Fast and accurate chest pain risk stratification in the emergency department (ED) is critical. The HEART score predicts the short-term incidence of major adverse cardiac events (MACE) in this population, dividing it in three risk categories. We aimed to describe the population with chest pain, to characterize the subgroup of patients with acute coronary syndrome (ACS) and to assess the prognostic value of Manchester triage system and of HEART score. Retrospective observational study including patients admitted to the ED of a tertiary hospital with chest pain as the presenting symptom. The primary outcome was a composite of all-cause mortality, myocardial infarction or unscheduled revascularization at 6 weeks. We enrolled 233 patients (age 58 ± 19; 55.4 % males). The most common final diagnosis was non-specific chest pain (n = 86, 36.9 %), followed by ACS (n = 22, 9.4 %). Male gender, smoking and chronic kidney disease were associated with higher risk of ACS. According to Manchester triage system, chest pain patients stratified with red or orange priority had a higher incidence of ACS (16.5 % vs. 3.8 %, p = 0.006). The application of HEART score showed that most patients were in low risk category (56.3 %). The six-week incidence of MACE in each category was 2 %, 15.6 % and 76.9 % (p < 0.001). HEART score accurately predicted the short-term incidence of MACE in chest pain patients (c-statistic 0.880; 95 % CI, 0.807–0.950, p < 0.001). Chest pain patients have very different levels of severity and the discriminatory power of Manchester triage system should be used in the assessment of this population. The HEART score seems to be an effective tool for risk stratification in the ED.

Hepcidin plays a crucial role in iron metabolism, preventing its absorption at the basolateral enterocyte membrane. Hepcidin regulation is complex and regulated at the transcriptional level. The relation between iron overload and alcoholic liver disease is well known, but its mechanism is not clear. We present an observational, case-control study, aimed at evaluating the effects of alcohol on the expression of hepcidin in human participants. We intended to assess whether iron overload related to alcohol ingestion was caused by hepcidin-impaired expression by determining hepcidin mRNA expression and relating it to iron stores, both in alcoholic patients and in normal controls. We compared liver hepcidin mRNA expression between 25 active drinkers with alcoholic liver disease, without cirrhosis, and 20 healthy controls. All individuals were evaluated for HFE mutations, complete blood count, coagulation, glucose, kidney function, liver function, viral hepatitis, C-reactive protein, interleukin 6, tumor necrosis factor α, and serum iron, ferritin, and transferrin saturation. Total RNA was isolated from liver samples, cDNA was obtained by reverse transcription, and hepatic expression levels of hepcidin were determined by real-time PCR using the comparative Ct method (2(-ΔΔCt)). Serum ferritin and transferrin saturation were significantly higher in patients. Hepcidin was downregulated in patients compared with the controls by a mean factor of -0.44 (log10 2(-ΔΔCt)) (P=0.009). Hepcidin expression was not significantly different between the several grades of fibrosis, necroinflammatory activity, and liver iron stores. Heavy alcohol consumption caused the highest hepcidin mRNA suppression. The hepcidin mRNA expression/serum ferritin ratio was significantly lower in alcoholic patients (P<0.0001). Hepcidin liver expression is inappropriately low in alcoholic patients with active alcoholism and preserved hepatic function, and we conclude that this is the mechanism for alcohol consumption-associated iron overload in humans.

AIM: To compare lymphocyte subsets between healthy controls and alcoholics with liver disease. METHODS: The patient cohort for this study included individuals who were suspected to have alcoholic liver disease (ALD) and who had undergone liver biopsy (for disease grading and staging, doubts about diagnosis, or concurrent liver disease; n = 56). Normal controls included patients who were admitted for elective cholecystectomy due to non-complicated gallstones (n = 27). Formalin-fixed, paraffin-embedded liver biopsy specimens were sectioned and stained with hematoxylin and eosin and Perls’ Prussian blue. The non-alcoholic steatohepatitis score was used to assess markers of ALD. Lymphocyte population subsets were determined by flow cytometry. T lymphocytes were identified (CD3⁺), and then further subdivided into CD4⁺ or CD8⁺ populations. B lymphocytes (CD19⁺) and natural killer (NK) cell numbers were also measured. In addition to assessing lymphocyte subpopulation differences between ALD patients and controls, we also compared subsets of alcoholic patients without cirrhosis or abstinent cirrhotic patients to normal controls. RESULTS: The patient cohort primarily consisted of older men. Active alcoholism was present in 66.1%. Reported average daily alcohol intake was 164.9 g and the average lifetime cumulative intake was 2211.6 kg. Cirrhosis was present in 39.3% of the patients and 66.1% had significant fibrosis (perisinusoidal and portal/periportal fibrosis, bridging fibrosis, or cirrhosis) in their liver samples. The average Mayo end-stage liver disease score was 7.6. No hereditary hemochromatosis genotypes were found. ALD patients (n = 56) presented with significant lymphopenia (1.5 × 10⁹/L ± 0.5 × 10⁹/L vs 2.1 × 10⁹/L ± 0.5 × 10⁹/L, P < 0.0001), due to a decrease in all lymphocyte subpopulations, except for NK lymphocytes: CD3⁺ (1013.0 ± 406.2/mm³vs 1523.0 ± 364.6/mm³, P < 0.0001), CD4⁺ (713.5 ± 284.7/mm³vs 992.4 ± 274.7/mm³, P < 0.0001), CD8⁺ (262.3 ± 140.4/mm³vs 478.9 ± 164.6/mm³, P < 0.0001), and CD19⁺ (120.6 ± 76.1/mm³vs 264.6 ± 88.0/mm³, P < 0.0001). CD8⁺ lymphocytes suffered the greatest reduction, as evidenced by an increase in the CD4⁺/CD8⁺ ratio (3.1 ± 1.3 vs 2.3 ± 0.9, P = 0.013). This ratio was associated with the stage of fibrosis on liver biopsy (r_s = 0.342, P = 0.01) and with Child-Pugh score (r_s = 0.482, P = 0.02). The number of CD8⁺ lymphocytes also had a positive association with serum ferritin levels (r_s = 0.345, P = 0.009). Considering only patients with active alcoholism but not cirrhosis (n = 27), we found similar reductions in total lymphocyte counts (1.8 × 10⁹/L ± 0.3 × 10⁹/L vs 2.1 × 10⁹/L ± 0.5 × 10⁹/L, P = 0.018), and in populations of CD3⁺ (1164.7 ± 376.6/mm³vs 1523.0 ± 364.6/mm³, P = 0.001), CD4⁺ (759.8 ± 265.0/mm³vs 992.4 ± 274.7/mm³, P = 0.003), CD8⁺ (330.9 ± 156.3/mm³vs 478.9 ± 164.6/mm³, P = 0.002), and CD19⁺ (108.8 ± 64.2/mm³vs 264.6 ± 88.0/mm³, P < 0.0001). In these patients, the CD4⁺/CD8⁺ ratio and the number of NK lymphocytes was not significantly different, compared to controls. Comparing patients with liver cirrhosis but without active alcohol consumption (n = 11), we also found significant lymphopenia (1.3 × 10⁹/L ± 0.6 × 10⁹/L vs 2.1 × 10⁹/L ± 0.5 × 10⁹/L, P < 0.0001) and decreases in populations of CD3⁺ (945.5 ± 547.4/mm³vs 1523.0 ± 364.6/mm³, P = 0.003), CD4⁺ (745.2 ± 389.0/mm³vs 992.4 ± 274.7/mm³, P = 0.032), CD8⁺ (233.9 ± 120.0/mm³vs 478.9 ± 164.6/mm³, P < 0.0001), and CD19⁺ (150.8 ± 76.1/mm³vs 264.6 ± 88.0/mm³, P = 0.001). The NK lymphocyte count was not significantly different, but, in this group, there was a significant increase in the CD4⁺/CD8⁺ ratio (3.5 ± 1.3 vs 2.3 ± 0.9, P = 0.01). CONCLUSION: All patient subsets presented with decreased lymphocyte counts, but only patients with advanced fibrosis presented with a significant increase in the CD4⁺/CD8⁺ ratio.

ContextAlcoholic liver disease (ALD) is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE) gene mutations and the severity of liver disease in alcoholic patients.ObjectivesTo compare the prevalence of mutations in the hemochromatosis (HFE) gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity.MethodsLiver biopsy specimens were obtained from 63 ALD patients (during routine treatment) and 52 healthy controls (during elective cholecystectomy). All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations). Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis.ResultsALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05), but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI): 2.09-142.34, P = 0.008). However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003).ConclusionsALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no detectable effects on liver disease activity or severity.