Editor's note: Many countries and health systems around the world have been overwhelmed by the COVID-19 pandemic.Importantly, there is increasing data on how COVID-19 affects the liver and how the underlying liver disease will affect the clinical course of SARS-COV-2.Experience tells us that we must keep in mind the existing liver disease and liver damage during the course of the disease.
At EASL2020, the organizing committee specially set up an important topic of "COVID-19 and liver disease", and invited world-renowned hepatologists Sandra Ciesek, Tom Hemming Karlsen, Eleanor Barnes, Marina Berenguer Haym and Alessio Aghemo to give special reports and conduct interactive discussions.
We invited EASL Council member Prof. Tobias Bottler from University Hospital freiburg, Germany, to conduct an in-depth interview on the issues related to chronic liver disease care in the context of COVID-19.
IH:Based on clinical data,whether SARS-CoV-2 can directly infect the liver ?and what other mechanisms for SARS-CoV-2-induced liver injury have been discussed?
Dr Böttler: To answer the first part of the question whether SARS-CoV-2 can directly infect the liver, we still don’t know. There are data out there suggesting that the liver might be susceptible to SARS-CoV-2 infection because the receptor that is required for SARS-CoV-2 infection is actually expressed to a degree on hepatocytes, but even moreso on cholangiocytes. So, in principle, at least in vitro, SARS-CoV-2 should be able to infect the liver. However, whether this would cause the damage we observe in patients who are infected, we don’t know at this point. That brings me to the second part of the question of what other mechanisms for SARS-CoV-2-induced liver injury have been discussed? This is something we don’t know at this point either. The liver is very sensitive to all sorts of systemic infections. What we currently believe is that a large part of what is happening in the liver in patients with elevated liver function tests and COVID-19 is due to systemic inflammation. Pro-inflammatory cytokines that circulate cause damage to the liver, but there could be other factors that play into this, for example, medications that patients then receive where there is a severe course of infection or where there is hepatic congestion. We outlined a lot of these different factors that might contribute to liver injury in the EASL-ESCMID position paper recently updated and published in the Journal of Hepatology Reports.
IH:What is the general and liver-specific risk factors for SARS-CoV-2 infection and what is for severe COVID-19?
Dr Böttler: In terms of the general risk factors for COVID-19, I think these are quite well established – older age, male gender, metabolic comorbidities such as diabetes, arterial hypertension and obesity. Those are risk factors for severe COVID-19. Whether they also increase the risk of getting SARS-CoV-2 infection, I don’t think this has been firmly established, but they most certainly contribute to patients who have a severe course of COVID-19. For liver-specific risk factors, we really don’t know whether there is any chronic liver disease that will increase a person’s susceptibility to SARS-CoV-2 infection. So far, patients in these large cohorts that have been published with COVID-19, those with chronic liver disease have not been over-represented, suggesting that chronic liver disease may not be a risk factor for SARS-CoV-2 infection.
IH:Based on your clinical experience,what is the impact of pre-existing liver disease on the outcome of SARS-CoV-2?
Dr Böttler: What we know is that increasing severity of a chronic liver disease (mostly cirrhosis, and the different classes of cirrhosis, ranging from compensated to decompensated and ultimately Child class C cirrhosis) increases the risk of severe courses of COVID-19. Patients with advanced liver disease and cirrhosis are most certainly at higher risk for a fatal course of disease. These data have been published by many different groups, and show that patients with advanced liver disease do have a significantly increased risk for a severe course. Whether this is, again, liver-specific, or whether this is a multiplication of the two severe diseases is not really known. But certainly, if a patient with advanced liver disease acquires a SARS-CoV-2 infection, they are at a high risk for a severe course.
IH:Would you please share your opinions on the management of patients with liver disease during the COVID-19 crisis?
Dr Böttler: In the first phases of the pandemic, at least here in Europe when the infection rate rose in March and April, many centers closed down or significantly reduced care for patients with chronic liver disease. This did result in a backlog of patients in the months to come. Also perhaps, there was a reduced quality of care for these patients. Now, I think we should focus on resuming patient care for patients with chronic liver disease despite the COVID pandemic. We really should not forget about patients with liver disease, and we need to maintain the care for those who need it. After all, preventing progression of chronic liver disease may also prevent these patients acquiring severe forms of COVID-19. We need to make a concerted effort to maintain care for patients with chronic liver disease, despite the COVID-19 pandemic.
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