Liver cirrhosis in southern Sweden. Epidemiology and clinical course.

Background: Liver cirrhosis is the end-stage of many liver diseases. It is characterized by a silent phase until decompensation, defined by ascites, variceal bleeding, or hepatic encephalopathy. In Sweden, the most common cause is alcohol overconsumption, followed by hepatitis C (HCV). Recent Swedish data on the clinical characteristics and survival are scarce. Further, survival after decompensation is presumed to be the same once it has occurred, yet little data support this presumtion. Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC), but the risk is not fully established in all etiologies. Aims: The aims of this thesis were to determine the incidence of cirrhosis, to describe the clinical presentation and clinical course, to study the pattern of survival and causes of death, and to study the risk and outcome of HCC by etiology of liver cirrhosis. We also aimed to study the impact of time of decompensation on the clinical course and survival. Methods: We used population-based medical registries to identify patients diagnosed with cirrhosis between 2001 and 2010, in the Scania region in southern Sweden. Medical records and histopathology data were reviewed to classify patients by etiology and to register clinical parameters. Patients were followed clinically until death, transplantation or December 2011 in Paper I and II with the addition of follow-up for death or transplantation until December 2014 in Paper II. In Paper III and IV, the follow-up period was prolonged until December 2017. Results: A total of 1,317 patients were identified. The crude annual incidence of cirrhosis was estimated at 14.1/100,000. The most common etiologies were alcohol overconsumption, with or without additional causes of cirrhosis, (58%), HCV (13%) and cryptogenic cirrhosis (12%). At diagnosis, 631 patients were decompensated, with ascites in 43%, variceal bleeding in 6% and hepatic encephalopathy in 4%. An additional 387 decompensated during follow-up until December 2017. The cumulative ten-year incidence of decompensation, with death and transplantation as competing risks, was 89% in alcoholic cirrhosis, 58% in HCV and 75% in cryptogenic cirrhosis. By December 2017, 991 patients had died and 91 were transplanted. The total one- and five-year transplantation-free survival were 78% and 43%. Patients with ascites as first complication showed worse survival than patients with ascites at diagnosis (HR 1.60; 95% CI 1.34-1.90). The lowest ten-year survival rates were seen in cryptogenic cirrhosis (11%), alcoholic cirrhosis (18%) and alcohol combined with HCV (12%). Decompensation at diagnosis was an important predictor for death in all etiologies except alcoholic cirrhosis. HCC developed in 200 patients, of which 75 were prevalent (within six months) at cirrhosis diagnosis. The annual incidence of HCC was 1.5% in alcoholic cirrhosis and 4.7% in HCV cirrhosis. The median survival after HCC diagnosis was 4.5 months in alcoholic cirrhosis, 11 months in HCV cirrhosis, and 9.3 months in cirrhosis of remaining causes. Conclusions: We found a low incidence of cirrhosis compared to other European countries. The clinical course and survival in cirrhosis varied by both etiology and disease severity at diagnosis. We also found an association between transplantation-free survival after decompensation and time of decompensation in liver cirrhosis, with better survival if decompensated at diagnosis. In patients with alcoholic cirrhosis, the annual incidence of HCC was 1.5%, supporting a continued need for surveillance. Survival after HCC diagnosis was worst in alcoholic cirrhosis.