Serum Alanine Aminotransferase Concentrations Research Articles

Hepatotoxic Effects of Microcystis aeruginosa (PCC 7820) on Wister Rats

The potential toxic effect of Microcystis aeruginosa through oral contamination is becoming important. The present study was carried out to find the possible hepatotoxic effects of toxic M. aeruginosa (PCC 7820) on male Wistar rats as animal model. Hepatotoxicity assessment 1vas done by estimation of serum hepatic enzyme levels of r-Glutamyl transferase (GGT). Alkaline phosphatase (ALP). Alanine aminotransferase (ALT/GPT), Aspartate aminotransferese (GOT/AST). Rat treated with non toxic (CYA -/3) and toxic non homogenized M. aeruginosa (PCC 7820) were normal in appearance where as rats receiving homogenized toxic M aeruginosa (PCC 7820) were lethargic and gained less weight which indicates a possible toxic effect on the test animals. The absolute and relative (% body weight) mean weight of liver and kidneys ofthe homogenous toxic M aeruginosa (PCC 7820) treated animal lj'ere lower than those who received non homogenized toxic M aeruginosa (PCC 7820) and the difference is statistically significant (p<0. 00J). Liver sections of rats receiving fresh toxic M aeruginosa and the homogenized toxic M aeruginosa did not show lymphatic infiltration or signs of necrosis. Rats treated 'with homogenized M aeruginosa showed lowering of absolute liver weight compared to the fresh M aeruginosa treated rats. Statisticcally significant (p<0.005) increase levels of serum y-Glutamyl transferase (GGT) was detected in rats 14 days after oral administration with homogenized toxic M aeruginosa (PCC 7820). There was no significant differentfound in serum Alanine aminotransferase (ALT/GPT) concentration between treated and control groups. The results indicate that prolonged oral administration of homogenized M. aeruginosa lead to functional hepatotoxicity in male Wister rats without evident histopathological liver necrosis.

Allylpyrocatechol, isolated from betel leaf ameliorates thyrotoxicosis in rats by altering thyroid peroxidase and thyrotropin receptors

Allylpyrocatechol (APC) was isolated from betel leaf and its possible role in L-thyroxin (L-T4)-induced thyrotoxic rats was evaluated. The disease condition, thyrotoxicosis was confirmed by higher levels of thyroid hormones and low thyrotropin (TSH) in serum. Increased hepatic activities of 5′-mono-deiodinase(5′D1), glucose-6-phospatase (G-6-Pase); serum concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase(LDH) and tumour necrosis factor-alpha(TNF-α) were observed in thyrotoxic rats. Hepatic lipid peroxidation(LPO) was also increased and the endogenous antioxidants were depleted in these rats. In western blot analysis thyroid peroxidase expression was found to be reduced, whereas thyrotropin receptor(TSHR) expression was enhanced in thyroid gland of these animals. On the other hand, APC treatment in thyrotoxic rats decreased the levels of serum thyroid hormones, ALT, AST, TNF-α and LDH, as well as hepatic 5′ D1 and G-6-Pase activities. However, it increased the serum TSH levels. APC also reduced the hepatic LPO and increased the cellular antioxidants in thyrotoxic rats. However, expression of TSHR was inhibited and TPO was increased by APC. The test compound also improved histological features in both liver and thyroid. Present report appears to be the first one that indicates the positive role of APC in ameliorating T4-induced thyrotoxicosis.

Early ALT response to corticosteroid treatment distinguishes idiosyncratic drug-induced liver injury from autoimmune hepatitis.

Drug-induced liver injury (DILI) and idiopathic autoimmune hepatitis (AIH) are competing diagnoses in patients with acute liver injury (ALI) and drug intake. In absence of unequivocal markers, scores like RUCAM and AIH are used to distinguish both entities. However, in some cases the diagnosis remains ambiguous. Our aim was to identify a simple parameter to discriminate DILI and AIH shortly after starting corticosteroid treatment. For the current analysis, 44 patients with ALI who took at least one drug and who received corticosteroids were included and comprised 22 DILI and 22 AIH cases. Scores of AIH and RUCAM were calculated at initial presentation, the final diagnosis was made from analysing the course of disease. Changes in the serum alanine aminotransferase (ALT) concentrations after starting corticosteroid treatment were determined and compared between the DILI and AIH groups. Fifty-nine per cent of patients (n=26) were correctly classified at presentation by AIH score and RUCAM respectively. However, in one-third (n=13) of the 44 patients, results were inconclusive and five other patients were misclassified. The decrease in ALT levels 1week after the initiation of steroid therapy was significantly more pronounced in patients with the final diagnosis of DILI than in AIH patients (accuracy 77%). This difference was also observed in the 18 initially misclassified or inconclusive cases (accuracy 83%). Short-term response of ALT to corticosteroid therapy helps to differentiate DILI and AIH. This finding may be helpful in treatment decision for patients with inconclusive diagnostic scores.

Dietary supplementation of astaxanthin enhances hemato-biochemistry and innate immunity of Asian seabass, Lates calcarifer (Bloch, 1790)

This study aimed to evaluate the impacts of dietary astaxanthin supplementation on hematology, blood biochemistry and innate immunity of Asian seabass Lates calcarifer, with special reference to dose-response associations and variations over different phases of feeding (short-term, medium-term and long-term). Triplicate groups of fish (n = 30) with an average weight of 28 g were fed astaxanthin-incorporated diets (AX50, 50 mg kg−1 diet; AX100, 100 mg kg−1 diet; AX150, 150 mg kg−1 diet) for 90 days. A diet without astaxanthin supplement (CD) served as the control. Our findings demonstrated that fish displayed significant enhancements (P < .05) in hematological indices (white blood cell count, red blood cell count, hemoglobin and hematocrit) when fed various diets with elevated doses of astaxanthin throughout the specified phases of feeding. Serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose, and cortisol in fish fed the supplemented diets decreased significantly (P < .05) with increasing dietary inclusion levels. Moreover, the provision of dietary astaxanthin at escalating doses markedly reduced (P < .05) the circulating levels of serum cholesterol (proportionately) and triglyceride (dose-dependently) in fish, following three consecutive feeding phases. Correspondingly, the supplemented fish exhibited much higher (P < .05) serum total protein content associated with astaxanthin administration. Immunological parameters (respiratory burst activity, lysozyme activity, phagocytic activity, and serum total immunoglobulin) of fish were significantly stimulated (P < .05) in response to dietary intervention with astaxanthin. The present investigation highlights the ameliorating effect of dietary astaxanthin on hemato-biochemical and immunological variables of Asian seabass and could be administered in culture protocols to improve fish immunocompetence and health.

Norursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial

Norursodeoxycholic acid is an orally administered side chain-shortened homologue of ursodeoxycholic acid that undergoes hepatic enrichment with hepatoprotective, anti-inflammatory, and antifibrotic activity. We assessed the efficacy of two doses of norursodeoxycholic acid versus placebo for the treatment of non-alcoholic fatty liver disease. We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 dose-finding clinical trial in tertiary referral hospitals and medical centres in Austria (n=6) and Germany (n=23) for patients with non-alcoholic fatty liver disease with or without diabetes. Patients with a clinical diagnosis of non-alcoholic fatty liver disease and serum alanine aminotransferase (ALT) concentrations of more than 0·8 times the upper limit of normal were randomly assigned (1:1:1) using a computer-generated central randomisation. Patients were randomly assigned to receive either norursodeoxycholic acid capsules at 500 mg per day or 1500 mg per day, or placebo, for 12 weeks with a subsequent 4-week follow-up period. All individuals involved in the trial were masked to treatment allocation. The primary efficacy endpoint was the mean relative percentage change in ALT concentrations between baseline and end of treatment assessed in the intention-to-treat population. This trial is registered with EudraCT, number 2013-004605-38. Between March 30, 2015, and Sept 20, 2016, of 198 individuals included in the analysis, 67 patients were randomly assigned to receive 500 mg norursodeoxycholic acid, 67 to 1500 mg norursodeoxycholic acid, and 64 to placebo. A dose-dependent reduction in serum ALT between baseline and end of treatment was observed with norursodeoxycholic acid versus placebo, with a significant effect in the 1500 mg group (mean change -27·8%, 95% repeated CI -34·7 to -14·4; p<0·0001). Serious adverse events (n=6) and treatment-emergent adverse events (n=314) were reported in a similar proportion of patients across groups. 112 treatment-emergent adverse events occurred in the 1500 mg group, 99 in the 500 mg group, and 103 in the placebo group. The most frequent adverse events were headache, gastrointestinal disorders, and infections (eg, diarrhoea, abdominal pain, or nasopharyngitis). Norursodeoxycholic acid at 1500 mg resulted in a significant reduction of serum ALT within 12 weeks of treatment when compared with placebo. Norursodeoxycholic acid was safe and well tolerated encouraging further studies. Dr Falk Pharma GmbH.

Effects of dietary isomaltooligosaccharide and Bacillus spp. supplementation during perinatal period on lactational performance, blood metabolites, and milk composition of sows.

In this study, we evaluated the effects of isomaltooligosaccharide (IMO) and Bacillus spp. in perinatal diets on lactational performance, blood metabolites, and milk composition of sows. Multiparous gestating sows (N= 130) with similar body conditions were fed diets without containing IMO (control, CON group), IMO (IMO group), IMO and Bacillus subtilis (IMO + S group), IMO and Bacillus licheniformis (IMO + L group), and IMO and both B.subtilis and B.licheniformis (IMO + S + L group). The average daily feed intake of lactating sows in the IMO + S group (P<0.05) and the average litter gain and total milk yield in the IMO + S + L group (P<0.01) were significantly higher than those of the sows in the other treatment groups. In addition, the serum alanine aminotransferase and alkaline phosphatase concentrations in all treatment groups were lower than those in the CON group (P < 0.05). Furthermore, the highest proportion of fat in colostrum (0.05 <P<0.1) and lowest proportion of lactose in milk were observed in the IMO + L group (P < 0.05). The concentrations of growth hormone and immunoglobulins A and G in milk were higher in sows supplemented with IMO, IMO + S, IMO + L, or IMO + S + L (P < 0.05). IMO and Bacillus spp. supplementation during the perinatal period improved the sows' lactational performance by affecting their metabolism and milk quality. Sows in the IMO + S and IMO + S + L treatment groups exhibited the best performance. © 2019 Society of Chemical Industry.

Curcuminoids plus piperine improve nonalcoholic fatty liver disease: A clinical trial.

Nonalcoholic fatty liver disease (NAFLD) as a prevalent hepatic disease is associated with an increased risk of morbidity and mortality related to the liver and cardiovascular disease (CVD). Lifestyle modification and good metabolic control is the first line of treatment, but not always efficacious in reversing NAFLD pathogenesis. Curcumin is a dietary phytochemical with hepatoprotective activities, though its low bioavailability is considered as a major challenge for clinical applications. Therefore, in this study, in order to improve the bioavailability of curcumin, it was coadministered with piperine and we investigated the effects of this bioavailability-enhanced curcumin on serum hepatic enzymes, lipid profile, and glycemic indices in patients with NAFLD. In this randomized controlled parallel-group trial, 70 subjects with ultrasound-determined NAFLD were randomized to either 500 mg curcuminoids coadministered with 5 mg piperine daily or placebo for 12 weeks. NAFLD severity (on the basis of sonography) and hepatic function was assessed at baseline and at the study end. Seventy subjects completed the study. Supplementation with curcuminoids plus piperine significantly reduced the hematocrit (P = 0.027), erythrocyte sedimentation rate (P = 0.048) and the serum concentrations of alanine aminotransferase (P = 0.035), aspartate aminotransferase (P = 0.042), alkaline phosphatase (P = 0.004), cholesterol (P < 0.016), low-density lipoprotein cholesterol (P < 0.017), Iron (P = 0.026), and Hemoglobin (P = 0.025) and increased total iron-binding capacity (P = 0.003). However, except albumin, changes in other parameters were not statistically different between groups. In addition, administration of curcuminoids plus piperine significantly improved NAFLD severity (P < 0.001), which was statistically different compared with the placebo group (P = 0.022). Also, the percentage of improved patients was marginally higher in the curcuminoids plus piperine group when compared with the placebo group (P = 0.058). This study suggested beneficial effects of combined curcuminoids and piperine supplementation on disease severity in patients with NAFLD.

Histological evaluation of nintedanib in non-alcoholic steatohepatitis mice

AimsIn addition to potentially progressing to either cirrhosis or hepatocellular carcinoma, non-alcoholic steatohepatitis (NASH) is currently the leading indication for liver transplantation. Nintedanib has been clinically used to treat idiopathic pulmonary fibrosis for many years, but its effects in an animal model of NASH have not been tested. The purpose of this study was to evaluate the effects of nintendanib on NASH in choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD)-fed mice. Main methodsMale C57BL/6 mice were fed a CDAHFD for 6 weeks to induce NASH with liver fibrosis, and they were administered nintedanib (60 mg/kg/day) or distilled water orally in the last 2 weeks of the feeding period. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride, and non-esterified fatty acids concentrations were measured. Serum cytokeratin 18 fragment (CK18) was detected using ELISA. Liver tissue sections from mice were stained with hematoxylin-eosin and Masson's trichrome to assess the level of steatohepatitis and fibrosis. Key findingsCDAHFD-fed mice exhibited higher serum ALT, AST, and ALP levels compared with Control mice. A significant increase in the serum CK18 level was observed in the NASH group compared with the Control group. CDAHFD feeding also enhanced steatohepatitis and hepatic fibrosis pathological features, which were reduced after nintedanib treatment. SignificanceNintedanib exerted anti-inflammatory and anti-fibrotic effects in CDAHFD-induced NASH mice.

Effect of berberine on fatty liver ischemia-reperfusion injury in rats: the relationship with endoplasmic reticulum stress in liver tissues

Objective To evaluate the effect of berberine on fatty liver ischemia-reperfusion(I/R) injury and the relationship with endoplasmic reticulum stress in liver tissues. Methods Thirty-two male Wistar rats, aged 4 weeks, weighing 100-150 g, were divided into 4 groups(n=8 each) using a random number table method: control group(group C), fatty liver group(group FL), I/R group and berberine group(group BBR ). Rats were fed a normal fat diet for 12 weeks, normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and rats only underwent simple laparotomy in group C. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, and the other treatments were similar to those previously described in group C. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, normal saline 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and then the model of liver I/R injury was established in group I/R. Rats were fed a high-fat diet(45% energy originating from fat) for 12 weeks, berberine solution(300 mg/kg) 3.5 ml was given intragastrically for 4 weeks starting from 9th week, and then the model of liver I/R injury was established in group BBR. Hepatic ischemia was induced by clamping the portal vein, hepatic artery, right gastric vein, and supra- and inferior-hepatic vena cava to perform cold perfusion with 4 ℃ lactated Ringer′s solution lasting for 30 min, followed by reperfusion. The serum triglyceride(TG) concentrations were determined after 4, 8 and 12 weeks of diet. Blood samples were collected at 6 h of reperfusion for measurement of serum aspartate transminase(AST )and alanine transaminase(ALT)concentrations. Livers were removed after blood sampling at 6 h of reperfusion and liver tissues were obtained and stained with oil red O and haematoxylin and eosin for examination of pathological changes and for determination of the expression of Bip, CCAAT/enhancer-binding protein homologous protein(CHOP), protein kinase RNA-like endoplasmic reticulum kinase(PERK) and phosphorylated PERK(p-PERK)(by Western blot). p-PERK/PERK ratio was calculated. Results Compared with group C, the serum TG, ALT and AST concentrations were significantly increased, the expression of Bip and CHOP was up-regulated, p-PERK/PERK ratio was increased(P<0.05), lipid deposition was increased, and liver steatosis was found in group FL. Compared with group FL, the serum AST and ALT concentrations were significantly increased, the expression of Bip and CHOP was up-regulated, p-PERK/PERK ratio was increased(P<0.05), and the pathological changes of liver tissues were accentuated in group I/R. Compared with group I/R, the serum TG, ALT and AST concentrations were significantly decreased, the expression of Bip and CHOP was down-regulated, p-PERK/PERK ratio was decreased(P<0.05), lipid deposition was reduced, and the pathological changes of liver tissues were significantly attenuated in group BBR. Conclusion Berberine can ameliorate fatty liver I/R injury, and the mechanism may be related to inhibiting endoplasmic reticulum stress in liver tissues of rats. Key words: Berberine; Fatty liver; Reperfusion injury; Endoplasmic reticulum; Stress

Safety and efficacy of stopping tenofovir disoproxil fumarate in patients with chronic hepatitis B following at least 8 years of therapy: a prespecified follow-up analysis of two randomised trials

Effective and well tolerated nucleos(t)ide analogue treatment exists for patients with chronic hepatitis B, although treatment is generally anticipated to be life-long, with concomitant costs and treatment-related side-effects. We aimed to characterise the outcomes of patients with persistent viral suppression who discontinued nucleotide analogue use after extended treatment. The primary objective of this prespecified analysis was to evaluate the safety of stopping long-term tenofovir disoproxil fumarate therapy in patients enrolled in two (completed) randomised controlled studies, GS-US-174-0102 (ClinicalTrials.gov, number NCT00117676) and GS-US-174-0103 (ClinicalTrials.gov, number NCT00116805). In those studies, patients who had completed 8 years or more of nucleotide analogue treatment, were hepatitis B surface antigen (HBsAg)-positive with hepatitis B virus (HBV) DNA concentration of less than 29 IU/mL, and were unwilling or unable to continue therapy were required by protocol to enter a 24-week treatment-free follow-up (TFFU) phase. We present data for patients in the TFFU phase who were assessed at baseline and monitored every 4 weeks for changes in qualitative serum HBsAg, HBV DNA, and alanine aminotransferase (ALT) concentrations in addition to standard safety assessments. Of 124 patients who entered the TFFU phase, 54 (44%) patients did not complete 24 weeks of follow-up (median 12 weeks; IQR 0-20). Overall, 32 (26%) patients reported an adverse event. Serious adverse events occurred in five (4%) patients, including elevated ALT concentrations in two patients, hepatic flare in two patients, and increased lipase in one patient. 38 (31%) of patients had grade 3 or higher laboratory abnormalities, the majority of which were ALT elevations (36 patients). Of the 106 hepatitis B e antigen (HBeAg)-negative patients who entered the TFFU phase, 63 (59%) were followed for 24 weeks. HBsAg loss was observed in five (5%) of the 106 HBeAg-negative patients who entered the TFFU phase, and 37 (35%) had both HBV DNA concentrations of less than 2000 IU/mL and ALT concentrations less than the ULN at TFFU week 24. 18 HBeAg-positive patients entered the TFFU phase, of whom seven (39%) were followed up for 24 weeks. Of these seven patients, none had HBsAg loss or HBV DNA of less than 2000 IU/mL and one (14%) had an ALT less than the ULN at week 24. Within 24 weeks of stopping 8 years or more of nucleotide analogue therapy almost a third of patients experienced a grade 3 or higher laboratory abnormality. Although few patients achieved HBsAg loss, a subgroup of HBeAg-negative patients can achieve a low-replicative state within a short duration of follow-up. Gilead Sciences, Inc.

Does turmeric/curcumin supplementation improve serum alanine aminotransferase and aspartate aminotransferase levels in patients with nonalcoholic fatty liver disease? A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis to evaluate the efficacy of turmeric/curcumin supplementation on serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with nonalcoholic fatty liver disease (NAFLD). We searched PubMed, Scopus, Cochrane Library, ISI Web of Science, and Google Scholar up to November 20, 2018. Studies that examined the effect of turmeric/curcumin on serum concentrations of ALT and AST among patients with NAFLD were included. The mean difference and standard deviation (SD) of changes in ALT and AST between intervention and control groups were used as effect size for the meta-analysis. A total of six randomized controlled trials (RCTs) were eligible for meta-analysis. Results from pooled analysis revealed that turmeric/curcumin supplementation reduced ALT (MD: -7.31 UL/L, 95% CI [-13.16, -1.47], p=0.014) and AST (MD: -4.68 UL/L, 95% CI [-8.75 -0.60], p=0.026). When RCTs stratified on the basis of their treatment duration, the significant reduction in serum concentrations of ALT and AST was observed only in studies lasting less than 12weeks. This review suggests that turmeric/curcumin might have a favorable effect on serum concentrations of ALT and AST in patients with NAFLD. However, further clinical trials are needed to confirm these findings.

Identification of changes in serum analytes and possible metabolic pathways associated with canine obesity-related metabolic dysfunction

The main objective of this study was to identify analytes that could change and that could help to clarify the metabolic and physiopathological changes related to canine obesity-related metabolic dysfunction (ORMD). For this, serum from 35 overweight/obese dogs, with and without ORMD, was submitted to a comprehensive panel of biochemistry analysis, a gel-free tandem mass tag isobaric label-based proteomic analysis, and, finally, selected proteins were used as a starting point for creating a protein interaction network.Dogs with ORMD showed significantly higher serum concentrations of alanine aminotransferase (ALT), alkaline phosphatase (ALP), Ca, total proteins, albumin, total cholesterol, triglycerides, glucose, and butyrylcholinesterase (BChE) activity in comparison with dogs without ORMD. Proteomic analysis revealed that 23 proteins related to lipid metabolism, the complement factor system, cellular adhesion and functionality, inflammation, and coagulation were altered in dogs with ORMD. Finally, the obtained protein interaction network highlighted that the central term of this network was the negative regulation of the immune response. These data suggest that canine ORMD is associated with changes in analytes that reflect altered lipid metabolism, and liver and immune function impairment and suggests the potential for a prothrombotic state and lung function alterations.

Serum Alanine Aminotransferase Level as a Risk Factor for Coronary Heart Disease Prediction in Koreans: Analysis of the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011).

BackgroundThe blood level of alanine aminotransferase (ALT) is associated with increased coronary heart disease (CHD) risk. However, its use as an independent factor for CHD risk prediction remains unclear in Asian populations. The purpose of this study was to examine the association between serum ALT levels and CHD risk in Koreans.MethodsThis was a cross-sectional study using data from the Korea National Health and Nutrition Examination Survey (V-1, 2010 and V-2, 2011). The ALT levels of 3,215 individuals were analyzed. The Framingham Risk Score (FRS) modified by the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) was used to compute the 10-year CHD risk prediction.ResultsPositive correlations were established between log-transformed ALT concentration and FRS (r=0.433, P<0.001). After adjusting for body mass index, low-density lipoprotein cholesterol, the amount of alcohol intake, and gamma-glutamyl transferase, the odds ratio (95% confidence interval) for intermediate or greater risk of 10-year CHD prediction (10-year risk ≥10%) for the lowest quartile of participants was 2.242 (1.405–3.577) for the second quartile, 2.879 (1.772–4.679) for the third quartile, and 3.041 (1.789–5.170) for the highest quartile.ConclusionIn Koreans, a higher serum ALT concentration was significantly correlated with 10-year CHD risk prediction according to NCEP ATP III guidelines.

Clinical efficacy and mechanism of Pralatrexate combined with Palbociclib Isethionate in treatment of bladder cancer patients.

The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer.

ASSOCIATION OF GHRELIN GENE POLYMORPHISMS AND EXPRESSION LEVELS WITH SOME BIOCHEMICAL TRAITS IN BROILER CHICKENS

This study was conducted to investigate the association of Ghrelin gene polymorphisms and expression levels with some biochemical traits of broiler chickens. Two hundred broiler chicks Ross308, one-day old were wing-tagged and reared under optimal conditions. Blood samples were collected individually from all birds on 21 and 35 days of age. Proventriculus was collected at 35 days of age from thirty birds of each of groups sorted according to growth rate for high, moderate and low to measure ghrelin gene expression by real-time RT-PCR. The serum traits of glucose, uric acid, cholesterol, triglyceride, high density lipoproteins (HDL), low density lipoproteins LDL, total protein, albumin, globulin, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were not influenced by ghrelin gene polymorphisms. While significant (P &lt; 0.01) differences were recorded among the three chicken groups with high, moderate and low ghrelin expression in serum glucose, uric acid, total protein, albumin, cholesterol, triglyceride, HDL, AST, ALT and ALP concentrations at 21 and 35 days of age which increased with increasing ghrelin gene expression. The PCR- RFLP technique revealed no significant differences between GG and LL genotypes of ghrelin gene in all biochemical traits at 21 and 35 days of age, whereas ghrelin gene expression had a significant effect on serum glucose, uric acid, total protein, albumin, cholesterol, triglyceride, HDL, AST,ALT and ALP.

Preconception alanine aminotransferase concentrations and risk of preterm birth in rural Chinese women aged 20–49 years: a population-based cohort study

BackgroundPrevious studies have shown maternal hepatitis B virus infection is associated with preterm birth. However, whether liver dysfunction caused by hepatitis B virus infection or other factors can lead to preterm delivery needs further exploration. Serum alanine aminotransferase (ALT) is a sensitive indicator of liver function, but few studies have investigated the association between serum ALT concentrations and preterm birth. We aimed to examine the relationship between maternal preconception ALT concentration and risk of preterm birth. MethodsWe did a population-based cohort study of 4832887 women aged 20–49 years old, who participated in the National Free Pre-pregnancy Checkups Project (NFPCP) in 2013–16, and delivered a livebirth before Dec 31, 2017, in rural China. We collected information about demographic characteristics, history of pregnancy and diseases, serum ALT concentration, hepatitis B surface antigen (HBsAg) status, and other variables. We divided participants into five groups according to serum ALT concentration (≤20 U/L, 21–40 U/L, 41–60 U/L, 61–80 U/L, and ≥ 81 U/L). The primary outcome was preterm birth (gestational age 28 to <37 weeks). We used logistic models to estimate odds ratios (ORs) and 95% CIs, after adjusting for confounding variables. We applied restricted cubic splines to investigate the dose-response relationship. The study was approved by the Institutional Research Review Board at the National Health Commission, and all participants gave written consent. FindingsBy Dec 31, 2017, 324207 (6·71%) preterm birth events were documented in the 4832887 participants. Incidence of preterm birth was lowest in women with ALT concentrations of 21–40 U/L (93685 [6·42%] of 1 458 233 women), whereas the preterm birth incidence was highest in women with ALT concentrations of 81 U/L or higher (3302 [7·52%] of 43912 women). There was a non-linear dose-response relationship between serum ALT concentration and risk of preterm birth (U-shaped, p<0·001). In women who were HBsAg negative, the multivariable-adjusted OR for preterm birth was 1·07 (95% CI 1·06–1·08) for ALT concentrations of 20 U/L or less, 1·19 (1·16–1·22) for concentrations of 41–60 U/L, 1·16 (1·11–1·20) for concentrations of 61–80 U/L, and 1·16 (1·12–1·21) for concentrations of 81 U/L or higher, when compared to women with ALT concentrations of 21–40 U/L. In women who were HBsAg positive, there were significant associations between preterm birth and ALT concentrations of 61–80 U/L (OR 1·17, 95% CI 1·05–1·29), and 81 U/L or higher (1·21, 1·11–1·31). InterpretationOur study identified a U-shaped relationship between maternal preconception ALT concentration and risk of preterm birth. The association between ALT concentration and risk of preterm birth was independent of hepatitis B virus infection. The surveillance of ALT among women planning pregnancy should be warranted, given the increased risk of preterm birth. FundingThis study was supported by the National Key Research and Development Program (number 2016YFC10003007).

Role of necroptosis in liver injury in rats undergoing autologous orthotopic liver transplantation

Objective To evaluate the role of necroptosis in liver injury in rats undergoing autologous orthotopic liver transplantation (AOLT). Methods Twenty-four SPF adult male Sprague-Dawley rats, weighing 250-280 g, were divided into 3 groups (n=8 each) using a random number table method: sham operation group (group S), AOLT group (group T) and necroptosis inhibitor necrostatin-1 group (group N). Rats were anesthetized using intraperitoneal 5% chloral hydrate 0.5 ml/100 g. A standard model of OALT was established as previously described by Yao et al.in T and N groups.Necrostatin-1 1.0 mg/kg and the equal volume of dimethyl sulfoxide were intraperitoneally injected at 30 min before surgery in N and T groups, respectively.Blood samples were collected from the inferior vena cava at 6 h after opening the portal vein (at 6 h after operation in group S) for determination of serum aspartate amino-transferase (AST) and alanine amino- transferase (ALT) concentrations.The livers were removed for examination of the pathological changes (with a light microscope) and for determination of the malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity (using a spectrophotometer) and expression of receptor-interacting protein kinase-1 (RIPK1), RIPK3 and mixed lineage kinase domain-like (MLKL) in liver tissues (by Western blot). The damage to livers was evaluated using Suzuki′s scoring system. Results Compared with group S, the serum AST and ALT concentrations, Suzuki′s score of liver tissues and MDA content were significantly increased, the SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in group T (P<0.05). Compared with group T, the serum AST and ALT concentrations, Suzuki′s score of liver tissues and MDA content were significantly decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group N (P<0.05). Conclusion Necroptosis is involved in liver injury in rats undergoing AOLT. Key words: Liver transplantation; Reperfusion injury; Necrosis

Administration of Nigella sativa during neonatal and juvenile growth period improved liver function of propylthiouracil-induced hypothyroid rats

Aim: Propylthiouracil (PTU) is frequently used as an antithyroid medication. It is also commonly used to induce hypothyroidism in rodents. PTU administration and hypothyroidism have been shown to affect the liver function. Nigella sativa (NS) has been suggested to have antioxidant and hepatoprotective effects. The objective of this study was to investigate the effects of NS extract administration during neonatal and juvenile growth period on liver function of PTU-induced hypothyroid rats.Methods: The pregnant rats were kept in separate cages. After delivery, the mothers and their offspring were randomly divided into five groups and were treated with the following programs: (1) control; (2) PTU, 0.005% in their drinking water (3–5); PTU-plus 100, 200, or 400 mg/kg NS extract. After lactation period, the offspring continued to receive the same experimental treatment for the first 8 weeks of their life. Ten offspring of each group were randomly selected and weighted at days 10, 30, and 60 after delivery. Their blood samples were collected and the liver tissues were removed.Results: Malondialdehyde (MDA) concentration was increased while, thiol concentration and superoxide dismutase (SOD) and catalase (CAT) activity were decreased in the liver tissues of PTU-treated rats. Serum aspartate amino transferase (AST), alkaline phosphatase (ALK-P), and alanine aminotransferase (ALT) levels in the PTU group were higher than the control group. Treatment with 200 and 400 mg/kg decreased MDA while increasing thiol concentration in the liver tissues compared to the PTU group. Treatment with all doses of the extract decreased serum ALK-P concentration compared with the PTU group. Treatment with 400 mg/kg NS increased CAT and SOD concentrations in the liver tissues and decreased serum AST and ALT concentrations compared to the PTU group. PTU decreased body weight gain of offspring and while, the extract increased the body weight gain of offspring rats.Conclusion: The results of this study demonstrated that administration of NS hydroalcoholic extract in the neonatal and juvenile growth period has an improving effect on the liver function of PTU- induced hypothyroid rats.

Daily Consumption of Synbiotic Yogurt Decreases Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed and developing countries. The use of synbiotics has been proposed as a probable management strategy for patients with NAFLD. We investigated the effects of synbiotic yogurt on hepatic steatosis and liver enzymes as primary outcomes and on oxidative stress markers, adipokine concentration, and gut peptide concentration as secondary outcomes in patients with NAFLD. In this 24-wk, open-label, randomized controlled clinical trial, 102 patients [50 men and 52 women; mean age: 40 y; body mass index (in kg/m2) (mean±SD): 31.2±4.9] were randomly assigned to 3 groups, including 2 intervention groups and 1 control group. The intervention groups consumed 300 g synbiotic yogurt containing 108 colony-forming units Bifidobacterium animalis/mL and 1.5 g inulin or conventional yogurt daily and were advised to follow a healthy lifestyle (i.e., diet and exercise). The control group was advised to follow a healthy lifestyle alone. We evaluated differences between groups in liver function measures by using repeated-measures ANOVA, ANCOVA, and logistic regression. At the end of the study, the grades of NAFLD, as determined by ultrasonography, showed a significant decrease in the synbiotic group compared with the conventional and control groups (P<0.001). The following significant mean±SD decreases were seen in the synbiotic, conventional, and control groups, respectively: serum concentration of alanine aminotransferase (-14.5±15.6 compared with 4.6±15.4 and 3.1±14.4 IU/L; P=0.008), aspartate aminotransferase (-7.5±6.1 compared with 3.0±8.2 and 3.1±5.7 IU/L; P<0.001), alkaline phosphatase (-26.2±16.8 compared with 3.4±30.1 and 1.5±31.9 IU/L; P=0.024), and γ-glutamyltransferase (-6.0±6.0 compared with 1.0±6.4 and 7.6±11.4 IU/L; P<0.001). Synbiotic yogurt consumption improved hepatic steatosis and liver enzyme concentrations in patients with NAFLD. This trial was registered at the Iranian Registry of Clinical Trials website (www.irct.ir) as IRCT2017020932417N2.

Effect of Liraglutide, Metformin, and Gliclazide on Body Composition in Type 2 Diabetic Patients with Nonalcoholic Fatty Liver Disease—A Randomised Trial

Objective: To compare the effects of gliclazide, liraglutide, and metformin on body composition in type 2 diabetes mellitus (T2DM) patients with nonalcoholic fatty liver disease (NAFLD). Methods: Eighty-five subjects were randomly allocated and received gliclazide (n=27), liraglutide (n=29), or metformin (n=29) monotherapy for 24 weeks. Body composition was measured using dual-energy x-ray absorptiometry. Results: Liraglutide and metformin reduced weight and total, trunk, limb, android, and gynoid fat mass. However, no significant changes in weight or fat mass occurred with gliclazide. In the liraglutide and metformin arms, weight loss was mainly due to reductions in total, trunk, limb, android, and gynoid fat mass. The stable weight obtained with gliclazide resulted from identical reductions in fat mass and increases in lean tissue mass. Blood glucose concentrations and glycated haemoglobin A1c (HbA1c) levels improved in all treatment arms, but lower HbA1c levels were found with liraglutide and metformin. Serum alanine aminotransferase (ALT) concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase (AST) concentrations reduced with liraglutide and metformin only. For all subjects, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with reductions in serum ALT and AST concentrations, and reductions in waist circumference were positively correlated with reductions in serum ALT concentrations. Conclusions: As compared with gliclazide monotherapy, liraglutide and metformin monotherapies resulted in greater weight loss, reductions in body fat mass, and improvements in liver function and blood glucose control among patients with T2DM and NAFLD. Disclosure W. Feng: None. Y. Bi: None. P. Li: None. T. Yin: None. C. Gao: None. S. Shen: None. L. Gao: None. C. Jiang: None. D. Zhu: None.