The Liver Meeting Digital Experience, held this past weekend by the American Association for the Study of Liver Diseases, provided new insights on the hepatic manifestations of COVID-19, the impacts of infection on patients with liver diseases, and the discovery of hepatitis C virus.
First, it's important for clinicians to know that liver enzyme elevations are common in patients with COVID-19, Elizabeth C. Verna, MD, MSc, a hepatologist at Columbia University Irving Medical Center in New York City, said during the meeting's COVID-19 and the Liver Clinical Symposium. “Since the very first published descriptions of the clinical manifestations of COVID-19 from China, there have been reports of liver enzyme elevation as a common phenomenon,” she noted, adding that the literature on the association between COVID-19 and elevated liver tests is now extensive, with several meta-analyses and systematic reviews. “Overall, elevation in liver tests have been reported in 14% to 53% of inpatients with COVID-19.”
Aspartate aminotransferase (AST) is generally the most commonly elevated value in studies of patients with COVID-19. In one meta-analysis, largely of reports from China, the pooled prevalence of liver injury was 19% in 12 studies. The pooled prevalence of increased AST was 21%, followed by increased alanine aminotransferase (ALT) at 18% and increased total bilirubin at 6%, according to results published online on May 12 by The Lancet Gastroenterology & Hepatology. In addition, Dr. Verna's group found that the overall initial and peak AST and ALT levels were elevated among patients with confirmed COVID-19 compared to controls who tested negative, according to results published online on May 30 by Hepatology. “But these elevations were generally mild, with the peak ALT over the upper limit of normal in 45% [of patients with COVID-19] but over five times the upper limit of normal in only 6%,” she noted.
While liver enzyme elevation in patients with COVID-19 is generally mild and does not require a specific intervention, it may be an important prognostic marker, even at lower levels of elevation, Dr. Verna said. For example, a meta-analysis published online on Aug. 31 by Annals of Hepatology showed a significant association between elevated AST and elevated ALT and critical illness related to COVID-19. She added that in data from her center, “We did find that peak ALT was highly predictive of death or discharge to hospice [after] controlling for advanced age, comorbidities that have been associated with COVID-19, and … markers of critical illness, including the need for intubation or renal replacement therapy.”
During a patient-centered update, Ryan M. Kwok, MD, FACP, reviewed the clinical outcomes of patients with chronic liver disease and COVID-19. Compared to patients without chronic liver disease, those with pre-existing liver diseases had a 2.8 times increased risk for death, and those with cirrhosis had a 4.6 times increased risk for death in a study published online on May 3 by Gastroenterology. “We know that COVID-19 has had unprecedented impacts on the care of chronic liver disease patients, but thankfully, knowledge and experience are rapidly evolving,” said Dr. Kwok, an associate professor of medicine at Uniformed Services University and associate program director of the gastroenterology and hepatology fellowship for the National Capital Consortium in Bethesda, Md.
He offered the following pearls about COVID-19 for chronic liver disease patients, based on the evidence to date.
- Viral hepatitis: There is no evidence that patients with these infections who do not have advanced fibrosis or cirrhosis are at higher risk of infection with the novel coronavirus or of having a more severe course when infected.
- Autoimmune hepatitis: Immunosuppressed patients, such as those with autoimmune hepatitis controlled with immunosuppressive medications, do not seem to be at increased risk for severe complications of COVID-19.
- Alcoholic liver disease: Even prior to the pandemic, the literature suggested that alcohol may suppress the immune system, which may lead to increased susceptibility to severe respiratory complications associated with COVID-19.
- Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Patients with these diseases appear to have more severe liver injury, to be at higher risk for hospitalization, and to have a more severe course of COVID-19 infection in studies comparing them to those without.
- Cirrhosis: Patients with cirrhosis are at increased risk for infection and, when infected, may experience a more severe course, with an increased risk of decompensation and death in some cases.
- Hepatocellular carcinoma: Patients with any form of cancer may be at increased risk of infection and of having a more severe course if infected.
- Liver transplant candidates: Those with cirrhosis or some chronic liver diseases may have an increased risk for liver-related and even fatal complications of COVID-19.
- Liver transplant recipients: Immunosuppressed patients do not seem to be at increased risk for having severe complications of COVID-19 or a more severe course.
The meeting also featured a discussion with the winners of the Nobel Prize in Physiology or Medicine 2020: Harvey J. Alter, MD, MACP; Michael Houghton, PhD; and Charles M. Rice, PhD. The scientists' combined discoveries led to the identification of hepatitis C virus. In the 1970s, Dr. Alter led methodical studies of transfusion-associated hepatitis that showed an unknown, “non-A, non-B” virus was a common cause of hepatitis after blood transfusion. Dr. Houghton and colleagues then isolated the genetic sequence of the new virus, named hepatitis C virus, using DNA fragments found in the blood of an infected chimpanzee. Finally, Dr. Rice provided the evidence showing that hepatitis C virus alone could cause the unexplained cases of transfusion-mediated hepatitis.
The Nobel Laureates, whose research has led to the current age of robust testing for hepatitis C virus and the development of direct-acting antivirals, discussed potential future approaches to eradicating the virus. While a vaccine is conceivable, Dr. Alter said, he questioned whether it would be necessary given the curative treatments that are currently available, albeit expensive. “My short answer is yes, I think it would be still the best way to get global eradication. But I'd like to think of the possibility that even if a vaccine is not developed that we could eradicate hepatitis, both B and C. … I hope my legacy will be that I played a role in improving the safety of the blood supply to virtual zero risk for hepatitis viruses and that I laid the groundwork with my many collaborators,” he said.