Liver Fibrosis in Alpha-1 Antitrypsin Deficiency (Liver AATD)
Condition: Liver Fibrosis; Alpha-1 Antitrypsin Deficiency; AAT Deficiency; AATD
MeSH terms: Liver Cirrhosis; Alpha 1-Antitrypsin Deficiency; Fibrosis
Study type: Observational

Summary: 
      We hypothesize that individuals with Alpha-1 Antitrypsin (AAT) deficiency have ongoing liver
      injury which is not detected by the usual blood tests used to look at liver function. This
      ongoing liver injury leads to cirrhosis in a significant number of adults with AAT
      deficiency.
    

Detailed description: 
      Our overarching hypothesis is that liver disease in adults with AAT deficiency is the result
      of the accumulation of the abnormally folded protein within the endoplasmic reticulum of the
      hepatocyte. In some individuals, the intrinsic cellular mechanisms of the hepatocyte are
      sufficient to clear adequate amounts of the abnormally folded protein such that liver disease
      does not occur. In AAT deficient individuals who develop liver disease, environmental and
      other genetic factors stress the hepatocyte, and the normal cellular mechanisms that maintain
      homeostasis are disrupted, leading to liver disease.

      For this proposal, our hypothesis is that the prevalence of liver disease in adults with AAT
      is higher than previously reported because liver injury and fibrosis is not accurately
      detected by available routine liver testing. Testing this hypothesis will require an initial
      evaluation for liver disease with liver function testing and imaging, and then histologic
      confirmation by liver biopsy.
    

Intervention name(s): Abdominal ultrasound; History and physical; Intravenous catheter; Blood draw; Liver questionnaire; Liver Biopsy; Midazolam; Fentanyl; Lidocaine; Acetaminophen; Lorazepam; Oxycodone/Acetaminophen; Ondansetron
Intervention type(s): Device; Procedure; Procedure; Procedure; Other; Procedure; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Abdominal ultrasound will be done at the liver biopsy visits. The purpose of the ultrasound is to evaluate for the presence of liver fibrosis and identify the biopsy site.; Every study participant will be asked about their medical history and will have a physical exam done at the screening, year 1, year 2, and year 3 visits.; Every study participant will have and intravenous catheter (IV) placed at every study visit. The IV will be used for the collection of blood at the screening, year 2, year 2, and year 3 visits. It will also be used for the administration of medication at the first liver biopsy, as well as the year 3 visit if the biopsy is repeated.; At the screening, year 1, year 2, and year 3 visits, every participant will have blood collected from the IV that is placed in one of their veins.; At the screening and year 3 visits, every subject will complete a questionnaire which involves questions regarding liver health.; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine (a numbing medicine) injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. Once the relaxation medication and numbing medicine have been given, a sample of liver tissue will be collected using a needle biopsy device.; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).; Every participating subject who passes the screening visit, will have a liver biopsy done with the use of lidocaine injected into skin where the biopsy will be collected. At the time of the biopsy, either lorazepam (a medicine used to treat anxiety and cause relaxation) or midazolam (a medicine used to cause sleepiness and amnesia) and fentanyl (a medicine used to relieve pain) will be used. After the biopsy is done, participants who continue to have pain may receive either oxycodone/acetaminophen or acetaminophen (medicines used to relieve pain). Any participant who experiences nausea may receive ondansetron (a medicine used to relieve nausea).
Other intervention name(s): SonoSite Edge Ultrasound System; H&P; exam; medical history; IV; Phlebotomy; Questionnaire; Biopsy; Versed; Fentora; Onsolis; Xylocaine; Tylenol; Ativan; Percocet; Tylox; Zofran
Intervention MeSH terms: Acetaminophen; Acetaminophen, hydrocodone drug combination; Lidocaine; Midazolam; Fentanyl; Oxycodone; Lorazepam; Ondansetron; Liver Extracts
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pulmonary clinic, hepatology clinic, and the Alpha-1 Antitrypsin Tissue and Data Bank.
      
Biospecimen description: 
      Liver tissue and whole blood.
    
Keywords: Liver; Fibrosis; Alpha-1; AAT; AATD