Serum Alanine Aminotransferase Values Research Articles

Low Serum Alanine Aminotransferase Blood Activity Is Associated with Shortened Survival of Renal Cell Cancer Patients and Survivors: Retrospective Analysis of 1830 Patients

Background: Sarcopenia is characterized by a loss of muscle mass and function and is often associated with frailty, a syndrome linked to physical disability and shortened survival in various patient populations, including cancer patients. Low serum alanine aminotransferase (ALT) values, serving as a biomarker for sarcopenia, were previously associated with frailty and shortened survival in several cancers. In the current study, we aimed to test the association between low ALT and shorter survival in renal cell carcinoma (RCC) patients and survivors. Methods: This was a retrospective analysis of RCC patients and survivors, both in- and outpatients. We defined patients with sarcopenia as those presenting with ALT < 17 IU/L. Results: We identified records of 3012 RCC patients. The cohort included 1830 patients (mean age 65.6 ± 13.3 years, 68% were men) of whom only 179 underwent surgical treatment. Out of the eligible cohort, 811 patients (44.3%) had ALT < 17 IU/L, with a mean ALT value of patients within the low-ALT group of 11.79 IU/L, while the mean value in the higher ALT level group was 24.44 IU/L (p < 0.001). Patients in the low-ALT group were older (67.9 vs. 63.7 years; p < 0.001) and had lower BMIs (26.6 vs. 28; p < 0.001). In addition, patients with low ALT had lower hemoglobin values (12.14 vs. 12.91 g/dL; p < 0.001), higher serum creatinine (1.49 vs. 1.14; p < 0.001) and higher platelet to lymphocyte ratios (178 vs. 156; p < 0.001). In a univariate analysis, low ALT levels were associated with a 72% increase in mortality (95% CI 1.46–2.02, p < 0.001). In a multivariate model controlled for age, gender, hemoglobin, platelets, LDH, neutrophil to lymphocyte ratios and platelet to lymphocyte ratios, low ALT levels were still associated with a 27% increase in mortality (HR = 1.27, 95% CI 1.08–1.51; p = 0.005). Conclusion. Low ALT values, associated with sarcopenia and frailty, are also associated with shortened survival in RCC patients, and survivors and could potentially be applied for optimizing individual treatment decisions.

Antiviral activity of lactoferrin: a focus on hepatitis C chronic

Introduction: The Hepatitis C virus (HCV) is one of the main causes of chronic liver disease in the world, and despite having a treatment with sustained virologic response rate, this therapy is not resolutive for all patients. Objectives: To carry out a literature review on the action of bovine lactoferrin (bLf) on chronic hepatitis C to find evidence of its antiviral effect for a possible treatment associated with conventional therapy. Methodology: 49 articles were found according to the descriptors “lactoferrin” “immunotherapy” “chronic hepatitis C” in the pre-selected databases and seven were chosen according to the inclusion and exclusion criteria for writing the review in question. Results: The benefit of bLF use was related to the reduction of serum HCV RNA levels (1106 kIU/ml to 612 kIU/ml), plasma 8-isoprostane (8.6 ± 3.7 to 6.9 ± 2.1 pg/ml) and alanine aminotransferase (ALT) values (85 ± 80 to 63 ± 55 IU/l). Conclusion: The studies showed a possible antiviral effect of bovine lactoferrin that should be explored, through further studies, for adjuvant use in patients with chronic hepatitis C who do not show complete efficacy with the pre-established treatment for the disease.

Exploring Individual Variability in Drug-Induced Liver Injury (DILI) Responses through Metabolomic Analysis.

Drug-induced liver injury (DILI) is a serious adverse hepatic event presenting diagnostic and prognostic challenges. The clinical categorization of DILI into hepatocellular, cholestatic, or mixed phenotype is based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values; however, this classification may not capture the full spectrum of DILI subtypes. With this aim, we explored the utility of assessing changes in the plasma metabolomic profiles of 79 DILI patients assessed by the RUCAM (Roussel Uclaf Causality Assessment Method) score to better characterize this condition and compare results obtained with the standard clinical characterization. Through the identification of various metabolites in the plasma (including free and conjugated bile acids and glycerophospholipids), and the integration of this information into predictive models, we were able to evaluate the extent of the hepatocellular or cholestatic phenotype and to assign a numeric value with the contribution of each specific DILI sub-phenotype into the patient's general condition. Additionally, our results showed that metabolomic analysis enabled the monitoring of DILI variability responses to the same drug, the transitions between sub-phenotypes during disease progression, and identified a spectrum of residual DILI metabolic features, which can be overlooked using standard clinical diagnosis during patient follow-up.

Chronic Hepatitis B In Children: Case Series From A Tertiary Paediatric Hospital.

Chronic hepatitis B (CHB) remains an important global public health problem. Seroconversion is highly correlated with favourable long-term outcome. There is no consensus on the treatment method, onset time and duration for paediatric CHB patients. In this study, we aimed to evaluate the course of children with CHB, to determine the characteristics of the patients who developed spontaneous seroconversion and treatment indications, and to compare the effectiveness of different treatment modalities. Patients aged 1-18 years with a diagnosis of CHB were included in this study and evaluated for the development of spontaneous hepatitis B envelope antigen (HBeAg)/surface antigen (HBsAg) seroconversion and treatment modalities. The treated patients were divided into two groups according to their treatment regimen. Of the 114 patients, the median age at diagnosis was 8.4 years and median follow-up period was 5.2 years. Spontaneous HBeAg and HBsAg seroconversion developed in 18 (20.6%) of 87 HBeAg positive patients and two (1.8%) patients, respectively. Thirty-one patients were treated. The follow-up period was higher in the group with HBeAg seroconversion (p:0.005). There was no statistical difference between the patients in terms of seroconversion development and treatment status. The serum alanine aminotransferase (ALT) values at the time of diagnosis were statistically higher in treated patients. HBV infection and CHB continue to be an important problem for children in our country. Consensus on the appropriate ALT ULN is needed for the treatment of hepatitis in children.

Influence of dietary mannan-oligosaccharides supplementation on hematological characteristics, blood biochemical parameters, immune response and histological state of laying hens

This study aimed to determine the influence of dietary mannan-oligosaccharides (MOS) on the immune system, hematological traits, blood biochemical parameters, and histological state of laying hens. At 34 wk of age, The Mandarah chicken strain's 120 laying hens and 12 cocks were divided into 4 groups, each with 30 hens and 3 cocks. The first group performed as a control group, which nourished on a basal diet. The second, third, and fourth experimental groups received 0.1, 0.2, and 0.5 g/kg of MOS and a base diet, respectively. Birds obtained MOS at numerous doses significantly (P ˂ 0.05) raised serum levels of immunoglobulin Y (IgY), immunoglobulin M (IgM), and avian influenza (AI) antibodies compared to control birds. Furthermore, adding MOS at a level of 0.1 g/kg diet significantly improved the immune response of the control group. Additionally, compared to the control group, treated birds with MOS at various dosages did not significantly enhance hematological parameters such as red blood cells (RBCs), white blood cells (WBCs), hemoglobin, and hematocrit. Compared to control birds, birds fed MOS at all levels exhibited considerably lower serum cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) values. Also, compared to other treated birds, MOS-treated birds displayed improved histological examination of the small intestine, isthmus, and testis compared to the control group, particularly in birds fed MOS at 0.1 and 0.2 g/kg diet. It could be concluded that using MOS at 0.1 or 2 g/kg diet can successfully improve the physiological performance and overall health of laying hens.

Association between Asia–Pacific body mass index classification and serum liver enzymes: alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase in healthy individuals

BackgroundElevated levels of serum liver transaminases are good indicators of liver cell damage, and elevated serum gamma-glutamyl transferase (GGT) level is a good indicator of both bile duct and hepatocellular damage. At early stages, elevated serum levels of these liver enzymes can be mostly prevailed as an asymptomatic condition and therefore in an undiagnosed state. This may be resulted in a number of complications and may lead to chronic hepatic damage that will be more severe and difficult to care. Serum liver enzyme levels are affected by age, gender, body mass index (BMI), ethnicity, drugs and viruses. Obesity has been an epidemic in nearly every country in the world. BMI is the best parameter to assess the magnitude of obesity. Having this background, the present study was designed to investigate the correlation between the levels of serum liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and GGT and Asia–Pacific cut-off points of BMI in healthy individuals.MethodsA descriptive cross-sectional study was conducted using 120 Sinhala, Buddhist subjects which belonged to 18–32 years. BMI was calculated according to the standard protocol. The serum ALT and AST concentrations were measured by UV assay according to the IFCC method without pyridoxal phosphate activation, and the serum GGT concentration was measured by UV assay according to Szasz method, using the Mindray BS-240 Full Automatic Biochemistry Analyser.ResultsSerum levels of liver enzymes were significantly higher in males than females. In females, serum levels of ALT (r = 0.312, p < 0.001), AST (r = 0.138, p = 0.071) and GGT (r = 0.212, p = 0.047) positively correlated with BMI. In males too, serum levels of ALT (r = 0.431, p < 0.001), AST (r = 0.324, p = 0.013) and GGT (r = 0.314, p = 0.031) were positively correlated with BMI. The minimum values of serum ALT, AST and GGT levels were observed in underweight group, while the maximum values were observed in obese group in both genders.ConclusionsALT had the strongest correlation with BMI in both females and males. Therefore, ALT can be suggested as the best liver enzyme that can be used in screening purposes by concerning BMI.

Predictive factors to estimate the severity of nonalcoholic fatty liver disease in candidates for Roux-en-Y gastric bypass

ObjectivesNon-alcoholic fatty liver disease (NAFLD) is related to obesity, insulin resistance, dyslipidemia, and metabolic syndrome. The increasing prevalence of NAFLD results in a significant number of patients manifesting chronic liver disease over time. The aim of this study was to analyze the predictive factors to estimate NAFLD severity in patients who are candidates for Roux-en-Y gastric bypass. MethodsThis descriptive observational study was conducted with 136 obese patients who were candidates for Roux-en-Y gastric bypass and had mild, moderate, or severe NAFLD. ResultsSevere NAFLD was more prevalent among the men (P = 0.007), and mild NAFLD was more prevalent among the women (P = 0.007). Hyperferritinemia was observed in the group with severe NAFLD (P = 0.01). Neck circumference and waist-to-height ratio were associated with an increased risk when comparing the groups with mild and severe NAFLD and those with moderate and severe NAFLD (P = 0.023 and P = 0.001, respectively); the alanine aminotransferase (ALT) and aspartate aminotransferase ratio values were >1 (P = 0.002) in the same comparisons. The regression analyses showed that an increase of 1 ng/mL in vitamin D reduced the chances of severe steatosis by 10% (P = 0.043), and an increase of 1 U/L ALT increased the chances of severe steatosis by 13% (P = 0.002). ConclusionHigh neck circumference and low waist-to-height ratio values, male sex, hyperferritinemia, increased serum ALT values, and decreased vitamin D levels were related to the risk for severe NAFLD.

Pot Marigold (Calendula officinalis) Powder in Rainbow Trout (Oncorhynchus mykiss) Feed: Effects on Growth, Immunity, and Yersinia ruckeri Resistance

The current research investigated the effects of pot marigold (Calendula officinalis) powder on growth, biochemical parameters, digestive enzymes, serum and mucus immune responses, antioxidant defense, and resistance of rainbow trout (Oncorhynchus mykiss) against Yersinia ruckeri. Fish (No. 450, 15.06 ± 0.11 g; mean ± SE ) were randomly distributed to five groups fed with a diet containing 0 (control group), 0.5%, 1%, 1.5%, and 2% of pot marigold powder (MP) for 60 days. Then, fish were challenged with Y. ruckeri infection. Specific growth rate (SGR), weight gain (WG), final weight (FW), feed conversion ratio (FCR), mucus lysozyme (LYZ), mucus protease, serum nitroblue tetrazolium test (NBT), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) values in the 1%, 1.5%, and 2% MP groups significantly increased ( P &lt; 0.05 ) compared to the other groups. Regression analysis exhibited that rainbow trout growth indices were polynomially linked to dietary MP concentrations. In this regard, the optimal levels of MP, according to growth parameters (SGR and FCR), were 1.31 and 1.4% diet, respectively. The intestinal protease, serum complement component 3 (C3), complement component 4 (C4), and LYZ activities in fish fed with the 1% and 1.5% MP-supplemented regime were higher ( P &lt; 0.05 ) compared to the other groups. Also, fish fed with diets containing 1.5% MP had significantly higher intestinal lipase and mucus ALP activities than the other groups ( P &lt; 0.05 ). Aspartate aminotransferase (AST) activity in all MP groups remarkably increased ( P &lt; 0.05 ) compared to the control. Moreover, fish fed with a diet containing 1.5% MP had remarkably higher ( P &lt; 0.05 ) lactate dehydrogenase (LDH) and total protein (TP) values than the other groups. Serum myeloperoxidase (MPO), total immunoglobulin (Ig), and mucus peroxidase values in the 1% MP group remarkably increased ( P &lt; 0.05 ) compared to the other groups. In addition, catalase (CAT) and superoxide dismutase (SOD) activities in the 1.5% and 2% MP groups were significantly higher ( P &lt; 0.05 ) compared to the others. However, malondialdehyde (MDA) levels in fish fed with the 1%, 1.5%, and 2% MP-supplemented diet remarkably decreased than in the other groups ( P &lt; 0.05 ). The highest survival rate after a challenge with Y. ruckeri was recorded in the 1.5% group compared to the control group. Our findings revealed that using pot marigold powder in diets, especially at the 1.5% level, has positive effects on growth, digestive enzyme activities, antioxidant capacity, immune response, and disease resistance in O. mykiss.

Camel milk protectiveness toward multiple liver disorders: A review.

Camel milk is known as the white gold of the desert because it contains within it a variety of nutrients which play a key role in the human diet. The health benefits of camel milk have been described for a variety of diseases such as diabetes, kidney disease, hepatitis, etc. including improved overall survival. A major health burden worldwide is liver diseases, and the ninth leading cause of death in Western countries is due to liver cirrhosis. Treatment is mostly ineffective for cirrhosis, fatty liver, and chronic hepatitis which are the most common diseases of the liver; furthermore current treatments carry the risk of side effects, and are often extremely expensive, particularly in the developing world. A systematic review of studies was performed to determine the association of consumption of camel milk on multiple diseases of the liver. The impact of camel milk on the laboratory tests related to the liver disorders, viral hepatitis, non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC) were evaluated. The consumption of camel milk was accompanied by modulation of the values of serum gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase in persons who are at risk of liver disease. In the patients with chronic liver disease, it was observed that they have low rates of mortality and low chances of progression to cirrhosis when they consume camel milk. Therefore, in patients with liver diseases, the addition of camel milk to their normal daily diet plan should be encouraged. In this review, camel milk's impact on the different kinds of liver diseases or any disorder associated with liver functioning was evaluated. Camel milk has a therapeutic as well as a preventive role in the maintenance and improving the metabolic regulations of the body.

Hematological and Biochemical changes in Schistosoma mansoni infected patients at Haik Primary Hospital, North-East Ethiopia: A comparative cross-sectional study.

Schistosomes are blood dwelling parasites that affect more than 260 million people globally, and over 800 million people are at risk of infection in 74 countries. It causes acute and chronic debilitating diseases. The parasite is reported to alter the hematological and biochemical parameters in humans. Therefore, this study was aimed to evaluate the hematological and biochemical changes in S. mansoni infected adult patients compared to apparently healthy controls. A comparative cross-sectional study was conducted at Haik Primary Hospital from February to April 2021. One hundred and eighty study participants consisting of 90 S. mansoni infected patients and 90 apparently healthy controls were recruited using systematic random sampling method. Socio-demographic characteristics and other variables were collected using questionnaires. Stool sample was examined microscopically to detect S. mansoni infection using direct wet mount and Kato Katz technique. In apparently healthy controls, S. mansoni infection was rule out using direct wet mount and Kato Katz technique. Moreover, the intensity of S. mansoni infection was assessed using Kato Katz technique. Blood sample was collected from each study participant to determine the hematological and biochemical profiles. Data were entered in to Epi Data version 3.1 and analyzed using SPSS version 26.0 software. Kolmogorov-Smirnov and Shapiro Wilk normality tests were done to assess the distribution of continuous variables. The Mann-Whitney U test and Kruskal Wallis H test was done to compare the differences among nonnormally distributed variables between S. mansoni infected patients and healthy controls. P-values <0.05 at 95%CI were considered as statistically significant. The mean age (SD) of S. mansoni infected patients and apparently healthy controls was 30.33 (±12.26) and 31.2 (±12.85) years old, respectively. The prevalence of anemia, and thrombocytopenia among S. mansoni infected patients were 23.3% and 26.7%, respectively. Erythrocytic sedimentation rate (ESR) was significantly elevated among S. mansoni infected patients than apparently healthy controls. The median white blood cell count, red blood cell count, red blood cell indices, and platelet indices were significantly lower among S. mansoni infected patients compared to apparently healthy controls (P<0.05). On the other hand, the median eosinophil count was significantly elevated among S. mansoni infected patients compared to apparently healthy controls (P<0.05). This study also showed significantly elevated values of serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct bilirubin and lower albumin, total cholesterol and triglycerides among S. mansoni infected patients compared to apparently healthy controls. Kruskal Wallis H test showed a significant difference in the median of most hematological and biochemical parameters between moderate and heavy intensity of infection with light intensity of infection and apparently healthy controls. The findings of this study showed significantly altered hematological values and liver function tests among S. mansoni infected patients compared to apparently healthy controls. Therefore, screening of S. mansoni infected patients for various hematological and biochemical parameters and providing treatment to the underlying abnormalities is very crucial to avoid schistosomiasis associated morbidity and mortality.

Updated upper limit of normal for serum alanine aminotransferase value in Vietnamese population

BackgroundAlanine aminotransferase (ALT) is a marker of hepatic damage and its range can be affected by viral hepatitis, alcoholic hepatitis and non-alcoholic fatty liver diseases. We aimed to study the...

The hepato-renal protective potential of walnut seed skin extract against acute renal ischemia/reperfusion damage

Acute kidney damage is defined as a sudden change in kidney functions that prevents the removal of nitrogenous wastes from the body, thus disrupting the body's fluid and electrolyte balance. When acute kidney injury occurs, the kidneys and liver are most affected in the body. Agents used in the treatment of acute kidney injury often have nonsteroidal anti-inflammatory properties that can produce toxic effects on the gastrointestinal tract and kidneys. Natural antioxidants can be recommended as an alternative to existing treatment or in combination to protect tissues against these toxic effects. Therefore, we conducted our current study on whether walnut seed skin (WSS) extract might have hepato-renal protective effects in kidney-damaged Sprague-Dawley rats. This study is the first to use walnut seed skin extract in liver and kidney tissues in renal ischemia/reperfusion (IR) injury. Female Sprague-Dawley rats were randomly divided into three groups: Healty control (HC), renal IR (50 min ischemia – 3 h reperfusion), and renal IR + 450 mg/kg/p.o. WSS extract (the rats were treated with WSS extract orally once 1 h before the IR procedure). For this purpose, blood, liver and kidney tissues of rats were used. In serum samples, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine values were determined separately for the administration groups. We also performed histopathological studies on liver and kidney tissues. Finally, gene markers (endothelial nitric oxide synthase (eNOS), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), Caspase-4 and Caspase-9) determined to evaluate the anti-oxidant, anti-inflammatory and apoptotic effect of walnut seed skin were measured by q-RT PCR method. As a result of the study it was determined that pre-application of WSS extract improved the deteriorated serum parameters in rats with renal ischemia. In the histopathological analysis results, it was observed that WSS had a protective effect on kidney and liver tissue. In studies on gene expression, although there were different and contradictory results for liver and kidney tissue, we determined that WSS was more protective on liver tissue. In conclusion, the healing potential of WSS in renal and hepatic tissues seems to act by inhibiting the inflammatory response, oxidative stress and apoptosis. Therefore, the potential of this extract is remarkable and may serve as a potential therapeutic that may protect against acute organ damages due to renal IR.

Evaluation Of The Connection Between Serum Tumor Necrosis Factor-Alpha, Transforming Growth Factor-Beta, Interleukin-10 And Alanine Aminotransferase Levels And Treatment In Naive Chronic Hepatitis C Patients

Patients with naive CHC were included in the study. All of the patients were genotype 1b and all of them were treated with pegylated interferon and ribavirin combined. 43 people were included in the patient group and 43 people in the control group. Of the patients in both the patient and control groups, 23 were male and 20 were female. The mean age of the patient group was 49.54±13.02, and the mean age of the control group was 47.98±14.1. Serum alanine aminotransferase (ALT), TNF-alpha, TGF-beta, IL-10 values were studied in the patient and control groups. To measure TNF-alpha, TGF-beta and IL-10 values, 10 cc of venous blood was taken into biochemistry tubes containing paraffin. Blood was centrifuged at 5000 rpm for 5 minutes. These procedures were carried out within 1 hour. After centrifugation, the serums placed in the Eppendorf tube were stored in a deep freezer at -80 degrees until the study day. Serum cytokine levels were measured by ELISA method according to kit procedures. Levels of Human TNF-alpha (DIAsource TNF-alpha - ELISA Kit), Human IL-10 (DIAsource IL-10-ELISA Kit), Human TGF-beta ELISA-Multispecies TGF-beta kit) in the patient group at 0. 12. And it was studied from serum samples at week 48 and from a single serum sample in the control group. Values detected in serum samples were recorded as pg/ml. Serum ALT values in the patient and control groups were routinely studied in the biochemistry laboratory of our hospital. Combined treatment was started in the case group and the patients were evaluated in terms of response to the treatment at the 12th and 48th weeks. They were divided into 2 groups as responding and non-responsive to treatment. TNF-alpha, TGF-beta and IL-10 serum cytokine values of these two groups were 0-12 weeks, 12-48 weeks and 0-48. Pairwise comparisons were made within weeks. Finally, cytokine values at 0, 12, 48 weeks were compared with ALT. Spearman's correlation test was used for statistical analysis. The limit of significance was taken as p&lt;0.05 in the interpretations. SPSS (version: 17.0) package program was used for statistical analysis. A statistical difference was found in serum TNF-alpha, TGF-beta and IL-10 serum cytokine values in patients who responded to treatment.

Comparison of Tenofovir Alafenamide and Entecavir Therapy in Patients with Chronic Hepatitis B Initially Treated with Tenofovir Disoproxil: A Retrospective Observational Survey

Background: In chronic hepatitis B patients with or exposed to the risk of osteoporosis or renal dysfunction, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) or entecavir (ETV) may be the right choice. Objectives: This study aimed to present real-life data in terms of the efficacy and safety of a TAF/ETV treatment change while receiving TDF. Methods: This retrospective study was conducted on 344 adult patients from 10 centers. The data of patients who had changed to ETV (n = 107) and TAF (n = 237) while receiving TDF were analyzed. The data collected at 0 and 6 months of treatment were analyzed. The virological response was assessed based on undetected hepatitis B virus (HBV) DNA. Serum alanine aminotransferase (ALT) values were used to evaluate the biochemical response. For renal function, serum creatinine and phosphorus, as well as estimated glomerular filtration rate (eGFR), were recorded. Moreover, lumbar spine and hip T-scores along with the serum lipid profile were evaluated. Results: The mean age of patients was 41.14 ± 13.46 years, and 224 (65.1%) of the participants were male. The treatment arms were not significantly different in terms of demographic characteristics, comorbid diseases, infection duration, family history of HBV infection, blood platelet count, serum biomarkers, such as ALT, phosphorus, creatinine, total bilirubin, albumin, lipid profile, and HBV DNA levels at the beginning. No statistically significant difference was found between the proportion of undetectable HBV DNA of the two treatment groups after 6 months (P = 0.221). The ALT normalization in the ETV and TAF groups at the sixth month compared to the baseline levels was not significantly different (P = 0.853, P = 0.330, respectively). There was no statistically significant difference between the two treatment arms regarding changes in eGFR, creatinine, phosphorus, hip, and spine T-scores from baseline to 6 months (P = 0.296, P = 0.78, P = 0.141, P = 0.832, P = 0.947, respectively). In those who switched to TAF or ETV, low-density lipoproteins cholesterol were observed to be significantly higher after 6 months compared to baseline values (P = 0.002, P = 0.049, respectively). The TC increased significantly in the TAF group (P = 0.035). Conclusions: Our study showed that switching to ETV and TAF sustained the viral suppression and biochemical response achieved by TDF therapy. The treatment switch to TAF of ETV can control renal dysfunction and reduce bone mineral density caused by TDF.

The clinical characteristics, biochemical parameters and insulin response to oral glucose tolerance test (OGTT) in 25 transfusion dependent β-thalassemia (TDT) patients recently diagnosed with diabetes mellitus (DM).

Background:Patients with transfusion dependent β-thalassemia (TDT) are at high risk for developing, over the time, a form of diabetes distinct from type 1 and type 2 diabetes, but with similarities to both.Aims of study:The aim of this study is to describe the clinical and laboratory data, and the insulin secretion and sensitivity, in TDT patients recently diagnosed with diabetes mellitus (DM).Materials and Methods:The medical records of 25 TDT patients with DM, diagnosed by standardized oral glucose tolerance test (OGTT) and insulin secretion, were analysed; data were compared to TDT patients without diabetes and to a group of healthy subjects. Natural history of glucometabolic status before the diagnosis of DM was also reviewed.Results:On average, the TDT patients with DM were younger compared to TDT patients without diabetes. The mean age at diagnosis of DM in female and male TDT patients was 24.0 ± 7.1 years and 31.9 ± 5.6 years, respectively (P: 0.007). Serum alanine aminotransferase values, basal insulin levels and prevalence of hypogonadism were consistently higher in TDT patients with DM compared to those without diabetes. Decreased insulin secretion and increased insulin resistance was observed in patients with DM.Conclusion:The natural history of glucometabolic status in TDT patients is characterized by a deterioration of glucose tolerance over time. Iron overload and liver dysfuction are the main factors responsible for glucose disturbances (GD) in TDT patients. The therapeutic approach must be individualized and followed by a multidisciplinary team. (www.actabiomedica.it)

Histopathological, immunohistochemical and biochemical alterations in liver tissue after fungicide-mancozeb exposures in Wistar albino rats.

ABSTRACTPurpose:To evaluate the histopathological, immunohistochemical, and biochemical effects of liver changes after mancozeb administration.Methods:Rats were divided into groups–the control group (n=7) and the mancozeb group (n=7)–, given 500 mg/kg mancozeb dissolved in corn oil daily for four weeks by an orogastric tube. Caspase-3 and tumor necrosis factor-alpha (TNF-α) primary antibodies were used for immunohistochemical analysis.Results:Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values of the mancozeb group increased significantly than ones of the control group. Venous dilatation, inflammation, hepatocyte degeneration, TNF-α, and caspase-3 expression scores increased significantly in the mancozeb group. In the mancozeb group, intensive caspase-3 expression was observed in hepatocyte cells around the central vein in the center of the liver lobule, and there was an increase in TNF-α expression in the inflammatory cells around the enlarged central vein and Kupffer cells and apoptotic hepatocyte cells.Conclusions:Subacute mancozeb exposure in rats leads to elevated toxicity with impaired liver function, increased inflammation in tissue and increased apoptosis due to cellular damage in the liver, and decreased liver regeneration ability due to congestion and degeneration of blood vessels.

Metabolomic analysis to discriminate drug-induced liver injury (DILI) phenotypes

Drug-induced liver injury (DILI) is an adverse toxic hepatic clinical reaction associated to the administration of a drug that can occur both at early clinical stages of drug development, as well after normal clinical usage of approved drugs. Because of its unpredictability and clinical relevance, it is of medical concern. Three DILI phenotypes (hepatocellular, cholestatic, and mixed) are currently recognized, based on serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) values. However, this classification lacks accuracy to distinguish among the many intermediate mixed types, or even to estimate the magnitude and progression of the injury. It was found desirable to have additional elements for better evaluation criteria of DILI. With this aim, we have examined the serum metabolomic changes occurring in 79 DILI patients recruited and monitored using established clinical criteria, along the course of the disease and until recovery. Results revealed that free and conjugated bile acids, and glycerophospholipids were among the most relevant metabolite classes for DILI phenotype characterization. Using an ensemble of PLS–DA models, metabolomic information was integrated into a ternary diagram to display the disease phenotype, the severity of the liver damage, and its progression. The modeling implemented and the use of such compiled information in an easily understandable and visual manner facilitates a straightforward DILI phenotyping and allow to monitor its progression and recovery prediction, usefully complementing the concise information drawn out by the ALT and ALP classification.

Changes in liver function test levels in HIV patients undergoing highly active antiretroviral therapy (HAART). Longitudinal study in Lima, Peru

Introduction: Estimating and monitoring changes in liver function tests is necessary to prevent the occurrence of chronic liver disease in HIV patients undergoing highly active antiretroviral therapy (HAART). Objective: To determine the variation liver profile test levels in HIV patients undergoing HAART. Materials and methods: Retrospective longitudinal study conducted in 100 HIV patients treated at the Hospital Nacional Hipólito Unanue, Lima, Peru, between 2015 and 2017. Patients in all stages of clinical infection under HAART and with liver function panel results for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and total protein (TP) were included. Three follow-up liver function tests (every 3 months) were performed while undergoing HAART and participants were categorized as having normal or elevated levels for all liver markers. Differences between the samples analyzed were determined using the paired-samples T test, with a 95% confidence interval and a significance level of p&lt;0.05. Results: Participants’ mean age was 33±9.56 years and 67% were male. Mean serum AST, ALT and ALP values decreased between the first and the third measurement (p=0.021, p=0.076 and p=0.002, respectively). No significant differences in GGT and TP levels were observed between the three measurements, nor between patients with normal and elevated AST, ALT, ALP and TP values, but significant differences were observed for GGT (p=0.010). Conclusions: Variations in liver marker levels were observed in all participants, with a decreasing trend in AST, ALT and ALP between the early and late stages of HAART, implying that this therapy could play a role in liver tissue damage.

Nutritional, Biochemical and Haematological Indices of White Albino Rats Fed Complementary Diets Developed from Selected Cereals and Legumes

Background: Childhood malnutrition is a common public health problem in Ethiopia. This animal study aims to evaluate the haematological, biochemical, and nutritional indices of weanling albino rats fed on complementary diets developed from selected cereals and legumes. Methods: The nutritional qualities of the formulated blends were assessed biologically by feeding white albino rats in order to determine feed intake, the growth rate, protein quality parameters, biochemical and haematological properties. The commercial weaning diet (cerifam) and casein were used as control diets. On the 28th day, blood samples were collected from three randomly selected rats by decapitation. Full blood count analysis was carried out using the Automated Haematologic Analyzer to determine haematological parameters. All the biochemical parameters were determined using Mindray diagnostic kits. Results and Discussion: The food intake pattern showed that animals placed on diet 3, diet 4, casein, and cerifam consumed more food than those fed on diet 1, diet 2, and diet 7. The mean growth rate of animals fed on diet 3 and diet 4 was significantly (p&lt;0.05) higher than those placed on diet 1, diet 2, and diet 7 but similar to those fed with commercial diet and casein. The protein quality evaluation of the diets showed that the protein efficiency ratio ranged from 1.20 to 2.43 while the biological value was in the range of 54.53 to 69.48%. The net protein utilization and true digestibility were 65.62 to 70.21% and 59.01 to 64.01%, respectively. Serum total protein, albumin, and globulin levels in rats given diet 3 and diet 4 were comparable to the controls and within the normal range. Comparatively, the creatinine and urea levels of rats fed on the control and formulated diets were within the normal range. The serum alanine aminotransferase values of rats fed on the control and formulated diets ranged from 22.03 IU/L in diet 2 to 37.76 IU/L in diet 4 and were not significantly different from each other. In this study, the packed cell volume and haemoglobin values of the control and formulated diets were within the recommended range. Evidently, diet 3 and diet 4 gave the best growth performance after the feeding trials. Conclusion: The haematological and biochemical indices indicate that these diets can support effective growth and development in rats, and consumption of these diets has no detrimental effects on the liver and renal function.

Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.