Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on ...increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.
Portal hypertension (PH) drives the progression of liver cirrhosis to decompensation and death. Hepatic venous pressure gradient (HVPG) measurement is the standard of PH quantification, and HVPG≥10 ...mmHg defines clinically significant PH (CSPH). We performed proteomics-based serum profiling to search for a proteomic signature of CSPH in patients with compensated advanced chronic liver disease (cACLD).
Consecutive patients with histologically confirmed cACLD and results of HVPG measurements were prospectively included. Serum samples were pooled according to the presence/absence of CSPH and analysed by liquid chromatography-mass spectrometry. Gene set enrichment analysis was performed, followed by comprehensive literature review for proteins identified with the most striking difference between the groups.
We included 48 patients (30 with, and 18 without CSPH). Protein CD44, involved in the inflammatory response, vascular endothelial growth factor C (VEGF-C) and lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), both involved in lymphangiogenesis were found solely in the CSPH group. Although identified in both groups, proteins involved in neutrophil extracellular traps (NET) formation, as well as tenascin C, autotaxin and nephronectin which mediate vascular contractility and lymphangiogenesis were more abundant in CSPH.
We propose that altered inflammatory response, including NET formation, vascular contractility and formation of new lymph vessels are key steps in PH development. Proteins such as CD44, VEGF-C, LYVE-1, tenascin C, Plasminogen activator inhibitor 1, Nephronectin, Bactericidal permeability-increasing protein, Autotaxin, Myeloperoxidase and a disintegrin and metalloproteinase with thrombospondin motifs-like protein 4 might be considered for further validation as potential therapeutic targets and candidate biomarkers of CSPH in cACLD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The potentially inappropriate medications (PIMs) and drug–drug interactions (DDIs) can significantly affect patient safety in the elderly, especially at transition of health care.
...Objective
The aim of this study is to evaluate PIMs involved in potentially clinically significant DDIs in prescribed pharmacotherapy of elderly patients at hospital discharge.
Setting
Internal Medicine Clinic of University Hospital Dubrava, Zagreb, Croatia.
Method
During a 16-month period, the pharmacotherapy data were assessed using Lexicomp Online screening software to identify category C (monitor drug therapy), D (consider therapy modification) and X (avoid combination) DDIs. The European Union (EU)(7)-PIM criteria were applied to detect inappropriately prescribed medications involved in DDIs. Clinical pharmacists obtained data from patients’ medical records and patient/caregiver interviews.
Main outcome measure
The incidence of PIMs involved in potentially clinically significant DDIs.
Results
A total of 364 consecutive elderly patients were enrolled in the study. The mean number of prescription medications at discharge was 9.3. Overall, 2833 potentially clinically significant DDIs were identified: 2445 (86.3%) of them were category C, 347 (12.3%) category D and 41 (1.4%) were category X interactions. A total of 1164 PIMs were involved in 31.2% of category C interactions, 60.2% of category D interactions and 43.9% of category X interactions. The most frequent PIMs involved in potentially clinically significant DDIs were tramadol, benzodiazepines, moxonidine, vildagliptin and metoclopramide.
Conclusion
A very high incidence of DDIs in elderly patients and a high incidence of PIMs involved in DDIs was determined at hospital discharge.
To compare and evaluate the hepatoprotective effect of remote ischemic preconditioning (RIPC) with local ischemic preconditioning (LIPC) of the liver during human liver resections.
A prospective, ...single-centre, randomised control trial was conducted in the Clinical Hospital “***” from April 2017 to January 2018. A total of 60 patients, who underwent liver resection due to colorectal cancer liver metastasis, were randomised to one of three study arms: 1) a RIPC group, 2) an LIPC group and 3) a control group (CG) in which no ischemic preconditioning was done before liver resection. The hepatoprotective effect was evaluated by comparing serum transaminase levels, bilirubin levels, albumin, and protein levels, coagulograms and through pathohistological analysis. The trial was registered on ClinicalTrials.gov (NCT***).
Significant differences were found in serum levels of liver transaminases and bilirubin levels between thegroups, the highest level in the CG and the lowest level in the LIPC group. Levels of cholinesterase were also significantly higher in the LIPC group. Pathohistological findings graded by the Rodriguez score showed favourable changes in the LIPC and RIPC groups versus the CG.
Strong evidence supports the hepatoprotective effect of RIPC and LIPC preconditioning from an ischemia-reperfusion injury of the liver. Better synthetic liver function preservation in these two groups supports this conclusion.
•Ischemia-reperfusion injury.•Remote ischemic preconditioning.•Local ischemic preconditioning.•Liver resection.
Abstract
Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to ...assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml;
p
< 0.001 and 482.1 vs. 814.3 ng/ml;
p
= 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity.
Liver cirrhosis is an increasing public health problem and a major cause of morbidity and mortality. Accordingly, cirrhotic cardiomyopathy, a frequently underdiagnosed condition, is becoming a ...growing health problem. In the last 20 years, cardioselective biomarkers have been investigated for their diagnostic and prognostic properties for numerous conditions. The aim of this article is to review the literature on the relationship between the most commonly used cardioselective biomarkers (cardiac troponins I and T, N-terminal pro-B-type natriuretic peptide, brain natriuretic peptide, and heart-type fatty-acid binding protein) and the presence, functional stage, and clinical outcomes of liver cirrhosis. Elevated plasma levels of these biomarkers have been reported in patients with liver cirrhosis, and there is mounting evidence on their predictive value for clinical outcomes in this disease. In addition, elevated plasma levels of these biomarkers have been reported in patients before, during, and after liver transplantation, but in fewer studies. Due to their predictive value for clinical outcomes, we advocate the use of these markers in patients with liver cirrhosis and cirrhotic cardiomyopathy, as well as in candidates for liver transplant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver morbidity worldwide and, as such, represents the pathogenic background for the increasing incidence of hepatocellular ...carcinoma (HCC). The annual incidence of NAFLD-related HCC is expected to increase by 45-130% by 2030. Diabetes mellitus is the most important risk factor for HCC development in NAFLD, with the risk further increased when associated with other metabolic traits, such as obesity, arterial hypertension and dyslipidemia. The highest risk of HCC exists in patients with advanced fibrosis or cirrhosis, although 20-50% of HCC cases arise in NAFLD patients with an absence of cirrhosis. This calls for further investigation of the pathogenic mechanisms that are involved in hepatocarcinogenesis, including genetics, metabolomics, the influence of the gut microbiota and immunological responses. Early identification of patients with or at risk of NAFLD is of utmost importance to improve outcomes. As NAFLD is highly prevalent in the community, the identification of cases should rely upon simple demographic and clinical characteristics. Once identified, these patients should then be evaluated for the presence of advanced fibrosis or cirrhosis and subsequently enter HCC surveillance programs if appropriate. A significant problem is the early recognition of non-cirrhotic NAFLD patients who will develop HCC, where new biomarkers and scores are potential solutions to tackle this issue.
Prediction of short-term mortality in patients with acute decompensation of liver cirrhosis could be improved. We aimed to develop and validate two machine learning (ML) models for predicting 28-day ...and 90-day mortality in patients hospitalized with acute decompensated liver cirrhosis. We trained two artificial neural network (ANN)-based ML models using a training sample of 165 out of 290 (56.9%) patients, and then tested their predictive performance against Model of End-stage Liver Disease-Sodium (MELD-Na) and MELD 3.0 scores using a different validation sample of 125 out of 290 (43.1%) patients. The area under the ROC curve (AUC) for predicting 28-day mortality for the ML model was 0.811 (95%CI: 0.714- 0.907;
< 0.001), while the AUC for the MELD-Na score was 0.577 (95%CI: 0.435-0.720;
= 0.226) and for MELD 3.0 was 0.600 (95%CI: 0.462-0.739;
= 0.117). The area under the ROC curve (AUC) for predicting 90-day mortality for the ML model was 0.839 (95%CI: 0.776- 0.884;
< 0.001), while the AUC for the MELD-Na score was 0.682 (95%CI: 0.575-0.790;
= 0.002) and for MELD 3.0 was 0.703 (95%CI: 0.590-0.816;
< 0.001). Our study demonstrates that ML-based models for predicting short-term mortality in patients with acute decompensation of liver cirrhosis perform significantly better than MELD-Na and MELD 3.0 scores in a validation cohort.
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