Penetrance, cancer incidence and survival in HFE haemochromatosis-A population-based cohort study.

BACKGROUND AND AIMS: Haemochromatosis is characterized by progressive iron overload affecting the liver and can cause cirrhosis and hepatocellular carcinoma. Most haemochromatosis patients are homozygous for p.C282Y in HFE, but only a minority of individuals with this genotype will develop the disease. The aim was to assess the penetrance of iron overload, fibrosis, hepatocellular carcinoma and life expectancy. METHODS: A total of 8839 individuals from the Austrian region of Tyrol were genotyped for the p.C282Y variant between 1997 and 2021. Demographic, laboratory parameters and causes of death were assessed from health records. Penetrance, survival, and cancer incidence were ascertained from diagnosed cases, insurance- and cancer registry data. Outcomes were compared with a propensity score-matched control population. RESULTS: Median age at diagnosis in 542 p.C282Y homozygous individuals was 47.8 years (64% male). At genotyping, the prevalence of iron overload was 55%. The cumulative penetrance of haemochromatosis defined as the presence of provisional iron overload was 24.2% in males and 10.5% in females aged 60 years or younger. Among p.C282Y homozygotes of the same ages, the cumulative proportion of individuals without fibrosis (FIB-4 score < 1.3) was 92.8% in males and 96.7% in females. Median life expectancy was reduced by 6.8 years in individuals homozygous for p.C282Y when compared with population-matched controls (p = .001). Hepatocellular carcinoma incidence was not significantly higher in p.C282Y homozygotes than in controls matched for age and sex. CONCLUSION: Reduced survival and the observed age-dependent increase in penetrance among p.C282Y homozygotes call for earlier diagnosis of haemochromatosis to prevent complications.

Impact of preoperative anemia, iron-deficiency and inflammation on survival after colorectal surgery-A retrospective cohort study.

BACKGROUND: Anemia is present in up to two-thirds of patients undergoing colorectal surgery mainly caused by iron deficiency and inflammation. As anemia is associated with increased risk of perioperative death, diagnosis and treatment of preoperative anemia according to etiology have been recommended. OBJECTIVE: The aim of the present study was to assess if the association between anemia and survival in patients undergoing colorectal surgery was determined by the severity of anemia alone or also by anemia etiology. METHODS: To determine the prevalence of anemia and etiology, preoperative hematological parameters, C-reactive protein, ferritin and transferrin saturation were retrospectively assessed and correlated with outcome in a cohort of patients undergoing colorectal surgery between 2005 and 2019 at the University Hospital of Innsbruck. Anemia was defined as hemoglobin <120 g/L in females and <130 g/L in males. The etiology of anemia was classified on the basis of serum iron parameters, as iron deficiency anemia, anemia of inflammation or other anemia etiologies. RESULTS: Preoperative anemia was present in 54% (1316/2458) of all patients. Anemia was associated with iron deficiency in 45% (134/299) and classified as anemia of inflammation in 32% (97/299) of patients with available serum iron parameters. The etiology of anemia was a strong and independent predictor of survival, where iron deficiency and anemia of inflammation were associated with better postoperative survival than other anemia etiologies. One year survival rates were 84.3%, 77.3% and 69.1% for patients with iron deficiency anemia, anemia of inflammation and other anemia types. Inflammation indicated by high C-reactive protein is a strong negative predictor of overall survival. CONCLUSIONS: Anemia has a high prevalence among patients undergoing colorectal surgery and rational treatment requires early assessment of serum iron parameters and C-reactive protein.

Association of the metabolic syndrome with mortality and major adverse cardiac events: A large chronic kidney disease cohort.

BACKGROUND: Metabolic syndrome with its key components insulin resistance, central obesity, dyslipidaemia, and hypertension is associated with a high risk for cardiovascular events and all-cause mortality in the general population. However, evidence that these findings apply to patients with chronic kidney disease (CKD) with moderately reduced estimated glomerular filtration rate and/or albuminuria is limited. OBJECTIVES: We aimed to investigate the association between metabolic syndrome and its components with all-cause mortality and cardiovascular outcomes in CKD patients. METHODS: Prospective observation of a cohort of 5110 CKD patients from the German Chronic Kidney Disease study with 3284 (64.3%) of them having a metabolic syndrome at baseline. RESULTS: During the follow-up of 6.5 years, 605 patients died and 650 patients experienced major cardiovascular events. After extended data adjustment, patients with a metabolic syndrome had a higher risk for all-cause mortality (hazard ratio [HR] = 1.26, 95% confidence interval [CI]: 1.04-1.54) and cardiovascular events (HR = 1.48, 95% CI: 1.22-1.79). The risk increased steadily with a growing number of metabolic syndrome components (increased waist circumference, glucose, triglycerides, hypertension and decreased HDL cholesterol): HR per component = 1.09 (95% CI: 1.02-1.17) for all-cause mortality and 1.23 (95% CI: 1.15-1.32) for cardiovascular events. This resulted in hazard ratios between 1.50 and 2.50 in the case when four or five components are present. An analysis of individual components of metabolic syndrome showed that the glucose component led to the highest increase in risk for all-cause mortality (HR = 1.68, 95% CI: 1.38-2.03) and cardiovascular events (HR = 1.81, 95% CI: 1.51-2.18), followed by the HDL cholesterol and triglyceride components. CONCLUSIONS: We observed a high prevalence of metabolic syndrome among patients with moderate CKD. Metabolic syndrome increases the risk for all-cause mortality and cardiovascular events. The glucose and lipid components seem to be the main drivers for the association with outcomes.