The most visible public health official in the United States during the COVID-19 pandemic spoke to the public health and scientific challenges of combating the virus, and reviewed progress toward development of a vaccine, at the American Association for the Study of Liver Diseases (AASLD) virtual annual meeting on November 15, 2020.

Anthony Fauci, MD, director of the National Institute on Allergies and Infectious Diseases (NIAID), reviewed the history of coronaviruses and experience with the diseases they cause as he opened a panel discussion on “COVID-19 and the Liver.”

“We’ve had decades and decades of experience with coronaviruses,” Dr Fauci stated, including the viruses that caused the outbreak of severe acute respiratory syndrome (SARS) in 2002 and the Middle Eastern respiratory syndrome (MERS) in 2012. Although both resulted in high rates of fatality, they did not spread widely. 

However, the third coronavirus that appeared in December 2019 has created “a global pandemic of historic proportions,” Dr Fauci said. “We haven’t seen anything like this in 102 years,” when the so-called Spanish influenza pandemic claimed millions of lives. To date, Dr Fauci said, the SARS-CoV-2 virus has infected at least 10 million people worldwide and resulted in 1.2 million deaths. In the United States, there have been 10 million cases and more than 250,000 deaths.

Dr Fauci commented that unlike Europe, the United States never came back to a very low baseline of COVID-19 cases after the initial spike, except in specific areas, such as New York City, which implemented strict lock-down measures. Both the United States and Europe are now seeing a very high resurgence of cases, attributable in part to cooler weather driving people indoors.

“It is clear from previous experience we would not be having the surge of cases we’re seeing” if the public health measures advised—wearing masks, washing hands, avoiding crowds, and keeping physical disease— were being widely adhered to, he said.

In regard to COVID-19’s impact on the liver, Dr Fauci noted that the most severe outcomes are consistently seen among patients who are older and among those of any age with underlying medical conditions, including liver diseases such as hepatocellular carcinoma, cirrhosis, and hepatitis.

He expressed “cautious optimism” that a vaccine could be available by the end of this year for administration to the most at-risk individuals and could be more widely available in 2021. Using harmonized protocols, common endpoints, and common data and safety monitoring board companies, 6 companies have undertaken vaccine development, including Pfizer, whose vaccine candidate has shown more than 90% efficacy in early trials.

Elizabeth Verna, MD, from Columbia University, explained liver enzymes may be an important prognostic factor for the severity of COVID-19 among patients. “Meta-analyses have shown a significant association between elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST) and critical illness related to COVID-19.” She noted that peak ALT “is  highly predictive of discharge to hospice and death after controlling for other factors.”

Dr Verna also noted that there is a “clear association of liver injury with other inflammatory markers, even after controlling for other risk factors, such as age.” It is likely that the cause of liver injury among these patients is multifactorial, she said.

For patients with existing liver disease, Dr Verna stated that the “biggest impact of COVID-19 is among patients with decompensated cirrhosis,” with a stepwise increase in major adverse outcomes found at each stage of cirrhotic disease. She further noted that because of warnings against using remdesivir among patients with AST/ALT elevation, “a minimal initial workup” of patients with testing for hepatitis A, B, and C is now advised.

There does not appear to be an over-representation of patients with chronic liver diseases or patients who have undergone liver transplant in cohorts of patients with COVID-19, Dr Verna said. Nonalcoholic fatty liver disease (NALFD) and metabolic liver disease are somewhat more associated with severe outcomes, but other risk factors, such as obesity, are typically present among patients with these conditions.

Mark Sulkowski, MD, chief of the Division of Infectious Diseases at Johns Hopkins Bayview Medical Center in Baltimore, Maryland, discussed the treatment of COVID-19, noting that the use of antiviral drugs such as remdesivir appear to be most effective in the early stages of infection, while host modifiers such as dexamethasone are best utilized at later stages of illness.

Dr Sulkowski noted that in a trial of remdesivir in which the primary outcome was time to recovery after diagnosis, patients who received remdesivir recovered in 10 days, compared with 15 days for patients who did not receive remdesivir. The patients who benefitted were receiving oxygen, but those with the most severe disease, such as those on ventilation, did not appear to benefit from remdesivir.

However, the patients with the most severe COVID-19 illness do appear to benefit from the use of dexamethasone. The RECOVERY trial, conducted in the United Kingdom and enrolling 11,500 participants, randomized some patients to standard-of-care and others to various other treatments including dexamethasone. The primary outcome was all-cause mortality at 28 days. “Patients on mechanical ventilation benefited from dexamethasone but those who did not require ventilation did not. There was a clear benefit to the use of this corticosteroid in patients with more severe disease.”

—Rebecca Mashaw

References:

1. Fauci A. COVID-19 overview and vaccine summary. Talk presented at: American Association for the Study of Liver Diseases annual meeting. November 15, 2020. Virtual.

2. Verna E. Hepatic manifestations of COVID-19. Talk presented at: American Association for the Study of Liver Diseases annual meeting. November 15, 2020. Virtual.

3. Sulkowski M. Current therapy of COVID-19 and hepatic issues related to therapy. Talk presented at: American Association for the Study of Liver Diseases annual meeting. November 15, 2020. Virtual.