Markers Of Liver Dysfunction Research Articles

Use of bile acids as potential markers of liver dysfunction in humans: A systematic review.

Objective:This study aimed to determine the effectiveness of using total, individual serum, or urinary bile acids (BA) as potential markers of liver dysfunction.Methods:We searched the PubMed and Web of Science databases using the following keywords- “serum bile acids,” “liver dysfunction,” “liver injury,” “liver disease,” “traditional liver function tests,” “Chronic liver disease,” “acute liver injury”. The search was complemented by manual screening of the list of references for relevant articles. We selected only English-language manuscripts for adult patients based on predetermined inclusion and exclusion criteria. Animal studies and studies on neonates and children were not included.Outcome measures:Changes in BA concentrations or ratios at or prior to changes in liver function tests.Results:A total of 547 studies were identified, of which 28 were included after reading the entire manuscript. These studies included 1630 patients and 836 controls published between 1990 and 2017. The methods used in BA assays varied significantly, and the studies did not agree. on specific individual BA or BA ratios as biomarkers of specific liver injury or dysfunction. Except for the prognostic value of BA in intrahepatic cholestasis of pregnancy (ICP), studies have failed to provide evidence for BA as a liver biomarker.Conclusions:Despite the research conducted on BA for over 27 years, there are inconsistencies in the reported results and a lack of solid evidence to support the use of individual BA or BA ratios as biomarkers of liver injury. Adequately conducted studies needed to resolve this limitation in the literature.

Liver Dysfunction Associated With In-Hospital Mortality in Adult Extracorporeal Membrane Oxygenation Support.

OBJECTIVES:Extracorporeal membrane oxygenator support is a powerful clinical tool that is currently enjoying a resurgence in popularity. Wider use of extracorporeal membrane oxygenator support is limited by its significant risk profile and extreme consumption of resources. This study examines the role of markers of liver dysfunction in predicting outcomes of adult patients requiring extracorporeal membrane oxygenator support.DESIGN:Retrospective review.SETTING:Large extracorporeal membrane oxygenator center, Chicago, IL.PATIENTS:This study reports a single institution experience examining all adult patients for whom extracorporeal membrane oxygenator support was used over an 8-year period. Data were collected regarding patient demographics, details of extracorporeal membrane oxygenator support provided, laboratory data, and outcomes. Trends in liver function were examined for their ability to predict survival.INTERVENTION:Extracorporeal membrane oxygenator support, critical care.MEASUREMENTS AND MAIN RESULTS:Mean age was 50 years (range, 19–82 yr). There were 86 male patients (56.6%) and 66 female patients (43.4%). Indications for initiation of extracorporeal membrane oxygenator support included cardiac 76 patients (50.0%), respiratory 48 patients (31.6%), extracorporeal cardiopulmonary resuscitation 21 patients (13.3%), and combined cardiac/respiratory seven patients (4.6%). Mean duration of extracorporeal membrane oxygenator support was 17 days (range 1–223 d) or median 8 days (interquartile range, 4–17 d). Overall, in-hospital mortality was 56% (86/152). Forty-five percent of adult patients (68/152) surpassed at least one of the following established liver dysfunction thresholds: total bilirubin greater than 15 mg/dL, aspartate aminotransferase greater than 20× upper limit of normal, and alanine aminotransferase greater than 20× upper limit of normal. The multivariable logistic analysis yielded three significant findings associated with in-hospital mortality: highest total bilirubin greater than 15 (adjusted odds ratio = 4.40; 95% CI, 1.19–21.87; p = 0.04), age (adjusted odds ratio = 1.03; 95% CI, 1.00–1.05; p = 0.04), and highest lactate (adjusted odds ratio = 1.15; 95% CI, 1.06–1.26; p = 0.002).CONCLUSIONS:Increases in age, highest total bilirubin, and lactate all correlated with in-hospital mortality in multivariable analysis of patients requiring extracorporeal membrane oxygenator support.

Supplementation of cumin seed powder prevents oxidative stress, hyperlipidemia and non-alcoholic fatty liver in high fat diet fed rats

The present investigation was an attempt to evaluate the hypoglycemic, lipid-lowering, antioxidant and hepatoprotective effects of cumin (Cuminum cyminum family: Apiaceae) supplementation in high fat (HF) diet fed rats. Male Wistar rats were divided into four groups, such as control, control+ cumin, HF and HF+ cumin. Oral glucose tolerance test, plasma lipids, oxidative stress parameters, antioxidant enzymes activities, and liver dysfunction marker enzyme activities were evaluated. Additionally, histological staining of liver tissue was performed to evaluate the inflammatory cells infiltration, iron deposition and fibrosis. The current investigation demonstrated that 1% (w/w) supplementation of cumin powder significantly reduced HF diet-induced glucose intolerance, epididymal and mesenteric fat wet weights and lipid parameters like triglycerides, total cholesterol and low-density lipoproteins. Oxidative stress-related biomarkers including thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and advanced oxidation protein product (APOP) were also reduced by cumin supplementation. Moreover, HF-diet increased the activity of hepatic biomarker enzymes such as alanine transaminase (ALT) and alkaline phosphatase (ALP) activities which were significantly reduced by cumin powder supplementation. On the other hand, cumin powder supplementation was able to restore the reduced glutathione level with parallel augmentation of the antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase in liver of HF diet-fed rats. Additionally, histological assessments confirmed that cumin powder supplementation also normalized the fat droplet deposition and inflammatory cells infiltration in the liver of HF diet-fed rats. This study suggests that cumin powder supplementation ameliorates dyslipidemia, oxidative stress and hepatic damage in HF diet-fed rats.

Effect of Mediterranean diet on liver enzymes: a systematic review and meta-analysis of randomised controlled trials.

Elevated levels of liver enzymes are the main markers of liver dysfunction. Liver enzymes are the important indicators of non-alcoholic fatty liver disease (NAFLD) in the general population. Previous randomised clinical trials (RCT) investigated the effects of Mediterranean diet (MedDiet) as a plant-based diet on features of NAFLD like liver enzymes, but their results are contradictory. This study aimed to systematically review and meta-analyse RCT investigating the effect of MedDiet on liver enzymes. PubMed, Web of Science, Scopus and Google Scholar were searched until December 2020. A total of ten RCT (n 705 participants) evaluating the effect of MedDiet on liver enzymes including aspartate aminotransferase (AST), alanine transaminase (ALT) and γ-glutamyltransferase (GGT) were included. A random effects model was used to estimate the pooled effect size. To evaluate the heterogeneity among the included studies, the Cochran's Q-test and I-squared test were used. The MedDiet significantly reduced AST (weighted mean difference (WMD) = -0·38 IU/l; 95 % CI - 0·73, -0·03 IU/l; P = 0·03) and GGT (WMD = -0·16 IU/l; 95 % CI - 0·32, -0·006 IU/l; P = 0·04) but had no significant effect on ALT (WMD = -0·55 IU/l; 95 % CI - 1·25, 0·13 IU/l; P = 0·11). However, sensitivity analysis revealed that the overall effects of MedDiet on AST, GGT and ALT were significantly influenced by removing some studies. There was no publication bias based on Begg's and Egger's tests. Generally, MedDiet can improve liver enzymes. To better conclusion, further RCT investigating the effect of MedDiet on liver enzymes, especially in patients with NAFLD, are still required.

Cross talk of serum elements, cardiac and liver enzymes in patients with HCV chronic hepatitis and hepatocellular carcinoma in Pakistani population

HCV-associated hepatic pathologies are now the frequent inducer of cardiac abnormalities because of cardio-hepatic interaction. Studies are going on to elucidate and highlight the possible factors involved in this complex interaction, but this paradigm is still unclear. Here, we aimed to explore the interrelationship among electrolytes, cardiac, and liver enzymes in HCV-associated hepatic abnormalities, including chronic hepatitis and hepatocellular carcinoma in the Pakistani population. 100 Hepatitis C virus (HCV) infected patients with liver disorders and 50 healthy individuals were recruited in the present analysis. Trace elements, ions, and enzyme concentrations were quantified via an automatic analyzer, while HCV was confirmed by enzyme-linked immunosorbent assay (ELISA). Our results demonstrated that serum Ca++, Mg++, Fe++, Cl-, and PO4- levels were significantly increased in HCV patients with hepatic pathologies, including cirrhosis and carcinoma. Cardiac enzymes, including aspartate aminotransferase (AST), creatine kinase (CK2), and lactate dehydrogenase (LDH) concentration, were also elevated in HCV patients. Furthermore, serum cholesterol and triglyceride levels significantly differed in HCV patients than in normal individuals. Impaired alkaline transaminase (ALT) and alkaline phosphatase levels in HCV patients further validate the HCV patients' hepatic pathologies. Interestingly, all these impaired factors were positively correlated with the progression of hepatic disorders. In conclusion, altered ionic concentrations, cardiac enzymes, and liver dysfunction markers suggest their significant relationship to HCV leading liver pathologies in the Pakistani population.

Maximum Perioperative and Early Postoperative Arterial Lactate Concentrations Predict Post-hepatectomy Liver Failure and Associated Morbidity after Liver Resection

Introduction: Post-hepatectomy liver failure (PHLF) remains a critical complication after liver surgery. In contrast to liver transplantation evidence for lactate as a marker of liver dysfunction after resections is limited. We evaluated perioperative lactate dynamics to predict PHLF and associated morbidity.

Bilirubin Nanoparticles Reduce Diet-Induced Hepatic Steatosis, Improve Fat Utilization, and Increase Plasma β-Hydroxybutyrate.

The inverse relationship of plasma bilirubin levels with liver fat accumulation has prompted the possibility of bilirubin as a therapeutic for non-alcoholic fatty liver disease. Here, we used diet-induced obese mice with non-alcoholic fatty liver disease treated with pegylated bilirubin (bilirubin nanoparticles) or vehicle control to determine the impact on hepatic lipid accumulation. The bilirubin nanoparticles significantly reduced hepatic fat, triglyceride accumulation, de novo lipogenesis, and serum levels of liver dysfunction marker aspartate transaminase and ApoB100 containing very-low-density lipoprotein. The bilirubin nanoparticles improved liver function and activated the hepatic β-oxidation pathway by increasing PPARα and acyl-coenzyme A oxidase 1. The bilirubin nanoparticles also significantly elevated plasma levels of the ketone β-hydroxybutyrate and lowered liver fat accumulation. This study demonstrates that bilirubin nanoparticles induce hepatic fat utilization, raise plasma ketones, and reduce hepatic steatosis, opening new therapeutic avenues for NAFLD.

An experience of using Laennec in patients at high risk of a cytokine storm with COVID-19 and hyperferritinemia

The probability of formation of the so-called “cytokine storm” accompanied by an avalanche-like growth of inflammatory markers – interleukins (IL)-1β, -6, interferon-γ, tumor necrosis factor-α, C-reactive protein (CRP), ferritin, etc. is high at a heavy current of COVID-19. In the absence of adequate treatment in the development of “cytokine storm” increases the risk of death, especially against the background of comorbid pathology. Methods . In April-May 2020, patients ( n = 28: 12 men, 16 women; age 39 – 86 years) with long, chronic COVID-19 course were under observation, hospitalized on critical days of the disease. All patients reported anosmia, cough with poor sputum, signs of conjunctivitis. The patients had chronic diseases ( n = 22: coronary heart disease, diabetes mellitus type 2, scleroderma). All patients were given standard therapy; half ( n = 14) were additionally prescribed Laennec for 3 – 10 days (6 ml per 350 ml of 0.9% NaCl solution, intravenous infusion for the first 3 days, from day 4 – 6 ml per 250 ml of 0.9% NaCl solution) until stable remission is achieved. Results . The majority state ( n = 25) stabilized; several patients died in the control group ( n = 3; p = 0.067). In spite of the state stabilization, no reliable positive dynamics was noted in the control group for the tested parameters. Initially, liver dysfunction (level of alanine aminotransferase (ALT) – 113 ± 121, aspartate aminotransferase (AST) – 90.8 ± 87) was registered in 71% of patients, 8 units/l) and high risk of “cytokine storm” development (ferritin levels in men – 480 – 1 072 µg/l, in women – 274.7 – 493 µg/l, C-reactive protein – 5.0 – 52.6 mg/l, lymphocytes – < 25%). Positive clinical dynamics, a decrease in the level of ferritin (–282 µg/l – in men, –80 µg/l – in women; p = 0.039), an increase in blood oxygenation to normal values ( p = 0.0029), a decrease in the area of lung injury according to CT data (on average – 10%); p = 0.0027), increase in relative lymphocyte content (+8%; p = 0.04), normalization of markers of liver dysfunction (AST, ALT), creatinine and systolic blood pressure ( p < 0.05) were observed on prescription of Laennec. All patients who received Laennec recovered within 3 – 15 days from the start of the drug and were discharged with a negative test for SARS-CoV-2. Conclusion . Health condition is significantly improved, a wide range of hepatoprotective, immunomodulatory and regenerative effects are observed when the polypeptide Laennec is included in the complex therapy in patients with severe COVID-19. Laennec should be used primarily in patients with liver pathology, diabetes mellitus type 2, coronary heart disease, including high ferritin levels.

Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection.

The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography–mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, α-1-acid glycoprotein, glucose, and biogenic amines were made on samples from symptomatic coronavirus disease 19 (COVID-19) patients who had tested positive for the SARS-CoV-2 virus (n = 17) and from age- and gender-matched controls (n = 25). Data were analyzed using an orthogonal-projections to latent structures (OPLS) method and used to construct an exceptionally strong (AUROC = 1) hybrid NMR-MS model that enabled detailed metabolic discrimination between the groups and their biochemical relationships. Key discriminant metabolites included markers of inflammation including elevated α-1-acid glycoprotein and an increased kynurenine/tryptophan ratio. There was also an abnormal lipoprotein, glucose, and amino acid signature consistent with diabetes and coronary artery disease (low total and HDL Apolipoprotein A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus multiple highly significant amino acid markers of liver dysfunction (including the elevated glutamine/glutamate and Fischer’s ratios) that present themselves as part of a distinct SARS-CoV-2 infection pattern. A multivariate training-test set model was validated using independent samples from additional SARS-CoV-2 positive patients and controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2 positivity. The breadth of the disturbed pathways indicates a systemic signature of SARS-CoV-2 positivity that includes elements of liver dysfunction, dyslipidemia, diabetes, and coronary heart disease risk that are consistent with recent reports that COVID-19 is a systemic disease affecting multiple organs and systems. Metabolights study reference: MTBLS2014.

The effectiveness and safety of a polypeptide drug (Laennec) for the treatment of COVID-19

Hyperferritinemia in patients with COVID-19 is associated with liver dysfunction and an increased risk of the “cytokine storm”. The polypeptide preparation Laennec (6 ml per 350 ml of 0.9% NaCl solution, iv, cap. The first 3 days, from 4 days — 6 ml per 250 ml of 0.9% NaCl solution) was used in 14 patients (age 39–86 years old, 6 men, 8 women) with a long, stagnant course of COVID-19 as a hepatoprotector and immunomodulator as part of complex therapy until a stable remission is achieved. Patients in the control group (n = 14) received only standard therapy. The use of Laennec led to positive clinical dynamics: a decrease in ferritin levels (in men by –282 mcg / l, in women by –80 mcg / l, P = 0.039), an increase in blood oxygenation to the normal range (P = 0.0029), and a decrease in the area of damage lung according to CT data (on average, —10%, P = 0.0027), an increase in the relative content of lymphocytes (+ 8%, P = 0.04), normalization of markers of liver dysfunction (AST, ALT), creatinine and systolic blood pressure (P <0.05). All patients treated with Laennec recovered within 3–15 days after the start of the drug and were discharged with a negative test for the SARS-CoV-2 virus.

1444-P: Discordance between Insulin and C-Peptide Is Associated with Liver Function and Ethnicity

Introduction and Hypothesis: Insulin and c-peptide are co-secreted in a 1:1 ratio, but cleared from the blood by different mechanisms. Insulin is cleared by the liver (t1/2 ∼ 4 min), while c-peptide is cleared by the kidney (t1/2∼ 40 min). Thus, differences between steady-state serum insulin and c-peptide may reflect subject-to-subject variation in liver and/or kidney clearance rates. Specific Aim: In lieu of direct measures of clearance, the aim was to examine the association of insulin/c-peptide residuals with markers of liver and kidney function. Associations were analyzed using cross-sectional data from the 1999-2000 U.S. National Health and Nutrition Examination Survey. Methods: The inclusion criterion was age ≥ 12, and the exclusion criteria were diabetes, pregnancy, fasting < 8 h, serum creatinine > 2, or missing insulin or c-peptide values, yielding 2,417 subjects. Insulin residuals were calculated as the difference between observed Ln insulin and the predicted value from the regression line for Ln insulin vs. Ln c-peptide. Results: Insulin residuals were positively correlated with insulin levels (r=0.55, p<0.0001). After adjusting for serum creatinine (kidney function), the association of insulin residuals with other markers was assessed using multiple linear regression. Positive associations were observed with ALT, LDH, CRP and urinary NTx/creatinine, as well as Hispanic ethnicity. Negative associations were observed with age, male gender, white and black race, total serum protein and bilirubin. Conclusion: Insulin residuals, adjusted for creatinine, are associated with markers of liver dysfunction, inflammation, bone resorption and race/ethnicity. The hepatic clearance rate of insulin is known to be affected by some of these factors. Higher insulin residuals presumably reflect slower hepatic insulin clearance, which promotes hyperinsulinemia. Insulin residuals could be a simple surrogate for assessing differences in insulin clearance. Further studies are warranted. Disclosure C. Perkins: None. E. Campbell: None. D.P. Cistola: None. Funding National Institutes of Health (R21HL143030)

FONTAN-ASSOCIATED LIVER DISEASE: IS INSULIN SENSITIVITY IMPORTANT?

Adults with a Fontan palliation are known to have Fontan-associated liver disease (FALD). Traditional markers of liver dysfunction, however, have not correlated with the degree of FALD. Based upon the role of the liver in glucose homeostasis, we sought to determine if insulin sensitivity may be a

Antioxidant status and hepato-protective role of Anchomanes difformis in streptozotocin-induced diabetes in male Wistar rats

Summary Introduction: The liver is involved in the metabolism of xenobiotics and their metabolites and it is vulnerable to oxidative damage. Hyperglycaemia is highly implicated in the progression of diabetes mellitus, and adversely affects the liver. Though, conventional hypoglycaemic drugs may be effective in reducing blood glucose, they do not appear to be effective in attenuating the progression of diabetes and its complications. Objective: This study evaluated the ameliorative effects of Anchomanes difformis on hyperglycaemia and hepatic injuries in type 2 diabetes. Methods: Type 2 diabetes was induced in male Wistar rats with a single intraperitoneal injection of streptozotocin (40 mg/kg BW) after two weeks of fructose (10%) administration. Aqueous extract of A. difformis (200 and 400 mg/kg BW) and glibenclamide (5 mg/kg BW) were administered orally for six weeks. Blood glucose concentrations were measured. Serum levels of liver dysfunction markers (ALT, AST, and ALP), total cholesterol, triglycerides, HDL- and LDL-cholesterol were investigated. Total protein, albumin, and globulin were also assessed. Antioxidant parameters: ORAC, GSH, GSSG, SOD, CAT and FRAP were evaluated in the liver while ORAC, FRAP and lipid peroxidation were determined in the serum. Histological examination of the liver tissue was carried out. Results: Treatment with aqueous extract of A. difformis significantly (p<0.05) reduced blood glucose and reversed steatosis in the diabetic-treated rats. The antioxidant status of diabetic-treated rats was significantly (p<0.05) improved. Serum levels of liver dysfunction markers were significantly (p<0.05) reduced in diabetic-treated rats. Conclusion: The findings in this study revealed that 400 mg/kgBW Anchomanes difformis was more effective than 200 mg/kg BW in ameliorating diabetes-induced hepatopathy, however, both doses of Anchomanes difformis demonstrated more antidiabetic ability than glibenclamide. Anchomanes difformis may be a novel and potential therapeutic agent in the management of diabetes and resulted hepatic injuries.

P-Methoxycinnamic Acid Diesters Lower Dyslipidemia, Liver Oxidative Stress and Toxicity in High-Fat Diet Fed Mice and Human Peripheral Blood Lymphocytes.

The pursuit of cholesterol lowering natural products with less side effects is needed for controlling dyslipidemia and reducing the increasing toll of cardiovascular diseases that are associated with morbidity and mortality worldwide. The present study aimed at the examining effects of p-methoxycinnamic acid diesters (PCO-C) from carnauba (Copernicia prunifera)-derived wax on cytotoxic, genotoxic responses in vitro and on dyslipidemia and liver oxidative stress in vivo, utilizing high-fat diet (HFD) chronically fed Swiss mice. In addition, we evaluated the effect of PCO-C on the expression of key cholesterol metabolism-related genes, as well as the structural interactions between PCO-C and lecithin-cholesterol acyl transferase (LCAT) in silico. Oral treatment with PCO-C was able to reduce total serum cholesterol and low-density lipoprotein (LDL) levels following HFD. In addition, PCO-C reduced excessive weight gain and lipid peroxidation, and increased the gene expression of LCAT following HFD. Furthermore, the high affinity of the studied compound (ΔG: −8.78 Kcal/mol) towards the active sites of mutant LCAT owing to hydrophobic and van der Waals interactions was confirmed using bioinformatics. PCO-C showed no evidence of renal and hepatic toxicity, unlike simvastatin, that elevated aspartate aminotransferase (AST) levels, a marker of liver dysfunction. Finally, PCO-C showed no cytotoxicity or genotoxicity towards human peripheral blood lymphocytes in vitro. Our results suggest that PCO-C exerts hypocholesterolemic effects. The safety of PCO-C in the toxicological tests performed and the reports of its beneficial biological effects render this a promising compound for the development of new cholesterol-lowering therapeutics to control dyslipidemia. More work is needed for further elucidating PCO-C role on lipid metabolism to support future clinical studies.

Clinical and Prognostic Values of ALBI Score in Patients With Acute Heart Failure

Although liver dysfunction is one of the common complications in patients with acute heart failure (AHF), no integrated marker has been defined. The albumin-bilirubin (ALBI) score has recently been proposed as a novel, clinically-applicable scoring system for liver dysfunction. We investigated the utility of the ALBI score in patients with AHF compared to that for a preexisting liver dysfunction score, the Model of End-Stage Liver Disease Excluding prothrombin time (MELD XI) score. We evaluated ALBI and MELD XI scores in 1,190 AHF patients enrolled in the prospective, multicentre Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure study. The associations between the two scores and the clinical profile and prognostic predictive ability for 1-year mortality were evaluated. The mean MELD XI and ALBI scores were 13.4±4.8 and -2.25±0.48, respectively. A higher ALBI score, but not higher MELD XI score, was associated with findings of fluid overload. After adjusting for pre-existing prognostic factors, the ALBI score (HR 2.11, 95% CI: 1.60-2.79, p<0.001), but not the MELD XI score (HR1.02, 95% CI: 0.99-1.06, p=0.242), was associated with 1-year mortality. Likewise, area under the receiver-operator-characteristic curves for 1-year mortality significantly increased when the ALBI score (0.71 vs. 0.74, p=0.020), but not the MELD XI score (0.71 vs. 0.72, p=0.448), was added to the pre-existing risk factors. The ALBI score is potentially a suitable liver dysfunction marker that incorporates information on fluid overload and prognosis in patients with AHF. These results provide new insights into heart-liver interactions in AHF patients.

Investigation of Hematological and Biochemical Profiles of Tannery Workers Exposed to Chromium in Hazaribagh, Bangladesh

Occupational exposure to chromium used in mineral tanning processes cause adverse health effects on workers of leather tanning industries. This study aimed to evaluate the hematological and biochemical profiles in tannery workers of Hazaribagh, Bangladesh compared with a control group. A total of 225 participants, 121 tannery workers and 104 controls, were enrolled. All subjects completed interviewer-administered questionnaires; their physical health was examined, blood samples were collected and the hematological and biochemical parameters were analyzed. The tannery workers had mean duration of work exposure at tanneries for 13.1±9.7 years, and working hours per day of 10.7±2.3 which were significantly higher than 7.6±2.2 of the controls. Previous results showed long-term exposed tannery workers had significantly higher serum chromium concentrations than controls. The tanners had dermatological problems, infections on body surfaces, and respiratory ailments, among other complaints. The red blood cell count, hematocrit (48.91 %) and mean corpuscular hemoglobin concentration (29.39 g/dL) were lower in tannery workers but hemoglobin (14.58±1.30 g/dL) was significantly lower than in the controls (15.96±0.88 g/dL). The tanners had significantly lower neutrophil (51.31 %), higher lymphocyte (41.82 %), monocyte (2.44 %) and eosinophil (4.17 %) counts. Their mean creatinine and alkaline phosphatase values were normal but markers of liver damage, alanine transaminase (42.7±39.3 U/L) and aspartate transaminase (44.3±20.5 U/L), and liver dysfunction marker - bilirubin (1.04±0.85 mg/dL) levels were significantly higher. These findings suggest that exposure to chromium poses serious threats to the health of tannery workers who are at risk of toxicity related liver damage and hematological disorders.

Neurocognitive impairment is worse in HIV/HCV-coinfected individuals with liver dysfunction.

Infections with HIV and hepatitis C virus (HCV) can individually and jointly contribute to neurocognitive impairment (NCI). Rates of NCI in HIV/HCV-coinfected persons range from 40 to 63% but its correlates have not been described. In this study, we examined HIV/HCV-coinfected adults on antiretroviral therapy (ART) with undetectable HIV RNA in blood (n = 412) who were assessed using a comprehensive neuropsychological test battery. Demographics, host and viral biomarkers, and markers of liver dysfunction were compared between impaired (n = 198) and unimpaired (n = 214) participants using logistic regression. The cohort was predominantly middle-aged men, half of whom (48%) had NCI. The odds of NCI increased by almost two-fold when serum albumin was < 4g/dL, 1.7-fold when alanine aminotransferase (ALT) levels were > 50IU/L, and 2.2-fold with every unit increase in log10 AST to Platelet Ratio Index (APRI). These readily available clinical biomarkers of NCI measure hepatic injury and/or dysfunction, suggesting a mechanism for the effects of HCV infection on NCI. They may identify patients at increased risk of NCI who could be prioritized for early initiation of HCV treatment to protect or improve cognition.

Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study.

Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus (T2DM)1. The gut microbiota is considered as a new key contributor involved in the onset of obesity-related disorders2. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated T2DM, or hypertension3–8. As the administration of A.muciniphila has never been investigated in humans, we conducted a randomized double-blind placebo-controlled pilot study in overweight/obese insulin resistant volunteers, 40 were enroled and 32 completed the trial. The primary endpoints were on safety, tolerability and metabolic parameters (i.e., insulin resistance, circulating lipids, visceral adiposity, body mass). The secondary outcomes were the gut barrier function (i.e., plasma lipopolysacharrides (LPS) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 bacteria either alive or pasteurized A.muciniphila for 3 months was safe and well tolerated. Compared to the Placebo, pasteurized A.muciniphila improved insulin sensitivity (+28.62±7.02%, P=0.002), reduced insulinemia (-34.08±7.12%, P=0.006) and plasma total cholesterol (-8.68±2.38%, P=0.02). Pasteurized A.muciniphila supplementation slightly decreased body weight (-2.27±0.92kg, P=0.091) as compared to the Placebo group, and fat mass (-1.37±0.82kg, P=0.092) and hip circumference (-2.63±1.14cm, P = 0.091) as compared to baseline. After 3 months of supplementation, A.muciniphila reduced the levels of relevant blood markers of liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (NCT02637115) shows that the intervention was safe and well-tolerated and that the supplementation with A.muciniphila improves several metabolic paramaters.

Asarone and metformin delays experimentally induced hepatocellular carcinoma in diabetic milieu

AimsThe evidence suggests that the hyperglycemia and hyperinsulinemia of diabetes mellitus (DM) are risk factors for the development of hepatocellular carcinoma (HCC). The aim of the present study was to examine the effect of streptozotocin (STZ)-induced DM on promoting diethylnitrosamine (DEN) induced HCC in male wistar rats. Further, we investigated the administration of (α)-and (β)-asarone and metformin HCl on experimentally induced diabetic-hepatocellular carcinoma. Materials and methodsDiabetes was induced by single dose of STZ (55 mg/2 ml/kg b.w. i.p.) and HCC by single dose of DEN (200 mg/ml/kg b.w. i.p.). Another group received the STZ followed by DEN two weeks later to mimic diabetic-HCC. The combined dose of (α)-and (β)-asarone (50 μg/1.5 ml/kg b.w. p.o. in the ratio of 1:1) and metformin HCl (250 mg/1.5 ml/kg b.w. p.o.) treatment was compared with the STZ + DEN group. The blood and liver samples were collected at the end of 12 and 18-weeks to study biochemical and histopathological changes in liver. Key findingsThe STZ induced diabetes promoted the tumor progression due to administration of DEN. The treatment of asarones and metformin significantly reduced the levels of glucose, glycosylated hemoglobin, liver dysfunction markers and tumor biomarkers along with an increase in level of insulin when compared to diabetic-HCC group. Histopathological examination indicated that asarones and metformin attenuate the inflammation, fibrosis, cirrhosis and development of spontaneous HCC. SignificanceThe STZ can be used to promote the DEN induced HCC. Treatment with (α)-and (β)-asarone attenuates the effect of STZ + DEN induced HCC akin to metformin.

Predicting Postoperative Liver Dysfunction Based on Blood-Derived MicroRNA Signatures.

There is an urgent need for an easily assessable preoperative test to predict postoperative liver function recovery and thereby determine the optimal time point of liver resection, specifically as current markers are often expensive, time consuming, and invasive. Emerging evidence suggests that microRNA (miRNA) signatures represent potent diagnostic, prognostic, and treatment‐response biomarkers for several diseases. Using next‐generation sequencing as an unbiased systematic approach, 554 miRNAs were detected in preoperative plasma of 21 patients suffering from postoperative liver dysfunction (LD) after liver resection and 27 matched controls. Subsequently, we identified a miRNA signature—consisting of miRNAs 151a‐5p, 192‐5p, and 122‐5p—that highly correlated with patients developing postoperative LD after liver resection. The predictive potential for postoperative LD was subsequently confirmed using real‐time PCR in an independent validation cohort of 98 patients. Ultimately, a regression model of the two miRNA ratios 151a‐5p to 192‐5p and 122‐5p to 151a‐5p was found to reliably predict postoperative LD, severe morbidity, prolonged intensive care unit and hospital stays, and even mortality before an operation with a remarkable accuracy, thereby outperforming established markers of postoperative LD. Ultimately, we documented that miRNA ratios closely followed liver function recovery after partial hepatectomy. Conclusion: Our data demonstrate the clinical utility of an miRNA‐based biomarker to support the selection of patients undergoing partial hepatectomy. The dynamical changes during liver function recovery indicate a possible role in individualized patient treatment. Thereby, our data might help to tailor surgical strategies to the specific risk profile of patients.