Biochemical Indices Of Liver Function Research Articles

Bioinformatics-led discovery of liver-specific genes and macrophage infiltration in acute liver injury.

Acute liver injury (ALI) is an important global health concern, primarily caused by widespread hepatocyte cell death, coupled with a complex immune response and a lack of effective remedies. This study explores the underlying mechanisms, immune infiltration patterns, and potential targets for intervention and treatment ALI. The datasets of acetaminophen (APAP), carbon tetrachloride (CCl4), and lipopolysaccharide (LPS)-induced ALI were obtained from the GEO database. Differentially expressed genes (DEGs) were individually identified using the limma packages. Functional enrichment analysis was performed using KEGG, GO, and GSEA methods. The overlapping genes were extracted from the three datasets, and hub genes were identified using MCODE and CytoHubba algorithms. Additionally, PPI networks were constructed based on the String database. Immune cell infiltration analysis was conducted using ImmuCellAI, and the correlation between hub genes and immune cells was determined using the Spearman method. The relationship between hub genes, immune cells, and biochemical indicators of liver function (ALT, AST) was validated using APAP and triptolide (TP) -induced ALI mouse models. Functional enrichment analysis indicated that all three ALI models were enriched in pathways linked to fatty acid metabolism, drug metabolism, inflammatory response, and immune regulation. Immune analysis revealed a significant rise in macrophage infiltration. A total of 79 overlapping genes were obtained, and 10 hub genes were identified that were consistent with the results of the biological information analysis after screening and validation. Among them, Clec4n, Ms4a6d, and Lilrb4 exhibited strong associations with macrophage infiltration and ALI.

An open-label, controlled trial of the clinical effects of Laennec® in patients with nonalcoholic steatohepatitis or cirrhosis

Objective: to evaluate the efficacy and safety of human placenta hydrolysate (HPH) Laennec® in the treatment of nonalcoholic fatty liver disease (NAFLD) in a clinical trial.Material and methods. The study involved hospitalized NAFLD patients (with non-alcoholic steatohepatitis, cirrhosis) (n=34, mean age 53±14 years). In the therapy group (n=17), patients received Laennec® HPH (4 ml intravenous drip infusion in a solution of 5% glucose 5 times a week for 2 weeks). In the control group (n=17), patients hospitalized in other departments of the clinic did not receive any therapy for NAFLD. The effectiveness of therapy was assessed after 2 and 3 weeks by subjective NAFLD symptoms (fatigue, anorexia, bloating, constipation, nausea, and pain in hypochondrium) and biochemical indicators of liver function: levels of blood serum aspartate aminotrans-ferase (AST), alanine notransferase (ALT), gamma-glutamyltransferase (GGT).Results. At the start of the study, there were no significant differences between the groups in the values of the studied indicators of liver function: blood levels of AST, ALT, GGT, etc. By the end of Week 1, a significant decrease in AST levels was registered in the group receiving Laennec® (–35 U/l; control: –8 U/l; p<0.001), ALT (–45 U/l; control: –10 U/l; p<0.001), and GGT (–23 U/l; control: –8 U/l; p=0.084; trend). At the end of the study (Week 3), the decrease in AST, ALT and GGT levels towards the normal range was even more pronounced for all three biomarkers: AST (–62 U/l; control: –23 U/l; p<0.001), ALT (–78 U/l; control: –20 U/l; p<0.001), GGT (–40 U/l; control: –15 U/l; p=0.005). Subjective NAFLD symptoms significantly improved after 3 weeks. No adverse effects were identified with the use of HPH. Conclusion. Laennec® is an effective and safe treatment for NAFLD.

A Novel Quinazoline Derivative Prevents and Treats Arsenic-Induced Liver Injury by Regulating the Expression of RecQ Family Helicase.

Arsenic is a carcinogenic metalloid toxicant widely found in the natural environment. Acute or prolonged exposure to arsenic causes a series of damages to the organs, mainly the liver, such as hepatomegaly, liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Therefore, it is imperative to seek drugs to prevent arsenic-induced liver injury. Quinazolines are a class of nitrogen heterocyclic compounds with biological and pharmacological effects in vivo and in vitro. This study was designed to investigate the ameliorating effects of quinazoline derivatives on arsenic-induced liver injury and its molecular mechanism. We investigated the mechanism of the quinazoline derivative KZL-047 in preventing and ameliorating arsenic-induced liver injury in vitro by cell cycle and apoptosis. We performed real-time fluorescence quantitative polymerase chain reaction (qPCR) and Western blotting combined with molecular docking. In vivo, the experiments were performed to investigate the mechanism of KZL-047 in preventing and ameliorating arsenic-induced liver injury using arsenic-infected mice. Physiological and biochemical indices of liver function in mouse serum were measured, histopathological changes in liver tissue were observed, and immunohistochemical staining was used to detect changes in the expression of RecQ-family helicases in mouse liver tissue. The results of in vitro experiments showed that sodium arsenite (SA) inhibited the proliferation of L-02 cells, induced apoptosis, blocked the cell cycle at the G1 phase, and decreased the expression of RecQ family helicase; after KZL-047 treatment in arsenic-induced L-02 cells, the expression of RecQ family helicase was upregulated, and the apoptosis rate was slowed, leading to the restoration of the cell viability level. KZL-047 inhibited arsenic-induced oxidative stress, alleviated oxidative damage and lipid peroxidation in vivo, and ameliorated arsenic toxicity-induced liver injury. KZL-047 restored the expression of RecQ family helicase proteins, which is consistent with the results of in vitro studies. In summary, KZL-047 can be considered a potential candidate for the treatment of arsenic-induced liver injury.

TOXICITY OF AFLATOXIN B1 TOWARDS THE INDUCING ALTERATIONS IN THE LIVER FUNCTIONS

Since 2003, the world's developing countries are home to more than 5 billion people thought to be at danger of prolonged consumption of contaminated foods that are aflatoxic according to a number of study efforts conducted in South Africa, Egypt, and other countries in west and east Africa. Additionally, the presence occurrence of aflatoxins and their byproducts in animal tissues used to make food (such as beef and sheep meat) may contaminate human diets. As a result of their increasing prevalence, aflatoxins have recently been identified as a significant public health concern.Aflatoxins are dangerous second-generation byproducts of Aspergillus species. Due to their chemical makeup, the majority of aflatoxins are highly liposoluble substances that can be absorption from the exposed site, such as the gastro-intestinal and respiratory tracts, into the bloodstream, where they can then spread throughout the body and reach various organs, including the liver and kidneys. The primary goals of the study were to monitor and screen for levels of aflatoxin B1 in the Karbala Province using a case-control study. The connection between Aflatoxin B1 concentrations and the common biochemical indicators of liver function as well investigated. How alter liver function by Aflatoxin B1. The study also emphasised the necessity to determine the pathophysiology of AFB1's involvement in the rising number of patients with liver dysfunction. AFB1 levels were quantitated using utilising thin layer chromatography, together with High Pressure liquid chromatography being employed for the quantitative identification (HPLC). In the province of Karbala, an analysis of case-control studies was done to look at the Aflatoxin B1 affects (AFB1) exposure on kidney disease patients. AFB1 levels were quantitated using utilising thin layer chromatography with high-performance liquid chromatography to provide quality results. The evaluations of the samples that tested positive for AFB1 as well as the lipid profile and indicators of liver function tests. The findings indicated that the population under investigation had afflatoxins exposure. AFB1 was found in 100% of individuals with unknown kidney disease (KD) and in 24%, 20%, and 100% of patients with known CKD, respectively. AFB1 concentrations in serum samples ranged from 0.68 to 8.33 ng/mL for patients with questionable KD, 1.21 to For patients, 5.60 ng/mL with known KD, likewise, healthy controls ranged from 0.11 to 1.30 ng/mL. The presence of AFB1 was positively and strongly linked with liver enzymes, specifically ALT and ALP. AFB1 levels among serum samples from KD sufferers and wholesome controls showed a prolonged contact with the poison, suggesting an unknown cause. The evaluation of the biochemical marker of liver functioning supported the effect of AFB1 exposure. This work may help build effective nationwide programmes for tracking AFs exposure. The study also emphasised the necessity to determine the pathophysiology of AFB1's involvement in the rising number of patients with liver dysfunction. Future research is urged to concentrate on more comprehensive topics that cover the entire nation (Iraq).

Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat.

Aging is a naturally occurring physiological process with a deleterious impact on various body organs and humans' well-being. The aging population is increasing worldwide, which imposes the need for the exploration of nutritional options that can intercept the impact of the aging processed on various body organs. Vitamin K2 (VK2) is a fat-soluble vitamin with emerging evidence on its therapeutic merits. In the current study, natural aging induced a significant liver deterioration with a disrupted Keap-1/Nrf-2/HO-1 axis and increased COX-2, iNOS and TNF-α expression and apoptotic and fibrotic changes. VK2 administration, on the other hand, improved the biochemical indices of liver function (total protein, albumin, ALT and AST); the suppressed hepatic expression of Keap-1 and increased the hepatic expression of Nrf-2 with a parallel increase in the hepatic activity of HO-1. Subsequently, the liver content and hepatic expression of TNF-α, COX-2 and iNOS were significantly retracted. In context, the liver content and hepatic expression of the fibrotic biomarkers TGFβ and TIMP significantly retracted as well. Moreover, the TUNEL assay confirmed the retraction of liver apoptotic changes. Of notice, electron transmission microscope examination confirmed the preservation of mitochondrial functions and preservation of the ultra-microscopical structures. In conclusion, the VK2-mediated interception of aging-induced Keap-1/Nrf-2/HO-1 signaling suppressed the hepatic contents of inflammatory and fibrotic biomarkers, as well as apoptotic changes with preservation of the hepatic architectural and functional status. VK2 can be presumed to be an effective nutritional supplement to the aging population to spare the liver, amongst other body organs, against aging-induced deleterious injury.

Debating capabilities of biochemical markers of liver function in patients with alcoholic liver cirrhosis

Introduction. The diagnosis of alcohol-related liver disease is limited by the lack of a tool to reliably identify whether the present deterioration in the patient’s condition is due to alcohol consumption or other causes.Purpose. to conduct a comparative assessment of the clinical and diagnostic significance of liver function biochemical indicators (AST, ALT, GGT, ALP) and their calculated derivatives (AST/ALT, GGT/ALP, GGT/GGTn, ALP/ALPn) as markers of alcohol consumption in patients with alcoholic liver cirrhosis.Material and methods. The observational study included 112 men over 18 years of age with alcohol-related liver cirrhosis. The patients were assessed the severity of liver cirrhosis according to the Child-Pugh scale, performed general and biochemical blood tests, coagulation test, assessment of the fact of alcohol consumption by the level of phosphatidylethanol. An analysis was made of the relationship between alcohol consumption and changes in laboratory parameters of liver function, with the determination of their sensitivity and specificity.Results. Patients with Child-Pugh B cirrhosis who consumed alcohol on phosphatidylethanol had higher levels of plasma albumin, GGT, and lower values of creatinine, direct and total bilirubin, urea, and aPTT compared with patients who did not drink alcohol (p < 0.05). Alcohol-drinking patients with class C cirrhosis have higher ALT levels compared with abstinent patients with the same severity of cirrhosis (p < 0.05). The relationship between the fact of alcohol consumption, determined by the level of phosphatidylethanol, and the ratio of GGT of patients to the normal GGT value, as well as between the ratio of GGT to alkaline phosphatase and the degree of increase in GGT, turned out to be statistically significant. To assess the fact of alcohol consumption, the level of serum GGT > 65 IU/ l (75.5%) has the highest sensitivity, the highest specificity is the ratio of the patient’s GGT to the normal value of GGT > 2 (82.9%).Conclusion. Compared with the known 100% sensitivity and > 92% specificity of Peth as a alcohol biomarker, among the biochemical indicators of liver function and their calculated derivatives, GGT > 65 IU/l have the greatest sensitivity or specificity (respectively, 75.5% and 65%) and GGTnorm. > 2 (37.7% and 82.9%, respectively), which makes it possible to use the totality of these parameters as an indicator of the continued impact on the patient of the main etiological factor of alcohol-related liver cirrhosis in the routine practice of most medical organizations of the Russian Federation.

Dietary Vitamin C Intake Is Associated With Improved Liver Function and Glucose Metabolism in Chinese Adults.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases worldwide. Dietary vitamin C intake might play an important role in reducing the risk of NAFLD. This study assesses the relationship between dietary vitamin C intake and diagnostic biomarkers of NAFLD.MethodsThe data from the 2009 China Health and Nutrition Survey (CHNS), nine provinces across four diverse regions (Northeast, East Coast, Central, and West) were included in the study. The dietary vitamin C intake of participants was calculated based on 3-day 24-h diet questionnaires at the individual level. The associations of dietary vitamin C intake and the biochemical indicators of liver function and glucose/lipid metabolism were determined.ResultsA total of 8,307 participants were included in the final analysis. The mean dietary vitamin C intake for the overall, male and female subjects was 79.8 ± 58.6, 81.6 ± 55.3, and 78.2 ± 61.2 mg/day, respectively. The prevalence of inadequate dietary vitamin C intake for the overall, male and female subjects was 24.4, 26.5, and 22.6%, respectively. Intake of vitamin C was associated with both lower concentrations of plasma ferritin and hemoglobin A1c (HbA1c). Higher dietary vitamin C intake was associated with higher albumin, even further adjusted for body mass index (BMI), residence, and smoking status. No improvement in lipid metabolism was found.ConclusionThis study demonstrated that higher dietary vitamin C intake is a benefit for improving glucose metabolism and liver function in which reducing ferritin, a biomarker of iron accumulation, may be involved.

Correlation between liver lipidosis, body condition score variation, and hepatic analytes in dairy cows.

Liver lipidosis is a metabolic disorder mostly observed in high yielding dairy cattle, especially during the transition period. The aim of this study was to determine the correlation between hepatic lipid infiltration, biochemical indicators of liver function, and body condition score (BCS) variation in dairy cows. Fifty-one multiparous Holstein cows raised in a confined system were evaluated. Liver biopsies and blood samples were collected, and BCS was measured on days 3 and 28 postpartum. Lipid infiltration was determined by histologic examination. The plasma activity of aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase and concentration of beta-hydroxybutyrate, non-esterified fatty acids, albumin, total bilirubin, and cholesterol were determined. BCS was measured using objective (camera) and subjective (visual) methods. Mild lipid infiltration was found in 3.92% of cows sampled on day 3 and 5.88% on day 28. Bilirubin was significantly higher on day 3 than on day 28 postpartum, and cholesterol was significantly higher on day 28 than on day 3 in all cows. There was no difference in biochemical analytes between cows with and without lipidosis. On day 3, mean subjective BCS was 3.10 and objective BCS was 3.16, while on day 28, these scores were 2.91 and 2.99, respectively. The calculated liver function index (LFI) was found to be a more sensitive indicator of liver function than the hepatic analytes evaluated. No correlation between BCS variation and lipid infiltration was found. Cholesterol and bilirubin levels showed the most remarkable changes during the early postpartum period. LFI is a potential indicator of postpartum liver function.

Feasibility of liver stiffness measured using two-dimensional shear wave elastography in assessing preoperative liver function for patients with hepatocellular carcinoma.

To evaluate the feasibility of liver stiffness (LS) measured using two-dimensional shear wave elastography (2D SWE) in assessing preoperative liver function for patients with hepatocellular carcinoma (HCC). A total of 143 patients who underwent surgical resection for HCC between August 2018 and December 2019 were enrolled prospectively. LS measurement, liver function tests including serum biochemical indicators, and indocyanine green (ICG) clearance test were performed preoperatively. Child-Pugh (CP) score, Albumin-bilirubin (ALBI) score and Model for End-Stage Liver Disease score were calculated. ICG retention rate at 15min (ICG R15) and ICG elimination rate constant (ICG K) were determined automatically. Fibrosis stage was determined based on pathological findings. The association between LS and serum biochemical indicators, liver function scores, and the ICG results were analyzed. Weak to moderate correlations were identified between LS and biochemical indicators of liver function (all p < 0.01). Weak correlation was identified between LS and CP score, and between LS and ALBI score (all p < 0.001). Moderate correlation was identified between LS and ICG R15 (Pearson r = 0.62, p < 0.001), and between LS and ICG K value (Pearson r = - 0.49, p < 0.001). The best cutoff of LS to discriminate a normal ICG R15 was 10.6kPa, with area under the curve (AUC), sensitivity, specificity of 0.874, 0.900 and 0.724, respectively. LS determined using 2D SWE could be a potential tool for the preoperative evaluation of liver function in patients with HCC.

Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan.

BackgroundCoronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients.MethodsPatient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality.ResultsLogistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19.ConclusionElevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

Clinical Efficacy of Diammonium Glycyrrhizinate on Drug Induced Liver Injury and Influence on Related Inflammatory Factors

To assess the clinical efficacy of diammonium glycyrrhizinate on drug induced liver injury and its effect on related inflammatory factors in the real world. A total of 234 inpatients diagnosed with drug induced liver injury in our hospital were continuously enrolled in this retrospective real world study, of whom 110 were treated with diammonium glycyrrhizinate and divided into three groups according to drug combination. Treatment group A (n=34) received diammonium glycyrrhizinate injection+reduced glutathione injection, treatment group B (n=45) received Kuhuang injection based on administration for treatment group A, and treatment group C (n=31) received ursodeoxycholic acid capsules based on administration for treatment group B. The remaining 124 cases did not undergo diammonium glycyrrhizinate treatment, including 37 cases in control group A receiving reduced glutathione injection alone, 55 cases in control group B receiving Kuhuang injection based on treatment for control group A, and 32 cases in control group C receiving ursodeoxycholic acid capsules based on treatment for control group B. The treatment lasted for 2 w. The biochemical indices such as serum gamma glutamyl transpeptidase, total bilirubin, alkaline phosphatase, glutamic pyruvic transaminase, tumor necrosis factor-α and interleukin-6 were observed before treatment and 1 w and 2 w after treatment, and adverse reactions were recorded. The efficacy was evaluated and compared. Compared with before treatment, the levels of alkaline phosphatase, glutamic pyruvic transaminase, tumor necrosis factor-α, interleukin-6 and total bilirubin in treatment group A, the levels of alkaline phosphatase, glutamic pyruvic transaminase, gamma glutamyl transpeptidase, tumor necrosis factor-α, interleukin-6 and total bilirubin in treatment group B, and the levels of alkaline phosphatase, glutamic pyruvic transaminase, tumor necrosis factor-α, interleukin-6 and gamma glutamyl transpeptidase in treatment group C all significantly declined (p<0.05). The levels of total bilirubin, tumor necrosis factor-α and interleukin-6 significantly declined in control group C (p<0.05), while the changes in biochemical indices had no significant differences in other control groups (p>0.05). Compared with before treatment, the levels of tumor necrosis factor-α, interleukin-6 and total bilirubin in treatment group A, the levels of alkaline phosphatase, glutamic pyruvic transaminase, tumor necrosis factor-α, interleukin-6 and gamma glutamyl transpeptidase in treatment group B, and the levels of alkaline phosphatase, tumor necrosis factor-α and interleukin-6 in treatment group C significantly declined (p<0.05), but the level of total bilirubin in treatment group C significantly rose (p<0.05). The response rates in treatment group A and B were higher than those in control group A and B, respectively (p<0.05), but it was lower in treatment group C than that in control group C (p<0.05). The response rates in treatment group A and B exceeded than in treatment group C (p<0.167), while it had no significant difference between treatment group A and B (p>0.167). The adverse reactions were all mild in treatment group A, B and C (p>0.05). Compared with reduced glutathione injection alone (control group A) and reduced glutathione injection+Kuhuang injection (control group B), double combination of reduced glutathione injection+diammonium glycyrrhizinate (treatment group A) and triple combination of reduced glutathione injection+Kuhuang injection+diammonium glycyrrhizinate (treatment group B) can improve the biochemical indices of liver function and increase the response rate, with a higher response rate than quadruple combination of reduced glutathione injection+Kuhuang injection+ursodeoxycholic acid capsules+diammonium glycyrrhizinate (treatment group C). The response rate had no clinical significance between quadruple combination and reduced glutathione injection+Kuhuang injection+ursodeoxycholic acid capsules (control group C). The administration for each treatment group was safe.

Protective effects of molecular hydrogen on hepatotoxicity induced by sub-chronic exposure to chlorpyrifos in rats.

Chlorpyrifos (CPF) is a organophosphate insecticide widely used in agriculture with attendant adverse health outcomes. Chronic exposure to CPF induces oxidative stress and elicits harmful effects, including hepatic dysfunction. Molecular hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. The aim of this study was to determine whether the intake of hydrogen-rich water (HRW) could protect rats from hepatotoxicity caused by sub-chronic exposure to CPF. Rats were treated with hydrogen-rich water by oral intake for 8 weeks. Biochemical indicators of liver function, SOD and CAT activity, GSH and MDA levels were determined by the spectrophotometric method. Liver cell damage induced by CPF was evaluated by histopathological and electron microscopy analysis. PCR array analysis was performed to investigated the effects of molecular hydrogen on the regulation of oxidative stress related genes. Both the hepatic function tests and histopathological analysis showed that the liver damage induced by CPF could be ameliorated by HRW intake. HRW intake also attenuated CPF induced oxidative stress, as evidenced by restored SOD activities and MDA levels. The results of PCR Array identified 12 oxidative stress-related genes differentially expressed after CPF exposure, 8 of chich, including the mitochondrial Sod2 gene, were significantly attenuated by HRW intake. The electron microscopy results indicated that the mitochondrial damage caused by CPF was alleviated after HRW treatment. The results obtained suggest that HRW intake can protect rats from CPF induced hepatotoxicity, and the oxidative stress signaling and the mitochondrial pathway may be involved in the protection of molecular hydrogen.

Long-term environmental exposure to microcystins increases the risk of nonalcoholic fatty liver disease in humans: A combined fisher-based investigation and murine model study

Microcystins (MCs) produced by cyanobacteria pose serious threats to human health. However, the contribution of long-term exposure to MCs to the development of nonalcoholic fatty liver disease (NAFLD) remains poorly documented. In this study, we estimated the environmental uptake of MCs by a small population of fishers who have lived for many years on Meiliang Bay of Lake Taihu, where cyanobacterial blooms occur frequently. Serum biochemical indices of liver function and their relationships with MC contamination in these people were also investigated. Moreover, to mimic the long-term effects of MC on the livers of fishers, an animal model was established in which mice were exposed to MC-LR at an environmentally relevant level, a reference level (the no-observed adverse effect level, NOAEL), and three times the NOAEL through drinking water for 12 months. We estimated the total daily intake of MCs by fishers through contaminated lake water and food to be 5.95 μg MC-LReq, far exceeding the tolerable daily intake (2.40 μg MC-LReq) proposed by the World Health Organization (WHO). More than 80% of participants had at least one abnormal serum marker. The indices of aspartate aminotransferase (AST)/alanine aminotransferase (ALT), triglyceride (TG), globulin (GLB), and lactate dehydrogenase (LDH) had close positive associations with MC contamination, indicating that both liver damage and lipid metabolism dysfunction were induced by chronic MC exposure. Furthermore, the animal experimental results showed that long-term exposure to MC-LR at the environmentally relevant level led to hepatic steatosis with molecular alterations in circadian rhythm regulation, lipid metabolic processes, and the cell cycle pathway. Exposure to MC-LR at or above the NOAEL worsened the pathological phenotype towards nonalcoholic steatohepatitis disease (NASH) or fibrosis. These results suggest that prolonged exposure to the reference level (NOAEL) of MC-LR could cause severe liver injury to mammals. People with long-term environmental exposure to MCs might be at high risk for developing NAFLD.

Fructus Psoraleae-Induced Severe Liver Injury and Treatment With Two Artificial Liver Support Systems: A Case Series Study.

To describe the clinical features and outcomes of patients with suspected Fructus Psoraleae (FP)-induced severe liver injury who underwent treatment with two artificial liver support systems (ALSSs). The cases of 12 patients with severe liver injury by FP were enrolled. We evaluated the tolerability of, and changes in biochemical parameters after treatment with plasma exchange combined with hemofiltration and double plasma molecular absorption system, and 6-month follow-up information were collected. The median age of the 12 patients was 60 years and nine (75%) patients were females. All patients had jaundice as the initial symptom. Two ALSS types were used to treat the patients. The group that underwent plasma exchange combined with hemofiltration showed remarkable improvements in ALT, AST, total bilirubin (TB), GGT and international normalized ratio levels (AST, TB, international normalized ratio, P < 0.01; ALT, GGT, P < 0.05), and the levels of AST, ALP, TB, and total bile acid decreased significantly in the double plasma molecular absorption system group after treatment (TB, P < 0.01; AST, ALP, total bile acid P < 0.05). During 6 months of follow-up, two patients died, two became chronic, and eight recovered to normal. FP can cause clinically severe liver injury, characterized by gastrointestinal symptoms and jaundice, which can lead to death or become chronic. Both ALSSs were safe and well tolerated in drug-induced liver injury patients. After ALSS treatment, the levels of biochemical indicators of liver function improved significantly, indicating that ALSS might be beneficial for patients with severe drug-induced liver injury.

Preparation of high Fischer’s ratio corn oligopeptides using directed enzymatic hydrolysis combined with adsorption of aromatic amino acids for efficient liver injury repair

Directed hydrolysis of corn crude peptides was performed by sequential digestion with α-chymotrypsin and carboxypeptidase A. With the additional step of adsorption of aromatic amino acids by activated carbon, corn oligopeptides with a Fischer’s ratio of 41.87 and low bitterness were prepared. The fraction with molecular weight of 180–1000 Da was found to constitute 71.37% of these oligopeptides, where the proportion of Phe and Tyr among all amino acid residues was only 0.73%. In addition, a model of liver injury induced by carbon tetrachloride was established. Through the analysis of the body–mass index, liver index, liver histopathological features, and various serum biochemical indicators of liver function, high Fischer’s ratio corn oligopeptides were found to be safe and slightly superior in terms of liver injury repair when compared with a commercial high Fischer’s ratio amino acid product. Crude corn peptides (raw material) and skimmed milk powder had no effect on repairing liver injury.

Acute liver injury in the course of lymphoplasmacytic lymphoma

Abstract Non-Hodgkin lymphomas are malignant neoplasms whose incidence rates increase each year. These also include neoplasms rare in the general population. The present case report described a patient with lymphoplasmacytic lymphoma (LPL) and rapid liver damage. In most cases, infiltration of the liver is rare in advanced stages of hematopoietic malignancies when hepatomegaly, cholestatic jaundice and organ failure are observed. The patient’s history includes non-specific abdominal pain that was accompanied by general symptoms such as nocturnal hyperhidrosis, subfibrile temperature and fever, as well as weight loss. The above complaints aggravate with an increase in organ size. The laboratory findings initially demonstrated moderately elevated concentrations of transaminases. In our case, the baseline biochemical indices of liver function were found to be normal. During the next days of hospitalisation, the features of liver damage intensified and were accompanied by liver failure. The gold diagnostic standard is a biopsy of the bone marrow and the organ affected. Since the patient’s condition deteriorated and liver failure developed, the diagnosis was established based on trephine biopsy of the bone marrow. Chemotherapy was implemented; despite the treatment applied, the patient’s clinical condition did not improve. Two months after the onset of first symptoms the patient died.

Metabolomic study on the susceptible factors of idiosyncratic Traditional Chinese Medicine-induced liver injury: Exemplification of a &amp;lt;italic&amp;gt;Polygonum multiflorum&amp;lt;/italic&amp;gt; preparation

The underlying mechanism(s) that govern idiosyncratic drug-induced liver injury (IDILI) have remained poorly defined. Several studies have shown that IDILI was caused by body diathesis, environment, metabolism, immunization, etc. However, the underlying mechanism(s) of IDILI was still ambiguous, which led to an unsolved issue in clinical toxicology. Understanding of such mechanisms is critical not only for the prevention of such DILI adverse effect as well as the clinical diagnosis, intervention or management of the affected individuals. In this study, we carried out a metabolomic study on mice treated with Runzao Zhiyang Capsule (RZZY), since Polygonum multiflorum , a key ingredient in this preparation, is known to cause DILI. Clinical case analysis showed that a small number of patients developed drug-induced liver injury (DILI) in a dose-independent manner. Meanwhile, the affected individuals often exhibited skin conditions associated with features of abnormal inflammatory responses. In normal mice, treatment with RZZY alone had no significant effects on biochemical indices of liver function, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. At the same time, it had no significant effects on liver histopathology either. Moreover, we used non-toxic dose of lipopolysaccharide (LPS) pretreatment to produce mild inflammatory stress mice model, which showed no significant liver injury phenotype, except for a small number of inflammatory immune cells infiltration in portal areas of liver. However, by metabolomics profiling, we found significant alterations of plasma metabolites in the LPS treated mice, including up-regulated histidine and alanine metabolic pathways ( P (P beta -alanine, l -histidine, cortexolone, cortisone, dihydrocortisol, melatonine and 18-hydroxycorticosterone, which may provide potential application value for recognition of susceptible individuals in clinical.

Chronic liver disease increases with damage to intestinal barrier function

Objective: To probe into the correlation between chronic liver disease and intestinal barrier function. Methods: 1 491 cases of hospitalized patients were enrolled, of which 741 cases were of chronic liver diseases, including 397 cases of fatty liver diseases, 230 cases of chronic hepatitis, 114 cases of liver cirrhosis, and 750 cases of non-hepatic diseases. All admitted patients' intestinal barrier function like diamine oxidase (DAO), D-lactate, lipopolysaccharide, and biochemical indicators of liver functions were tested. According to different data, statistical analysis was done using t-test, ANOVA, Dunnett's test, χ (2) test of fourfold table, Pearson's correlation, and binary logistic regression. Results: The intestinal barrier dysfunction was more likely to occur in the chronic liver disease group than that of non-hepatic disease group [54.15% (379/741) vs. 18.53% (139/750), χ (2) = 193.58, P < 0.001]. The correlation analysis between biochemical indicators of liver function and intestinal barrier function in chronic liver disease group showed that alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin levels were more susceptible to intestinal barrier dysfunction than those with normal indexes (P < 0.05 ). GGT had stimulated DAO (P < 0.05, OR > 1), D-lactate (P < 0.05, OR > 1), lipopolysaccharide (P < 0.05, OR > 1), ALT and AST. Conclusion: Chronic liver disease increases with damage to intestinal barrier function.

99mTc-Phy portal perfusion index imaging helps predict the severity of hepatitis B virus cirrhosis: a preliminary study.

ObjectiveThe aim was to perform exploratory research on the application of technetium phytate (99mTc-Phy) portal perfusion index (PPI) imaging in predicting the complications of hepatitis B cirrhosis and their severity.Patients and methodsA total of 65 hepatitis B cirrhosis patients were stratified, respectively, into three groups from classes A to C according to Child–Pugh scores and five groups from stages 1 to 5 according to the five-stage prognostic system. PPIs were compared and analyzed, respectively, among the three and five groups. The correlations between PPIs and major biochemical indices of liver function were also analyzed. One-way analysis of variance was used to compare the PPIs among the various groups and a nonparametric Spearman test was used to analyze the correlations between PPIs and various biochemical indices.ResultsPPIs of the five groups decreased gradually from stage 1 to stage 5 (73.03±8.49, 52.96±16.22, 46.24±15.25, 29.99±17.36, and 11.50±6.37, respectively); with the exception of the difference between stages 2 and 3 (P=0.252), the differences between the remaining groups were statistically significant (P<0.05). The PPI showed positive correlations with serum total protein, serum albumin, and albumin/globulin results (r=0.292, 0.559, 0.520, respectively; P<0.05), and negative correlations with serum globulin (r=−0.366, P<0.05).ConclusionTechnetium phytate PPI could be a promising noninvasive and effective method for predicting the complications of hepatitis B cirrhosis and their severity; a lower PPI value indicates a higher severity of complications for hepatitis B cirrhosis patients. PPI can provide very meaningful reference data for clinical practice.

The role of ursodeoxycholic acid on cholestatic hepatic fibrosis in infant rats.

The aim of the present study was to identify the impact of ursodeoxycholic acid (UDCA) on liver function and fibrosis markers in infant rats by establishing a cholestatic‑induced hepatic fibrosis model. α‑naphthylisothiocyanate (ANIT) was administrated by gavage to induce cholestatic hepatic fibrosis in infant rats. UCDA treatment was performed to assess its impact on biochemical indicators of liver function, four serum biomarkers of hepatic fibrosis, hepatic fibrosis indices in liver tissues and the pathology of liver tissues. Colorimetric assays and biochemical assays based on the initial rate method were performed to determine the levels of liver function markers in the serum, whereas the serum biomarkers of hepatic fibrosis were measured via radioimmunoassay. Sections of liver tissue were harvested and stained with hematoxylin‑eosin or picric acid‑Sirius red, and subjected to immunohistochemical staining to analyze liver pathology. All indicators of liver function, except for cholinesterase, were significantly higher in the ANIT model than in the control group (P<0.01). γ‑glutamyl transpeptidase and total bile acids of the UDCA treatment group were significantly lower than the ANIT model (P<0.05); whereas no significant differences were observed in alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin between the two groups. Serum laminin protein (LN) and type‑IV collagen (cIV) in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01); whereas no significant differences were observed in hyaluronic acid and type‑III procollagen between the two groups. Liver LN and cIV in the UDCA treatment group were significantly lower than in the ANIT model (P<0.01). The degree of hepatic fibrosis in the UDCA treatment group was significantly lower than in the ANIT model (P<0.01). The results of the present study demonstrated that UDCA is able to reduce LN and cIV in serum and protect liver tissues against hepatic fibrosis.