Systemic Inflammation in COVID-19 Could Be Responsible for Liver Damage

liver disease
liver disease
In patients with COVID-19, hepatic injury was associated with elevated levels of IL-6, CRP, ferritin, and lactate dehydrogenase.

Hepatic injury in coronavirus disease 2019 (COVID-19) may be a result of systemic inflammation, according to study data published in Digestive and Liver Disease. In a cohort of patients with suspected COVID-19, liver damage was associated with elevated levels of systemic interleukin (IL)-6, C-reactive protein (CRP), ferritin, and lactate dehydrogenase (LDH).  

While prior studies have identified liver injury as a potential complication of COVID-19, the underlying cause of poor hepatic outcomes with COVID-19 remains unclear. This cross-sectional study enrolled 655 patients with suspected COVID-19 who received care at the University Hospital of Innsbruck in Austria. Patient evaluations took place between February 26 and April 21, 2020.

The primary outcome was acute liver injury, defined by the following parameters: aspartate transaminase (AST) ≥50 Units/liter (U/l), alanine aminotransferase (ALT) ≥50 U/l, gamma-glutamyl transferase (GGT) ≥71 U/l, alkaline phosphatase (AP) ≥129 U/l, and total bilirubin ≥1.28 U/l. Levels of systemic IL-6 and acute phase proteins were assessed by standard clinical assays. Associations between liver damage and markers of inflammation were determined using the Student’s t-test, the non-parametric Mann-Whitney U test, or the Wilcoxon signed-rank test.

Mean patient age was 60.69 years, and 37.5% were women. The majority of patients presented with fever (75.8%), cough (88.9%), muscle pain (66.7%), and fatigue (67.8%). An additional 50% experienced dyspnea. On admission day, 39.5% of patients who were not admitted to the ICU displayed elevated AST, compared with 60% of patients in the ICU. Systemic IL-6 was positively correlated with AST in all patients (r2 =0.481; P <.001), though the effect was more pronounced in patients admitted to the ICU (r2 =0.610; P =.016).

AST levels were also positively correlated with CRP (r2 =0.38; P <.001), ferritin (r2 =0.6; P <.001), and LDH (r2 =0.6; P <.001) concentrations. In longitudinal analyses, patients with higher IL-6 levels presented with elevated liver values, including AST, ALT, and bilirubin. IL-6 levels were positively correlated with duration of hospital stay (r2 =0.109; P <.01), duration of ICU stay (r2 =0.162; P <.001), and number of days on mechanical ventilation (r2 =0.146; P<.001).

Study limitations include the cross-sectional design.

These results implicate systemic inflammation in liver damage among patients with COVID-19. Further study is necessary to clarify the origin of liver damage in COVID-19. “[W]e propose that the systemic inflammatory response to SARS-CoV-2 infection…serves as a fuel of hepatic injury,” investigators wrote.

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Effenberger M, Grander C, Grabherr F, et al. Systemic inflammation as fuel for acute liver injury in COVID-19 [published online August 10, 2020]. Dig Liver Dis. doi: 10.1016/j.dld.2020.08.004