Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID‐19

Abstract

Summary Background & Aims Little is known about cholestasis including its most severe variant secondary sclerosing cholangitis (SSC), in critically ill patients with coronavirus disease 19 (COVID‐19). In this study we analyzed the occurrence of cholestatic liver injury and SSC, including clinical, serological, radiological and histopathological findings. Methods We conducted a retrospective single‐center analysis of all consecutive patients admitted to the intensive care unit (ICU) due to severe COVID‐19 at the University Hospital Zurich to describe cholestatic injury in these patients. The findings were compared to a retrospective cohort of patients with severe influenza A Results 34 patients with severe COVID‐19 admitted to the ICU were included. 14 patients (41%) had no cholestasis (group 0), 11 patients (32%, group 1) developed mild and 9 patients (27%, group 2) severe cholestasis. Patients in group 2 had a more complicated disease course indicated by significantly longer ICU stay (median 51 days IQR 25‐86.5) than the other groups (group 0 median 9.5 days IQR 3.8‐18.3 p =0.001 and group 1 median 16 days IQR 8‐30 p < 0.05 respectively). Four patients in group 2 developed SSC compared to none in the influenza A cohort. The available histopathological findings suggest an ischemic damage to the perihilar bile ducts. Conclusions The development of SSC represents an important complication of critically ill COVID‐19 patients and needs to be considered in the diagnostic work up in prolonged cholestasis. The occurrence of SSC is of interest in the ongoing pandemic since it is associated with considerable morbidity and mortality.

Ketamine-induced cholangiopathy in ARDS patients

“…Ketamine has been widely used as a second-line sedative agent in intensive care units (ICUs) during the COVID-19 pandemic [ 2 , 3 ]. In 2021, Bütikofer and colleagues compared 34 critically ill COVID-19 patients with 34 critically ill influenza patients [ 4 ]. Four patients in the COVID-19 group developed SCC compared to none in the influenza group despite a higher severity of influenza patients (i.e., higher sepsis related organ failure assessment (SOFA) score, higher simplified acute physiology (SAP) score II).…”

Covid‐19 and Liver Injury: Role of Inflammatory Endotheliopathy, Platelet Dysfunction, and Thrombosis

“…In addition to a hepatocellular pattern of enzyme elevation, liver injury in COVID‐19 can manifest with a cholestatic pattern as well. ( 103 , 104 ) This has been hypothesized to be due to ACE2 expression on biliary epithelial cells leading to direct viral infection. Interestingly, however, two reports of cholestasis following COVID‐19 infection suggest a possible role for endotheliopathy, noting hepatic artery branches in the portal tract with endothelial swelling with luminal narrowing, portal vein endophlebitis (inflammation of the intima area of a vein), and endothelialitis (leukocyte attachment to the vascular wall) and thrombotic material in portal vein branches.…”

Liver histopathological changes and COVID-19: What does literature have to tell us?

“…According to the literature, the most common histopathological changes associated with SARS-CoV-2 were hepatic steatosis (HS), thrombosis or/and portal and periportal inflammatory infiltrate, Kupffer cell hyperstimulation and cholestasis [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] . We summarize the main histopathological findings of COVID-19 in the liver in Figure 1 , Figure 2 .…”

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Figure 1 [Adapted] A. Macrovesicular and microvesicular steatoses are demonstrated with platelet-fibrin thrombi are present in the sinusoidal spaces and central vein (H&E, ×400) [5] . B. Ductular (black arrowhead) and canalicular (white arrowheads) cholestasis (H&E; scale bar 50µm) [10] .

Figure 2 A: Example of genuine thrombosis: portal with clearly enlarged lumen obliterated by red cell mixed andstratified with lymphocytes and granulocytes (H&E,100 ×); B: smooth musde layer of portal vein lamina media extremely irregular fragmented (SMA, 100 ×); SAR-CoV-2 virions are demonstrated within vessel lumen and onendothelial cells (ISH) (inset); C: medium layer of a portal vein, partially lost and infiltrated by inflammatory cellslymphocytes, also attaching endothelial layer (AMA, 400×); CD3-positive lymphocytes attack endotelium andmedium vessel layer (inset); D: severe confluent haemorrhagic necrosis in a patient with elevation of ALT> 10 N(H&E, 100×); inset showing liver necrosis by apoptosis (H&E, 400×) [Adapted] [3] .

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“… [Adapted] A. Macrovesicular and microvesicular steatoses are demonstrated with platelet-fibrin thrombi are present in the sinusoidal spaces and central vein (H&E, ×400) [5] . B. Ductular (black arrowhead) and canalicular (white arrowheads) cholestasis (H&E; scale bar 50µm) [10] . …”