Tag Archives: sickle cell

Sickle Cell Related Liver Disease

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A terrific review of sickle cell disease (SCD) associated liver problems: F Lacaille et al. JPGN 2021; 72: 5-10. The Liver in Sickle Cell Disease

While the most frequent liver-related problem in individuals is cholelithiasis (>25% after age 5 yrs), a host of other problems can develop –this article is a good reference.

Key points:

  • Acute Sickle Cell Hepatic Crisis, Intrahepatic cholestasis, and acute hepatic sequestration
    • ~6% of children and 10% of adults develop severe liver complications of SCD
    • With sequestration, indications include pain with acute drop in hemoglobin (>2 g/dL)
    • Acute hepatic crisis is often signaled by elevated conjugated bilirubin
    • With severe liver disease/liver ischemia, authors advocated for exchange transfusion which “more efficiently decreases HbS percentage, faster restoring the blood flow than simple transfusion.” Consider after excluding biliary complication if INR is >1.4 with increased conjugated bilirubin (>3 mg/L). “Simple transfusion should be discussed in other cases.”
  • Cholangiopathy and autoimmune liver disease
    • Although autoimmune sclerosing cholangitis/autoimmune hepatitis are rare, it may account for 8% of children with SCD referred for hepatic dysfunction
    • Liver biopsy, needed for diagnosis, “is a dangerous procedure in SCD, which cannot be performed without at least a transfusion”
    • “Steroids can induce sickle crisis”
    • Look for ANA, SMA, LKM, and ANCA
  • Iron Overload
    • “It is not usually a significant concern in children…In our patients, the median ferritin level was about 3000 ng/mL, and none had a severe overload on MRI”
  • Infections/Drug toxicity
    • Need to consider hepatitis B, hepatitis C, and hepatitis E in particular
    • Inquire about herbal medicines and recreative drugs
  • Liver transplantation
    • Results are often poor.
    • Problems include sickle cell crisis in the transplanted liver, and drug toxicity which can add to the neurological and renal morbidities of SCD
  • Stem cell transplantation
    • Consider for severe complications of SCD including hepatic complications

Related blog posts: 

From NY Times

Blood is not enough

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…to resolve the problems of sickle cell anemia.  The effects of transfusions for sickle cell patients’ hepatobiliary function are poorly understood.  By lowering the level of hemoglobin S and reducing sickling, can this lead to improvement in organs damaged by sinusoidal congestion and infarction?  Well probably not (J Pediatr 2012; 160: 281-85).

Strokes are known to occur in 5-10% of sickle cell patients by 20 years of age and if untreated, >50% have recurrence.  This has led to transfusion programs.  The ‘Stroke with Transfusions Changing to Hydrdoxyurea’ (SWiTCH) study is a multi-center randomized trial trying to determine how current treatment (transfusions and chelation) compares with hydroxyurea/phlebotomy for preventing stroke and managing iron overload.  As part of this study, a baseline assessment with ultrasound showed widespread problems -despite an average of 7 years of transfusions.  In this cohort of 149 patients, the following findings were identified:

  • Spleen volumes were increased in more than 1/3rd of patients leading to hypersplenism (low platelet counts). 12 subjects had nonvisible spleens due to autoinfarction.
  • Nephromegaly was present.  This finding is known to occur with sickle cell disease and is a marker of glomerular hyperfiltration.
  • Hepatobiliary disease was nearly ubiquitous.  37 of 148 had previous cholecytectomy; of the remaining, 46 of 111 (41%) had gallstones and 14% had gallbladder sludge.  Liver lengths were significantly longer as well.

Conclusions: Transfusion therapy was insufficient to reverse or prevent organ damage in children with sickle cell anemia.  An important limitation– the severity of the underlying prevalence of organ dysfunction prior to initiation of transfusion therapy was not known.

Additional references:

  • -Blood 2011; 117: 772-9.  Silent cerebral infarcts occur despite regular blood transfusions.
  • -Clin Gastro & Hep 2007; 5: 1469.  Reviews types of sickle cell associated liver disease.
  • -Pediatric Hematology and Oncology.  2006 Mar;23(2): 95-102(8).  Sickle cell intrahepatic cholestasis (SCIC), which is related to intrahepatic sinusoidal RBC sickling (due to relative hypoxia) and can be associated with progressive hepatomegaly, mild transaminitis, extreme hyperbilirubinemia
  • -JPGN 2004; 39: 200.  Review of sickle cell hepatic crisis.  Cholestasis resolves over 3 months.  Acute crisis treated with hyperhydration & transfusion. Cohort of 350; 6 developed hepatic crisis.
  • -J Pediatr 2001; 139: 785-789 & 790-796.  Transfusions and hydroxyurea for SS dz.