High mortality from COVID-19 in patients with chronic liver disease

How does COVID-19 affect patients with liver disease? This was the topic of a special online session at the EASL digital congress 2020.

How does COVID-19 affect patients with liver disease? This was the topic of a special online session at the EASL digital congress 2020.

Prof. Dr. Sandra Ciesek, Director of the Institute for Medical Virology at the University Hospital Frankfurt (in German: Universitätsklinikum Frankfurt), made it clear that COVID-19 is a multi-organ disease. There are two possible treatments - vaccination and antiviral therapies. Two drugs have shown positive prospects in clinical trials: remdesivir and dexamethasone. Several vaccine candidates are currently in phase-III trials. Dr. Ciesek reported that SARS-CoV-2 also replicates in the liver.

Prof. Dr. Johannes R. Hov from the Oslo University Hospital, Norway, determined which risk factors play a role in COVID-19. According to Dr. Hov, severe COVID-19 courses are associated with older age and male sex. And with comorbidities such as cardiovascular disease, diabetes, and obesity. High blood pressure, chronic kidney disease, and chronic lung disease are also among the risk factors for a severe course.

Are liver diseases a risk factor? There is some evidence of this from general patient/hospital cohorts, according to Dr. Hov. Data from the UK (OpenSafely NHS, Williamson et al. Nature 2020) with 17,278,392 individuals, including 10,926 COVID-19 deaths, show an increased risk of death for patients with liver disease: HR: 1.75. However, less than 2% of patients who die from COVID-19 have chronic liver disease.

And furthermore, smoking increases the risk: Current and past smokers are associated with a more severe disease course and mortality (Reddy et al. J Med Virol). Socio-economic deprivation is associated with increased mortality from COVID-19, something is shown by the NHS data. Genetic risk factors for COVID-19 have been identified with respiratory failure; this may, according to Dr. Hov, provide clues to pathogenesis, but has no clinical implications so far.

Data from international registries show high mortality

International registry data - from the SECURE-Cirrhosis Registry and the COVID HEP Registry - were presented by Dr. Thomas Marjot, from the Liver Unit, Oxford University Hospitals, UK. In their analysis (Moon AM, et al. J Hep, May 2020), the researchers examined data from 1027 cases of liver disease and COVID-19; including 424 with a chronic liver disease without cirrhosis, 506 with cirrhosis, and 167 patients who had received a liver transplant.

There is a high mortality rate in patients with SARS-CoV-2 infection with pre-existing chronic liver disease and cirrhosis. With each further stage of liver disease, there is a gradual increase in the rates of adverse outcomes, including death. Patients with liver disease and COVID-19 infections died of pneumonia in 71% of cases, liver-associated deaths in 19%, and heart-associated deaths in 5%.

For patients with decompensated cirrhosis, the figures were glaring: among patients with a Child-Pugh Score C (classification for the severity of liver cirrhosis) 79% died after admission to intensive care, and among those who had to be intubated the figure was as high as 90%.

46% of cirrhosis patients decompensate as a result of SARS-CoV-2 infection. Of those who decompensated, 22% showed no signs of respiratory disease. Among those who decompensated and died as a result, COVID-19-induced pneumonia was the leading cause of death with 64%, while liver-associated complications caused 24% of deaths.

One-third of acutely decompensated patients with liver cirrhosis in hospitals show acute-to-chronic liver failure (ACLF). Due to infection with SARS-CoV-2, those patients with ACLF showed higher mortality than those without ACLF: 46% vs. 14%.

COVID-19 led to an abrupt decline in transplantation

Dr. Marjot stressed the importance of international cooperation during a pandemic. This would enable the rapid collection and evaluation of register data with well-characterized patient cohorts. When comparing patients with and without liver disease, there is a gradually increasing risk of mortality with each stage of liver disease. Patients with advanced cirrhosis have very poor survival chances after admission to intensive care and ventilation. The predominant cause of death is COVID-19-induced pneumonia - even in people with acute liver decompensation. Independent risk factors for death in patients with chronic liver disease include age, disease severity, and alcohol-induced liver disease.

Dr. Marina Berenguer Haym, from Spain, made it clear that COVID-19 had a profound impact on the liver transplantation environment and led to an abrupt decline in transplantation in areas where SARS-CoV-2 was prevalent.

Those who have undergone liver transplantation show an increased risk of COVID-19 infection, but the severity of the disease appears to be in line with that of the general population. The guidelines also advise against reducing immunosuppressive therapy because it has not been shown to increase the risk of a severe course.

References:
EASL The Digital international Liver Congress, 27 to 29 August 2020 COVID-19 and the Liver, 15:30 to 17:00 hrs, Saturday 29 August

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