Changes In ALT Research Articles

단시간 고강도 다빈치바디보드 운동이 중년여성들의 만성질환에 미치는 영향

Recently, as women enter middle age and old age, they are exposed to various diseases that worsen their health. In middle-aged women, physical activity is rapidly reduced due to family and social life, which is hampering health. Therefore, the purpose of this study was to investigate the effects of short-term high-intensity exercise on da Vinci bodyboard exercise for middle-aged women who had insufficient time to affect various chronic diseases (liver level, kidney function). The 12 middle-aged women who did not experience the da Vinci bodyboard exercise were selected. In the change of liver level, AST and ALT decreased after the da Vinci bodyboard exercise, which was statistically significant. In the changes in kidney function, Creatine decreased after the da Vinci bodyboard exercise, which was statistically significant. Urea decreased after the da Vinci bodyboard exercise but did not show statistically significant levels. Taken together, the Da Vinci Bodyboard exercise is thought to improve liver and kidney function in middle-aged women who lack physical activity. As such, if middle-aged women who are in short of time and continue to exercise to improve their health by short-term high-intensity exercise, it is thought that they will be able to live a healthy life by preventing various chronic diseases coming in middle and old age.

A 12-week, randomized, double-blind study to evaluate the efficacy and safety of liver function after using fermented ginseng powder (GBCK25).

BackgroundRecently, clinical research has suggested that red ginseng components play a role in liver protection and combating fatigue. However, fermented ginseng has not been analyzed for liver-protective or anti-fatigue effects.ObjectiveThis study evaluates the positive effects of fermented ginseng powder (GBCK25) on liver function.MethodsNinety participants with elevated alanine aminotransferase levels (35 ≤ ALT ≤1 05 IU/L) were randomized to one of three groups. The participants were treated with GBCK25 tablets at a dose of 500 mg/day (high dose), 125 mg/day (low dose), or placebo group daily for 12 weeks. The primary outcomes included changes in ALT and gamma-glutamyl transferase (GGT) levels. The secondary outcomes included changes in aspartate amino-transferase (AST), high-sensitivity C-reactive protein (hs-CRP), multidimensional fatigue scale, lipid profile, and antioxidant markers.ResultsIn male subjects, after 12 weeks of low-dose GBCK25 (125 mg) supplementation, the GGT (P = 0.036) and hs-CRP (P = 0.021) levels decreased significantly more than those in the placebo group. High-dose GBCK25 (500 mg) supplementation significantly decreased the fatigue score compared with the placebo group. There were no clinically significant differences between the groups when studying any safety parameter.ConclusionOur results suggest that GBCK25 supplementation has beneficial effects on liver function.Trial registrationThis study was registered at Clinical Trials.gov (NCT03260543).

Comparison of the Postoperative Liver Function Between Total Intravenous Anesthesia and Inhalation Anesthesia in Patients with Preoperatively Elevated Liver Transaminase Levels: A Retrospective Cohort Study.

BackgroundAnesthesia and surgery may deteriorate liver function in patients with elevated liver enzyme levels; therefore, in these patients, choosing anesthetics with less hepatotoxicity is important.MethodsThis retrospective study investigated the effect of total intravenous anesthesia (TIVA) versus inhalation anesthesia (INHA) on the postoperative liver function in patients with preoperatively elevated liver enzyme levels (aspartate transaminase [AST] or alanine transaminase [ALT] >40 U/L) who underwent non-hepatic surgery under general anesthesia. We compared the changes in enzyme levels within 24 hrs before and after surgery.ResultsIn 730 patients (TIVA: n=138; INHA: n=592), the baseline characteristics were comparable, except for higher comorbidity rates in the TIVA group. The median anesthesia and operation times were significantly longer in the TIVA group because approximately 50% of the TIVA group (vs 19.7% of the INHA group) underwent neurosurgery, which had a relatively longer operation time than other surgeries. Intraoperative hypotensive events and vasopressor use were more frequent in the TIVA group. After 1:4 propensity score matching (TIVA: n=94; INHA: n=376), the baseline characteristics and surgical variables were comparable, except for longer anesthesia time. Before matching, postoperative AST and ALT changes were significantly lower in the TIVA group than in the INHA group. After matching, only the ALT change was significantly lower after TIVA than after INHA [median (interquartile range), −16.7 (−32 to −4) % vs −12.0 (−28.6–6.5) %, P=0.025].ConclusionTIVA may be safer for patients with preoperatively elevated liver transaminase levels.

Dietary supplementation of CinnamomumverumJ.Presl and Curcuma longa L. extract on growth performance, antioxidant and metabolic enzymes activities in experimental rats

Cinnamomumverum J. Presl and Curcuma longa L. have many biologically active metabolites, such as sterpenoids, phenolics with proven health benefits. The present study was undertaken to analyze the effect of cinnamon and turmeric extract on growth, blood parameters, and metabolic enzyme activities of albino wistar rats. Methanol extract of cinnamon and turmeric mixture was supplemented in rat feed at 2.5 and 5% concentration, respectively and administered for 30 days. During the course of study, body weight, feed given, feed consumed data were collected at regular intervals. After the experimental period, animals were sacrificed, tissues separated, homogenized and assayed for the activity of catalase, superoxide dismutase (SOD), glutathione-s-transferase (GST), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), alanine aminotransferase (AAT) and aspartate aminotransferase (AST). The results showed significant increase in liver catalase activity of treated animals and no significant changes in LDH, MDH, ALT and AST. No abnormalities were observed in the histopathology staining of tissue section. Overall, output of the present study could be useful for production of spices based antioxidant rich products for human health.

A Randomized, Placebo‐Controlled, Double‐Blind Clinical Investigation on a Patent‐Pending KD120 Metabolically Activated Enzyme Formulation, N‐SORB, in Healthy Young Volunteers

Impaired digestive competence and consequential sluggish immune and metabolic sequela are epidemic‐sized health problems in modern cultures. Since digestion is the first step of metabolism, implementing novel strategies to restore digestive and metabolic competence are important health priorities. N‐SORB is a patent‐pending KD120 multienzyme complex composed of metabolically activated natural digestive‐type enzymes encapsulated in a high‐potency phosphatidylcholine non‐GMO soy lecithin SK713 SLP absorption technology (Prodosome®). A randomized, double‐blind placebo‐controlled study was conducted in 46 male and female healthy volunteers (age: 25.8 ± 12.1 years) to assess the safety and efficacy of N‐SORB. Subjects received either N‐SORB (1 mL, twice daily) or the same amount of placebo for 90 consecutive days. Body weight, blood pressure, physical health, and complete blood chemistries including blood glucose, liver enzymes, and lipid profiles; and immune health, physical health, sleep quality and quality of life parameters were assessed pre‐ and post‐intervention. Serum cytokine levels were determined by using a Bio‐Plex Pro Human Cytokine 8‐plex assay and ELISA. Whole body composition analysis was performed by dual‐energy X‐Ray absorptiometry (DEXA) to determine body fat mass, lean mass and android and gynoid fat. Quality of life (QOL) and sleep quality were assessed using WHOQOL‐BREF and Pittsburgh Sleep Quality Index (PSQI) questionnaire. Adverse events were strictly monitored. 40 subjects completed the study. Hematocrit, hemoglobin, mean corpuscular volume, platelets and lymphocytes provide evidence indicating consistent trends of improvement in the N‐SORB group. QOL parameters showed a small but significant improvement in the N‐SORB group. A significant increase was observed in AST levels in the placebo group at the end of 90 days of treatment, indicating increased liver distress. However, no increase was observed in the N‐SORB group. No significant changes in BUN, serum creatinine, ALP, ALT, and lipid profile were observed between the placebo and treatment groups before and after the 90‐day intervention. No adverse effects were reported. This 90‐day intervention study with N‐SORB clearly exhibited trends of improvement in RBC and immune parameters and found improvements in QOL and sleep quality scivnin already healthy volunteers. The N‐SORB treatment group experienced significant improvement in gastrointestinal functions, immune and metabolic parameters and other systemic improvements. No adverse events were reported.Support or Funding InformationThe Project was partially sponsored by VNI Inc, Lederach, PA

Switching protease inhibitors to rilpivirine in HIV‐positive individuals with complete viral suppression and without prior HIV drug resistance in a resource‐limited setting: a randomized controlled trial

IntroductionPrior to the availability of rilpivirine (RPV), patients who could not tolerate efavirenz and nevirapine (NVP) were treated with protease inhibitor (PI)‐based antiretroviral therapy (ART). Dyslipidaemia and other metabolic complications are commonly associated with PI use. This study aimed to compare the efficacy and adverse events between switching from PI‐based to RPV‐based regimen, versus continuing PI‐based regimens in HIV‐positive individuals with complete viral suppression.MethodsA randomized controlled trial was conducted in HIV‐positive individuals receiving PI‐based regimens with undetectable HIV RNA and without prior HIV drug resistance. Patients were enrolled between July and December 2017 in a university medical centre in Bangkok, Thailand. They were randomized to switch from PIs to RPV (switch group) or continue ritonavir‐boosted PI (control group). Primary endpoint was the proportion of patients with undetectable HIV RNA at 48 weeks. Changes in CD4 cell counts, lipid profiles and adverse events were also analysed.Results and discussionA total of 84 patients were enrolled, 42 in each group. Mean age was 47.7 years and 53.6% were males. At 48 weeks, 95.2% of patients in the switch group and 92.9% of control group had maintained undetectable HIV RNA (difference rate 2.4%; 95% CI, −9.6 to 14.7). Means of CD4 cell counts were 611 and 641 cells/mm3 in switch and control groups respectively (p = 0.632). Mean changes in lipid profiles (switch vs. control groups) were: total cholesterol, −12.5 versus + 12.2 (p = 0.024); LDL, −3.4 versus + 6.2 (p = 0.040); HDL, +1.6 versus + 1.9 (p = 0.887); and triglycerides, −82.6 versus − 24.4 mg/dL (p = 0.031). The mean changes of glucose and eGFR were similar (p > 0.05) between the two groups. The mean change of ALT was significantly greater in switch group (18.2 vs. 4.0 U/L, p = 0.017). One patient in switch group had anorexia and elevated ALT at 14 weeks and completely recovered after RPV discontinuation.ConclusionsSwitching PIs to RPV, in patients with complete viral suppression and without prior HIV drug resistance, sustains viral suppression and yields better lipid profiles. This finding supports its use as switching therapy in patients receiving PI‐based regimens due to intolerance to efavirenz and NVP and previous alternatives limited to PI in resource‐limited settings.

Numerical Simulation of the Influence of Geometric Configurations on Pressure Difference in the Intraventricular Tunnel.

ObjectiveThe geometric configuration of the intraventricular tunnel is related to the re-intervention of left ventricular outflow tract stenosis after double outlet right ventricle (DORV) correction. Hemodynamic simulation was performed in order to study the influence of the geometric configuration of the IVT on the pressure difference.MethodsCT images of DORV were processed to reconstruct 3D models of left and right ventricular flow chambers and aortic valve orifice, and then the size and relative position of the aortic valve orifice and ventricular septal defect were determined. Twenty five groups of the idealized models were established according to orthogonal test design and computational fluid dynamics method was applied to simulate hemodynamics. Three factors of geometric configuration were considered for the study of their influences on the pressure difference. The first factor is the distance between the ventricular septal defect and the plane of the aortic valve (DSA), the second factor is the ejection angle of blood from left ventricle flowing into the IVT (ALT), and the third factor is the turning radius of the IVT (RTT). SPSS software was employed to perform the orthogonal analysis. Additionally, twelve models with different turning radii were established for hemodynamic analysis, with the turning radii increasing from 0 mm with an interval of 1 mm, so as to study the influence of turning radius on pressure difference of IVT.ResultsThe analysis of variance showed that only the change of RTT had a significant effect on the pressure difference (P = 0 < 0.05), while the change of DSA and ALT had no significant effect on the pressure difference (P = 0.459 > 0.05, P = 0.263 > 0.05). The pressure difference decreases with the increase of RTT. When RTT reaches 6 mm, the pressure difference gradually remains unchanged with the increase of RTT, and the rate of change is less than 5%.ConclusionRTT in the IVT is the main factor affecting the pressure difference. A small RTT will lead to a large pressure difference in the IVT. When RTT increases to 6 mm, the pressure difference in the IVT remains nearly unchanged. When performing the right ventricular double outlet correction; the turning radius of the IVT should be about 6 mm to ensure relatively small pressure difference.

Exploring the mechanism of liver enzyme abnormalities in patients with novel coronavirus-infected pneumonia

Objective: To explore and analyze the possible mechanism of liver injury in patients with coronavirus disease 2019 (novel coronavirus pneumonia, NCP). Methods: The correlation between ALT, AST and other liver enzyme changes condition and NCP patients' disease status reported in the literature was comprehensively analyzed. ACE2 expression in liver tissue for novel coronavirus was analyzed based on single cell sequencing (GSE115469) data. RNA-Seq method was used to analyze Ace2 expression and transcription factors related to its expression in liver tissues at various time-points after hepatectomy in mouse model of acute liver injury with partial hepatectomy. t-test or Spearman rank correlation analysis was used for statistical analysis. Results: ALT and AST were abnormally elevated in some patients with novel coronavirus infection, and the rate and extent of ALT and AST elevation in severe NCP patients were higher than those in non-severe patients. Liver tissue results of single cell sequencing and immunohistochemistry showed that ACE2 was only expressed in bile duct epithelial cells of normal liver tissues, and very low in hepatocytes. In a mouse model of acute liver injury with partial hepatectomy, Ace2 expression was down-regulated on the first day, but it was elevated up to twice of the normal level on the third day, and returned to normal level on seventh day when the liver recovered and hepatocyte proliferation stopped. Whether this phenomenon suggests that the bile duct epithelial cells with positive expression of Ace2 participate in the process of liver regeneration after partial hepatectomy deserves further study. In RNA-Seq data, 77 transcription factors were positively correlated with the expression of Ace2 (r > 0.2, FDR < 0.05), which were mainly enriched in the development, differentiation, morphogenesis and cell proliferation of glandular epithelial cells. Conclusion: We assumed that in addition to the over activated inflammatory response in patients with NCP, the up-regulation of ACE2 expression in liver tissue caused by compensatory proliferation of hepatocytes derived from bile duct epithelial cells may also be the possible mechanism of liver tissue injury caused by 2019 novel coronavirus infection.

Histopathological features of chronic hepatitis B reactivation

It was aimed to investigate histopathological changes in acute hepatic exacerbations. A total of 20 patients, who developed acute hepatic exacerbation on the base of chronic hepatitis B infection, were enrolled in the study and liver biopsy was performed. Histological activity index (HAI) and its components, fibrosis scores and total HAI score were calculated according to the Ishak scoring system. All of the patients enrolled in the study had portal inflammation and spotty necrosis. Fibrosis was present in 17 patients. The median grade, stage and total HAI scores of the patients were 7 (2-14), 2 (0-3) and 8.5 (4-16), respectively. Positive correlation was determined between necroinflammation and ALT. While grade and total HAI score did not show significant difference among genders, fibrosis was significantly higher in males (p=0.008). The findings of this study showed that there are significant correlation between histopathologic changes (grade and total HAI score) in liver biopsy and plasma ALT, AST and Total bilirubin levels during acute hepatic exacerbation in patients with chronic hepatitis B infection.

Lactobacillus plantarum SN13T Cells Improve Hepatic Dysfunction And Fecal Microbiota: A Randomized Pilot Study

The liver dysfunction is a worldwide health problem. It has been suggested that an imbalance of gut microbiome is associated with a variety of diseases. The goal of the present clinical trial is to evaluate the effectiveness of Lactobacillus plantarum SN13T on hepatic function and fecal microbiota. This study enrolled 22 subjects, aged between 20 and 70 years, and who had any of the following conditions: 40<AST<100 U/L, 40<ALT<100 U/L, or 70<γ-GTP<210 U/L for males; 30<γ-GTP<90 U/L for females. The subjects were assigned to the live or heat-killed SN13T group. The intake period was 16 weeks followed by an 8-week follow-up period. Although no difference was observed between the two groups in the changes of AST, ALT, and γ-GTP, the subgroup analyses of subjects with over a certain level at baseline showed significant decreases in AST (-14.6 U/L, P=0.028) and ALT (-15.4 U/L, P=0.023) by SN13T, regardless of live or dead. The fecal microflora analysis showed an increase of Firmicutes and the decreases of Bacteroidetes and Fusobacteria in both groups. Bifidobacterium was increased only in the live SN13T group. In conclusion, Lactobacillus plantarum SN13T alters the composition of gut microbiota and improves liver function in subjects with mild liver dysfunction. This clinical trial was registered with University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as UMIN000027440.

Toxicidad crónica del Cadmio y sus efectos sobre actividad de TGO, TGP, creatinina y alteración histológica en riñón e hígado en Rattus norvegicus variedad SPRAGUE DAWLEY

Se evaluó los efectos del cadmio sobre el peso corporal, la actividad de TGO, TGP, creatinina y los cambios histológicos en hígado y riñón de Rattus norvegicus variedad Sprague Dawley. La evaluación experimental se realizó en el Laboratorio de Fisiología Animal del Departamento Académico de Biología de la U.N.S.A.-Arequipa, durante los meses de Enero a Junio 2015. Se utilizaron 24 Rattus norvegicus variedad Sprague Dawley asignados en cuatro grupos:Control (Agua destilada), Grupo 2 (5 mg/Kg de cloruro de cadmio), Grupo 3 (10 mg/Kg. de cloruro de cadmio) y Grupo 4 (20 mg/Kg. de cloruro de cadmio) durante 4 semanas. Se encontró diferencia significativa (p&lt;0,05) en el peso corporal de las ratas en los diferentes grupos de evaluación. Al aplicar la prueba de postcomparación de Tukey se encontró que en el tratamiento con cloruro de cadmio en dosis de 20 mg/kg/día, los pesos corporales de las ratas intoxicadas disminuyeron significativamente. Se observó diferencia significativa (p&lt;0.01) en la actividad de TGO, TGP creatinina de las ratas en los diferentes grupos de evaluación. Al aplicar la prueba de postcomparación de Tukey, se encontró que en los tratamientos con cloruro de cadmio en dosis de 10 y 20 mg/kg/día los niveles de TGO, TGP y creatinina de las ratas intoxicadas se incrementaron significativamente. La exposición crónica de cloruro de cadmioprovocó congestión leve con dilatación de los sinusoides hepáticos y alteración del arreglo arquitectural de los hepatocitos; congestión vascular y aumento de la celularidad glomerular de moderado a severo, degeneración hialina del epitelio tubular en el riñón de las ratas que se les administró cloruro de cadmio en dosis de 10, 20 mg/kg/día durante 30 días.

Protective effects of Croton hookeri on streptozotocin-induced diabetic nephropathy

In this study, the protective effects of Croton hookeri (CH) extract on renal injury were investigated in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single injection of STZ (45 mg/kg) to Sprague-Dawley rats. After 5 days, CH extract (200 mg/kg) was administered daily by oral gavage for 2 weeks. Administration of CH extracts significantly reduced blood glucose levels in STZ-induced diabetic rats. STZ-induced changes in total cholesterol, LDL, HDL, ALT, AST, BUN, and serum creatinine levels were significantly restored by treatment with CH extract. Abnormal levels of SOD, catalase, glutathione, and oxidized GSH (GSSG) in STZ-treated rats were also significantly recovered by CH extract treatment. CH extract markedly reduced the expression of collagen-1, fibronectin, and α-SMA in the kidney of STZ-induced diabetic rats. In particular, oxidative DNA damages, MDA, TGF-β, IL-1β, and IL-6 levels were significantly reduced in STZ-treated rats following treatment with CH extract, whereas IL-10 showed opposite trend. STZ-induced SIRT1, SIRT3 downregulation and cloudin-1 upregulation in the kidney were dramatically recovered by CH extract treatment. Our data suggest that CH extract protects against diabetic-induced nephropathy by inhibiting oxidative stress and inflammation. Therefore, it has potential as a food supplement to alleviate renal dysfunction caused by diabetes-induced nephropathy.

2360 Progression of Post-Islet Cell Transplantation Hepatic Steatosis to Cirrhosis: A Rare Complication of a Common Finding

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a growing cause of liver disease in the USA and throughout the rest of the world and is predicted to soon become the leading indication for liver transplantation. NAFLD exists on a spectrum from hepatic steatosis to non-alcoholic steatohepatitis (NASH) to cirrhosis. It is closely related to metabolic syndrome and insulin resistance. A lesser known cause of hepatic steatosis is islet cell allotransplantation and autotransplantation, which are experimental treatments for Type 1 Diabetes Mellitus and FDA- approved treatment for patients with chronic pancreatitis who have undergone pancreatectomy, respectively. In this case, we present the first case of post-islet cell transplantation hepatic steatosis progressing to cirrhosis. CASE DESCRIPTION/METHODS: The patient is a 27 year old female with a history of chronic pancreatitis secondary to cystic fibrosis, status-post total pancreatectomy and islet cell autotransplantation, complicated by development of non-alcoholic steatohepatitis. Her NASH was treated with probiotics and vitamin E supplementation. Eight years after her islet cell transplant, she was hospitalized for nausea, vomiting, and abdominal pain. A CT scan showed that she had developed severe, diffuse hepatic steatosis. Her ALP and AST were mildly elevated. ALT and total bilirubin were normal. She had facial and pedal edema, but no other stigmata of cirrhosis. She underwent a liver biopsy which showed bridging fibrosis and a small regenerative nodule with steatohepatitis. It was with these findings that she was diagnosed with cirrhosis. DISCUSSION: Hepatic steatosis has been reported with a prevalence of 20-40% of patients following islet cell transplantation. These reports have not been associated with any long term liver or graft survival outcomes. The usual onset of histological findings in one study was approximately 3 years after transplant, and some of these cases resolved over time. These reported cases did not have any changes in total bilirubin, ALP, AST, or ALT. Hepatic steatosis from islet transplantation is thought to develop due to the paracrine effect of localized hyperinsulinemia and fatty acid infiltration from the islet cells, which are inserted into the portal vein and taken to the liver during transplant. To our knowledge, this is the only reported case in which post-islet cell transplantation hepatic steatosis progressed to NASH cirrhosis along with abnormal liver biomarkers.

Comparison of changes in liver function in patients with different types of hepatic alveolar echinococcosis after radiofrequency ablation

Objective To compare the changes in liver function in patients with different types of hepatic alveolar echinococcosis after radiofrequency ablation. Methods The data of 32 patients with hepatic alveolar echinococcosis treated by radiofrequency ablation from December 2016 to December 2018 at the Qinghai Provincial People's Hospital were retrospectively analyzed. There were 12 males and 20 females. The patients were divided into the single lesion group (n=17) and the multiple lesions group (n=15) according to the number of hydatid lesions. The lesions were further divided into the small lesion group (n=12) and the large or medium lesion group (n=20). The operation time, changes in AST and ALT were compared among these groups. Results The operation time of the single lesion group was 1.5 (1.0, 1.8) hour, and that of the multiple lesions group was 3.0 (1.5, 3.5) hour. The difference was statistically significant (P<0.05). On the 1st and 3rd day after treatment, ALT in the multiple lesions group was significantly higher than that in the single lesion group (P<0.05). Compared with the 1st day after operation, ALT of the two groups decreased on the 5th day after treatment, and the difference was statistically significant (P<0.05). The changes in AST in the two groups were basically the same as that of ALT. The operation time of the small lesion group was 1.0 (1.0, 1.9) hour, and of the large and medium lesion group was 2.5 (1.5, 3.0) hour. The difference was statistically significant (P<0.05). On the 1st, 3rd and 5th day after treatment, ALT in the small lesion group was significantly lower than the large or medium lesion group (P<0.05). Compared with the 1st day after treatment, ALT of the two groups decreased on the 5th day after treatment, and the difference was statistically significant (P<0.05). There was a significant difference in AST between the small lesion group and the large or medium lesion group only on the 1st day after operation (P<0.05). Conclusion Radiofrequency ablation for hepatic alveolar echinococcosis with a single lesion and a small lesion had shorter operation time with less changes in liver function after treatment. Key words: Echinococcosis, hepatic; Radiofrequency ablation; Liver function

Sustained Improvements in Markers of Liver Disease Severity After Hepatitis C Treatment

Although serological markers of disease severity improve after hepatitis C virus (HCV) treatment, it is unclear if all patients experience sustained improvement. We aim to evaluate longitudinal changes in aspartate (AST), alanine (ALT) aminotransferase, platelet count (PLT), and fibrosis-4 (FIB-4) after HCV treatment. All adult chronic HCV patients who received antiviral therapy from January 2011 to February 2017at four large urban hospital systems were evaluated to assess changes in AST, ALT, PLT, and FIB-4 from pre-treatment to post-treatment annually up to 4 years after HCV therapy. Comparisons used Student's t-test and analysis of variance, and were stratified by sex, race, ethnicity, age, body mass index (BMI), and diabetes mellitus. Among 2691 patients (62.2% men, 76.9% aged 45-65 years, 56.5% white), all markers of disease severity demonstrated sustained improvements from pre-treatment to 4 years post-treatment (AST 53 U/L to 27.5 U/L, ALT 53 U/L to 29 U/L, PLT 168×103 to 176×103, FIB-4 2.51 to 1.68). However, Hispanics and patients with BMI >30kg/m2 experienced rebound increases in AST, ALT, and FIB-4 at 4 years post-treatment after experiencing initial improvements in these serological markers in the first-year post-treatment. Sustained improvements in PLT were observed in all groups, including Hispanics and patients with BMI >30kg/m2. HCV treatment in a large community-based cohort demonstrated sustained improvements in AST, ALT, PLT, and FIB-4. Rebound increases in AST, ALT, and FIB-4 observed in Hispanics and those with BMI >30kg/m2 may reflect persisting nonalcoholic fatty liver disease.

Therapeutic and Protective Effects of Liposomal Encapsulation of Astaxanthin in Mice with Alcoholic Liver Fibrosis.

Astaxanthin (Asta) has been demonstrated to possess anti-inflammatory, antitumor, and free radical-clearing activities. However, the poor stability and low water solubility of Asta hamper its bioavailability. The objectives of this study were to fabricate Asta-loaded liposomes (Asta-lipo) and investigate the therapeutic effects of Asta-lipo on alcoholic liver fibrosis in mice. The mice were administered with Asta-lipo or liposomes alone prior to a 3-week dose containing 30% alcohol with or without feeding with a second dose of 30% alcohol. The prepared Asta-lipo of 225.0 ± 58.3 nm in diameter, had an encapsulation efficiency of 98%. A slow release profile of 16.2% Asta from Asta-lipo was observed after a 24-h incubation. Restorative actions against alcoholic liver fibrosis were observed after oral administration of Asta-lipo for 4 weeks. Hepatic repair, followed by a second dose of 30% alcohol, suggested that Asta-lipo exerted protective and reparative effects against liver injuries induced by repeated consumption of alcohol. The changes of serum ALT and AST values were principally in consistence with the histopathologic findings. Asta-lipo exerted rapid and direct effects against repeated alcohol-induced liver disease, whereas Asta-lipo given orally could boost recovery from liver injuries obtained due to previous long-term alcohol use. These data demonstrate that Asta-lipo has applicable protective and therapeutic potential to treat alcohol-induced liver diseases.

Presence of Precore (C)/C Promoter Mutants in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B (CHB) Carriers During Pregnancy Does Not Correlate with Increased Risk of Liver Disease in 4Years of Follow-Up.

HBV precore (PC) and basal core promoter (BCP) mutants are associated with liver disease severity, yet have been suggested to protect against HBV vertical transmission. HBV within peripheral blood mononuclear cells (PBMC) has been reported in association with intrauterine HBV infection. We analyzed HBV replication status in PBMC and PC/BCP mutants in PBMC from pregnant chronic hepatitis B (CHB) patients. Pregnant CHB carriers were assessed for HBeAg, HBV-DNA, ALT in second-third trimester and liver stiffness measurement (LSM) postpartum. HBV-DNA, HBV-cccDNA, and HBV-mRNA were tested in PBMC by in-house PCR. BCP/PC variants were determined by Sanger sequencing and analyzed using MEGA7. In 37 CHB pregnant carriers, median age 32years, 53% Asian, median ALT 19 versus 26U/L, median HBV-DNA 2.6 versus 8.1logIU/mL (untreated vs. treated), eight HBeAg+, with genotype 10%A, 29%B, 21%C, 10%D, 19%E, eight received tenofovir in pregnancy to reduce vertical transmission risk. HBV-DNA was detected in ~ 55% (25/45) PBMC, and PC/BCP mutations were found in 36% (9/25) and 4% (1/25), respectively. All infants received HBV immunoprophylaxis and tested HBV surface antigen negative at 9-12months of age. During a median 4years (IQR 3-5), follow-up all mothers showed normal LSM, with no significant change in ALT, HBeAg status, or HBV-DNA levels compared to baseline in untreated CHB carriers. In this multiethnic cohort of pregnant CHB carriers, HBV replicative intermediates and PC/BCP mutants were found in significant proportion of PBMC, but were not associated with increased risk of HBV immunoprophylaxis failure or liver disease severity over long-term follow-up.

Azoramide ameliorates fructose-induced nonalcoholic fatty liver disease in mice

Nonalcoholic fatty liver disease (NAFLD) is a frequent health problem. The insulin resistance and endoplasmic reticulum (ER) stress have been suggested to play important roles in the development and progression of NAFLD. However these processes and correlations have not fully been understood yet. Azoramide, an antidiabetic drug, has the potential for reducing insulin resistance and ER stress in obese mice. To date, there is no study on the effects of azoramide in NAFLD. The aim of this study was to investigate the potential role of azoramide on insulin resistance and ER stress in NAFLD induced mice.Forty Swiss Albino mice were assigned into control, azoramide, fructose and fructose + azoramide groups. Azoramide group received a single dose of azoramide at 150 mg/kg/day by gavage between 71–77th days. Fructose group was treated with 30% fructose solution for 70 days to generate NAFLD. Fructose + azoramide group was treated with 30% fructose for 70 days and then with a single dose of 150 mg/kg/day azoramide for 7 days. At the end of experiment, blood of mice was taken via cardiac puncture, and the livers were excised and weighted. GRP78 and XBP-1 levels were examined with immunohistochemistry in liver tissues. Liver steatosis was evaluated with H&E, Oil-Red O and Sudan-Black staining. ALT, AST, triglyceride, total cholesterol, VLDL, LDL, HDL, fasting glucose and insulin levels were measured in serum.The body and liver weights, insulin resistance, ER-stress markers, lipid profile, AST, ALT and histopathological changes increased by fructose treatment. Azoramide treatment was generally reversed all these changes.These data offer the first evidence to show that azoramide may serve as a potential treatment agent in NAFLD through decreasing the ER-stress and insulin resistance.

163-LB: Impact of SGLT2 Inhibitors on Liver Function Test in Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-analysis

Background: Nonalcoholic fatty liver disease (NAFLD) has been found to be a chronic and precarious metabolic complication from diabetes mellitus. Due to the limitation of treatment options for NAFLD, we postulated that SGLT2 inhibitors would have a potential benefit for NAFLD. None of the previous studies have comprehensively addressed multiple different classes of SGLT2 inhibitor in type 2 DM individuals with NAFLD. We conducted the first meta-analysis investigating the impact of SGLT2 inhibitors on liver function test in type2DM and NAFLD. Methods: We comprehensively searched the databases of MEDLINE, EMBASE, and Cochrane databases. The inclusion criteria were published randomized control trials (RCT), prospective studies, and retrospective studies comparing SGLT2 inhibitors to placebo or controls in NAFLD and type 2 DM individuals. The primary outcome was the differences in the change of ALT and AST. We also examined the changes of NAFLD risk factors including body composition, lipid profile, HbA1C as secondary outcomes. Pooled odds ratio and 95% confidence interval were calculated using a random-effects model (generic inverse variance method). The between-study heterogeneity of effect size was quantified using the Q statistic and I. Results: Eight RCTs, one prospective study, and one retrospective study with 4698 patients were included in the analysis. There was a statistically significant reduction of AST (MD=-2.09, 95% CI:-3.65to-0.52) and ALT (MD=-6.02, 95% CI: -8.35to-3.70) favoring SGLT2 inhibitor groups. Conclusion: SGLT2 inhibitor groups were shown to have a statistically significant reduction of ALT and AST compared to placebo or control groups. SGLT2 inhibitor might be considered as a conjunctive treatment for NAFLD in type2DM individuals. Further studies regarding the optimal dosage and duration of SGLT2 inhibitors are helpful to assess potentially favorable effects in type 2 DM individuals and NAFLD. Disclosure S. Thavaraputta: None. K. Wirunsawanya: None. P. Laoveeravat: None.

Low-dose ethanol ameliorates amnesia induced by a brief seizure model: the role of NMDA signaling

ABSTRACTObjective: The present study aimed to evaluate the ameliorative effect of low-dose ethanol (Eth) on amnesia induced by a brief seizure model and the role of N-methyl D-aspartate (NMDA) signaling in this event.Materials and Methods: Four groups of rats (total number = 36; n = 9, each group) were used: control, Eth (0.5 g/kg/i.p.), pentylenetetrazole (PTZ) (60 mg/kg/i.p.), and Eth+PTZ. Eth was administered for 6 days before the single injection of PTZ, at minute dose that cannot induce memory impairment. The consequences of Eth pretreatment, coadministered with PTZ, were studied in an inhibitory avoidance (IA) memory model. The PTZ was injected 30 min prior to the IA memory test. Thereafter, locomotion, liver enzymes, and the Real-time PCR for NR1 subunit of NMDA receptor were studied. The statistical analyses were performed using the parametric/nonparametric ANOVA and the post-hoc tests.Results: Our findings revealed that Eth pretreatment significantly improved the IA memory impairment induced by PTZ (P < 0.001), and indicated no change in locomotion and serum ALT, but significantly differed for AST between the PTZ and PTZ groups (P = < 0.05). The Real-time PCR results indicate the decreased NR1 mRNA expression in Eth and PTZ groups and the increased NR1 mRNA expression in Eth+PTZ group, compared to the control group (P < 0.001); however, the NR1 mRNA expression was increased in the Eth+PTZ group, compared to PTZ group (P < 0.001).Conclusion: The present study provides evidence that the low-dose Eth can improve the amnesia induced by a brief seizure model presumably via NMDA signaling in a rat.