SARS-CoV-2 Infection Induces a Dual Response in Liver Function Tests: Association with Mortality during Hospitalization

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with abnormal liver function tests. We hypothesized that early altered liver biochemistries at admission might have different clinical relevance than subsequent changes during hospitalization. A single-center retrospective study was conducted on 540 consecutive hospitalized patients, PCR-diagnosed with SARS-CoV-2. Liver test abnormalities were defined as the elevation of either gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), or aspartate aminotransferase (AST), above the upper limit of normality set by our laboratory. Linear mixed models (LMM) evaluated longitudinal associations, incorporating all available follow-up laboratory chemistries. By the end of the follow-up period, 502 patients (94.5%) were discharged (109 (20.5%) died). A total of 319 (64.3%) had at least one abnormal liver test result at admission. More prevalent were elevated AST (40.9%) and GGT (47.3%). Abnormalities were not associated with survival but with respiratory complications at admission. Conversely, LMM models adjusted for age and sex showed that longitudinal increases during hospitalization in ferritin, GGT, and alkaline phosphatase (ALP), as well as a decreased albumin levels, were associated with reduced survival. This dual pattern of liver damage might reconcile previous conflicting reports. GGT and ALP trajectories could be useful to determine who might need more surveillance and intensive care.

COVID‐19 and the liver – Lessons learned

“…The authors concluded that SARS‐CoV‐2 may have a dual effect on the liver, characterized by elevated aminotransferases on admission followed by a marked cholestasis in patients with a fatal outcome (Figure 1). Median albumin levels were already lower on admission in non‐survivors than in survivors (3 g/dL vs 3.4 g/dL, respectively, P < .001), and further decreased in these patients during hospitalization 9 . In conclusion, abnormal liver function tests are common in COVID‐19, mainly in the form of transient increases in aminotransferases.…”

“…There was a negative correlation between initial oxygen saturation and ASAT but not GGT ( P <.001 and P =.944 respectively). A longitudinal analysis showed that the progression of GGT levels was positively correlated with inflammatory markers such as C‐reactive protein (CRP) and strongly increased in non‐survivors but not in survivors during hospitalization ( P < .001) 9 . The authors concluded that SARS‐CoV‐2 may have a dual effect on the liver, characterized by elevated aminotransferases on admission followed by a marked cholestasis in patients with a fatal outcome (Figure 1).…”

Abnormal Liver Biochemistry Tests and Acute Liver Injury in COVID-19 Patients: Current Evidence and Potential Pathogenesis

“…Decreased levels of albumin and higher levels of AST were also associated with the mortality of COVID-19 patients [191]. However, abnormal liver function tests were not associated with survival in hospitalized COVID-19 patients [192] but with increased risk of ICU admission [193].…”

Pathophysiological mechanisms of liver injury in COVID‐19

“…While elevations of cholestatic liver enzymes [alkaline phosphatase (ALP) and gamma glutamyl transferase (γGT)] were initially considered rather rare, 4,22,23,46 recent systemic reviews highlight elevations of ALP and γGT in 6.1% and 21.1% of COVID‐19 patients respectively 35,45 . Moreover, a biphasic pattern with initial transaminase elevations followed by cholestatic liver enzymes has been reported, which could reflect SIRS‐induced cholestasis at the hepatocellular/canalicular level or more severe bile duct injury in the later stage of the disease 47 . Although COVID‐19‐associated liver injury has been reported to be mild, it may affect a significant proportion of patients, especially those with a more severe disease course.…”