Systematic Reviews
Copyright ©The Author(s) 2023.
World J Methodol. Sep 20, 2023; 13(4): 296-322
Published online Sep 20, 2023. doi: 10.5662/wjm.v13.i4.296
Table 1 Baseline features in 540 patients with post-COVID-19 cholangiopathy, n (%)
Variable
Patients, n = 540 (100)
Sex
Male69 (12.7)
Female26 (4.8)
Age > 50 year66 (12.2)
Liver enzymes
High (> 45)507 (93.8)
Total bilirubin
High (> 1.2 mg/dL)343 (63.5)
Alkaline phosphatase
High (> 147 IU/L)488 (90.3)
Ultrasound findings
Biliary ductal dilatation with fibrosis225 (41.6)
MRI Findings
Bile duct thickening and enhancement258 (47.7)
Beading of intrahepatic ducts247 (45.7)
Peribiliary diffusion155 (28.7)
Histopathology with secondary sclerosing cholangitis402 (74.4)
Orthotopic liver transplantation 16 (2.96)
Table 2 Summary of systemically reviewed clinical cases
Ref.
Age, yr
Sex
Clinical presentation
Elevated liver enzyme
U/S findings
MRI findings
Respiratory failure
Renal failure
Histopathology
OLT
Outcome
Roth et al[28], 202138MalePost-COVID-19 cholangiopathyYesIntrahepatic bile ducts beading, with sub-segmental strictures and dilatationBeading of intrahepatic ductsYes, required MV; On supplemental oxygen, then off on day 63 and decannulatedYes, recoveredPortal tract findings; Mild duct paucity, moderate bile duct swelling & reaction; Mild portal tract inflammation; Endothelial hepatic artery swelling; Portal veins with focal endo phlebitisNot doneRecovered
25MalePost-COVID-19 cholangiopathyYesHepatomegaly, extrahepatic bile duct dilatation, intrahepatic bile duct dilatationBeading of intrahepatic ductsYes, required MV; On supplemental oxygen, then off on day 112 and decannulatedYes, recoveredPortal tract findings; Moderate duct paucity, moderate bile duct swelling & reaction. Moderate portal tract inflammation; Endothelial hepatic artery swelling; Portal veins with focal endo phlebitis Not doneRecovered
40FemalePost-COVID-19 cholangiopathyYesHepatomegaly, no dilatation Peribiliary diffusion, moderate portal and periportal fibrosisYes, remains with tracheostomy & MV, and then off MV on day 63 Yes, recoveredPortal tract findings; Moderate duct paucity, moderate bile duct swelling & reaction; Severe portal tract inflammation; Endothelial hepatic artery swelling; Portal veins with focal endo phlebitis Not doneDeath, cardiac arrest
Faruqui et al[13], 2021Mean age 58MalePost-COVID-19 cholangiopathyYesU/S showed; extrahepatic bile duct dilatation and intrahepatic bile duct dilatation and periportal diffusionMRI showed, beading of intrahepatic ducts (11/12, 92%); Peribiliary diffusion (10/12, 83%); Bile duct wall thickening (7/12, 58%)Patients required MVYes, recoveredLarge duct obstruction without clear bile duct loss Done OLT Had t successful recovery and rapid clinical improvement
Mean age 58FemalePost-COVID-19 cholangiopathyYesExperiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitisBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredLarge duct obstruction without clear bile duct lossHighly recommended for OLT. Patient on transplantation waiting list, still not done OLT at time of studyRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesExperiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitisBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredLarge duct obstruction without clear bile duct lossHighly recommended for OLT. Patient on transplantation waiting list, still not done OLT at time of studyRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesExperiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitisBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredLarge duct obstruction without clear bile duct lossHighly recommended for OLT. Patient on transplantation waiting list, still not done OLT at time of studyRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesExperiencing persistent jaundice, hepatic insufficiency, and/or recurrent bacterial cholangitisBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredSecondary sclerosing cholangitisHighly recommended for OLT, patient on transplantation waiting list, still not done OLT at time of studyRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ducts; Peribiliary diffusion; Bile duct wall thickeningPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ducts; Peribiliary diffusionPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ducts; Peribiliary diffusionPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ducts; Peribiliary diffusionPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionBeading of intrahepatic ductsPatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Mean age 58MalePost-COVID-19 cholangiopathyYesIntrahepatic bile duct dilatation and periportal diffusionMRI not availablePatients required MVYes, recoveredSecondary sclerosing cholangitisOLT Not doneRecovery with long-term liability and comorbidity
Li et al[29], 2022N/ATwo sample mendelian randomization The autoimmune diseases showed not associated with COVID-19 infection N/AN/AN/AN/AN/AN/AN/AN/A
Hunyady et al[30], 2023N/A24 Patients Post-COVID-19 cholangiopathy developed after a median of 91 dYesN/AN/APatients required MV, the median was 48 d among all patients N/ACOVID-SSC and CIP-SSC share the same clinical phenotypeN/AUDCA showed great improvement in patients without liver cirrhosis and reduced severity in patients with liver cirrhosis, while OLT showed significant improvement in patient with liver cirrhosis
Weaver et al[31], 202163MalePost-COVID-19 cholangiopathyYesSludge in the gallbladder, no biliary ductal dilation, and patent vasculatureN/APatients required MVN/AFilling defects in the common bile duct as well as an irregular and beaded appearance of the intrahepatic ductsNot doneRecovered, after ERCP sphincterotomy followed by balloon sweep of the biliary ducts and removal of thick stone
Hartl et al[32], 2022N/AN/APost-COVID-19 cholangiopathy (65 patients with CLD of 496 patients included in the study, around 24.6% non-ACLD vs ACLD 10.6% associated with COVID Yes. Alkaline phosphatase showed (pre: 91.0 vs T1: 121.0 vs last: 175.0 U/L) and gamma glutamyl transferase GGT (pre: 95.0 vs T1: 135.0 vs last: 202.0 U/L)N/AN/AN/AN/A20% of patients with CLD developed progressive cholestasis post-COVID-19 cholangiopathy, and patients with NASH/NAFLD also have a risk of developing cholestatic liver failure and secondary sclerosing cholangitis post-COVID-19N/AN/A
Duengelhoef et al[33], 2022N/AN/APost-COVID-19 cholangiopathy, associated more with Autoimmune hepatitis AIH as well as post COVID vaccine than PBC and PSC patients YesN/AN/AN/AN/AN/AN/AN/A
John et al[34], 2023N/AN/APost-COVID -19 cholangiopathy study included 1607 patients with liver cirrhosis used UDCAYesN/AN/AN/AN/AN/AN/AUDCA showed great improvement in patients with liver cirrhosis, by decreased symptoms and decreased COVID-19 infection
Heucke et al[35], 2022N/A48Post-COVID-19 cholangiopathy 13% from 496 patients developed CLD; 23% of patients with CLD developed cholestasis/cholangiopathyYes (ALT & AST were elevated in 50 patients less than 5 times upper limit of normal. While in late-stage alkaline phosphatase and GGT were highly progressively elevatedN/AN/AYes, require oxygen supply & some patients MVYes, some patients required dialysis for renal failureThe histopathology reported SARS-CoV-2 RNA and/or proteins in human liver tissue and bile samples, this SARS-CoV-2 RNA may lead to provoke a strong proinflammatory cytokine response (TNF, IL‐1, IL‐6) with hypercoagulation, endothelial damage, consecutive venous and arterial embolism, as well as secondary parenchymal damage9 patients listed for OLT and 6 patients done OLT with good recovery16 patients died, and 24 patients were treated with ketamine during the acute phase of COVID-19 and around 28 patients with SSC from 48 were reduced after using UDCA treatment
Bazerbachi et al[36], 202256FemalePost-COVID-19 cholangiopathy Yes alkaline phosphatase 1574U/L, total bilirubin 11 mg/dL, ALT 88 U/L, AST 101 U/LEUS showed a left hepatic duct stricture and heterogenous, non-shadowing cylindric objects in the main bile ductN/AYes, require tracheostomy & MVYes, developed renal failure and required hemodialysisLHD stricture with upstream dilation of the left ducts, and obliteration of right intrahepatic with secondary sclerosing changesNot done Improved, casts were swept and removed, and left lobe was stented with a 10 Fr 20 cm plastic stent improving bilirubin level to a baseline of 3 mg/dL
Cho et al[37], 202247FemalePost-COVID-19 cholangiopathyYes, highly elevated ALP-positive ANA, anti-mitochondrial highly positiveN/AN/AN/AN/AN/AN/APost-COVID-19 cholangiopathy may be due to direct cytotoxicity from SARS-CoV-2 active replication, hypoxia induced respiratory failure, drug induced liver injury, vascular coagulopathy, immune mediated liver damage
57MalePost-COVID-19 cholangiopathyYes, hypogammaglobinemia, high GGT, elevated AST/ALT, positive anti-mitochondrial antibody, anti-smooth muscle antibodies, and anti-double stranded DNA antibodiesN/AN/AN/AN/AN/AOLT Considered for some patients
N/AN/APost-COVID-19 cholangiopathyYes, ALP > three timesN/AMRCP showed dilatation of hepatic ducts with stenosis and beading of intrahepatic ducts N/AN/AN/A
N/A24 Patients Post COVID-19 CholangiopathyYesN/AN/AN/AN/AN/A
Yu et al[38], 2022N/AN/APost-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AN/AThe patients are not only related to liver disease, but also cholangitis may be due to viral cholangitis, systemic inflammation response, and hypoxic liver injury
Sanders et al[39], 202157MalePost-COVID-19 cholangiopathyYesDilated CBD with a distal CBD stoneN/AYes, required MV. (Tracheostomy & gastrostomy)Renal impairment required fluid resuscitationN/AN/AImproved, biliary cast removed by ERCP, and bile duct stent and patient referred for cholecystectomy
López Romero-Salazar et al[40], 202276MalePost-COVID-19 cholangiopathyYes, elevated ALT & AST developed AIH and complicated to liver cirrhosis secondary to primary biliary cholangitis (PBC) igg positive, ANA U/S showed hepatic fibrotic inflammation, dilated lobes, and biliary ductsN/AN/AN/ABiopsy showed lobular hepatitis, with intense interface, centrilobular necrosis with lymphoplasmacytic inflammationN/AThe patient has poor prognosis due to liver cirrhosis, the study emphasizes the hypothesis that AIH induced due to or post COVID-19 vaccination. Patient given UDCA and obeticholic acid
Wall et al[41], 2022N/AN/APost-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AN/AThe study showed to avoid using SARS-CoV-2-positive donors for liver transplantation unless there is a justifying indicator such as recipient illness severity
Ghafoor et al[42], 2022Mean Age 60.515 Male patientsPost-COVID-19 cholangiopathyYesN/AAll patients had intrahepatic bile duct strictures and 10 patients had associated upstream dilatation. Fourteen patients showed intrahepatic bile duct beading. One patient had extrahepatic bile duct structuring; 9 patients showed high signal on T2 and diffusion weighted images & 7 patients showed patchy arterial phase hyperenhancement; 2 patients showed biliary casts. Vascular complication, and periportal lymphadenopathy were not seen on MRI/MRCPN/AN/AN/AN/AThe post-COVID-19 cholangiopathy patients showed on MRI/MRCP multiple intrahepatic bile duct strictures with intrahepatic bile duct beading
Singh et al[43], 202157MalePost-COVID-19 cholangiopathyYes, elevated ALT, AST, GGT, hypergammaglobulinemia and anti-mitochondrial antibody, anti-smooth muscle antibody and anti-double stranded DNA antibodiesN/AN/AN/AN/AN/AN/AThe patient diagnosed with auto immune hepatitis with primary biliary cholangitis overlap syndrome triggered by COVID-19
Seifert et al[44], 2023N/A7 patients (3 males & 4 females)Post-COVID-19 cholangiopathy among 7 patients of 544 patients with cholangitis. 4 patients had SSC due to other reasonsYes, elevated GGT, Alkaline phosphatase ALP among 7 patients more than 4 patients non COVID-19N/AN/AN/AN/AN/AN/AThe 7 patients with post-COVID-19 cholangiopathy showed more hepatitis and cholangitis than other group non-COVID cholangitis most probably due to direct cytopathologic effect of COVID virus
Lee et al[45], 202164Male Post-COVID-19 cholangiopathyYesU/S intrahepatic bile ducts lossMRI not available Required MVYes, RecoveredDiffuse hepatic injury, onion skinning of the bile ducts and bile duct loss in scattered portal tractsOLT not done; patient need to be stable for the operationNot recovered
Cunha-Silva et al[46], 202345MalePost-COVID-19 cholangiopathy Yes, elevated in the first 2-wk AST, ALT, GGT, Alkaline phosphatase post SARS-CoV-2 infection: ANA and anti-smooth muscle-positive. Negative viral hepatitis & anti-mitochondrial antibodiesN/ANo dilatation of biliary ductsN/AAKI after recovering 2 wk from COVID-19 Numerous foci of lobular necrosis but with no ductopenia or portal biliary reaction. After 2 mo: Biopsy showed: extensive areas of confluent necrosis, hepatocytes regenerating into pseudorosettes and numerous plasma cells, non-suppurative cholangitis all these features diagnosed by PARIS Criteria as AIH-PBC-OSN/AThe patient is given prednisolone in the first phase, then after 2 mo added azathioprine and UDCA to management and showed great response and recovery
Hamid et al[47], 2021N/AN/APost-COVID-19 cholangiopathyYes, elevated AST, ALT, low albumin, and low platelet N/AN/AN/AN/AEndoscopy and ERCP are recommended by WGON/AOLT is advised to be postposed till SARS-CoV-2 infection treated and patient recovered
Kroepfl et al[48]N/A2 patients Post-COVID-19; cholangiopathyYesN/AN/AN/AN/AERCP biopsy showed severely destructed biliary mucosa with ischemia and epithelial roughnessN/AN/A, early cholangioscopy can confirm the diagnosis
Mayorquín-Aguilar et al[24]3 CasesPost-COVID-19 cholangiopathyYesNot available Mild intrahepatic; Biliary ductal; Dilatation with; Multifocal strictures or; Beading without; Extrahepatic biliary; DilatationYes, required MV Yes, recovered SSC-CIP beading of intrahepatic ducts, bile duct wall thickening with enhancement, and peribiliary diffusion high signal2 Done OLT, 1 Not done 2 males death; 1 female recovered
45Male
52Male
46Female
Graciolli et al[49]63MalePost-COVID-19 cholangiopathyYesNot availableDilations with intercalated stenotic segments in intra and extrahepatic bile ducts and edema of the bile ducts corresponding to inflammation of the adjacent parenchymaYesNot availableIntrahepatocellular cholestasisNot doneDeath, infected ulcer, palliative care
Keta-Cov research group[50] Median Age 59 (35-65)MalePost-COVID-19 cholangiopathyYes, elevated AST, ALTGGT, ALP, total bilirubin all elevated N/AAspects of sclerosing cholangitis, with strictures and dilatations of intrahepatic bile ducts, peribiliary cysts and multiple biliary castsAll patients required M/VAll patients developed acute kidney injury required renal replacement therapyERCP showed filling defects in the common bile duct and rarefication of the intrahepatic biliary tract and biopsy showed biliary obstructions, including cholangiolar proliferation, biliary plugs, portal inflammation with neutrophil infiltrates, extensive biliary fibrosis and cirrhosisN/AIntravenous ketamine is dose dependant and used for maintenance sedation of patients required M/V for acute respiratory distress syndrome ARDS, and showed associated with biliary obstructions, cholestatic liver injury, biliary cirrhosis, and end-stage liver disease, that’s the reason the new guidelines is not recommend ketamine especially if prolonged or at higher dose
Male
Male
Female
Female
Zdanowicz et al[51], 2022Paediatric patientMalePost-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AN/APatient developed autoimmune hepatobiliary diseases, autoimmune sclerosing cholangitis ASC which required long-term liver function monitoring
Schwarz et al[52], 2022N/A15 patientsPost-COVID-19 cholangiopathyYes, GGT is elevated in 15 patients with SSC-CIP after lung transplantation out of 40 patients in the study. ALP is elevated after lung transplantN/AN/A15 patients out of 40 developed SSC-CIP underwent lung transplantN/AN/AN/AGGT showed to be a sensitive parameter to predict severity in SSC-CIP
Keskin et al[53], 2022N/A32 patients Post-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AN/ATechnical problems with ECRP were more common in biliary patients with delay group than in those without delay, while 7 pancreatic patients showed no difference in ERCP with or without delay of intervention. Technical issues considered such as abundant stone sludge in bile duct, stent migration, etc
Bartoli et al[54], 202144FemalePost-COVID-19 cholangiopathyYes, AST, ALT elevated and GGT, ALP elevated more ANA positive, anti-mitochondrial-positive, anti-smooth muscle negativeU/S showed slightly enlarged liver with moderate steatosis and a mildly enlarged spleenN/AYes, required intubation and MV N/AFlorid ductal lesions, moderate peri-portal fibrosis, portal chronic inflammatory infiltrateNot donePatient treated with UDCA and discharged and breathing normally, also treated from Guillain barre syndrome GBS by intravenous immunoglobulin
Ferreira et al[55], 2022N/A4 casesPost-COVID-19 cholangiopathyYesN/AN/AN/AN/AERCP showed beaded appearance of intrahepatic bile ducts and bile casts N/AOne patient undergone stone removal, and one patient complicate with liver cirrhosis, the other two progressed to advanced chronic liver disease
Bütikofer et al[56], 2021N/A20 CasesPost-COVID-19 cholangiopathyYes 9 patients with severe cholestasis 11 patients with mild cholestasis N/AN/AN/AN/AIschemic changes to the perihilar bile ductsN/ASSC is more common and severe in critically COVID-19 patients, with prolonged ICU period
Zafar et al[57], 2022N/A2 CasesPost-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AN/ABoth patients developed SSC post-COVID-19 vaccination, which lead to hepatitis and eventually cholangitis
Otani et al[58], 2022N/AN/APost-COVID-19 cholangiopathy in some cases of 166 casesYesN/AN/AN/AN/AN/AN/A166 cases for endoscopic procedures for causes; Cholangitis, GI bleeding, Obstructive jaundice, neoplasia, COVID-19 led to delay in endoscopic procedures which led to delayed diagnosis of cholangitis, cancers, etc.
Cesar Machado et al[59], 202266Male Post-COVID-19 cholangiopathyYesUltrasound showed slight hepatomegaly and no bile duct dilatationMRI showed biliary cast, also revealed. Diffuse irregularity of intra- and extrahepatic bile ducts, with multiple focal strictures alternating with mild focal dilations of the biliary tree, suggesting a sclerosing cholangiopathyYes, required MVYes, required haemodialysis Biopsy showed a prominent bile ductular reaction, cholangiocyte injury, inflammatory infiltrate rich in neutrophils, biliary infarctions, marked cholestasis, and portal fibrosisNot done OLT, due to poor clinical conditionSlight recovery, under observation & follow-up
Steiner et al[60], 202233FemalePost-COVID-19 cholangiopathyYes, elevated liver enzymes AST, ALT, marked elevated GGT, ALP N/AMRCP done showed cholangiopathy Yes hypoxia required intubation and MV, patient developed respiratory distress syndrome in which she was given veno-venous extracorporeal membrane oxygenationYes renal failure, and went through haemodialysis frequentlyERCP done showed cholangiopathyOLT not donePatient passed away, her clinical condition deteriorated, with severe hypoxia, renal failure, and multi-organ failure
Gourjault et al[61], 202155MalePost-COVID-19 cholangiopathyYes, elevated AST, ALT high GGT, ALP, elevated bilirubin, LDHN/APeriportal hypersignal without hepatic biliary dilatationYes, Required intubation& MV for 20 d with four sessions prone positionN/AInterlobular biliary lesions with cholestasisWaiting list for OLTDischarged home, he had sphincterotomy and stone removal, planned for OLT
45MaleHepatic steatosis without hepatomegaly or biliary dilatationDiffuse intra-hepatic dilatation and liver steatosis without any focal obstructing lesionMV for 26 d and sedated with ketamine for 24 d then he was on ECMO for 18 d Fifteen sessions of hemodialysisDischarged home, improved, not done OLT
30MaleUS normalProgressive irregular intrahepatic ductal dilatationMV for 12 d with ketamine sedation, then replaced by ECMO for 29 d with 6 sessions of prone position30 sessions of hemodialysisBiopsy showed cholestatic hepatitis, bile ducts dystrophyOLT done 11 mo after his admissionDeveloped liver failure with ascites, prolonged prothrombin, OLT done
Tafreshi et al[62], 2021 38MalePost-COVID-19 cholangiopathyYes, mildly elevated AST, ALT and GGT mild bilirubin levelIntrahepatic biliary ductal irregularity and a markedly thickened common bile ductDiffuse mild intrahepatic biliary distention, marked beading and irregularity& mild irregularity of the extra hepatic common bile ductRequired intubation & MV N/ABiopsy showed cholestatic hepatitis with cholangiocyte injury, bile ductular proliferation, canalicular cholestasisWaiting list for OLTImproved by treatment, waiting list for OLT
Leonhardt et al[63], 2023N/AN/APost-COVID-19 cholangiopathyYesN/AN/AYes. Intubated on MVN/AN/AN/AOne patient developed SSC-CIP in every 43 invasive ventilated COVID-19 patients (total 1082 patients)
Zengarini et al[64], 202230FemalePost-COVID-19 cholangiopathy YesN/AN/AN/AN/AN/AN/APatient developed subacute cutaneous lupus erythematosus post COVID-19 vaccination in patient with PBC
Wendel-Garcia et al[65], 2022N/AN/APost-COVID-19 cholangiopathy Yes. High total bilirubinN/AN/AN/AN/AN/AN/AThe study showed 243 patients; 170 Patients infused with ketamine developed post-COVID-19 cholangiopathy while other patients received propofol, fentanyl were not associated with cholestatic liver injury
Morão et al[66], 202246FemalePost-COVID-19 cholangiopathyYesN/AMRCP; liver abscesses, intrahepatic bile duct dilation with multiple strictures and some linear repletion defects at the bifurcation of the common hepatic ductIntubation with MV 12 dN/AERCP Showed; biliary castsN/AN/A
Lee et al[67], 202256FemalePost-COVID-19 cholangiopathy Yes, hepatitis C, AST, 243, ALT 630, ALP 449, GGT 2765N/AN/AN/AN/AGranulomatous cholangitis, nonsuppurative with destruction and proliferation of bile ducts with PBC Also immune infiltrations of CD3 T-cells, CD8 T-cellsN/APatient improved and discharged after high dose UDCA treatment, liver enzymes become normal
Nikoupour et al[68], 202035MalePost-COVID-19 cholangiopathyYesN/AN/AN/AN/AN/AOLT done before 3 yr from COVID-19 infectionTwo identical twins had COVID-19 infection, both developed PSC, one of them who had OLT showed improvement with mild symptoms, while the other twin had more severe symptoms
35MaleDid not have OLT
Arnstadt et al[69], 202162N/APost-COVID-19 cholangiopathyYesEchogenic intraductal longitudinal structures characteristic for intraductal casts and for SSC-CIPMRCP showed irregular intrahepatic bile ductsYes, need long-term ventilationN/ANecrotic bile ductsN/AN/A
Meersseman et al[70], 2021Mean age 48-68MalePost-COVID-19 cholangiopathyYes, elevated GGT, ALP, AST, ALTN/AMRCP showed focal strictures in intrahepatic bile ducts with intraluminal sludge and castsYes, intubated & MV then VV- ECMO Yes, required renal supportERCP: Patient 1 diffuse beading of the intrahepatic biliary system, patient 2 & 3 diffuse beading of the intrahepatic biliary ducts, patient 4 focal strictures on the right hepatic ductOLT done for patient 1 and 2patient 3 & 4 did not undergo OLTPatient 1 is doing well, patient 2 died due to septic shock and pneumonia, patient 3 have mild SSC-CIP, patient 4 died due to lethal liver hemorrhage
Durazo et al[5], 202147MalePost-COVID cholangiopathyYesCholelithiasis without evidence of acute cholecystitisMild intrahepatic biliary ductal dilatation with multifocal strictures and beading with intra hepatic dilatation but without extrahepatic biliary dilatationYes, off MV on day 29Yes, recoveredLiver abscess; Bile collection associated with bile duct dilatation with vacuolization and neutrophilia. Endothelial hepatic arteries swelling. Severe portal tract inflammation with Obliterative venopathyOLT doneRecovered
Raes et al[71], 202264MalePost-COVID-19 cholangitisYesN/AN/AYes, MV then venovenous ECMO VV-ECMON/AN/AN/APassed away; patient having CAHA, progressive liver failure, secondary to ischemic cholangitis
Fajardo et al[72], 202124Female Post-COVID-19 cholangitisYes, GGT, ALP, AST, ALT, bilirubinUS: thickening of the gallbladder without stonesMRI: showed normal biliary tree and wall oedema of the gallbladderN/AN/ACholangitis of the small bile ducts consisting of a mixed inflammatory infiltrate with lymphocytes, plasma cells and neutrophils, accompanied by eosinophils, localized around and within the bile ductsNot done OLTImproved, patient discharged after laparoscopic cholecystectomy and liver biopsy
Pizarro Vega et al[73], 202363MalePost-COVID-19 cholangiopathyYes, GGT high in all patients especially in patient NO. 3 to 143 U/L then reached to 1130 U/L and patient 4 reached 3550 U/L. AST is high and higher in patient 4 to 82 U/L and patient 5 to 85 U/L then reached maximum 250 and 148, respectively. And patient 1 reached 1520 U/L. High tot. Bilirubin, ALT, ALPN/AMRI showed intrahepatic duct dilatations, stenosis without lithiasis, no extrahepatic duct alterationYes, required intubation, MV. PronosupinationYes, impaired renal function, required vasoactive drugsNo liver biopsyOne patient planned for OLTAll patients treated with UDCA and discharge. 3 patients re-admitted due to complication, patient 4 had pleural empyema. Patient 5 had cholecystectomy, patient 6 readmitted for acute cholangitis without lithiasis, no patients died during follow up
66Female
60Male
65Male
44Female
68Male
Knooihuizen et al[74], 202154FemalePost-COVID-19 cholangiopathy KISCYes, ALP peaked 2239 U/L, GGT 773 U/L, AST 1260 U/L, ALT 1729 U/LN/AMRI showed intrahepatic biliary dilatation with a beaded appearance & dilated common bile duct with distal narrowingYes Yes Liver biopsy showed minimal infiltration of neutrophils in the portal tract and lobule without cholestasis, also showed portal tract with bile duct injuryNot donePatient have KISC during intensive sedation, then ceased the KISC is transient, patient for repeat MRCP
Zhou et al[75], 202236FemalePost-COVID-19 vaccination leading autoimmune hepatitisYes, AST 581, ALT 588 elevated, GGT, ALP slight elevation, bilirubin 1.4N/AN/AN/AN/ALiver biopsy showed interface hepatitis with portal infiltration and discrete presence of rosette formation and apoptotic hepatocytesNot done Patients have Autoimmune hepatitis AIH post vaccination (Moderna mRNA), treatment given after 2nd dose vaccine with prednisolone PSC treated with UDCA and ERCP
Muehlenberg et al[76], 202180FemalePost-COVID-19 cholangiopathyYes, AST 100 U/L, ALT 113 U/L, bilirubin 12 mg/dLUS of liver and bile duct were normalN/AYes, intubation and MV with antibiotics and catecholamine treatmentN/AN/AN/APatient done ERCP with papillotomy and foreign body extraction
Soldera and Salgado[77], 2021 62MalePost-COVID-19 cholangiopathyYesNot AvailableDiffuse irregularity of the intrahepatic bile ducts associated with sacular dilations suspicious for cholangiolithic abscessesYesNot availableIntense cytoplasmic vacuolization of cholangiocytes and microvascular alterationsOLT doneRecovery
Rojas et al[78], 202129FemalePost-COVID-19 cholangiopathyYesResemble SSC (secondary sclerosing cholangitis) but no portal inflammation, dilatation, or fibrosis)MRI is negative Yes, off MV on day 30Yes, recoveredLow periportal inflammatory infiltrate without necrosis but with a severe obstructive cholestatic patternNot doneNot recovered
Dhaliwal et al[23], 202242FemalePost-COVID-19 cholangiopathyYesNot AvailableMild intrahepatic biliary ductal dilation. With subtle central biliary enhancement concerning for. Cholangitis along with hypodense material hin extrahepatic. Biliary system likely representing transiting gallbladder. SludgeNot required MVNoFilling defects secondary to multiple large biliary casts (Biliary case syndrome)OLT DoneRecovery with long-term liability and comorbidity
Caballero-Alvarado et al[79], 20237 cases7 casesPost-COVID-19 cholangiopathyYesNot availableNot available Not available Yes, recoveredSecondary sclerosing cholangitis1 done OLT 6 send for consideration of OLTOne recovered, 6 no data available
Soldera et al l[26], 202350One malePost-COVID-19 cholangiopathyYesNot available MRI showed intra-hepatic sclerosing cholangitis and a dilated chilidium, with no signs of lithiasis (11 mm)Yes, required MVYes, required haemodialysis ERCP which showed a cast in the format of the external biliary tract, which was removedNot done OLTRecovered post cast removal
Franzini et al[80], 202265MalePost-COVID-19 cholangiopathyYesU/S showed no abnormalities MRI Not availableYes, required MV; under Fentanyl, Midazolam, and Ketamine sedationYes, required haemodialysis ERCP revealed rarefaction of intrahepatic bile ducts, and removal of biliary castsOLT Not doneNo improvement
Roda et al[81], 202263MalePost-COVID-19 cholangiopathyYesUltrasound results was inconclusiveMRI not doneYes, required MV, and veno-venous extracorporeal membrane oxygenation support (VV-ECMO). And eventually done bilateral lung transplantAcute renal failure (AKI III); chronic illness neuropathy; several episodes of bacterial superinfections and lastly, PLS, characterized by severe haemolysisTransjugular hepatic biopsy was performed with histopathological evidence of portal and periportal fibrosis, and intraparenchymal cholestasis with cholangiopathy and vasculopathyOLT not done, patient did bilateral lung transplantNot recovered, patient passed away due to Multiorgan failure MOF due to septic shock
Tebar et al[82], 202243MalePost-COVID-19 cholangiopathyYesUltrasound Not availableMRI not doneYes, required MVNot available ERCP, MRCP Showed: Bile cholestatic, toxic. Cause necrosis of cholangiocytes and stenosis, determining persistent and irreversible biliary obstruction, with rapid progression to liver cirrhosisNot available Not available
Santisteban Arenas et al[83], 20226 casesPost-COVID-19 cholangiopathyYesUltrasound not availableDestruction and curling of the pathway, beading of the intrahepatic bile ductYes, all 6 cases required MV1 male not having renal failure or haemodialysis. All other 5 cases have renal failure; 2 females not required haemodialysis; 2 males required haemodialysis; 1 male have renal failure but not required haemodialysis MRCP/ERCP showed destruction of biliary tract. In three of the six patients underwent liver biopsy, the most frequent findings were the presence of a reaction. Ductular, proliferation of cholangioles, infiltrate. Inflammatory associated with the biliary epithelium with component. Lymphoplasmocyte and polymorphonuclear neutrophilsNot available 1 patient died, 5 other survived with severe comorbidities such as pneumonia, tracheal stenosis, pressure ulcers etc.
55Male
54Male
62Male
56Female
73Female
34Male