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Background: The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Methods: Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. Results: There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P < 0.001 (95% CI: 3.0–8.7) and 17.1 (14.9, 21.0) vs. 20.5 (16.5, 25.3) μmol/L, P = 0.02 (95% CI: 0.0–5.0) respectively). Moreover, the incidence of severe acute kidney injury was significantly lower in group P compared to that in group D (15.8% vs. 39.5%, P = 0.038). Conclusions: Propofol-based TIVA might improve liver and kidney functions after LRLT in infants and reduce the incidence of serious complications, which may be related to the reduction of HIRI. However, further biomarkers will be necessary to prove these associations. [ABSTRACT FROM AUTHOR]

The increase in imaging technologies as well as many disease conditions requiring contrast media for diagnosis makes it important to investigate the effect of contrast media on hepato-renal function and its relation to oxidant and antioxidant status. To achieve this, twenty-five male albino rats were divided into 5 groups and administered with different doses of contrast agents (urografin and iohexol). After 48 hours of administration, 5 ml of blood samples was collected for the assessment of renal function, hepatic function and oxidative stress. The liver and kidneys were also excised for histological analysis. The result showed a significant increase (p=0.003) in the mean serum creatinine and urea in animals treated with either iohexol or urografin at different doses compared to the control. There was a significant increase (p=0.003) in serum malondialdehyde (MDA) level in contrast media group when compared with the control but serum total antioxidant status (TAS) level decreased in the groups administered with contrast media though the difference was not significant (p=0.003). Groups injected with iohexol showed no obvious histopathological alteration in both renal and hepatic tissues. In the groups treated with urografin, especially in higher dose, inflammatory cellular infiltration was observed at the peri-glomerular region and within the medulla in the kidney, while in the liver the portal tract appeared enlarged with infiltration of inflammatory cells. The result suggests that both iohexol and urografin are risk factors of kidney and liver damage as a result of increase in the pro-oxidant MDA and marked histomorphological alteration. [ABSTRACT FROM AUTHOR]

This phase 1, open‐label, three‐arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK‐935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child‐Pugh B) or mild (Child‐Pugh A) hepatic impairment or normal hepatic function (matched to hepatic‐impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose. Pharmacokinetic parameters of soticlestat and its metabolites TAK‐935‐G (M3) and M‐I were assessed and compared by group. The incidence of treatment‐emergent adverse events (TEAEs) and other safety parameters were also monitored. The pharmacokinetic analyses comprised 35 participants. Participants with moderate hepatic impairment had lower proportions of bound and higher proportions of unbound soticlestat than participants with mild hepatic impairment and normal hepatic function. Total plasma soticlestat pharmacokinetic parameters (maximum observed concentration [Cmax], area under the concentration‐time curve from time 0 to time of last quantifiable concentration [AUClast], and AUC from time 0 to infinity [AUC∞]) were approximately 115%, 216%, and 199% higher with moderate and approximately 45%, 35%, and 30% higher with mild hepatic impairment, respectively, than healthy matched participants. Moderate hepatic impairment decreased the liver's ability to metabolize soticlestat to M‐I; glucuronidation to M3 was also affected. Mild hepatic impairment resulted in a lower total plasma M‐I exposure, but glucuronidation was unaffected. TEAEs were similar across study arms, mild, and no new safety findings were observed. A soticlestat dose reduction is required for individuals with moderate but not mild hepatic impairment. [ABSTRACT FROM AUTHOR]

Abstract Background The effects of anesthetics on liver and kidney functions after infantile living-related liver transplantation (LRLT) are unclear. This study aimed to investigate the effects of propofol-based total intravenous anesthesia (TIVA) or desflurane-based inhalation anesthesia on postoperative liver and kidney functions in infant recipients after LRLT and to evaluate hepatic ischemia–reperfusion injury (HIRI). Methods Seventy-six infants with congenital biliary atresia scheduled for LRLT were randomly divided into two anesthesia maintenance groups: group D with continuous inhalation of desflurane and group P with an infusion of propofol. The primary focus was to assess alterations of liver transaminase and serum creatinine (Scr) levels within the first 7 days after surgery. And the peak aminotransferase level within 72 h post-surgery was used as a surrogate marker for HIRI. Results There were no differences in preoperative hepatic and renal functions between the two groups. Upon the intensive care unit (ICU) arrival, the levels of aspartate aminotransferase (AST, P = 0.001) and alanine aminotransferase (ALT, P = 0.005) in group P were significantly lower than those in group D. These changes persisted until the fourth and sixth days after surgery. The peak AST and ALT levels within 72 h after surgery were also lower in group P than in group D (856 (552, 1221) vs. 1468 (732, 1969) U/L, P = 0.001 (95% CI: 161–777) and 517 (428, 704) vs. 730 (541, 1100) U/L, P = 0.006, (95% CI: 58–366), respectively). Patients in group P had lower levels of Scr upon the ICU arrival and on the first day after surgery, compared to group D (17.8 (15.2, 22.0) vs. 23.0 (20.8, 30.8) μmol/L, P

Xylanase is a heteropolysaccharide found in the plant cell wall, which aids in the absorption and utilisation of nutrients. When embedded in animal feed, it enhances nutrient availability, leading to improved animal performance. The aim of this study was to explore the effect of xylanase supplementation in wheat-based feeds on the hepatic development, antioxidant capacity, and immune response in Tibetan sheep. Sixty healthy, weaned, non-neutered male lambs (19.35 ± 2.18 kg) were randomly assigned to two equal groups (n = 30 per group). Dietary treatments were: basal diet (H group), and basal diet with 0.2% xylanase supplementation (E group). After a 10–day adaptation period, the feeding trial was carried out for 90 days. The live weight, morphology, antioxidant capacity and immune response were measured. The differential genes in liver were identified by RNA-sequencing. Our results showed that the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were significantly higher in E group than in H group (p

Abstract This phase 1, open‐label, three‐arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK‐935) in participants with hepatic impairment. Participants aged ≥18 to

Objective: This cross‐sectional study investigated the association of periodontitis with the metabolic status and hepatic function in pregnant women. Materials and Methods: Full‐mouth periodontal conditions, metabolic profiles, and hepatic function were assessed in 219 self‐reported healthy pregnant females. The association of periodontal status with the systemic parameters was evaluated by parametric and non‐parametric tests, and multivariate logistic regression analysis. Results: Overall, periodontal status was positively associated with the metabolic profiles and hepatic function test results. The subjects with periodontitis exhibited higher levels of body mass index (BMI) (p < 0.01) and serum aspartate transaminase (AST) (p < 0.05), elevated diastolic blood pressure (DBP) (p < 0.05), and lower levels of high‐density lipoprotein cholesterol (p < 0.05) than those of the counterparts. The periodontitis severity was strongly correlated with BMI and AST levels, and the extent of periodontal inflammation was related to DBP (p < 0.01). The periodontitis patients at 34–36 gestational weeks showed higher blood pressure and AST levels than those of non‐periodontitis subjects (p < 0.05). Conclusion: Our findings on the notable links of periodontitis to concurrent metabolic disorders and abnormal liver function in pregnant women highlight the need of proactive integration of regular periodontal screening and healthcare in maternal programs for promoting optimal health and wellbeing of mothers‐to‐be and newborns. [ABSTRACT FROM AUTHOR]

Adrenaline is widely used drug to combat several conditions such as allergy and anaphylaxis. The current work was to investigate the renal and hepatic complications following adrenaline injection, in addition, the impact of Cleome (SAMWA) methanolic extract on adrenaline- induced renal and hepatic alterations. Twenty- four male Wister rats were divided equally into four groups; Normal control group received oral distilled water for 30 consecutive days and administered subcutaneous saline on the 31st and 32nd days. The Cleome extract (200 mg/kg) group received Cleome methanolic extract (200 mg/kg, P.O) for 30 consecutive days and administered subcutaneous saline on the 31st and 32nd days. The adrenaline group received distilled water orally for 30 consecutive days and administered subcutaneous adrenaline (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. Cleome extract (200 mg/kg)/ adrenaline received Cleome methanolic extract (200 mg/kg, P. O) for 30 consecutive days and administered subcutaneous adrenaline (2 mg/kg, s.c.) divided into two doses (1 mg/kg, s.c) each on the 31st and 32nd days. Liver and kidney function biomarkers in addition to histopathological analyses were evaluated. Adrenaline caused alteration in liver and kidney function biomarkers without affecting the histological structure of the liver and the kidney. SAMWA methanolic extract pretreatment significantly decreased serum urea, uric acid, aspartate aminotransferase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). SAMWA ameliorated serum albumin reduction and total protein induced by adrenaline injection. SAMWA methanolic extract could protect liver and kidney of rats exposed to adrenaline. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of supplementing rumen-protected choline with soluble vitamins (RPCSV) on growth performance, plasma profiles, and carcass characteristics in Hanwoo steers. Forty-five steers were fed 0 (T0), 50 (T50), or 100 g (T100) of RPCSV daily for 6 months. The average daily gain was not affected by RPCSV supplementation. The concentrations of total bilirubin (P < 0.05), aspartate glutamyltransferase (P < 0.01), alanine aminotransferase (P < 0.01), glucose (P < 0.01), nonesterified fatty acids (P < 0.05), blood urea nitrogen (P < 0.01), and triglycerides (P < 0.01) differed depending on the RPCSV supplementation period in each treatment group. Backfat thickness (P < 0.05) and yield index (P < 0.01) were affected by RPCSV supplementation. Thus, the results of this study indicated that plasma profiles related to energy, protein, and lipid metabolism increased due to improved liver function with RPCSV supplementation. [ABSTRACT FROM AUTHOR]

To explore the application effect of transitional nursing in patients with TIPS. A total of 368 patients were allocated to control group (conventional care) and intervention group (conventional care combined with transitional care). The Child–Pugh scores, blood ammonia levels, compliance behavior, medication compliance, and adverse event incidence rates were compared at 1, 3, 6, 9, and 12 months post-TIPS. There were significant differences in compliance behavior scores, Child–Pugh scores for group effects, time effects, and group × time interaction between the two groups at 1, 3, 6, 9, and 12 months post-TIPS, significant differences in blood ammonia levels at 9 months, and incidence of postoperative adverse events at 12 months after TIPS. Post-TIPS transitional care interventions increased patients' access to scientifically informed nursing, significantly improved patients' compliance behavior and health and decreased the incidence of postoperative adverse events. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP) is the most extensively used and safest analgesic and antipyretic drug worldwide; however, its toxicity is associated with life-threatening acute liver failure. Cardamom (CARD), a sweet, aromatic, commonly used spice, has several pharmacological actions. In the current study, we tried to explore the chemical composition and the hepato-protective effect of ethanolic aqueous extract of CARD to mitigate APAP-induced hepatic toxicity and elucidate its underlying mechanism of action. Material and methods: Aqueous CARD extract was subjected to LC-TOF-MS analysis to separate and elucidate some of its components. In vivo animal experiments involved five groups of animals. In the normal and cardamom groups, mice were administered either saline or CARD (200 mg/kg), respectively, orally daily for 16 days. In the APAP group, the animals were administered saline orally daily for 15 days, and on the 16th day, animals were administered APAP (300 mg/kg) IP for the induction of acute hepatic failure. In the CARD 200 + APAP group, mice were administered CARD (200 mg/kg) for 15 days, followed by APAP on the 16th day. Results: The aqueous extract of CARD showed several compounds, belonging to polyphenol, flavonoids, cinnamic acid derivatives and essential oil components. In the in vivo investigations, APAP-induced impaired liver function, several histopathological alterations, oxidative stress and inflammatory and apoptotic status signified severe hepatic failure. Whereas, pretreatment with the CARD extract prior to APAP administration diminished serum levels of the hepatic function test and augmented Nrf2 nucleoprotein and HO-1 and NQO-1. CARD down-regulated MDA, inflammatory mediators (IL-1β, IL-6, TNF-α and NF-κB) and apoptotic markers (caspase 3 and 9 and Bax) and amplified the activities of SOD, catalase, GSH-Px and GSH-R in hepatic tissue samples. Conclusion: CARD extract mitigated the hepatic toxicity induced by APAP. The underlying mechanism of action of such hepato-protective action may be through upregulation of the Nrf2/HO-1/NQO-1 pathway with subsequent alleviation of the oxidative stress, inflammation and apoptosis induced by APAP. Many of the compounds identified in the CARD extract could be attributed to this pharmacological action of the extract.

Background & Objective: Acetaminophen overdose can result in hepatic injury, mainly through oxidative stress. We investigated the protective effect of Cuminum cyminum (C. cyminum) seeds powder after acetaminophen administration. Materials & Methods: In this study, 30 male rats were allocated into five groups of six in number as follows: control, acetaminophen (A), and acetaminophen + C. cyminum 200, 400, and 800 mg/kg (A+C). After 24 hours of fasting, the control group received distilled water, and groups A and A+C received acetaminophen 1,000 mg/kg orally through gavage. Six hours later, the control group and group A were given distilled water, and groups A+C received C. cyminum 200, 400, and 800 mg/kg by gavage. Twelve hours after the second gavage, hepatic markers of oxidative stress and serum ALT and AST were assessed. Results: In group A, the activities of serum ALT and AST, the concentration of hepatic malondialdehyde and H2O2 increased, and peroxidase & catalase activities decreased substantially compared to the control group. C. cyminum administration in groups A+Cs resulted in the return of these changes toward group control. Conclusion: These results suggest that C. cyminum, due to its flavonoid and polyphenol contents, could diminish hepatic injury induced by acetaminophen. [ABSTRACT FROM AUTHOR]

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5 −/− mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5 −/− mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates. [ABSTRACT FROM AUTHOR]

Nano and microplastics are defined as particles smaller than 100 nm and 5 mm respectively. The widespread production and use of plastics in everyday life has resulted in significant accumulation of plastic debris in the environment. Over the last two decades there are increased concerns regarding the potential entry and accumulation of plastics in the human body with ingestion being one of the most important routes of exposure. However, the magnitude and nature of potential toxic effects of plastic exposure to human health is not yet fully understood. The liver is the body's principal detoxification organ and critically to this study recognized as the main accumulation site for particulates. In this study as the first of its kind the health impacts of long term low repeated polystyrene microplastics (1 and 5 μm) exposure was investigated in a functionally active 3D liver microtissue model, composed of primary human hepatocytes, Kupffer cells, sinusoidal endothelial cells and hepatic stellate cells. The highlight from the data includes microplastic-induced dose (3.125–25 μg/ml) and time dependent (up to 504 h) increase in cell death and inflammation manifested by enhanced release of IL6, IL8 and TNF-α. The exposure to repeated dosing of the plastics also resulted in notable pathology manifested as aberrant tissue architecture, such as dilated bile canaliculi and large lipid droplets inside the hepatic cells. This toxicity matched extremely well to the accumulation of the materials with the cells of microtissue predominately in the organ macrophages. This study highlights the real issue and danger of microplastic exposure with potential for long-term accumulation and adverse effects of non-biodegradable plastics within the liver. [Display omitted] • The small microplastic (1 μm) induced dose and time dependent increase in cell cytotoxicity. • The small microplastic (1 μm) induced dose and time dependent increase in inflammation. • Repeated dosing of the smaller plastic resulted in significant pathology in the liver tissue. • Adverse effects observed following repeated exposure and not after acute exposure high dosing. • Plastic induced toxicity matched well to the accumulation of the materials in liver Kupffer cells. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of ethyl acetate gum resin extract of Boswellia serrata on lipopolysaccharide (LPS) induced inflammation and oxidative damage in hepatic and renal tissues of rats. Methods: The rats were divided into four groups: control, LPS, LPS+Boswellia serrata extracts (100 mg/kg and 200 mg/kg). LPS (1 mg/kg) and the extract (100 and 200 mg/kg, 30 min before LPS) were administered intraperitoneally for 3 weeks. The levels of liver enzymes, albumin, total protein, creatinine, blood urea nitrogen (BUN), interleukin (IL)-6, malondialdehyde (MDA), and total thiol groups and superoxide dismutase (SOD) and catalase (CAT) activities were measured. Results: The levels of liver enzymes, creatinine, and BUN, IL-6, MDA in the LPS group were markedly increased (P

Aims: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium–glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. Methods and results: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA‐HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end‐of‐study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT‐proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37–2.17], p < 0.001; and 1.52 [1.12–2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow‐up, dapagliflozin had no effect on liver tests. Conclusion: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. Clinical Trial Registration: ClinicalTrials.gov NCT03036124. [ABSTRACT FROM AUTHOR]

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. 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). 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. 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. • Adults with CHD undergoing isolated heart transplant had significant improvement in hepatic and renal function. • There was a continuous improvement in hepatic and renal function for several months after normalization of cardiac hemodynamics. • Selected CHD patients with hepatic and renal dysfunction may do well with isolated heart transplant alone. [ABSTRACT FROM AUTHOR]

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI. Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS. Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3. Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: Oxidative stress is a key player in intestinal ischemia/reperfusion (I/R) injury (IIRI) with a tendency to trigger systemic inflammatory response, resulting in progressive distal organ injury. To date, the role of Bax/caspase 3 signaling in IIRI has not been reported. Furthermore, the discovery of a safe and effective drug remains pertinent in improving the outcome of IIRI. Therefore, this study investigated the role of Bax/caspase 3 signaling in intestinal I/R-induced intestinal and hepatic injury. In addition, the protective effect and possible associated mechanism of action of methanolic Phyllanthus amarus leaf extract (PA) against intestinal I/R-induced intestinal and hepatic injury were evaluated. Materials and methods: Fifty male Wistar rats were randomized into five groups (n = 10). The sham-operated group was received 0.5 mL of distilled water for seven days prior to the sham surgery, while the IIRI, febuxostat (FEB) + IIRI, low-dose PA (LDPA) + IIRI, and high-dose PA (HDPA) + IIRI groups underwent the I/R procedure. In addition to the procedure, IIRI, FEB + IIRI, LDPA + IIRI, and HDPA + IIRI received 0.5 mL of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of PA, and 400 mg/kg of PA, respectively, for seven days prior to the I/R procedure. Results: Administration of methanolic Phyllanthus amarus leaf extracts attenuated the intestinal I/R-induced rise in intestinal and hepatic injury markers, malondialdehyde, nitric oxide, TNF-α, IL-6, and myeloperoxidase activities. In addition, Phyllanthus amarus ameliorated I/R-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase, and glutathione peroxidase activities in intestinal and hepatic tissues. These were coupled with the suppression of I/R-induced bacterial translocation, downregulation of I/R-induced activation of Bax/caspase 3 signaling, and improvement of I/R-induced distortion of intestinal and hepatic histoarchitecture by Phyllanthus amarus. Conclusion: Methanolic Phyllanthus amarus leaf extract protects against intestinal and hepatic injuries associated with intestinal I/R by suppressing oxidative-stress-mediated activation of Bax/caspase 3 signaling. The beneficial effects of Phyllanthus amarus may be ascribed to its constituent bioactive molecules, especially tannins, anthocyanin, alkaloids, and phenolics. [ABSTRACT FROM AUTHOR]

Background: Activation of caspase 3 has been implicated in the pathogenesis of I/R injury in various organs, but there is a paucity of data on its role in IIRI. Also, no reports were found on the beneficial role of methanolic Moringa oleifera leaf extract (MMOLE) in IIRI. This study investigated the involvement of caspase 3 in IIRI, and the impact of MMOLE in IIRI.Methods: Male Wistar rats were randomized into five groups; the sham-operated group that was sham-operated and received 0.5 ml of distilled water for 7 days prior to sham surgery, and the IIRI, febuxostat (FEB) +IIRI, low dose MMOLE (LDMO)+IIRI, and high dose MMOLE (HDMO)+IIRI groups that underwent I/R and also received 0.5 ml of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of MMOLE, and 400 mg/kg of MMOLE respectively for 7 days prior to I/R. Markers of hepatic function, oxidative stress, and inflammation as well as enteric bacterial translocation and histoarchitecture integrity of intestinal and hepatic tissues were evaluated. The bioactive components of MMOLE were also determined by GC-MS.Results: As revealed by GC-MS, the active bioactive components of MMOLE were thiosemicarbazone, hydrazine, 1,3-dioxolane, octanoic acid, 1,3-benzenediamine, 9-octadecenoic acid, oleic acid, nonadecanoic acid, 3-undecanone, phosphonic acid, and cyclopentanecarboxylic acid. MMOLE alleviated IIRI-induced rise in intestinal and hepatic injury markers, malondialdehyde, TNF-α, IL-6, and myeloperoxidase activities. MMOLE improved IIRI-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase and glutathione peroxidase activities. These were associated with suppression of IIRI-induced caspase 3 activity and bacterial translocation. Histopathological evaluation revealed that MMOLE attenuated IIRI-induced alterations in intestinal and hepatic histoarchitecture integrity. MMOLE also militated against increased absolute and relative intestinal and hepatic weight, intestinal and hepatic injuries, epithelial mucosal barrier dysfunction, and enteric bacterial translocation associated with IIRI by downregulating oxidative stress-mediated activation of caspase 3.Conclusion: IIRI is associated with a rise in caspase 3 activity. Also, MMOLE confers protection against IIRI, possibly due to its constituent bioactive molecules, especially hydrazine, 9-octadecenoic acid, 1,3-dioxolane, oleic acid, and nonadecanoic acid.

BackgroundBiliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.MethodPlasma samples of 11 BA and 24 controls were collected for liver function test, Aβ40 and Aβ42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann–Whitney U test was performed to assess differences between groups. Correlation between Aβ42/Aβ40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of Aβ42/Aβ40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aβ42/Aβ40 combined with other hepatic function parameters.ResultsPlasma Aβ42/Aβ40 was elevated in BA patients. Aβ42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson’s correlation = 0.349), while there was no correlation for Aβ40 with hepatic functions. Aβ42/Aβ40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson’s correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson’s correlation = 0.337). Aβ42/Aβ40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552–0.941), p

Background: The incidence of opioid-related fatality has reached unparalleled levels across North America. Patients with comorbid hepatitis C virus (HCV) remain the most vulnerable and difficult to treat. Considering the unique challenges associated with this population, we aimed to re-examine the impact of HCV on response to medication assistant treatment for opioid use disorder and establish sex-specific risk factors affecting care. Methods: This study employs a multi-center prospective cohort design, with 1-year follow-up. Patients aged ≥18, receiving methadone for opioid use disorder were recruited from a network of outpatient opioid addiction treatment centers across Southern Ontario, Canada. Patients with ≥50% positive opioid urine screens over 1 year of follow-up were classified as poor responders. The prognostic impact of HCV on response was established using a propensity score matched analysis. Sex-specific regression models were constructed to evaluate risk factors for treatment response. Results: Among participants eligible for inclusion (n = 1234), HCV was prevalent in 25% (n = 307). HCV patients exhibited significantly higher rates of high-risk opioid consumption patterns 35.29% (standard deviation 0.478). Sex-specific examination revealed females with HCV incur a 2 times increased risk for high-risk opioid consumption behaviors (female odds ratio: 1.95, 95% confidence interval 1.23, 3.10; P = 0.01). Conclusions: Findings from this study establish the link between HCV and poor treatment response, with differentially higher risk among female patients. In light of the high potential for overdose among this population, concerted efforts are required for distinguishing the source for sex-based disparities, in addition to establishing trauma and gender informed treatment protocols. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows that the liver is the major target of PFOS, and that PFOS can damage liver tissue and disrupt its function; however, the exact mechanisms remain unclear. In this study, we reviewed the adverse effects of PFOS on liver tissue and cells, as well as on liver function, to provide a reference for subsequent studies related to the toxicity of PFOS and liver injury caused by PFOS. [ABSTRACT FROM AUTHOR]

A 10-week feeding trial was conducted to investigate the beneficial effects of bile acids (BAs) on hepatic health status in tongue sole (Cynoglossus semilaevis). Three experimental diets were prepared with different levels of BA inclusion in the commercial basal diet: control group (CT: 0 mg/kg basal diet), low-level group (BA1: 300 mg/kg basal diet), and high-level group (900 mg/kg basal diet). At the end of the feeding trial, growth performance and survival rate were measured, as well as numerous physiological and biochemical parameters of the liver, including four hepatic function indices, five antioxidant indices, five lipid metabolism parameters, and three digestive enzyme activities. Moreover, the mRNA expression levels of three growth-related genes and three immune-related genes in the liver were assayed. Results showed that growth performance and survival were substantially improved in both low- and high-level BA inclusive groups. Further, the tested liver physiological and biochemical parameters combined with the quantitative real-time PCR results revealed enhanced antioxidant capacity, energy metabolism, digestive ability, and immune response. Finally, these findings provide a wider spectrum of the beneficial effects of dietary BAs on liver health in tongue sole.

Alcohol dependence is one of the main reasons for inpatient admission to psychiatric hospitals. The abuse of this chemical substance can cause modifications in our organism and among them, variations in the oxidative stress parameters. Therefore, the aim of this study is to evaluate patients admitted to a psychiatric hospital unit to treat alcohol dependence, comparing oxidative stress, renal and hepatic function parameters from the moment of admission to those obtained at discharge. Hepatic function was verified through gamma-glutamyl-transferase (GGT), alkaline-phosphatase (ALP), aspartate-aminotransferase (AST) and alanine-aminotransferase (ALT) activity measurements. Urea and creatinine serum levels were measured for kidney function evaluation. Oxidative stress was evaluated by superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), ferric reducing antioxidant power (FRAP) and malondialdehyde (MDA). Medications used during hospital stay were record and their influence over the measured parameters analyzed. Twenty-eight patients (82% male, 44 ± 13 years old) were included in this study. A significant increase in BMI of patients after the period of hospitalization could be observed. There were reductions in creatinine, AST, ALT, GGT and ALP serum levels. SOD levels were lower at discharge, while GPx and FRAP presented higher levels. Chlorpromazine use showed influence over some hepatic function markers (ALT, GGT and ALP) and oxidative stress parameters (CAT and GPx); while carbamazepine use influenced GGT and FRAP. Patients on alcohol dependence treatment had significant improvements of renal and hepatic function parameters and higher GPx and FRAP values after the hospitalization period, which indicates reversion of alcohol effects over oxidative stress parameters. [ABSTRACT FROM AUTHOR]

Background and Aim: Direct‐acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long‐term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. Methods: This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon‐free DAA treatment before September 2016. The impact of treatment on long‐term hepatic function was followed for at least 4 years after the end of treatment, and the progression to decompensation was evaluated. Results: The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin‐bilirubin (ALBI) grade 2b. During a short‐term follow‐up 1 year after the end of treatment, FIB‐4 index and ALBI score significantly improved. The achievement rates of FIB‐4 < 3.25 (40%) and ALBI grade 1 (70%) reached their plateau in the first year; however, there were significant further improvements in platelet count and α‐fetoprotein level after the first year. The annual incidence of decompensation was 1.30 (95% confidence interval 0.83–2.02) per 100 person‐years. In multivariable analysis, male sex and modified ALBI grade 2b at baseline were associated with decompensation. Conclusions: In a large real‐world cohort of patients with compensated cirrhosis treated with a DAA, remarkable improvement in hepatic function was seen after HCV cure, especially during the first year after the end of treatment. Treatment in the early stage of cirrhosis would be of great benefit for preventing liver deterioration to decompensation. [ABSTRACT FROM AUTHOR]

Background: Although living donor liver transplantation (LDLT) is the standard treatment option for patients with end‐stage liver disease, it always entails ethical concerns about the risk of living donors. Recent studies have reported a correlation between sarcopenia and surgical prognosis in recipients. However, there are few studies of donor sarcopenia and the surgical prognosis of donors. This study investigated the association between sarcopenia and postoperative acute kidney injury in liver donors. Methods: This retrospective study analysed 2892 donors who underwent donor hepatectomy for LDLT between January 2008 and January 2018. Sarcopenia was classified into pre‐sarcopenia and severe sarcopenia, which were determined to be −1 standard deviation (SD), and −2 SD from the mean baseline of the skeletal muscle index, respectively. Multivariate regression analysis was performed to evaluate the association between donor sarcopenia and postoperative AKI. Additionally, we assessed the association between donor sarcopenia and delayed recovery of liver function (DRHF). Results: In the multivariate analysis, donor sarcopenia was significantly associated a higher incidence of postoperative AKI (adjusted odds ratio [OR]: 2.65, 95% confidence interval [CI]: 1.15–6.11, P =.022 in pre‐sarcopenia, OR: 5.59, 95% CI: 1.11–28.15, P =.037 in severe sarcopenia, respectively). Additionally, hypertension and synthetic colloid use were significantly associated with postoperative AKI. In the multivariate analysis, risk factors of DRHF were male gender, indocyanine green retention rate at 15 minutes, and graft type, however, donor sarcopenia was not a risk factor. Conclusions: Donor sarcopenia is associated with postoperative AKI following donor hepatectomy. [ABSTRACT FROM AUTHOR]

Abstract Background Although atezolizumab plus bevacizumab (Atez/bev) treatment has been developed for unresectable hepatocellular carcinoma (u‐HCC), changes in hepatic function during therapy have yet to be reported. Aim This retrospective clinical study aimed to elucidate early responses to Atez/Bev. Methods From September 2020 to April 2021, 171 u‐HCC patients undergoing Atez/Bev treatment were enrolled (BCLC stage A:B:C:D = 5:68:96:2). Of those, 75 had no prior history of systemic treatment. Relative changes in hepatic function and therapeutic response were assessed using albumin‐bilirubin (ALBI) score and Response Evaluation Criteria in Solid Tumors (RECIST), ver. 1.1, respectively. Results In initial imaging examination findings, objective response rates for early tumor shrinkage and disease control after 6 weeks (ORR‐6W/DCR‐6W) were 10.6%/79.6%. Similar response results were observed in patients with and without a past history of systemic treatment (ORR‐6W/DCR‐6W = 9.7%/77.8% and 12.2%/82.9%), as well as patients in whom Atez/Bev was used as post‐progression treatment following lenvatinib (ORR‐6W/DCR‐6W = 7.7%/79.5%), for which no known effective post‐progression treatment has been established. In 111 patients who underwent a 6‐week observation period, ALBI score was significantly worsened at 3 weeks after introducing Atez/Bev (−2.525 ± 0.419 vs −2.323 ± 0.445, p

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). The role of CHS in patients undergoing T-TEER for severe TR has not been studied. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: Volumetric and health assessment of the liver is crucial to avoid poor post-operative outcomes following liver resection surgery. No current methods allow for concurrent and accurate measurement of both Couinaud segmental volumes for future liver remnant estimation and liver health using non-invasive imaging. In this study, we demonstrate the accuracy and precision of segmental volume measurements using new medical software, Hepatica™. Methods: MRI scans from 48 volunteers from three previous studies were used in this analysis. Measurements obtained from Hepatica™ were compared with OsiriX. Time required per case with each software was also compared. The performance of technicians and experienced radiologists as well as the repeatability and reproducibility were compared using Bland–Altman plots and limits of agreement. Results: High levels of agreement and lower inter-operator variability for liver volume measurements were shown between Hepatica™ and existing methods for liver volumetry (mean Dice score 0.947 ± 0.010). A high consistency between technicians and experienced radiologists using the device for volumetry was shown (± 3.5% of total liver volume) as well as low inter-observer and intra-observer variability. Tight limits of agreement were shown between repeated Couinaud segment volume (+ 3.4% of whole liver), segmental liver fibroinflammation and segmental liver fat measurements in the same participant on the same scanner and between different scanners. An underestimation of whole-liver volume was observed between three non-reference scanners. Conclusion: Hepatica™ produces accurate and precise whole-liver and Couinaud segment volume and liver tissue characteristic measurements. Measurements are consistent between trained technicians and experienced radiologists. [ABSTRACT FROM AUTHOR]

Liver-associated diseases and tissue engineering approaches based on in vitro culture of functional Primary human hepatocytes (PHH) had been restricted by the rapid de-differentiation in 2D culture conditions which restricted their usability. It was proven that cells growing in 3D format can better mimic the in vivo microenvironment, and thus help in maintaining metabolic activity, phenotypic properties, and longevity of the in vitro cultures. Again, the culture method and type of cell population are also recognized as important parameters for functional maintenance of primary hepatocytes. Hepatic organoids formed by self-assembly of hepatic cells are microtissues, and were able to show long-term in vitro maintenance of hepato-specific characteristics. Thus, hepatic organoids were recognized as an effective tool for screening potential cures and modeling liver diseases effectively. The current review summarizes the importance of 3D hepatic organoid culture over other conventional 2D and 3D culture models and its applicability in Liver tissue engineering. [ABSTRACT FROM AUTHOR]

Aim: 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., Methods: 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., Results: 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., Conclusions: 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.

Development of obesity is associated with excessive fat accumulation and oxidative stress along with chronic inflammation. Goji berries (Lycium barbarum) are high in polyphenolic compounds and have anti-inflammatory, anti-oxidant, and hypolipidemic properties that may alleviate the pathogenesis of obesity and related metabolic complications. Thus, the aim of this study was to investigate potential metabolic benefits of GB supplementation against high fat (HF) diet-induced obesity and its comorbidities in HF diet-fed rats (male Sprague–Dawley, n = 8/group, 6 weeks old). We also sought to examine the potential metabolic benefits of fermented GB (FGB) with L. plantarum CB3 and possible distinctions in the degree and/or mechanism of action compared to GB. GB and FGB supplementation suppressed the gene expression of inflammation indices at the local (adipose tissues) and systemic (liver) levels. In addition, GB and FGB supplementation upregulated the gene expression of antioxidant enzymes compared to the HF and/or even low fat (LF) group with more remarkable antioxidant effects by GB supplementation. Also, GB and FGB supplementation protected from HF-induced damages of the liver and dyslipidemia. In conclusion, we demonstrated that GB and FGB supplementation protected from HF-induced metabolic complications primarily by improving hepatic function and corresponding lipid metabolism via their anti-inflammatory and antioxidant properties. To our knowledge, this is the first in vivo study confirming metabolic benefits of GB in a fermented form. Thus, these findings support the potential application of both GB and FGB to ameliorate obesity-associated metabolic abnormalities. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance: Oxidative stress is a key player in intestinal ischemia/reperfusion (I/R) injury (IIRI) with a tendency to trigger systemic inflammatory response, resulting in progressive distal organ injury. To date, the role of Bax/caspase 3 signaling in IIRI has not been reported. Furthermore, the discovery of a safe and effective drug remains pertinent in improving the outcome of IIRI. Therefore, this study investigated the role of Bax/caspase 3 signaling in intestinal I/R-induced intestinal and hepatic injury. In addition, the protective effect and possible associated mechanism of action of methanolic Phyllanthus amarus leaf extract (PA) against intestinal I/R-induced intestinal and hepatic injury were evaluated. Materials and methods: Fifty male Wistar rats were randomized into five groups (n = 10). The sham-operated group was received 0.5 mL of distilled water for seven days prior to the sham surgery, while the IIRI, febuxostat (FEB) + IIRI, low-dose PA (LDPA) + IIRI, and high-dose PA (HDPA) + IIRI groups underwent the I/R procedure. In addition to the procedure, IIRI, FEB + IIRI, LDPA + IIRI, and HDPA + IIRI received 0.5 mL of distilled water, 10 mg/kg of febuxostat, 200 mg/kg of PA, and 400 mg/kg of PA, respectively, for seven days prior to the I/R procedure. Results: Administration of methanolic Phyllanthus amarus leaf extracts attenuated the intestinal I/R-induced rise in intestinal and hepatic injury markers, malondialdehyde, nitric oxide, TNF-α, IL-6, and myeloperoxidase activities. In addition, Phyllanthus amarus ameliorated I/R-induced suppression of reduced glutathione, thiol and non-thiol proteins, and superoxide dismutase, catalase, and glutathione peroxidase activities in intestinal and hepatic tissues. These were coupled with the suppression of I/R-induced bacterial translocation, downregulation of I/R-induced activation of Bax/caspase 3 signaling, and improvement of I/R-induced distortion of intestinal and hepatic histoarchitecture by Phyllanthus amarus. Conclusion: Methanolic Phyllanthus amarus leaf extract protects against intestinal and hepatic injuries associated with intestinal I/R by suppressing oxidative-stress-mediated activation of Bax/caspase 3 signaling. The beneficial effects of Phyllanthus amarus may be ascribed to its constituent bioactive molecules, especially tannins, anthocyanin, alkaloids, and phenolics.

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p

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. [ABSTRACT FROM AUTHOR]

Abstract Background/aim We assessed suitable factors indicating newly developed lenvatinib (LEN) treatment for unresectable hepatocellular carcinoma (u‐HCC) by investigating real‐world clinical features of patients. Materials/methods One hundred fifty two u‐HCC patients, who receive LEN treatment from March to December 2018, were enrolled. (Child‐Pugh score [CPS] 5/6/7/8 = 76/61/13/2, modified albumin‐bilirubin grade [mALBI] 1/2a/2b/3 = 53/35/60/4). Clinical features were evaluated retrospectively. Results Overall‐response rate (ORR)/disease control rate (DCR) at 1 month after starting LEN were 38.7%/86.0%, respectively. Estimated median time to progression (TTP) was 7.0 months, while median survival time was not reached within the observation period. CPS (≥7) and past history of tyrosine‐kinase inhibitor (TKI) were not significant prognostic factors. mALBI ≥2b was an only significant prognostic factor (HR 4.632, 95%CI 1.649‐13.02, P = 0.004) in Cox‐hazard multivariate analysis. In patients with Child‐Pugh A, c‐index/Akaike's information criterion (AIC) of prognostic predictive value of mALBI were superior to CPS (0.682/135.6 vs 0.652/138.7), while those of stopping LEN also showed that mALBI was better (0.575/447.3 vs 0.562/447.8). Additional analysis of patients with good mALBI (1/2a) revealed that time to stopping LEN was significantly shorter in those with the adverse event (AE) of appetite loss (any grade) than those without (P = 0.006) and body mass index (BMI) was also lower in patients with that AE (20.3 ± 3.0 vs 23.6 ± 4.0kg/m2, P

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1–8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20–50 mg), epirubicin (30–60 mg), lipiodol (5–25 mL) and gelatin sponge particles (350–560 μm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55–32.45 months), and the median PFS was 4.8 months (95% CI 4.26–5.34 months). Patients with a ablation margin size of 11–15 mm experienced better PFS than those with a margin size of 6–10 or 0–5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p

Perfluorooctane sulfonate (PFOS) is a persistent, widely present organic pollutant. PFOS can enter the human body through drinking water, ingestion of food, contact with utensils containing PFOS, and occupational exposure to PFOS, and can have adverse effects on human health. Increasing research shows that the liver is the major target of PFOS, and that PFOS can damage liver tissue and disrupt its function; however, the exact mechanisms remain unclear. In this study, we reviewed the adverse effects of PFOS on liver tissue and cells, as well as on liver function, to provide a reference for subsequent studies related to the toxicity of PFOS and liver injury caused by PFOS.

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P

Purposes: For the first time in China, the current study was designed to compare the clinical outcomes between Chinese patients receiving hepatectomy with or without the enhanced recovery after surgery (ERAS) strategy.Methods: The current study enrolled 250 patients who would receive hepatectomy. Patients were randomized into two groups: ERAS group (n = 125, ERAS strategy) and control (n = 125, conventional care). Mortality, length of hospital stay, readmission, and complications were assessed over 30 days after the operation.Results: The average age of the whole cohort was 65 (63–68) years, with 152 males (60.8%). There was no difference between two groups in baseline features, such as age, sex, medical history, Child–Pugh hepatic function, American Society of Anaesthesiologists physical status, operative type, hepatectomy type, and hepatic pathology (P > 0.05 for all). There was no occurrence of death in the two groups. Patients in the ERAS group had significantly less occurrence of post-operative complications and a shorter length of hospital stay (P < 0.05 for all). Deep vein thrombosis occurred in seven patients in the control group, but did not occur in the ERAS group (P < 0.05). Patients in the two groups had similar occurrence of readmission (P > 0.05).Conclusions: ERAS strategy significantly decreased the occurrence of operative complications and shortened the length of hospital stay without any increase in mortality or readmission in Chinese patients receiving hepatectomy.

This study tested the possible protective and therapeutic effects of Viscum album extract and probiotics against carbon tetrachloride (CCl4)-induced acute/chronic liver injury. Male Wistar rats were assigned to seven groups: Control, acute CCl4, acute V. album + CCl4, acute V. album + Probiotics + CCl4, chronic CCl4, chronic CCl4 + V. album, and chronic CCl4 + V. album + Probiotics. Acute and chronic liver injuries were induced by 2 mg/kg CCl4 (i.p.) and 1 mg/kg CCl4 (i.p.), respectively. The extract and probiotics were administered daily to related groups. Serum enzyme activities, lipid profile, total protein, albumin, bilirubin, heme oxgenase-1 and 8-hydroxydeoxyguanosine levels were measured. Liver tissue sections stained with Hematoxylin-Eosin. Acute or chronic CCl4-exposure caused to significant changes in concentrations/activities of the measured parameters. The oral administration of extract and probiotics showed protective and therapeutic effects against CCl4-induced liver-injury. The supplementation of intestinal flora by the use of probiotics may enhance the efficacy of orally given therapeutic extracts. [ABSTRACT FROM AUTHOR]

Background: New evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury. Methods: We enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models. Results: The composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P <0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P < 0.001). Conclusions: These findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus , as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus Type 2 presents with major serious complications such as chronic kidney failure, liver disease, diabetic neuropathy, cerebrovascular disease created by metabolic dysfunction that leads to a state of chronic inflammation in these patients. With the objective of evaluating the influence of rectal ozone therapy as complementary therapy in patients with Type 2 diabetes Mellitus. 38 patients suffering Diabetes Mellitus Type 2 were selected and randomly divided into two groups. The first group (Ozone) received conventional treatment plus rectal ozone therapy and the second (Conventional) only received conventional treatment. Blood glucose, glycosylated hemoglobin, LDL-cholesterol, VLDL-cholesterol and triglycerides were measured in blood, markers of liver and kidney damage and the DNA-4 scale of neuropathic pain were measured at the beginning and at end of treatments with rectal ozone therapy. The group of patients who received rectal ozone therapy plus conventional treatment showed a significant decrease in glycemic, glycated hemoglobin, VLDL-cholesterol, triglyceride, LDL-cholesterol values compared to the group with conventional treatment. It reflected significant improvement in the liver and kidney damage markers as well as the levels of the DNA.-4 pain scale, compared to the group that only received conventional treatment. The complementary application of rectal ozone therapy showed a protective effect on metabolic, liver and kidney function in patients with Type 2 Diabetes Mellitus, and also showed a certain analgesic character by reducing pain in said disease. [ABSTRACT FROM AUTHOR]

Post hepatectomy liver failure (PHLF) could occur even though an adequate liver volume is preserved. Liver function is not strictly related to the volume and the necessity to pre-operatively predict the future liver remnant (FLR) function is emerging, together with the wide spreading of techniques, aiming to optimize the FLR. The aim of this study was to systematically review all the available tests, to pre-operatively assess the liver function and to estimate the risk of PHLF. A systematic literature research of Medline, Embase, Scopus was performed in accordance to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, to identify all the studies available for pre-operative liver function tests to assess the risk of PHLF and/or complications. From the 1122 references retrieved, 79 were included in the review. Dynamic functional tests, such as indocyanine green test (ICG), could evaluate only global liver function, with no definition of functional capacity of the remnant. Magnetic resonance imaging (MRI) with liver-specific contrast agents enables both liver function and volume evaluation; the absence of ionizing radiation showed a better patient's compliance. Nuclear imaging studies as hepatobiliary scintigraphy (HBS) present the unique ability to allow a precise evaluation of the segmental liver function of the remnant liver. Liver volume could overestimate liver function. Several liver function tests are available to evaluate the risk of PHLF in the pre-operative setting. However, no single test alone could accurately predict PHLF. Pre-operative combination between a dynamic quantitative test, such as ICG, with MRI or HBS, should enable a more complete functional evaluation. Functional tests to predict PHLF should be chosen according to patient's characteristics, disease, and center experience. [ABSTRACT FROM AUTHOR]

The current study determines the possible antitumor and immunomodulatory effects of thymosin against the in vivo and in vitro growth of tumor-derived cell line in mice. Peritoneal phagocytes count, Ehrlich ascites tumor (EAT) cells, T-lymphocytes, and B-lymphocytes activities were determined. In addition, serum level of interleukin 2 (IL-2) and liver functions were measured. In animal testing, thymosin at doses of 0.50 and 1mg activated the phagocytic function of macrophages, as well as T- and B-cell function. Thymosin caused a marked shortage in the proliferation of EAT cells in the peritoneal fluid with dose 0.50g as compared with that of the corresponding control group. Furthermore, treatment with thymosin caused effectively elevate in serum level of IL-2, on the contrary reduce in serum levels of ALT, AST and total proteins. The size of solid Ehrlich tumor was significantly decreased, as measured morphologically with the doses 0.50 and 1 mg (P<0.01). These results confirmed that many biological activities attributed to thymosin and is as an adjuvant for immune enhancement. [ABSTRACT FROM AUTHOR]