Increased Hospitalization and Mortality in Patients With COVID-19 and Pre-existing Liver Disease

More than half of patients with COVID-19 have markers of liver injury, researchers report in Gastroenterology. However, patients with pre-existing liver disease, and even more so those with cirrhosis, have increased risks for hospitalizations and death, the study found.

Levels of ALT in COVID-19 patients with and without pre-existing liver disease

Shailendra Singh and Ahmad Khan studied the effects pre-existing liver disease on outcomes of a large cohort of patients with COVID-19 in the United States. They performed a real-time search for patients with a diagnosis of COVID-19 the using the TriNETX Research Network of more than 49 million patients from 37 healthcare organizations.

Patients with COVID-19 were assigned to 2 groups, based on the presence or absence of pre-existing liver disease. The liver disease group comprised patients with a diagnosis of chronic liver disease, cirrhosis, or related complications, before or at the time of diagnosis of COVID-19. The authors analyzed outcomes of mortality, hospitalization, and laboratory findings for up to 30 days after diagnosis of COVID-19.

Singh and Khan identified a total of 2780 patients with COVID-19 at 34 health care organizations: 250 patients (9%) had pre-existing liver disease (1.8% with cirrhosis, 42% with fatty liver disease or nonalcoholic steatohepatitis) and the remaining 2530 did not have liver disease (controls). The authors performed propensity score matching for body mass index, hypertension, diabetes, age, race, and nicotine use.

Mean levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased from baseline after COVID-19 in the liver disease group (ALT 100±444 U/L and AST 221±1799 U/L) and the control group (ALT 80±227 U/L and AST 133±678 U/L) (see figure). Increased levels of ALT (>50 U/L) were observed in 46.1% of patients with liver disease and 50.6% of controls.

Levels of gamma-glutamyl transferase, alkaline phosphatase, total bilirubin, ferritin, C-reactive protein, lactate dehydrogenase, IL6, creatine kinase, and D-dimer were also increased in both groups.

However, patients with pre-existing liver disease had a significant increase in risk of death compared with controls (relative risk, 2.8; 95% CI 1.9–4.0; P<.001); risk was even higher after propensity matching of the groups (relative risk, 3.0; 95% CI 1.5–6.0; P<.001). Risk of hospitalization was also higher in the liver disease group.

In subgroup analysis, patients with cirrhosis had the highest risk of death, compared with controls (relative risk, 4.6; 95% CI 2.6–8.3; P<.001).

How does COVID-19 cause liver injury? Singh and Khan explain that SARS-CoV-2 binds to the angiotensin-converting enzyme 2 (ACE2), which are expressed on liver and bile duct cells, among other cell types. Previous studies have reported abnormal levels of ALT and AST in up to 53% of patients with COVID-19. However, these might be caused by medications or other factors; the authors were not able to specify a pattern of liver injury. Hypoxia in patients with COVID-19 can also result in liver injury and organ failure.

COVID-19 patients with pre-existing liver dysfunction, especially with cirrhosis, appear to be more susceptible to poor outcomes from these direct injuries to liver. Moreover, the immune deficiency and accompanying persistent systemic inflammation caused by activated circulating immune cells and increased serum levels of inflammatory cytokines in patients might result in an uncontrollable inflammatory resposne. Many patients with cirrhosis also have hepatopulmonary syndrome, porto-pulmonary hypertension, or hepatic hydrothorax, which could increase risk of respiratory failure.

Singh and Khan conclude that early isolation, intensive surveillance, and timely diagnosis are essential for patients with COVID-19 who have pre-existing liver disease.

<<