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Background: Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy. Aim: We compare the clinical course, patterns of survival and causes of death by etiology during long-term follow-up in a large population-based cohort of patients with incident cirrhosis. Material and methods: We used population-based medical registries for a cohort study of patients with liver cirrhosis diagnosed January 2001 to December 2010, in the Scania region of Sweden. Medical records were reviewed. Patients were classified according to etiology and clinical parameters were registered. Patients were followed until December 2017. Results: The cohort comprised 1317 patients, 631 were decompensated at diagnosis and 387 decompensated during follow-up. The cumulative 10-year incidence of decompensation, with death and transplantation as competing risks, was 89% in alcoholic cirrhosis, 58% in hepatitis C and 75% in cryptogenic cirrhosis. The lowest 10-year transplantation-free survival rates were found in cryptogenic cirrhosis (11%), alcohol-related cirrhosis (18%) and alcohol combined with hepatitis C (12%). Autoimmune hepatitis cirrhosis showed the best 10-year survival (53%) and hepatitis C, non-alcoholic steatohepatitis, primary biliary cholangitis, and primary sclerosing cholangitis and other causes averaged 30%. Decompensation at diagnosis was an important predictor for death in all etiologies apart from alcoholic cirrhosis. 991 patients died and 91 were transplanted. Conclusion: Our results show that the clinical course and survival in cirrhosis differ considerably by both etiology and state at diagnosis. (Less)

Objectives: Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by onset of ascites, variceal bleeding, or encephalopathy. Although it is presumed that the survival of decompensated patients is the same regardless of when decompensation occurs, data to support this are scarce. We aimed to study the impact of time of decompensation on the clinical course and survival of patients with cirrhosis in a large population-based cohort. Materials and methods: We used medical registries to define a 10-year cohort of 1317 patients with incident liver cirrhosis in the Scania region of Sweden. Medical records were reviewed. Patients were followed until December 2011, and for death or transplantation until December 2014. Results: In the cohort, 629 patients were decompensated at diagnosis, of which 505 had ascites and 44 variceal bleeding only. During follow-up, 228 patients developed ascites and 39 variceal bleeding as first complication. Patients with ascites as first complication showed worse survival than patients who had ascites at diagnosis. (5-year survival 33% vs. 15%, HR 1.60 (95% CI 1.34–1.90)). This difference persisted after adjustment for confounders, including hepatocellular cancer (HR 1.38 (95% CI 1.15–1.67)). Worse survival was also seen when bleeding from varices occurred during follow-up rather than at diagnosis. Conclusions: Our results provide evidence for an association between transplantation-free survival after decompensation and the time of decompensation in liver cirrhosis, with worse survival when decompensation occurs during follow-up, thus challenging the generally held, view that the survival after decompensation is independent of when decompensation occurs.

Summary Background In Sweden, the most common causes of liver cirrhosis are alcohol overconsumption and hepatitis C. However, recent data on the clinical characteristics of Swedish patients with cirrhosis are scarce. Aims To determine the incidence, clinical presentation, aetiological spectrum and survival rates of liver cirrhosis in Southern Sweden from 2001 to 2011. Methods We used population-based medical registries to conduct a cohort study of all patients with liver cirrhosis in the southernmost region of Sweden with a population of 1.17 million. Medical records and histopathology data were reviewed. Patients were classified according to aetiology, and clinical parameters were registered. Patients were followed until death or December 2014. Results A total of 1317 patients with cirrhosis were identified. The crude annual incidence of cirrhosis was estimated at 14.1/100 000. The most common aetiology was alcohol overconsumption with or without additional causes of cirrhosis (58%) followed by HCV alone (13%) and cryptogenic cirrhosis (12%). At diagnosis, ascites occurred in 43%, variceal bleeding in 6% and overt encephalopathy in 4%. The median follow-up was 4.3 years. The total 1-, 5- and 10-year survival rates were 79%, 47% and 27% respectively. Survival rates were better for women than for men. A 10-year cumulative incidence of transplantation was 7.3%. Mortality was worst for alcoholic cirrhosis with concomitant HCV when adjusted for age and gender. Conclusions Sweden continues to have a low incidence of cirrhosis compared with other European countries. Mortality varies with gender, aetiology and severity at diagnosis. Patients with alcoholic cirrhosis with concomitant HCV infection fare worst. (Less)

Longitudinal, population-based data on the occurrence, localization, and severity of bacterial infections over time in patients with alcoholic compared with nonalcoholic cirrhosis are limited.All patients with incident cirrhosis diagnosed in 2001-2010 (area of 600,000 inhabitants) were retrospectively identified. All bacterial infections resulting in or occurring during an inpatient hospital episode during this period were registered. The etiology of cirrhosis (alcoholic vs. nonalcoholic), infection localization, and outcome as well as bacterial resistance patterns were analyzed. Patients were followed until death, transplant, or the end of 2011.In all, 633 cirrhotics (363 alcoholic, 270 nonalcoholic) experienced a total of 398 infections (2276 patient-years). Among patients diagnosed with cirrhosis each year from 2001 to 2010, increasing trends were noted in the occurrence of infection (from 13 to 27%, P0.001) and infection-related in-hospital mortality (from 2 to 7%, P=0.05), the latter mainly in the alcoholic group. Although alcoholic etiology was related to the occurrence of more frequent infection (Kaplan-Meier, P0.001), this relationship was not significant after adjustment for confounders in Cox regression analysis (P=0.056). Resistance to piperacilin-tazobactam and carbapenems was more common in infections occurring in alcoholic versus nonalcoholic cirrhosis (13 vs. 5%, P=0.057 and 12 vs. 2%, P=0.009). Alcoholic etiology predicted pneumonia and infections caused by Gram-positive bacteria in multivariate analysis (P0.05 for both).In a population-based cirrhotic cohort, bacterial infections increased over time, which, in the case of alcoholic cirrhosis, was associated with pneumonia and bacterial resistance to antibiotics. However, alcoholic etiology was not related indepedently to the occurrence of bacterial infections.

Population-based data on the impact of bacterial infections on the course of compensated and decompensated cirrhosis as well as the occurrence, predictors of infection-related acute-on-chronic liver failure (ACLF) and its fatal outcome are limited.All patients with incident cirrhosis in the period 2001-2010, residing in an area of 600,000 inhabitants, were retrospectively identified. All serious bacterial infections (resulting in or occurring during an inpatient hospital episode) during this period were analyzed. Infection site and acquisition type, comorbid illness (Charlson comorbidity index) and infection severity features were analyzed. Patients were followed up until death, transplant, or the end of 2011.Overall, 398 serious bacterial infections occurred in 241/633 (38%) patients (106/332 diagnosed with compensated and 135/301 with decompensated disease; follow-up time was 2276 patient-years). ACLF occurred in 95/398 (24%) serious infections with an in-hospital mortality of 50%. In logistic regression analysis, the model for end-stage liver disease score, active alcohol misuse and healthcare-associated infections were predictors of infection-related ACLF (p0.05 for all). In-hospital mortality in infections with ACLF was related to albumin levels, Charlson comorbidity index1 and occurrence of one or more organ failures (p0.05 for all). In Cox regression analysis, infection-related ACLF was an independent negative predictor of transplant-free survival in decompensated patients (p = 0.049).In a population-based cirrhotic cohort, infection-related ACLF was a negative predictor of survival in decompensated disease. Infection-related ACLF was frequent and related to cirrhosis severity and infection acquisition type, as well as to high inpatient mortality, in particular in patients with significant comorbidity.

Cirrhosis is a well-known risk factor for hepatocellular cancer, but the true risk in autoimmune hepatitis (AIH) is scarcely studied. Other cancers may arise after prolonged use of immune-modulating drugs. The aim of this study was to investigate the cancer risk in a large cohort of AIH patients.Six hundred and thirty-four Swedish patients in a well-defined cohort were matched to the Cause of Death Registry and the Cancer Registry. Standard incidence ratios were calculated by relating the incidences in the cohort to an age-matched material from the Swedish background population.A higher overall incidence of malignancies than the background population was found, counting from the date of diagnosis (standard incidence ratio (SIR) 2.08, 95% CI 1.68-2.55). The highest risk was found for hepatocellular carcinoma (HCC). We found 10 cases (4.0%) in 248 patients with cirrhosis, which gives an incidence rate of 0.3%. Standard incidence ratio for developing hepatobiliary cancer was 54.55 (95% CI 19.92-99.99). HCC only occurred in cirrhotic patients. There was also an increased risk for non-melanoma skin cancer (SIR 9.87, 95% CI 6.26-14.81).A slightly enhanced risk for malignancies in general compared to the background population was found. The risk of hepatobiliary cancer was increased, but the annual risk over the observational period was well under the postulated 1.5% when surveillance in cirrhotic patients is considered to be cost-effective.