Status
Completed
Title
CCCC-UK’: Characteristics of Chronic Hepatitis B associated with Cirrhosis and Cancer: analysis of a large UK primary care database
What were the objectives of the study?
Hepatitis B virus (HBV) infection is a major contributor to morbidity and mortality worldwide, with an estimated 300 million people infected with HBV globally. Chronic infection, through its progression to cirrhosis and/or primary liver cancer, represents a substantial global disease burden, leading to close to a million deaths each year worldwide. There are hundreds of thousands of individuals infected with HBV in the UK, and in 2016 there were 5,933 incident cases of primary liver cancer, translating to age-standardised incidence rate of 9.8 cases per 100,000 population.
Despite the substantial burdens of both HBV and primary liver cancer & cirrhosis in the UK, little is known about the risk factors for progression of chronic HBV infection to cirrhosis and primary liver cancer. Additionally the HBV population in the UK is not well characterised, and little is known about the burden of comorbid conditions in this population.
This study aims to characterise the morbidity and mortality burdens of HBV-associated cirrhosis and liver cancer, and identify risk factors for progression to these endpoints, using data from all adults (aged ≥18 years) chronically infected with HBV between 1999 and 2019 in the QResearch database.
How was the research done?
The dataset will be organised and managed using Microsoft SQL server. The dataset will be processed and analysed by python and R software. Descriptive statistical analysis will be conducted to describe the study cohort. Logistics regression and Cox regression models will be used to investigate the risk factors of HBV-associated cirrhosis and liver cancer.
Chief Investigator
Cori Campbell
Lead Applicant Organisation Name
Sponsor
Oxford
Location of research
Nuffield Dept of Medicine, Experimental Medicine Division, University of Oxford
Date on which research approved
27-Feb-2020
Project reference ID
OX54
Generic ethics approval reference
18/EM/0400
Are all data accessed are in anonymised form?
Yes
Brief summary of the dataset to be released (including any sensitive data)
This cohort includes all adults aged ≥18 years chronically infected with HBV between 1999 and 2019.
Variables obtained from primary care data will include age, sex, height, weight, ethnicity, socioeconomic status, smoking status, alcohol consumption, liver function tests and relevant medications (including antiviral treatment, antihypertensive medication, antidiabetic medication and statin use).
Variables for comorbidities of interest (including alcoholic liver disease, non-alcoholic fatty liver disease[NAFLD], toxic liver injury, autoimmune hepatitis, diabetes, hypertension, coronary heart disease, congestive heart failure, co-infection with other blood-borne viruses, renal dysfunction, rheumatic disease, cerebrovascular disease, varices, and peptic ulcer disease) and cirrhosis will be constructed using information from both primary care data and Hospital Episode Statistics.
Comorbidities of non-liver malignant neoplasms and a variable for primary liver cancer will be constructed using information from primary care data, Hospital Episode Statistics and Cancer Registry Diagnoses.
What were the main findings?
Summary of findings: This study aimed to characterise chronic hepatitis B (CHB) in the primary care population in England and investigate risk factors for progression primary liver cancer. Undertaking a retrospective cohort study, we identified 8039 individuals with CHB in individuals aged ≥18 years between 1999 and 2019 in the English primary care database QResearch. To our knowledge, this is the largest CHB cohort characterised in the UK to date. Most individuals with CHB were males (60%) of non-White ethnicity (>70%), and a high proportion were in the most deprived Townsend deprivation quintile (44%). Among 7029 individuals with longitudinal data, 161 liver cancer cases occurred. Increased cancer risk associated with male sex (adjusted hazards ratio [aHR] 3.17, 95% confidence interval [95% CI] 1.92–5.23), belonging the fifth (most deprived) deprivation quintile as compared to the third (middle) quintile (aHR 1.69, 95% CI 1.01–2.84), with older age (for age groups 56–65 and ≥66 years, compared to 26–35 years, aHRs 2.82 [95% CI 1.45–5.46] and 3.76 [95% CI 1.79–7.9], respectively), Caribbean ethnicity (aHR 3.32, 95% CI 1.43–7.71, compared to White ethnicity), ascites (aHR 3.15, 95% CI 1.30–7.67), cirrhosis (aHR 6.55, 95% CI 4.57–9.38) and peptic ulcer disease (aHR 2.26, 95% CI 1.45–3.51). Targeting interventions and HCC surveillance at vulnerable groups is essential to improve CHB outcomes and to support progress towards international goals for the elimination of hepatitis infection as a public health threat.
Implications and Impact
This study will help to characterise the chronic HBV-infected population in a large-scale primary care dataset and identify the burdens and risk factors of primary liver cancer and cirrhosis in this population. This will ultimately serve to better inform management of chronic HBV infection and improve prevention of cirrhosis and primary liver cancer.
Public Benefit Statement
Research Team
Cori Campbell, DPhil Candidate, Nuffield Dept of Medicine, Experimental Medicine Division, University of Oxford
Dr Tingyan Wang, Postdoctoral Scientist/Data Analyst, Nuffield Dept of Medicine, Experimental Medicine Division, University of Oxford
Professor Philippa Matthews, Francis Crick Institute, also affiliated with University of Oxford,
Professor Ellie Barnes, Professor, MRC Senior Research Fellow/Experimental Medicine and Jenner Investigator, Nuffield Dept of Medicine, Experimental Medicine Division, University of Oxford
Publications
-
Estimating the epidemiology of chronic Hepatitis B Virus (HBV) infection in the UK: what do we know and what are we missing?
Authors: Campbell C, Wang T, Burrow R, Mandal S, Hippisley-Cox J, Barnes E, Matthews PC
Ref:
https://wellcomeopenresearch.org/articles/7-203/v2 -
Analysis of primary care electronic health record data of people living with hepatitis B virus: infection and hepatocellular carcinoma risk associated with socio-economic deprivation
Authors: Campbell C, Wang T, Gillespie I, Barnes E, Matthews PC
Ref:
https://www.sciencedirect.com/science/article/pii/S0033350623004134
Access Type
Trusted Research Environment (TRE)