Melissa officinalis extract palliates redox imbalance and inflammation associated with hyperthyroidism-induced liver damage by regulating Nrf-2/ Keap-1 gene expression in γ-irradiated rats.

BACKGROUND: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. METHODS: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-ß1) were determined. RESULTS: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-ß1/Smad pathway. CONCLUSION: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.

The Impact of Red Yeast Rice Extract Use on the Occurrence of Muscle Symptoms and Liver Dysfunction: An Update from the Adverse Event Reporting Systems and Available Meta-Analyses.

Red yeast rice (RYR) has a cholesterol-lowering effect due to the presence of bioactive components (monacolins, mainly monacolin K) that act by inhibiting the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. The European Food Safety Authority (EFSA) assessed the use of RYR and, while pointing out several uncertainties regarding the available data, raised a warning related to the safety of RYR when used as a food supplement at a dose of monacolin as low as 3 mg/day. In their decision in June 2023, EFSA approved the use of monacolins from RYR at doses less than 3 mg/day. We therefore decided to interrogate the different adverse event reporting systems (FAERS and CAERS) and analyse the characteristics of the cases reported to be associated with RYR supplements, and we reviewed the most recent meta-analyses with a focus on the occurrence of muscle symptoms and liver dysfunction. In terms of all musculoskeletal disorders from September 2013 (when the first case related to RYR consumption was recorded) to 30 September 2023, 363,879 cases were reported in the FAERS, with the number of cases related to RYR consumption being very small and accounting for 0.008% of cases. In the same time frame, 27,032 cases of hepatobiliary disorders were reported, and the cases attributable to RYR ingestion accounted for 0.01% of all cases. A low rate of muscle symptoms and liver dysfunction attributed to RYR ingestion was also observed in the CAERS database, where only 34 cases of adverse muscle events and 10 cases of adverse liver events reported RYR as the suspect product, while 19 cases of both muscle events and 10 cases of adverse liver events reported it as a concomitant product. This profile mirrors that of meta-analyses of randomised clinical trials of RYR, in which RYR use was not associated with either liver dysfunction or muscular adverse symptoms.

Assessment of the need for routine intraoperative cell salvage in liver transplantation.

PURPOSE: This study aimed to assess the necessity of routine intraoperative cell salvage in liver transplantations. METHODS: A total of 327 liver transplants performed between 2014 and 2016 was included in the analysis. Patient data, including pre-transplant examinations, intraoperative red blood cell transfusions, and procedural information, were collected. RESULTS: The median age of the patients was 54 years old, with 67% (219) being male. The most prevalent ABO blood type was O, accounting for 48% (155) of cases. The leading causes of liver disease were hepatitis C (113 cases, 34.6%) and alcohol-related liver disease (97 cases, 29.7%). Out of the 327 liver transplants, allogeneic red blood cell transfusions were administered in 110 cases (34%) with a median of two units of red blood cells per case. Cell salvage was employed in 237 transplants (73%), and successful blood recovery was achieved in 221 cases (93%). Among the group that recovered more than 200 mL of blood, the median volume of recovered blood was 417 mL, with no transfusion of allogeneic blood required. A total of 90 transplants was performed without utilizing cell salvage, and, among these cases, 19 required blood transfusions, with a median of zero units transfused. CONCLUSIONS: This study suggests that routine cell salvage is unnecessary for all liver transplantations. The most suitable indication for its use is in patients presenting with portal vein thrombosis and abnormal creatinine levels.

Use of complementary and alternative medicine in children affected by oncologic, neurologic and liver diseases: a narrative review.

Complementary and alternative medicine (CAM) consist of a broad group of restorative resources often linked to existing local cultures and established health care systems and are also increasingly used in children with some serious illnesses. In this narrative review, we examine the epidemiology of the use, efficacy, and safety of complementary and alternative medicine in pediatric oncology, neurology, and hepatology. We searched for relevant articles published in Pubmed evaluating CAM use and its efficacy in safety in children affected by oncologic, neurologic and liver diseases. CAM is used to improve the success of conventional therapies, but also to alleviate the pain, discomfort, and suffering resulting from the diseases and their treatment, which are often associated with a significant burden of adverse effects. CAM use must be evaluated in children with neurological, oncological and liver diseases.

A Case of Abnormal Liver Function Tests in a Patient Receiving Total Parenteral Nutrition.

Hepatic dysfunction is prevalent in patients receiving total parenteral nutrition (TPN), resulting from steatosis, cholestasis, and cholecystitis. Regular assessments and monitoring of TPN patients are essential, even for clinically stable patients on long-term TPN. Furthermore, it is crucial to establish a differential diagnosis for hepatic dysfunction and investigate for other possible causes of elevated liver enzymes and underlying liver conditions. We present the case of a 56-year-old female patient with severe protein-calorie malnutrition on TPN, who exhibited significantly elevated liver enzymes during the routine periodic assessment. Subsequent investigation revealed that the patient had been taking traditional Chinese herbal medications concurrently with TPN. After discontinuing the herbal medications, the patient's liver enzymes returned to normal levels within 3 weeks.

Proinflammatory mediators in lipid emulsions and parenteral nutrition-associated liver disease: Review of leading factors.

Lipid injectable emulsions have been in clinical use for over 60 years. The first product launched was Intralipid, which consisted of an emulsion of soybean oil in water for intravenous administration. It was a key source of essential fatty acids and an alternative source of energy for patients with gastrointestinal dysfunction requiring long-term parenteral nutrition. With clinical experience, a condition known as parenteral nutrition-associated liver disease (PNALD), or intestinal failure-associated liver disease (IFALD), was observed, with a focus on carbohydrate and fat energy. Modifying the daily doses and infusion rates had some salutary effects, but PNALD persisted. Subsequently, on closer inspection of the fatty acids profile and phytosterol concentrations, degradation products arising from chemical and physical stability issues of the available lipid injectable emulsions were implicated. Recently, the US Food and Drug Administration convened an online workshop entitled "The Role of Phytosterols in PNALD/IFALD," with an emphasis on (1) the multifactorial pathophysiology of PNALD/IFALD, (2) risk associated with phytosterols, and (3) regulatory history. The scope of this review includes the multifactorial pathophysiology of PNALD/IFALD as it relates to the pharmaceutical aspects of the various lipid injectable emulsions on the market, with respect to potential proinflammatory components, as well as physical and chemical stability issues that may also affect products' safe intravenous administration to patients.

Chronic Liver Disease Secondary to Chronic Budd Chiari Causing Osteomalacia Leading to Pathological Fractures.

INTRODUCTION: Metabolic disturbances of bone are common in patients of CLD manifesting as osteoporosis and osteopenia while osteomalacia is rare. MATERIALS: 34 years old lady with history of portal vein thrombosis and CLD since 2008 presented with complaints of anorexia, early satiety, nausea, vomiting weight loss for 8 months and syncopal attack followed by fall on ground leading to multiple fractures in both lower limbs and left upper limb. Investigations including hemogram, metabolic profile, X-rays, anemia workup, Vitamin D3, parathyroid hormone (PTH), hormone profile, CA-125, 24-hour urinary calcium, USG were planned. RESULT: On presentation her BP=106/64 mm Hg, PR = 98, RBS = 104. GPE showed cachexia, severe pallor, bipedal edema, deformed elbow joint, thoracic kyphosis with cervical lordosis. Hemogram and metabolic panel were suggestive of severe anemia, thrombocytopenia, deranged LFT, increased ALP, anemia of chronic disease (AOCD), X-rays suggestive of multiple fractures. Possiblity of metabolic bone disease (hepatic osteodystrophy) was kept. Further investigations showed Vitamin D deficiency, raised PTH, low 24-hour urinary calcium and FSH was raised for age. Diagnosis of osteomalacia was made and patient was started vitamin D and calcium supplementation, normocalcemia achieved and PTH and ALP settled in months. CONCLUSION: Patients with liver disease should be investigated for the presence of hepatic osteodystrophy, to allow the identification and the correction of risk factors and start of the therapeutic program. Niranjan Gangoor, Sanjay Neeralagi, Gayathri Karnataka Institute of Medical Sciences, Hubballi, Karnataka, India Introduction: Liver plays an important role in the metabolism of thyroid hormones, as it is the most important organ in the peripheral conversion of tetraiodothyronine (T4) to triiodothyronine (T3) by Type 1 deiodinase. MATERIALS: This Prospective observational study included 100 liver cirrhosis patients Serum FT3, FT4, and thyroid-stimulating hormone (TSH) levels were measured using electrochemiluminescence immunoassay. Results were also analyzed for severity of liver disease according to Child-Turcotte-Pugh (CTP) (Class A, B, and C), model for end-stage liver disease (MELD) score, and HE grades. RESULT: Most common etiology was alcohol (58%) and presentation was gross ascites (77%). Cirrhosis patients had statistically significant lower level of FT3 and FT4 but had higher level of TSH. Cirrhosis with HE (n = 38) had significantly lower lever of FT3 compared with cirrhosis without HE (n = 62). In all cirrhotic patients, FT3 and FT4 were negatively correlated, but TSH level was positively correlated with total leukocyte counts, serum total bilirubin, aspartate transaminase, alanine transaminase, globulin, prothrombin time blood urea, serum creatinine, CTP, and MELD score. CONCLUSION: The mean FT3 and FT4 levels were significantly decrease and mean TSH levels were significantly increase in liver cirrhosis patients. Level of FT3, FT4, and TSH also correlate with the severity of liver disease, level of FT3 can be used as prognostic marker for liver cirrhosis patients. References Patira NK, Salgiya N, Agrawal D. Correlation of thyroid function test with severity of liver dysfunction in cirrhosis of liver. J Assoc Physicians India 2019;67(3):51-54. Kumar A, Ahuja V, Kaur I, et al. Prevalence of thyroid dysfunction in patients of cirrhosis of liver and its correlation with severity of cirrhosis. Int J Adv Res 2020;8:91-95.

Role of ER Stress in Xenobiotic-Induced Liver Diseases and Hepatotoxicity.

The liver is a highly metabolic organ and plays a crucial role in the transportation, storage, and/or detoxication of xenobiotics. Liver damage induced by xenobiotics (e.g., heavy metal, endocrine disrupting chemicals, Chinese herbal medicine, or nanoparticles) has become a pivotal reason for liver diseases, leading to great clinical challenge and much attention for the past decades. Given that endoplasmic reticulum (ER) is the prominent organelle involved in hepatic metabolism, ER dysfunction, namely, ER stress, is clearly observed in various liver diseases. In response to ER stress, a conserved adaptive signaling pathway known as unfolded protein response (UPR) is activated to restore ER homeostasis. However, the prolonged ER stress with UPR eventually leads to the death of hepatocytes, which is a pathogenic event in many hepatic diseases. Therefore, analyzing the perturbation in the activation or inhibition of ER stress and the UPR signaling pathway is likely an effective marker for investigating the molecular mechanisms behind the toxic effects of xenobiotics on the liver. We review the role of ER stress in hepatic diseases and xenobiotic-induced hepatotoxicity, which not only provides a theoretical basis for further understanding the pathogenesis of liver diseases and the mechanisms of hepatotoxicity induced by xenobiotics but also presents a potential target for the prevention and treatment of xenobiotic-related liver diseases.

Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases.

There is consistent evidence that vitamin D deficiency is strongly associated with liver dysfunction, disease severity, and poor prognosis in patients with liver disease. Vitamin D and its receptor (VDR) contribute to the regulation of innate and adaptive immune responses. The presence of genetic variants of vitamin D- and VDR-associated genes has been associated with liver disease progression. In our recent work, we summarized the progress in understanding the molecular mechanisms involved in vitamin D-VDR signaling and discussed the functional significance of VDR signaling in specific cell populations in liver disease. The current review focuses on the complex interaction between immune and liver cells in the maintenance of liver homeostasis and the development of liver injury, the interplay of vitamin D and VDR in the development and outcome of liver disease, the role of vitamin D- and VDR-associated genetic variants in modulating the occurrence and severity of liver disease, and the therapeutic value of vitamin D supplementation in various liver diseases. The association of the vitamin D-VDR complex with liver dysfunction shows great potential for clinical application and supports its use as a prognostic index and diagnostic tool.

Lactobacillus plantarum supplementation alleviates liver and intestinal injury in parenteral nutrition-fed piglets.

OBJECTIVE: Long-term parenteral nutrition (PN) causes PN-associated liver disease, for which therapeutic approaches are limited. This study aimed to investigate the effects of Lactobacillus plantarum CGMCC 1258 (LP) on liver and intestinal injury in PN-fed neonatal piglets. METHODS: The piglets received PN with or without oral LP for 14 days. The levels of liver enzymes and inflammatory markers were measured using biochemical kits and quantitative real-time polymerase chain reaction. Serum fibroblast growth factor 19 (FGF19) was detected using an enzyme-linked immunosorbent assay. The bile acid (BA) profiles in the liver, serum, and intestinal contents were determined using ultraperformance liquid chromatography coupled with mass spectrometry. The composition of intestinal bacteria was analyzed with 16S rRNA gene amplicon sequencing. RESULTS: LP supplementation was associated with improved markers of liver disease, inflammation, and oxidative stress in PN-fed piglets. Moreover, markers of intestinal injury and inflammation were alleviated by LP in PN-fed piglets. Mechanistically, LP increased the abundance of Lactobacillus in ileal contents and stimulated FGF19 expression in ileal mucosa. Subsequently, it increased the expression of small heterodimer partner (SHP) and inhibited cholesterol 7α-hydroxylase (CYP7A1) expression in the liver. Additionally, LP altered the systemic composition and metabolism of BAs. CONCLUSIONS: LP alleviated liver and intestinal injury in PN-fed neonatal piglets by altering the composition of intestinal bacteria and BAs.

Thyme Oil and Thymol Counter Doxorubicin-Induced Hepatotoxicity via Modulation of Inflammation, Apoptosis, and Oxidative Stress.

Doxorubicin (DOX) is an effective anticancer agent with a wide spectrum of activities. However, it has many adverse effects on various organs especially on the liver. Thymol, one of the major components of thyme oil, has biological properties that include anti-inflammatory and antioxidant activities. Thus, this study was designed to examine thyme oil and thymol for their ability to prevent doxorubicin-induced hepatotoxicity in Wistar rats. Hepatotoxicity was induced by an intraperitoneal injection of doxorubicin, at a dose of 2 mg/kg bw/week, for seven weeks. Doxorubicin-injected rats were supplemented with thyme oil and thymol at doses 250 and 100 mg/kg bw, respectively, four times/week by oral gavage for the same period. Treatment of rats with thyme oil and thymol reversed the high serum activities of AST, ALT, and ALP and total bilirubin, AFP, and CA19.9 levels, caused by doxorubicin. Thyme oil and thymol also reduced the high levels of TNF-α and the decreased levels of both albumin and IL-4. These agents ameliorated doxorubicin-induced elevation in hepatic lipid peroxidation and associated reduction in GSH content and GST and GPx activities. Further, the supplementation with thyme oil and thymol significantly augmented mRNA expression of the level of antiapoptotic protein Bcl-2 and significantly downregulated nuclear and cytoplasmic levels of the hepatic apoptotic mediator p53. Thus, thyme oil and thymol successfully counteracted doxorubicin-induced experimental hepatotoxicity via their anti-inflammatory, antioxidant, and antiapoptotic properties.

Intestinal failure-associated liver disease in the neonatal ICU: what we know and where we're going.

PURPOSE OF REVIEW: Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. RECENT FINDINGS: The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. SUMMARY: Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.

Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events.

OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.

Trends in liver profile and nutrition outcomes in children undergoing intestinal rehabilitation using a mixed lipid injectable emulsion.

BACKGROUND: Pediatric patients undergoing intestinal rehabilitation (IR) using parenteral nutrition (PN) are at higher risk for intestinal failure-associated liver disease (IFALD). Nutrition support, growth, and liver enzymes must be closely monitored while incorporating hepatoprotective lipid injectable emulsions for optimal patient outcomes. OBJECTIVE: Describe trends of liver profile and nutrition outcomes for pediatric patients undergoing IR using SMOFlipid[SO,MCT,OO,FO-ILE]). METHODS: After IRB approval, patients undergoing IR using SO,MCT,OO,FO-ILE were observed prospectively from January 1, 2017, through December 1, 2019. The following values were documented monthly: aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), triene/tetraene ratio (TTR), micronutrient and trace element levels, z-scores for growth, and nutrition support regimen. Values were compared. RESULTS: The group involved 16 pediatric patients for an average of 16.4 months on SO,MCT,OO,FO-ILE. By the end of the study, mean PN hours per day decreased by 34.7%, P < 0.0001. Mean PN calories per kilogram decreased from 60.4 to 48.3, P = 0.004. SO,MCT,OO,FO-ILE calories met the recommended dietary intake goal of 30% at the average 1.6 g/kg. Growth z-scores increased in those <2 YOA , although the body mass index decreased in our >2 YOA cohort. Total nutrition received from PN decreased to 62%: a 32% change, P = 0.001. There were no statistically significant changes in AST or ALT. TB decreased by 67.08%, P <0.05. No essential fatty acid deficiency was reported (TTR < 0.02). There were no changes in micronutrient and trace element deficiencies. There was zero new incidences of IFALD. CONCLUSIONS: SO,MCT,OO,FO-ILE may be used long term in pediatric patients while promoting growth and development.

Treatment and outcomes of dogs with hepatocutaneous syndrome or hepatocutaneous-associated hepatopathy.

BACKGROUND: Superficial necrolytic dermatitis (SND) in dogs is a rare disorder most commonly associated with hepatocutaneous syndrome. Although often reported as fatal, sporadically reported long-term remissions might be more common than previously believed and linked to treatment regimens. HYPOTHESIS/OBJECTIVES: Evaluate treatments and associated outcomes in dogs with hepatocutaneous-associated hepatopathy (HCH) with or without SND, designated collectively aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES). ANIMALS: Forty-one dogs of various breeds and ages diagnosed with ACHES. METHODS: Retrospective study. Electronic surveys, medical records (2014-2019), and communication with veterinarians provided data. Three treatment categories were each dichotomized: IV amino acid (IV-AA) infusions (≥2 vs <2), supplements including S-adenosylmethionine (SAMe), arginine with ornithine, glutathione, lysine, proline, omega-3 fatty acids, or zinc (≥3 vs <3), and diet type (home-cooked vs commercial). Optimal treatment was defined as receiving ≥2 IV-AA treatments, ≥3 nutritional supplements, and a home-cooked diet. RESULTS: Most dogs (29/41, 71%) received IV-AA infusions (23/29, ≥2 infusions). Twenty-one dogs (51%) were fed commercial diets; 17/41 (41%) were fed home-cooked diets. Most dogs received SAMe (32/41, 78%) and a median of 3 supplements. In 4 dogs, HCH remission occurred. Overall all-cause median survival time (MST) was 359 days, and disease-specific MST was 557 days (range, 1-1783 days). Optimally treated dogs (n = 9) lived significantly longer (MST, >1783 days, P = .02) than variably treated dogs (MST, 214 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Optimized ACHES management can resolve SND and HCH and confer long-term survival.

Clinical and economic impact of an alert system in primary care for the detection of patients with chronic hepatitis C.

INTRODUCTION: Prevalence of chronic hepatitis C (CHC) is higher in patients born between 1955-1975. The aim was to perform an economic evaluation of an age-based electronic health record (EHR) alert in primary care to detect patients with undiagnosed CHC and its treatment in comparison with non-use of the alert system, in Valencian Community, Spain. MATERIALS AND METHODS: Decision trees and Markov model were used to evaluate the diagnosis and progression of the disease, respectively. CHC was diagnosed by serology and viral load in seropositive subjects. Epidemiological data and diagnostic costs were extracted from public sources of the Valencian Community. Probabilities, utilities and costs of model states were obtained from the literature. The impact on mortality and hepatic complications avoided by the implementation of the alert were estimated, and efficiency was measured as an incremental cost-utility ratio (ICUR) based on quality-adjusted life years (QALYs) and the costs of both alternatives. RESULTS: The EHR alert detected 269,548 patients, of whom 1,331 had CHC (vs. 23 patients with non-alert). Over the patients' lifetime, the alert would prevent 93% of decompensated cirrhosis cases, 87% of hepatocellular carcinomas, 90% of liver transplants, and 89% of liver related deaths compared to non-use of the alert system. In addition, it would obtain an additional 3.3 QALY per patient, with an incremental cost of €10,880 and an ICUR of €3,321. CONCLUSIONS: The implementation of an age-based EHR alert in primary care to detect patients with CHC reduces hepatic complications and mortality and is an efficient strategy.

Zinc supplementation and its benefits in the management of chronic liver disease: An in-depth literature review.

Malnutrition among patients with chronic liver disease (CLD) is a common complication with significant prognostic implications for patients with liver cirrhosis. Micronutrient deficiency has been associated with an increased risk of hepatic decompensation and is an independent risk factor for mortality among cirrhotic patients. Micronutrient deficiencies in patients with CLD include zinc, vitamin A, vitamin D and selenium. This review article aims to evaluate the literature to date on the complications of zinc deficiency in patients with CLD. A management algorithm for zinc replacement has also been proposed.

Pomegranate Polyphenols Attenuate Inflammation and Hepatic Damage in Tumor-Bearing Mice: Crucial Role of NF-κB and the Nrf2/GSH Axis.

It has been widely reported that cancer, along with its treatment regimens, cause severe toxicity in the host. A suitable agent having chemopreventive properties as well as capabilities of ameliorating tumor- and drug-induced toxicities is of imminent need. Pomegranate has been projected as an excellent anti-tumor, anti-inflammatory and anti-oxidant agent. In this study, for the first time, we delineated the exact signaling cascade by which dietary supplementation of pomegranate fruit extract (PFE) protects tumor-bearing mice from tumor-induced hepatotoxicity. Increased activities of serum Alanine transaminase, Aspartate transaminase, Lactate dehydrogenase and Alkaline phosphatase, as well as histological studies confirmed the establishment of a state of hepatic dysfunction in tumor-bearers. Further investigations revealed that increased hepatic reactive oxygen species content and glutathione depletion-initiated apoptosis in these hepatocytes as we observed an alteration in the apoptotic proteins. PFE supplementation in tumor-bearing mice, on the other hand, differentially modulated redox-sensitive transcription factors Nrf2 and NF-κB, ultimately decreasing tumor-induced hepatic oxidative damage and cell death. siRNA-mediated inhibition of Nrf2 and NF-κB completely abolished the hepato-protective activities of PFE while pre-treatment of tumor-conditioned hepatocytes with N-acetyl cysteine augmented the cyto-protective properties of PFE. The present study clearly identified Nrf2/NF-κB/glutathione axis as the key factor behind the hepatoprotective potential of PFE. These findings would add to the existing knowledge about cancer chemoprevention by dietary polyphenols and might lead to the application of pomegranate polyphenols as supplement to escalate the effectiveness of cancer therapy by protecting normal cells from cancer related toxicities.

Liver injury in COVID-19: clinical features and treatment management.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.

Alleviation of diabetes-induced hepatotoxicity by date palm hydroalcoholic extract in rat model; a biochemical, immunohistochemical and stereological study / Alivio de la hepatotoxicidad inducida por diabetes mediante el extracto hidroalcohólico de palmera datilera en modelo de rata: un estudio bioquímico, inmunohistoquímico y estereológico

SUMMARY: The present study was aimed to investigate the hepatoprotective effects of date palm hydroalcoholic extract (DP)in diabetic rats using biochemical and histopathological approaches. Diabetes was induced by administration of 60 mg/kg of streptozotocin intraperitoneally. In this analysis 32 adult rats were randomly divided into four groups; group 1: non-diabetic control whic received 0.1 mL normal saline, group 2:served as non-diabetic control which treated with 270 mg/kg of DP, group 3: served as untreated diabetic, and group 4: diabetic rats treated with 270 mg/kg of DP. Diabetic rats treated with the DP extracts exhibited lower hepatic oxidative stress and lower hepatic enzymes level. Extract treatment decreased the level of malondealdehyde (MDA) as a marker of lipid peroxidation. Stereological estimations revealed a significant increase in the liver volume in diabetic rats which was reduced in DP-treated rats. Immunofluorescence staining showed high synthesis of acrolein as a byproduct of lipid proxidation. While, optical density measurement revealed significant decrease in acrolein after DP administration. Histopathological examination showed severe changes in untreated diabetic liver tissue manifested by dilated portal vein, leukocytic infiltration, fatty degeneration and necrotic nuclei, whereas, DP treatment attenuated the adverse effects of diabetes on the liver represented by relatively healthy hepatocytes and sinusoids. The obtained results indicated that date pam extract was beneficial in the prevention of diabetes-induced hepatotoxicity due to its natural antioxidant constituents. Further preclinical and clinical studies are needed for considering this plant in management of prediabetes and diabetes hepatic complications.

RESUMEN: El presente estudio tuvo como objetivo investigar los efectos hepatoprotectores del extracto hidroalcohólico (DP) de la palmera datilera en ratas diabéticas utilizando enfoques bioquímicos e histopatológicos. La diabetes fue inducida mediante la administración de 60 mg / kg de estreptozotocina por vía intraperitoneal. Se dividieron al azar 32 ratas adultas en cuatro grupos; grupo 1: control no diabético que recibió 0,1 mL de solución salina normal, grupo 2: control no diabético tratado con 270 mg / kg de DP, grupo 3: fue separado como diabético no tratado, y grupo 4: ratas diabéticas tratadas con 270 mg / kg de DP mg / kg de DP. Las ratas diabéticas tratadas con los extractos de DP mostraron menor estrés oxidativo hepático y menor nivel de enzimas hepáticas. El tratamiento con extracto disminuyó el nivel de malondealdehído (MDA) como marcador de la proxidación de lípidos. Las estimaciones estereológicas revelaron un aumento significativo en el volumen del hígado en ratas diabéticas que se redujo en las ratas tratadas con DP. La tinción por inmunofluorescencia mostró una alta síntesis de acroleína como subproducto de la proxidación de lípidos. Mientras que, la medición de la densidad óptica reveló una disminución significativa de la acroleína después de la administración de DP. El examen histopatológico mostró cambios significativos en el tejido hepático diabético no tratado manifestados por vena porta dilatada, infiltración leucocítica, degeneración grasa y núcleos necróticos, mientras que el tratamiento con DP atenuó los efectos adversos de la diabetes en el hígado representados por hepatocitos y sinusoides relativamente sanos. Los resultados obtenidos indicaron que el extracto de palmera datilera fue beneficioso en la prevención de la hepatotoxicidad inducida por diabetes debido a sus constituyentes antioxidantes naturales. Se necesitan más estudios clínicos para considerar esta planta en el manejo de la prediabetes y las complicaciones hepáticas de la diabetes.