Changes In Hepatic Function Research Articles

Altered blood microbiome in patients with HCV-related Child-Pugh class B cirrhosis

BackgroundAltered bacterial translocation is associated with changes in hepatic function and the progression from compensated to decompensated cirrhosis. Child-Turcotte-Pugh (CTP) score is an essential indicator of liver severity. Thus, we aimed to study differences in the blood microbiome together with metabolome profile between HCV-infected patients with CTP class B (CTP-B, significant functional compromise) and patients with CTP class A (CTP-A, well-compensated cirrhosis). MethodsWe conducted a cross-sectional study in patients with advanced HCV-related cirrhosis (n = 88) stratified by CTP-B and CTP-A. Bacterial 16S rRNA sequencing was sequenced by MiSeq Illumina technology and non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI- to complement the analysis. ResultsPatients with CTP-B had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level than patients with CTP-A. Likewise, we observed significant differences in beta diversity between groups at phylum, class, and order levels, showing lower diversity in patients with CTP-B. Higher relative abundance of Proteobacteria (p = 0.012), Alphaproteobacteria (p = 0.005), Sphingomonadales (p = 0.012) and Sphingomonadaceae (p = 0.016) were significantly associated with CTP-B. The phylum Proteobacteria was positively correlated with ethanolamine and oleic acid (p = 0.005 and p = 0.004, respectively) and negatively with p-cresol (p = 0.006). In addition, the order Sphingomonadales and the family Sphingomonadaceae was also negatively correlated with p-cresol (p = 0.001 and p = 0.001). ConclusionsBlood microbial diversity was significantly decreased in patients with CTP-B, who presented an enrichment of Proteobacteria, Alphaproteobacteria, Sphingomonadales and Sphingomonadaceae compared to patients with CTP-A.

"Fontan Conduit Stent-Angioplasty and Progression of Fontan-Associated Liver Disease".

Patients with Fontan circulation insidiously develop congestive hepatopathy related to chronically reduced cardiac output and central venous hypertension, also known as Fontan-associated liver disease (FALD). Fontan pathway obstruction is increasingly detected and may accelerate FALD. The impact of conduit stent angioplasty on FALD is unknown. Retrospective, single-center review of patients with Fontan circulation who underwent conduit stent angioplasty at cardiac catheterization over 5-year period. Demographics and cardiac histories were reviewed. Labs, liver ultrasound elastography, echocardiogram, hemodynamic and angiographic data at catheterization were recorded pre- and post-stent angioplasty. Primary outcome was change in hepatic function via MELD-XI scores and liver stiffness (kPa), with secondary outcomes of ventricular function, BNP, and repeat catheterization hemodynamics. 33 patients underwent Fontan conduit stent angioplasty, 19.3 ± 7.0years from Fontan operation. Original conduit diameter was 19.1 ± 1.9mm. Prior to angioplasty, conduit size was reduced to a cross-sectional area 132 (91, 173)mm2 and increased to 314 (255, 363)mm2 post-stent. Subjects' baseline median MELD-XI of 11 (9, 12) increased to 12 (9, 13) at 19 ± 15.5months post-angioplasty (n = 22, p = 0.053). There was no significant change in liver stiffness at 12.1 ± 8.9months post-angioplasty (n = 15, p = 0.13). Median total bilirubin significantly increased (1.4 [0.9, 1.8]), from baseline 1.1 [0.7, 1.5], p = 0.04), as did median BNP (41 [0, 148] from baseline 34 [15, 79]; p = 0.02). There were no significant changes in ventricular function or repeat invasive hemodynamics (n = 8 subjects). Mid-term follow-up of Fontan subjects post-conduit stent angioplasty did not show improvements in non-invasive markers of FALD.

Assessing regional hepatic function changes after hypertrophy induction by radioembolisation: comparison of gadoxetic acid-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy

BackgroundTo compare Gd-ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and 99mTc-labelled mebrofenin hepatobiliary scintigraphy (HBS) as imaging-based liver function tests after unilateral radioembolisation (RE) in patients with primary or secondary liver malignancies.MethodsTwenty-three patients with primary or secondary liver malignancies who underwent Gd-EOB-DTPA-enhanced MRI within a prospective study (REVoluTion) were evaluated. REVoluTion was a prospective open-label, non-randomised, therapy-optimising study of patients undergoing right-sided or sequential RE for contralateral liver hypertrophy at a single centre in Germany. MRI and hepatobiliary scintigraphy were performed before RE (baseline) and 6 weeks after (follow-up). This exploratory subanalysis compared liver enhancement on hepatobiliary phase MRI normalised to the spleen (liver-to-spleen ratio (LSR)) and the muscle (liver-to-muscle ratio (LMR)) with mebrofenin uptake on HBS for the total liver (TL) and separately for the right (RLL) and left liver lobe (LLL).ResultsMebrofenin uptake at baseline and follow-up each correlated significantly with LSR and LMR on MRI for TL (≤ 0.013) and RLL (≤ 0.049). Regarding the LLL, mebrofenin uptake correlated significantly with LMR (baseline, p = 0.013; follow-up, p = 0.004), whereas with LSR, a borderline significant correlation was only seen at follow-up (p = 0.051; p = 0.046).ConclusionLSRs and LMR correlate with mebrofenin uptake in HBS. This study indicates that Gd-EOB-DTPA-enhanced MRI and 99mTc-labelled mebrofenin HBS may equally be used to assess an increase in contralateral liver lobe function after right-sided RE.Relevance statementMRI may be a convenient and reliable method for assessing the future liver remnant facilitating treatment planning and monitoring of patients after RE-induced hypertrophy induction.Key points• Both MRI and HBS can assess liver function after RE.• Liver enhancement on MRI correlates with mebrofenin uptake on HBS.• MRI might be a convenient alternative for estimating future liver remnants after hypertrophy induction.Graphical

Compensatory Enlargement of the Liver after Proton Beam Therapy for Hepatocellular Carcinoma

Charged particle therapy (CPT) has been applied as a safe and effective treatment option for hepatocellular carcinoma (HCC). Although most HCC patients have cirrhosis, favorable treatment outcome has been achieved with CPT preserving liver function. After proton beam therapy (PBT) for patients with HCC, the liver volume in the non-irradiated area is often enlarged. Here, we evaluated whether enlargement of the non-irradiated liver affects preserving hepatic function and prognosis in HCC patients treated with PBT. Among consecutive patients with HCC treated with PBT between April 2011 and July 2017, we retrospectively identified patients who fulfilled the following criteria: (i) receiving PBT to the right hepatic lobe, (ii) the left lateral segment was not irradiated, (iii) no local treatment was performed for liver within 12 months after PBT, and (iv) the albumin-bilirubin (ALBI) score was evaluable at 12 months after PBT. The left lateral segment was defined as the non-irradiated region and measured by contrast-enhanced CT just before and 3 months after PBT. ALBI scores just before and 12 months after PBT were compared to evaluate changes of hepatic function. Overall survival rate was estimated using the Kaplan-Meier method, and differences in survival between subgroups were examined using the log-rank test. The ALBI scores were compared using the Wilcoxon signed-rank test. We identified 40 patients (male/female = 32/8). The median age at the start date of PBT was 72 (range, 54-87) years. The prescribed dose was 66.0-76.0 Gy (relative biological effectiveness) delivered in 10-38 fractions. The median follow-up was 61 (range, 12-126) months. The 5-year overall survival rates were 79.0% (95% CI: 60.4-100.0%) in the larger enlargement group (n = 16, enlarged volume of non-irradiated region 3 months after PBT ≥75 cm3) and 53.7% (95% CI: 36.0-79.9%) in the smaller enlargement group (n = 24, as above, <75 cm3), respectively (p = 0.21). The median ALBI scores just before and 12 months after PBT were -3.14 (95% CI: -3.22- (-2.53)) and -2.74 (95% CI: -3.07- (-2.42)) in the larger enlargement group (p = 0.09), and -2.91 (95% CI: -3.15- (-2.40)) and -2.59 (95% CI: -2.74- (-2.12)) in the smaller enlargement group (p = 0.006), respectively. Our study suggests that larger enlargement of the non-irradiated liver after PBT is related to well-preserved liver function at 1 year and modestly associated with a favorable prognosis.

Cardio-hepatic syndrome in patients undergoing transcatheter mitral valve edge-to-edge repair.

The impact of the cardio-hepatic syndrome (CHS) on outcomes in patients undergoing transcatheter edge-to-edge repair (M-TEER) for relevant mitral regurgitation (MR) is unknown. The objectives of this study were three-fold: (I) to characterize the pattern of hepatic impairment, (II) to investigate the prognostic value of CHS, and (III) to evaluate the changes in hepatic function after M-TEER. Hepatic impairment was quantified by laboratory parameters of liver function. In accordance with existing literature, two types of CHS were distinguished: Ischemic type I CHS (elevation of both transaminases) and cholestatic type II CHS (elevation of two out of three parameters of hepatic cholestasis). The impact of CHS on two-year mortality was evaluated using a Cox model. The change in hepatic function after M-TEER was assessed by laboratory testing at follow-up. We analyzed 1083 patients who underwent M-TEER for relevant primary or secondary MR at four European centers between 2008 and 2019. Ischemic type I and cholestatic type II CHS were observed in 11.1% and 23.0% of patients, respectively. Predictors for two-year all-cause mortality differed by MR etiology. While in primary MR cholestatic type II CHS was independently associated with two-year mortality, ischemic CHS type I was an independent mortality predictor in SMR patients. At follow-up, patients with MR reduction ≤2+ (obtained in 90.7% of patients) presented with improved parameters of hepatic function (median reduction of 0.2mg/dl, 0.2U/l and 21U/l for bilirubin, ALT and GGT, respectively, p<0.01). CHS is frequently observed in patients undergoing M-TEER and significantly impairs two-year survival. Successful M-TEER may have beneficial effects on CHS.

Initial Experience With Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma: A Real-world Retrospective Study

The current study evaluated the efficacy and toxicity of atezolizumab plus bevacizumab in patients with advanced-stage hepatocellular carcinoma in a real-world setting. This retrospective study enrolled 23 patients. The primary endpoint was progression-free survival (PFS). Antitumor responses 6 weeks after initiation of atezolizumab plus bevacizumab were assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and the modified RECIST (mRECIST). The Common Terminology Criteria for Adverse Events version 5.0 was used to evaluate the severity of adverse events. Relative changes in hepatic function and nutritional status were investigated. The median PFS was 119 days. The objective response rate (ORR) and disease control rate (DCR) at 6 weeks based on RECIST were 21.7% and 60.9%, respectively. The ORR and DCR based on mRECIST were 26.1% and 69.6%, respectively. The group with hepatitis B/C-related HCC had a higher ORR based on mRECIST than the non-hepatitis B and C-related group. Patients with Barcelona Clinic Liver Cancer (BCLC) stage A and B disease had a higher DCR based on RECIST than those with BCLC stage C disease. The incidence rates of any grade and grade ≥3 adverse events were 65.2% and 21.7%, respectively. The albumin-bilirubin and Child-Pugh scores, neutrophil-to-lymphocyte ratio and skeletal muscle index did not significantly worsen within 6 weeks after treatment initiation. Atezolizumab plus bevacizumab is effective and safe and can help achieve complete remission in patients with advanced-stage hepatocellular carcinoma in a real-world setting. Nevertheless, large-scale studies must be conducted to validate its outcomes in this patient group.

Efficacy and safety of caspofungin for patients with hepatic insufficiency

BackgroundTo observe the changes of hepatic function and efficacy of conventional dosage of caspofungin in the treatment of patients with different Child–Pugh scores.MethodsIn total, 200 patients (Child–Pugh A group: 66 patients, Child–Pugh B group: 83 patients, Child–Pugh C group: 51 patients) treated with caspofungin from May 2018 to March 2021 in the Second Affiliated Hospital of Chongqing Medical University were enrolled. Main investigation items were as follows: sex, age, weight, duration of treatment, dosage, department, underlying diseases, risk factors for fungal infection, albumin, liver enzyme, total bilirubin, serum creatinine, estimated glomerular filtration rate. To investigate the changes of liver, kidney function tests and efficacy during the treatments of caspofungin. Patients were divided into three groups according to the duration of treatment of caspofungin:1-week group, 2-week group and 3-week group, respectively.ResultsIn the three groups, albumin, liver enzyme levels, total bilirubin and serum creatinine, estimated glomerular filtration rate had no significant difference (P > 0.05). The efficacy of different Child–Pugh scores and different duration of treatment was also significantly different (P > 0.05).ConclusionsCaspofungin is well tolerated and highly effective. And it will not exacerbate the hepatic and renal function when administered with the not-reducing dose, which indicate the clinical application value of caspofungin. Besides, extending the treatment duration has little effect on improving the efficacy of caspofungin. The drug should be withdrawn timely according to the patients’ clinical condition in order to reduce the adverse reactions and economic burden.

Intestinal Continuity Alleviates Pediatric Intestinal Failure-Associated Liver Disease.

BackgroundType I short bowel syndrome (SBS) occurs after a critical reduction in the functional gut mass and resection of intestinal continuity after ileostomy or jejunostomy for necrotizing enterocolitis (NEC), intestinal atresia or other causes. SBS is often accompanied with intestinal failure-associated liver disease (IFALD) who requires long-term parenteral nutrition (PN). Our study aimed to observe the effect of intestinal continuity on the hepatic function of pediatric intestinal failure (IF) patients with type I SBS.MethodsThe pre-and post-anastomosis medical records of 35 pediatric patients with type I SBS from April 2013 to April 2019 were reviewed retrospectively. The average growth (cm/month) in the proximal and distal small bowel lengths was calculated as the growth in intestinal length (cm)/the duration (month) from enterostomy to anastomosis. The changes in hepatic function from enterostomy to anastomosis were evaluated by assessment of hepatic function before anastomosis for 6 weeks and after anastomosis for 4 weeks.ResultsThe average growth in proximal intestinal length was 9.3 cm/month (±7.2) in neonates and 2.8 cm/month (1.3, 11.9) in infants and children, and in distal intestinal length was 1.5 cm/month (0, 2.7) in neonates and 0.4 cm/month (0, 1.4) in infants and children. The incidence of IFALD was 28.6% 1 month before anastomosis and 20.0% 1 month after anastomosis (p < 0.05).ConclusionIn pediatric type I SBS with IFALD, restoration of intestinal continuity may alleviate liver injury. There was an intestinal compensatory effect on the growth in the intestinal length after resection, and better results were seen in neonates in terms of intestinal length growth.

Fatty acids mediate hepatocyte calcium release and ER stress induction after traumatic injury

Burn injury is one of the most severe injuries affecting almost every organ system. It produces a hypermetabolic stress response characterized by increased free fatty acids in serum. Burn injury is known to adversely alter liver function resulting in metabolic dysfunction. Hepatic changes at the cellular level after burn injury include chronic induction of the ER stress response and insulin resistance, which contributes to liver dysfunction. However, the mechanisms by which burn injury induces acute and lasting changes in hepatic function are poorly understood.

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity In Vitro.

DILI is a major cause of attrition in drug development with over 1000 FDA-approved drugs known to potentially cause DILI in humans. Unfortunately, DILI is often not detected until drugs have reached clinical stages, risking patients' safety and leading to substantial losses for the pharma industry. Taking into account that standard 2D models have limitations in detecting DILI it is essential to develop in vitro models that are more predictive to improve data translatability. To understand causality and mechanistic aspects of DILI in detail, a human liver MPS consisting of human primary liver parenchymal and non-parenchymal cells (NPCs) and cultured in 3D microtissues on an engineered scaffold under perfusion has been developed. Cryopreserved primary human hepatocytes (PHHs) and Kupffer cells (HKCs) were cocultured as microtissues in the MPS platform for up to two weeks, and each compound of interest was repeatably dosed onto liver microtissues at seven test concentrations for up to four days. Functional liver-specific endpoints were analyzed (including clinical biomarkers such as alanine aminotransferase, ALT) to evaluate liver function. Acute and chronic exposure to compounds of various DILI severities can be assessed by comparing responses to single and multi-dosed microtissues. The methodology has been validated with a broad set of severe and mildly hepatotoxic compounds. Here we show the data for pioglitazone and troglitazone, well-known hepatotoxic compounds withdrawn from the market for causing liver failures. Overall, it has been shown that the liver MPS model can be a useful tool to assess DILI and its association with changes in hepatic function. The model can additionally be used to assess how novel compounds behave in distinct patient subsets and how toxicity profiles may be affected by liver disease states (e.g., viral hepatitis, fatty liver disease).

Human Liver Microphysiological System for Assessing Drug-Induced Liver Toxicity &lt;em&gt;In Vitro&lt;/em&gt;

DILI is a major cause of attrition in drug development with over 1000 FDA-approved drugs known to potentially cause DILI in humans. Unfortunately, DILI is often not detected until drugs have reached clinical stages, risking patients' safety and leading to substantial losses for the pharma industry. Taking into account that standard 2D models have limitations in detecting DILI it is essential to develop in vitro models that are more predictive to improve data translatability. To understand causality and mechanistic aspects of DILI in detail, a human liver MPS consisting of human primary liver parenchymal and non-parenchymal cells (NPCs) and cultured in 3D microtissues on an engineered scaffold under perfusion has been developed. Cryopreserved primary human hepatocytes (PHHs) and Kupffer cells (HKCs) were cocultured as microtissues in the MPS platform for up to two weeks, and each compound of interest was repeatably dosed onto liver microtissues at seven test concentrations for up to four days. Functional liver-specific endpoints were analyzed (including clinical biomarkers such as alanine aminotransferase, ALT) to evaluate liver function. Acute and chronic exposure to compounds of various DILI severities can be assessed by comparing responses to single and multi-dosed microtissues. The methodology has been validated with a broad set of severe and mildly hepatotoxic compounds. Here we show the data for pioglitazone and troglitazone, well-known hepatotoxic compounds withdrawn from the market for causing liver failures. Overall, it has been shown that the liver MPS model can be a useful tool to assess DILI and its association with changes in hepatic function. The model can additionally be used to assess how novel compounds behave in distinct patient subsets and how toxicity profiles may be affected by liver disease states (e.g., viral hepatitis, fatty liver disease).

Haematological, renal, and hepatic function changes among Rayong oil spill clean-up workers: a longitudinal study.

The Rayong oil spill incident of 2013 leaked over 50,000 barrels of crude oil into the Gulf of Thailand. This study assessed trends and changes in the haematological, renal, and hepatic indices among the Rayong oil spill clean-up workers 5years after the spill. Haematological, renal, and hepatic indices measured for 570 oil spill clean-up workers at baseline and annually during 5-year follow-ups were analysed. Haemoglobin (Hb), haematocrit (Hct), white blood cell (WBC) count, red blood cell (RBC) count, and platelet count for haematological function, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for hepatic function, and creatinine (Cr) and blood urea nitrogen (BUN) for renal function were assessed. The longitudinal measures of haematological, renal and hepatic indices were analysed using analysis of variance for repeated measures. The generalised estimating equations (GEE) were used to assess trends of these indices and associated factors, including exposure level. Increasing trends were observed per year for WBC (0.52 ± 0.03 × 103 cells/μL), Cr (0.01 ± 0.00mg/dL), platelet (0.31 × 103 μL per year), and BUN (0.24 ± 0.03mg/dL). Decreasing trends of aspartate aminotransferase (AST) were observed (1.54 ± 0.21IU/L per year). Clean-up workers with high exposure to the oil spill had a significantly higher average of WBC and lower average of BUN than low-exposure and unknown-exposure workers. Gender and age were significantly associated with creatinine changes. Results of this study show the differences between baseline and follow-up haematological, renal, and hepatic indices and trends of these indices. The long-term changes in the indices in this study show worsening renal functions after oil spill and possibility of cardiovascular effects. These findings contribute to expanding knowledge on the long-term health effects of oil spills.

Impact of the cardio-hepatic syndrome on outcomes after transcatheter mitral valve edge-to-edge repair

Abstract Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p&amp;lt;0.01). In a multivariate Cox regression model, CHS was identified as a strong and independent predictor of increased two-year mortality (hazard ratio 1.49, p=0.03). In patients with successful MR reduction ≤2+ (90.7% of patients), parameters of hepatic function significantly improved from baseline to follow-up (−0.2 mg/dl for bilirubin; −21 U/l for GGT, respectively, p&amp;lt;0.01), while they did not in case of residual postprocedural MR &amp;gt;2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. Funding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER

Characterization of Seasonal Pharmacokinetic Variability in Woodchucks.

The eastern woodchuck (Marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis B virus infection. Under laboratory conditions, woodchucks develop a pseudohibernation condition; thus, the pharmacokinetics (PK) of small-molecule therapeutics may be affected by the seasonal change. The seasonal PK of four probe compounds were characterized over 12 months in seven male and nine female laboratory-maintained woodchucks. These compounds were selected to study changes in oxidative metabolism [antipyrine (AP)], glucuronidation [raltegravir (RTG)], renal clearance [lamivudine (3TC)], and hepatic function [indocyanine green (ICG)]. Seasonal changes in physiologic parameters and PK were determined. Seasonal body weight increases were ≥30%. Seasonal changes in body temperature and heart rate were <10%. The mean AP exposure remained unchanged from April to August 2017, followed by a significant increase (≥1.0-fold) from August to December and subsequent decrease to baseline at the end of study. A similar trend was observed in RTG and 3TC exposures. The ICG exposure remained unchanged. No significant sex difference in PK was observed, although female woodchucks appeared to be less susceptible to seasonal PK and body weight changes. Significant seasonal PK changes for AP, RTG, and 3TC indicate decreases in oxidative metabolism, phase II glucuronidation, and renal clearance during pseudohibernation. The lack of seasonal change in ICG exposure suggests there are no significant changes in hepatic function. This information can be used to optimize the scheduling of woodchuck studies to avoid seasonally driven variation in drug PK. SIGNIFICANCE STATEMENT: Woodchuck is a hibernating species and is commonly used as a nonclinical model of hepatitis B infection. Investigation of seasonal PK changes is perhaps of greater interest to pharmaceutical industry scientists, who use the woodchuck model to optimize the scheduling of woodchuck studies to avoid seasonally driven variation in drug PK and/or toxicity. This information is also valuable to drug metabolism and veterinary scientists in understanding woodchuck's seasonal metabolism and behavior under the pseudohibernation condition.

Association of long-term consumption of repeatedly heated mix vegetable oils in different doses and hepatic toxicity through fat accumulation

BackgroundHepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation.MethodsIn this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups.ResultsSignificantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40–60% increased oxidative stress compared to control, in a dose-dependent manner.ConclusionsThese results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.

A Preclinical Porcine Model of Portal Vein Thrombosis in Liver Cirrhosis.

Background This study aimed at presenting a novel method of developing a porcine model of portal vein thrombosis (PVT) in cirrhosis by intravenous administration of thrombin and insertion of a fibered coil. We further investigated changes of biochemical parameters, coagulation, and proinflammatory cytokine expression in the cirrhosis-PVT group. Methods Twelve male pigs were randomized into the control group (n = 3) and cirrhosis group (n = 9). In cirrhotic pigs, three were randomly selected to establish PVT by ultrasound-guided percutaneous puncture of the main portal vein (MPV) followed by intravenous thrombin administration and fibered coil insertion. Thrombosis in the MPV was detected by abdominal enhanced computer tomography (CT). The changes of hepatic function, coagulation system, and inflammation cytokines were compared among normal, cirrhosis, and cirrhosis with PVT groups. Results As manifested by the presence of a filling defect in MPV on portal venous-phase CT angiography, fibrin thrombi were formed in the MPV in cirrhotic pigs within one week and persisted for four weeks. Five weeks after surgery, abnormal liver functions occurred in association with PVT formation in cirrhosis. Both coagulation and thromboelastography parameters showed that cirrhosis-PVT pigs exhibited a procoagulant state through hyperfunction of platelets and clotting factors. Interleukin 6 (IL-6) as a potential inflammatory marker stimulated PVT-mediated inflammation activation in cirrhosis. Conclusions Our study provides in vivo evidence that intravenous injection of a coil and thrombin into MPV under interventional guided devices enables a feasible method in thrombus creation. Further exploration and validation of large-sample cases are required to characterize utilities of this model.

Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon).

Oral transmission of Chagas disease has been increasing in Latin American countries. The present study aimed to investigate changes in hepatic function, coagulation factor levels and parasite load in human acute Chagas disease (ACD) secondary to oral Trypanosoma cruzi transmission. Clinical and epidemiological findings of 102 infected individuals attended in the State of Pará from October 2013 to February 2016 were included. The most common symptoms were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache (74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of 30 ACD patients were higher compared with controls, and this increase was independent of the treatment with benznidazole. Moreover, ACD individuals had higher plasma levels of activated protein C and lower levels of factor VII of the coagulation cascade. Patients with the highest parasite load had also the most increased transaminase levels. Also, ALT and AST were associated moderately (r = 0.429) and strongly (r = 0.595) with parasite load respectively. In conclusion, the present study raises the possibility that a disturbance in coagulation and hepatic function may be linked to human ACD.

The impact of maternally derived dioxins on embryonic development and hepatic AHR signaling in a long-lived apex predator

Dioxins and related contaminants are highly pervasive in aquatic systems and elicit deleterious effects in exposed organisms. Because dioxins exhibit a proclivity to bioaccumulate, long-lived predatory species are particularly vulnerable to their persistence in the environment. We have previously reported elevated expression of CYP1A2, a biomarker of dioxin exposure, in American alligator embryos collected from the Tom Yawkey Wildlife Center (YWC). This coastal population inhabits a system with historical dioxin contamination associated with industrial activities. Herein, we utilize ecological attributes of the alligator to address the persistence of dioxins and furans in yolk and their potential to drive changes in hepatic function. Specifically, we assess variation in expression of AHR signaling components in embryos and its connection to contaminant levels in matched yolk samples. Compared to a reference population, TEQ levels and total penta-, hexa-, octa-substituted CDDs were elevated at YWC. Contrary to predictions, TEQ levels were not significantly related to hepatic AHR1B or CYP1A2 expression. However, a significant association was detected between expression of both factors and embryo:yolk mass ratios, wherein decreasing embryo mass was negatively associated with CYP1A2 but positively associated with AHR1B. These findings suggest that variation in embryonic metabolism and developmental progression likely influence AHR signaling and dioxin toxicity in alligators and potentially other oviparous species. While dioxin concentrations observed in alligators in this study are lower than historical values reported for other wildlife species inhabiting this system, they indicate the continued presence and possible long-term influence of these contaminants in a high trophic status species.

Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis

Background/Aim: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. Methods: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143). Changes in hepatic function along with CP and albumin-bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after introducing sorafenib in Study 2 were evaluated. Results: Hepatic function worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of classification from ALBI-1 to ALBI-2. When the prognosis of patients with the best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI-1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4 months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4 vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. Conclusion: The rate of patients with downgraded hepatic function during r-TACE, especially with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better hepatic function assessment tool than CP in patients receiving sorafenib treatment. Strict judgment of TACE-refractory status in patients with unresectable HCC is needed to improve prognosis before downgrading the hepatic function.

Imaging Findings Within the First 12 Months of Hepatocellular Carcinoma Treated With Stereotactic Body Radiation Therapy

To correlate the imaging findings of treated hepatocellular carcinoma (HCC) after stereotactic body radiation therapy (SBRT) with explant pathology and alpha-fetoprotein (AFP) response. From 2007 to 2015, of 146 patients treated with liver SBRT for Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma, 10 were identified with inclusion criteria and had regular interval follow-up magnetic resonance imaging/triple phase computed tomography and explant pathology or declining AFP values for radiology-pathology response correlation. Reference standards for successful response were >90% necrosis on explant pathology or pretreatment AFP >75ng/mL normalizing to <10ng/mL within 1year after SBRT without other treatment. Subjects were treated with 24 to 50Gy in 3 to 5 fractions. Multiphasic magnetic resonance imaging or computed tomography performed at 3, 6, 9, and 12months after SBRT was compared with pretreatment imaging by 2 expert radiologists. Descriptive statistics were calculated. There were 10 subjects with 10 treated HCCs, classified as 3 Organ Procurement and Transplantation Network (OPTN) 5a, 4 OPTN 5b, and 3 OPTN 5x. All had successfully treated HCCs, according to explant pathology or declining AFP. Four of 10 HCCs had persistent central arterial hyperenhancement 3 to 12months after SBRT; persistent wash-out was common up to 12months (9 of 10). Of 10 treated HCCs, 9 exhibited decreased size at 12months. Liver parenchyma adjacent to the lesion showed early (3-6months) hyperemia followed by late (6-12months) capsular retraction and delayed enhancement. No patient had a significant decline in liver function. In the absence of increasing size, persistent central arterial hyperenhancement and wash-out can occur within the first 12months after SBRT in successfully treated HCCs and may not represent residual viable tumor. Liver parenchyma adjacent to the treated lesion showed inflammation followed by fibrosis, without significant change in hepatic function. Until a radiologic signature of tumor control is determined, freedom from local progression seems to be the best measure of HCC control after SBRT.