Assessment of the Association of Progression to High-Risk Varices With Death and Liver Transplantation Rates in Patients With Compensated Cirrhosis

Study type

• Study topic:
  Disease /health condition
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Hypothesis generation (including signal detection)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medical condition to be studied:
  Metabolic dysfunction-associated steatohepatitis

  Hepatic cirrhosis
• Additional medical condition(s):
  Liver decompensation

Population studied

• Short description of the study population:
  Adults with compensated cirrhosis without a previous history of protocol-defined events
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Estimated number of subjects:
  58197

Study design details

• Study design:
  An observational cohort study utilizing data from 2005-2022 in Swedish national and regional (Stockholm regional electronic health records [EHRs]) registers. The study will conduct secondary data analysis via the Health Outcomes and Risk Assessment in Chronic Liver Disease (HERALD) platform.
• Main study objective:
  The main objective of this study is to identify and characterize patients with compensated cirrhosis (any etiology) belonging to study cohorts defined based on earliest protocol defined event, along with estimating the risk of liver transplantation and all-cause, cardiovascular-specific, and liver-specific mortality from the index date in patients across all cohorts.; ;
• Setting:
  - Swedish National Cohort: ; - Patient has at least one (≥1) primary or secondary diagnosis of compensated cirrhosis recorded in the national in- or outpatient secondary care registers or in the regional EHRs during the inclusion period between 01 January 2006 and 01 November 2021 (National population); - Patient has a first occurrence of any of the protocol defined events during the inclusion period ; - Stockholm Cohort:; - Patient has at least one (≥1) primary or secondary diagnosis of compensated cirrhosis recorded in the national in- or outpatient secondary care registers or in the regional EHRs during the inclusion period between 1 January 2011 and 26 October 2020 ; - Patient has a first occurrence of any of the protocol defined events during the inclusion period ; - Patient has at least one observation in the TakeCare EHR data; ; Exclusion Criteria:; ; - Patient has evidence of decompensated cirrhosis prior to their first protocol defined event; ;
• Outcomes:
  • Liver transplantation; • All-cause mortality; • Cardiovascular-related mortality; • Liver-related mortality;
• Data analysis plan:
  Descriptive statistics will be generated to summarize patient characteristics. Continuous covariates will be described by mean, standard deviation (SD), and interquartile range (IQR). Categorical covariates will be described by proportion and frequency in each category. ; ; For Time-to-event analyses: Counts (proportions) and cumulative incidence and 95% confidence interval (CI) stratified by cohort and subcohort at 1-, 3-, 5-years post-index and overall will be described. Median time to survival and 95% CI by cohort and subcohort; cumulative incidence plots by cohort and subcohort; unadjusted and adjusted hazard ratios (95% CI) for study cohorts defined based on protocol defined events will be generated.;