Advertisement

Escherichia coli-associated hemolytic uremic syndrome and severe chronic hepatocellular cholestasis: complication or side effect of eculizumab?

  • Mathilde Mauras
  • Justine Bacchetta
  • Anita Duncan
  • Marie-Pierre Lavocat
  • Barbara Rohmer
  • Etienne Javouhey
  • Sophie Collardeau-Frachon
  • Anne-Laure Sellier-LeclercEmail author
Brief Report
  • 31 Downloads

Abstract

Background

Liver lesions of hemolytic uremic syndrome due to Shiga-toxin-producing Escherichia coli (STEC-HUS) are uncommon.

Case-diagnosis/treatment

We report three observations of severe STEC-HUS with delayed hepatic involvement. They presented with multiple organ failure and received eculizumab; 15 days after the onset of STEC-HUS, cholestasis appeared and cytolysis worsened. Abdominal ultrasonography showed vesicular sludge. Liver biopsy performed 3 to 6 months after the STEC-HUS found cholangiolar proliferation and inflammatory portal fibrosis. Despite renal recovery, cholestasis persisted and worsened in two cases, leading to biliary cirrhosis and subsequent liver transplantation. Pathological examination of one native liver found thrombotic microangiopathy.

Conclusions

Even though the pathological examination performed on one native liver demonstrated areas of thrombotic microangiopathy, we cannot completely rule out that eculizumab may have worsened the liver lesions. Before the efficacy of eculizumab in STEC-HUS is formally demonstrated, physicians should stay cautious in its use.

Keywords

HUS Pediatrics Eculizumab Cholestatis Liver transplantation 

Notes

Acknowledgements

The authors would like to thank Pr Chantal Loirat for her expertise and skillful help during the management of the cases, as well as Dr Véronique Frémeaux-Bacchi for genetic explorations.

Compliance with ethical standards

This retrospective series of cases was approved by the local IRB (Comité d’éthique des Hospices Civils de Lyon, session May 3, 2017).

Conflict of interest

Justine Bacchetta and Anne-Laure Sellier-Leclerc received travel grants and honoraria from Alexion (2013, 2014).

Supplementary material

467_2019_4234_MOESM1_ESM.pptx (596 kb)
Chart 1 Chart: iconography of case report. Patient 1: a. Partially opacified cholangiography due to porous gallbladder walls with contrast product leaks. b. Simultaneous ultrasound found: an obstruction of the extrahepatic bile ducts by a mixture of sludge and microlithiasis, moderate dilation of the upstream bile ducts and inflammatory thickening of the gallbladder walls, seat of an infundibular macrolithiasis. c. Histology of hepatectomy with a diffuse greenish cholestatic aspect of the hepatic parenchyma. d. Electron microscopy of histology HESPortal area ×200: portal tract enlargement and fibrosis with acute inflammation, cholangitis and ductular proliferation. Patient 2: e. Homogeneous liver parenchyma. No intra or extrahepatic dilation of the bile ducts. Vesicular sludge associated with hydrocholecyst. f. Electron microscopy of histology HESPortal area ×200: mild chronic inflammation concerning a few portal tracts. Patient 3: g. BiliMRI: Hepatosplenomegaly. Moniliform dilation of the biliary tract suggestive of cholangitis with periportal hyper signal. Obstacle free vesicular distention. h. HES Centrolobular Area ×200: no lesions suggestive of thrombotic microangiopathy. i. Masson’s trichrome stain ×40: portal bridges. (PPTX 595 kb)

References

  1. 1.
    Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C (2017) Haemolytic uraemic syndrome. Lancet 390:681–696.  https://doi.org/10.1016/S0140-6736(17)30062-4 CrossRefGoogle Scholar
  2. 2.
    de Buys Roessingh AS, de Lagausie P, Baudoin V, Loirat C, Aigrain Y (2007) Gastrointestinal complications of post-diarrheal hemolytic uremic syndrome. Eur J Pediatr Surg 17:328–334.  https://doi.org/10.1055/s-2007-965013 CrossRefGoogle Scholar
  3. 3.
    Lapeyraque A-L, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, Proulx F, Clermont MJ, Le Deist F, Niaudet P, Schaefer F (2011) Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med 364:2561–2563.  https://doi.org/10.1056/NEJMc1100859 CrossRefGoogle Scholar
  4. 4.
    Brady TM, Pruette C, Loeffler LF, Weidemann D, Strouse JJ, Gavriilaki E, Brodsky RA (2016) Typical Hus: evidence of acute phase complement activation from a daycare outbreak. J Clin Exp Nephrol 1:11CrossRefGoogle Scholar
  5. 5.
    Urushihara N, Ariki N, Oyama T, Chouda Y, Yagi T, Inoue T, Tomiyama Y, Nishiuchi R, Oda M, Tanaka N (2001) Secondary sclerosing cholangitis and portal hypertension after O157 enterocolitis: extremely rare complications of hemolytic uremic syndrome. J Pediatr Surg 36:1838–1840.  https://doi.org/10.1053/jpsu.2001.28858 CrossRefGoogle Scholar
  6. 6.
    Matthies J, Hünseler C, Ehren R, Volland R, Körber F, Hoppe B, Weber LT, Habbig S (2016) Extrarenal manifestations in Shigatoxin-associated haemolytic uremic syndrome. Klin Padiatr 228:181–188.  https://doi.org/10.1055/s-0042-108444 CrossRefGoogle Scholar
  7. 7.
    Riley MR, Lee KK (2004) Escherichia coli O157:H7-associated hemolytic uremic syndrome and acute hepatocellular cholestasis: a case report. J Pediatr Gastroenterol Nutr 38:352–354CrossRefGoogle Scholar
  8. 8.
    McCarthy DW, Mutabagani K, Mahan JD, Caniano DA, Cooney DR (2000) Infarction of the choledochus, liver, gallbladder, and pancreas: a unique complication of the hemolytic uremic syndrome. J Pediatr Surg 35:502–504.  https://doi.org/10.1016/S0022-3468(00)90223-9 CrossRefGoogle Scholar
  9. 9.
    Anastaze Stelle K, Cachat F, Perez M-H, Chehade H (2016) Streptococcus pneumoniae-associated hemolytic and uremic syndrome with cholestasis: a case report and brief literature review. Clin Pediatr (Phila) 55:189–191.  https://doi.org/10.1177/0009922815580406 CrossRefGoogle Scholar
  10. 10.
    Gallo EG, Gianantonio CA (1995) Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome. Pediatr Nephrol 9:117–119CrossRefGoogle Scholar
  11. 11.
    Delmas Y, Vendrely B, Clouzeau B, Bachir H, Bui HN, Lacraz A, Hélou S, Bordes C, Reffet A, Llanas B, Skopinski S, Rolland P, Gruson D, Combe C (2014) Outbreak of Escherichia coli O104:H4 haemolytic uraemic syndrome in France: outcome with eculizumab. Nephrol Dial Transplant 29:565–572.  https://doi.org/10.1093/ndt/gft470 CrossRefGoogle Scholar
  12. 12.
    Wijnsma KL, Schijvens AM, Rossen JWA, Kooistra-Smid AMDM, Schreuder MF, van de Kar NCAJ (2017) Unusual severe case of hemolytic uremic syndrome due to Shiga toxin 2d-producing E. coli O80:H2. Pediatr Nephrol 32:1263–1268.  https://doi.org/10.1007/s00467-017-3642-3 CrossRefGoogle Scholar
  13. 13.
    Hayes W, Tschumi S, Ling SC, Feber J, Kirschfink M, Licht C (2015) Eculizumab hepatotoxicity in pediatric aHUS. Pediatr Nephrol 30:775–781.  https://doi.org/10.1007/s00467-014-2990-5 CrossRefGoogle Scholar
  14. 14.
    Brodsky A, Mazzocchi O, Sánchez F, Khursigara G, Malhotra S, Volpacchio M (2012) Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation. Exp Hematol Oncol 1:26.  https://doi.org/10.1186/2162-3619-1-26 CrossRefGoogle Scholar
  15. 15.
    Hillebrandt S, Wasmuth HE, Weiskirchen R, Hellerbrand C, Keppeler H, Werth A, Schirin-Sokhan R, Wilkens G, Geier A, Lorenzen J, Köhl J, Gressner AM, Matern S, Lammert F (2005) Complement factor 5 is a quantitative trait gene that modifies liver fibrogenesis in mice and humans. Nat Genet 37:835–843.  https://doi.org/10.1038/ng1599 CrossRefGoogle Scholar

Copyright information

© IPNA 2019

Authors and Affiliations

  • Mathilde Mauras
    • 1
  • Justine Bacchetta
    • 2
    • 3
  • Anita Duncan
    • 2
  • Marie-Pierre Lavocat
    • 1
  • Barbara Rohmer
    • 4
  • Etienne Javouhey
    • 3
    • 5
  • Sophie Collardeau-Frachon
    • 3
    • 6
  • Anne-Laure Sellier-Leclerc
    • 2
    Email author
  1. 1.Service de Pédiatrie, Hôpital de Saint EtienneSaint-EtienneFrance
  2. 2.Centre de Référence des Maladies Rénales RaresHôpital Femme Mère EnfantBronFrance
  3. 3.Faculté de Médecine Lyon EstUniversité Lyon 1LyonFrance
  4. 4.Service de Gastro Entérologie PédiatriqueHFMEBronFrance
  5. 5.Service de Réanimation PédiatriqueHFMEBronFrance
  6. 6.Service d’AnatomopathologieHFMEBronFrance

Personalised recommendations