CCCC-UK’: Characteristics of Chronic Hepatitis B associated with Cirrhosis and Cancer: analysis of a large UK primary care database
What is the aim of the study and why is it important?
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 is the research being 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.
Lead Applicant Organisation Name
Location of research
Nuffield Dept of Medicine, Experimental Medicine Division, University of Oxford
Date on which research approved
Project reference ID
Generic ethics approval reference
Are all data accessed are in anonymised form?
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.
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
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
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
Trusted Research Environment (TRE)