;p=0.001) but there was no difference in rates of intensive care unit admission (27% v. 23%;p=0.496), invasive ventilation (14% v. 18%;p=0.567), or death (22% v. 20%;p=0.857) (figure 1A). Rates of mortality were similar between AIH and CLD of other aetiologies when stratified by liver disease stage (figure 1B). In multivariable analysis of the entire cohort, AIH was not significantly associated with death unlike age and baseline liver disease severity.Abstract P50 Figure 1DiscussionThis is the largest reported cohort of patients with AIH and SARS-CoV-2 infection. Major outcomes in AIH did not differ from those seen in other CLD patients despite widespread use of immunosuppression. This will help guide treatment decisions and need for social distancing for AIH patients during the COVID-19 pandemic.

BackgroundChronic liver disease (CLD) and cirrhosis are associated with immune dysregulation leading to concerns that these patients may be at risk of adverse outcomes following SARS-CoV-2 infection. However, the impact of COVID-19 among patients with pre-existing liver disease remains poorly defined.MethodsData were collected through two international reporting registries (COVID-Hep.net and SECURE-Cirrhosis) on the clinical course of laboratory-confirmed SARS-CoV-2 infection in patients with CLD.ResultsBetween 25th March and 30th June 2020, 354 patients with cirrhosis and 325 with non-cirrhotic CLD were reported from 31 countries (63% male; median age 58 years; non-alcoholic fatty liver disease (38%), alcohol (17%), hepatitis B (10%), hepatitis C (9%)). Overall mortality in patients with cirrhosis was 32% and correlated with baseline Child-Turcotte-Pugh (CTP) class (figure 1A). Causes of death were respiratory (71%), liver-related (16%), and cardiac-related (5%). After adjusting for baseline characteristics, factors associated with death included age (OR 1.32/10 years; 95%CI 1.11–1.58), CTP-A (OR 2.27; 1.27–4.09), CTP-B (OR 4.88; 2.72–8.77), and CTP-C (OR 12.04; 6.50–22.30). In patients with cirrhosis, hepatic decompensation occurred in 47%, of which 22% had no respiratory symptoms; Acute-on-chronic liver failure (ACLF) occurred in 56% and ACLF score strongly correlated with mortality (figure 1B).Abstract O5 Figure 1DiscussionThis is the largest reported cohort of CLD patients with SARS-CoV-2 infection. We show that baseline liver disease severity is strongly associated with COVID-19 related morbidity and mortality, which has important prognostic implications. In addition, we demonstrate an association between SARS-CoV-2 and new hepatic decompensation.