Metabolic liver function is significantly decreased in patients with advanced chronic heart failure (CHF). The purpose of the study was to evaluate correlation of NT-proBNP with metabolic liver ...function as assessed with
13C-methacetin breath test in patients with acute decompensation of chronic heart failure (ADHF). NT-proBNP,
13C-methacetin breath test and investigation of other biochemical parameters were realized on days 0–2 (V1) and 2–7 (V2) after hospital admission in 13 consecutive ADHF patients. NT-proBNP and metabolic liver function as assessed with
13C-methacetin breath test didn't change in the first days after hospital admission in ADHF patients. Correlation of NT-proBNP with the degree of metabolic liver function impairement was not significant. The study revealed significant correlation of NT-proBNP with serum ceruloplasmin and significant inverse correlation of liver function with total iron binding capacity in patients with ADHF. The results of this pilot study should be confirmed in a study with larger patient population.
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.
Abstract
Introduction: The main objective of this study was to identify the best combination of admission day parameters for predicting COVID-19 mortality in hospitalized patients. Furthermore, we ...sought to compare the predictive capacity of pulmonary parameters to that of renal parameters for mortality from COVID-19. Methods: In this retrospective study, all patients admitted to a tertiary hospital between September 1st, 2020, and December 31st, 2020, who were clinically symptomatic and tested positive for COVID-19, were included. We gathered extensive data on patient admissions, including laboratory results, comorbidities, chest X-ray (CXR) images, and SpO2 levels, to determine their role in predicting mortality. Experienced radiologists evaluated the CXR images and assigned a score from 0 to 18 based on the severity of COVID-19 pneumonia. Further, we categorized patients into two independent groups based on their renal function using the RIFLE and KDIGO criteria to define the acute kidney injury (AKI) and chronic kidney disease (CKD) groups. The first group (“AKI&CKD”) was subdivided into six subgroups: normal renal function (A); CKD grade 2+3a (B); AKI-DROP (C); CKD grade 3b (D); AKI-RISE (E); and grade 4 + 5 CKD (F). The second group was based only on estimated glomerular filtration rate (eGFR) at the admission, and thus it was divided into four grades: grade 1, grade 2+3a, grade 3b, and grade 4 + 5. Results: The cohort comprised 619 patients. Patients who died during hospitalization had a significantly higher mean radiological score compared to those who survived, with a p value <0.01. Moreover, we observed that the risk for mortality was significantly increased as renal function deteriorated, as evidenced by the AKI&CKD and eGFR groups (p < 0.001 for each group). Regarding mortality prediction, the area under the curve (AUC) for renal parameters (AKI&CKD group, eGFR group, and age) was found to be superior to that of pulmonary parameters (age, radiological score, SpO2, CRP, and D-dimer) with an AUC of 0.8068 versus 0.7667. However, when renal and pulmonary parameters were combined, the AUC increased to 0.8813. Optimal parameter combinations for predicting mortality from COVID-19 were identified for three medical settings: Emergency Medical Service (EMS), the Emergency Department, and the Internal Medicine Floor. The AUC for these settings was 0.7874, 0.8614, and 0.8813, respectively. Conclusions: Our study demonstrated that selected renal parameters are superior to pulmonary parameters in predicting COVID-19 mortality for patients requiring hospitalization. When combining both renal and pulmonary factors, the predictive ability of mortality significantly improved. Additionally, we identified the optimal combination of factors for mortality prediction in three distinct settings: EMS, Emergency Department, and Internal Medicine Floor.
The aim of the study was to identify the prevalence of
HFE
gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of
HFE
gene ...mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of
HFE
gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of
HFE
gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of
HFE
mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but
HFE
mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.
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.
The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene ...mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.
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 4-month period (September 1 to December 31, 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 grades 2 + 3a), group 3 (AKI-DROP defined as whose s-Cr level 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 level was elevated by ≥50% within 7 days or by ≥26.5 μmol/L within 48 h 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: A total of 680 patients were included in our cohort; among them, 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 versus normal renal function – 37.2% and 32.3% versus 9.4%, respectively (p < 0.001). In addition, the groups 1–6 divided by severity of renal damage reported mortality of 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 it was 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 renal damage type, was an excellent tool for predicting mortality. Further, the change in s-Cr levels during hospitalization reflected the mortality prognosis.
The non-invasive (13)C-methacetin ((13)C-MBT) breath test has been proposed as a measure of metabolic liver function that improves the diagnostic efficacy of serologic and biochemical tests in ...assessing hepatic functional capacity and liver disease severity, The goal of this study was to establish the clinical utility of this test in quantifying hepatic metabolic function in patients with liver cirrhosis of varying severity and to compare (13)C-MBT measurements with the AST/ALT ratio, APRI score, and other routine liver tests.
Routine liver function tests including serum bilirubin, aspartate aminotransferase activity (AST), alanine aminotransferase (ALT), AST/ALT ratio, the APRI score, the percentage of dose rate (PDR) and cumulative percentage of dose rate (CPDR) of the (13)C-MBT were evaluated in 52 cirrhotic patients of alcohol etiology (Child-Pugh A/B/C 10/28/14) and 37 healthy controls.
The (13)C-MBT differed significantly between healthy controls and cirrhotic patients at all time intervals measured. It also proved the ability to differentiate patients with liver cirrhosis based on severity of hepatic impairment corresponding to the Child-Pugh classification A vs. B vs. C. The ROC curve analysis suggested that the best prediction is provided by time intervals between the 10th - 20th or 10th - 40th minute of PDR.
The (13)C-MBT offers a reliable means for quantification of hepatic metabolic function over the complete range of functional liver impairment. It is non-invasive, easy to perform and completely safe.
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