Risk and outcome of hepatocellular carcinoma in liver cirrhosis in Southern Sweden: a population-based study.

Background and aims: Liver cirrhosis is a risk factor for hepatocellular carcinoma (HCC). While the HCC risk is thought to be highest in hepatitis B and hepatitis C, the risk in other cirrhosis etiologies is not fully established. Therefore, we aimed to study the risk and outcome of HCC in alcoholic cirrhosis compared to cirrhosis of other etiologies, in Sweden. Material and methods: We used population-based medical registries to identify patients diagnosed with cirrhosis in the Scania region in southern Sweden between 2001 and 2010. Medical records were reviewed to identify all HCC cases and to register clinical parameters. All patients were followed until death, emigration or December 2017. Results: The cohort comprised 1317 patients with cirrhosis. A total of 200 patient developed HCC, including 75 with prevalent HCC. The annual incidence of HCC after six months was 1.5% in alcoholic cirrhosis and 4.7% in hepatitis C cirrhosis. In alcoholic cirrhosis, 40 patients were diagnosed with HCC during follow-up, of which 15 patients fulfilled the Milan criteria and 10 received treatment, curative or palliative. The overall median survival after HCC diagnosis was 7.7 months, with 4.5, 11 and 9.3 months, in cirrhosis due to alcohol, hepatitis C or remaining causes, respectively. Conclusion: We find an annual incidence of HCC in alcoholic cirrhosis of 1.5% indicating need for surveillance in these patients. Survival after HCC diagnosis was worst in alcoholic cirrhosis due to more advanced stage at diagnosis with few patients eligible for treatment.

Patients with liver cirrhosis show worse survival if decompensation occurs later during course of disease than at diagnosis.

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.

Dysfunction of Circulating Polymorphonuclear Leukocytes and Monocytes in Ambulatory Cirrhotics Predicts Patient Outcome.

BACKGROUND: Cirrhosis represents a state of functional immune paresis with increased infection risk. AIMS: To investigate polymorphonuclear (PMN) leukocyte and monocyte function in ambulatory cirrhotics, and their potential relation with cirrhosis etiology or patient outcome. METHODS: Consecutive ambulatory cirrhotics without current or recent (<1 month) infection or acute decompensation were prospectively enrolled in 2013 and followed for a median time of 20 months until death, transplant or end of 2014. Oxidative burst and phagocytosis of circulating PMNs and monocytes were investigated at baseline and after in vitro Escherichia coli stimulation. Seventeen healthy blood donors served as controls. Baseline clinical and laboratory data as well as follow-up data on the development of cirrhosis complications, including acute-on-chronic liver failure (ACLF), and bacterial infections were collected. RESULTS: Sixty patients were included (70 % male, median age 63 years, 52 % with alcoholic cirrhosis). Compared to controls, cirrhotics showed increased resting and stimulated burst as well as reduced phagocytosis of PMNs, and increased stimulated monocyte burst (p < 0.05 for all). Alcoholic etiology was not related to PMN or monocyte dysfunction (p > 0.05 for all). In Cox regression analysis, increased stimulated monocyte and PMN burst were independent predictors of sepsis, severe sepsis and ACLF occurrence. Also, increased stimulated monocyte burst was associated with worse transplant-free survival (p < 0.05 for all). CONCLUSIONS: Stimulated PMN and monocyte oxidative burst are increased in ambulatory cirrhotics without acute decompensation. In turn, these changes are associated to sepsis and ACLF occurrence.

Healthcare-associated and nosocomial bacterial infections in cirrhosis: predictors and impact on outcome.

BACKGROUND & AIMS: Population-based data on the occurrence of healthcare-associated (HCA) and hospital-acquired (HA) bacterial infections in cirrhosis, their predictors, and their impact on outcome are limited. METHODS: All patients with incident cirrhosis in 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 registered. Acquisition type, site of infection, occurrence of infection-related acute-on-chronic liver failure (ACLF), acute kidney injury (AKI) and bacterial resistance were analysed. Patients were followed longitudinally until death, transplant or end of 2011. RESULTS: A total of 398 serious infections occurred in 241/633 (38%) patients. Forty-seven per cent were HCA and 21% HA. Proton pump inhibitor (PPI) use was more common in HA (80%) vs. HCA (64%) vs. community-acquired (44%) infections (P < 0.001). In regression analysis, decompensated status, use of antibiotics and PPIs at infection diagnosis were independent predictors of HCA/HA infections (P < 0.05). After adjustment for confounders, HCA/HA infections were significantly related to infection-related ACLF (P < 0.05), but not severe sepsis, AKI or infection-related mortality (P > 0.05). Antibiotic-resistant infections were more frequent among HA (17%) than HCA (6%) or community-acquired (8%) infections (P < 0.05). Antibiotic-resistant HCA/HA infections were independently related to severe sepsis (P < 0.05). CONCLUSIONS: In a population-based cirrhotic cohort, two-thirds of serious bacterial infections were HCA or HA. Decompensated liver disease, antibiotics and PPIs were predictors of serious HCA/HA infections, which were associated with the development of ACLF. Antibiotic resistance was frequent, especially in HA infections, and contributed to risk of severe sepsis.

Predictors of mortality among patients with compensated and decompensated liver cirrhosis: the role of bacterial infections and infection-related acute-on-chronic liver failure.

OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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 (p < 0.05 for all). In-hospital mortality in infections with ACLF was related to albumin levels, Charlson comorbidity index >1 and occurrence of one or more organ failures (p > 0.05 for all). In Cox regression analysis, infection-related ACLF was an independent negative predictor of transplant-free survival in decompensated patients (p = 0.049). CONCLUSIONS: 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.

Clinical course and mortality by etiology of liver cirrhosis in Sweden: a population based, long-term follow-up study of 1317 patients.

BACKGROUND: Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy. AIM: To 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. 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.

Bacterial infections in alcoholic and nonalcoholic liver cirrhosis.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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%, P<0.001) 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, P<0.001), 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 (P<0.05 for both). CONCLUSION: 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.