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Liver disease is common in equine practice, and treatment and prognosis are dependent on histopathologic examination of biopsies. Liver biopsy is invasive and expensive which restricts its use. Serum markers are used to predict hepatic fibrosis in humans. This study aimed to investigate the enhanced liver fibrosis (ELF) test, based on serum Hyaluronic Acid (HA), procollagen III N-terminal peptide (PIIINP), and tissue inhibitor of metalloproteinase 1 (TIMP-1) to detect hepatic fibrosis in equids. Four groups were included; two with increased serum concentrations of liver-derived enzymes and a liver biopsy (group H; 10 horses and ponies and group D; 10 donkeys) and two without any evidence of liver disease (group HC; 10 horses and ponies and group DC; 10 donkeys). All samples were analyzed for concentrations of HA, PIINP, and TIMP-1. Given the failure to detect TIMP-1 in most subjects, a novel eELF (equid ELF) score was calculated, based on HA and PIIINP. HA and PIIINP concentrations and the eELF score, were compared with determined hepatic fibrosis. HA, PIIINP, and eELF were significantly greater in horses and ponies with a histopathologic fibrosis score ≥ 2 compared with those < 2. A similar observation was found with donkeys for HA and eELF. A significant correlation was found between fibrosis score and HA, PIIINP, and eELF for horses and ponies, and between fibrosis score and HA and eELF in donkeys. Serum HA and the eELF score might be useful serum markers to predict and monitor hepatic fibrosis in horses, ponies, and donkeys., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Lonicera caerulea fruit is a polyphenol-rich berry. The protective effects of L. caerulea berry extract before and after in vitro digestion on hepatitis were investigated using lipopolysaccharide-induced BRL-3A cell model in this study. The results demonstrated that both undigested extract and digested extract pre-treatment observably inhibited oxidative stress, as evidenced by the reduction in the production of reactive oxygen species, malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyls; significantly maintained energy metabolism and cellular structure, which were verified by the suppression of decline in the activities of ATP synthetase, cytochrome c oxidase and succinate dehydrogenase, and changes in histological structure; markedly modulated hepatic function by attenuating the enhancement in aspartate aminotransferase and alanine aminotransferase activities and the decrease in acetylcholine esterase activity; and remarkably attenuated the production of pro-inflammatory factors such as interleukin-1beta and interleukin-6. Taken together, the application of L. caerulea berry extract protects liver against the damage caused by lipopolysaccharide.

In the present review, the authors, based on the multiple functions performed by the liver, analyze the multiple biochemical and hematological changes as an expression of altered liver function in the horse. The liver performs important metabolic functions related to the synthesis, degradation, and excretion of various substances. Modification of these functions can be evaluated and diagnosed by determining serum concentrations of several serum analytes, including enzymes and other endogenous substances. Hepatocellular enzymes, such as sorbitol dehydrogenase-SDH and glutamate dehydrogenase-GLDH, are released following hepatocellular necrosis. Hepatobiliary enzymes, such as γ-glutamyl transferase-GGT, increase in response to necrosis, cholestasis, and other alterations in bile conducts. Serum concentrations of mainly endogenous and exogenous substances that the liver should synthesize or eliminate, such as proteins (albumin and globulins), bile acids, urea, glucose, total and direct bilirubin, and coagulation factors, and fibrinogen should be included in the liver function test profile. The interpretation of laboratory tests of liver function will allow the diagnosis of functional loss of the organ. Some of the analytes considered provide information on the prognosis of liver disease. This review will provide an accurate and objective interpretation of the common biochemical and hematological tests in use in the diagnosis of equine hepatic disease patients, aiding still further the veterinary activity on the applied equine clinical cases., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: There are limited data about postoperative changes in hepatic and renal function in adults with congenital heart disease (CHD) undergoing isolated heart transplant. The purpose of this study was to assess postoperative changes in hepatic and renal function in this population., Methods: Retrospective cohort study of adults with CHD undergoing isolated heart transplant at Mayo Clinic (2003-2019). Global hepatic function was assessed using the model for end-stage liver disease excluding international normalized ratio [MELD-XI]) score; hepatic fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate/platelet ratio index (APRI); and renal function was assessed using estimated glomerular filtration rate (GFR). All indices were measured preoperatively and postoperatively (at 6 months, 1 year, 2 years)., Results: Of 40 patients (age 41 ± 8 years) in the study, 35 had complete preoperative and postoperative data. There was a temporal improvement in hepatic and renal indices from preop (MELD-XI 14 ± 5, APRI 0.60 ± 0.23, FIB-4 1.44 ± 0.38, GFR 59 [44-83]) to 6 months postop (MELD-XI 12 ± 6, APRI 0.49 ± 0.17, FIB-4 1.29 ± 0.33, GFR 68 [54-96]) and 1-year postop (MELD-XI 9 ± 3, APRI 0.41 ± 0.16, FIB-4 1.12 ± 0.29, GFR 82 [69-108]), p < 0.05 for all comparisons., Conclusions: CHD patients undergoing isolated heart transplant had significant improvement in hepatic and renal function. These data suggests that selected CHD patients may do well with isolated heart transplant despite reduced hepatic and renal function, and hepatic fibrosis preoperatively. More rigorous prospective studies are required to determine the relative outcomes of isolated versus combined heart-liver transplant in this population., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Streptococcus pneumoniae is an uncommon etiologic organism in children with hemolytic uremic syndrome (HUS). Historically, severe S. pneumoniae-associated HUS usually has a poor clinical outcome. The clinical manifestations of marked jaundice and hepatic dysfunction in this form of HUS are extremely rare. We report a 10-month-old female infant with S. pneumoniae-associated HUS who had the unusual manifestation of severely elevated conjugated bilirubin and hepatic transaminases. Screening for viral hepatitis was negative, and evidence of biliary obstruction and hepatotoxic drug exposure was also absent. The patient was treated with antihypertensive agents for 2.5 months and required peritoneal dialysis for a period of 26 days. Hepatic function returned to normal on the 8th day of hospitalization. Renal function was mildly impaired at 1-year follow-up. Our report suggests that severe conjugated hyperbilirubinemia is a rare manifestation of S. pneumoniae-associated HUS in children. It is important for pediatricians that pneumococcal infection with severe hematologic and renal disorders should be investigated for evidence of S. pneumoniae-associated HUS. [J Formos Med Assoc 2007;106(2 Suppl):S17-S22]

Some events of hepatotoxicity have been linked to consumption of green tea supplements. The association between consumption of green tea or green tea supplements and abnormal liver biomarkers in adults was investigated using cross-sectional data from the 2009-2014 United States National Health and Nutrition Examination Survey (U.S. NHANES). Individuals with levels of either bilirubin or GGT, ALT, AST, and/or ALP in excess of the age- and gender-specific upper limits of normal ranges were classified as having abnormal liver biomarkers. Associations between green tea or green tea supplement use (consumption vs. not) and liver function were determined using multiple logistic regression modelling. 12,289 persons were included in the green tea analyses and 12,274 in the green tea supplement analyses. The odds of having one or more abnormal liver biomarkers were significantly reduced (p = 0.01) with consumption of green tea (OR: 0.49; 95% CI: 0.28, 0.85), while no significant association (p = 0.78) was determined for consumption of green tea supplements (OR: 0.92; 95% CI: 0.52, 1.64). Based on data from the 2009-2014 U.S. NHANES, green tea consumption was associated with reduced odds of having one or more abnormal liver biomarkers; whereas, no significant association was determined with consumption of green tea supplements., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the prevalence and prognostic implications of cardiohepatic syndrome (CHS) in patients with tricuspid regurgitation (TR) treated with tricuspid transcatheter edge-to-edge valve repair (T-TEER)., Background: The role of CHS in patients undergoing T-TEER for severe TR has not been studied., Methods: This study included patients who underwent T-TEER for TR between 2016 and 2020 at 2 high-volume academic centers. CHS was defined as elevation of at least 2 of 3 cholestatic hepatic enzymes. The impact of CHS on 1-year all-cause mortality and clinical outcomes after T-TEER was investigated., Results: T-TEER reduced TR severity to ≤2+ in 257 of 305 included patients (86.2%). CHS was present in 45.2% of patients and was associated with a higher rate of mortality and of first hospitalization for heart failure (HHF) (CHS vs no CHS: estimated 1-year mortality, 34.0% vs 15.9% [P < 0.01]; HHF, 23.0% vs 12.2% [P = 0.01]). CHS was identified as an independent predictor of 1-year all-cause mortality (HR: 1.86; 95% CI: 1.10-3.14; P < 0.05). Irrespective of CHS, T-TEER improved New York Heart Association functional class and 6-minute walk distance in the majority of patients. In patients with impaired baseline hepatic function, laboratory liver parameters improved after T-TEER., Conclusions: CHS is a strong predictor of mortality and HHF after T-TEER and should be evaluated in the process of procedural decision making for T-TEER. Nevertheless, T-TEER is associated with relevant symptomatic alleviation irrespective of CHS., Competing Interests: Funding Support and Author Disclosures Drs Näbauer and Braun have received speaker honoraria from Abbott Vascular. Dr Orban has received speaker fees from Abbott Vascular and TomTec Imaging Systems; and has received speaker honoraria from Abbott Medical, AstraZeneca, Abiomed, Bayer Vital, Biotronik, Bristol Myers Squibb, CytoSorbents, Daiichi-Sankyo Deutschland, Edwards Lifesciences Services, and Sedana Medical. Dr Higuchi has received lecture fees from Medtronic Japan, Daiichi-Sankyo, and Ono Pharmaceutical Company. Dr Lurz has been a consultant to Abbott Structural Heart, Edwards Lifesciences, and Medtronic. Dr Hausleiter has received speaker honoraria and research support from and serves as consultant for Abbott Vascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents' occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (β = 0.296, P = 0.036) and DMP (β = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (β = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (β = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (β = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5-14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Simultaneous exposure to multiple pollutants has received great concerns considering that the interactions between pollutants can alter the environment fate and bioavailability of pollutants with potentially deleterious effects. Graphene oxide (GO) has been widely used in many areas including environmental remediation, biology and agriculture. However, researchers have largely ignored the combined toxicity of GO with coexisting toxicants. Cis-bifenthrin (cis-BF), a typical synthetic pyrethroid insecticide, was frequently detected in the environment, which raised the possibility of interaction between cis-BF and GO. Our study investigated the toxic effects of cis-BF alone or combined with GO on the lipid homeostasis in Xenopus laevis. Tadpoles at 51 stage were exposed to cis-BF (0, 12, 60 and 300 ng/L) or in their combination with GO (0.1 mg/L) for 21 days. Coexposure to cis-BF and GO deteriorated the lipid homeostasis disruption in tadpoles. The up- or down-regulation of lipogenesis genes expression and enzymes activity were amplified in the coexposure groups. Furthermore, the presence of GO enhanced the deleterious impacts of cis-BF on the hepatic function in tadpoles. This study uniquely shows that GO promotes the lipotoxicity and hepatic function deficit caused by cis-BF exposure in frog., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: The liver receives gut-derived endotoxin via the portal vein, clearing it before it enters systemic circulation. Hemodialysis negatively impacts the perfusion and function of multiple organs systems. Dialysate cooling reduces hemodialysis-induced circulatory stress and protects organs from ischemic injury. This study examined how hemodialysis disrupts liver hemodynamics and function, its effect on endotoxemia, and the potential protective effect of dialysate cooling., Methods: Fifteen patients were randomized to receive either standard (36.5°C dialysate temperature) or cooled (35.0°C) hemodialysis first in a two-visit crossover trial. We applied computed tomography (CT) liver perfusion imaging to patients before, 3 hours into and after each hemodialysis session. We measured hepatic perfusion and perfusion heterogeneity. Hepatic function was measured by indocyanine green (ICG) clearance. Endotoxin levels in blood throughout dialysis were also measured., Results: During hemodialysis, overall liver perfusion did not significantly change, but portal vein perfusion trended towards increasing ( P  = 0.14) and perfusion heterogeneity significantly increased ( P  = 0.038). In addition, ICG clearance decreased significantly during hemodialysis ( P  = 0.016), and endotoxin levels trended towards increasing during hemodialysis ( P  = 0.15) and increased significantly after hemodialysis ( P  = 0.037). Applying dialysate cooling trended towards abrogating these changes but did not reach statistical significance compared to standard hemodialysis., Conclusion: Hemodialysis redistributes liver perfusion, attenuates hepatic function, and results in endotoxemia. Higher endotoxin levels in end-stage renal disease (ESRD) patients may result from the combination of decreased hepatic clearance function and increasing fraction of liver perfusion coming from toxin-laden portal vein during hemodialysis. The protective potential of dialysate cooling should be explored further in future research studies., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Previous studies have suggested that sodium-glucose co-transporter-2 (SGLT2) inhibitors may improve hepatic function; however, the evidence is scarce. Hence, we performed a meta-analysis of randomized controlled trials to evaluate the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hepatic parameters. PubMed, Web of Science, Scopus, and Google Scholar databases were searched to identify randomized controlled trials examining the effect of SGLT2 inhibitors on hepatic parameters. Meta-analysis was performed using a random-effects model and sensitivity analysis. Meta-analysis revealed that SGLT2 inhibitors therapy significantly lowered alanine aminotransferase (ALT) (WMD: -4.79 U/L, 95 % CI: -6.10, -3.47, I 2 = 62 %, p < 0.00001), aspartate aminotransferase (AST) (WMD: -2.49 U/L, 95 % CI: -3.30, -1.68, I 2 = 54 %, p < 0.00001), alkaline phosphatase (AP) (WMD: -1.13 U/L, 95 % CI: -2.03, -0.22, I 2 = 23 %, p = 0.02), and gamma-glutamyl transferase (GGT) (WMD: -7.77 U/L, 95 % CI: -9.33, -6.21, I 2 = 5 %, p < 0.00001). Additionally, SGLT2 inhibitors showed a significant increase in bilirubin levels (WMD: 0.64 U/L, 95 % CI: 0.27, 1.00, I 2 = 53 %, p < 0.0006. Finally, no significant changes were found on albumin levels (WMD: 0.13 U/L, 95 % CI: -0.06, 0.32, I 2 = 53 %, p < 0.0006) after SGLT2 inhibitors treatment. In conclusion, our results suggest that treatment with SGLT2 inhibitors exerts a beneficial effect on liver function tests through decreased ALT, AST, AP, and GGT concentrations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To describe the longitudinal changes in hepatic function among HIV-infected tuberculosis (TB) patients receiving once-daily nevirapine (NVP)- or efavirenz (EFV)-based antiretroviral treatment (ART) along with rifampin-containing anti-TB treatment., Methods: This was a nested study within a randomized clinical trial, taking place between May 2006 and June 2008 at the National Institute for Research in Tuberculosis, Chennai, India. Antiretroviral-naïve HIV-infected TB patients were initiated on an intermittent short-course regimen and randomized to receive didanosine and lamivudine with either NVP (400 mg) or EFV (600 mg) once-daily. Blood was analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum alkaline phosphatase (SAP), and bilirubin at baseline, at ART initiation, fortnightly after ART initiation until 2 months, then monthly until 6 months and 6-monthly thereafter., Results: Of the 168 patients included (79% men, median CD4 count 93 cells/mm3, median viral load 242,000 copies/ml), 104 were on EFV-based ART and 64 on NVP-based ART. There was a small but statistically significant elevation in ALT and SAP at 2 weeks and AST at 6 weeks after ART initiation. The proportion of patients with rate-limiting toxicity of liver enzymes was small. None had treatment terminated because of hepatotoxicity., Conclusion: Hepatotoxicity is not a major concern when HIV-infected TB patients, with normal baseline liver function initiate treatment for both infections simultaneously., (Copyright © 2013 International Society for Infectious Diseases. All rights reserved.)