Evaluation of Sickle Cell Liver Disease
Evaluation of Sickle Cell Liver Disease
Background:

 - Sickle cell disease changes the shape of red cells. This makes them more likely to break
 down as they get stuck in small blood vessels. This leads to low red cell count and also
 damage to small blood vessels that supply many organs. One of the affected organs is the
 liver. Sickle cell disease and its treatment through blood transfusion can lead to
 significant liver damage. This disease also can cause the liver to regrow abnormally after
 damage. This can cause high blood pressure in the liver. Researchers want to know if curing
 sickle cell disease with a stem cell transplant improves liver damage.

 Objectives:

 - To explore specific factors that improve or worsen sickle cell liver disease after a stem
 cell transplant.

 Eligibility:

 - Adults ages 18 and older with sickle cell liver disease.

 Design:

 -  Participation will take approximately 7 days over 2 years.

 -  Visit 1: participants will be screened with medical history and review of current
 treatment regimen.

 -  Visit 2: participants will return to the clinic for explanation of the study and
 physical exam. They will also have blood and urine tests, and scans of the liver.

 -  All participants will have a 2-night stay at the clinic. They will have a liver biopsy
 and a test of liver pressure. They will be sedated and a tube will be inserted in a vein
 in their neck.

 -  Participants who have a stem cell transplant will have a second biopsy about 24 months
 later.

 -  Over the 2-year study period, participants will have blood drawn 2-4 times and stool
 samples collected 2 times.
Sickle cell disease (SCD) causes multi-organ dysfunction and early death in affected
 individuals. Many succumb to complications of chronic organ dysfunction and eventual organ
 failure one of which is the liver.

 Spectrum of sickle cell liver disease ranges from hepatic sequestration crisis, intrahepatic
 cholestasis, gallstones, non-cirrhotic portal hypertension, chronic sickle hepatopathy and
 cirrhosis to complications of the treatment of the disease including secondary iron overload
 and viral hepatitis. Though liver transplantation has been performed for SC-induced liver
 failure, a crude mortality rate of 60% makes it a poor choice. It is therefore imperative to
 identify patients with liver dysfunction and damage for possible early intervention.

 Stem cell transplant is currently the only cure for SCD and at the NIH SCD hepatopathy is one
 of the indications for transplant. It is currently not known if stem cell transplant reverses
 SCD liver disease hence we intend to study and compare the nature of SCD liver disease pre
 and post stem cell transplant and in transplant ineligible patients. All SCD patients will be
 screened for liver disease prior to enrollment including fibroscan evaluation. Primary end
 point is histological evidence of regression of liver disease. Hence all patients in the
 transplant eligible arm will undergo liver biopsy pre and 12-24 months post transplant.
 Transplant ineligible patients will be offered liver biopsy when clinically indicated.
 Patients that have already undergone transplant will be included and their data evaluated
 retrospectively. Serum and plasma, liver tissue and stool samples will be evaluated
 extensively for parameters such as liver function tests, iron metabolism, clotting factors,
 and inflammatory markers including microbial products. The intention of the study is to use
 sickle cell disease as a model of predicting markers of progression and regression of liver
 disease.
-  INCLUSION CRITERIA

 1. All age greater than 18 able to consent, male or female

 2. Capacity to provide written informed consent

 3. All ethnicities

 4. Sickle cell genotypes; Homozygous Hemoglobin S Disease, Heterozygous Hemoglobin
 SC and S beta thalassemia including SB+ and SB0

 5. Evidence of SCD liver dysfunction by abnormal liver laboratory parameters in at
 least 2 of the following; alanine aminotransferase (ALT), aspartate
 aminotransferase (AST), alkaline phosphatase (ALP), direct and total serum
 bilirubin > 1 times ULN)

 EXCLUSION CRITERIA:

 1. If not taking measures to prevent pregnancy during the period of study

 2. Incapacity to provide informed consent