Increased Alanine Aminotransferase Levels Research Articles

Association of perfluoroalkyl substances (PFAS) with liver function biomarkers in the highly exposed population of the veneto region

IntroductionEpidemiological studies highlight the presence of associations between per- and polyfluoroalkyl substances (PFAS) exposure with liver damage. In 2013, PFAS contamination was discovered in Veneto (Italy), leading to the implementation of a Surveillance Program (SP). Our objective is to investigate the association between PFAS exposure and biomarkers of liver function using single-pollutant and mixture approaches, while exploring the sex-specific differences and the mediating role of obesity in the association. MethodsThe study included 42,094 subjects aged ≥20 years participating in the SP. We used generalized additive models to investigate the association between several PFAS and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, adjusting for possible confounders and stratifying by sex. Results were back-transformed to show predicted percentage changes in outcomes per ln-unit increase in PFAS levels; furthermore, we explored the role of BMI in the abovementioned causal pathway, considering it as a potential confounder or mediator PFAS joint effect was investigated using Quantile G-computation. ResultsOne ln-unit increase in PFHxS concentrations was associated with a 1.49% (95%CI: 0.87, 2.12) and a 0.84% (95% CI: 0.27, 1.40) increase in ALT levels, in males and females respectively; one ln-unit increase in PFOA concentrations was associated with a 1.03% (95%CI: 0.50, 1.55) increase in ALT levels in males, and a 0.52% (95% CI: 0.22, 0.82) and a 0.60% (95% CI: 0.25, 0.96) increase in AST levels in females and males. PFOS showed no association with ALT and AST levels. Quantile G-computation revealed that an interquartile increase in the PFAS mixture was associated with a 3.02% increase (95% CI: 1.65, 4.43) and a 1.65% (95% CI: 0.77, 2.5) increase in ALT levels, in females and males. Mediation analysis suggested that BMI suppressed the association between PFAS and ALT levels, with positive direct effects higher than the total effects. ConclusionOur findings suggest sex-specific associations between PFAS exposure and liver function biomarkers and underscore the need for additional studies on potential mediators.

Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients

BackgroundResults of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy.MethodsPatients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle.ResultsTwenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell’s syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively.ConclusionTargeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing.Trial registrationNCT04446962.

Long-term clinical outcomes of healthy dogs with increased alanine aminotransferase.

To define a reference interval for alanine aminotransferase for the practice laboratory and then identify and longitudinally follow the clinical health and alanine aminotransferase levels in a cohort of clinically healthy dogs with increased alanine aminotransferase levels documented during wellness screening. Alanine aminotransferase levels of 125 clinically healthy dogs were used to define a reference interval for the practice laboratory. The electronic records of 315 clinically healthy dogs which had undergone wellness screening including assessment of alanine aminotransferase levels at a first-opinion veterinary hospital in the UK were reviewed between January 2012 and January 2023. Clinically healthy dogs with increased alanine aminotransferase levels relative to the top of the reference interval determined for the practice on at least one test during the study period were identified. These were longitudinally followed through electronic medical records to determine their long-term clinical outcomes over a period of up to 11 years. The reference interval for alanine aminotransferase in the practice laboratory was calculated as 10.6 to 181.8 U/L. Nineteen clinically healthy dogs were identified as having increased alanine aminotransferase levels. One dog from the group with increased alanine aminotransferase levels was diagnosed with chronic hepatitis and died of liver failure, while the other 18 dogs died of other causes, or were still alive at the end of the study, with no clinical signs associated with liver disease. One dog in the group with consistently normal alanine aminotransferase levels also died from clinical signs attributed to liver disease. Only a small proportion of clinically healthy dogs with increased alanine aminotransferase levels documented on wellness screening developed clinically relevant liver dysfunction over long-term follow-up.

A Perspective Study on Therapeutic Drug Monitoring of Voriconazole in Pediatric Patients with Hematologic Disorders

Background: The incidence of invasive aspergillosis and the administration of voriconazole have risen among immunocompromised patients. Objectives: This study aimed to evaluate serum voriconazole concentration and its corresponding influential factors in pediatric patients with hematologic disorders. Methods: A total of 132 blood samples were collected from 44 pediatric patients with hematologic disorders infected with invasive aspergillosis and treated with voriconazole. Among these patients, 20.5% were classified as having proven invasive aspergillosis, 77.2% as probable, and 2.3% as possible. Voriconazole serum levels were evaluated using HPLC on the 3rd, 5th, and 7th days of treatment. Genotyping of the CYP2C19 alleles (*2, *3, and *17) was performed, and demographic and clinical data were gathered from records between 2018 to 2020. Results: The voriconazole concentration in 70.5% of patients and 77.3% of treatment cases (complete or partial) ranged from 1 to 5.5 µg/mL. Adverse events were observed in 4.5% of the patients. Genotyping of CYP2C19 genes revealed CYP2C1911 (5.4%), CYP2C19117 (16.2%), CYP2C1912 (51.4%), and CYP2C19217 (27%). Multivariate analysis using linear regression demonstrated that serum voriconazole concentration increased by 0.037 µg/mL per year of age and by 0.06 µg/mL for each unit increase in C-reactive protein (on the 3rd day of voriconazole therapy). Additionally, an increase in alanine aminotransferase level by 1 unit decreased the mean voriconazole concentration by 0.03 µg/mL. Of these patients, 65.9% were completely treated, 11.4% were partially treated, and 22.7% died. Conclusions: Serum voriconazole concentrations varied among pediatric hematologic patients receiving standard doses, with age, C-reactive protein, and alanine aminotransferase levels affecting the concentration of voriconazole in the sera of pediatric patients.

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.

Incidence of Elevated Liver Enzyme Levels in Patients Receiving Remdesivir and Its Effective Factors.

Emergency use of remdesivir was approved for COVID-19 in some countries. Based on the promising results of remdesivir, the most common side effects were nausea, worsening respiratory failure, increased alanine aminotransferase levels, and constipation. The aim of this study was to determine the incidence of elevated liver enzymes in patients with COVID-19 receiving remdesivir. In this retrospective study, information was collected from patients' files. The study population included patients with moderate to severe COVID-19 who were admitted to Rouhani Babol Hospital. For daily patient selection, the list of patients was extracted from the system, and based on the census, the patient file was selected. Data were analyzed using Stata 16. 620 patients suffering from moderate to severe COVID-19 were included in this study, 43% of whom were men. Of these patients, 120 were selected as the control group who did not receive remdesivir. The increase in liver enzymes in patients receiving remdesivir compared with the control, for alanine transaminase (ALT) and aspartate transaminase (AST), respectively, was 6.20 and 3.64 times, but it was not statistically significant for alkaline phosphatase (ALP). Also, the increase in bilirubin levels in patients receiving remdesivir was not statistically significant. The recipients of remdesivir had high liver enzymes, which is one of the possible side effects of this drug. The intensity of the enzymes was mild and moderate, and they were not dangerous to the health of any of the consumers. Deaths in patients with COVID-19 were not due to drug-induced liver complications but to other factors such as disease-related complications.

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.