Increased Alanine Aminotransferase Levels Research Articles

Radiofrequency ablation combined with transcatheter arterial chemoembolization for recurrent liver cancer.

The recurrence rate of liver cancer after surgery is high. Radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) is an effective treatment for liver cancer; however, its efficacy in recurrent liver cancer remains unclear. To investigate the clinical effect of TACE combined with RFA in the treatment of recurrent liver cancer. Ninety patients with recurrent liver cancer were divided into 2 groups according to treatment plan: Control (RFA alone); and experimental [TACE combined with RFA (TACE + RFA)]. The incidence of increased alanine aminotransferase levels, complications, and other indices were compared between the two groups before and after the procedures. One month after the procedures, the short-term efficacy rate and Karnofsky Performance Status scores of the experimental group were significantly higher than those of the control group (P < 0.05). Alpha-fetoprotein (AFP) and total bilirubin levels were lower than those in the control group (P < 0.05); The overall response rate was 82.22% and 66.67% in the experimental and control groups, respectively; The disease control rate was 93.33% and 82.22% in the experimental and control groups, respectively, the differences are statistically significant (P < 0.05). And there were no statistical differences in complications between the two groups (P > 0.05). TACE + RFA was effective for the treatment of recurrent liver cancer and significantly reduced AFP levels and improved various indices of liver function.

Pathogenicity of two different genotypes avian hepatitis E strains in laying hens and silkie fowl

To determine the pathogenicity of two different genotypes of avian hepatitis E strains in two species of birds, a total of thirty healthy 12-week-old birds were used. After inoculation, fecal virus shedding, viremia, seroconversion, serum alanine aminotransferase (ALT) increases and liver lesions were evaluated. The results revealed that CHN-GS-aHEV and CaHEV could both infect Hy-Line hens and silkie fowls, respectively. Compared to the original avian HEV strain, the cross-infected virus exhibited a delay of 2 weeks and 1 week in emerged seroconversion, viremia, fecal virus shedding, and increased ALT level, and also showed mild liver lesions. These findings suggested that CHN-GS-aHEV may have circulated in chickens. Overall, these two different genotypes of avian HEV showed some variant pathogenicity in different bird species. This study provides valuable data for further analysis of the epidemic conditions of two avian HEVs in Hy-Line hens and silkie fowls.

Serum Biochemical Parameters of Broilers Affected by Wooden Breast Myopathy.

Wooden breast (WB) myopathy is a pathology of the pectoralis major muscle. Wooden breast is caused by multiple factors. The exact etiopathogenesis of this myodegenerative pathology is still unclear. Fast-growing commercial lines of broilers that are selected for high breast muscle yields are more susceptible to this myopathy. The biochemical analysis of blood is used to diagnose pathologies and understand disease processes. Therefore, the objective of this research was to determine and compare the changes in the blood serum biochemical parameters of Ross 308 chicken broilers without myopathy and those affected by WB myopathy. Blood samples were collected from male and female Ross 308 broilers that were 43 days old, with an average live weight of 2.98-3.09 kg. Representative blood samples were selected from broilers with WB (n = 33) and without WB (n = 33). In the laboratory, the blood was centrifugated, and biochemical tests were performed with an automated computerized biochemistry analyzer. The research results showed that broilers with WB had elevated blood serum levels of creatine kinase (CK) (p = 0.018), potassium (p = 0.010), and alanine aminotransferase (ALT) (p = 0.012). In conclusion, elevated serum levels of CK and potassium indicated that skeletal muscle cells were damaged. Moreover, increased ALT levels suggested a possible association between WB myopathy and liver damage. Additionally, these research findings underscore the diagnostic significance of CK and hint at its potential as a WB biomarker.

Zinc-associated phospholipid metabolic alterations and their impacts on ALT levels in workers

Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) μg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) μg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.

Hepatotoxic effects of Stevia rebaudiana leaf extract and commercial stevia on rats: a comparative study

The popularity of stevia is high, especially among diabetics and those looking to reduce their calorie-intake. The aim of this study was to compare the effects of a commercially-available stevia and of a Stevia rebaudiana leaf extract on the liver function and histology of rats. After preparing the Stevia rebaudiana leaf extract, 60 healthy adult male rats were randomly separated into three groups: untreated control, commercial stevia treatment (25 mg/kg), and Stevia rebaudiana leaf extract treatment (25 mg/kg). Our results show that after 60 days of treatment (oral administration), a significant elevation of the alanine aminotransferase (ALT) levels was observed in the commercial stevia-treated group, suggesting potential effects on liver function. The Stevia rebaudiana leaf extract-treated group also exhibited increased ALT levels. Moreover, the aspartate aminotransferase (AST) levels were found significantly increased in both of these treatment groups (when compared to the control group). Alkaline phosphatase levels were not found altered between groups. Histological-examinations, in spite of the elevated ALT and AST levels, exhibited no abnor¬malities in the liver. Although stevia is generally regarded as safe, this study underlines the importance of considering the type and form of stevia when evaluating its effects on liver health. Further study is warranted so as to elucidate the specific components and mechanisms responsible for the observed variations in liver enzymes, and to confirm the overall safety of stevia products.

Interferon-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon-α (PEG-IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG-IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP-1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN-γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell-associated chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN-γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue-resident memory T cells with increased ALT levels. IFN-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.

A silicone disc for liver retraction in laparoscopic gastrectomy reduces the postoperative increase in the liver enzyme level.

To compare changes in liver enzyme levels on postoperative day 1 between patients with and without silicone disc (SD) use during liver retraction in laparoscopic gastrectomy for gastric cancer and laparoscopic gastric mobilization for esophageal cancer. This prospective randomized controlled phase II trial was conducted between June 30, 2020, and November 30, 2022, to investigate the benefits of using an SD with a Nathanson liver retractor (NLR) compared with those using an NLR in laparoscopic gastrectomy and gastric mobilization. The primary endpoint was the change in transaminase level on postoperative day 1. A total of 86 patients received randomized assignments and were included in the analysis, with 44 assigned to the SD (-) group and 42 to the SD (+) group. On postoperative day 1, the SD (+) group showed a significantly lower increase in the aspartate aminotransferase levels than the SD (-) group (SD [+], 94.4% vs. SD [-], 179.8%; p = 0.012). Similarly, the SD (+) group showed a significantly lower increase in alanine aminotransferase levels than the SD (-) group (SD [+], 71.6% vs. SD [-], 201.5%; p = 0.014). In laparoscopic gastrectomy, the use of an SD combined with an NLR appears to mitigate postoperative liver dysfunction.

Genetic Causal Relationship Between Alanine Aminotransferase Levels and Risk of Gestational Diabetes Mellitus: Mendelian Randomization Analysis Based on Two Samples.

Gestational diabetes mellitus (GDM) is a frequent complication of pregnancy. The specific mechanisms underlying GDM have not yet been fully elucidated. Contemporary research indicates a potential association between liver enzyme irregularities and an increased risk of metabolic disorders, including diabetes. The alanine aminotransferase (ALT) level is recognized as a sensitive marker of liver injury. An increase in ALT levels is hypothesized to be linked to the pathogenesis of insulin resistance and diabetes. Nonetheless, the definitive causal link between ALT levels and GDM still needs to be determined. This investigation utilized two-sample Mendelian randomization (MR) to examine the genetic causation between alanine aminotransferase (ALT) and GDM. We acquired alanine aminotransferase (ALT)-related GWAS summary data from the UK Biobank, Million Veteran Program, Rotterdam Study, and Lifeline Study. Gestational diabetes data were obtained from the FinnGen Consortium. We employed various MR analysis techniques, including inverse-variance weighted (IVW), MR Egger, weighted median, simple, and weighted weighting. In addition to MR-Egger intercepts, Cochrane's Q test was also used to assess heterogeneity in the MR data, and the MR-PRESSO test was used to assess horizontal pleiotropy. To assess the association's sensitivity, a leave-one-out approach was employed. The IVW results confirmed the independent risk factor for GDM development, as indicated by the ALT level (p = .011). As shown by leave-one-out analysis, horizontal pleiotrophy did not significantly skew the causative link (p > .05). Our dual-sample MR analysis provides substantiated evidence of a genetic causal relationship between alanine aminotransferase (ALT) levels and gestational diabetes.

Treatment with Remdesivir of Children with SARS-CoV-2 Infection: Experience from a Clinical Hospital in Romania.

The COVID-19 pandemic was characterized by mild-to-moderate disease in children and adolescents, with low incidences of severe cases and mortality. Most of the information on drug therapy in COVID-19-positive children was derived from research in adult patients. Remdesivir, an inhibitor of viral RNA polymerase, was shown to be effective in COVID-19 patients with moderate-to-severe disease. In this study, we present our experience of the use of remdesivir in pediatric patients hospitalized with COVID-19. This retrospective study was based on the early use of remdesivir in 14 children with mild, moderate, and severe clinical forms of COVID-19, who were hospitalized between 1 January 2022, and 30 September 2023. The patients included eight infants and six children older than 1 day (the age range was 2 months to 17 years). Most of them (92.85%) had documented pneumonia. Four patients had associated acute laryngitis, and another had bronchiolitis. Coinfections with Streptococcus pneumoniae were diagnosed in two patients. The clinical course was favorable in 12/14 (85.71%) children. Two patients were transferred to the pediatric intensive care unit because of aggravation of associated acute diseases (acute laryngitis and bronchiolitis, respectively). Mild increases in alanine aminotransferase levels occurred in two patients, with no increase in serum creatinine, during treatment with remdesivir. The appropriate use of remdesivir proved safe and efficient in our group of patients. However, further studies are required to support the efficiency, tolerability, and safety of remdesivir in children.

Green robusta coffee and its hepatoprotective effect on ALT levels of white mice induced with Monosodium Glutamate

Background of the study: Liver injury or damage to liver function, also known as hepatotoxicity, can occur due to various reasons, including chemical substances. Monosodium Glutamate (MSG) is one such chemical that can cause liver damage if consumed in large amounts for a prolonged period. This study aimed to determine the effect of green Robusta Coffee extract on the alanine aminotransferase (ALT) levels of white mice induced with MSG. Material and methods: This research study used 24 male white mice (Rattus norvegicus) divided into three groups. The negative control group (C-) was given nothing, the positive control group (C+) was given MSG at a dosage of 5 mg/g/day, and the experimental group (E) was given MSG at a dosage of 5 mg/g/day and green Robusta Coffee extract at a dosage of 250 mg/kg/day for 14 days. Results: On the 15th day, blood was drawn from all three groups to measure ALT levels. The ALT levels were then analyzed using SPSS statistics. The study found a significant increase in ALT levels in the C+ group compared to the C- group (P&lt;0.05). However, there was no significant increase or decrease in ALT levels between the experimental group (E) and the C- and C+ groups (P&gt;0.05). Conclusion: The study concluded that MSG induction of 5 mg/g/day for 14 days significantly increased the ALT levels of white mice. However, giving green Robusta Coffee (Coffea canephora) extract at a dosage of 250 mg/kg/day did not have a significant effect on the increased ALT enzyme levels of white mice induced with MSG at a dosage of 5 mg/g/day for 14 days.

Vitamin D was Superior to Omega-3 as a Simvastatin Adjuvant in Improving Blood Lipids and Atherogenic Index in Type-I Dyslipidemic Rats.

Adjuvant therapy is often used to optimize the antihyperlipidemic effect of simvastatin. Omega-3 and vitamin D supplementation are recommended as adjuvant therapies to low-intensity statins. This study aimed to compare the effects of vitamin D and omega-3 as adjuvant therapy to simvastatin to improve the lipid profiles and atherogenic index of plasma (AIP) in type-I dyslipidemic rats. Thirty-six male rats were randomized and divided into six groups: healthy control, dyslipidemic rats with no treatment, and dyslipidemic rats treated with either low-dose simvastatin only or omega-3 or vitamin D at low and high doses. Dyslipidemia was induced with high-fat diets for four weeks, followed by treatment for the next two weeks. Blood samples were withdrawn before and after simvastatin treatment. In addition, aspartate transaminase (AST) and alanine transaminase (ALT) levels were analyzed to assess liver function. Administration of a high-fat diet-induced type 1 dyslipidemia and increased ALT levels (p < 0.05). Treatment with low-dose simvastatin did not significantly improve triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc) or non-HDLc levels. When combined with a high-dose vitamin D, simvastatin significantly reduced TG and increased HDLc levels (p < 0.05), thereby improving AIP levels. This improvement was not observed in rats treated with omega-3 or vitamin D at a lower dose. We concluded that high-dose vitamin D as an adjuvant to simvastatin therapy was superior to omega-3 in improving TG, HDL, and AIP levels. High-dose vitamin D also improved ALT levels in type-I dyslipidemic rats. This result may be translated in clinics to reduce the risk of coronary syndrome in patients with type-I dyslipidemia.

Role of Alanine Transaminase and Transient Elastography in Categorising Nonalcoholic Fatty Liver Disease Subgroups.

To investigate the association of alanine transaminase (ALT) with transient elastography grades to define various nonalcoholic fatty liver disease (NAFLD) groups for disease status. Cross-sectional, descriptive study. Place and Duration of the Study: Gastroenterology Outpatient Clinic, Ziauddin Hospital, from January to December 2022. This study included 194 NAFLD patients. Demographic data, body mass index, enzymes, and transient elastography (TE) findings were recorded. NAFLD patients were categorised as nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH), steatofibrosis (significant fibrosis F2-F3 with normal ALT), and cirrhosis using TE grades. The median age of the patients was 44 [IQR 18.25] years; 146 (75.3%) were males. Out of 194 NAFLD patients, 21 (10.8%) were NAFL, 116 (59.8%) were NASH, 14 (7.2%) showed steatofibrosis, and 43 (22.2%) were cirrhotic. On transient elastography, the majority were with S3 steatosis (n=107, 55.2%) and 59 (30.2%) had F0-F1 fibrosis. There was a statistically significant difference in the mean rank of age, ALT, AST, and GGT levels within 4 groups of NAFLD (p <0.001). Most of the patients with all the stages of fibrosis had increased ALT levels (p=0.034). This study concluded that a combination of ALT levels and transient elastography findings could be considered for differentiating uncomplicated steatosis from NASH, steatofibrosis, and cirrhosis, hence limiting the use of liver biopsy. This may prove a reliable way to measure the severity of the disease. Nonalcoholic fatty liver disease, Cirrhosis, Transient elastography.

A285 CHANGE IN ALT DURING MODIFIED OPTIFAST WEIGHT LOSS PROGRAM IN INDIVIDUALS AT RISK FOR NON-ALCOHOLIC FATTY LIVER DISEASE

Abstract Background Obesity is linked to various health complications, including diabetes, metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent cause of abnormally high alanine aminotransferase (ALT) levels. ALT is released at higher levels during hepatocellular injury and represents a simple, low cost and non-invasive method of assessing liver damage. There are conflicting data on ALT response to weight loss between men and women, with some evidence of transient increase in ALT levels in women. Purpose The aim of this study was to assess the impact of a dietary weight loss intervention with Optifast on ALT in patients with obesity who have baseline elevated ALT levels. Method This was a retrospective cohort study of Ontario adults who participated in a 26 week weight loss program, including 6 or 12 weeks of low-calorie liquid diet meal replacement with Optifast 900® (Nestlé, Canada), between 1992 and 2015. We included patients with elevated baseline ALT levels, defined by &amp;gt; 40 U/L, who had at least one follow-up ALT between week 15 and 26. We excluded patients with nonadherence to dietary intervention, established liver disease or using hepatotoxic drugs, excessive alcohol intake (&amp;gt;11U/wk for females and &amp;gt;14U/wk for males), and insufficient data to calculate FIB-4. The primary outcome was change in ALT levels, measured by normalization (post-intervention ALT &amp;lt; 40 U/L), percentage decrease and absolute decrease. Multiple linear regressions were obtained for the relationship between ALT changes and age, sex, body mass index (BMI) and FIB-4. All analyses were conducted in SPSS. P value of ≤0.05 was considered statistically significant. Result(s) 444 patients met study criteria. Mean age was 47.1 years +/- 10.9, 49 % of patients were female, and mean BMI was 43.5 kg/m2 +/- 7.9. All patients lost weight, with mean weight loss 27.3 kg +/- 11.5 and a mean 20.7% decrease from baseline weight. Mean ALT at baseline was 58.9 U/L +/- 25.4 and mean ALT post intervention was 32.3 U/L +/- 28.1 (p &amp;lt;0.01). 85.1% of patients had normalization of ALT. Mean % decrease in ALT was 41.9% and mean absolute decrease in ALT was 26.6 U/L +/- 25.4. Younger age and higher baseline FIB-4 were significantly associated with a larger decrease in ALT levels, while sex and initial BMI were not significantly associated with changes in ALT. Conclusion(s) In patients with obesity and baseline elevated ALT, dietary weight loss intervention with Optifast leads to ALT normalization in most patients, regardless of sex. Younger age at baseline and higher baseline FIB-4 are significantly associated with greater decrease in ALT. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Association Between Serum Trace Heavy Metals and Liver Function Among Adolescents.

Exposure to metals has been associated with liver-related disease. Few studies have explored the effect of sex stratification on adolescent liver function. From the National Health and Nutrition Examination Survey (2011-2016), 1143 subjects aged 12-19 years were selected for analysis. The outcome variables were the levels of alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transpeptidase. The results showed a positive association between serum zinc and ALT in boys (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.11-5.06). Serum mercury was associated with an increase in ALT level in girls (OR, 2.73; 95% CI, 1.14-6.57). Mechanistically, the efficacy mediated by total cholesterol accounted for 24.38% and 6.19% of the association between serum zinc and ALT. The results imply that serum heavy metals were associated with the risk of liver injury, possibly mediated by serum cholesterol, in adolescents.

Association of HSD17B13 and PNPLA3 With Liver Enzymes and Fibrosis in Hispanic/Latino Individuals of Diverse Genetic Ancestries

Genetic variants affecting liver disease risk vary among racial and ethnic groups. Hispanics/Latinos in the United States have a high prevalence of PNPLA3 I148M, which increases liver disease risk, and a low prevalence of HSD17B13 predicted loss-of-function (pLoF) variants, which reduce risk. Less is known about the prevalence of liver disease-associated variants among Hispanic/Latino subpopulations defined by country of origin and genetic ancestry. We evaluated the prevalence of HSD17B13 pLoF variants and PNPLA3 I148M, and their associations with quantitative liver phenotypes in Hispanic/Latino participants from an electronic health record-linked biobank in New York City. This study included 8739 adult Hispanic/Latino participants of the BioMe biobank with genotyping and exome sequencing data. We estimated the prevalence of Hispanic/Latino individuals harboring HSD17B13 and PNPLA3 variants, stratified by genetic ancestry, and performed association analyses between variants and liver enzymes and Fibrosis-4 (FIB-4) scores. Individuals with ancestry from Ecuador and Mexico had the lowest frequency of HSD17B13 pLoF variants (10%/7%) and the highest frequency of PNPLA3 I148M (54%/65%). These ancestry groups had the highest outpatient alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and the largest proportion of individuals with a FIB-4 score greater than 2.67. HSD17B13 pLoF variants were associated with reduced ALT level (P= .002), AST level (P< .001), and FIB-4 score (P= .045). PNPLA3 I148M was associated with increased ALT level, AST level, and FIB-4 score (P < .001 for all). HSD17B13 pLoF variants mitigated the increase in ALT conferred by PNPLA3 I148M (P= .006). Variation in HSD17B13 and PNPLA3 variants across genetic ancestry groups may contribute to differential risk for liver fibrosis among Hispanic/Latino individuals.

Outcomes in Patients with FLT3-Mutated Relapsed/ Refractory Acute Myelogenous Leukemia Who Underwent Transplantation in the Phase 3 ADMIRAL Trial of Gilteritinib versus Salvage Chemotherapy

The fms-like tyrosine kinase 3 (FLT3) inhibitor gilteritinib improved the survival of patients with relapsed or refractory (R/R) FLT3-mutated acute myelogenous leukemia (AML) in the phase 3 ADMIRAL trial. In this study, we assessed survival and relapse rates of patients in the ADMIRAL trial who underwent hematopoietic stem cell transplantation (HSCT), as well as safety outcomes in patients who received post-transplantation gilteritinib maintenance therapy. ADMIRAL was a global phase 3 randomized controlled trial that enrolled adult patients with FLT3-mutated R/R AML. Patients with R/R AML who harbored FLT3 internal tandem duplication mutations in the juxtamembrane domain or D835/I836 point mutations in the tyrosine kinase domain were randomized (2:1) to gilteritinib (120 mg/day) or to preselected high- or low-intensity salvage chemotherapy (1 or 2 cycles). Patients in the gilteritinib arm who proceeded to HSCT could receive post-transplantation gilteritinib maintenance therapy if they were within 30 to 90 days post-transplantation and had achieved composite complete remission (CRc) with successful engraftment and no post-transplantation complications. Adverse events (AEs) during HSCT were recorded in the gilteritinib arm only. Survival outcomes and the cumulative incidence of relapse were assessed in patients who underwent HSCT during the trial. Treatment-emergent AEs were evaluated in patients who restarted gilteritinib as post-transplantation maintenance therapy. Patients in the gilteritinib arm underwent HSCT more frequently than those in the chemotherapy arm (26% [n = 64] versus 15% [n = 19]). For all transplantation recipients, 12- and 24-month overall survival (OS) rates were 68% and 47%, respectively. Despite a trend toward longer OS after pretransplantation CRc, post-transplantation survival was comparable in the 2 arms. Patients who resumed gilteritinib after HSCT had a low relapse rate after pretransplantation CRc (20%) or CR (0%). The most common AEs observed with post-transplantation gilteritinib therapy were increased alanine aminotransferase level (45%), pyrexia (43%), and diarrhea (40%); grade ≥3 AEs were related primarily to myelosuppression. The incidences of grade ≥III acute graft-versus-host disease and related mortality were low. Post-transplantation survival was similar across the 2 study arms in the ADMIRAL trial, but higher remission rates with gilteritinib facilitated receipt of HSCT. Gilteritinib as post-transplantation maintenance therapy had a stable safety and tolerability profile and was associated with low relapse rates. Taken together, these data support a preference for bridging therapy with gilteritinib over chemotherapy in transplantation-eligible patients.

Safety of oral nemonoxacin: A systematic review of clinical trials and postmarketing surveillance.

Background: Postmarketing safety analysis is an effective supplement for new drugs in clinical practice. Therefore, we aimed to systematically assess the safety of oral nemonoxacin malate, the first approved C-8-methoxy non-fluorinated quinolone, in clinical studies and via postmarketing safety surveillance. Methods: We electronically and manually searched and screened safety data (including premarketing and postmarketing data) of oral nemonoxacin from clinical registries. We standardized and summarized the reported adverse events according to the Medical Dictionary for Regulatory Activities System Organ Class and Preferred Terms. We summarized and reported the number and frequency (%) of the AEs and serious AEs in patients with community-acquired pneumonia and in specific patients. Results: Three Phase II/III comparator studies (n = 670, nemonoxacin), one Phase IV study (n = 461), two special population pharmacokinetic studies (n = 40), four observational studies (n = 1,852), and one 5-year postmarketing surveillance project (n = 257,420) were included in this study. The Phase II/III studies showed that the commonly reported drug-related AEs were similar for oral 500mg nemonoxacin and levofloxacin treatments, which mainly included increased alanine aminotransferase levels (4.4% vs. 2.5%), neutropenia (2.5% vs. 4.4%), nausea (2.5% vs. 1.6%), and leukopenia (2.3% vs. 3.2%). No drug-related deaths were reported. Postmarketing safety surveillance revealed that known adverse drug reaction characteristics were generally unchanged. Pharmacokinetic data suggested that dose adjustment was not necessary in elderly patients, which was confirmed by a Phase IV study in an elderly population, in patients with renal impairment with CLcr ≥50ml/min, and in those with mild-to-moderate hepatic impairment. Conclusion: Clinical trial data of approximately 1,450 patients and postmarketing data of >257,420 patients suggest that nemonoxacin is generally well tolerated and can be a suitable alternative to fluoroquinolones for patients with CAP.

Efficacy and Safety of Bepirovirsen in Chronic Hepatitis B Infection

BackgroundBepirovirsen is an antisense oligonucleotide that targets all hepatitis B virus (HBV) messenger RNAs and acts to decrease levels of viral proteins.MethodsWe conducted a phase 2b, randomized, investigator-unblinded trial involving participants with chronic HBV infection who were receiving or not receiving nucleoside or nucleotide analogue (NA) therapy. Participants were randomly assigned (in a 3:3:3:1 ratio) to receive weekly subcutaneous injections of bepirovirsen at a dose of 300 mg for 24 weeks (group 1), bepirovirsen at a dose of 300 mg for 12 weeks then 150 mg for 12 weeks (group 2), bepirovirsen at a dose of 300 mg for 12 weeks then placebo for 12 weeks (group 3), or placebo for 12 weeks then bepirovirsen at a dose of 300 mg for 12 weeks (group 4). Groups 1, 2, and 3 received loading doses of bepirovirsen. The composite primary outcome was a hepatitis B surface antigen (HBsAg) level below the limit of detection and an HBV DNA level below the limit of quantification maintained for 24 weeks after the planned end of bepirovirsen treatment, without newly initiated antiviral medication.ResultsThe intention-to-treat population comprised 457 participants (227 receiving NA therapy and 230 not receiving NA therapy). Among those receiving NA therapy, a primary-outcome event occurred in 6 participants (9%; 95% credible interval, 0 to 31) in group 1, in 6 (9%; 95% credible interval, 0 to 43) in group 2, in 2 (3%; 95% credible interval, 0 to 16) in group 3, and 0 (0%; post hoc credible interval, 0 to 8) in group 4. Among participants not receiving NA therapy, a primary-outcome event occurred in 7 participants (10%; 95% credible interval, 0 to 38), 4 (6%; 95% credible interval, 0 to 25), 1 (1%; post hoc credible interval, 0 to 6), and 0 (0%; post hoc credible interval, 0 to 8), respectively. During weeks 1 through 12, adverse events, including injection-site reactions, pyrexia, fatigue, and increased alanine aminotransferase levels, were more common with bepirovirsen (groups 1, 2, and 3) than with placebo (group 4).ConclusionsIn this phase 2b trial, bepirovirsen at a dose of 300 mg per week for 24 weeks resulted in sustained HBsAg and HBV DNA loss in 9 to 10% of participants with chronic HBV infection. Larger and longer trials are required to assess the efficacy and safety of bepirovirsen. (Funded by GSK; B-Clear ClinicalTrials.gov number, NCT04449029.)

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

Use of serum Golgi protein 73 for screening chronic hepatitis B virus infection patients needing antiviral therapy in the community.

The Effect of Paracetamol and Codeine Analgesic Combination on Serum Alanine Aminotransferase and Aspartate Aminotransferase Levels in Male Wistar Rats

BACKGROUND: Paracetamol and codeine are classified as different analgesic categories with different mechanism. The combination of both paracetamol and codeine as an analgesic works synergistically and may give better outcome in pain management in moderate-to-severe degree. However, the combination of those analgesics might bring side effects in liver. AIM: This study was to determine the effect of analgesic combination of paracetamol and codeine on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels of Wistar rats. METHODS: This study was an experimental study with a pre- and post-test control group design. The study objects were 20 male Wistar rats with certain criteria, which were randomly divided into four groups, that is, control group (C), group with paracetamol therapy alone (32 mg/kgBW), group with codeine therapy alone (1.9 mg/kgBW), and group with combination therapy of paracetamol (32 mg/kgBW) and codeine (1.9 mg/kgBW). Analgesic drugs were administered orally 4 times a day for 28 days with gastric sonde. On the 29th day, blood samples were collected through retro-orbital blood vessels for measuring ALT and AST levels. Statistical tests used were one-way ANOVA and Kruskal–Wallis test. RESULTS: They showed that there were no differences in ALT levels between C, P1, P2, and P3 in both at baseline and post-treatment. However, there were significant increases in ALT levels after treatment in comparison to baseline in the control group (C) (87.2 ± 18.43 vs. 40.6 ± 5.02; p &lt; 0.05), P1 (78.9 ± 8.52 vs. 44.4 ± 1.14; p &lt; 0.05), and P3 (86.4 ± 17.22 vs. 44.0 ± 1.00; p &lt; 0.05). There were no differences in AST levels between C, P1, P2, and P3 at baseline, but there were significantly higher AST levels in P1, P2, and P3 in comparison to control at post-treatment (p &lt; 0.05). There were no differences in AST levels between P1, P2, and P3 at post-treatment (p &gt; 0.05). There were also significant increases in AST levels after treatment in comparison to baseline in the control group (C) (93.9 ± 1.10 vs. 37.7 ± 1.69; p &lt; 0.05), P1 (97.6 ± 1.85 vs. 36.3 ± 1.22; p &lt; 0.05), P2 (97.6 ± 1.70 vs. 37.7 ± 1.73; p &lt; 0.05), and P3 (98.6 ± 0.79 vs. 36.4 ± 1.20; p &lt; 0.05). CONCLUSION: The combination therapy of paracetamol and codeine might not bring difference in serum ALT and AST levels compared to paracetamol therapy alone or codeine therapy alone.