Baseline Alanine Aminotransferase Research Articles

Improvement of hepatic fibrosis after tenofovir disoproxil fumarate switching to tenofovir alafenamide for three years.

Both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line treatments for chronic hepatitis B (CHB). We have showed switching from TDF to TAF for 96 weeks resulted in further alanine aminotransferase (ALT) improvement, but data remain lacking on the long-term benefits of TDF switching to TAF on hepatic fibrosis. To assess the benefits of TDF switching to TAF for 3 years on ALT, aspartate aminotransferase (AST), and hepatic fibrosis improvement in patients with CHB. A single center retrospective study on 53 patients with CHB who were initially treated with TDF, then switched to TAF to determine dynamic patterns of ALT, AST, AST to platelet ratio index (APRI), fibrosis-4 (FIB-4) scores, and shear wave elastography (SWE) reading improvement at switching week 144, and the associated factors. The mean age was 55 (28-80); 45.3%, males; 15.1%, clinical cirrhosis; mean baseline ALT, 24.8; AST, 25.7 U/L; APRI, 0.37; and FIB-4, 1.66. After 144 weeks TDF switching to TAF, mean ALT and AST were reduced to 19.7 and 21, respectively. From baseline to switching week 144, the rates of ALT and AST < 35 (male)/25 (female) and < 30 (male)/19 (female) were persistently increased; hepatic fibrosis was also improved by APRI < 0.5, from 79.2% to 96.2%; FIB-4 < 1.45, from 52.8% to 58.5%, respectively; mean APRI was reduced to 0.27; FIB-4, to 1.38; and mean SWE reading, from 7.05 to 6.30 kPa after a mean of 109 weeks switching. The renal function was stable and the frequency of patients with glomerular filtration rate > 60 mL/min was increased from 86.5% at baseline to 88.2% at switching week 144. Our data confirmed that switching from TDF to TAF for 3 years results in not only persistent ALT/AST improvement, but also hepatic fibrosis improvement by APRI, FIB-4 scores, as well as SWE reading, the important clinical benefits of long-term hepatitis B virus antiviral treatment with TAF.

Incidence, clinical classification and risk factors of cyclosporin A-induced liver injury in allogeneic haematopoietic stem cell transplant recipients.

There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI. Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included. Patient information was collected to assess suspicious CILI by the Roussel Uclaf causality assessment method (RUCAM) scale. We evaluated the pattern and severity of CILI. The independent risk factors of CILI were identified by multivariable logistic regression. A total of 216 allogeneic HSCT (allo-HSCT) recipients were included in this study. The incidence of CILI was 15.3% (95% confidence interval [CI]: 10.4%-20.1%). Among these cases, 84.8% displayed a hepatocellular pattern, and 90.9% of CILI was of mild severity. Baseline alanine aminotransferase (ALT) level (OR = 1.030, 95% CI: 1.008-1.053, P = .008) and trough concentration level of CsA (OR = 1.007, 95% CI: 1.002-1.012, P = .009) were identified as independent risk factors for CILI. The incidence of CILI in allo-HSCT recipients is notably high. Recipients with elevated baseline ALT levels and higher exposure to CsA are more susceptible to developing CILI.

PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study.

The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.

Kinetics of the hepatitis B core-related antigen and treatment responses in chronic hepatitis B patients treated with tenofovir alafenamide.

An association between hepatitis B core-related antigen (HBcrAg) kinetics and hepatocarcinogenesis during nucleoside (t)id analog (NA) treatment has recently been reported. HBcrAg kinetics and factors associated with HBcrAg response during tenofovir alafenamide (TAF) administration remain unclear. In this multicenter retrospective study, we aimed to clarify the efficacy and safety of TAF in treatment-naïve patients with chronic hepatitis B, focusing on the reduction in HBcrAg levels. Patients were treated with TAF monotherapy for 96weeks, and the kinetics of HBcrAg during treatment and the factors associated with HBcrAg response (defined as a change in HBcrAg of -1logIU/mL from baseline) were evaluated. The study population comprised 241 patients, 36.9% of whom were HBeAg-positive. The median baseline HBcrAg level was 4.7logIU/mL. The median change in HBcrAg from baseline was -1.1logIU/mL at 96weeks after treatment. The HBcrAg response rate at 96weeks was 56.6% (43/76). Multivariate analysis revealed high alanine transaminase level as an independent baseline factor associated with HBcrAg response at 96weeks of treatment (p=4.53×10-6). No correlation was found between the HBcrAg and hepatitis B surface antigen kinetics in patients treated with TAF monotherapy. In TAF monotherapy for patients with chronic hepatitis B, HBcrAg levels were significantly decreased and baseline alanine transaminase level is an important factor associated with HBcrAg reduction. As no correlation was found between HBcrAg and reduced hepatitis B surface antigen levels in this study, HBcrAg kinetics in addition to hepatitis B surface antigen may need to be monitored during TAF treatment.

Effect of Low dose Isotretinoin on Lipid Profile and Liver enzymes in Acne Patients: A Cross Sectional Study

Introduction: Oral isotretinoin remains the most clinically effective anti-acne therapy. However, a myriad of adverse effects are associated with isotretinoin use. Elevated liver enzymes and an altered lipid profile are well documented side effects of prolonged oral isotretinoin usage. Objectives: To assess the alteration in liver enzymes and lipid profiles of acne patients on isotretinoin therapy. Materials and Methods: The current prospective hospital based study, was carried out from September 2022 to December 2023, and included 150 patients with acne vulgaris on isotretinoin therapy. All consenting patients were then subjected to a detailed history and clinical examination. Subsequently, baseline Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Triglyceride (TG), Low density Lipoprotein (LDL), and High density Lipoprotein levels (HDL) levels were measured. Patients were then started on oral isotretinoin therapy at conventional dosages. Levels of ALT, AST, TG, LDL and HDL were repeated at 3- month and 6- month follow-up visits. A self-designed proforma was used to collect all relevant data. The collected data was analyzed as per standard statistical protocol. Repeated measures analysis of variance was used to compare means between 3 groups (baseline, 3-month, and 6-month values). Results with a p&lt;.05 were considered statistically significant. Results: The mean age of patients was 22.31(±SD 4.44) years. Females comprised the majority of our study subjects (n = 95; 63.33%). Levels of Alanine (F2,226=30.73, p&lt;.0005) and Aspartate transaminase (F2,232=13.13, p&lt;.0005) were increased significantly at 3 and 6 month follow up visits. Levels of TG were, also, increased significantly at follow up visits (F2,239=14.45, p&lt;.0005). Similarly, levels of low density lipoprotein increased significantly when compared to baseline levels (F1,215=38.43, p&lt;.0005). High density lipoprotein levels were decreased significantly when compared to baseline levels (F1,209=105.83, p&lt;.0005). Conclusion: Our study has highlighted the significant alterations that occur in liver function tests and lipid profiles in patients on isotretinoin therapy.

Abstract MP25: Effect of Marine Omega-3 Fatty Acids on Risk of Incident Cardiovascular Disease Among Individuals With Non-Alcoholic Fatty Liver Disease: Secondary Analysis of a Randomized Clinical Trial

Background: Individuals with non-alcoholic fatty liver disease (NAFLD) are at increased risk for developing cardiovascular disease (CVD), often attributed to adverse metabolic derangements such as insulin resistance and elevated triglycerides. Marine omega-3 (n-3) fatty acids may partially ameliorate these metabolic consequences. Whether supplementation with n-3 fatty acids can reduce the risk of CVD in NAFLD remains unknown. Aims: To investigate the association between a NAFLD phenotype and incident CVD as well as assess whether randomization to n-3 fatty acids can modify this risk. Methods: Among 16,824 participants from the Vitamin D and Omega-3 Trial (VITAL; NCT01169259; a 2x2 factorial randomized trial of 1 g/d of EPA+DHA or 2000 IU/d of vitamin D 3 ) who provided baseline blood samples, we measured liver function tests. NAFLD was defined as baseline alanine aminotransferase (ALT)&gt;40 U/L and/or aspartate aminotransferase (AST)&gt;35 U/L, per guidance from the American Association for the Study of Liver Diseases. Incident CVD was a composite of myocardial infarction (MI), stroke, and CVD death. Multivariable-adjusted Cox models (adjusted for demographics, cardiovascular risk factors, and treatment assignment) were used to estimate hazard ratios (aHRs) and 95% confidence intervals (CI) for NAFLD with incident CVD. Effect of randomization to n-3 fatty acids was assessed among individuals with and without NAFLD. Results: We identified 2,495 participants with NAFLD at baseline, who tended to be younger, male, and non-White compared to individuals without NAFLD. After a median follow-up of 5.3 years, 522 CVD events were ascertained, with 101 occurring among those with NAFLD. Compared to individuals without NAFLD, those with NAFLD were at higher risk of developing CVD, aHR (95%CI): 1.48 (1.19, 1.84), P =0.0004. This association was predominantly driven by a higher incidence of total stroke, 1.53 (1.08, 2.17), P =0.02, compared with MI, 1.15 (0.81, 1.64), P =0.43. Randomization to n-3 fatty acids did not significantly reduce CVD incidence among individuals with, 1.13 (0.77, 1.68) or without NAFLD, 1.02 (0.85,1.24), P interaction =0.70. Conclusion: In a large primary prevention trial of older individuals, NAFLD was associated with a higher risk of CVD, particularly stroke. Randomization to n-3 fatty acids did not significantly reduce CVD outcomes in this high-risk population.

Liver toxicity in oncology trials and beyond: a simplified concept for management of hepatocellular drug-induced liver injury in patients with abnormal baseline liver tests

ABSTRACT Background Management of side effects in clinical trials has to balance generation of meaningful data with risk for patients. A toxicity area requiring detailed management guidelines is drug-induced liver injury (DILI). In oncology trials, patients are often included despite baseline liver test abnormalities, for whom there is no consensus yet on levels of liver test changes that should trigger action, such as drug interruption or discontinuation. Methods We provide an innovative approach to manage hepatocellular DILI in oncology trials for patients with abnormal baseline alanine aminotransferase (ALT) levels. The algorithm proposed is based on mathematical derivation of action thresholds from those generally accepted for patients with normal baselines. Results The resulting algorithm is grouped by level of baseline abnormality and avoids calculation of baseline multiples. Suggested layered action levels are 4, 6, and 11 × Upper Limit of Normal (ULN) for patients with baseline ALT between 1.5 and 3 × ULN, and 6, 8, and 12 × ULN for patients with baseline ALT between 3 and 5 × ULN, respectively. Conclusions Our concept and resulting algorithm are consistent, transparent, and easy to follow, and the method for derivation from consensus-based thresholds may also be applicable to other drug toxicity areas.

Oral Insulin Alleviates Liver Fibrosis and Reduces Liver Steatosis in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes: Results of Phase II Randomized, Placebo-controlled Feasibility Clinical Trial

Background and AimsMetabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of NAFLD and a leading cause of end-stage liver disease and transplantation. Insulin resistance and inflammation underlie the pathogenesis of the disease. MethodsThis double-blind, randomized, placebo-controlled, multicenter feasibility clinical trial aimed to determine the safety of ORMD-0801 in patients with MASH and T2DM. Patients were treated twice daily for 12 weeks with an 8 mg insulin (n=21) or placebo (n=11) capsule. Safety was monitored throughout the study. MRI-PDFF assessed liver fat content, and Fibroscan® measured liver fibrosis and steatosis levels at screening and after 12 weeks of treatment. ResultsNo severe drug-related adverse events were reported during the study. After 12 weeks of treatment, mean percent reductions in whole-liver (-11.2% vs. -6.5%, respectively) and liver segment 3 (-11.7% vs. +0.1%, respectively) fat content was higher in the insulin than in the placebo arm. Patients receiving insulin showed a median -1.2 kPa and -21.0 dB/m reduction from baseline fibrosis and steatosis levels, respectively, while placebo-treated patients showed median increases of 0.3 kPa and 13.0 dB/m, respectively. At Week 12, oral insulin was associated with a mean of 0.27% reduction and placebo with a 0.23% increase from baseline HbA1c levels. Mean percent changes from baseline alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were -10% and -0.8%, respectively, in the oral insulin and 3.0% and 13.4%, in the placebo arm. ConclusionThe results of this feasibility study support the safety and potential therapeutic effect of orally delivered insulin on liver fibrosis, fat accumulation, and inflammatory processes (NIH Clinical Trials No. NCT04618744).

Efficacy of pegylated interferon α-2b plus entecavir therapy and predictors of treatment success in children with chronic hepatitis B.

Interferon therapy, used in the treatment of chronic hepatitis B (CHB), is one of the means by which patients can achieve a functional cure. Pegylated interferon is currently used in the treatment of CHB. There are two main types of pegylated interferon: α-2b and α-2a. This study explored the efficacy, safety, and predictors of treatment response for α-2b plus entecavir among children in a real-world setting. The study included 76 patients aged 3-18 years, all of whom were treated with interferon α-2b plus entecavir. The mean duration of treatment was 401.99 days, and 31.6% (24/76) of patients achieved HBsAg clearance. Competing risk model analyses showed that children with baseline HBsAg <1500 IU/mL (subdistribution hazard ratio [sHR]=2.643, P=0.022) and a higher baseline alanine aminotransferase (ALT) level (sHR=1.005, P=0.000) had a higher probability of achieving HBsAg clearance during treatment. Conversely, children with a higher hepatitis B virus loading level (sHR=0.835, P=0.043) and age ≥10 years (sHR=0.243, P=0.002) had a lower probability of achieving HBsAg clearance during treatment. A decrease of >1 log10 in HBsAg level (sHR=3.479, P=0.001) at 12 weeks of treatment was associated with a higher probability of achieving surface antigen clearance. These results indicated that interferon plus entecavir therapy is a promising means of achieving HBsAg clearance in children with CHB. Moreover, HBsAg, ALT, virus loading, and age are indicators of treatment success probability.

Modelling HDV kinetics under the entry inhibitor bulevirtide suggests the existence of two HDV-infected cell populations

Bulevirtide (BLV) was approved for the treatment of compensated chronic hepatitis D virus (HDV) infection in Europe in 2020. However, research into the effects of the entry inhibitor BLV on HDV-host dynamics is in its infancy. Eighteen patients with HDV under nucleos(t)ide analogue treatment for hepatitis B, with compensated cirrhosis and clinically significant portal hypertension, received BLV 2mg/day. HDV RNA, alanine aminotransferase (ALT), and hepatitis B surface antigen (HBsAg) were measured at baseline, weeks 4, 8 and every 8 weeks thereafter. A mathematical model was developed to account for HDV, HBsAg and ALT dynamics during BLV treatment. Median baseline HDV RNA, HBsAg, and ALT were 4.9 log IU/ml [IQR: 4.4-5.8], 3.7 log IU/ml [IQR: 3.4-3.9] and 106 U/L [IQR: 81-142], respectively. During therapy, patients fit into four main HDV kinetic patterns: monophasic (n= 2), biphasic (n= 10), flat-partial response (n= 4), and non-responder (n= 2). ALT normalization was achieved in 14 (78%) patients at a median of 8 weeks (range: 4-16). HBsAg remained at pre-treatment levels. Assuming that BLV completely (∼100%) blocks HDV entry, modeling indicated that two HDV-infected cell populations exist: fast HDV clearing (median t1/2= 13 days) and slow HDV clearing (median t1/2= 44 days), where the slow HDV-clearing population consisted of ∼1% of total HDV-infected cells, which could explain why most patients exhibited a non-monophasic pattern of HDV decline. Moreover, modeling explained ALT normalization without a change in HBsAg based on a non-cytolytic loss of HDV from infected cells, resulting in HDV-free HBsAg-producing cells that release ALT upon death at a substantially lower rate compared to HDV-infected cells. The entry inhibitor BLV provides a unique opportunity to understand HDV, HBsAg, ALT, and host dynamics. Mathematical modeling of hepatitis D virus (HDV) treatment with the entry inhibitor bulevirtide (BLV) provides a novel window into the dynamics of HDV RNA and alanine aminotransferase. Kinetic data from patients treated with BLV monotherapy can be explained by hepatocyte populations with different basal HDV clearance rates and non-cytolytic clearance of infected cells. While further studies are needed to test and refine the kinetic characterization described here, this study provides a new perspective on viral dynamics, which could inform evolving treatment strategies for HDV.

Air pollution impede ALT normalization in chronic hepatitis B patients treated with nucleotide/nucleoside analogues.

Biochemical response is an important prognostic indicator in chronic hepatitis B (CHB) patients receiving nucleotide/nucleoside analogues (NAs). However, the effects of air pollution in alanine aminotransferase (ALT) normalization remain elusive. This longitudinal study recruited 80 hepatitis B e antigen-negative CHB patients who received NAs. ALT levels were measured during the first year of anti-hepatitis B virus therapy. Normal ALT levels were defined as <19 U/L for females and <30 U/L for males, and the risk factors associated with ALT abnormalities were analyzed. The daily estimations of air pollutants (particulate matter ≤2.5 µm in diameter (PM2.5), nitrogen dioxide, ozone (O3), and benzene) were aggregated into the mean estimation for the previous month based on the date of recruitment (baseline) and 1 year later. Sixteen patients (20.0%) had a baseline ALT > 40 U/L; overall, 41 (51.6%) had an abnormal ALT (≥19 U/L for females and ≥ 30 U/L for males). After 1 year of NA therapy, 75 patients (93.8%) had undetectable hepatitis B virus DNA levels. Mean post-treatment ALT levels were significantly lower than mean pretreatment levels (21.3 vs 30.0 U/L, respectively; P < .001). The proportion of patients with a normal ALT was also significantly higher after versus before treatment (71.2% vs 51.2%, respectively; P = .001). The strongest factors associated with ALT abnormality after 1 year of NA treatment were body mass index (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.05-1.54; P = .01) and ozone level (OR, 1.11; 95% CI, 1.02-1.22; P = .02). Among hepatitis B e antigen-negative CHB patients with relatively low viral loads, 1 year of NA treatment improved ALT levels after the adjustment for confounding factors and increased the proportion of patients with normal ALT levels. Air pollution affects the efficacy of ALT normalization.

Symptoms of Liver Disease During Tenofovir Therapy With or Without Peginterferon: Results from the Hepatitis B Research Network Immune Active Trial.

Evaluate patient-reported liver symptoms during treatment for chronic hepatitis B viral (HBV) infection and associations between changes in symptoms and levels of alanine aminotransferase (ALT) and viral markers. Data from 200 participants in the Hepatitis B Research Network Immune Active Trial who completed symptom assessments were analyzed. Patients were treated with tenofovir, with or without peginterferon (TDF + PegIFN vs. TDF alone) for 192weeks. Participants completed a Symptom Checklist at baseline and every 4-12weeks. A total symptom score was created, ranging from 0 (none) to 40 (severe). The SF-36 was completed every 48weeks. Associations of symptom scores with ALT and viral markers were evaluated at baseline and end of treatment. Participants were 65% male, 83% Asian, with a mean age of 42. Baseline symptoms were mild (median = 2, range 0-25) and associated with baseline ALT, HBV DNA levels and HBeAg + status. Patients on TDF alone experienced a more rapid and greater improvement in symptoms, but by week 192, symptom improvement was similar in both groups (54% vs 36%). Symptom improvements correlated with ALT and HBV DNA, most markedly among those with symptoms at baseline. Most patients (4 out of 6) who achieved HBsAg loss experienced symptom improvements. Overall, SF-36 scores did not change with treatment. Reduction in ALT and HBV DNA levels with therapy are associated with significant improvement in liver symptoms such as fatigue and pain over the liver, especially among those with higher ALT, HBV DNA, symptoms and HBeAg + status prior to treatment.

One-Year Survival for Developing Acute Kidney Injury in Adult Patients with AMI Cardiogenic Shock Receiving Venoarterial Extracorporeal Membrane Oxygenation.

The incidence of cardiogenic shock cases treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support has been on the rise. Acute kidney injury (AKI) is a significant complication of cardiogenic shock and a frequent serious complication in patients requiring ECMO-supported therapy. AKI is strongly associated with unfavorable patient prognosis. However, there is a paucity of data on the influence of AKI on the prognosis of patients with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who are receiving ECMO support, particularly with regard to long-term outcomes. This retrospective observational study included 103 patients in the People's Hospital of Guangxi Zhuang Autonomous Region from January 2017 and June 2022. AKI was defined according to Kidney Disease Improving Global Outcome (KDIGO) criteria. Cox regression and logistic regression were used to identify risk factors. In this study, the incidence of AKI was 63.11%, with AKI stage 1, 2, and 3 accounting for 21.36%, 12.62%, and 29.13%, respectively. Patients with severe AKI had significantly higher in-hospital mortality (43.33% vs 27.40%, P < 0.001), 30-day mortality (60.00% vs 31.51%, P = 0.001), and 1-year mortality (63.67% vs 34.25%, P<0.001) than those without severe AKI. Furthermore, severe AKI significantly increased the risk of one-year mortality (HR 10.816, CI 3.118-37.512, P<0.001). Baseline serum creatinine, baseline platelet, and active cardiopulmonary resuscitation were independent predictors of one-year mortality. In addition, baseline white blood cell count, baseline aspartate aminotransferase, baseline alanine aminotransferase (ALT), baseline serum creatinine, preoperative lactate, and postoperative mean arterial pressure were independent risk factors of severe AKI during hospitalization. In patients with AMI-CS receiving ECMO support, AKI is highly prevalent. Development of severe AKI significantly increased the risk of one-year mortality.

Evaluation of alanine aminotransferase responses in chronic hepatitis B patients using entecavir or tenofovir disoproxil fumarate

Background/Aim: An estimated 300 million individuals worldwide live with hepatitis B virus (HBV) infection. Alanine aminotransferase (ALT) levels, which indicate liver damage when elevated, are among the crucial laboratory parameters frequently monitored in the follow-up of chronic hepatitis B patients. The primary objectives of antiviral treatment are to reduce liver inflammation and prevent the development of hepatocellular carcinoma or cirrhosis by inhibiting HBV replication. This study evaluated ALT responses and identified factors influencing patient responses following initiating entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment. Methods: This retrospective cohort study collected data from treatment-naive and treatment-experienced patients with elevated ALT levels who received either ETV (0.5 or 1 mg per day) or TDF (245 mg per day) treatment between 2008 and 2018. Pregnant women and patients under 18 were excluded from the study. Elevated ALT levels were defined as greater than 35 IU/L for men and 25 IU/L for women. All patients underwent examinations for ALT, HBV DNA levels, HBeAg, and antiHBe at baseline and every 3–6 months. ALT levels of the patients were monitored for 60 months, and the presence of fatty liver was also documented. Results: Our study comprised 192 patients with a mean age of 53.7 (13.42) years. The majority of patients, 130 (67.7%), were male. Of these, 97 (50.5%) started ETV treatment, while 95 (49.5%) began TDF treatment. The median baseline ALT levels of the patients were 68 (44–133.5) IU/L, and the median ALT levels at the 60th month were 24 (18–32) IU/L. The median initial HBV DNA level was 114,282 (267.5–5,029,875) IU/mL, and the median HBV DNA levels from the 6th month onwards were 0 (0–0). ALT normalization was observed in 44.8% of men and 28.1% of women at 3 months, which was statistically significant (P=0.034). Normalization rates by gender remained consistent in all other months. No significant differences were noted in this regard. ALT normalization rates were 58.5% at the 6th month and 74.7% at the 24th month in the ETV group, significantly higher than in the TDF group (P=0.01, P=0.02, respectively). In patients with fatty liver, ALT normalization rates were significantly lower at 6, 12, 24, and 48 months than those without fatty liver (P=0.01, P=0.01, P=0.009, P=0.002, respectively). Conclusion: Although ALT responses to ETV treatment were more pronounced in specific months, both drugs demonstrated overall efficacy. ALT levels in patients with fatty liver remained elevated despite antiviral treatment. Therefore, patients with chronic hepatitis B and fatty liver may require additional support beyond antiviral therapy, including metabolic, nutritional, and lifestyle recommendations.

The impact of bariatric surgery on liver enzymes in people with obesity: A 5-year observational study

Background and purposeNon-alcoholic fatty liver disease (NAFLD) has increasing worldwide prevalence, fuelled by rising obesity rates, and weight reduction is the mainstay of its management. We sought to study the effect of bariatric surgery, the most effective long-term treatment for obesity and associated metabolic disorders, on liver function in people with obesity. MethodsWe performed a retrospective longitudinal cohort study of 511 patients who had undergone bariatric surgery (71 sleeve gastrectomy and 440 gastric bypass) over 60 months of follow-up. Patients were stratified into groups based on their baseline alanine aminotransferase (ALT) into Group A (ALT < 40 U/L) and Group B (ALT > 40 U/L). Postoperative follow-up weight loss, liver function tests, HbA1c, blood pressure and lipid profiles were collected. FindingsBariatric surgery resulted in nadir total weight loss of 33.1% by 24 months (p < 0.001) with no significant difference between groups. In people with raised baseline ALT (Group B), ALT and gamma glutamyl transferase (GGT) levels decreased significantly by 4 months postoperatively (p < 0.001) and sustained over 60 months of follow-up. There was also significant and sustained reduction in HbA1c, blood pressure, total cholesterol, and non-HDL cholesterol overall with no differences between groups. ConclusionsBariatric surgery results in significant weight loss, improves liver function tests and metabolic outcomes in people with obesity. Bariatric surgery could be a therapeutic consideration for patients with NAFLD associated with severe obesity who have otherwise been unresponsive to conservative management.

Development of prediction model for alanine transaminase elevations during the first 6 months of conventional synthetic DMARD treatment

Frequent laboratory monitoring is recommended for early identification of toxicity when initiating conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). We aimed at developing a risk prediction model to individualize laboratory testing at csDMARD initiation. We identified inflammatory joint disease patients (N = 1196) initiating a csDMARD in Turku University Hospital 2013–2019. Baseline and follow-up safety monitoring results were drawn from electronic health records. For rheumatoid arthritis patients, diagnoses and csDMARD initiation/cessation dates were manually confirmed. Primary endpoint was alanine transaminase (ALT) elevation of more than twice the upper limit of normal (ULN) within 6 months after treatment initiation. Computational models for predicting incident ALT elevations were developed using Lasso Cox proportional hazards regression with stable iterative variable selection (SIVS) and were internally validated against a randomly selected test cohort (1/3 of the data) that was not used for training the models. Primary endpoint was reached in 82 patients (6.9%). Among baseline variables, Lasso model with SIVS predicted subsequent ALT elevations of > 2 × ULN using higher ALT, csDMARD other than methotrexate or sulfasalazine and psoriatic arthritis diagnosis as important predictors, with a concordance index of 0.71 in the test cohort. Respectively, at first follow-up, in addition to baseline ALT and psoriatic arthritis diagnosis, also ALT change from baseline was identified as an important predictor resulting in a test concordance index of 0.72. Our computational model predicts ALT elevations after the first follow-up test with good accuracy and can help in optimizing individual testing frequency.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load &lt; 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (−0.36, p &lt; 0.0001) than in the RPV cohort (−0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT &gt; 40 IU/L experienced a significant decline (−14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Pretreatment Predictors Associated with Improvement in Hepatitis C Virus Related Decompensated Cirrhosis after Direct-Acting Antiviral Therapy

Background and Aim: The availability of hepatitis C virus (HCV) direct-acting antivirals (DAAs) has led to a paradigm change in the care of HCV related decompensated cirrhosis. Achieving a stained virologic response (SVR) is associated with considerable improvements in both Child-Turcotte- Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores in decompensated cirrhosis. We aimed to evaluate the pretreatment predictors associated with improvement in CTP B cirrhosis after DAAs and evaluate the efficacy and safety of DAAs in these patients.&#x0D; Patients and Methods: A prospective study conducted on 213 decompensated patients (CTP B, 134 received DAAs for 24 weeks and 79 for 12 weeks). Clinical and laboratory data obtained at baseline, during treatment, 12 weeks after end of treatment (EOT), 36 weeks after treatment start, and 24 weeks after SVR.&#x0D; Results: We had 48.4 % and 55.9 % had improved to CTP A at 36 weeks of treatment start and 24 weeks after SVR respectively. A high baseline BE3A score (which includes Body mass index (BMI), Encephalopathy, Ascites, Alanine aminotransferase (ALT) and Albumin) was the significant predictor of attaining CTP A at 36 weeks of treatment start, while high baseline ALT (&gt; 60 IU/L) was the significant predictor of attaining CTP A at 24 weeks after SVR. SVR 12 achieved in 97.3% and DAAs were safe with mild tolerable adverse events.&#x0D; Conclusion: High baseline ALT and BE3A score were the significant predictors of hepatic improvement from CTP B to CTP A after DAAs. HCV DAAs were safe and effective with high SVR rates (97.3%) in decompensated cirrhosis.

Effects of sodium glucose cotransporter 2 inhibitors and pioglitazone on FIB-4 index in metabolic-associated fatty liver disease.

The antidiabetic drugs sodium glucose cotransporter 2 inhibitors (SGLT2is) and thiazolidinediones have beneficial effects on the liver dysfunction of patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). We aimed to determine the efficacy of these drugs for the treatment of liver disease in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and T2DM. We undertook a retrospective study of 568 patients with MAFLD and T2DM. Of these, 210 were treating their T2DM with SGLT2is (n=95), 86 with pioglitazone (PIO), and 29 with both. The primary outcome was the change in Fibrosis-4 (FIB-4) index between baseline and 96weeks. At 96weeks, the mean FIB-4 index had significantly decreased (from 1.79±1.10-1.56±0.75) in the SGLT2i group, but not in the PIO group. The aspartate aminotransferase to platelet ratio index, serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c, and fasting blood sugar significantly decreased in both groups (ALT: SGLT2i group, -17±3IU/L; PIO group, -14±3IU/L). The bodyweight of the SGLT2i group decreased, but that of the PIO group increased (-3.2kg and +1.7kg, respectively). When the participants were allocated to two groups according to their baseline ALT (>30IU/L), FIB-4 index significantly decreased in both groups. In patients taking pioglitazone, the addition of SGLT2i improved liver enzymes but not FIB-4 index for 96weeks. Treatment with SGLT2i causes a larger improvement in FIB-4 index than PIO in patients with MAFLD over 96weeks.