International registries provide more information about COVID-19 and liver disease

People with advanced liver cirrhosis are more likely to develop severe COVID-19 complications and to die from it, but those who have received liver transplants do not appear to be at greater risk, researchers reported at the recent 2020 Digital International Liver Congress.

People with various co-morbidities or advanced immune suppression are more prone to severe COVID-19, and this may include those with liver disease. An Asian study found that people with cirrhosis – especially those with diabetes or obesity – are at greater risk for serious COVID-19 complications. Early studies of people with fatty liver disease who develop COVID-19 have yielded conflicting findings.

Aiming to shed more light on the topic, Dr Thomas Marjot of the University of Oxford and colleagues analysed data from two international registries of people with liver disease and COVID-19. The SECURE-Cirrhosis registry collects case reports from North and South America and parts of Asia, while EASL's COVID-HEP registry includes reports from the rest of the world.

As of 14 August 2020, the registries had collected reports of 1097 cases from 35 countries. As previously reported, an earlier analysis looked at data collected through 20 April. Dr Marjot presented an updated analysis of reports through 8 July.

This analysis included 745 patients with chronic liver disease and COVID-19, of whom 386 had progressed to cirrhosis. The majority of reports came from the United Kingdom and the United States (each contributing about 25% of cases) and China (16% of cases). Non-alcoholic fatty liver disease (NAFLD) was the most common cause (38%), followed by alcoholic liver disease (18%), hepatitis B (10%) and hepatitis C (9%). Liver transplant recipients were excluded.

The analysis compared patients without cirrhosis and those with three levels of cirrhosis severity: Child-Pugh (CP) class A, B and C, with C being most severe.

For each higher level of liver disease severity, the risk of adverse outcomes, including intensive care unit admission, mechanical ventilation and death, increased in a stepwise fashion.

Most people without cirrhosis survived, with mortality rates of 8% for those who were hospitalised and 21% for those put on ventilators. Among those with CP class A, mortality rates were 22% once hospitalised and 52% once put on a ventilator. Among those with CP class B, the respective rates were 39% and 74%. Among those with CP class C, more than half of hospitalised patients (54%), and most of those put on ventilators (90%) died.

The most common cause of death for people with cirrhosis and COVID-19 was respiratory disease (71%), far exceeding liver-related deaths (19%) and cardiac deaths (5%). Nearly half of people with cirrhosis (46%) experienced liver decompensation, but even in this subgroup lung disease led to higher mortality than liver-related complications (64% versus 24%, respectively).

Mortality rates were much higher for people with cirrhosis compared with those without cirrhosis in all age groups except those age 80 and older, who had high mortality regardless of cirrhosis status. In addition to age and cirrhosis severity, alcoholic liver disease was an independent risk factor for death, but NAFLD and viral hepatitis were not linked to elevated mortality after controlling for other factors.

Comparing these results against a UK cohort of COVID-19 patients without liver disease, those in the registry who had chronic liver disease but had not yet progressed to cirrhosis appeared to have similar mortality after adjusting for sex, age and other co-morbidities.

A limitation of this analysis is that most reports involved hospitalised patients. Dr Marjot noted that the findings may not be applicable to people with milder cases of COVID-19.

"There are diminishing chances of survival as chronic liver disease patients require increasing levels of medical support and diminishing chances with more severe baseline liver disease," the researchers concluded.

Prof. Marina Berenguer Haym of the University of Valencia in Spain presented an analysis of outcomes among liver transplant recipients with COVID-19 in the same two registries. The findings were published in The Lancet Gastroenterology and Hepatology.

Experts have cautioned that transplant recipients could be at higher risk for coronavirus infection because drugs used to prevent organ rejection suppress the immune system. But there has been little research on outcomes among those who do get COVID-19. Some complications of advanced COVID-19 appear to be attributable to an excessive immune response, and immunosuppressive therapies actually help some patients.

This analysis included 181 liver transplant recipients with COVID-19 in 18 countries. The control group included 627 COVID-19 patients who had not received transplants.

Transplant recipients and non-transplant patients with COVID-19 were hospitalised at similar rates (82% vs 76%, respectively). However, the transplant patients were more likely to be admitted to intensive care (28% vs 8%) and to be put on ventilators (20% vs 5%). Nonetheless, the transplant group had a somewhat lower mortality rate than those who did not receive transplants (19% vs 27%).

"We should be reassured that clinicians and health policy makers should be aware liver transplantation does not confer major additional susceptibility to adverse outcomes," Prof. Thomas Berg of the University of Leipzig in Germany said at a press briefing in advance of the conference. He suggested that a bigger concern is that people with liver disease may avoid medical care due to fear of COVID-19, which could lead to subsequent waves of advanced liver complications in the future.