Table 2.

Published Literature on COVID-19-Induced Cholestasis.

Serial no.	First author ref, month, year	N	Age/gender	Comorbidities	Complications during COVID-19 illness	Time to rise in ALP	MRCP	Liver biopsy	ERCP	Outcome
1	Edwards et al.16 Nov. 2020, UK	1	59Y/M	–	MV/bacterial sepsis/vasopressor	Time to elevation-15 days. Peak at 79 days (4000 U/L))	Beading of intrahepatic ducts	Not done	ERCP for sludge clearance	Alive ¶ ? LT after liver biopsy
2	Sadeghi et al.19 2020. Iran	1	67Y/F	None	–	At admission (966 U/L). Peak at day 3 (1353 U/L)	Normal	Diffuse cholestasis with fibrosis and inflammatory infiltrates	–	Alive
3	Roth et al.9 January 2021, USA.	3	Age: 25, 38, 40 Y Males: 2	1/3 had DM	MV/AKI/Vasopressor support-100%. RRT-2/3 Secondary bacterial infections-3/3	–	Beading, with multiple short segmental strictures and intervening dilatation in 1/3 (33%) patients	Ductopenia-2/3 patients. Ductular reaction, portal tract inflammation and portal and periportal fibrosis-100%	ERCP for 2 patients-sludge and stone extracted	Alive ¶
4	The Keta-Cov research group17∗ May 2021, France.	5	Median age: 59Y Males: 3	HTN-3 DM-2 HBV-2	MV/AKI/vasopressor support −100% All had received intravenous ketamine	–	Strictures and dilatations of intrahepatic bile ducts in 1/5 (20%) patient	Cholangiolar proliferation, biliary plugs, portal inflammation, extensive biliary fibrosis, and cirrhosis	ERCP-1 patient for removal of bile duct cast.	Two died (one died while waiting for LT)
5	Butikofer et al.18 May 2021. Switzerland	20/34 severe cases: 11—mild and 9— severe cholestasis.ǁ	Median age: 59Y Males: 16	DM-1 in mild and 7 in severe group. HTN-8 in mild and 7 in severe group.	Vasopressors: mild: 100%; severe: 89%; and MV: 100%	6–20 days after admission to ICU.	Diffuse irregularities of the bile ducts with dilatations and strictures—4/9 (44%) severe cholestasis patients	Portal inflammation with pericellular fibrosis.	UDCA for all four patients who developed SSC. 1—listed for LT (MELD-17)	Four died in the mild group. Five died in the severe group. Four developed SSC.
6	Durazo et al.10 May 2021, USA	1	47Y/M	HTN	MV AKI required RRT	At day 58 ALP 1644 U/L. At day 81–2730 U/L	Diffuse intrahepatic biliary stricture	Hilar bile duct injury with hepatic abscess	ERCP removal of choledocholithiasis.	LT on day 108 (MELD-37)
7	Faruqui et al.15 July 2021.USA	12	Mean age: 58Y Males: 11	DM: 4/12 HTN: 8/12	MV—100% Vasopressors—10/12. Thrombosis—8/12 Sepsis—12/12 All had received intravenous ketamine	118 days	Beading of intrahepatic ducts in 11/12 (92%)	Fibrosis and ductular reaction in four patients. No ductopenia.	4-ERCP	4—died. 1—LDLT 7—alive. (1—listed for LT and 2 declined LT)
8	Da et al.7 August. 2021. USA	72	65Y Males: 43	DM: 31/72 HTN: 41/72 CLD: 4/72	MV: 20.8% Vasopressor: 22.2%	–	–	–	–	33.3% (24/72)—died versus 19.2% (23/120) in the control group
9	Current study. India	15	Median age-56Y Males-13	DM-9/15	MV + NIV-13/15 Vasopressors-1/15	36 days	Normal	Architectural distortion, fibrosis, cholestasis, and ductular reaction with ductopenia in unvaccinated group. Cholestasis and inflammation in vaccinated group	Plasma exchange- 5. Oral steroids- 4	2-died 2-LT 2-listed for LT 1-declined LT 2-recovered. All 7 in vaccinated group recovered

COVID-19, coronavirus disease 2019; ALP, alkaline phosphatase; MRCP, magnetic resonance cholangiopancreatography, ERCP, endoscopic retrograde cholangiopancreatography; Y, years; MV, mechanical ventilation; LT, liver transplantation; DM, diabetes mellitus; AKI, acute kidney injury; RRT, renal replacement therapy; HTN, hypertension; HBV, hepatitis B virus; ICU, intensive care unit; UDCA, ursodeoxycholic acid; MELD, model for end-stage liver disease, NIV, non-invasive ventilation.

ǁ (ALP ≥1.5 ULN and GGT≥3 ULN with bilirubin≥ 2 ULN).

¶At last follow-up patients still had elevated bilirubin and ALP.