<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01661842</url>
  </required_header>
  <id_info>
    <org_study_id>Beijing302-006</org_study_id>
    <nct_id>NCT01661842</nct_id>
  </id_info>
  <brief_title>Umbilical Cord Mesenchymal Stem Cells for Patients With Autoimmune Hepatitis</brief_title>
  <official_title>Phase 1/2 Study of UC-MSC Treatment for Evaluation the Efficacy and Safety in Patients With Autoimmune Liver Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing 302 Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing 302 Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface&#xD;
      hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Disease presentation&#xD;
      is varied but typically is based on characteristic aminotransferase elevations, histological&#xD;
      abnormalities, elevated levels of serum globulins, and the presence of one or more&#xD;
      autoantibodies. Two types of juvenile AIH have been identified according to seropositivity&#xD;
      for smooth muscle and /or antinuclear antibody (AIH type 1) or liver kidney microsomal&#xD;
      antibody (AIH type 2). Standard therapy in clinic consists of a combination of&#xD;
      corticosteroids and azathioprine, which displays the efficacy in 80% of patients. However, 7%&#xD;
      of patients deteriorate despite compliance with the standard corticosteroid regiments&#xD;
      (treatment failure),13% of patients improve but not to a degree that satisfies remission&#xD;
      criteria (incomplete response), 13% of patients develop serious drug-induced complications,&#xD;
      and 50%-86% of patients will relapse after drug withdrawal. These serious drawbacks&#xD;
      counterbalance the benefits of conventional therapy, and they are compelling reasons to&#xD;
      refine current treatment strategies and pursue alternative therapies. UC-MSC has been the&#xD;
      application for the treatment of several severe autoimmune diseases, such as immune&#xD;
      thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.&#xD;
      In this study, the safety and efficacy of UC-MSC transplantation for AIH patients will be&#xD;
      evaluated.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver&#xD;
      characterized by elevation of IgG, presence of characteristic autoantibodies, and&#xD;
      histological feature of interface hepatitis. Standard therapy consists of a combination of&#xD;
      corticosteroids and azathioprine, which is efficacious in 80% of patients. However, current&#xD;
      treatment strategies are complicated by frequent relapse after drug withdrawal, medication&#xD;
      intolerance, and refractory disease. Alternative medical therapy may be need for AIH.&#xD;
&#xD;
      The potential for stem cells to differentiate into hepatocytes cells was recently confirmed.&#xD;
      In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been&#xD;
      applicated in the clinic for treat several human disease such as GVHD, cardiac injury and&#xD;
      brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived&#xD;
      MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as immune&#xD;
      thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.&#xD;
&#xD;
      The purpose of this study is to learn whether and how UC-MSC can improve the disease&#xD;
      condition in patients with autoimmune hepatitis (AIH). This study will also look at how well&#xD;
      UC-MSC is tolerated and its safety in AIH patients&#xD;
&#xD;
      Participants in the study will be randomly assigned to one of two treatment arms:&#xD;
&#xD;
      Arm A: Participants will receive 12 weeks of UC-MSC treatment plus conventional treatment&#xD;
      (combination of corticosteroids and azathioprine) Arm B: Participants will receive 12 weeks&#xD;
      of placebo plus conventional treatment. (combination of corticosteroids and azathioprine)&#xD;
      UC-MSC will be prepared according to standard procedures and is collected in plastic bags&#xD;
      containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell&#xD;
      therapy, patients are followed up at week 12, 24, 36, 48, 72, 96. The evaluation of some&#xD;
      clinical parameters such as the level of serum alanine aminotransferase (ALT), aspartate&#xD;
      aminotransferase (AST), γ-globulin, total bilirubin (TB), prothrombin time (PT), albumin&#xD;
      (ALB), prealbumin (PA) and IgG, are detected at these time points. MELD score, Liver&#xD;
      histology, treatment side effects, relapse rate and clinical symptoms were also observed&#xD;
      simultaneously.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2011</start_date>
  <completion_date type="Anticipated">October 2014</completion_date>
  <primary_completion_date type="Anticipated">October 2014</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Liver Histology change</measure>
    <time_frame>baseline and 96 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Serum alanine aminotransferase (ALT)</measure>
    <time_frame>0,12, 24, 36, 48, 72, 96 weeks after treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum AST</measure>
    <time_frame>At baseline and at week 12, 24, 36, 48, 72, 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Tbil</measure>
    <time_frame>At baseline and at week 12, 24, 36, 48, 72, 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum immunoglobulin G (IgG)</measure>
    <time_frame>At baseline and at week 12, 24, 36, 48, 72, 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum γ-globulin</measure>
    <time_frame>At baseline and at week 12, 24, 36, 48, 72, 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MELD score</measure>
    <time_frame>At base line and at week 12, 24, 36, 48, 72, 96</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment side effects</measure>
    <time_frame>At base line and at week 12, 24, 36, 48, 72, 96</time_frame>
    <description>weight gain, acne, facial rounding, dorsal hump formation, hirsutism, osteopenia and diabetes mellitus, et al</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with improvement of clinical symptoms</measure>
    <time_frame>At base line and at week 12, 24, 36, 48, 72, 96</time_frame>
    <description>diffuse arthralgias, fatigue, generalized malaise, jaundice, abdominal pain, nausea, and loss of appetite</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Autoimmune Hepatitis</condition>
  <arm_group>
    <arm_group_label>Conventional plus UC-MSC treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit.&#xD;
Participants will then be followed until the week 96 study visit.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional plus placebo treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 96 study visit.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>conventional plus UC-MSC treatment</intervention_name>
    <description>Received conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks.</description>
    <arm_group_label>Conventional plus UC-MSC treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Conventional plus placebo treatment</intervention_name>
    <description>Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks</description>
    <arm_group_label>Conventional plus placebo treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent&#xD;
&#xD;
          2. Autoimmune hepatitis (according to the criteria defined by the international&#xD;
             autoimmune hepatitis Group ,Hepatology, 2008;48:169-176)&#xD;
&#xD;
          3. Negative pregnancy test (female patients in fertile age)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hepatocellular carcinoma or other Malignancies&#xD;
&#xD;
          2. Pregnant or lactating women&#xD;
&#xD;
          3. Viral Hepatitis ( HAV,HBV,HCV, et al )&#xD;
&#xD;
          4. Vital organs failure (Cardiac, Renal or Respiratory, et al)&#xD;
&#xD;
          5. Sepsis&#xD;
&#xD;
          6. Active thrombosis in the portal or hepatic veins&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Fu-Sheng Wang, professor</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing 302 Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Fu-Sheng Wang, professor</last_name>
    <phone>86-10-63879735</phone>
    <phone_ext>2015.12</phone_ext>
    <email>fswang302@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zheng Zhang, Doctor</last_name>
    <phone>86-10-63879735</phone>
    <phone_ext>2015.12</phone_ext>
    <email>Zhangzheng1975@yahoo.com.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beijing 302 Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100039</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fu-Sheng Wang, professor</last_name>
      <phone>86-10-63879735</phone>
      <phone_ext>2015.12</phone_ext>
      <email>fswang302@163.com</email>
    </contact>
    <contact_backup>
      <last_name>Lifeng Wang, Doctor</last_name>
      <phone>86-10-63879735</phone>
      <phone_ext>2015.12</phone_ext>
      <email>wanglf76@gmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Fu-Sheng Wang, Professor</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Czaja AJ. Advances in the current treatment of autoimmune hepatitis. Dig Dis Sci. 2012 Aug;57(8):1996-2010. doi: 10.1007/s10620-012-2151-2. Epub 2012 Apr 3.</citation>
    <PMID>22476586</PMID>
  </reference>
  <reference>
    <citation>Montano-Loza AJ, Carpenter HA, Czaja AJ. Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease. Hepatology. 2007 Oct;46(4):1138-45. doi: 10.1002/hep.21787.</citation>
    <PMID>17668882</PMID>
  </reference>
  <reference>
    <citation>Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des. 2011;17(29):3120-40. doi: 10.2174/138161211798157568.</citation>
    <PMID>21902661</PMID>
  </reference>
  <reference>
    <citation>Gossard AA, Lindor KD. Autoimmune hepatitis: a review. J Gastroenterol. 2012 May;47(5):498-503. doi: 10.1007/s00535-012-0586-z. Epub 2012 Apr 17.</citation>
    <PMID>22526272</PMID>
  </reference>
  <reference>
    <citation>Malekzadeh Z, Haghazali S, Sepanlou SG, Vahedi H, Merat S, Sotoudeh M, Nasseri-Moghaddam S, Malekzadeh R. Clinical features and long term outcome of 102 treated autoimmune hepatitis patients. Hepat Mon. 2012 Feb;12(2):92-9. doi: 10.5812/hepatmon.808. Epub 2012 Feb 29.</citation>
    <PMID>22509185</PMID>
  </reference>
  <reference>
    <citation>Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res. 2012 Feb;35(2):213-21. doi: 10.1007/s12272-012-0202-z. Epub 2012 Feb 28.</citation>
    <PMID>22370776</PMID>
  </reference>
  <reference>
    <citation>Holbro A, Abinun M, Daikeler T. Management of autoimmune diseases after haematopoietic stem cell transplantation. Br J Haematol. 2012 May;157(3):281-90. doi: 10.1111/j.1365-2141.2012.09070.x. Epub 2012 Feb 24.</citation>
    <PMID>22360687</PMID>
  </reference>
  <verification_date>May 2013</verification_date>
  <study_first_submitted>August 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 10, 2012</study_first_posted>
  <last_update_submitted>May 30, 2013</last_update_submitted>
  <last_update_submitted_qc>May 30, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">May 31, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing 302 Hospital</investigator_affiliation>
    <investigator_full_name>Fu-Sheng Wang</investigator_full_name>
    <investigator_title>Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology</investigator_title>
  </responsible_party>
  <keyword>Autoimmune Hepatitis</keyword>
  <keyword>Mesenchymal stem cells</keyword>
  <keyword>serum albumin</keyword>
  <keyword>serum Tbil</keyword>
  <keyword>serum immunoglobulin G(IgG)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hepatitis A</mesh_term>
    <mesh_term>Hepatitis</mesh_term>
    <mesh_term>Hepatitis, Autoimmune</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01661842
org study id: Beijing302-006
nct id: NCT01661842
lead sponsor: 
has dmc: Yes
Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, interface
      hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Disease presentation
      is varied but typically is based on characteristic aminotransferase elevations, histological
      abnormalities, elevated levels of serum globulins, and the presence of one or more
      autoantibodies. Two types of juvenile AIH have been identified according to seropositivity
      for smooth muscle and /or antinuclear antibody (AIH type 1) or liver kidney microsomal
      antibody (AIH type 2). Standard therapy in clinic consists of a combination of
      corticosteroids and azathioprine, which displays the efficacy in 80% of patients. However, 7%
      of patients deteriorate despite compliance with the standard corticosteroid regiments
      (treatment failure),13% of patients improve but not to a degree that satisfies remission
      criteria (incomplete response), 13% of patients develop serious drug-induced complications,
      and 50%-86% of patients will relapse after drug withdrawal. These serious drawbacks
      counterbalance the benefits of conventional therapy, and they are compelling reasons to
      refine current treatment strategies and pursue alternative therapies. UC-MSC has been the
      application for the treatment of several severe autoimmune diseases, such as immune
      thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.
      In this study, the safety and efficacy of UC-MSC transplantation for AIH patients will be
      evaluated.
Autoimmune hepatitis (AIH) is an immune-mediated necroinflammatory disease of the liver
      characterized by elevation of IgG, presence of characteristic autoantibodies, and
      histological feature of interface hepatitis. Standard therapy consists of a combination of
      corticosteroids and azathioprine, which is efficacious in 80% of patients. However, current
      treatment strategies are complicated by frequent relapse after drug withdrawal, medication
      intolerance, and refractory disease. Alternative medical therapy may be need for AIH.

      The potential for stem cells to differentiate into hepatocytes cells was recently confirmed.
      In particular, bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation has been
      applicated in the clinic for treat several human disease such as GVHD, cardiac injury and
      brain injury, and displayed good tolerance and efficiency. Recently, umbilical cord-derived
      MSCs (UC-MSC) has also been used to treat severe autoimmune diseases, such as immune
      thrombocytopenia, systemic lupus erythematosus, and therapy-resistant rheumatoid arthritis.

      The purpose of this study is to learn whether and how UC-MSC can improve the disease
      condition in patients with autoimmune hepatitis (AIH). This study will also look at how well
      UC-MSC is tolerated and its safety in AIH patients

      Participants in the study will be randomly assigned to one of two treatment arms:

      Arm A: Participants will receive 12 weeks of UC-MSC treatment plus conventional treatment
      (combination of corticosteroids and azathioprine) Arm B: Participants will receive 12 weeks
      of placebo plus conventional treatment. (combination of corticosteroids and azathioprine)
      UC-MSC will be prepared according to standard procedures and is collected in plastic bags
      containing anticoagulant. UC-MSCs are given via i.v. under sonography monitoring. After cell
      therapy, patients are followed up at week 12, 24, 36, 48, 72, 96. The evaluation of some
      clinical parameters such as the level of serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), γ-globulin, total bilirubin (TB), prothrombin time (PT), albumin
      (ALB), prealbumin (PA) and IgG, are detected at these time points. MELD score, Liver
      histology, treatment side effects, relapse rate and clinical symptoms were also observed
      simultaneously.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Liver Histology change
time frame: baseline and 96 weeks
measure: Serum alanine aminotransferase (ALT)
time frame: 0,12, 24, 36, 48, 72, 96 weeks after treatment
measure: Serum AST
time frame: At baseline and at week 12, 24, 36, 48, 72, 96
measure: Serum Tbil
time frame: At baseline and at week 12, 24, 36, 48, 72, 96
measure: Serum immunoglobulin G (IgG)
time frame: At baseline and at week 12, 24, 36, 48, 72, 96
measure: Serum γ-globulin
time frame: At baseline and at week 12, 24, 36, 48, 72, 96
measure: MELD score
time frame: At base line and at week 12, 24, 36, 48, 72, 96
measure: Number of participants with treatment side effects
time frame: At base line and at week 12, 24, 36, 48, 72, 96
description: weight gain, acne, facial rounding, dorsal hump formation, hirsutism, osteopenia and diabetes mellitus, et al
measure: Number of participants with improvement of clinical symptoms
time frame: At base line and at week 12, 24, 36, 48, 72, 96
description: diffuse arthralgias, fatigue, generalized malaise, jaundice, abdominal pain, nausea, and loss of appetite
arm group label: Conventional plus UC-MSC treatment
arm group type: Experimental
description: Participants will receive conventional treatment plus a dose of UC-MSC from day 0 through the week 12 study visit.
Participants will then be followed until the week 96 study visit.
arm group label: Conventional plus placebo treatment
arm group type: Experimental
description: Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until the week 96 study visit.
intervention type: Other
intervention name: conventional plus UC-MSC treatment
description: Received conventional treatment and taken i.v., once per 4 week, at a dose of 1×106 UC-MSC/kg body weight for 12 weeks.
arm group label: Conventional plus UC-MSC treatment
intervention type: Other
intervention name: Conventional plus placebo treatment
description: Received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks
arm group label: Conventional plus placebo treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Fu-Sheng Wang, professor
role: Principal Investigator
affiliation: Beijing 302 Hospital
last name: Fu-Sheng Wang, professor
phone: 86-10-63879735
phone ext: 2015.12
email: fswang302@163.com
last name: Zheng Zhang, Doctor
phone: 86-10-63879735
phone ext: 2015.12
email: Zhangzheng1975@yahoo.com.cn
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: China
citation: Czaja AJ. Advances in the current treatment of autoimmune hepatitis. Dig Dis Sci. 2012 Aug;57(8):1996-2010. doi: 10.1007/s10620-012-2151-2. Epub 2012 Apr 3.
PMID: 22476586
citation: Montano-Loza AJ, Carpenter HA, Czaja AJ. Features associated with treatment failure in type 1 autoimmune hepatitis and predictive value of the model of end-stage liver disease. Hepatology. 2007 Oct;46(4):1138-45. doi: 10.1002/hep.21787.
PMID: 17668882
citation: Czaja AJ. Promising pharmacological, molecular and cellular treatments of autoimmune hepatitis. Curr Pharm Des. 2011;17(29):3120-40. doi: 10.2174/138161211798157568.
PMID: 21902661
citation: Gossard AA, Lindor KD. Autoimmune hepatitis: a review. J Gastroenterol. 2012 May;47(5):498-503. doi: 10.1007/s00535-012-0586-z. Epub 2012 Apr 17.
PMID: 22526272
citation: Malekzadeh Z, Haghazali S, Sepanlou SG, Vahedi H, Merat S, Sotoudeh M, Nasseri-Moghaddam S, Malekzadeh R. Clinical features and long term outcome of 102 treated autoimmune hepatitis patients. Hepat Mon. 2012 Feb;12(2):92-9. doi: 10.5812/hepatmon.808. Epub 2012 Feb 29.
PMID: 22509185
citation: Yi T, Song SU. Immunomodulatory properties of mesenchymal stem cells and their therapeutic applications. Arch Pharm Res. 2012 Feb;35(2):213-21. doi: 10.1007/s12272-012-0202-z. Epub 2012 Feb 28.
PMID: 22370776
citation: Holbro A, Abinun M, Daikeler T. Management of autoimmune diseases after haematopoietic stem cell transplantation. Br J Haematol. 2012 May;157(3):281-90. doi: 10.1111/j.1365-2141.2012.09070.x. Epub 2012 Feb 24.
PMID: 22360687
responsible party type: Principal Investigator
investigator affiliation: Beijing 302 Hospital
investigator full name: Fu-Sheng Wang
investigator title: Director of both the Research Center for Biological Therapy and the Beijing Institute of Translational Hepatology
mesh term: Hepatitis A
mesh term: Hepatitis
mesh term: Hepatitis, Autoimmune