Secondary sclerosing cholangitis after critical COVID-19: Three case reports

Table 1 Clinical, images and histological characteristics of the patients reported with post-coronavirus disease 2019 cholangiopathy

Ref.	Patients	Underlying conditions	Drugs	ERCP	MR cholangiography	Liver biopsy	Follow-up
Knooihuizen et al[5]	Female, 54 yr	Diabetes, hypothyroidism, hypertension, and hyperlipidemia	Hydromorphone, midazolam, propofol and ketamine	No reported	Intrahepatic dilatationwith a beaded appearance and dilated common bile duct with distal narrowing	Biliary ductular reaction with lobular inflammation and one small non-necrotizing lobular granuloma without viral inclusions	Continued improvement
Edwards et al[6]	Male, 59 yr	None	Vancomycin and co-trimoxazole	Sclerosing cholangitis in the intrahepatic ducts	Hypointense filling defects within the common bile duct and intrahepatic bile ducts were also dilated and demonstrated some beading	Not reported	Not reported
Mallet et al[7]	3 males and 2 females	Hypertension, diabetes, one with KT and one with HBV infection	Ketamine and no other drugs reported	Filling defects in CBD and rarefication of the intrahepatic biliary tract	Sclerosing cholangitis, with strictures and dilatations of intrahepatic bile ducts, peribiliary cysts and multiple biliary casts	Biliary obstructions, cholangiolar proliferation, biliary plugs, portal inflammation with neutrophil infiltrates, extensive biliary fibrosis and cirrhosis	1 died SSC and cirrhosis, 1 died biliary sepsis, 1 pruritus without jaundice and 2 recurrent biliary sepsis
Sanders et al[8]	Male, 57 yr	Hypertension and diabetes	No reported	Bile duct stone cast and intrahepatic duct stenosis without dilation	No reported	No reported	No reported
Durazo et al[9]	Male, 47 yr	Obesity, OSA, hypertension, and hyperlipidemia	HCQ	Small pigment stone and diffuse intrahepatic biliary strictures	Mild intrahepatic biliary ductal dilatation with multifocal strictures or beading without extrahepatic biliary dilatation	Mononuclear inflammatory infiltration within the wall of the bile duct, bile lake associated with bile duct injury, microarteriopathy with endothelial cell swelling and obliteration of the lumen and obliterative portal venopathy	On day 108, the patient underwent an OLT
Roth et al[2]	2 males and 1 female	None	Multiple antibiotics	2 sludge and stone extracted	Beading, with multiple short segmental strictures	Ductal reaction, bile duct paucity, cholangiocyte swelling, cholangiocyte regenerative change, portal tract inflammation, endothelial swelling, focal endophlebitis portal veins, cholestasis hepatocanalicular and fibrosis	No reported
Bütikofer et al[10]	3 males and 1 female	Diabetes	Ketamine	No reported	Diffuse irregularities of the bile ducts with dilatations and strictures	Portal edema, mixed portal inflammation and pronounced bile duct damage with ductular reaction as well as lobular bile infarcts and severe hepatocellular, canalicular, focally ductular cholestasis and pericellular fibrosis around portal tracts and central veins	1 cirrhosis Child B, MELD 17, 2 died pulmonary infection and 1 persistently increased ALP

ALP: Alkaline phosphatase; CBD: Common bile duct; ERCP: Endoscopic retrograde cholangiopancreatography; HBV: Hepatitis B virus; HCQ: Hydroxychloroquine; KT: Kidney transplantation; MELD: Model for End-stage Liver Disease; MR: Magnetic resonance; OLT: Orthotopic liver transplantation; OSA: Obstructive sleep apnea; SSC: Sclerosing secondary cholangiopathy.

Table 2 Clinical characteristics

	Patient 1	Patient 2	Patient 3
Demographics
Age (yr)	45	52	46
Sex	Male	Male	Female
Comorbidities	T2D, HT, CKD KDIGO III	T2D, HT, CKD KDIGO V	T2D, HT, CKD KDIGO V
COVID-19 infection
ICU admission	Yes	Yes	Yes
Mechanical ventilation	Yes	Yes	Yes
Vasopressor support	Yes	Yes	Yes
Renal replacement therapy	Yes	Yes (on hemodialysis before admission)	Yes (on hemodialysis before admission)
Secondary infections	Ventilator-associated pneumonia due to Enterobacter cloacae, Stenotrophomonas maltophilia and Klebsiella pneumoniae	Streptococcus pneumoniae and Staphylococcus aureus bacteremia. Ventilator-associated pneumonia due to Stenotrophomonas maltophilia, Enterobacter cloacae and Aspergillus fumigatus	Ventilator associated pneumonia due to Pseudomonas aeruginosa
Antibiotics	Meropenem, vancomycin, ceftriaxone and co-trimoxazole	Meropenem, vancomycin, moxifloxacin, co-trimoxazole and voriconazole	Imipenem, piperacillin/tazobactam and moxifloxacin
COVID-19 specific therapy	Dexamethasone	Dexamethasone	Dexamethasone
Liver chemistries on admission
TB (mg/dL)	0.36	0.37	0.47
ALT (U/L)	37	20	11.8
AST (U/L)	33	46	35.9
ALP (U/L)	89	128	91
Peak liver chemistries
TB (mg/dL)	11.72	22.7	17.32
ALT (U/L)	63	62.7	7.9
AST (U/L)	119	184.1	46.4
ALP (U/L)	2146	2370	705
Last liver chemistries
TB (mg/dL)	6.41	8.82
ALT (U/L)	48	9.3
AST (U/L)	129	52.6
ALP (U/L)	3250	1870
Sclerosing cholangitis imaging findings (CT, ERCP, MRI)	Yes	Yes	Yes
Histology	Intracanalicular cholestasis, portal inflammation, ductular reaction and moderate portal fibrosis	None	None
Evidence of liver fibrosis	Yes (histology)	Yes (VCTE)	No
Death	No	No	Yes

ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; COVID-19: Coronavirus disease 2019; CKD: Chronic kidney disease; CT: Computed tomography; ERCP: Endoscopic retrograde cholangiopancreatography; HT: Hypertension; ICU: Intensive care unit; MRI: Magnetic resonance imaging; TB: Total bilirubin; T2D: Type 2 diabetes; VCTE: Vibration-controlled transient elastography.