Evaluation of Sickle Cell Liver Disease
Condition: Sickle Cell Disease
MeSH terms: Liver Diseases; Anemia, Sickle Cell
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Sickle cell disease (SCD) causes multi-organ dysfunction and early death in affected
        individuals (1-4). 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 (5). It is therefore imperative to identify patients with liver
        dysfunction and damage for possible early intervention.
      
Keywords: Microbiome; Sickle Cell Disease; Bone Marrow Transplant; Natural History