Patients with alcoholic liver disease (ALD) often display disturbed iron indices. Hepcidin, a key regulator of iron metabolism, has been shown to be down-regulated by alcohol in cell lines and animal models. This down-regulation led to increased duodenal iron transport and absorption in animals. In this study, we investigated gene expression of duodenal iron transport molecules and hepcidin in three groups of patients with ALD (with anaemia, with iron overload and without iron overload) and controls. Expression of DMT1, FPN1, DCYTB, HEPH, HFE and TFR1 was measured in duodenal biopsies by using real-time PCR and Western blot. Serum hepcidin levels were measured by using ELISA. Serum hepcidin was decreased in patients with ALD. At the mRNA level, expressions of DMT1, FPN1 and TFR1 genes were significantly increased in ALD. This pattern was even more pronounced in the subgroups of patients without iron overload and with anaemia. Protein expression of FPN1 paralleled the increase at the mRNA level in the group of patients with ALD. Serum ferritin was negatively correlated with DMT1 mRNA. The down-regulation of hepcidin expression leading to up-regulation of iron transporters expression in the duodenum seems to explain iron metabolism disturbances in ALD. Alcohol consumption very probably causes suppression of hepcidin expression in patients with ALD.

Iron accumulation does not play a major role in the pathogenesis of DD. However, sex, age, manual labour and alcohol consumption are risk factors for progression of DD. We observed a high incidence of chronic liver disease in patients with DD.

Introduction: Our study aimed to analyze whether renal parameters can predict mortality from COVID-19 disease in hospitalized patients. Methods: This retrospective cohort includes all adult patients with confirmed COVID-19 disease who were consecutively admitted to the tertiary hospital during the four-month period (1.9. - 31.12.2020). We analyzed their basic laboratory values, urinalysis, comorbidities, length of hospitalization, and survival. The RIFLE and KDIGO criteria were used for AKI and CKD grading, respectively. To display renal function evolution and the severity of renal damage, we subdivided patients further into 6 groups as follows: group 1 (normal renal function), group 2 (CKD grade 2+3a), group 3 (AKI-DROP defined as whose s-Cr dropped by >33.3% during the hospitalization), group 4 (CKD 3b), group 5 (CKD 4+5) and group 6 (AKI-RISE defined as whose s-Cr was elevated by ≥ 50% within 7 days or by ≥26.5 μmol/L within 48-hours during hospitalization). Then, we used eGFR on admission independently of renal damage to check whether it can predict mortality. Only 4 groups were used: Group I – normal renal function (eGFR>1.5 ml/s), group II mild renal involvement (eGFR 0.75-1.5), group III - moderate (eGFR 0.5-0.75) and group IV – severe (GFR<0.5). Results: 680 patients were included in our cohort. 244 patients displayed normal renal function, 207 patients fulfilled AKI, and 229 patients suffered from CKD. In total, a significantly higher mortality rate was found in the AKI and the CKD groups vs. normal renal function - 37.2% and 32.3% vs. 9.4%, respectively (P<0.001). In addition, the groups 1-6 divided by severity of renal damage reported mortality as 9.4%, 21.2%, 24.1%, 48.7%, 62.8% and 55.1%, respectively (P<0.001). The mean hospitalization duration of alive patients with normal renal findings was 9.5 days, while 12.1 days in patients with any renal damage (P<0.001). When all patients were compared according to eGFR on admission, the mortality was as follows: Group I (normal) 9.8%, Group II (mild) 22.1%, group III (moderate) 40.9% and group IV (severe) 50.5%, respectively (P<0.001). It was a significantly better mortality predictor than CRP on admission (AUC 0.7053 vs. 0.6053). Conclusions: Mortality in patients with abnormal renal function was 3 times higher compared to patients with normal renal function. Also, patients with renal damage had a worse and longer hospitalization course. Lastly, eGFR on admission, independently of any renal damage, was an excellent tool for predicting mortality. Further, the change in s-Cr levels during hospitalization reflected the mortality prognosis.

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Disturbances of iron metabolism are observed in chronic liver diseases. In the present study, we examined gene expression of duodenal iron transport molecules and hepcidin in patients with hereditary hemochromatosis (HHC) (treated and untreated), involving various genotypes (genotypes which represent risk for HHC were examined), and in patients with iron deficiency anaemia (IDA). Gene expressions of DMT1, ferroportin, Dcytb, hephaestin, HFE and TFR1 were measured in duodenal biopsies using real-time PCR and Western blot. Serum hepcidin levels were measured using ELISA. DMT1, ferroportin and TFR1 mRNA levels were significantly increased in post-phlebotomized hemochromatics relative to controls. mRNAs of all tested molecules were significantly increased in patients with IDA compared to controls. The protein expression of ferroportin was increased in both groups of patients but not significantly. Spearman rank correlations showed that DMT1 versus ferroportin, Dcytb versus hephaestin and DMT1 versus TFR1 mRNAs were positively correlated regardless of the underlying cause, similarly to protein levels of ferroportin versus Dcytb and ferroportin versus hephaestin. Serum ferritin was negatively correlated with DMT1 mRNA in investigated groups of patients, except for HHC group. A decrease of serum hepcidin was observed in IDA patients, but this was not statistically significant. Our data showed that although untreated HHC patients do not have increased mRNA levels of iron transport molecules when compared to normal subjects, the expression is relatively increased in relation to body iron stores. On the other hand, post-phlebotomized HHC patients had increased DMT1 and ferroportin mRNA levels possibly due to stimulated erythropoiesis after phlebotomy.