Hepatic encephalopathy (HE) is a severe complication of liver failure. When the liver becomes damaged, it can no longer remove harmful toxins from the body, and this causes damage to the brain. An effective therapy in patients with HE that has been shown to reduce the number and length of hospitalisations and is associated with reduced mortality is rifaximin-α 550mg. Rifaximin-α is an antibiotic used to treat HE by preventing the production and absorption of toxic compounds that arise in the gut. There is, however, no known research into the effect that the length of time between HE diagnosis and treatment initiation with rifaximin-α has on mortality outcomes and health service utilisation. This study aims to investigate the existence of any such effect.
We aim to model the effect on mortality and healthcare resource utilisation of a delay in treatment initiation with rifaximin-α 550mg (denoted rifaximin-α) for patients diagnosed with hepatic encephalopathy (HE). Patients associated with a Read or SNOMED code for HE and product codes for rifaximin-α will be selected from a population of research-quality patients in CPRD eligible for linkage to HES data. Patients will be split into two groups based on the time taken to begin treatment following their diagnosis. Those receiving treatment within six months will be directly matched to those treated after six months using potential confounders, including age, presence of ascites, presence of non-alcoholic fatty liver disease, albumin-bilirubin score, prior gastroenterology consultation, and differences in baseline characteristics. All-cause mortality will be compared using a hazard ratio calculated from a Cox proportional hazards model and ONS Death Registration data. Measures of healthcare resource use will be modelled using conditional Poisson regression. All-cause hospitalisation, liver-related hospitalisation and length of hospital stay will be derived from HES Admitted Patient Care data. The frequency of GP visits, outpatient appointments and accident and emergency attendance will be derived from Primary Care data (CPRD Aurum and GOLD), HES Outpatient data and HES A&E data, respectively. Understanding the effect of a delay in treatment with rifaximin-α on mortality outcomes and health service utilisation for patients diagnosed with HE will help inform clinical practice guidelines concerning treatment timing and enable more informed decision-making by health care practitioners concerning the cost of health service provision.
Primary outcome: All-cause mortality.
Secondary outcome: Healthcare resource use - All-cause hospitalisation (inpatient), Liver related hospitalisation (inpatient), Length of stay (inpatient), GP visits, Outpatient appointments, Accident & emergency attendance.
Ellen Hubbuck - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Aron Buxton - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Elena Subbotina - Collaborator - Norgine
James Orr - Collaborator - University Hospitals Bristol NHS Foundation Trust
Justin Thomas - Collaborator - Norgine
Richard Hinde - Collaborator - Norgine
Roland Henrar - Collaborator - Norgine
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data