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Background and Aim: Methotrexate is an important drug for treatment of rheumatoid arthritis (RA) but is associated with adverse side effects on liver. In this study we evaluated the effect of silymarin on methotrexate induced hepatotoxicity and its analgesic effects in the patients taking this drug. Materials and Methods: This study inclouded 58 patients with RA. Patients who had been treated with 2.5 mg methotrexate three times a week for six months were randomly divided into two groups of A and B. Group A received methotrexate and group B treated with 280 mg of silymarin tablets daily (two doses for 2 months) in addition to methotrexate. At baseline (before tests) and after two months, both groups completed the VAS (Visual Analogue Scale) questionnaire and Cr (Creatinine), BUN (Blood Urea Nitrogen), ESR (Erythrocyte Sedimentation Rate), Hemoglobin, WBC (white blood cell), PLT (Platelet) and the liver tests including ALT (Alanine Transaminase) and AST (Aspartate Aminotransferase) were evaluated. We used t-test for data analysis. Results: In the group B, ALT, AST and ESR, Cr and BUN decreased significantly. Also clinical signs of pain which were indicative of pain intensity were decreased. Conclusion: Use of silymarin in the patients with RA reduced liver enzymes, liver toxicity and renal complications, which may be due to its antioxidant and cell membrane stabilization properties.

Context The relationship between food restriction (FR) and liver enzyme levels, such as alanine transferase (ALT), aspartate transferase (AST), and γ-glutamyl transferase (GGT), has not yet been confirmed. Objective A meta-analysis of research articles was conducted to investigate the association of FR and liver enzyme levels. Data sources The PubMed, Web of Science, Embase, and Cochrane Library databases were screened for articles published up to April 30, 2022. Data extraction Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement methodology was used to search for research articles. Publication bias was detected using Begg's test. Finally, 17 trials involving 1982 participants and that reported mean value, mean difference, and standard deviation were identified. Data analysis Data were described as the weighted mean difference of body mass index, body weight, and standardized mean difference (SMD) of ALT, AST, and GGT. A reduction in ALT level was observed after a FR intervention (total SMD, –0.36, 95% confidence interval [CI], –0.68 to –0.05). GGT levels also were decreased in 4 studies (total SMD, –0.23; 95%CI, –0.33 to –0.14). According to subgroup analysis, serum AST levels decreased in the medium-term (between 5 wk and 6 mo) group (subtotal SMD, –0.48; 95%CI, –0.69 to –0.28). Conclusion Existing evidence suggests that dietary restriction improves adult liver enzyme levels. The long-term maintenance of healthy liver enzyme levels, particularly in real-world applications, necessitates additional consideration. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease (COVID-19) has spread worldwide, and the pathogenic mechanism is still under investigation. Preliminary reports suggest a link between ABO blood groups and susceptibility to severe COVID-19. Aim: The aim of this study was to confirm the link between ABO blood type, the risk of coronavirus infection, and the severity of COVID-19 disease. Setting and Design: This was a retrospective cohort study. Materials and Methods: The study was carried out at tertiary care rural hospital in Central India. The patients admitted to the COVID unit over 6 months were enrolled in the study. The data further statistically analyzed the outcome of COVID-19 disease and its relation with the patient's blood group and serum ferritin levels. Results: The data analysis observed no significant impact of blood group on the outcome of COVID-19 in terms of death and cured cases. The mortality rate was 27.2% in the AB blood group, with the highest reported serum ferritin levels (1007.78 ± 1301.25). Compared to other blood groups, A (8.1%), followed by O (13.5%), with the lowest mortality rate (P = 0.31). Alanine transferase and aspartate transferase were maximally seen in patients having blood group AB +, and lower values were observed in blood group A. Conclusions: Blood groups A and O were considered COVID-19 protective in mortality following the cytokine storm. AB blood group had high serum ferritin levels, so it can be a potential tool to predict mortality and may be considered the culprit for the triggering “cytokine storm.”

Background: The coronavirus disease (COVID-19) has spread worldwide, and the pathogenic mechanism is still under investigation. Preliminary reports suggest a link between ABO blood groups and susceptibility to severe COVID-19. Aim: The aim of this study was to confirm the link between ABO blood type, the risk of coronavirus infection, and the severity of COVID-19 disease. Setting and Design: This was a retrospective cohort study. Materials and Methods: The study was carried out at tertiary care rural hospital in Central India. The patients admitted to the COVID unit over 6 months were enrolled in the study. The data further statistically analyzed the outcome of COVID-19 disease and its relation with the patient's blood group and serum ferritin levels. Results: The data analysis observed no significant impact of blood group on the outcome of COVID-19 in terms of death and cured cases. The mortality rate was 27.2% in the AB blood group, with the highest reported serum ferritin levels (1007.78 ± 1301.25). Compared to other blood groups, A (8.1%), followed by O (13.5%), with the lowest mortality rate (P = 0.31). Alanine transferase and aspartate transferase were maximally seen in patients having blood group AB +, and lower values were observed in blood group A. Conclusions: Blood groups A and O were considered COVID-19 protective in mortality following the cytokine storm. AB blood group had high serum ferritin levels, so it can be a potential tool to predict mortality and may be considered the culprit for the triggering "cytokine storm.". [ABSTRACT FROM AUTHOR]

American alligators (Alligator mississippiensis) are a sentinel species whose health is representative of environmental quality. However, their susceptibility to various natural or anthropogenic stressors is yet to be comprehensively studied. Understanding hepatic function in such assessments is essential as the liver is the central organ in the metabolic physiology of an organism, and therefore influences its adaptive capability. In this study, a novel liver perfusion system was developed to study the hepatic physiology of juvenile alligators. First, a cannulation procedure was developed for an in situ liver perfusion preparation. Second, an optimal flow rate of 0.5 ml/min/g liver was determined based on the oxygen content in the effluent perfusate. Third, the efficacy of the liver preparation was tested by perfusing the liver with normoxic or hypoxic Tyrode's buffer while various biomarkers of hepatic function were monitored in the effluent perfusate. Our results showed that in the normoxic perfusion, the aspartate transferase (AST) and lactate/pyruvate ratio in the perfusate remained stable and within an acceptable physiological range for 6 h. In contrast, hypoxia exposure significantly increased the lactate/pyruvate ratio in the perfusate after 2 h, indicating an induction of anaerobic metabolism. These results suggest that the perfused liver remained viable during the perfusion period and exhibited the expected physiological response under hypoxia exposure. The liver perfusion system developed in this study provides an experimental framework with which to study the basic hepatic physiology of alligators and elucidate the effects of environmental or anthropogenic stressors on the metabolic physiology of this sentinel species., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background/Aims Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation. Methods A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation. Results METAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation. Conclusions ALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.

Background Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. Study Design Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. Results Twenty-nine neonates with NE and 84 age-matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. Conclusion Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma is the most common primary malignancy of the liver with poor prognosis. In this study novel, Schiff’s bases of 2-aminopyridine (SSSC-26 to 31) and 2-aminobenzothiazole (SSSC-32 to 37) were designed, synthesised and evaluated for antioxidant potential using DPPH method, and anti-hepatocellular carcinoma property using diethylnitrosamine (DEN) induced hepatocellular carcinoma rat model. The in-silico pharmacokinetic, rule of five and toxicity studies reveals that all the leads have an excellent intrinsic quality and sufficient structural features necessary for an oral activity. Molecular docking studies of all compounds into the ligand binding pocket of checkpoint kinase1 and vascular endothelial growth factor receptor-2 was also performed using Schrodinger software suite v 8.5, and which have shown good Glide scores. Further compounds were synthesised based on the docking score and ADMET profile. The 1,1-diphenyl­2-picrylhydrazil (DPPH) scavenging study was carried out, and results showed that SSSC-29 (IC 50 -63.60) and SSSC-33 (IC 50 -60.32) were having good anti-oxidant potential in comparison with ascorbic acid (IC 50 -55.27). SSSC-33 further evaluated for anti-cancer potential against diethylnitrosamine (200 mg/kg bw) induced hepatocellular carcinoma in rats. The biochemical, histopathological and morphological data showed that SSSC-33 can reverse the changes occurred in the cancerous liver significantly. All these findings suggested that SSSC-33-((benzo[d]thiazol-2-ylimino) methyl)phenol) could be a potential compound in combating the oxidative damage of hepatic cells occurred due to the development of hepatocellular carcinoma induced by a chemical carcinogen, DEN. [ABSTRACT FROM AUTHOR]

Background and Objective: Ecstasy [3,4 Methylendioxy Meth Amphetamine (MDMA)] exerts destructive effects on body organs particularly on the nervous system. The current study was carried out to measure the adverse effects of MDMA on hepatocyte and liver-specific enzymes. Materials and Methods: In this experimental study, 50 male Wistar rats were randomly divided in equal numbers into 5 groups: control, sham, experimental 1, 2, and 3. Animals in the experimental groups were received, intraperitoneally 2, 4 and 8 mg/kg of MDMA, respectively. The sham group were received normal saline but the control group was not subjected to any injection. Serum samples were collected and levels of three enzymes under study: alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were measured. The sections from the liver tissue were prepared counting the hepatocytes. Data were analyzed using SPSS-16 and One-way ANOVA and Tukey's HSD tests. Results: Data indicated the levels of all three enzymes had been elevated in the animal groups that received MDMA and that the increase was statistically significant compared to sham and control groups (P

Ischaemic reperfusion (IR) injury is a major cause of graft loss, morbidity and mortality following orthotopic liver transplantation (OLT). Demand for liver transplantation has resulted in increasing use of marginal grafts that are more prone to IR injury. Remote ischaemic preconditioning (RIPC) reduces IR injury in experimental models, but recipient RIPC has not been evaluated clinically. Methods: A single-centre double-blind randomized controlled trial (RCT) is planned to test the hypothesis that recipient RIPC will reduce IR injury. RIPC will be performed following recipient anaesthetic induction but prior to skin incision. The protocol involves 3 cycles of 5 min of lower limb occlusion with a pneumatic tourniquet inflated to 200 mmHg alternating with 5 min of reperfusion. In the control group, the sham will involve the cuff being placed on the thigh but without being inflated. The primary endpoint is ability to recruit patients to the trial and safety of RIPC. The key secondary endpoint is a reduction in serum aspartate transferase levels on the third post-operative day. Discussion: RIPC is a promising strategy to reduce IR injury in liver transplant recipients as there is a clear experimental basis, and the intervention is both inexpensive and easy to perform. This is the first trial to investigate RIPC in liver transplant recipients. [ABSTRACT FROM AUTHOR]

Ischemic hepatitis is an infrequent entity, usually associated with low cardiac out put. We present a case of a 57 year-old man with chronic renal failure and cardiac tamponade who developed elevation of serum alanine transferase level of 5,054 U/L, aspartate transferase level of 8,747 U/L and lactate dehydrogenasa level of 15,220 U/L. The patient developed hepatic encephalopathy and hypoglycemia. Liver Doppler ultrasound was normal. He was seronegative for HBV and HCV, drugs list was scrutinized for the names of known hepatotoxins. Ischemic hepatitis was diagnosed. The hypoglycemia and encephalopathy were solved and the patient was discharged with normal transaminase levels. Ischemic hepatitis is typically preceded by hypotension, hypoxemia, or both. As one would expect, the most common cause of sustained systemic hypotension is cardiovascular disease. Liver biopsy is usually not necessary. The best treatment is support measures and correct the underlying condition.

Background: Various hepatoprotective herbal products from plants are available in Mexico, where up to 85% of patients with liver disease use some form of complementary and alternative medicine. However, only few studies have reported on the biological evaluation of these products. Objective: Using a model of carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, we evaluated the effects of commercial herbal extracts used most commonly in the metropolitan area of Monterrey, Mexico. Materials and Methods: The commercial products were identified through surveys in public areas. The effect of these products given with or without CCl4 in rats was evaluated by measuring the serum concentrations of aspartate amino transferase (AST) and alanine amino transferase (ALT), and histopathological analysis. Legalon® was used as the standard drug. Results: The most commonly used herbal products were Hepatisan® capsules, Boldo capsules, Hepavida® capsules, Boldo infusion, and milk thistle herbal supplement (80% silymarin). None of the products tested was hepatotoxic according to transaminase and histological analyses. AST and ALT activities were significantly lower in the Hepavida+CCl4-treated group as compared with the CCl4-only group. AST and ALT activities in the silymarin, Hepatisan, and Boldo tea groups were similar to those in the CCl4 group. The CCl4 group displayed submassive confluent necrosis and mixed inflammatory infiltration. Both the Hepatisan+CCl4 and Boldo tea+CCl4 groups exhibited ballooning degeneration, inflammatory infiltration, and lytic necrosis. The silymarin+CCl4 group exhibited microvesicular steatosis. The Hepavida+CCl4- and Legalon+CCL4-treated groups had lower percentages of necrotic cells as compared with the CCl4-treated group; this treatment was hepatoprotective against necrosis. Conclusion: Only Hepavida had a hepatoprotective effect. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has a spectrum of clinical syndromes with serious involvement of the lung and frequent effection of the liver and hemostatic system. Blood biomarkers are affordable, rapid, objective, and useful in the evaluation and prognostication of COVID-19 patients., Aim: To investigate the association between aspartate transferase-to-platelet ratio index (APRI) and in-hospital mortality to develop a COVID-19 mortality prediction model., Methods: A multicenter cohort study with a retrospective design was conducted. Medical records of all consecutive adult patients admitted to Al-Azhar University Hospital (Assiut, Egypt) and Chest Hospital (Assiut, Egypt) with confirmed COVID-19 from July 1, 2020 to October 1, 2020, were retrieved and analyzed. The patient cohort was classified into the following two categories based on the APRI: (1) COVID-19 presenting with APRI ≤ 0.5; and (2) COVID-19 presenting with APRI (> 0.5 and ≤ 1.5). The association between APRI and all-cause in-hospital mortality was analyzed, and the new model was developed through logistic regression analyses., Results: Of the 353 patients who satisfied the inclusion criteria, 10% were admitted to the intensive care unit ( n = 36) and 7% died during the hospital stay ( n = 25). The median age was 40 years and 50.7% were male. On admission, 49% had aspartate transferase-dominant liver injury. On admission, APRI (> 0.5 and ≤ 1.5) was independently associated with all-cause in-hospital mortality in unadjusted regression analysis and after adjustment for age and sex; after stepwise adjustment for several clinically relevant confounders, APRI was still significantly associated with all-cause in-hospital mortality. On admission, APRI (> 0.5 and ≤ 1.5) increased the odds of mortality by five-times ( P < 0.006). From these results, we developed a new predictive model, the APRI-plus, which includes the four predictors of age, aspartate transferase, platelets, and serum ferritin. Performance for mortality was very good, with an area under the receiver operating curve of 0.90., Conclusion: APRI-plus is an accurate and simplified prediction model for mortality among patients with COVID-19 and is associated with in-hospital mortality, independent of other relevant predictors., Competing Interests: Conflict-of-interest statement: No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hepatoprotective effect of Gentiana olivieri Griseb. (Gentianaceae) flowering herbs on subacute administration were studied using in vivo models in rats. For the activity assessment on carbon tetrachloride-induced hepatic damage following biochemical parameters were evaluated; plasma and hepatic tissue malondialdehyde formation, and liver tissue glutathione level, as well as plasma transaminase enzyme levels (aspartate transferase and alanine transferase). Results of biochemical tests were also confirmed by histopathological examination. Through bioassay-guided fractionation procedures isoorientin, a known C-glycosylflavone, was isolated from the ethyl acetate fraction as the active antihepatotoxic constituent by silica gel column chromatography. Isoorientin exhibited significant hepatoprotective effect at 15 mg/kg b.w. dose. [Copyright &y& Elsevier]

Background/aims: Enzymatic analysis of aspartate/alanine aminotransferase (AST/ALT) does not exactly represent the progression of liver fibrosis or inflammation. Immunoassay for AST (cytoplasmic [c] AST/mitochondrial [m] AST) and ALT (ALT1/ALT2) has been suggested as one alternatives for enzymatic analysis. The objective of this study was to evaluate the efficacy of immunoassay in predicting liver fibrosis and inflammation., Methods: A total of 219 patients with chronic hepatitis B (CHB) who underwent hepatic venous pressure gradient (HVPG) and liver biopsy before antiviral therapy were recruited. Serum samples were prepared from blood during HVPG. Results of biochemical parameters including enzymatic AST/ALT and immunological assays of cAST, mAST, ALT1, and ALT2 through sandwich enzyme-linked immunosorbent assay (ELISA) immunoassay with fluorescence labeled monoclonal antibodies were compared with the results of METAVIR stage of live fibrosis and the Knodell grade of inflammation., Results: METAVIR fibrosis stages were as follows: F0, six (3%); F1, 52 (24%); F2, 88 (40%); F3, 45 (20%); and F4, 28 patients (13%). Mean levels of AST and ALT were 121 ± 157 and 210 ± 279 IU/L, respectively. Mean HVPG score of all patients was 4.7 ± 2.5 mmHg. According to the stage of liver fibrosis, HVPG score (p < 0.001, r = 0.439) and ALT1 level (p < 0.001, r = 0.283) were significantly increased in all samples from patients with CHB. ALT (p < 0.001, r = 0.310), ALT1 (p < 0.001, r = 0.369), and AST (p < 0.001, r = 0.374) levels were positively correlated with Knodell grade of inflammation., Conclusion: ALT1 measurement by utilizing sandwich ELISA immunoassay can be useful method for predicting inf lammation grade and fibrosis stage in patients with CHB.