Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients

Abstract

Background Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. Methods This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. Results SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. Conclusions COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

Endoscopic Features of Post–COVID-19 Cholangiopathy and Its Management Using ERCP

“…It most likely occurs when the patient's condition is most critical, i.e., around the time of intubation. Both the peracute onset of post–COVID-19 cholangiopathy and the distribution pattern of bile duct lesions are reminiscent of ischemic cholangitis and confirm our recent findings ( 9 ). PCR testing, although not performed in all of our patients, did not detect any viral components of SARS-COV-2 in the bile.…”

“…Other authors postulated that this cholangiopathy observed in patients with COVID-19 was ketamine induced ( 7 ). Exclusively observed in critically ill patients, increasing evidence suggests that post–COVID-19 cholangiopathy is (merely) a variant of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) ( 9 , 10 ). As recently shown, the incidence of this post–COVID-19 cholangiopathy is high—up to 2.3 cases per 100 invasively ventilated patients with COVID-19 ( 9 ).…”

“…Exclusively observed in critically ill patients, increasing evidence suggests that post–COVID-19 cholangiopathy is (merely) a variant of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) ( 9 , 10 ). As recently shown, the incidence of this post–COVID-19 cholangiopathy is high—up to 2.3 cases per 100 invasively ventilated patients with COVID-19 ( 9 ). Accordingly, a high prevalence of patients with post–COVID-19 cholangiopathy can be expected in the post–COVID-19 era.…”

Clinical and Histopathological Discoveries in Patients with Hepatic Injury and Cholangiopathy Who Have Died of COVID-19: Insights and Opportunities for Intervention

“…Risk factors identified include signs of systemic reduced blood oxygen supply, multi-organ failure, high fibrinogen levels, and intravenous ketamine use. 84 Additionally, disease severity and the need for ICU admission have been linked to an increased risk of cholangiopathy. 85 These findings suggest that certain demographic and clinical factors contribute to the development of cholangiopathy in individuals affected by COVID-19.…”

“Dosis sola facit venenum”—Evidence for causality in the association between ketamine and cholestatic liver injury

“…With great interest, we read the article by Leonhardt et al [ 1 ] describing diverse risk factors for developing secondary sclerosing cholangitis (SSC) following severe Covid-19.…”