Some epidemiological aspects of liver cirrhosis and hepatocellular carcinoma in Sweden

Sammanfattning: Background: Contemporary epidemiological studies examining incidence rates (IR) of cirrhosis and hepatocellular carcinoma (HCC) in Swedish populations are scarce. Cirrhosis and HCC are associated with a significant burden of health inequity and stigma. The importance of socioeconomic status (SES) in cirrhosis survival has scarcely been studied in Sweden. The impact of SES on HCC incidence and prognosis had never been investigated in Sweden. Aim: The overall aim of this thesis was to describe the contemporary epidemiology of cirrhosis and HCC in Swedish settings. We also aimed to improve the understanding of the importance of sociodemographic and clinical characteristics for the clinical course and early identification of cirrhosis and HCC. Methods: We used population-based medical registries to identify adult patients diagnosed with cirrhosis in the region of Halland between 2011 and 2018. Annual crude IR of cirrhosis were calculated (Paper I). Patients were followed-up until date of liver transplantation, death, moving from Halland, or until December 31st, 2019; whichever occurred first. Cox regression models were employed to estimate unadjusted and adjusted hazard ratios (HR and aHR) for several clinical and sociodemograhic variables (Paper II). The nationwide quality register for liver cancer was used to identify all adult patients diagnosed with HCC in Sweden between 2012 and 2018. Poisson regression was used to estimate IRs of HCC across several populations of interest (Paper III). Data extracted from the quality register were cross-linked to data from other nationwide registers. Multivariable logistic regression models were employed to identify factors associated with an increased likelihood for having unrecognized cirrhosis, or late-stage HCC at diagnosis. Patients were followed-up until the date of death, emigration from Sweden, or until December 31st, 2020; whichever occurred first. Cox regression modelling was used for the estimation of HRs and aHRs for several clinical variables (Paper IV). IRs of HCC were estimated for the whole adult population of Sweden and stratified by HCC etiologies (Paper V). Patients were stratified into those with non-alcoholic fatty liver disease (NAFLD) associated HCC and those with non-NAFLD-HCC. Furthermore, those with NAFLD-HCC were divided into those with and without underlying cirrhosis. Results: We identified a total of 598 patients with cirrhosis. The IR of cirrhosis in adults in Halland was estimated at 30 per 100,000 person-years, 39 for men, and 22 for women (Paper I). Patients with a low SES, defined as a low occupational skill level, had more advanced cirrhosis at diagnosis, lower mean survival, and higher mortality risk when compared to patients with high SES (Paper II). A total of 3,473 adult patients with HCC were identified and 68% were diagnosed with a late-stage HCC. Sex, country of birth, and individual- and contextual level SES were associated with the IRs of HCC. Men with a low household income and/or living in the most deprived neighborhoods had the highest IR of HCC (Paper III). Among patients with HCC, 2670 (77%) had underlying cirrhosis. Cirrhosis was unrecognized in 39% of all patients with underlying cirrhosis. Unrecognized cirrhosis was associated with more advanced HCC at diagnosis and worse survival (Paper IV). Among the 3,473 patients with HCC, 21% had underlying NAFLD, which also was the second-leading cause of HCC and the fastest- increasing cause of HCC (Paper V). Conclusions: The IRs of cirrhosis may be higher than previously estimated. Low SES was associated with a worse prognosis in cirrhosis, higher IRs of HCC, and increased risk of unrecognized cirrhosis in HCC. NAFLD is an increasing cause of cirrhosis and has become a leading cause of HCC. NAFLD is also associated with an increased risk of cirrhosis unrecognition in HCC.