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.
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.
Nonalcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disease worldwide, associated with epidemics of overweight and resulting metabolic syndrome (MetS). Around 20–30% of ...patients with NAFLD develop progressive liver fibrosis, which is the most important predictor of liver-related and overall morbidity and mortality. In contrast to classical understanding, no significant association has been demonstrated between the inflammatory component of NAFLD, i.e., nonalcoholic steatohepatitis (NASH), and the adverse clinical outcomes. Older age (>50 years) and presence of type 2 diabetes mellitus, in addition to some genetic variants, are most consistently reported indicators of increased risk of having liver fibrosis. However, critical driving force for the progression of fibrosis and risk factors for this have still not been fully elucidated. Apart from the genetic profile, gut dysbiosis, weight gain, worsening of insulin resistance, and worsening of liver steatosis represent candidate factors associated with unfavourable development of liver disease. Cardiovascular events, extrahepatic malignancies, and liver-related deaths are the leading causes of mortality in NAFLD. As patients with advanced fibrosis are under highest risk of adverse clinical outcomes, efforts should be made to recognize individuals under risk and rule out the presence of this stage of fibrosis, preferably by using simple noninvasive tools. This process should start at the primary care level by using validated biochemical tests, followed by direct serum tests for fibrosis or elastography in the remaining patients. Patients with advanced fibrosis should be referred to hepatologists for aggressive lifestyle modification and correction of the components of MetS, and cirrhotic patients should be screened for hepatocellular carcinoma and oesophageal varices.
Background. Physical frailty increases susceptibility to stressors and predicts adverse outcomes of cirrhosis. Data on disease course in different etiologies are scarce, so we aimed to compare the ...prevalence and risk factors of frailty and its impact on prognosis in nonalcoholic fatty liver (NAFLD) and alcoholic (ALD) cirrhosis. Patients and Methods. Cirrhosis registry RH7 operates since 2014 and includes hospitalized patients with decompensated cirrhosis, pre-LT evaluation, or curable hepatocellular carcinoma (HCC). From the RH7, we identified 280 ALD and 105 NAFLD patients with at least 6 months of follow-up. Results. Patients with NAFLD compared with ALD were older and had a higher proportion of females, higher body mass index (BMI) and mid-arm circumference (MAC), lower MELD score, CRP, and lower proportion of refractory ascites. The liver frailty index did not differ, and the prevalence of HCC was higher (17.1 vs. 6.8%, p=0.002). Age, sex, serum albumin, and C-reactive protein (CRP) were independent predictors of frailty. In NAFLD, frailty was also associated with BMI and MAC and in ALD, with the MELD score. The Cox model adjusted for age, sex, MELD, CRP, HCC, and LFI showed that NAFLD patients had higher all-cause mortality (HR = 1.88 95% CI 1.32–2.67, p<0.001) and were more sensitive to the increase in LFI (HR = 1.51, 95% CI 1.05–2.2). Conclusion. Patients with NAFLD cirrhosis had a comparable prevalence of frailty compared to ALD. Although prognostic indices showed less advanced disease, NAFLD patients were more sensitive to frailty, which reflected their higher overall disease burden and led to higher all-cause mortality.
Among adipose-derived factors, adipocytokines play roles as hormones and signaling mediators for apoptotic pathway. Among of them, vaspin, regulates the metabolism of adipose tissue itself as an ...endocrine organ, and stimulates adipocytes to maturation, differentiation, etc. Damaged adipocytes, present in obesity and hepatocellular carcinoma (HCC) respond with over-production of inflammatory cytokines. Such pro-inflammatory stimulation remains under adipokine control. Pro-inflammatory pathways are connected to oxidative stress and apoptosis, reported as co-existing with an elevated level of some adipokines in cancer cell lines. However, some hormones, such as vaspin, reduce apoptosis, have anti-inflammatory and anti-oxidative roles in cancer cell lines.
Hep-3B cells were cytometrically evaluated under vaspin treatment for reactive oxygen species (ROS) and apoptosiss induction. The statistical significant changes to the untreated controls was calculated by T-tests (indicated at value p < 0.05).
Here we studied the production of reactive oxygen and nitrogen species in cells of HCC line Hep-3B after vaspin treatment. A decreased level of nitric oxide and superoxide anion 24 h after vaspin addition at 5 ng/ml was correlated with restricted, to the physiological level, apoptosis. A protective role of vaspin was displayed as enhanced cell viability and proliferation, which could be a poor prognostic in liver cancer.
Apoptosis was suppressed after vaspin treatment, together with low levels of nitric oxide and superoxide anions.
Coffee is one of the most popular beverages worldwide. Coffee contains bioactive compounds that affect the human body such as caffeine, caffeic acid, chlorogenic acids, trigonelline, diterpenes, and ...melanoidins. Some of them have demonstrated potential anticarcinogenic effects in animal models and in human cell cultures, and may play a protective role against colorectal cancer. Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the USA and other countries. Dietary patterns, as well as the consumption of beverages, may reduce the risk of CRC incidence. In this review, we focus on published epidemiological studies concerning the association of coffee consumption and the risk of development of colorectal cancer, and provide a description of selected biologically active compounds in coffee that have been investigated as potential cancer-combating compounds: Caffeine, caffeic acid (CA), chlorogenic acids (CGAs), and kahweol in relation to colorectal cancer progression in in vitro settings. We review the impact of these substances on proliferation, viability, invasiveness, and metastasis, as well as on susceptibility to chemo- and radiotherapy of colorectal cancer cell lines cultured in vitro.
The gut microbiota has recently been recognized as a major environmental factor in the pathophysiology of several human diseases. The anatomical and functional association existing between the gut ...and the liver provides the theoretical basis to assume that the liver is a major target for gut microbes. In the last decades, many studies have reported an altered composition of gut microbiota in patients with chronic liver diseases and liver cirrhosis, suggesting a progressively marked dysbiosis to be related to worsening of the liver disease. Modifications of microbiota result in alteration in providing signals through the intestine and bacterial products, as well as hormones produced in the bowel that affect metabolism at different levels including the liver. There is increasing evidence for a correlation between intestinal microbiota, bacterial translocation and hepatic steatosis. Intestinal microbiota affects nutrient absorption and energy homeostasis. Altered intestinal permeability may favor the passage of bacteria derived compounds into the systemic circulation, causing a systemic inflammatory state, characteristic of the metabolic syndrome. At present, an increasing number of studies indicate a close relationship between dysbiosis, defined as abnormal composition and the amount of intestinal bacteria (gut microbiota), intestinal permeability and some metabolic, inflammatory, degenerative and even psychiatric diseases. Microbiota pharmacological modulation seems to be a promising tool for a new therapeutic approach to non-alcoholic fatty liver disease and in prevention of cirrhosis. The following study aims to briefly discuss the role of microbiota disorder (dysbiosis), and in particular small intestinal bacterial overgrowth (SIBO), in the pathogenesis of nonalcoholic fatty liver disease (NAFLD).
Background: Liver involvement in Coronavirus disease 2019 (COVID-19) has been recognised. We aimed to investigate the correlation of non-invasive surrogates of liver steatosis, fibrosis and ...inflammation using transient elastography (TE) and FibroScan-AST (FAST) score with (a) clinical severity and (b) 30-day composite outcome of mechanical ventilation (MV) or death among patients hospitalized due to COVID-19. Method: Patients with non-critical COVID-19 at admission were included. Liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) were assessed by TE. Clinical severity of COVID-19 was assessed by 4C Mortality Score (4CMS) and need for high-flow nasal cannula (HFNC) oxygen supplementation. Results: 217 patients were included (66.5% males, median age 65 years, 4.6% with history of chronic liver disease). Twenty-four (11.1%) patients met the 30-day composite outcome. Median LSM, CAP and FAST score were 5.2 kPa, 274 dB/m and 0.31, respectively, and neither was associated with clinical severity of COVID-19 at admission. In multivariate analysis FAST > 0.36 (OR 3.19, p = 0.036), 4CMS (OR 1.68, p = 0.002) and HFNC (OR 7.03, p = 0.001) were independent predictors of adverse composite outcome. Conclusion: Whereas LSM and CAP failed to show correlation with COVID-19 severity and outcomes, FAST score was an independent risk factor for 30-day mortality or need for MV.
The novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has been predominantly linked to respiratory distress syndrome, but gastrointestinal symptoms and hepatic ...injury have also been reported. The mechanism of liver injury is poorly understood and may result as a consequence of viral hepatitis, systemic inflammatory response, gut barrier and microbiome alterations, intensive care treatment or drug toxicity. The incidence of hepatopathy among patients with coronavirus disease 2019 (COVID-19) is unclear, but studies have reported liver injury in patients with SARS and Middle East respiratory syndrome (MERS). We aimed to systematically review data on the prevalence of hepatic impairments and their clinical course in SARS and MERS
infections. A systematic literature search (PubMed/Embase/Cinahl/Web of Science) according to preferred reporting items for systematic review and meta-analysis protocols (PRISMA) was conducted from database inception until 17/03/2020 for studies that evaluated the incidence of hepatic abnormalities in SARS CoV-1, SARS CoV-2 and MERS infected patients with reported liver-related parameters. A total of forty-three studies were included. Liver anomalies were predominantly mild to moderately elevated transaminases, hypoalbuminemia and prolongation of prothrombin time. Histopathology varied between non-specific inflammation, mild steatosis, congestion and massive necrosis. More studies to elucidate the mechanism and importance of liver injury on the clinical course and prognosis in patients with novel SARS-CoV-2 infection are warranted.
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