Alanine Aminotransferase Levels In Patients Research Articles

Network meta-analysis of different liver protective drugs in the treatment of drug-induced liver injury.

Currently, drug-induced liver injury (DILI) has become one of those public issues in society, which has added a huge burden to both the individuals and the society. In the current clinical stage, there are numerous drugs developed to treat this disease, and different drug treatment measures have been proven to achieve certain clinical efficacy in the corresponding randomized controlled trials. However, there are still many therapeutic drugs that have not been directly compared and studied. Therefore, it is difficult to directly compare the effectiveness and safety of various strategies for the treatment of DILI. In this regard, the present study collected the therapeutic efficacy of diverse treatments in DILI in recent years through network meta-analysis, evaluated and screened the existing optimal clinical therapeutic plan, and helped physicians formulate clinical therapeutic plans. Databases, including the Chinese Journal Full-text Database, Wanfang Data Journal Paper Resources (Wangfang), VIP Chinese Science and Technology Journal Full-text Database, The Cochrane Library, PubMed, and EMBASE, were searched using keywords from inception to January 2023. Eligible randomized controlled trials were selected in line with eligibility criteria, and mesh meta-analysis of binary variables was carried out using Stata 16 software. In combination with alanine aminotransferase, aspartate aminotransferase, and total bilirubin, MI may be the intervention measure for minimizing alanine aminotransferase levels in patients after treatment. Besides, compound glycyrrhizin may be the intervention for minimizing aspartate aminotransferase levels in patients after treatment, and polyene phosphatidylcholine may be the intervention for minimizing total bilirubin levels in patients after treatment. Placebo is the potential intervention that has the least adverse reactions post-treatment, and RT has the second least adverse reactions. Moreover, hepatocyte growth-promoting factors may be the most effective intervention after treatment. To sum up, the present work compared the clinical effects of 13 liver protective drugs through meta-analysis and provided a systematic understanding of commonly used drugs for the treatment of DILI in clinical practice.

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.

Abnormal alanine aminotransferase levels in patients with moderate or severe ovarian hyperstimulation result in an increased risk of obstetric complications.

To explore the effect of abnormally elevated serum alanine aminotransferase (ALT) on pregnancy outcomes in patients with moderate and severe ovarian hyperstimulation syndrome (OHSS) at disease onset. This was a single-center retrospective cohort study conducted between January 1, 2014 and October 31, 2021. A total of 3550 fresh in vitro fertilization/intracytoplasmic sperm injection embryo transfer cycles were included, using Golan's three-degree, five-level classification to diagnose patients with OHSS. According to the patient's ALT level after diagnosis of OHSS, 123 (3.46%) patients with moderate-to-severe OHSS were divided into two groups. A control group included 3427 (96.54%) non-OHSS patients, and 91 (2.56%) abnormal ALT patients were matched with the control group for propensity scores. There was no difference in baseline data between the abnormal ALT and matched control groups. The incidence of obstetric complications was significantly higher in the abnormal ALT group than in the matched control group (P< 0.05). After adjusting for confounding factors, the incidence of obstetric complications in the abnormal ALT group was still higher than that in the normal ALT group (P< 0.05). In patients with moderate and severe OHSS, higher ALT levels resulted in an increased risk of obstetric and neonatal complications.

Impact of l-Carnitine Supplementation on Liver Enzyme Normalization in Patients with Chronic Liver Disease: A Meta-Analysis of Randomized Trials.

The effectiveness of l-carnitine in chronic liver disease remains controversial. We conducted this meta-analysis to assess the efficacy of various forms of l-carnitine in the treatment of chronic liver disease. Methods: We searched the Cochrane Library, EMBASE, KMBASE, and Medline databases for all relevant studies published until April 2022 that examined the ability of l-carnitine or its derivatives to normalize liver enzymes in patients with chronic liver disease. We performed meta-analyses of the proportion of patients with alanine aminotransferase (ALT) normalization and post-treatment serum aspartate aminotransferase (AST) and ALT levels. A random effects model was used for meta-analyses. Results: Fourteen randomized controlled trials (1217 patients) were included in this meta-analysis. The proportion of patients in whom ALT normalized was higher in the carnitine-orotate treatment group than in the control group (pooled odds ratio (OR), 95% confidence interval (CI) = 4.61 (1.48–14.39)). The proportion of patients in whom ALT normalized was also higher among those who received the carnitine-orotate complex, a combination of carnitine-orotate, biphenyl dimethyl dicarboxylate, and other minor supplementary compounds than in those who did not without significant heterogeneity (pooled OR (95% CI) = 18.88 (7.70–46.27); df = 1; p = 0.51; I2 = 0%). l-carnitine supplementation effectively lowered serum ALT levels compared to controls (pooled mean difference (95% CI) = −11.99 (−22.48 to −1.49)). Conclusions: l-carnitine supplementation significantly lowered ALT and AST levels and normalized ALT levels in patients with chronic liver disease.

AACE2021-A-1084: Impact of Sodium Glucose Co-Transporter Type 2 Inhibitors on Alanine Amino-Transferase Levels of Patients with Type 2 Diabetes Having Nonalcoholic Fatty Liver Disease in Pakistani Population: A Retrospective Cohort Study

To determine the changes in ALT levels after initiation of SGLT2-i in T2DM patients aged 30 – 60 years having NAFLD over a period of one year presenting to an Endocrine outpatient clinic of tertiary care hospital in Karachi, accounting for dietary intake and physical activity level.

Flupirtine in the Management of Taxane-induced Pain in Cancer Patients.

Objectives:Paclitaxel and docetaxel are two commonly used chemotherapeutic agents in the treatment of various types of cancers. However, debilitating taxane-induced arthralgia and myalgia are among the most common adverse reactions associated with taxanes, which has greatly influenced medical practitioners. Most of the mild and moderate analgesics were found to be less effective in the management of taxane induced pain. So we used flupirtine, a non-opioid analgesic, in the treatment of taxane-induced pain.Materials and Methods:In this study, we analysed the baseline pain score and follow-up data of 60 patients receiving a taxane-based chemotherapy regimen. Baseline data of these study populations experiencing significant taxane-induced pain were compared with follow-up data after treating them with analgesic flupirtine (200 mg/day). The baseline and follow-up data representing pain were assessed with the help of the Visual Analogue Scale (VAS), and the quality of life was determined using the Brief Pain Inventory (BPI) scale questionnaire.Results:The mean baseline and follow-up VAS score was compared using paired sample t-test, which showed a significant reduction in taxane-induced pain after treatment with flupirtine (P < 0.001). Similarly, the mean BPI score representing the quality of life before and after treatment with flupirtine was compared, and a notable improvement in quality of life was seen after treatment with flupirtine. The mean and follow-up data of aspartate aminotransferase and alanine aminotransferase levels of patients were also compared to assess the adverse drug reaction profile of the drug, and the analyzed data was found to be statistically insignificant (no significant liver toxicity) which indicates that drug can be used effectively for a period of <2 weeks.Conclusion:We believe that flupirtine can be used as an effective analgesic in dire situations where patients require opioid analgesics for the management of taxane-induced pain, provided that the drug is given for <2 weeks to avoid drug-related hepatotoxicity.

What is the influence of cinnamon supplementation on liver enzymes? A systematic review and meta-analysis of randomized controlled trials.

Existing evidence has uncovered the potential health benefits of cinnamon intake; however, its effect on liver function is unclear. Thus, the aim of this systematic review and meta-analysis was to examine the effect of cinnamon supplementation on liver enzymes. Relevant articles were identified through a systematic search in PubMed/Medline, Scopus, Web of Science, Cochrane Library, and Embase up to September 2020. All trials assessing the effect of oral cinnamon supplementation on serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in adults were included. The pooled effect sizes were obtained using the random-effects model and expressed as mean difference (MD) and 95% confidence intervals (CI). A total of seven original trials (nine treatment arms) involving a total of 256 subjects were included in the final analysis. The pooled analysis indicated that cinnamon supplementation had no significant effect on serum levels of ALT, AST, and ALP. However, there was a significant reduction in ALT levels in patients with type 2 diabetes (MD: -4.01 U/L; 95% CI: -6.86, -1.15) and in trials with low-dose supplementation (<1,500 mg/d), follow-up duration longer than 12 weeks, and in the elderly patients (aged>50 years). The beneficial effects of cinnamon intake were also shown in AST levels in patients with type 2 diabetes and trials with long-term follow-up (>12 weeks). Longer-term, oral cinnamon supplementation may improve serum levels of liver enzymes in patients with type 2 diabetes. Further high-quality studies are needed, especially in populations with abnormal liver enzyme levels, to firmly establish the clinical efficacy of cinnamon on liver function.

Assessment of Severity of Dengue Fever by Deranged Alanine Aminotransferase Levels.

IntroductionDengue fever (DF) is the most common arbovirus-related infection worldwide. Most of the dengue infections are asymptomatic. The clinical presentation of DF varies from mild febrile illness to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Both DHF and DSS are severe forms of illness and carry higher rates of mortality. Various clinical parameters are associated with severe DF. The objective of this study was to determine any relation between elevated alanine aminotransferase (ALT) levels at presentation and development of severe DF.MethodsThis cross-sectional study was carried out at a large tertiary care hospital in Rawalpindi, Pakistan. Over a period of six months, 65 dengue patients were enrolled and their ALT levels were recorded at presentation. All the patients were managed as per guidelines in a similar way, and clinical course was followed for the development of severe forms of DF, such as DHF and DSS.ResultsOut of total 65 patients, 45 (69.2%) were males and 20 (30.8%) were females. Classical DF was present in 18 (27.7%) patients, whereas 47 (72.3%) patients developed DHF or DSS. Patients with DF had a mean ALT level of 131.67 (±244.48) U/L at presentation, whereas patients with DHF and DSS had a mean ALT level of 228.15 (±467.88) U/L at presentation. The Mann-Whitney U test was applied to compare differences between ALT levels of both groups, and p value was found to be 0.018 (<0.05). Thus, it was concluded that there was a statistical difference between ALT levels of patients with simple DF and patients with DHF or DSS. ConclusionHigher serum levels of ALT at presentation can give a clue about possibility of progression to severe forms of DF (DHF and DSS). Therefore, patients with higher ALT at presentation should be prioritized and monitored more rigorously.

1105-P: The Effect of Canagliflozin on Alanine Aminotransferase (ALT) Levels: Data from the Association of British Clinical Diabetologists (ABCD) Nationwide Audit Programme

Background: Nonalcoholic fatty liver disease (NAFLD) is common amongst those with type 2 diabetes (T2DM). Alanine aminotransferase (ALT) is known to correlate with levels of liver inflammation and fibrosis. Recent data from our audit programme showed promising reductions in ALT with dapagliflozin. Our aim was to test the same hypothesis, that canagliflozin may improve ALT levels in patients with T2DM, therefore possibly providing benefit in NAFLD. Methods: Data were extracted from the ABCD nationwide audit programme and then stratified into 4 groups based on gender and elevated or normal baseline ALT levels using gender specific references ranges (Prati et al). Baseline and follow-up ALT measurements in the 12-month (6-18months) period were required as a minimum. Data were analysed using Stata 16. Results: 730 datasets were included with mean (±SD) age 61.3yrs (±10.8), 60.1% male, 76% Caucasian (where known), BMI 32.5kg/m2 (±6.5), baseline HbA1c 8.9% (±1.6%) and weight 97.6kg (±22.2) and were broadly similar across all 4 sub-groups. For the entire population, median ALT decreased by 3U/L (95% CI -2, -3; P&amp;lt;0.01). Both male and female subgroups with normal ALT at baseline showed no significant change in ALT. In those with raised ALT at baseline (female ≥19U/L; male ≥30U/L) a change in ALT of -8U/L (95% CI -6, -9U/L; P&amp;lt;0.001) in men and -4U/L in women (95% CI -2, -5; P&amp;lt;0.05). Kruskal-Wallis test confirmed the difference between all groups was significant to P&amp;lt;0.01. No statistically significant correlation was noted between change in weight and change in ALT, which may suggest a weight-loss independent mechanism. Conclusion: Our data show that ALT decreases with canagliflozin, similar to that demonstrated with dapagliflozin. This decrease is greatest in those with elevated baseline levels. Weight-loss is not a predictor of change in ALT suggesting a potential weight-loss independent mechanism. Disclosure T.S.J. Crabtree: None. S.M. Phillips: None. A. Evans: Other Relationship; Self; AstraZeneca. D.K. Sennik: Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. A. Rohilla: None. A. Bickerton: None. K.H. Darzy: None. P. Winocour: Advisory Panel; Self; AstraZeneca, Novo Nordisk A/S. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Sanofi. M.L. Cull: None. A. Strzelecka: None. R.P. Raghavan: Research Support; Self; Allergan plc. Speaker’s Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Napp Pharmaceuticals, Takeda UK. Other Relationship; Self; Napp Pharmaceuticals. I.W. Gallen: None. M. Yadagiri: None. R.E. Ryder: Consultant; Self; GI Dynamics Inc. Other Relationship; Self; Novo Nordisk A/S.

Correlations Between METAVIR Staging, the Viral Load and Alanine Aminotransferase Levels in Patients with Chronic Hepatitis C, Before and after 12 Weeks of Antiviral Treatment

The World Health Organization (WHO) estimates that 170 million individuals worldwide are infected with hepatitis C virus (HCV). The aim of study was to evaluate possible correlations between METAVIR staging, the viral loads and alanine aminotransferase (ALT) levels in patients with chronic hepatitis C, before and after 12 weeks of treatment with PegInterferon a2a/a2b and Ribavirin. 93 consecutive patients with hepatitis C, were included in this study. The parameters followed were age, sex, Metavir histologic staging at the start of the treatment, hepatitis C virus ribonucleic acid (HCV-RNA) and ALT at start and after 12 weeks of treatment, as well as alcohol intake. The study group was composed by 58 women and 35 men, with a mean age of 44.47 � 11.17 years. At the beginning of the treatment, the mean value of HCV-RNA was 1327163 � 145001 UI/mL, with a CI95%=1327163 � 287986.36 UI/mL, and the mean value for ALT was 112.7124 � 68.7403 U/l. After 12 weeks of therapy, significant differences were found concerning both HCV-RNA and ALT values. HCV-RNA lowered to a mean value of 457.3978 � 402.653 (p[0.0001), while ALT lowered to a mean value of 37.90 � 16.43U/l (p[0.0001). Neither the initial HCV-RNA nor ALT values had any correlations with the METAVIR histological staging of the fibrosis. Initial ALT was higher in those with alcohol intake (p=0.000048). The ALT values instead, after 3 months of treatment, decreased significantly (p[0.0001), did correlate with the METAVIR groups (p=0.0019). The evolutionary stage of fibrosis didn�t correlate with gender of the patients or initial values of the HCV-RNA or ALT. There was no correlation between the age/gender of the patients and the determined METAVIR score.

Seroprevalence of hepatitis B virus co-infection among HIV-1-positive patients in North-Central Nigeria: The urgent need for surveillance.

We report the seroprevalence of hepatitis B surface antigen among HIV-positive patients at a clinic in North-Central Nigeria. Screening for hepatitis B virus was based on serological markers. Alanine aminotransferase levels and CD4+ T-lymphocyte counts were compared between patients. The study showed that 9.2% were positive for hepatitis B surface antigen with significant differences between alanine aminotransferase levels of patients with and without hepatitis B virus. We recommend a national surveillance system to monitor control efforts.

Efficacy of liraglutide in treating type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease.

Type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) is difficult to treat. The present study explored the efficacy of (liraglutide) Lira in treating T2DM complicated with NAFLD. A total of 127 patients suffering from T2DM complicated with NAFLD were enrolled in the present study, and randomly assigned to a Lira group (liraglutide injection: 0.6–1.2 mg/day, 12 weeks, n=52) or a Metformin (Met) group (oral metformin: 1000–1500 mg/day, 12 weeks, n=75). During the treatment phase, the values for fasting plasma glucose (FPG), 2 h plasma glucose (2hPG), glycated hemoglobin (HbA1c), aspartate aminotransferase (AST)/alanine aminotransferase (ALT), and adiponectin (APN) decreased in both the Lira and Met groups, and the levels of Δ2hPG, ΔAST/ALT, and ΔAPN in the Lira group were significantly lower than those in the Met group. The values for total cholesterol (TC), triglycerides (TG), low-and high-density lipoproteins (LDL and HDL), ALT, AST, weight, body mass index (BMI), waist to hip ratio (WHR), and C-reactive protein were markedly increased in both groups, and levels of ΔAST, ΔALT, Δweight, ΔBMI, ΔWHR, and ΔCRP (C-reactive protein) in the Lira group were significantly higher than those in the Met group. An analysis of treatment efficacy showed that liraglutide was better than metformin in its ability to significantly decrease the ALT levels in patients with combined T2DM and NAFLD. Furthermore, liraglutide was more effective than metformin at ameliorating the severity of T2DM complicated with NAFLD, and produced its effects by alleviating liver inflammation and improving liver function.

Treatment of non-alcoholic steatohepatitis patients with vitamin D: a double-blinded, randomized, placebo-controlled pilot study

Background: Non-alcoholic steatohepatitis (NASH) is defined by liver inflammation and consecutive fibrotic damage caused by a deposition of fat in the liver. No licensed medical treatments exist and lifestyle modification is difficult to incorporate into everyday life. We investigated the efficacy and safety of a 48-week treatment with vitamin D3 in NASH patients.Methods: Histologically determined NASH patients with elevated alanine aminotransferase (ALT) and decreased 25-OH vitamin D level at baseline received vitamin D3 or placebo orally over a 48-week period. The primary endpoint of this study was the change in ALT from baseline to the end-of-treatment. Steatohepatitis was categorized according to the Steatosis, Activity and Fibrosis Score and disease activity was assessed using the NAFLD activity score.Results: Serum 25-OH vitamin D levels significantly increased only in the vitamin D3 group over the 48-week treatment phase indicating compliance. In contrast to placebo, patients in the vitamin D group had markedly decreased ALT levels after the end-of-treatment phase. A significant decrease during treatment with vitamin D was also observed for cytokeratin-18 fragments compared with placebo. The study was not powered to detect changes in histological score, hence only descriptive results for histopathological characteristics are available.Conclusions: Treatment with 2100 IE vitamin D q.d. over 48 weeks was well tolerated and led to a significant improvement of serum ALT levels in patients with hypovitaminosis D and histology-proven NASH as the primary endpoint together with a trend toward reduction of hepatic steatosis, which was not significant due to a small number of available biopsy specimens.

Association of Cytokines with Alanine Aminotransferase, Hepatitis B Virus Surface Antigen and Hepatitis B Envelope Antigen Levels in Chronic Hepatitis B

Background:Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB).Methods:Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis.Results:IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = −0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = −2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ2= 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = −1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ2= 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = −0.358, t = −2.308, P = 0.024), HBsAg (β = −0.359, t = −2.288, P = 0.025), and HBeAg contents (β = −0.355, t = −2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = −0.459, t = −4.225, P = 0.000; β = −0.616, t = −6.334, P = 0.000; and β = −0.290, t = −2.433, P = 0.018; respectively).Conclusions:IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.

After successful hepatitis C virus antiviral therapy: It looks that normal alanine aminotransferase level is not the normal.

Normal serum alanine aminotransferase (ALT) levels differ with age, gender, and body mass index. Adjusting the upper limits of normal (ULN) for ALT needs further research in different populations. Aim of this work was to monitor the effect of successful chronic hepatitis C (CHC) treatment on the ALT levels in patients with normal pretreatment ALT. Data of 1160 CHC patients with persistent pretreatment normal liver enzymes were retrospectively analyzed. Treatment response to direct acting antiviral agents (DAAs) therapy was recorded. Changes in ALT levels before and after treatment were analyzed by patients' demographic, laboratory, and radiologic characteristics. Areas under the receiver operating characteristic curve (AUROC) of ALT after treatment were used to generate a new ALT ULN. Males were 568 (49%) and females 592 (51%) with a mean age of 50.7years. After treatment, mean (±SD) of ALT levels significantly decreased from (26.3±7.8) to (19.1±10.9). This reduction was more significant in interferon-free than interferon-based regimens. ROC curve analyses suggested a new ALT ULN cut off (26.4IU/L) in the treated patients (sensitivity=78.6%, specificity=83.8%, AUROC=0.89. This cutoff dropped to 14.7IU/L in cirrhotic patients (sensitivity=77.4%, specificity=44.7%, AUROC=0.612). The identified cutoffs were 16.3IU/L (sensitivity=66.7%, specificity=47.5%, AUROC=0.499) and 15.5IU/L (sensitivity=76.5%, specificity=51.3%, AUROC=0.576) in males and females, respectively. The current ALT ULN needs readjustment to identify new normal cutoffs in CHC patients. Posttreatment cutoffs differ according to gender, pretreatment liver affection, and treatment regimen.

Factors Associated With Persistent Increase in Level of Alanine Aminotransferase in Patients With Chronic Hepatitis B Receiving Oral Antiviral Therapy.

Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in ALT level in patients with CHB given long-term tenofovir disoproxil fumarate. We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials. We identified patients with an increased level of ALT (above the upper limit of normal range) after 5 years (240 weeks) of tenofovir disoproxil fumarate therapy. We analyzed findings from liver biopsy specimens collected from 467 patients (99%) at baseline and 339 patients (72%) at year 5 of treatment; biopsy specimens were evaluated by an independent pathologist. We performed stepwise, forward, multivariate regression analyses of specified baseline characteristics and on-treatment response parameters to identify factors associated with persistent increases in ALT level. Of the 471 patients, 87 (18%) still had an increased ALT level at year 5 of treatment. Factors associated significantly with a persistent increase in ALT level were a steatosis score of 5% or greater (grade 1 or more) at baseline (odds ratio [OR], 2.236; 95% confidence interval [CI], 1.031-4.852; P= .042) and at year 5 (OR, 3.392; 95% CI, 1.560 ≥ 7.375; P= .002), HBeAg seropositivity at baseline (OR, 3.297; 95% CI, 1.653-6.576; P < .001), and age 40 years or older (OR, 2.099; 95% CI, 1.014-4.342; P= .046). Of the 42 HBeAg-positive patients with steatosis at baseline, 21 (50%) had an increased ALT level at year 5 of treatment. Patients with persistent increases in ALT level were more likely to have an increase in steatosis at year 5 than those with a normal ALT level. HBeAg seropositivity and hepatic steatosis contribute to persistent increases in ALT level in patients with CHB receiving suppressive antiviral treatment. ClinicalTrials.gov registration numbers: NCT00117676 and NCT00116805.

Simple Resistance Exercise for 24 Weeks Decreases Alanine Aminotransferase Levels in Patients with Non-Alcoholic Fatty Liver Disease.

Exercise therapy is effective and recommended for non-alcoholic fatty liver disease (NAFLD) based on the efficacy of hepatic fat reduction. However, the efficacies of exercise therapy are based on short-term intervention. Moreover, no reports have examined whether significant reductions in serum levels of alanine aminotransferase (ALT) are achieved with exercise therapy in patients with NAFLD. The aim of this study is to assess the effects of simple resistance exercise for 24 weeks in NAFLD. 59 patients with NAFLD were assigned to a resistance exercise group ( n =28) or a control group ( n =31). The resistance exercise group performed 2 exercises (push-ups and squats) 3 times a week on nonconsecutive days for a trial periods of 24 weeks. Patients in the control group proceeded with regular physical activities under a restricted diet throughout the study. The effects of exercise were compared between groups after 24 weeks. Mean ALT level, homeostasis model assessment-estimated insulin resistance index and hepatic steatosis grade were all decreased in the resistance exercise group. Changes in ALT levels correlated negatively with changes in muscle:body weight ratio in the exercise group. These data demonstrate that 24 weeks of simple resistance exercise comprising squats and push-ups represents an effective treatment for NAFLD.

Evaluation of Racial Differences and Association of Obesity on Elevated ALT Level: 10-Year Analysis of the National Health and Nutrition Examination Survey (NHANES)

Introduction: Obesity is a risk factor for non-alcoholic fatty liver disease (NAFLD) and it has important public health impact. Racial differences in alanine aminotransferase (ALT) levels have not been well described. This study aimed to identify racial differences on abnormal ALT levels in patients without liver disease and evaluate the association between obesity and elevated ALT levels in adults without other metabolic risk factors. Methods: The National Health and Nutrition Examination Survey was used to compare ALT levels by race and gender. Logistic regression models were constructed to evaluate the impact of obesity on elevated ALT and to identify potential risk factors for abnormal ALT levels. Obesity was classified according to BMI with WHO classification. Serum ALT levels were considered abnormal if >47 mg/dL in males and >35 mg/dL in females. We constructed multivariable logistic regression models using STATA software version 13. Results: We analyzed 9,025 patients. 2,347 patients (26%) were obese or morbidly obese, 2,099 patients (23%) were overweight, 2,772 had normal weight (31%) and 1,807 patients had BMI below the normal range (20%). No significant difference in ALT levels across overall races was found, however on the Hispanic subgroup analysis we found significant differences between Mexican when compared to Other Hispanics (Latinos from Central America and South America); (aOR 1.76, p < 0.01; CI: 1.3-2.1). Whites were not associated with high ALT levels and African Americans were the most unlikely to have high ALT levels (aOR 0.30, p < 0.01; CI: 0.20-0.44). Obesity was not significantly associated with elevated ALT (aOR 1.05, p < 0.7; CI: 0.7-1.5). However, Waist circumference was (aOR 1.04, p < 0.01; CI: 1.02-1.4). Female gender was protective against high ALT level (aOR 0.31, p < 0.01; CI: 0.24-0.40). Conclusion: Limitations: Retrospective study. Strength: Nationwide patient cohort. Incomplete comorbidity adjustment. Conclusion: Racial differences in ALT levels among adults are plausible. Mexican ethnicity but not Hispanic overall were significantly associated with higher levels of ALT. Abdominal obesity but not Overall obesity, in the absence of metabolic risk factors and other causes of liver disease, is associated with elevated ALT, providing evidence that abdominal lipotoxicity has may do more harm. These findings have important epidemiologic implications and need more investigations as it is a possible target for new screening interventions.

Complex association of serum alanine aminotransferase with the risk of future cardiovascular disease in type 2 diabetes

Background and aimsWe aimed to determine the prospective association between baseline serum levels of alanine aminotransferase (ALT) and the incident cardiovascular disease (CVD) in people with type 2 diabetes. MethodsIn an open cohort setting, people with type 2 diabetes were followed for their first ever CVD presentation from 1995 to 2015. Statistical methods included Cox regression analysis for reporting of hazard ratios (HRs), artificial neural network modelings, and risk reclassification analyses. ResultsWe found a nearly constant CVD hazard with baseline serum ALT levels below the 30 IU/L mark, whereas baseline serum ALT levels ≥ 30 IU/L remained an independent predictor of lower CVD rates in patients with type 2 diabetes in the final multivariate Cox proportional hazards regression model (HR: 0.204, 95%CI [0.060–0.689], pfor trend value = 0.006). Age, male gender and fasting plasma insulin levels independently predicted baseline serum ALT ≥ 30 IU/L among the population cohort. Augmentation of serum ALT into the weighted Framingham risk score resulted in a considerable net reclassification improvement (NRI) of coronary heart disease (CHD) risk prediction in the study population (NRI = 9.05% (8.01%–10.22%), p value < 0.05). ConclusionsSerum ALT could successfully reclassify about 9% of the population with type 2 diabetes across the CHD-affected and CHD-free categories. Overall, our findings demonstrate a complex and nonlinear relationship for the risk of future CVD by baseline serum ALT levels in patients with type 2 diabetes. Further studies are warranted to confirm whether this complex association could be translated into a clearly visible U or J-shaped figure.

Significance of Alanine Aminotransferase Levels in Patients Admitted for Cocaine Intoxication

Experimental studies in animal models and case reports in humans have described the hepatotoxic potential of cocaine. However, there are few data regarding the clinical and laboratory characteristics of patients admitted for cocaine intoxication, particularly regarding the status of the liver enzymes. To investigate the significance of alanine aminotransferase (ALT) levels in individuals hospitalized for acute cocaine intoxication. Retrospective study with standardized chart review that included patients admitted between January 2003 and December 2010. Bivariate analyses were used to investigate factors associated with ALT above the upper tertile according to gender. Cases of marked ALT elevation were described in detail. Ninety-three patients were included (79% men, mean age of 27.73±9.97 y). ALT above the upper tertile was associated with higher aspartate aminotransferase (AST), creatine phosphokinase, creatinine, and international normalized ratio. Higher levels of ALT were also related to acute renal failure and death. Five subjects had severe ALT elevation during follow-up and all had evidence of hepatocellular dysfunction (jaundice, prolonged prothrombin time with or without hepatic encephalopathy), rhabdomyolysis, and acute renal failure. AST/ALT ratio <2 was present in 2 subjects with severe ALT elevation at admission, but AST/ALT ratio >2 was observed in 3 cases with evidence of progression to acute liver injury. In acute cocaine intoxication, higher ALT levels were associated with evidence of muscle damage, progression to acute renal failure, and death. Severe liver damage was observed in 5% of the sample and was associated with rhabdomyolysis and renal failure in all cases.