Early in the pandemic, four critically ill COVID-19 patients developed a complication similar to secondary sclerosing cholangitis, an inflammatory liver disease, researchers reported.
The case series involved four men, ages 48 to 68, who needed prolonged mechanical ventilation, renal support, and veno-venous extracorporeal membrane oxygenation (VV-ECMO) during the first 12 weeks of the pandemic in Belgium, according to Diethard Monbaliu, MD, PhD, from the University Hospitals Leuven, and colleagues, writing in Intensive Care Medicine.
While secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has an estimated prevalence of 0.05%, Monbaliu told MedPage Today that he was surprised with the high incidence in this cohort in the first 3 months of the pandemic.
He offered comparisons between COVID-19 patients and influenza patients, saying in 3 months, four COVID-19 patients out of a cohort of 114 patients meant that 5.4% of mechanically ventilated COVID-19 patients and 30.7% of VV-ECMO-treated COVID-19 patients developed the condition.
“In comparison, over a recent 28-month period” from April 2018 to 2020 “in our ICU, the incidence of SSC-CIP in VV-ECMO-treated influenza patients was 7%,” Monbaliu added.
Severe COVID-19 can result in multi-organ failure, associated with elevated bilirubin, jaundice, and gamma-glutamyl transferase levels. Previous research reported an increased frequency of bile duct injury leading to secondary sclerosing cholangitis arising from COVID-19 compared to other critical illnesses.
“Our data, although from a small cohort, indicate a spectrum of severity, ranging from asymptomatic bile duct abnormalities to cholangiosepsis,” the authors stated.
Interestingly, they cited specific COVID-19-related disease factors in addition to treatment factors that could cause cholangiopathy and biliary ischemia in patients, such as hemodynamic instability and anesthetic drug-induced bile duct injury from the prolonged use of ketamine or parenteral nutrition.
“Bile in itself may be toxic to the biliary epithelium due to its high content in hydrophobic bile acids. Ischemia and pro-inflammatory cytokines both inhibit the physiological defence of the biliary epithelium, in particular phospholipid secretion and the so-called bicarbonate umbrella, resulting in cholangiocyte necrosis,” Monbaliu said.
In their series, three COVID-19 patients admitted to the ICU from March to June 2020 developed cholestatic liver injury, which progressed rapidly after they recovered from acute respiratory distress syndrome. These cases of liver injury later evolved into secondary sclerosing cholangitis. During this time, a fourth patient with this condition was referred with the same condition, the authors said.
Researchers analyzed changes in liver enzymes, such as alkaline phosphatase, gamma-glutamyltransferase, alanine transaminase, and aspartate transaminase, as well as total bilirubin.
“SARS-CoV-2 RNA and nucleocapsid protein have been detected in the cholangiocytes and bile of patients with fatal COVID-19 pneumonia, suggesting that a direct cytopathic effect may occur,” wrote Monbaliu and coauthors.
Magnetic resonance cholangiopancreatography (MRCP) found focal strictures in the intrahepatic bile ducts of the ill patients in addition to intraluminal sludge and casts, described as “the radiological hallmark of SSC-CIP.” Biopsies revealed biliary obstruction of the liver.
Two of the patients required liver transplants due to refractory cholangitis, which led to irreversible damage. One of the transplant patients is doing well while the other died of septic shock after contracting pneumonia following transplant. Another of the patients in the series died after experiencing lethal hepatic hemorrhage. The fourth patient had a better outcome after experiencing only mild SSC-CIP.
Limitations of this case series include the short follow-up.
Authors added that the risk for mild forms of COVID-19 to develop into secondary biliary cirrhosis is still questionable. Additional studies are also needed for assessing the outcomes of COVID-19 with cholangiopathy after liver transplantation.
The authors urged all physicians to be on the lookout for this complication, as the severity of this condition may vary among patients.
“Because of the bad prognosis, diagnosis should not be delayed, even though diagnostic ERCP [endoscopic retrograde cholangiopancreatography] and/or MRCP may be logistically demanding in the COVID-19 ICU setting,” Monbaliu said. “Early referral to a liver transplant center to evaluate the potential benefit of treatment may be needed.”
The authors report no conflicts of interest.