Liver Injury in Patients with COVID-19 without Underlying Liver Disease.

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and-where it is particularly challenging-on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. MATERIAL AND METHODS: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. RESULTS: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. CONCLUSIONS: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values.

Simple demographic characteristics and laboratory findings on admission may predict in-hospital mortality in patients with SARS-CoV-2 infection: development and validation of the covid-19 score.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a major health burden worldwide due to high mortality rates and hospital bed shortages. SARS-CoV-2 infection is associated with several laboratory abnormalities. We aimed to develop and validate a risk score based on simple demographic and laboratory data that could be used on admission in patients with SARS-CoV-2 infection to predict in-hospital mortality. METHODS: Three cohorts of patients from different hospitals were studied consecutively (developing, validation, and prospective cohorts). The following demographic and laboratory data were obtained from medical records: sex, age, hemoglobin, mean corpuscular volume (MCV), platelets, leukocytes, sodium, potassium, creatinine, and C-reactive protein (CRP). For each variable, classification and regression tree analysis were used to establish the cut-off point(s) associated with in-hospital mortality outcome based on data from developing cohort and before they were used for analysis in the validation and prospective cohort. The covid-19 score was calculated as a sum of cut-off points associated with mortality outcome. RESULTS: The developing, validation, and prospective cohorts included 129, 239, and 497 patients, respectively (median age, 71, 67, and 70 years, respectively). The following cut of points associated with in-hospital mortality: age > 56 years, male sex, hemoglobin < 10.55 g/dL, MCV > 92.9 fL, leukocyte count > 9.635 or < 2.64 103/µL, platelet count, < 81.49 or > 315.5 103/µL, CRP > 51.14 mg/dL, creatinine > 1.115 mg/dL, sodium < 134.7 or > 145.4 mEq/L, and potassium < 3.65 or > 6.255 mEq/L. The AUC of the covid-19 score for predicting in-hospital mortality was 0.89 (0.84-0.95), 0.850 (0.75-0.88), and 0.773 (0.731-0.816) in the developing, validation, and prospective cohorts, respectively (P < 0.001The mortality of the prospective cohort stratified on the basis of the covid-19 score was as follows: 0-2 points,4.2%; 3 points, 15%; 4 points, 29%; 5 points, 38.2%; 6 and more points, 60%. CONCLUSION: The covid-19 score based on simple demographic and laboratory parameters may become an easy-to-use, widely accessible, and objective tool for predicting mortality in hospitalized patients with SARS-CoV-2 infection.

Effect of four different forms of high intensity training on BDNF response to Wingate and Graded Exercise Test.

This study examined the effects of a nine-week intervention of four different high-intensity training modalities [high-intensity functional training (HIFT), high-intensity interval training (HIIT), high-intensity power training (HIPT), and high-intensity endurance training (HIET)] on the resting concentration of brain-derived neurotropic factor (BDNF). In addition, we evaluated the BDNF responses to Graded Exercise Test (GXT) and Wingate Anaerobic Test (WAnT) in men. Thirty-five healthy individuals with body mass index 25.55 ± 2.35 kg/m2 voluntarily participated in this study and were randomly assigned into four training groups. During nine-weeks they completed three exercise sessions per week for one-hour. BDNF was analyzed before and after a GXT and WAnT in two stages: (stage 0-before training and stage 9-after nine weeks of training). At stage 0, an increase in BDNF concentration was observed in HIFT (33%; p < 0.05), HIPT (36%; p < 0.05) and HIIT (38%; p < 0.05) after GXT. Even though HIET showed an increase in BDNF (10%) this was not statistically significant (p > 0.05). At stage 9, higher BDNF levels after GXT were seen only for the HIFT (30%; p < 0.05) and HIIT (18%; p < 0.05) groups. Reduction in BDNF levels were noted after the WAnT in stage 0 for HIFT (- 47%; p < 0.01), HIPT (- 49%; p < 0.001), HIET (- 18%; p < 0.05)], with no changes in the HIIT group (- 2%). At stage 9, BDNF was also reduced after WAnT, although these changes were lower compared to stage 0. The reduced level of BDNF was noted in the HIFT (- 28%; p < 0.05), and HIPT (- 19%;p < 0.05) groups. Additionally, all groups saw an improvement in VO2max (8%; p < 0.001), while BDNF was also correlated with lactate and minute ventilation and selected WAnT parameters. Our research has shown that resting values of BDNF after nine weeks of different forms of high-intensity training (HIT) have not changed or were reduced. Resting BDNF measured at 3th (before GXT at stage 9) and 6th day after long lasting HITs (before WAnT at stage 9) did not differed (before GXT), but in comparison to the resting value before WAnT at the baseline state, was lower in three groups. It appears that BDNF levels after one bout of exercise is depended on duration time, intensity and type of test/exercise.

Serum concentrations of selected adipokines in virus-related liver cirrhosis and hepatocellular carcinoma.

AIM OF THE STUDY: Hepatotropic viruses cause metabolic disturbances such as insulin resistance and hepatosteatosis. Moreover, metabolic factors, such as insulin resistance, obesity, and type 2 diabetes mellitus, increase the risk for hepatocellular carcinoma (HCC) in patients with virus-related liver cirrhosis. Cytokines secreted by the adipose tissue (adipokines) may be implicated in these metabolic disturbances, but there is little evidence regarding the role of adipokines in virus-related cirrhosis and HCC. Thus, we studied whether serum concentrations of selected adipokines were altered in patients with virus-related liver cirrhosis, including patients with HCC. MATERIAL AND METHODS: We included 43 patients with liver cirrhosis due to chronic hepatitis B or chronic hepatitis C. Of these patients, 36 had HCC and 7 did not have any malignant lesions. In addition to routine clinical and laboratory variables, we analyzed serum concentrations of betatrophin, insulin, vaspin, visfatin, and irisin. RESULTS: Compared with healthy controls, patients with HCC had significantly increased vaspin concentrations and significantly reduced irisin concentrations. Compared with controls, patients with virus-related cirrhosis, with or without HCC, had significantly increased concentrations of insulin and betatrophin. The serum visfatin concentration was non-significantly higher in patients with virus-related cirrhosis than in controls. None of the studied adipokines was a significant predictor of HCC. Serum concentrations of the studied adipokines were not related to cirrhosis severity or HCC stage. CONCLUSIONS: Metabolic parameters, including serum adipokine concentrations, are altered in patients with virus-related liver cirrhosis. Adipokines might be related to the HCC risk in these patients.

Effect of HIIT with Tabata Protocol on Serum Irisin, Physical Performance, and Body Composition in Men.

High-intensity interval training (HIIT) is frequently utilized as a method to reduce body mass. Its intensity of work results in a number of beneficial adaptive changes in a relatively short period of time. Irisin is a myokine and adipokine secreted to the blood during exercise and it takes part in the regulation of energy metabolism. It is a vital issue from the prophylaxis point of view as well as treatment through exercise of different diseases (e.g., obesity, type-2 diabetes). The aim of this study was to evaluate changes in irisin concentration, body composition, and aerobic and anaerobic performance in men after HIIT. Eight weeks of HIIT following the Tabata protocol was applied in the training group (HT) (n = 15), while a sedentary group (SED) (n = 10) did not participate in fitness activities within the same time period. Changes of irisin, body composition, and aerobic and anaerobic performance were evaluated after graded exercise test (GXT) and Wingate anaerobic test (WAnT) before and after eight weeks of training. Training resulted in an increased of blood irisin concentration (by 29.7%) p < 0.05), VO2max increase (PRE: 44.86 ± 5.74 mL·kg-1·min-1; POST: 50.16 ± 5.80 mL kg-1·min-1; p < 0.05), reduction in percent body fat (PRE: 14.44 ± 3.33%; POST: 13.61 ± 3.16%; p < 0.05), and increase of WAnT parameters (p < 0.05) in the HT group. No changes were observed in the SED group. HIIT resulted in beneficial effects in the increase in blood irisin concentration, physical performance, and reduced fat content. The HIIT may indicate an acceleration of base metabolism. This effect can be utilized in the prevention or treatment of obesity.

Accurate prediction of significant liver fibrosis using the Pentra score model in patients with chronic hepatitis C.

INTRODUCTION: Noninvasive methods are increasingly used in the clinical assessment of patients with chronic hepatitis C (CHC). OBJECTIVES: We aimed to develop a predictive model for the evaluation of significant fibrosis in patients with CHC, based on serum biomarkers. We compared the accuracy of our model in detecting significant fibrosis with currently known markers / models of fibrosis (such as the aspartate aminotransferase to platelet ratio index [APRI], the Fibrosis­4 [FIB-4] score, and the Forns index). PATIENTS AND METHODS: A total of 242 patients with CHC not receiving antiviral treatment were divided into 2 groups: training group (n = 150) and validation group (n = 92). Significant fibrosis was defined as F2 or higher on the Meta­analysis of Histological Data in Viral Hepatitis (METAVIR) scale. RESULTS: Multivariable analysis revealed that age (P <0.001), pentraxin 3 (PTX3) levels (P = 0.009), γ­glutamyl transpeptidase (GGT) to platelet count (PLT) ratio (P = 0.08), and hyaluronic acid levels (HA) (P = 0.07) were independent predictors of significant fibrosis. Based on that, we developed a model for predicting significant fibrosis: Pentra score = 0.176 × PTX3 (ng/ml) + 0.522 × HA (ng/ml) + 0.29 × GGT (IU/l) to PLT (×109/l) ratio + 0.14 × age (years) - 3.9346. Then, we compared our model with the biomarkers and models currently used to predict liver fibrosis. The Pentra score yielded the largest area under the receiver operating characteristic curve for predicting significant fibrosis in the training and validation groups (0.894 and 0.867, respectively). It also had the highest diagnostic accuracy in both groups (90.6% and 87.0%, respectively). CONCLUSIONS: Our model for detecting significant fibrosis in patients with CHC using pentraxin 3 and other serum biomarkers compares well with the existing and previously published indices. However, further validation in larger cohorts is needed.

Serum visfatin and vaspin levels in hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is the most common liver cancer, accountable for 90% cases. Visfatin and vaspin are adipocytokines with various suggested functions and proven significant correlations between BMI and percentage of body fat. The aim was to assess visfatin and vaspin serum levels in HCC patients and controls, compare their levels in patients with different cancer etiology and grade assessed according to the Barcelona-Clinic Liver Cancer (BCLC) staging system. The additional aim was to analyze relationship between analyzed adipokines and metabolic abnormalities and liver disfunction severity. The study was performed on 69 cirrhotic patients (54 males/15 females) with HCC, aged 59.0 ± 12.1 years, and with BMI 29.0 ± 4.5 kg/m2 compared to 20 healthy volunteers. Serum visfatin and vaspin concentrations were significantly increased in HCC patients compared to controls (p = 0.01 and p = 0.02, respectively). Serum vaspin was significantly higher in HCC patients with viral compared to those with non-viral etiology (p = 0.02), with more evident increase in chronic hepatitis C patients (CHC). Serum visfatin levels were significantly higher in patients with higher insulin resistance (p = 0.04) and with platelets count > 100 000/mm3 (p<0.001). Patients with BMI >30 kg/m2 had markedly up-regulated vaspin levels (p = 0.04). There was no difference in vaspin and visfatin serum levels with respect to liver dysfunction and BCLC classification. In conclusion, our study revealed serum vaspin and visfatin to be significantly increased in HCC patients independently of cancer etiology compared to controls. Additionally, serum vaspin was elevated in viral disease, especially in CHC. Vaspin up-regulation can be a compensatory mechanism against IR in HCC patients. Serum visfatin and vaspin, although up-regulated, seem not to be associated with cancer grade and cirrhosis severity.

Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C.

Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor-ß 1 (TGF-ß 1), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.

Hepatitis B virus treatment in hepatocellular carcinoma patients prolongs survival and reduces the risk of cancer recurrence.

Chronic hepatitis B virus (HBV) infection and HBV-related liver disease are estimated to affect about 240 million people worldwide. Now that a vaccine is available, the number of new HBV infection cases has plummeted. Yet, there are still regions with very high incidence of HBV. Hepatocellular carcinoma (HCC) is the fourth to six most common malignancy in men and the ninth most common malignancy in women worldwide. 54% of all HCC cases are HBV-associated, making it the most common cause of cancer worldwide. Hepatitis B therapy prevents progression of chronic hepatitis to cirrhosis and HCC development, but even with the best HBV treatment, such patients are still at risk of HCC. Also in patients after transarterial chemoembolization (TACE), liver resection (hepatectomy) or liver transplant, suppression of hepatitis B virus (HBV) improves patient survival. In this paper we present current possibilities of HCC and HBV treatment, which lead to improved survival and quality of life.

Influence of Diabetes on Circulating Apoptotic Microparticles in Patients with Chronic Hepatitis C.

BACKGROUND/AIM: Type 2 diabetes mellitus (DM) frequently occurs in patients with chronic hepatitis C (CHC) and is associated with atherosclerosis, in which circulating microparticles (MPs) play an important role. We asked whether the presence of DM affects endothelial-derived (EMPs) and platelet-derived microparticles (PMPs) levels; and whether MPs levels associate with biomarkers of inflammation and oxidative stress in patients with CHC. MATERIALS AND METHODS: Overall, 136 patients were enrolled in the study, 86 CHC patients (41 with DM with moderate glycemic control), 20 outpatients with DM and 30 controls. Circulating MPs were phenotyped by flow cytometry. RESULTS: When the MPs levels were analyzed individually in CHC patients, there was a positive association of plasma apoptotic MPs with oxidative stress markers. We report a hitherto undescribed relationship between diabetes prevalence and apoptotic MPs-associated inflammation in patients with CHC. CONCLUSION: The presence of apoptotic MPs in the plasma of CHC patients, with increased levels being found in patients with DM and moderate glycemic control was herein demonstrated. The simultaneous monitoring of plasma apoptotic MPs, oxidative stress markers and inflammatory biomarkers can be helpful for the cardiovascular disease control in diabetic patients with CHC.

Nutrition principles and recommendations in different types of hepatic encephalopathy.

Appropriate nutrition - in terms of both quantity and quality - is not only one of the main life processes. A well-balanced diet including sufficient amounts of minerals and vitamins supports proper human development and functioning from fetal development to very advanced old age; it promotes regeneration after intensive exercise and is a key element for successful treatment of most acute and chronic diseases, including liver diseases.

Increased Circulating Advanced Oxidation Protein Products and High-Sensitive Troponin T in Cirrhotic Patients with Chronic Hepatitis C: A Preliminary Report.

AIM: To investigate the relationship between advanced oxidation protein products (AOPPs) and myocardial injury by comparing the selected biomarker for detecting myocardial injury [high-sensitive troponin T (hs-TnT)] in patients with chronic HCV infection. METHODS AND RESULTS: Eighty-eight patients with cirrhosis and 40 healthy control subjects were enrolled in the study. Circulating levels of AOPPs-albumin (the ratio of AOPPs to albumin content), hs-TnT, tumor necrosis factor α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were assessed. Compared with healthy controls, the cirrhotic patients with chronic HCV infection had higher levels of AOPPs-albumin, which were associated with increased hs-TnT. When the presence of ascites was considered, the plasma levels of AOPPs-albumin were higher, as well as TNF-α. AOPPs-albumin positively correlated with hs-TnT level in all cirrhotic patients with chronic HCV infection and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high AOPPs-albumin levels and elevated hs-TnT levels. CONCLUSION: The simultaneous monitoring of plasma AOPPs and hs-TnT can be helpful for the alterations in myocardial function control in cirrhotic patients with chronic HCV infection.

Diagnostic challenges in primary hepatocellular carcinoma: case reports and review of the literature.

Hepatocellular carcinoma is the fifth most common malignancy and the third leading mortality cause worldwide. It typically develops secondarily to liver cirrhosis, due to hepatitis B or C infection, alcohol abuse, metabolic disease, and so forth. According to the American Association for the Study of Liver Diseases (AASLD) guidelines, which constitute diagnostic standards, the diagnosis of primary hepatocellular carcinoma (HCC) should be based on contrast-enhanced imaging. Lesion hyperenhancement should be observed throughout the arterial phase, followed by the washout during the venous phase. The diagnosis can also be based on the histopathological evaluation of liver biopsy specimen. Although the standards are clear, we often see patients with advanced HCC in clinical practice, who cannot be offered any effective treatment. Patients with chronic liver disease, presenting with inconclusive and changeable test results, constitute a separate problem. In such cases the diagnostic process is typically long-term and delayed. In this paper we present three case reports where the diagnosis could not be made promptly and the patients died as a result of a delayed diagnostic process.

Elevated circulating endothelial cell-derived microparticle levels in patients with liver cirrhosis: a preliminary report.

AIM OF THE STUDY: To determine plausible associations between liver cirrhosis and circulating endothelial cell-derived microparticles (EMPs), vascular endothelial growth factor (VEGF) levels and plasma nitric oxide (NO) metabolites. MATERIAL AND METHODS: Sixty patients with cirrhosis and 20 healthy control subjects were enrolled in the study. Circulating EMPs from platelet-poor plasma samples were examined by flow cytometry. These microparticles were categorized into endothelial cell-derived activated MPs (EMP-ac) (CD31+ CD42b- AN-V-) and endothelial cell-derived apoptotic MPs (EMP-ap) (CD31+ CD42b- AN-V+). Plasma VEGF levels were measured by enzyme-linked immunosorbent assay. Plasma NO metabolites (NOx-) levels were determined using a Greiss reaction method. RESULTS: Compared with the healthy control subjects, the patients with cirrhosis showed a significant increase in plasma levels of both phenotypes of EMPs. When the presence of ascites was considered, the plasma levels of EMP-ap were higher (p < 0.01), as well as NOx- (p < 0.05). EMP-ap positively correlated with VEGF level in all cirrhotic patients and this correlation was stronger in decompensated cirrhotic patients. In multivariate logistic regression analysis, the independent factors associated with the presence of ascites were high EMP-ap levels and elevated VEGF levels. CONCLUSIONS: Elevated plasma levels of EMP-ap in addition to high levels of VEGF might be considered as valuable parameters for predicting the occurrence of ascites in cirrhotic patients.

Ischemia-modified albumin (IMA) is increased in patients with chronic hepatitis C infection and related to markers of oxidative stress and inflammation.

Inflammation and oxidative stress have been reported in patients with chronic hepatitis C (CHC) infection, but their influence on ischemia-modified albumin (IMA) levels and diabetes prevalence remains unknown. Sixty-three CHC patients, 28 with diabetes, and 40 healthy controls were enrolled in the study. Circulating levels of oxidative stress markers [Nε-(carboxymethyl)lysine- advanced glycation end products (CML-AGEs) and advanced oxidation protein products-(AOPPs)], pro-inflammatory cytokines (interleukin-6, and tumor necrosis factor α), and high-sensitivity C-reactive protein (hsCRP) were assessed. Compared with the controls, the CHC patients with diabetes showed a significant increase in plasma concentrations of IMA, AOPPs, interleukin-6 and hsCRP (P < 0.05). The values of IMA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were found between hsCRP and presence of diabetes, IMA (both P < 0.01) and AOPP levels (P < 0.05). CML-AGEs did not show any significant correlation with IMA, markers of inflammation and presence of diabetes. In conclusion, we have documented significant elevation in plasma levels of IMA and AOPPs in CHC patients. In addition, circulating IMA was associated with inflammation markers and diabetes prevalence. This observation suggests a relationship between IMA and inflammation in CHC patients with diabetes, which may represent one of the mechanisms involved in the accelerated atherosclerosis in this population.

Picolinic acid in patients with chronic hepatitis C infection: a preliminary report.

Macrophage activation seems to be a feature of chronic liver diseases. Picolinic acid (PA) as a macrophage secondary signal causes the activation of interferon-gamma- (IFN-γ-) prime macrophage and triggers cytokine-driven inflammatory reactions. The rationale for seeking increased PA formation in chronic viral hepatitis is based on the involvement of activated macrophages in chronic viral hepatitis-associated inflammation. The aim of this study was to determine serum PA levels in patients with chronic hepatitis C infection, taking into account the presence of diabetes. We assessed PA and high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation in 51 patients with chronic hepatitis C infection (CHC), both with and without diabetes and 40 controls. Compared with the controls, the patients with CHC showed a significant increase in plasma concentrations of PA and hsCRP (P < 0.01 and P < 0.05, resp.). The values of PA and hsCRP were more elevated in patients with diabetes than without diabetes (both P < 0.01). The positive relationships were between PA and hsCRP levels (P < 0.05) and the presence of diabetes (P < 0.001). We documented that significant elevation in serum PA levels is associated with diabetes prevalence and increased inflammatory response reflected in hsCRP levels in CHC patients.

Oxidative stress level in the testes of mice and rats during nickel intoxication.

The genotioxic and carcinogenic effect of nickel probably results from its capacity to produce reactive oxygen species (ROS) and disturb the redox balance. The aim of the study was to find out if rats lacking spermatic protamine 2 are less susceptible to Ni(II) than mice. Consequently, the levels of malondialdehyde + 4 hydroxynonenal (MDA+4HDA) - markers of lipid peroxidation, as well as the level of reduced glutathione (GSH) were measured within the rat and mouse testes. Our results showed that the levels of lipid peroxidation markers were elevated in testicular homogenates of intoxicated mice without any changes in rats. GSH level was lower in the group of intoxicated mice comparing to the control without statistically significant changes in rats' homogenates. Moreover, the level of GSH in the testes of intoxicated mice was lower than in rats. On the basis of our results, it appears that Ni(II) can initiate oxidative stress in the testes of mice but not of rats and can reduce GSH level. Consequently, the antioxidative defense of the testes is reduced. Ni(II) that causes oxidative stress in the testes may also contribute to infertility.

Advanced oxidation protein products and inflammatory markers in liver cirrhosis: a comparison between alcohol-related and HCV-related cirrhosis.

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.

Elevated advanced oxidation protein products levels in patients with liver cirrhosis.

Serum concentrations of advanced oxidation protein products (AOPPs) and glycation end products (AGEs) were assessed with respect to functional compromise of liver, as determined by the Child-Pugh and MELD scores. Patients with decompensated liver cirrhosis (Child-Pugh B and C) exhibited significantly higher serum concentrations of AOPPs than both patients with compensated liver cirrhosis (Child-Pugh A) and controls. The levels of plasma AGEs in all liver cirrhotic patients were higher when compared with those with the controls and this difference was statistically significant. Plasma total antioxidant status of the patients was significantly lower than that of controls. Significant positive correlations between AOPPs level and the MELD score and between the oxidative stress index and the MELD score were found in all patients with liver cirrhosis. Altered AOPPs levels in decompensated patients may influence the potency of oxidative stress and the progression of liver disease.

[Therapeutic intervention in diseases with advanced glycation end products in their pathogenesis]. / Terapia chorób z udzialem koncowych produktów zaawansowanej glikacji w ich patogenezie.

Nonenzymatic modification of proteins by reducing sugars, a process that is also known as the Maillard reaction, leads to the formation of advanced glycation end products (advanced glycation end-products--AGEs) in vivo. There is a growing body of evidence that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, and are thus involved in the pathogenesis of various diseases such as diabetic vascular complications, neurodegenerative diseases, renal failure, and liver cirrhosis. Therefore, inhibition of AGEs formation may be a promising target for therapeutic intervention in AGEs-related disorders. There is a growing body of evidence that AGEs and their receptor (receptor for advanced glycation endproducts--RAGE) axis are also implicated in the pathogenesis of various diseases. In the former part of this paper, we discuss several types of AGEs inhibitors and their therapeutic implications in diseases. Then we summarize in the latter part of this review recent findings regarding pathophysiological roles in diseases of RAGE and soluble RAGE and discuss their potential usefulness as therapeutic targets.