Hepatic Function In Patients Research Articles

Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study.

No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD. Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers. A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns. Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.

Association Between Immune-Inflammation Index (SII) and Ferritin with Hepatic Function in Patients with Thalassemia Major

Background: Thalassemia major is associated with ferritin levels and SII values with impaired liver function. Furthermore, the measurement of impaired liver function is carried out using Serum Glutamate Oxaloacetate Transaminase (SGOT) and Serum Glutamate Pyruvate Transaminase (SGPT) levels. Increased SGPT and SGOT levels are indicators of liver necrosis. Objective: This study aimed to prove the association between SII and ferritin with SGPT and SGOT levels in thalassemia major patients. Methods: An observational analysis with a cross-sectional approach was adopted to analyze the medical records of pediatric patients at the Kasuari Clinic of Dr. Kariadi Hospital Semarang from September to October 2023. SII value and ferritin level were the independent variables, while SGOT and SGPT were dependent. Data were collected and analyzed univariately for characteristic description and bivariately using the Spearman test. Results: The results showed that there was a moderately significant association between SII values and SGOT levels (p=0.010, r=-0.457) as well as ferritin and SGPT (p=007, r=0.475). There was no significant association between SII values and SGPT levels, as shown by a P-value of 0.122. Similarly, there was no association between ferritin and SGOT levels (p=0.088). Conclusion: A moderately significant association was found between SII values and SGOT levels, as well as ferritin levels and SGPT levels in thalassemia major patients. In the case of SII values and SGPT levels, as well as ferritin and SGOT, there was no significant association.

Evaluation of effectiveness, hyperkalaemia, and hepatotoxicity of trimethoprim-sulphamethoxazole prophylaxis for Pneumocystis jirovecii pneumonia in paediatric patients: A single-centre retrospective study

BackgroundAmerican guidelines recommend trimethoprim-sulphamethoxazole (TMP-SMX) for preventing Pneumocystis jirovecii pneumonia (PJP) in paediatric patients at doses of 5–10 mg/kg/d of the TMP component, administered either daily, three times weekly, or twice weekly. However, limited studies describe the effectiveness and safety of these prophylactic regimens. Our study aimed to assess the clinical effectiveness and incidence of adverse events associated with each TMP-SMX regimen in paediatric patients, and to identify risk factors for adverse events. MethodsWe collected data regarding the onset of PJP, hyperkalaemia, and hepatotoxicity in patients aged 0–18 years who underwent prophylaxis with TMP-SMX from July 2018 to June 2023. ResultsA total of 215 paediatric patients met the inclusion criteria. No patients developed PJP. Hyperkalaemia occurred in 14.7%, patients receiving TMP-SMX daily, 15.4% receiving it three times weekly, and 15.5% receiving it twice weekly. Hepatotoxicity was most frequent in patients receiving TMP-SMX twice weekly (19%), followed by those receiving it three times weekly (7.7%), and daily (5.9%). Younger patients were significantly more prone to developing hyperkalaemia or hepatotoxicity. Patients aged <1 year had the highest incidences of hyperkalaemia (56.5%), and those aged 1–2 years had the highest incidence of hepatotoxicity (25%). ConclusionsNo patient developed PJP under various dosage prophylactic regimens of TMP-SMX. However, our findings suggest the need to monitor potassium levels and hepatic function in patients undergoing any of the three TMP-SMX regimens. In particular, patients aged <1 year old and 1–2 years old face a higher risk of hyperkalaemia and hepatotoxicity, respectively.

582-P: Exercise Training Reverses NAFLD in Mice with Obesity Independent of Changes in Hepatic Mitochondrial Oxidative Capacity

Obesity is a primary cause of hepatic lipid accumulation, leading to nonalcoholic fatty liver disease (NAFLD). As there are no FDA-approved therapies for NAFLD treatment, weight loss through lifestyle intervention is the first-line therapy. Exercise improves hepatic function in patients with obesity related NAFLD. However, the mechanisms whereby exercise mediates the enhancement of liver function are largely unknown. This study evaluated the impact of exercise training on NAFLD in mice with obesity. At 8 weeks of age, mice were randomized to low-fat (LFD) or high-fat diet (HFD). After 4 weeks of dietary intervention, mice were randomized to either control (SED) or exercise training (ExT) with experimental diet for 10 weeks. ExT mice completed 45 minutes of moderate-intensity treadmill running 4 days/week. Body weight was measured weekly, and body composition and maximal treadmill running were evaluated at weeks 0, 4, and 14. Blood lactate accumulation was measured during the final treadmill test. Mice were euthanized 48 hours after the last exercise session for liver histopathology, blood chemistry, and ex vivo mitochondrial function analysis. Liver function was assessed via serum liver panel and quantification of hepatic lipids. High-resolution respirometry was used to determine maximal hepatic fatty acid oxidation, NADH- and succinate-linked oxidative phosphorylation (OXPHOS), and electron transfer capacity in tissue homogenates. HFD increased body mass, which was reduced with ExT. ExT increased maximal running time independent of diet. HFD worsened lactate metabolism, which was improved with ExT. HFD increased liver weight, which was decreased with ExT. HFD-induced increases in hepatic lipid and serum ALT and ALP were reversed with ExT. Hepatic mitochondrial OXPHOS and electron transfer were reduced with HFD relative to LFD. These data suggest that exercise-induced reversal of NAFLD is not mediated by hepatic mitochondrial oxidative capacity. Disclosure E.C. Heintz: None. W.S. Dantas: None. J.E. Stampley: None. G.M. Davis: None. B.A. Irving: None. C.L. Axelrod: None. J.P. Kirwan: None. Funding Nutrition Obesity Research Center (P30DK072476); Louisiana Clinical and Translational Science Center (U54GM104940); Centers of Biomedical Research Excellence (P20GM103528)

Characterization of endogenous markers of hepatic function in patients receiving itraconazole treatment for prophylaxis of deep mycosis

BackgroundLong-term use of itraconazole (ITZ) is associated with a risk of inducing hepatotoxicity. This study aimed to evaluate the associations of plasma concentrations of ITZ and its hydroxylated metabolite (OH-ITZ) with endogenous markers of hepatic function. MethodsThirty six patients treated with oral ITZ solution for prophylaxis of deep mycosis were enrolled. Plasma concentrations of ITZ and OH-ITZ were determined on the 14th day or later after administration of ITZ. Their associations with endogenous marker levels of hepatic function including plasma coproporphyrin (CP)-I and OATP1B1 genotypes were assessed. ResultsThe serum level of total bilirubin (T-Bil) was moderately correlated with the plasma concentration of total ITZ (tITZ) and OH-ITZ (tOH-ITZ). T-Bil elevation above 0.3 mg/dL was observed in 19% of patients, although statistically significant difference was not identified. The plasma concentration of tITZ had no correlation with other endogenous markers levels including AST, ALT, albumin, and plasma CP-I. The serum AST and plasma CP-I levels were correlated with the plasma concentration of free OH-ITZ (fOH-ITZ). T-Bil and plasma CP-I, a marker of OATP1B1 activity, were not correlated with each other, and neither was associated with the OATP1B1 genotypes. ConclusionsPlasma ITZ and OH-ITZ had a positive association with T-Bil. The patients with a higher fOH-ITZ level had lower OATP1B1 activity on the basis of plasma CP-I level. ITZ and OH-ITZ have the potential to slightly increase endogenous marker levels of hepatic function, although most likely by different mechanisms.

Short-term prognostic factors for hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUNDAcute-on-chronic liver failure (ACLF) is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease.AIMTo explore the independent predictors of short-term prognosis in patients with hepatitis B virus (HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF.METHODSFrom January 2016 to December 2019, 207 patients with HBV-related ACLF attending the 910th Hospital of Chinese People's Liberation Army were continuously included in this retrospective study. Patients were stratified based on their survival status 3 mo after diagnosis. Information was collected regarding gender and age; coagulation function in terms of prothrombin time and international normalized ratio (INR); hematological profile in terms of neutrophil-to-lymphocyte ratio (NLR) and platelet count (PLT); blood biochemistry in terms of alanine aminotransferase, aspartate aminotransferase, total bilirubin (Tbil), albumin, cholinesterase, blood urea nitrogen (BUN), creatinine, blood glucose, and sodium (Na); tumor markers including alpha-fetoprotein (AFP) and Golgi protein 73 (GP73); virological indicators including HBV-DNA, HBsAg, HBeAg, Anti-HBe, and Anti-HBc; and complications including hepatic encephalopathy, hepatorenal syndrome, spontaneous peritonitis, gastrointestinal bleeding, and pulmonary infection.RESULTSThere were 157 and 50 patients in the survival and death categories, respectively. Univariate analysis revealed significant differences in age, PLT, Tbil, BUN, NLR, HBsAg, AFP, GP73, INR, stage of liver failure, classification of liver failure, and incidence of complications (pulmonary infection, hepatic encephalopathy, spontaneous bacterial peritonitis, and upper gastrointestinal bleeding) between the two groups (P < 0.05). GP73 [hazard ratio (HR): 1.009, 95% confidence interval (CI): 1.005-1.013, P = 0.000], middle stage of liver failure (HR: 5.056, 95%CI: 1.792-14.269, P = 0.002), late stage of liver failure (HR: 22.335, 95%CI: 8.544-58.388, P = 0.000), pulmonary infection (HR: 2.056, 95%CI: 1.145-3.690, P = 0.016), hepatorenal syndrome (HR: 6.847, 95%CI: 1.930-24.291, P = 0.003), and HBsAg (HR: 0.690, 95%CI: 0.524-0.908, P = 0.008) were independent risk factors for short-term prognosis in patients with HBV-related ACLF. Following binary logistics regression analysis, we arrived at the following formula for predicting short-term prognosis: Logit(P) = Ln(P/1-P) = 0.013 × (GP73 ng/mL) + 1.907 × (middle stage of liver failure) + 4.146 × (late stage of liver failure) + 0.734 × (pulmonary infection) + 22.320 × (hepatorenal syndrome) - 0.529 × (HBsAg) - 5.224. The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Liver Disease (MELD) and MELD-Na score models (P < 0.05).CONCLUSIONThe stage of liver failure, presence of GP73, pulmonary infection, hepatorenal syndrome, and HBsAg are independent predictors of short-term prognosis in patients with HBV-related ACLF, and the GP73-ACLF model has good predictive value among these patients.

Effect of underdilated transjugular intrahepatic portosystemic shunt on prognosis in patients with prior splenectomy: a propensity score-matched case-control study.

This study aimed to investigate whether underdilated transjugular intrahepatic portosystemic shunt (TIPS) could reduce the risk of hepatic encephalopathy (HE) and ameliorate impaired hepatic function in patients with a history of splenectomy. A retrospective case-control study was conducted with 96 patients who had prior splenectomy and TIPS placement from August 2016 to May 2022. All patients were divided into two groups based on the diameter of expansion balloon catheters, the underdilated group (6-mm balloon catheter, n = 60) and a control group (8-mm balloon catheter, n = 36). Following the 1:1 propensity score matching (PSM), 33 patients in the underdilated group and 33 patients in the control group were included. During a median follow-up of 36months, a quicker recovery in liver function after TIPS placement was showed in the underdilated group. The mean TBIL content (16.562 ± 6.549μmol/L vs 23.871 ± 11.609μmol/L, P = 0.019) and the mean CLIF-C AD score (41.108 ± 5.223 vs 45.100 ± 4.429, P = 0.033) in the underdilated group were significantly lower than those in the control group during 6 to 12months after the procedure. In line with the control group, the ability to reduce portal pressure gradient (PPG) and achieve a significantly clinical remission of PVT and ascites severity was showed in the underdilated group 3months after TIPS creation (P < 0.001). The Kaplan-Meier analysis demonstrated that no statistically significant differences were found in the cumulative incidence of no overt HE (OHE) (log-rank P = 0.383), cumulative incidence without shunt dysfunction (log-rank P = 0.283), cumulative incidence of no variceal rebleeding (log-rank P = 0.696), and survival (log-rank P = 0.341) (log-rank P = 0.341) between the two groups during the follow-up period. For patients with prior splenectomy, it is safe to employ underdilated TIPS, as the stents will eventually self-expand to 8mm. The present study has shown some degree of liver function preservation in the underdilated group, which may be related to slower progressive changes in the portal hemodynamics.

Hepatic Function Predictive Value of Hepatic Venous Waveform versus Portal Vein Velocity in Liver Cirrhosis.

Background:This study assessed the hepatic vein waveform (HVW) and mean maximum portal vein velocity (MM-PVV) on Doppler ultrasound in patients with liver cirrhosis (LC) and compared it with that of age and sex-matched controls. It correlated the degree of HVW abnormality and MM-PVV changes with liver function based on Child-Turcotte-Pugh (CTP) to determine which was more predictive of CTP.Methods:Sixty patients with LC and 60 healthy controls were consecutively recruited into this study. Each patient was classed based on the CTP system after relevant tests. Doppler evaluation of the hepatic vein (HV) and MM-PVV were performed. HVW obtained was classified either into triphasic, biphasic, or monophasic.Results:Sixty cirrhotic and 60 age-matched control subjects aged 19–69 and 18–69 years, respectively, completed this study. All control subjects had a normal HVW pattern while 46 (76.7%) cirrhotic subjects had abnormal HVW (P < 0.001). The MM-PVV was significantly lower in cirrhotic subjects than in controls; 22.8 cm/s versus 33.6 cm/s (P < 0.001). The degree of HVW abnormality among cirrhotics showed a significant positive correlation with CTP (r = 0.283, P = 0.029). MM-PVV on the other hand showed no correlation with CTP class (r = −0.124; P = 0.346). Linear regression showed that HVW was a significant predictor of hepatic dysfunction based on CTP.Conclusion:Changes in the waveform pattern of the HVs are a good predictor of the derangement of hepatic function in patients with LC than changes in PVV. HVW pattern could therefore serve as an adjunct to CTP class in hepatic function assessment.

Renal and hepatic function of patients with severe tricuspid regurgitation undergoing inferior caval valve implantation

Due to progressive abdominal-venous congestion severe tricuspid regurgitation (TR) is a common cause of cardiorenal and cardiohepatic syndrome. We initiated the TRICAVAL study to compare interventional valve implantation into the inferior vena cava (CAVI) versus optimal medical therapy (OMT) in severe TR. In the present subanalysis, we aimed to evaluate the effects of CAVI on clinical signs of congestion, renal and hepatic function. TRICAVAL was an investigator-initiated, randomized trial. Twenty-eight patients with severe TR were randomized to OMT or CAVI using an Edwards Sapien XT valve. Probands who completed the 3-month follow-up (CAVI [n = 8], OMT [n = 10]) were evaluated by medical history, clinical examination, and laboratory testing at baseline, 3 and 12 months. After 3 months, the CAVI group exhibited a significant reduction of body weight (from 80.7 [69.0–87.7] kg to 75.5 [63.8–84.6] kg, p < 0.05) and abdominal circumference (from 101.5 ± 13.8 cm to 96.3 ± 15.4 cm, p ≤ 0.01) and a trend to lower doses of diuretics compared to OMT. Renal and hepatic function parameters did not change significantly. Within a short-term follow-up, CAVI led to an improvement of clinical signs of venous congestion and a non-significant reduction of diuretic doses compared to OMT.

Age Moderates the Impact of TRAbs on Thyroid Hormones and Hepatic Function in Patients with Graves' Disease.

Thyrotropin receptor antibodies (TRAbs) play a significant role in the course of hepatic dysfunction (HDF) in patients with Graves' disease (GD). However, few studies have considered the factors that influence the relationships among TRAbs, thyroid hormone levels, and hepatic function in subjects with newly diagnosed GD. Here we investigated the associations of TRAbs with thyroid hormones and hepatic function and assessed potential factors that can influence these associations among patients with GD. A total of 368 patients newly diagnosed with GD were collected in this cross-sectional study. Patients who had received antithyroid drugs, radioactive iodine, or surgery were excluded. Levels of TRAbs and thyroid hormones and hepatic function were recorded. Linear and binary logistic regression analysis models were applied to investigate associations among these variables after adjusting for confounding characteristics. There was a significant difference in TRAbs indices between the HDF and normal hepatic function groups (p <0.05). After adjusting for confounders, the relationship between TRAbs and thyroid hormones was nonlinear, showing a curve with an initial positive slope and a subsequent flattening (p <0.05). Higher TRAbs were associated with HDF [odds ratio (OR) 1.036, 95% confidence interval (CI) 1.018-1.053 per 1-IU/l increase]. These associations were modified by age, but not by gender, smoking status, Graves' orbitopathy, thyroid-peroxidase antibody levels, or thyroglobulin antibody levels. In younger patients, increasing TRAbs were correlated with higher thyroid hormones and HDF (OR 1.034, 95% CI 1.017-1.052) per1-IU/l increase). In older patients, TRAbs were not correlated with thyroid hormones or HDF (OR 1.024, 95% CI 0.993-1.056) per 1-IU/l increase. Age can affect the impact of TRAbs on thyroid hormone levels and hepatic function in GD. TRAb measurement can have good predictive value in younger patients.

Bioengineering a cryogel-derived bioartificial liver using particle image velocimetry defined fluid dynamics

Bioartificial Liver (BAL) devices are extracorporeal systems designed to support or recover hepatic function in patients with liver failure. The design of an effective BAL remains an open challenge since it requires a complex co-optimisation of cell colonisation, biomaterial scaffold and BAL fluid dynamics. Building on previous evidence of suitability as a blood perfusion device for detoxification, the current study investigated the use of RGD-containing p(HEMA)-alginate cryogels as BAL scaffolds. Cryogels were modified with alginate to reduce protein fouling and functionalised with an RGD-containing peptide to increase hepatocyte adhesion. A novel approach for characterisation of the internal flow through the porous matrix was developed by employing Particle Image Velocimetry (PIV) to visualise flow inside cryogels. Based on PIV results, which showed the laminar nature of flow inside cryogel pores, a multi-layered bioreactor composed of spaced cryogel discs was designed to improve blood/hepatocyte mass exchange. The stacked bioreactor showed a significantly higher production of albumin and urea compared to the column version, with improved cell colonisation and proliferation over time. The cell-free cryogel-based device was tested for safety in a bile-duct ligation model of liver cirrhosis. Thus, a stacked bioreactor prototype was developed based on a surface-engineered cryogel design with optimised fluid dynamics for BAL use.

Effects of modified ultrafiltration on postoperative hepatic and renal function of pediatric patients with congenital cyanotic/non-cyanotic heart defect who underwent open heart surgery: Retrospective study

Aim: Increased total body water and capillary permeabilty in pediatric cardiopulmonary bypass can cause organ disfunction. Modified ulltrafiltration is developed for decrease total body water and attenuate organ disfunction. The purpose of this study, is to investigate retrospective effects of modified ultrafiltration on postoperative hepatic and renal functions of pediatric patients with congenital siyanotic/nonsiyanotic heart defect who underwent open heart surgery. Material and methods: In this study, we assessed 93 children who underwent pediatric cardiac surgery with cardiopulmonary bypass from January 2009 to August 2011.Patients were divided into two groups. Group 1 (n=62) patiens, to whom modified ultrafiltration was performed, compared with 31control patients (group 2). Patients who had redo cardiac surgery, preoperative organ disfunction, otoimmune disease, genetic disorders, shunt and emergency operations were excluded. Pre and postoperative biochemical parameters, postoperative urine output, chest tube drenaige, diüretic usage, blood and blood product transfusion, dialysis requirement and mortality were compared. Results: Age, weight, body surface area, congenital defect type and number, preoperative and intraoperative blood samples measurement, cross clamp time, cardiopulmonary bypass time were similar between 2 groups (p&amp;gt;0,05).The difference in percent increase in creatinine leves of 2 group was statistically significant When these changes were re-evaluated according to the body surface area by univariate analysis(p&amp;lt;0,05). Percent increase in total plasma protein level was also statistically significant between the groups (p&amp;lt;0,05) (It was-6,5% in group 1 and -5,5% in group 2). Percent increase in plasma albumin level was -18,2% in group 1, and -13,4% in group 2. When these changes were re-evaluated according to the body surface area by univariate analysis, a significant statistical difference was detected. (p&amp;lt;0,05). While two patients required dialysis in group 1, dialysis was performed in 4 patients in group 2. There was no statistically difference between the groups in terms of dialysis needed(p&amp;lt;0,05). There was no difference between the groups in terms of mortality (p&amp;gt;0,05) Conclusion: Hemodynamic, pulmonary, hematologic and immunologic effects of modified ultrafiltration are well known. Although our study group was not big enough to get a conclusion, we believe that modified ultrafiltration can be an effective method in preservation of renal and hepatic function of the patients who underwent total reconstructive congenital heart surgery.

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification.

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray's Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.

Impact of caval vein implantation on severity of tricuspid regurgitation, renal and hepatic function in patients with severe secondary tricuspid regurgitation

Abstract Background Severe tricuspid regurgitation (TR) is an important determinant for functional capacity and survival. It frequently occurs in patients with advanced heart failure resulting in progressive venous congestion with cardiorenal and cardiohepatic syndrome. The prospective, randomized TRICAVAL study reported the effect of inferior caval vein implantation of an Edwards Sapien XT valve (CAVI) in comparison to optimal medical therapy (OMT) in patients with severe TR. The study did not detect a superior functional outcome after CAVI, but a significant improvement in quality of life. Due to safety concerns, the study was stopped prematurely after 4 periprocedural complications. Purpose We hypothesised that CAVI reduces reflux into the inferior vena cava and leads to an increase in systolic right atrial pressure, which may result in an improvement of TR severity. The present subanalysis of the TRICAVAL study evaluates the impact of inferior caval vein implantation on TR severity, right heart parameters and renal and hepatic function. Methods Twenty-eight patients with severe TR were randomized in either CAVI group (n=14) with caval vein implantation of an Edwards Sapien XT valve or OMT group (n=14). Medical history, clinical examination, laboratory testing and echocardiographic measurements were analysed in patients with completed FUP (OMT [n = 10], CAVI [n = 8]). Follow-up examinations were performed at baseline and three months after enrolment. Results After three months, the CAVI group exhibited a significant reduction of systolic hepatic vein reflux volume (5.0 [1.3–11.0] ml vs. 14.0 [10.3–18.0] ml, p&amp;lt;0.05) and hepatic vein diameter (10.8 [10.0–12.0] mm vs. 14.0 [11.5–15.0] mm, p&amp;lt;0.05) in comparison to OMT. Compared to baseline, CAVI improved body weight (80.7 [69.0–87.7] kg versus 75.5 [63.8–84.6] kg, p&amp;lt;0.05) and abdominal circumference (101.5±13.8 cm versus 96.3±15.4 cm, p≤0.01) paralleled by a trend to lower doses of diuretics. However, over the FUP period, there were no significant changes regarding TR severity, right heart function and morphology as well as renal and hepatic function within both groups, nor in the comparison between CAVI and OMT. Conclusion As a proof of our concept, CAVI resulted in a decrease in systolic hepatic vein reflux, hepatic vein diameter and clinical signs of venous congestion. However, TR severity, right heart function and morphology as well as renal and hepatic function remained stable. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Edwards Lifesciences, Incorporated (Irvine, CA)

Cellular Location of HNF4α is Linked With Terminal Liver Failure in Humans.

Hepatocyte nuclear factor 4 alpha (HNF4α) is a transcription factor that plays a critical role in hepatocyte function, and HNF4α‐based reprogramming corrects terminal liver failure in rats with chronic liver disease. In the livers of patients with advanced cirrhosis, HNF4α RNA expression levels decrease as hepatic function deteriorates, and protein expression is found in the cytoplasm. These findings could explain impaired hepatic function in patients with degenerative liver disease. In this study, we analyzed HNF4α localization and the pathways involved in post‐translational modification of HNF4α in human hepatocytes from patients with decompensated liver function. RNA‐sequencing analysis revealed that AKT‐related pathways, specifically phospho‐AKT, is down‐regulated in cirrhotic hepatocytes from patients with terminal failure, in whom nuclear levels of HNF4α were significantly reduced, and cytoplasmic expression of HNF4α was increased. cMET was also significantly reduced in failing hepatocytes. Moreover, metabolic profiling showed a glycolytic phenotype in failing human hepatocytes. The contribution of cMET and phospho‐AKT to nuclear localization of HNF4α was confirmed using Spearman's rank correlation test and pathway analysis, and further correlated with hepatic dysfunction by principal component analysis. HNF4α acetylation, a posttranslational modification important for nuclear retention, was also significantly reduced in failing human hepatocytes when compared with normal controls. Conclusion: These results suggest that the alterations in the cMET‐AKT pathway directly correlate with HNF4α localization and level of hepatocyte dysfunction. This study suggests that manipulation of HNF4α and pathways involved in HNF4α posttranslational modification may restore hepatocyte function in patients with terminal liver failure.

Validation set analysis to predict postoperative outcomes by technetium-99m galactosyl serum albumin scintigraphy for hepatectomy.

The indocyanine green retention rate at 15 min (ICGR15) is a gold standard parameter of liver function when deciding on the extent of hepatectomy. However, ICGR15 is influenced by several hepatic conditions. To evaluate auxiliary preoperative liver functional reserve, we examined the clinical significance of modified parameters by blood tests and technetium-99m galactosyl human serum albumin (Tc-GSA) scintigraphy. We measured liver function parameters, including the hepatic uptake ratio (LHL15) and the blood pool clearance index (HH15) of Tc-GSA and their modified formulae [LHL/HH15, LHL minus HH15, and converted ICGR15 (cICGR15) from a preliminary study] in 229 patients, including 18 with biliary obstruction. The mean values of LHL15/HH15, LHL minus HH15, and cICGR15 were 1.646 ± 0.295, 0.347 ± 0.116, and 13.2 ± 5.3%, respectively. These parameters correlated significantly with other liver functions measured by blood tests except for the bilirubin level (P < 0.05) although the actual ICGR15 level correlated positively with the bilirubin level. The difference of ICGR15 (ICGR15 minus cICGR15) in patients with biliary obstruction tended to be higher in comparison with that in patients without biliary obstruction (P = 0.044). Values of LHL/HH15, LHL minus HH15, and the cICGR15 were not significantly associated with postoperative complications. The modified parameters of Tc-GSA were useful for evaluating hepatic function in patients with high bilirubinemia due to biliary obstruction. However, it remains difficult to establish a more reliable parameter as a standard hepatic function test instead of ICGR15.

Amount of Cycloserine Emanating from Terizidone Metabolism and Relationship with Hepatic Function in Patients with Drug-Resistant Tuberculosis

Background and objectivesThe dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined.MethodsThis prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration (Cmax) and trough concentration (Cmin), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding affinity of UB to albumin (Kaf), using R statistical software version 3.5.3.ResultsThirty-eight patients took a daily dose of 750 mg terizidone, while one took 500 mg. The amount of cycloserine [median (range)] that emanated from terizidone metabolism was 51.6 (0.64–374) mg. Cmax (R2 = 22%, p = 0.003) and Cmin (R2 = 10.6%, p = 0.044) were significantly associated with increased CB concentration. Cmax was significantly associated with increased Kaf (R2 = 10.1%, p = 0.048), while high CLm/F was significantly associated with decreased AST/ALT (R2 = 21%, p = 0.003).ConclusionsCycloserine is not interchangeable with terizidone, as amounts are lower than expected. Cycloserine may be a predisposing factor to the development of hyperbilirubinaemia, as CLm/F is affected by hepatic function.

2347-PUB: Relationship between Aging and Effects of SGLT2 Inhibitors on Glucose and Lipid Metabolisms and Hepatic Function in Japanese Patients with Type 2 Diabetes

SGLT2 inhibitors (SGLT2is) have been found to improve blood glucose, HbA1c and triglyceride levels and also hepatic dysfunction in patients with type 2 diabetes. However, scarcely any studies have examined whether there are differences in the effects of SGLT2is according to patient age. In this study, we stratified the patients into 3 groups according to the age and investigated whether age influences the effects of SGLT2is on glucose and lipid metabolisms and hepatic function in these patients. The patients were stratified into the following 3 age groups: &amp;lt;50, 50 to 64, and ≥65 years. Five SGLT2is were administered for 6 months at the following doses: 2.5 mg/day luseogliflozin, 5 mg/day dapagliflozin, 20 mg/day tofogliflozin, 10 mg/day empagliflozin, and 100 mg/day canagliflozin. Blood samples were collected before and after the treatment to measure biochemical parameters. Significant decreases, compared to the baseline, of HbA1c, serum glucose and insulin, and HOMA-R were observed after the treatment with the SGLT2is in the &amp;lt;64 years age groups, but not the ≥65 years age group. With regard to the effects on lipid metabolism, increase in serum HDL cholesterol and decrease in LDL cholesterol/HDL cholesterol ratio were observed in the ≥65 years age group. In addition, hepatic function parameters improved significantly in the &amp;lt;64 years age groups, but to a lesser degree in the ≥65 years age group. The effects on BMI were not affected. The results revealed that some effects of SGLT2is were affected by aging. The SGLT2is improved glucose metabolism in the patients aged &amp;lt;64 years, but this effect was weaker in those aged ≥65 years. However, the SGLT2is led to a more anti-atherogenic serum lipid profile in patients aged ≥65 years than in those aged &amp;lt;65 years. In addition, it appears that the hepatic function-improving effect of SGLT2is decreases with age, especially in patients aged ≥65 years. The effects of SGLT2 inhibitors on BMI were not affected. Disclosure M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Natsume: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd. Y. Oshida: None. T. Miyata: Research Support; Self; Bayer AG, Daiichi Sankyo Company, Limited.

Blood lead and cadmium levels associated with hematological and hepatic functions in patients from an e-waste-polluted area

Chronic exposures to toxic trace metals have hazardous effects on human health, especially exposure to lead (Pb) and cadmium (Cd). Blood Pb and Cd reflect toxicity on human health. A total of 267 hospitalized patients, of which 158 were from Guiyu (exposed group) in China, and 109 from Jinping (reference group), were recruited in this study. Blood Pb and Cd were measured by graphite furnace atomic absorption spectrometry. Blood Pb and Cd levels from the exposed group were both higher than in the reference group. Blood Pb levels are positively associated with blood Cd levels from the two groups. Blood Pb and Cd levels are associated with elevated hematological and hepatic parameters in patients from the exposed and reference groups. The results suggest toxic trace metals may increase liver metabolic burden, inducing abnormal liver function.

PO-103 The mechanism of long-term regular exercise intervention on liver injury in patients with NAFLD based on miR-146a regulation of TLR4/NF-KB signaling pathway

Objective To investigate the effects of long-term regular exercise on hepatic function in patients with non-alcoholic fatty liver (NAFLD) using blood biochemistry and liver fibrosis markers, and to compare the differential expression of cytokines related to TLR4/NF-KB signaling pathway. A preliminary discussion was made on its regulation mechanism.&#x0D; Methods Forty patients with NAFLD diagnosed in the Hunan Normal University School of Medicine, according to the degree of steatosis and exercise intervention, the patients were divided into control group (NAFLD group) 20 cases and long-term regular exercise group 20 cases, and the same time in our hospital Twenty patients with physical examination were normal controls; general data of all subjects, ALT, AST, GGT, serum type III procollagen (PCIII), hyaluronan (HA), and type IV collagen (CIV) were examined; Fluorescent quantitative PCR was used to detect the differential expression of TLR4/NF-KB signaling pathway-related cytokines and miR-146a in the blood of each group of subjects, revealing the effects and possible mechanisms of long-term regular exercise on liver fibrosis.&#x0D; Results Compared with the normal group, the levels of serum ALT, AST, GGT, PCIII, HA, and CIV in the non-alcoholic fatty liver patients were significantly lower in the long-term regular exercise group than in the control group; blood TLR4, NF-KB, MY-D88 Compared with the control group, the gene expression level was significantly downregulated in the long-term regular exercise group. &#x0D; Conclusions Long-term regular exercise can effectively reduce nonalcoholic inflammatory liver injury and has a clear anti-fibrotic effect. Its mechanism may be related to long-term regular exercise through regulating the TLR4/NF-KB signaling pathway related factors and the regulation of molecular miR-146a, reducing inflammation and preventing the formation of fibrosis.