Liver Oxidative Status, Serum Lipids Levels after Bariatric Surgery and High-Fat, High-Sugar Diet in Animal Model of Induced Obesity.

Nutritional status is a major determinant of hepatocyte injuries associated with changed metabolism and oxidative stress. This study aimed to determine the relations between oxidative stress, bariatric surgery, and a high-fat/high-sugar (HFS) diet in a diet-induced obesity rat model. Male rats were maintained on a control diet (CD) or high-fat/high-sugar diet (HFS) inducing obesity. After 8 weeks, the animals underwent SHAM (n = 14) or DJOS (n = 14) surgery and the diet was either changed or unchanged. Eight weeks after the surgeries, the activity of superoxide dismutase isoforms (total SOD, MnSOD, and CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and lutathione S-transferase, as well as the thiol groups (-SH) concentration, total antioxidant capacity (TAC), total oxidative stress (TOS) levels, and malondialdehyde (MDA) concentration liver tissue were assessed. The total cholesterol, triglycerides (TG), and high-density lipoprotein (HDL) concentrations were measured in the serum. The total SOD and GPX activities were higher in the SHAM-operated rats than in the DJOS-operated rats. The MnSOD activity was higher in the HFS/HFS than the CD/CD groups. Higher CuZnSOD, GST, GR activities, -SH, and MDA concentrations in the liver, and the triglyceride and cholesterol concentrations in the serum were observed in the SHAM-operated rats than in the DJOS-operated rats. The CAT activity was significantly higher in the HFS-fed rats. Lower TAC and higher TOS values were observed in the SHAM-operated rats. Unhealthy habits after bariatric surgery may be responsible for treatment failure and establishing an obesity condition with increased oxidative stress.

The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

A 21-Day Individual Rehabilitation Exercise Training Program Changes Irisin, Chemerin, and BDNF Levels in Patients after Hip or Knee Replacement Surgery.

Osteoarthritis (OA) is the most frequent worldwide cause of adult population disabilities. The study evaluated the effects of a 21-day individual rehabilitation exercise training program focused on improving patients' functional capacity. The study analyzed the changes in irisin, chemerin, and BDNF serum levels in 36 OA patients subjected to an individually-adjusted rehabilitation program 90 days after surgical hip or knee replacement. The changes in irisin, chemerin, and BDNF serum levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. A 21-day individual rehabilitation exercise training program significantly increased irisin and BDNF, and decreased chemerin serum levels. The presented study indicates that individually-adjusted exercise training is an important modulator influencing serum levels of anti- and pro-inflammatory factors, leading to positive clinical outcomes in osteoarthritis therapy. Selected factors are considered potential markers of various pathophysiological conditions. The presented study brings new details to the discussion.

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection.

Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to evaluate the sequence of inflammatory responses in the acute COVID-19 phase throughout onset and resolution of inflammation. We evaluated changes in selected biomarkers in COVID-19 survivors on the 7-day and 28-day follow up. Chemerin was lower in patients with baseline moderate/severe disease at day 7 compared with asymptomatic patients and individuals with mild illness (7265 [5526−9448] vs. 8730 [6888−11,058] pg/mL; p = 0.03). Only in patients with moderate/severe disease, but not in those with mild symptoms, were chemerin concentrations decreased one week after infection onset compared with baseline (7265 [5526−9448] vs. 8866 [6383−10,690] pg/mL; p < 0.05) with a subsequent increase on the 28-day follow up (9313 [7353−11,033] pg/mL; p < 0.05). Resolution of inflammation in the group of moderate/severe SARS-CoV2 infection was associated with increasing serum concentrations of chemerin, contrary to pro-inflammatory cytokines and adipokines (pentraxin 3, TNFα, resistin, leptin). A similar pattern of angiopoietin-2 dynamics may suggest signs of enhanced vascularization as a consequence of acute SARS-CoV2 infection.

Hepatocellular cancer cell lines, Hep-3B and Hep-G2 display the pleiotropic response to resveratrol and berberine.

PURPOSE: Human carcinoma cells with different p53 status exposed to a combination of bioactive substances, resveratrol and berberine, revealed different responses in cell viability via p53-dependant apoptosis pathway activation. MATERIALS AND METHODS: Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we investigated various and opposing effects in hepatocellular carcinoma cells, Hep-G2 and Hep-3B with different p53-status. RESULTS: Cells decreased in viability after treatment with dose-dependent concentrations of resveratrol and berberine. Hep-3B p53 mutants were more sensitive in comparison to the p53 wild type Hep-G2 cell line. A synergistic effect was observed after treatment of Hep-3B cells with a combination of resveratrol/berberine ratios in favor of resveratrol (2:1, 3:1). The results suggest that an effective concentration of berberine, in the presence of resveratrol, could be decreased even to 50% (half the IC50 for berberine) in cancer treatment. Combined treatment with berberine and resveratrol, at the investigated concentrations and fractions, significantly reduces the viability of wild type p53 Hep-G2 and null p53-mutant Hep-3B cells by 20% and 40%, respectively. CONCLUSIONS: Stronger toxic effects on viability and proliferation were observed in Hep-3B cells what is consistent with the assumptions that null p53-mutants activate apoptosis canonical pathway. In conclusion, p53 status in human hepatocellular cancer cell lines modulates responses to plant-derived therapies.

Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022.

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.

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.

Predictive Role of Admission Venous Lactate Level in Patients with Upper Gastrointestinal Bleeding: A Prospective Observational Study.

Upper gastrointestinal bleeding (UGIB) is one of the most common emergencies. Risk stratification is essential in patients with this potentially life-threatening condition. The aim of this prospective study was to evaluate the usefulness of the admission venous lactate level in predicting clinical outcomes in patients with UGIB. All consecutive adult patients hospitalized due to UGIB were included in the study. The clinical data included the demographic characteristics of the observed population, etiology of UGIB, need for surgical intervention and intensive care, bleeding recurrence, and mortality rates. Venous lactate was measured in all patients on admission. Logistic regression analyses were used to calculate the odds ratios (OR) of lactate levels for all outcomes. The receiver operating characteristic (ROC) curve was used to determine the accuracy of lactate levels in measuring clinical outcomes, while Youden index was used to calculate the best cut-off points. A total of 221 patients were included in the study (151M; 70F). There were 24 cases of UGIB recurrence (10.8%), 19 patients (8.6%) required surgery, and 37 individuals (16.7%) required intensive care. Mortality rate was 11.3% (25 cases). The logistic regression analysis showed statistically significant association between admission venous lactate and all clinical outcomes: mortality (OR = 1.39, 95%CI: 1.22-1.58, p < 0.001), recurrence of bleeding (OR = 1.16, 95%CI: 1.06; 1.28, p = 0.002), surgical intervention (OR = 1.17, 95%CI: 1.06-1.3, p = 0.002) and intensive care (OR = 1.33, 95%CI: 1.19-1.5, p < 0.001). The ROC curve analysis showed a high predictive value of lactate levels for all outcomes, especially mortality: cut-off point 4.3 (AUC = 0.82, 95%CI: 0.72-0.92, p < 0.001) and intensive care: cut-off point 4.2 (AUC = 0.76, 95%CI: 0.66-0.85, p < 0.001). Admission venous lactate level may be a useful predictive factor of clinical outcomes in patients with UGIB.

Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.

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.

Anti-inflammatory adipokines: chemerin, vaspin, omentin concentrations and SARS-CoV-2 outcomes.

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.

Fetuin-A Deficiency but Not Pentraxin 3, FGF-21, or Irisin, Predisposes to More Serious COVID-19 Course.

Analysis of liver biopsy specimens showed that SARS-CoV-2 might have led to liver damage. This study aimed to evaluate the role of selected hepatokines and myokines in the development and progression of COVID-19. Seventy patients with laboratory-confirmed COVID-19 and 20 healthy volunteers were enrolled in the study. Irisin, pentraxin 3, fetuin-A, and FGF-21 serum concentrations and biochemical parameters were assessed using an immunoenzymatic method with commercially available enzyme immunoassay (EIA) or enzyme-linked immunosorbent assay (ELISA) kits. Serum fetuin-A concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers. The serum concentration of FGF-21 was significantly increased in obese COVID-19 patients compared to overweight ones. Moreover, the FGF-21 level was higher in COVID-19 patients diagnosed with metabolic syndrome than in patients without metabolic syndrome. PTX3 concentration was higher in COVID-19 patients with higher HOMA-IR values than those with lower HOMA-IR values. COVID-19 patients with HOMA-IR ≤ 3 and >3 had significantly lower fetuin-A levels than the control group. Irisin concentration was significantly decreased in the HOMA-IR ≤ 3 COVID-19 subgroup when comparing with the control group. Lower levels of fetuin-A observed in COVID-19 patients despite higher HOMA-IR, CRP, and ferritin levels, pneumonia, patients requiring ICU care suggests that fetuin-A deficiency predisposes to more severe COVID-19 course. Upregulated pentraxin 3 may be used as a potential predictor of COVID-19 severity.

FibroScan-AST Score Predicts 30-Day Mortality or Need for Mechanical Ventilation among Patients Hospitalized with COVID-19.

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.

Association of non-alcoholic fatty liver disease with coronary artery calcification progression: a systematic review and meta-analysis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, which is estimated to affect 20-30% of the adult population in Europe. Several studies have shown an association of NAFLD with multiple cardiovascular risk factors such as abdominal obesity, atherogenic dyslipidaemia, hypertension, insulin resistance, and impaired glucose tolerance. Atherosclerosis is a chronic, progressive, inflammatory disease, which begins early in life and follows a long asymptomatic phase. Coronary artery calcification (CAC) is the radiological confirmation of the presence of atherosclerotic coronary artery disease. The predictive value of CAC for future cardiac events is well established. Also, the progression of CAC is strongly associated with the development of cardiovascular events. AIM: To assess the association of NAFLD with the progression of subclinical atherosclerotic activity, reflected as the dynamic changes in CAC score over time. MATERIAL AND METHODS: The databases PubMed/Medline/Embase from inception until 31 December 2020 were searched for observational studies investigating NAFLD and CAC progression in adults. RESULTS: In total, 5 studies were included, 4 of which, including 10,060 patients, provided data regarding the association of NAFLD with the progression of CAC. The analysis showed that NAFLD is associated with significant odds of progression of CAC; OR = 1.5, 95% CI: 1.34-1.68, p = 0.001. No publication bias was detected (Egger's test p = 0.6). Meta-regression analyses proved that OR toward CAC progression is not significantly influenced by the time of follow-up (coefficient = 0.0083, Z = 1.14, p = 0.25). CONCLUSIONS: NAFLD increases the risk toward CAC progression over time.

Diagnostic Significance of Serum Galectin-3 in Hospitalized Patients with COVID-19-A Preliminary Study.

Severe coronavirus disease 2019 (COVID-19) is associated with hyperinflammation leading to organ injury, including respiratory failure. Galectin-3 was implicated in innate immunological response to infections and in chronic fibrosis. The aim of our preliminary study was the assessment of the diagnostic utility of serum galectin-3 in patients with COVID-19. The prospective observational study included adult patients admitted with active COVID-19 and treated in tertiary hospital between June and July 2020. The diagnosis was confirmed by the quantitative detection of nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. Galectin-3 was measured by enzyme immunoassay in serum samples obtained during the first five days of hospital stay. We included 70 patients aged 25 to 73 years; 90% had at least one comorbidity. During the hospital stay, 32.9% were diagnosed with COVID-19 pneumonia and 12.9% required treatment in the intensive care unit (ICU). Serum galectin-3 was significantly increased in patients who developed pneumonia, particularly those who required ICU admission. Positive correlations were found between galectin-3 and inflammatory markers (interleukin-6, C-reactive protein, ferritin, pentraxin-3), a marker of endothelial injury (soluble fms-like tyrosine kinase-1), and a range of tissue injury markers. Serum galectin-3 enabled the diagnosis of pneumonia with moderate diagnostic accuracy and the need for ICU treatment with high diagnostic accuracy. Our findings strengthen the hypothesis that galectin-3 may be involved in severe COVID-19. Further studies are planned to confirm the preliminary results and to verify possible associations of galectin-3 with long-term consequences of COVID-19, including pulmonary fibrosis.

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. MATERIAL AND METHODS: The study covered 472 girls (age: 11-19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = -0.46; p < 0.0001) and BMI (r = -0.67; p < 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p < 0.0001, respectively). CONCLUSIONS: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Frailty in Nonalcoholic Fatty Liver Cirrhosis: A Comparison with Alcoholic Cirrhosis, Risk Patterns, and Impact on Prognosis.

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.

Influence of ursodeoxycholic acid therapy on levels of fibroblast growth factor 21, adiponectin and biochemical parameters in intrahepatic cholestasis of pregnancy.

The aim was to assess whether fibroblast growth factor 21 (FGF-21) and adiponectin influence intrahepatic cholestasis of pregnancy (ICP) pathogenesis and whether ursodeoxycholic acid (UDCA) has an impact on their levels. 50 pregnant women with ICP (ICP PW), 50 with uncomplicated pregnancy (HPW) and 50 healthy nonpregnant women (HW) were included. In ICP PW the first blood sample was drawn at the time of diagnosis, while in HPW it was drawn in the 28th week of pregnancy. The next blood samples were drawn in the 32nd and 36th week of pregnancy and one day after delivery. UDCA was administered when ICP was diagnosed. In ICP PW serum FGF-21 concentration was the lowest at the time of diagnosis with an evident increase after UDCA administration. Serum FGF-21 levels were significantly higher in ICP PW than in HPW from the first to the last measurement. There was a negative association between adiponectin and bile acids (BAs) levels in the later stage of pregnancy in ICP PW. Up-regulated FGF-21 serum levels in ICP patients compared to HPW persisted after delivery, suggesting its role in disease pathophysiology. The negative association between serum adiponectin and BAs of the later stage of pregnancy may suggest its role in regulation of BAs concentration. UDCA exerts a beneficial effect on insulin sensitivity and up-regulates FGF-21 in ICP.

Effect of Ileal Transposition (IT) on Angiopoietin-Like Protein-8 (ANGPTL8) and Pentraxin (PTX3) Plasma Level in Sprague-Dawley Rats Fed High-Fat Diet (HFD).

BACKGROUND: Metabolic surgery procedures are designed not only for sustained weight loss but also for achieving positive metabolic changes, including improved glucose tolerance and insulin sensitivity, along with an increase in energy expenditure. Based on recent findings, the present study focuses on the relationship between the effects of ileal transposition (IT), high-fat diet (HFD), and selected markers of lipid metabolism and inflammation. METHODS: Forty-eight male rats were divided into two groups: HFD and control diet (CD) fed rats. After eight weeks, animals in each group were randomly assigned to two types of surgery: IT and SHAM. Thereafter, fifty percent of the animals in the HFD and CD groups had their diets changed, while the remaining half maintained their presurgery diets. Eight weeks after surgery, plasma levels of ANGPTL8, PTX3, leptin, and adiponectin were assessed. RESULTS: The IT group pre- and postoperatively maintained on the HFD showed higher ANGPTL8 level compared to SHAM operated animals (p=0.0041). The effect of IT on PTX3 level in the group pre- and postoperatively maintained on a CD was not significant, and there were no differences compared to SHAM. Only the postoperative diet change to HFD increased PTX3 level in the IT operated animals (p=0.0002). The IT group had increased plasma adiponectin (p=0.026) and leptin (p=0.0027) levels after dietary change to HFD compared to IT rats fed CD. CONCLUSIONS: This study indicates that the outcomes of metabolic surgery can be greatly modified by HFD. The effects of the IT procedure in this experiment are ambiguous and do not provide a clear answer as to whether or not they are beneficial.