Elevated Alanine Aminotransferase Levels Research Articles

A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase-based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia.

Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT-based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX-induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia. A retrospective study was conducted on paediatric patients who received high-dose (3-5g/m2 ) MTX treatment. MTX concentrations were assessed at 24-h intervals until the concentration dropped below 0.1μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semimechanistic hepatotoxicity model. The PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a 2-compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable interoccasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters. A semimechanistic model was developed to describe ALT-based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug-induced hepatotoxicity.

270 The Liberal Use of Magnetic Resonance Cholangiopancreatography (MRCP) can be switched over to its Selective use to detect choledocholithiasis

Abstract Background Gallstone disease is known in 10-15% of adults in Western populations. Cholangiopancreatography is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well-defined. The NICE guidelines recommend MRCP be done when common bile duct dilatation ≥ 8mm or liver function tests) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualized basis. Due to these reasons, MRCP is at times done unnecessarily which creates an economic burden and restricts access to patients in real need of imaging slots. Method It is a hospital-based retrospective observational study. The time frame was July 2021 to July 2022. The sample size was 230 patients. Result Our Study showed that isolated elevated Alanine Aminotransferase levels should not be a reason to evaluate patients for Choledocholithiasis. It concluded that elevated serum bilirubin levels, Alkaline Phosphatase, and Gamma Glutamyl Transferase are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Liver Enzymes and the Risk of Stroke among the General Japanese Population: A Prospective Cohort Study

Introduction: Stroke is a major cause of morbidity and mortality. Liver enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transpeptidase (GGT), are markers of liver diseases with potential cardiovascular implications. This study aimed to investigate the prospective association between liver enzymes and stroke risk. Methods: We analyzed data from 3,379 men and 4,007 women without cardiovascular disease and registered in the Suita Study, a Japanese population-based prospective cohort study. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of stroke risk were estimated per quintiles of ALT, AST, and GGT in men and women. Results: Within a median follow-up period of 16.7 years, 438 incident stroke events were diagnosed. In men, compared to the second quintiles, the fifth (highest) quintiles of liver enzymes showed increased stroke risks: HRs (95% CIs) = 2.07 (1.35, 3.18) in ALT, 1.66 (1.10, 2.53) in AST, and 1.76 (1.11, 2.81) in GGT. The associations did not change with cerebral infarction risk: HRs (95% CIs) = 2.09 (1.24, 3.50) in ALT, 1.84 (1.11, 3.06) in AST, and 1.74 (1.00, 3.04) in GGT. The lowest ALT, AST, and GGT quintiles tended to show increased stroke and cerebral infarction risks, yet these associations were statistically insignificant. No such associations were shown in women. Conclusion: Elevated ALT, AST, and GGT levels were associated with increased stroke and cerebral infarction risks among Japanese men.

Situation of HDV Infection in Adult Hepatitis B Patients at The Outpatient Clinic of Pasteur Institute in Ho Chi Minh City

Hepatitis D virus (HDV) infection, also known as delta virus, has been identified as a crucial risk factor contributing to severe complications among hepatitis B patients. Such complications arise as HDV accelerates the progression towards cirrhosis, exacerbates the risk of decompensated cirrhosis, and increases mortality rates compared to non-HDV hepatitis B infections. Despite its clinical significance, data on HDV infection remains scarce, and exhibits marked regional disparities in Viet Nam. This study endeavors to explore HDV co-infection in adult hepatitis B patients. A descriptive cross-sectional investigation was conducted, involving 539 hepatitis B subjects attending the Outpatient Clinic of the Pasteur Institute in Ho Chi Minh City between October 2021 and May 5, 2022. The study sample featured three hepatocellular carcinoma (HCC) patients, 148 patients with elevated alanine aminotransferase (ALT) levels, and nine patients whose ALT levels exceeded five times the upper limit of normal (ULN). Additionally, 11 patients reported a history of blood transfusion, while no participants had any history of intravenous drug use. Remarkably, the study did not document any instances of HDV co-infection among the subjects. These findings suggest that HDV screening may not be a routine recommendation for patients diagnosed with moderate or mild hepatitis B, particularly when presenting with low-risk factors. Further research is warranted to better understand the prevalence of HDV co-infection in this population and to guide the development of evidence-based screening guidelines.

Multiorgan failure caused by Chinese herbal medicine Xanthii Fructus poisoning: a case report

BackgroundXanthii Fructus was used in the treatment of rhinitis and related nasal disease. It is the most commonly used chemically active component in compounds formulated for the treatment of rhinitis. However, poisoning, resulting in serious consequences, can easily occur owing to cocklebur overdose, improper processing, or usage without processing.Case presentationWe reported on a 55-year-old man who experienced allergic rhinitis for 2.5 years. He ingested unprocessed Xanthii Fructus for 2 months as treatment. However, he developed anorexia; nausea; abdominal pain; general weakness; hiccups; oliguria and anuria; significantly elevated serum alanine aminotransferase, aspartate aminotransferase, and creatinine levels; and abnormalities in blood coagulation series. Nutritional support; daily drugs for liver protection, gastric protection, inflammation reduction; fresh plasma; and cryoprecipitate infusion were administered. Continuous venovenous hemodialysis (Prismaflex ST100) was also administered. However, the patient’s multiple organ failure gradually worsened, ultimately leading to death.ConclusionXanthii Fructus poisoning affects multiple systems, and its clinical manifestations are complex. Therefore, it is easily misdiagnosed and missed. Along with careful inquiry of medical and medication history, early diagnosis and intervention are vital for a successful treatment. It is also important to educate people and create awareness about this poisoning. Therefore, this intractable case has great clinical significance.

Phosphatidylserine decarboxylase downregulation in uric acid‑induced hepatic mitochondrial dysfunction and apoptosis.

The molecular mechanisms underlying uric acid (UA)-induced mitochondrial dysfunction and apoptosis have not yet been elucidated. Herein, we investigated underlying mechanisms of UA in the development of mitochondrial dysfunction and apoptosis. We analyzed blood samples of individuals with normal UA levels and patients with hyperuricemia. Results showed that patients with hyperuricemia had significantly elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, which may indicate liver or mitochondrial damage in patients with hyperuricemia. Subsequently, lipidomic analysis of mouse liver tissue mitochondria and human liver L02 cell mitochondria was performed. Compared with control group levels, high UA increased mitochondrial phosphatidylserine (PS) and decreased mitochondrial phosphatidylethanolamine (PE) levels, whereas the expression of mitochondrial phosphatidylserine decarboxylase (PISD) that mediates PS and PE conversion was downregulated. High UA levels also inhibited signal transducer and activator of transcription 3 （STAT3） phosphorylation as well as mitochondrial respiration, while inducing apoptosis both in vivo and in vitro. Treatment with allopurinol, overexpression of PISD, and lyso-PE (LPE) administration significantly attenuated the three above-described effects in vitro. In conclusion, UA may induce mitochondrial dysfunction and apoptosis through mitochondrial PISD downregulation. This study provides a new perspective on liver damage caused by hyperuricemia.

Hepatitis B induced fulminant liver failure: A call for prevention

Acute fulminant hepatic failure is a condition in which a healthy liver deteriorates rapidly following an insult, resulting in the impairment of its synthetic functions. This condition is rare and is associated with high fatality rates. We report the case of a 19-year-old male who was brought to the emergency room in an unconscious state with jaundice and persistent fever for 2–3 weeks after recently commencing intravenous use of morphine. He was found to be hepatitis B surface antigen reactive, and his laboratory tests indicated severe liver dysfunction with elevated levels of serum bilirubin, aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, and International normalized ratio. The patient was diagnosed with fulminant liver failure with coagulopathy and hepatic encephalopathy. The patient’s family was addressed and counseled regarding the urgent need for liver transplantation. However, due to a lack of funds and insurance, supportive treatment was the only option left. Despite all supportive measures, the patient expired within 48 h. This case highlights the importance of various socioeconomic issues involved with liver transplantation, as in a resource-limited setting, urgent transplantation seems nearly impossible. In addition, this case report raises certain ethical issues that need consideration, particularly in an injection drug use scenario. It also highlights the importance of addressing the rising issue of injection drug use among youth, particularly in the regions of Punjab.

The causal associations of non-alcoholic fatty liver disease with blood pressure and the mediating effects of cardiometabolic risk factors: A Mendelian randomization study

Background and aimsNon-alcoholic fatty liver disease (NAFLD) is prevalent in hypertensive people, but the causal effect remains unclear. We employed Mendelian randomization (MR) approach to assess the causality between NAFLD and different blood pressure (BP) parameters. Method and resultsInstrumental variables for genetically predicted NAFLD, including chronically elevated serum alanine aminotransferase levels (cALT) and imaging and biopsy-confirmed NAFLD, were obtained from a genome-wide association study (N = 164,197). Multiple MR methods were implemented, including Inverse variance weighted, MR-Egger, Maximum likelihood, Weighted median, Simple median, Penalised weighted median, MR-RAPS, and cML-MA. Outliers were detected using MR-PRESSO, and pleiotropy was assessed using MR-Egger intercept and Phenoscanner. Heterogeneity was quantified using Cochran's Q and Rucker's Q′ tests. Potential shared risk factors were analyzed to reveal the mediating effect. A higher genetic predisposition to cALT was causally associated with an increased risk of elevated BP levels, resulting in 0.65 mmHg (95% CI, 0.42–0.87), 0.38 mmHg (95% CI, 0.25–0.50) and 0.33 mmHg (95% CI, 0.22–0.44) higher for systolic BP, diastolic BP and pulse pressure, respectively. When more stringent criteria were used, imaging and biopsy-confirmed NAFLD showed a 1.12 mmHg (95% CI, 0.94–1.30) increase in SBP and a 0.55 mmHg (95% CI, 0.39–0.70) increase in DBP. Risk factor and mediation analyses suggested type 2 diabetes and fasting insulin levels might mediate the causal relationship between NAFLD and BP. ConclusionThe two-sample MR analyses showed robust causal effects of genetically predicted NAFLD on 3 different BP indices. The shared genetic profile between NAFLD and BP may suggest important therapeutic targets and early interventions for cardiometabolic risk factors.

Scrub Typhus in Children: A Prospective Observational Study in a Tertiary Care Hospital in Eastern India.

Background Scrub typhus is a reemerging, acute, undifferentiating febrile illness and one of the most neglected tropical diseases, calling for an in-depth investigation into its clinical diversity, complications, and mortality, which drives us to carry out this research work. Methods Over a year, prospective observational research was carried out after gaining parental consent and institutional ethical clearance, 206 children of either gender aged between one month and 12 years who had been hospitalized with a fever for at least five days and subsequently tested positive forOrientia​​​​tsutsugamushiwere included in the study. Basic demographic information, clinical characteristics, laboratory findings, complications, related coinfections, and results were gathered and analyzed.A P-value of 0.05 was set as the statistical benchmark. Results The current study found that boys outnumbered girls. The ratio of boys to girls was 1.22:1, and the average age was 5.18 years. All had a fever (100%), and the other most frequently occurring clinical signs and symptoms were abdominal pain (16.99%), vomiting (22.33%), hepatosplenomegaly (49.51%), facial puffiness (39.32%), edema (27.18%), lymphadenopathy (19.90%), eschar (19.90%), macular-erythematous rash (17.96%), cough (21.84%), conjunctival congestion (25.24%), and headache (13.59%). Anemia (81.55%), leucocytosis (20.39%), leucopenia (6.8%), thrombocytopenia (49.51%), thrombocytosis (2.43%), and elevated serum levels of alanine aminotransferase (ALT, 57.28%) and aspartate aminotransferase (AST, 63.59%) were characteristic laboratory results. The coinfections were dengue, enteric fever, urinary tract infections, and malaria.Children who also had dengue were more likely to develop thrombocytopenia, which was statistically significant (P-value = 0.008). With doxycycline medication, early defervescence of fever occurred earlier than with azithromycin, and it was statistically significant (P-value = 0.000). The complications were hepatitis (63.59%), lower respiratory tract infections (LRTIs, 22.82%),scrub typhus meningoencephalitis (STME, 3.88%), acute kidney injury (AKI, 2.91%), myocarditis (1.46%), and acute disseminated encephalomyelitis (ADEM, 0.49%). Except for one who had ADEM, everyone was sent back home after receiving the best care possible. The average duration of hospital stay was 6.89 days. Conclusions Even in the absence of eschar, scrub typhus should be suspected in any febrile child who experiences clinical signs of meningoencephalitis syndrome, capillary leakage, skin rash, conjunctival congestion, LRTI, AKI, lymphadenopathy, hepatosplenomegaly, thrombocytopenia, and liver dysfunction in the post-monsoon season. Strong clinical suspicion and prompt anti-scrub drug administration go a long way in preventing or decreasing the morbidity and mortality of the same.

Tokat ilinde İki İlçe Hastanesinde Kırım-Kongo Kanamalı Ateşi Ön tanısı ile Takipli Olguların Değerlendirilmesi

Objective: Tokat is one of the cities in Turkey where Crimean–Congo hemorrhagic fever (CCHF) is endemic. Given that CCHF is fatal and contagious, patients should be isolated and hospitalized. This study aimed to compare the epidemiological, clinical, and laboratory findings of CCHF-positive and CCHF-negative cases in two district hospitals in Tokat. Materials and Methods: Patients applied to Turhal and Zile State Hospitals between January 2018 and December 2019 and had a pre-diagnosis of CCHF were included in this case–control study. The patients’ demographic data, symptoms, treatment, and prognosis were recorded. “Pre-diagnosis for CCHF” was defined as the presence of leukopenia or thrombocytopenia, in addition to the presence of at least two symptoms. Cases had antibodies to CCHF virus or CCHF virus-RNA were defined as “CCHF-positive group” and the others were “CCHF-negative group”. Pearson’s chi-square test and Fisher’s test were used to compare the categorical variables. P values that are less than 0.05 were considered statistically significant. Results: Symptoms of headache (20 vs. 18), nausea and vomiting (20 vs. 16), myalgia (18 vs. 16), and diarrhea (11 vs. 5) were more common in the CCHF-positive group than CCHF-negative group. Leukopenia, thrombocytopenia, elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels, and prolongated prothrombin time (PT) and activated partial thromboplastin time (aPTT) levels were also more common. AST elevation and PT prolongation were statistically significant (p=0.01 and p=0.003, respectively). The mortality rate in the CCHF-positive group was 3.8%. Conclusion: Even if there is no history of tick bite in patients living in the endemic region and presenting with headache and gastrointestinal symptoms, CCHF probability is high in the presence of leukopenia, thrombocytopenia, elevated liver enzymes and LDH levels, prolonged PT and aPTT. CCHF should always be considered in patients with these symptoms and laboratory findings.

Pien Tze Huang attenuated acetaminophen-induced liver injury by autophagy mediated-NLRP3 inflammasome inhibition.

Pien Tze Huang is a classic traditional Chinese medicinal product, used for inflammatory diseases as stated in Chinese Pharmacopoeia. In particular, it is effective in treating liver diseases and pro-inflammatory conditions. Acetaminophen (APAP) is a widely used analgesic drug, but its over-dose is associated with acute liver failure where the clinical approved antidote treatment is limited. Inflammation has been considered as one of the therapeutic targets against APAP-induced liver injury. We aimed to explore the therapeutic potential of Pien Tze Huang tablet (PTH) on protecting liver against APAP-induced liver injury through its strong anti-inflammatory pharmacological action. Wild-type C57BL/6 mice were given PTH (75, 150 and 300mg/kg) by oral gavage 3 days before the APAP injection (400mg/kg). The protective effect of PTH was assessed by aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and pathological staining. The mechanisms underlying PTH's hepatoprotective effects were investigated in nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) knock-out (NLRP3-/-), over expression NLRP3 (oe-NLRP3) mice, and wild-type mice with the injection of autophagy inhibitor (3-methyladenine, 3-MA). APAP-exposed mice resulted in evident liver injury which was evidenced by hepatic necrosis and elevated levels of AST and ALT in the wild-type C57BL/6 mice. PTH dose-dependently reduced ALT, AST and upregulated autophagy activity. In addition, PTH significantly reduced elevated levels of proinflammatory cytokines and NLRP3 inflammasome. The liver protective effect of PTH (300mg/kg) was still obvious in the oe-NLRP3 mice, however, it became insignificant in the NLRP3-/- mice. When PTH (300mg/kg) was co-treated with 3-MA to the wild-type C57BL/6 mice, the NLRP3 inhibition were reversed when autophagy was blocked. PTH exerted a beneficial effect in protecting liver against APAP-induced liver injury. The underlying molecular mechanism was associated with the NLRP3 inflammasome inhibition which was likely driven by the upregulated autophagy activity. Our study underpins the traditional use of PTH in protecting liver through its anti-inflammatory action.

Reproductive and Biochemical Toxicity of Biobased Silver Nanoparticles against Toxocara vitulorum

Background: Toxocara vitulorum is a common parasitic worm of buffalo and cattle, causing livestock mortality and morbidity worldwide. Several countries suffered substantial eco-nomic losses due to animal death and reduced meat and milk production. Therefore, it became nec-essary to discover a new alternative drug, especially with the emerging resistance to current medica-tions. The present study aims to evaluate the in vitro anthelmintic effect of different concentrations of biobased silver nanoparticles on T. vitulorum adults. Methods: Different concentrations of silver nanoparticles were synthesised using lemon juice. Groups of male and female adult worms were incubated in 50, 100, and 200 mg/L silver nanoparti-cles for 48 h. The parasite motility, histology, and biochemical parameters were observed and com-pared to the control. Results: The results showed that silver nanoparticles decreased the worm motility, increased mor-tality rate, induced structural damage, caused collagen disruption, and showed elevated levels of as-partate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, total protein, urea, and creatinine, as well as reduced levels of acetylcholinesterase, lactate dehydrogenase, uric acid, total cholesterol, triglycerides, and high-density lipoprotein in a dose-dependent manner. Conclusion: Silver nanoparticles established a significant anthelmintic effect against T. vitulorum and could become one of the up-and-coming antiparasitic drugs in the future.

COVID-19-Triggered Acute Liver Failure and Rhabdomyolysis: A Case Report and Review of the Literature

COVID-19 is primarily known for its respiratory tract involvement, often leading to severe pneumonia and exacerbation of underlying diseases. However, emerging evidence suggests that COVID-19 can result in multiorgan failure, affecting organs beyond the respiratory system. We present the case of a 62-year-old male with COVID-19 who developed acute liver failure (ALF) and rhabdomyolysis in the absence of respiratory failure. Initially, the patient presented with significantly elevated aspartate transaminase (5398 U/L) and alanine transaminase (2197 U/L) levels. Furthermore, a prolonged prothrombin time international normalized ratio (INR) of 2.33 indicated the diagnosis of ALF without hepatic coma, according to Japanese diagnostic criteria. The patient also exhibited elevated creatine kinase (9498 U/L) and a mild increase in creatinine (1.25 mg/dL) levels, but both values improved with intravenous fluid support and molnupiravir administration. To our knowledge, this is the first reported case presenting with both ALF and rhabdomyolysis associated with COVID-19. In addition, we review the existing literature to summarize previously reported cases of ALF triggered by SARS-CoV-2. This case report underscores the significance of recognizing COVID-19 as a significant contributing factor in the development of multiorgan failure. Furthermore, it suggests that COVID-19 can lead to severe illness, irrespective of the absence of respiratory failure.

Improved on-treatment fibrosis-4 during antiviral therapy and lower hepatocellular carcinoma risk in cirrhotic patients with hepatitis B

Normalization of serum alanine aminotransferase (ALT) levels is one of the goals of hepatitis B treatment. However, ALT levels in cirrhosis patients might be normal or mildly elevated regardless of ongoing inflammation. Therefore, we examined whether on-treatment ALT and other potential on-treatment indicators could be clinical surrogates of antiviral therapy in HBV-related cirrhosis. A total of 911 patients with HBV-related liver cirrhosis who started treatment with entecavir or tenofovir were analyzed. At 1 year of antiviral therapy, we evaluated ‘ALT normalization’, ‘undetectable serum HBV DNA’, ‘fibrosis-4 (FIB-4) index improvement’, and ‘serum HBeAg loss’ as potential biomarkers for HCC development. During 6.6 (3.8–10.2) years of follow-up, 222 patients (24.3%) newly developed HCC. Undetectable HBV DNA levels at 1 year were observed in 667 patients (73.2%), and the HCC incidence was significantly lower in this population (adjusted hazard ratio (HR) 0.66, 95% CI 0.50–0.87). Improvement of the FIB-4 index (< 3.25) was associated with a lower risk of HCC in 478 patients with an elevated FIB-4 index (adjusted HR 0.59, 95% CI 0.55–0.82). However, there was no significant difference in HCC risk between those with and without normalization of ALT levels (p = 0.39) among those with elevated ALT levels or between those with and without HBeAg seroconversion (p = 0.55) among HBeAg-positive patients. Therefore, on-treatment FIB-4 levels at 1 year are clinically useful surrogates of antiviral therapy for HBV-related cirrhosis patients.

Assessment and Relationship of Elevated Serum Alanine Transaminase Level in Reference with Obesity

Imbalances between energy gained and exhausted results in abnormal fat accumulation in the tissues of human body and ultimately leads to obesity. Obese people vary not only in the quantity of extra fat that they store, but also in the local distribution of fat within the body. Proportions of obesity are increasing alarmingly in many portions of the world. Pakistan is ranked 9th among 188 countries in carrying obese population, in terms of absolute numbers. Alanine Transaminase is commonly used to identify patients with liver disease. This study was designed to access the level of alanine transaminase in obese subject in the population of Peshawar city, Khyber Pakhtunkhwa, Pakistan. To carry out this survey 300 subjects was examined for body mass index. Blood samples from only obese patients were collected at RMI Hospital, Peshawar, from December 2018 to June 2019 after taking inform consent. Whole blood samples were collected by venipuncture technique in gel tube, after blood clotting and serum was extracted after centrifugation at 3000 rpm for 5 minutes to analyze serum Alanine Aminotransferase level. Out of 300 cases, 148 (49.3%) cases were separated in the categories of obese individuals depending on body mass index values according to WHO criteria. Female with increased body mass index were 71 (48.0%) and 77 (52.0 %) were males. About 35 (46%) male patients showed elevated Alanine Aminotransferase level and 24 (33.8%) females. In both male and female with increase body mass index showed elevated serum Alanine Aminotransferase. From this study, it was concluded that there is relatively increase in serum Alanine Aminotransferase level with increase in body mass index and this raised enzyme levels is more common in obese males than obese females. Further study in this area with large sample size will be fruitful to find strong correlation between these two.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

Does Astragalus Membranaceus Polysaccharides in Astragalus Mongholicus as One of Six Herbs in Bushen Formula Can Be Effective to Decrease the Hepatitis B Viral Load and Alanine Aminotransferase of CHB Patients?

Hepatitis B was the most widespread viral disease and had a very high infection in China during the last 40 years of the 20th to 21st century. The traditional Chinese medicine Bushen formula can treat hepatitis B by lower the mildly elevated alanine aminotransferase and HBV DNA levels for patients. Previous research has shown that the organic compound Astragalus polysaccharide can increase the percentage of CD4+ and CD8+ lymphocyte subsets and reduce hepatic damage caused by chronic hepatitis B. This study investigates APS in treating mice’s hepatic injury by building a CCl4- induced liver failure model and CD4+ CD8+ lymphocyte subsets in peripheral blood analysis models.

A Phase I Study to Evaluate the Pharmacokinetic Drug‒Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia.

HP501 is a highly selective renal urate transporter 1 (URAT1) inhibitor that is being developed for the treatment of hyperuricemia and gout. The primary aim of the present study was to study the pharmacokinetic drug‒drug interactions (DDIs) of HP501, febuxostat, and colchicine in hyperuricemic patients. Hyperuricemic patients were randomly divided into group A, receiving HP501 40 mg once daily on days 1 and 4-10, and group B, receiving febuxostat 40 mg once daily on day 1 and HP501 40 mg plus febuxostat 40 mg on days 4-10. All patients received 0.5 mg colchicine once daily from day 4 to 12. Blood samples were collected for measurement of drug concentrations and serum uric acid (sUA) levels. Coadministration of colchicine with HP501 or HP501 plus febuxostat did not affect steady-state exposure to colchicine. Coadministration of HP501 and febuxostat did not significantly change the pharmacokinetic profiles of either drug. Following multiple administrations of HP501 40 mg once daily for 7 days, the maximal percent sUA change from baseline in group A was -24.77%. The coadministration of HP501 40 mg and febuxostat 40 mg in group B for 7 days resulted in a -55.82% maximal sUA reduction from baseline, and all patients achieved the goal of sUA < 360 μmol/L. All adverse events (AEs) were either mild or moderate, and the most frequently reported AEs were diarrhea and elevated alanine aminotransferase (ALT) levels. The concomitant use of HP501, febuxostat, and colchicine did not produce clinically meaningful DDIs in terms of their pharmacokinetic properties. No. CTR20212261 ( http://www.chinadrugtrials.org.cn/ ) registered September 2021.

Aptasensors Are Conjectured as Promising ALT and AST Diagnostic Tools for the Early Diagnosis of Acute Liver Injury.

Abnormal levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in human serum are the most sensitive indicator of hepatocellular damage. Because liver-related health problems are directly linked to elevated levels of ALT and AST, it is important to develop accurate and rapid methods to detect these enzymes for the early diagnosis of liver disease and prevention of long-term liver damage. Several analytical methods have been developed for the detection of ALT and AST. However, these methods are based on complex mechanisms and require bulky instruments and laboratories, making them unsuitable for point-of-care application or in-house testing. Lateral flow assay (LFA)-based biosensors, on the other hand, provide rapid, accurate, and reliable results, are easy to operate, and are affordable for low-income populations. However, due to the storage, stability, batch-to-batch variations, and error margins, antibody-based LFAs are considered unaffordable for field applications. In this hypothesis, we propose the selection of aptamers with high affinity and specificity for the liver biomarkers ALT and AST to build an efficient LFA device for point-of-care applications. Though the aptamer-based LFA would be semiquantitative for ALT and AST, it would be an inexpensive option for the early detection and diagnosis of liver disease. Aptamer-based LFA is anticipated to minimize the economic burden. It can also be used for routine liver function tests regardless of the economic situation in each country. By developing a low-cost testing platform, millions of patients suffering from liver disease can be saved.

Safety Profile of Eltrombopag in Different Age Groups: An Analysis of Real-World Pharmacovigilance and Randomized Clinical Trials.

Eltrombopag is clinically approved for use in immune thrombocytopenia (ITP), chronic hepatitis C-related thrombocytopenia, and aplastic anemia and suitable for children; however, data on its overall safety profile are scarce. This study aimed to explore the clinical features of adverse drug events (ADEs) associated with eltrombopag in different age groups using individual case safety reports (ICSRs) from the World Health Organization database VigiBase and the US Food and Drug Administration Adverse Event Reporting System database from 2008 to 2022 in combination with a meta-analysis of data from randomized clinical trials in the literature from inception to July 28, 2022. We conducted disproportionality analyses by grouping patients into the following age groups: 0-17 (0-23 months, 2-11 years, and 12-17 years), 18-64, and ≥ 65 years. The ADEs about hepatobiliary disorders, thrombosis, skin and subcutaneous tissue disorders, infections, and so on were observed more differently in each age group. Meta-analysis results showed differences in the four system organ classes between adults and children with ITP: infections and infestations, general disorders and administration site conditions, skin and subcutaneous tissue disorders, and investigations. The adverse drug reactions in the latest version of instructions were searched in the databases to analyze their postmarketing safety signal strength. We observed signals of elevated alanine aminotransferase, aspartate aminotransferase, and blood bilirubin levels in all age groups. For children, urinary tract infection and back pain showed signals. Due to the inherent limitations of pharmacovigilance studies, more experiments are needed to assess the risks of eltrombopag in different ages.