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

Pediatr Nephrol. 2019 Jul;34(7):1289-1293. doi: 10.1007/s00467-019-04234-6. Epub 2019 Apr 8.

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: Cholestatis; Eculizumab; HUS; Liver transplantation; Pediatrics.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Cholestasis / chemically induced*
  • Complement Inactivating Agents / adverse effects*
  • Escherichia coli Infections / complications*
  • Female
  • Hemolytic-Uremic Syndrome / drug therapy
  • Hemolytic-Uremic Syndrome / microbiology*
  • Humans
  • Infant
  • Liver Cirrhosis / chemically induced
  • Shiga-Toxigenic Escherichia coli*

Substances

  • Antibodies, Monoclonal, Humanized
  • Complement Inactivating Agents
  • eculizumab