This study is about a disease called Alpha-1 antitrypsin deficiency (AATD). It is caused by a problem in our genes. People with this disease can have problems with their lungs and liver. Some people with AATD can get very sick and need a new liver. We don't yet know much about liver problems in those patients.
We want to learn more about the liver problems that people with AATD can have. We will study a group of people who have just found out they have AATD. We will use information that is available from a database that covers more than 40 million people in England who have gone to the doctor. We will look at the medical information of people with AATD and a similar group of people without AATD to see how likely they are to get very sick with liver disease, lung disease, need a new liver, or even die. We hope this study will help doctors understand AATD and liver disease better. Then they can treat people with AATD better and help them stay healthy.
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder that commonly manifests as lung and/or liver disease. Although around 10% of those with AATD experience significant liver disease, the development and progression of liver disease remains poorly understood.
The overall aim is to characterise a population with AATD at time of diagnosis and to estimate the subsequent risk of severe liver disease.
Specific aims are to:
1. Characterise a population with AATD according to demographic and clinical parameters at time of AATD diagnosis and over time as compared with a matched reference population. Characterisations in sub-populations of special interest, i.e. according to liver function tests/non-invasive scores and clinical events will be explored
2. Estimate the incidence of liver events, liver transplants, pulmonary events, and all-cause mortality in a population with AATD as compared with a matched reference population. The incidence in sub-populations of special interest, i.e. according to liver function tests/non-invasive scores will be explored.
Using a longitudinal cohort design, adults (≥18years) diagnosed with AATD registered after 01 April 1997 in the AURUM Clinical Practice Research Datalink (CPRD) will be included if they are not prescribed drugs inducing liver disease prior to/at date of AATD diagnosis. Individuals are followed from date of inclusion until time of first outcome event (liver, pulmonary, transplant or all-cause mortality) recorded in the Hospital Episodes Statistics or the Office for National Statistics Death Registration Data or end of the HES/ONS registration period*, whichever comes first.
The characterisation of the study population is done by descriptive statistics and the incidence of outcome events is estimated with Aalen-Johansen cumulative incidence functions. This is done similarly in the reference population without AATD (matched according to year of birth, sex, length of observation period, year of AATD diagnosis) and in the subpopulations of special interest.
*currently 31 Mar 2021.
The four outcomes are listed below. Events in each outcome are defined by ICD10 or OPCS4 codes from Hospital Episodes Statistics (HES) Outpatient data, HES Admitted Patient Care Data or Office for National Statistics (ONS) Death Registration Data.
Liver event - using the first record of any of the below events captured in HES or ONS:
• Liver mortality (ONS)
• Hospital contact for hepatocellular carcinoma (HES)
• Hospital contact for liver transplant (HES)
• Hospital contact for chronic liver failure (HES)
• Hospital contact for liver cirrhosis (HES)
• Hospital contact for portal hypertension (HES)
• Hospital contact for decompensated liver events:
- Ascites (HES)
- Transjugular intrahepatic portal shunt (HES)
- Hepatorenal syndrome (HES)
- Hepatic encephalopathy (HES)
- Gastro-oesophageal varices with/without bleeding (HES)
Liver transplant - using the first record of the below event captured in HES:
• Hospital contact for liver transplant (HES)
Pulmonary event - using the first record of any of the below events captured in HES or ONS:
• Pulmonary mortality (ONS)
• Hospital contact for lung transplant (HES)
• Hospital contact for chronic lower respiratory disease:Bronchitis (HES)
- Emphysema (HES)
- Other chronic obstructive pulmonary disease (HES)
- Asthma (HES)
- Bronchiectasis (HES)
All-cause mortality – using a record in ONS Death Registration Data:
• Death record by any cause
All listed events are defined as presence of a code in HES or ONS and are assumed to be absent by the absence of a code. Please see Tables 3 to 6 in the appendix for the specific ICD10 and OPCS4 codes used to define the events.
Tina Landsvig Berentzen - Chief Investigator - Novo Nordisk A/S
Tina Landsvig Berentzen - Corresponding Applicant - Novo Nordisk A/S
Alice Turner - Collaborator - University of Birmingham
Kamal Kant Mangla - Collaborator - Novo Nordisk A/S
Klaus Andersen - Collaborator - Novo Nordisk A/S
Louise Maymann Nitze - Collaborator - Novo Nordisk A/S
Michael Soliman - Collaborator - Novo Nordisk A/S
Mohamed Tawfik - Collaborator - Novo Nordisk Denmark A/S
Pavel Strnad - Collaborator - University Hospital Aachen
Rikke Baastrup Nordsborg - Collaborator - Novo Nordisk A/S
Tina Landsvig Berentzen - Collaborator - Novo Nordisk A/S
HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data