Liver Injury in Liver Transplant Recipients With Coronavirus Disease 2019 (COVID‐19): U.S. Multicenter Experience

Abstract

Background Coronavirus disease 2019 (COVID-19) is associated with liver injury, but the prevalence and patterns of liver injury in liver transplant (LT) recipients with COVID-19 is not defined. Approach and Results We conducted a multicenter study in the US of 112 adult LT recipients with COVID-19. The median age was 61 years (IQR 20), 54.5% (n=61) were male, and 39.3% (n=44) Hispanic. The mortality rate was 22.3% (n=25); 72.3% (n=81) were hospitalized and 26.8% (n=30) admitted to the ICU. Analysis of peak values of alanine aminotransferase (ALT) during COVID-19 showed moderate liver injury (ALT 2-5x ULN) in 22.2% (n= 18) and severe liver injury (ALT > 5x ULN) in 12.3% (n= 10). Compared to age and gender matched non-transplant patients with CLD and COVID-19 (n=375), the incidence of acute liver injury was lower in LT recipients (47.5% vs. 34.6%; p=0.037). Variables associated with liver injury in LT recipients were younger age (p= 0.009, odds ratio (OR) 2.06 [1.20-3.54]), Hispanic ethnicity (p= 0.011; OR 6.01 [1.51-23.9]), metabolic syndrome (p= 0.016; OR 5.87 [1.38-24.99]), vasopressor use (p= 0.018; OR 7.34 [1.39-38.52]) and antibiotic use (p= 0.046; OR 6.93 [1.04-46.26]). Reduction in immunosuppression (49.4%) was not associated with liver injury (p= 0.156) or mortality (p= 0.084). Liver injury during COVID-19 was significantly associated with mortality (p= 0.007; OR 6.91 [95% CI: 1.68-28.48]) and ICU admission (p=0.007; OR 7.93[1.75-35.69]) in LT recipients. Conclusion Liver injury is associated with higher mortality and ICU admission in LT recipients with COVID-19. Hence, monitoring liver enzymes closely can help in early identification of patients at risk for adverse outcomes. Reduction of immunosuppression during COVID-19 did not increase risk for mortality or graft failure.

Covid-19 in liver transplant recipients: the French SOT COVID registry

“…Although not statistically significant, time since LT seems shorter for LT recipients remaining at home that those hospitalized, pointing towards lesser importance of level of immunosuppression (as compared to other major risk factors including age, but also past duration of immunosuppression). As previously reported in solid organ transplant recipients [5] , [16] , [17] , [18] , [19] , [21] , [28] , [29] , [30] , [31] , a reduction in maintenance immunosuppression was made in a large part of our hospitalized patients: antimetabolites, mTOR inhibitor, and CNIs were withdrawn in 41.9%, 30.0% and 12.5% of patients, respectively. According to the French recommendations on management of immunosuppressive (and also most recommendations for organ transplant recipients) modification ( i.e.…”

“…Rabiee and coll. conducted a multicenter comparative study in the US including 112 adult LT recipients with COVID-19 [21] . The mortality rate was 22.3%; 72.3% were hospitalized and 26.8% admitted to the ICU.…”

COVID-19 and liver disease: mechanistic and clinical perspectives

“…Among hospitalized patients with COVID-19, elevations of serum AST levels positively correlate with levels of ALT but not with markers of muscle breakdown (such as creatinine kinase) or systemic inflammation (such as C-reactive protein (CRP) and ferritin) 50 . These findings imply that elevated liver enzymes in COVID-19 result from direct hepatic injury, although COVID-19-associated rhabdomyolysis is rarely reported 51 .…”

“…These findings imply that elevated liver enzymes in COVID-19 result from direct hepatic injury, although COVID-19-associated rhabdomyolysis is rarely reported 51 . Lastly, AST is often found to exceed ALT during the course of COVID-19, which would be atypical for a classic hepatocellular pattern of liver injury outside of specific contexts such as alcohol-related liver disease, certain drug-induced liver injuries (for example, lamotrigine), ischaemic hepatitis and cirrhosis 50 . The mechanisms responsible for an AST-predominant aminotransferase elevation remain incompletely defined but could include COVID-19-related mitochondrial dysfunction 33 , SARS-CoV-2-induced hepatic steatosis 31 and altered hepatic perfusion secondary to microthrombotic disease 31 , 52 .…”

“…As already discussed, disturbances of liver biochemistry are frequent in COVID-19 but seem to be an indirect effect of SARS-CoV-2 infection analogous to that seen in the cytokine storm in other situations 55 , 57 , 130 . Although liver injury — as defined by elevated serum transaminase activities — occurs in LT recipients and is associated with mortality, it seems either no more frequent or less frequent than in comparison groups 117 , 127 .…”