1. Incidence and prognosis of hepatocellular adenoma in Denmark Lars Bossen Departments of Hepatology and Gastroenterology and Clinical Epidemiology Aarhus University Hospital, Aarhus, Denmark

2. Background and aim Hepatocellular adenoma is a benign liver tumour that may transform to HCC Most frequently diagnosed in women using oral contraceptives (OC) Identified risk factors for HCC development are; Male gender, size of the adenoma and the β-catenin mutated subtype In 1979 the incidence rate was estimated at 3-4 per 100,000 population per year for OC users vs. 0.1 per 100,000 population per year for non-users Aim: To investigate the incidence and prognosis of hepatocellular adenoma Rooks JB, et al. JAMA 1979;242:644-648

3. Nationwide healthcare registries Danish National Patient Registry (ICD-10 codes) Danish Cancer Registry (ICD-10 codes) Danish National Pathology Registry (SNOMED-codes) Danish Civil Registration System 1997-2012

4. Methods Incidence analysis – Incidence rates were age- and gender-standardized to the Danish population on 1 January 2015 using direct standardization Prognostic analyses – 10-year cumulative risk of HCC or death without HCC were calculated using the cumulative incidence function

5. Danish National Patient Registry N=1291 Danish National Pathology Registry N=103 Dead = 1 HCC = 4 Diagnosed in both registries N=68 Alive without HCC one year later, N=63 Included in the incidence analysis

6. Danish National Patient Registry N=1291 Danish National Pathology Registry N=103 Dead = 1 HCC = 4 Diagnosed in both registries, N=68 Alive without HCC one year later, N=63 Included in the incidence analysis Median age = 37.2 years 54 women, median age = 36.8 years 9 men, median age = 52.3 years

7. Danish National Patient Registry N=1291 Danish National Pathology Registry N=103 Dead = 1 HCC = 4 Diagnosed in both registries, N=68 Alive without HCC one year later, N=63 Included in the incidence analysis 1997-2012 Incidence rates per 100,000 population per year95% CI Overall0.080.06-0.10 Women0.130.10-0.17 Men0.030.01-0.04

8. Danish National Patient Registry N=1291 Danish National Pathology Registry N=103 Dead = 1 HCC = 4 Diagnosed in both registries, N=68 Alive without HCC one year later, N=63 Included in the incidence analysis Ready for follow-up and matching, N=49 Included in the prognostic analyses Adenoma resection before follow-up = 14

9. Danish National Patient Registry, N=1291Danish National Pathology Registry, N=103 Dead = 1 HCC = 4 Diagnosed in both registries, N=68 Alive without HCC one year later, N=63 Adenoma resection before follow-up = 14 HCCDeath without HCCAdenoma resection Two women, both above 70 years at adenoma diagnosis None Four men, all above 50 years at adenoma diagnosis. 3 of them died afterwards Follow-up start, N=49 Censored at emigration or 31 December 2013

10. Danish National Patient Registry, N=1291Danish National Pathology Registry, N=103 Dead = 1 HCC = 4 Diagnosed in both registries, N=68 Alive without HCC one year later, N=63 Resection = 14 HCCDeath without HCCAdenoma resection Follow-up start, alive without HCC, N=49 10-year cumulative risk of HCC for men above 50 years Patients80% (95% CI: 20.4% - 96.9%) 10-year cumulative risk of death without HCC, above 50 years Patients18.8% (95% CI: 2.9% – 45.6%) Matched controls34.4% (95% CI: 28.7% – 40.2%)

11. Limitations Unreliable diagnosis codes Underestimated incidence rate Few patients and few outcomes

12. Conclusion Hepatocellular adenoma is rarely diagnosed in Denmark Most frequently developed in women (86%) No increased risk of death without HCC Only men >50 years or older developed HCC Thank you!