Elevated Aspartate Aminotransferase to Alanine Aminotransferase Ratio Predicts Poor Outcome in Hepatocellular Carcinoma

Purpose: This study aimed to explore the molecular mechanism of microRNA-21 and smad family member 7 in hepatocellular carcinoma. Method: A total of 57 participants were divided into control group (healthy participants, n = 10) and hepatocellular carcinoma group (hepatocellular carcinoma patients, n = 37). The expression of microRNA-21 levels were first detected in these two groups. Cell transfection was performed on hepatoma cell lines, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay to reveal proliferation and invasion ability. Furthermore, the relation between microRNA-21 and smad family member 7 was revealed by luciferase reporter gene and RNA immunoprecipitation assay. Finally, a transplantation tumor model of breast cancer in mice was constructed. Results: The serum indicators including α-alanine aminotransferase, aspartate aminotransferase, and albumin were differentially expressed between hepatocellular carcinoma group and control group. Compared to the control group, there was a high expression of microRNA-21 in hepatocellular carcinoma group. Low expression of microRNA-21 inhibited the proliferation and invasion of HepG2.2.15 and Huh7-1.3 cells. Luciferase reporter gene and RNA innumoprecipitation assay showed that smad family member 7 was the target gene of microRNA-21. Moreover, mice model analysis showed that microRNA-21 might regulate the growth of the transplanted tumors in mice by targeting smad family member 7. Conclusion: The upregulated microRNA-21 might participate in the proliferation and migration in cells of hepatocellular carcinoma via suppression of smad family member 7. Furthermore, serum indicators such as alanine aminotransferase, aspartate aminotransferase, and albumin might be used as serum diagnostic markers for hepatocellular carcinoma.

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A retrospective pilot study to examine the potential of aspartate aminotransferase to alanine aminotransferase ratio as a predictor of postoperative acute kidney injury in patients with hepatocellular carcinoma

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563218817797 ◽

2019 ◽

Vol 56 (3) ◽

pp. 357-366

Author(s):

Jianjun Xu ◽

Yun Xia ◽

Suzhen Li ◽

Xiang Cheng ◽

Shaobo Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Acute Kidney Injury ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Independent Predictor ◽

Elevated Serum ◽

Multivariate Logistic Regression Analysis ◽

Kidney Injury ◽

Preoperative Serum ◽

The Mean

Background The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AST/ALT) is an independent predictor of hepatic disease. Objectives To evaluate the association between preoperative AST/ALT and postoperative acute kidney injury in hepatocellular carcinoma patients. Methods A total of 422 hepatitis B- or C- virus-associated hepatocellular carcinoma patients, who underwent hepatectomy between September 2012 and April 2018, were enrolled this retrospective study. From all patients, aspartate aminotransferase and alanine aminotransferase parameters were collected, and the AST/ALT ratio was calculated. For diagnostic criteria of postoperative acute kidney injury, the Kidney Disease Improving Global Outcomes (KDIGO) criteria guidelines were used. Results In 48 patients (11.4%), postoperative acute kidney injury was confirmed. In patients with postoperative acute kidney injury, the mean preoperative serum AST/ALT was significantly higher when compared with patients without postoperative acute kidney injury. After multivariate logistic regression analysis, AST/ALT, haemoglobin, age, hypertension, Child-Turcotte-Pugh classification and the Milan criteria were all confirmed as predictive factors of postsurgical acute kidney injury. We found that an AST/ALT of 1.29 was the best cut-off point for predicting postoperative acute kidney injury. The positive predictive value (23.9%) of the cut-off is actually poor. After matching the propensity score, AST/ALT ≥1.29 was still confirmed as an independent predictor of postoperative acute kidney injury by multivariate analysis. Conclusion Preoperative elevated serum AST/ALT may be a potential independent predictor of postoperative acute kidney injury in hepatocellular carcinoma patients who have undergone hepatectomy. This needs to be tested in further prospective studies.

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Diagnostic value of gamma‐glutamyl transpeptidase to alkaline phosphatase ratio combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio and alanine aminotransferase to aspartate aminotransferase ratio in alpha‐fetoprotein‐negative hepatocellular carcinoma

Cancer Medicine ◽

10.1002/cam4.4057 ◽

2021 ◽

Author(s):

Jiang Li ◽

Haisu Tao ◽

Erlei Zhang ◽

Zhiyong Huang

Keyword(s):

Hepatocellular Carcinoma ◽

Alkaline Phosphatase ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Diagnostic Value ◽

Alpha Fetoprotein ◽

Gamma Glutamyl Transpeptidase ◽

Gamma Glutamyl ◽

Glutamyl Transpeptidase

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Letter: elevated aspartate aminotransferase and aspartate aminotransferase to alanine aminotransferase ratio predicts poor survival in hepatocellular carcinoma after resection

Alimentary Pharmacology & Therapeutics ◽

10.1111/apt.16124 ◽

2020 ◽

Vol 52 (11-12) ◽

pp. 1762-1763

Author(s):

Zhi-Cheng Li ◽

Zhen Li ◽

Chuan Li ◽

Jin-Cheng Fang ◽

Xue-Zhuang Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Poor Survival

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Bergenin Exhibits Hepatoprotective Activity Against Ethanol-Induced Oxidative Stress in ICR Mice

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:297-302 ◽

2019 ◽

Vol 18 (4) ◽

pp. 297-302

Author(s):

Sriset Yollada ◽

Chatuphonprasert Waranya ◽

Jarukamjorn Kanokwan

Keyword(s):

Reactive Oxygen Species ◽

Gallic Acid ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Hepatic Injury ◽

Reduced Glutathione ◽

Reactive Oxygen ◽

Hepatoprotective Activity ◽

Oxygen Species ◽

Hepatic Glutathione

Bergenin is a C-glucoside derivative of gallic acid but its antioxidant and hepatoprotective effects have not previously been compared with gallic acid. Male ICR mice were administered bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 consecutive days before a single administration of ethanol (5 g/kg). Liver sections were histopathologically examined. Aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels were determined in plasma. Total glutathione, reduced glutathione, and oxidized glutathione levels were determined in liver homogenates. Ethanol induced hepatic injury with prominent histopathological markers including nuclear pyknosis and necrotic areas and this accorded with increases in the plasma levels of aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde. Moreover, ethanol disturbed hepatic glutathione homeostasis by reducing glutathione stores. Hepatic injury in the ethanol-induced mice was prevented with bergenin and gallic acid by significant decreases in plasma aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels and restoration of the hepatic glutathione profile through an increase in the reduced glutathione/oxidized glutathione ratio. Bergenin at 10 mg/kg/day showed comparable hepatoprotective activity to gallic acid in an ethanol-induced mouse model of oxidative stress. Therefore, bergenin might be a promising candidate for further development as a novel hepatoprotective product.

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Explore the mechanism of Swertia mussotii Franch. for hepatoprotective effects with iTRAQ-LC-MS/MS

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666201020111301 ◽

2020 ◽

Vol 23 ◽

Author(s):

Haixia Yun ◽

Xinyu Wu ◽

Yiwei Ding ◽

Wendou Xiong ◽

Xianglan Duan ◽

...

Keyword(s):

Lipid Metabolism ◽

Carbon Tetrachloride ◽

Liver Injury ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Total Bilirubin ◽

Acute Liver Injury ◽

Proteome Analysis ◽

Ppi Networks ◽

Hepatoprotective Effects

Background and Objective : A Tibetan traditional herb named Swertia mussotii Franch., also called “Zangyinchen” by the local people of Qinghai-Tibet area, has been used to protect the liver from injury for many years. However, the curative effect and molecular mechanism of the herb have not been demonstrated clearly. Materials and Methods: In our study, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin levels were examined after S. mussotii Franch. treatment in the acute liver injury of the carbon tetrachloride-induced rat model. Then, Proteome Analysis was applied to explore the potential mechanism of SMT for hepatoprotective effects after iTRAQLC-MS/MS analysis (isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer with tandem mass spectrometry). Results: Serum results showed, alanine aminotransferase, aspartate aminotransferase, total bilirubin levels of rats with acute liver injury were all improved with SMT treatment. Moreover, Proteome Analysis suggested that, with S. Mussotii Franch. treatment, the levels of lipid catabolic process and lipid homeostasis were all enhanced. And the results of protein-protein interaction (PPI) analysis illustrated that these proteins assembled in PPI networks were found almost significantly enriched in response to lipid, negative regulation of lipase activity, response to lipopolysaccharide etc. Furthermore, the downregulated MRP14 and MRP8 proteins were found involved in the lipid metabolism, which may indicate the mechanism of SMT protection liver from ALI induced by carbon tetrachloride. Conclusion: SMT herb could play a role in hepatoprotection and alleviate the effect of acute liver injury by impacting the lipid metabolism associated biological process.

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Elevated alanine aminotransferase and low aspartate aminotransferase/alanine aminotransferase ratio are associated with chronic kidney disease among middle-aged women: a cross-sectional study

BMC Nephrology ◽

10.1186/s12882-020-02144-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Hirotaka Ochiai ◽

Takako Shirasawa ◽

Takahiko Yoshimoto ◽

Satsue Nagahama ◽

Akihiro Watanabe ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Venous Blood ◽

Cross Sectional Study ◽

Middle Aged ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Relationship Of

Abstract Background Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to ALT ratio (AST/ALT ratio) have been shown to be related to non-alcoholic fatty liver disease or insulin resistance, which was associated with chronic kidney disease (CKD). However, it is unclear whether ALT and AST/ALT ratio are associated with CKD. In this study, we examined the relationship of ALT and AST/ALT ratio to CKD among middle-aged females in Japan. Methods The present study included 29,133 women aged 40 to 64 years who had an annual health checkup in Japan during April 2013 to March 2014. Venous blood samples were collected to measure ALT, AST, gamma-glutamyltransferase (GGT), and creatinine levels. In accordance with previous studies, ALT > 40 U/L and GGT > 50 U/L were determined as elevated, AST/ALT ratio < 1 was regarded as low, and CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or proteinuria. Logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for CKD. Results “Elevated ALT and elevated GGT” and “elevated ALT and non-elevated GGT” significantly increased the OR for CKD when compared with “non-elevated ALT and non-elevated GGT” (OR: 2.56, 95% CI: 2.10–3.12 and OR: 2.24, 95% CI: 1.81–2.77). Compared with “AST/ALT ratio ≥ 1 and non-elevated GGT”, “AST/ALT ratio < 1 and elevated GGT” and “AST/ALT ratio < 1 and non-elevated GGT” significantly increased the OR for CKD (OR: 2.73, 95% CI: 2.36–3.15 and OR: 1.68, 95% CI: 1.52–1.87). These findings still remained after adjustment for confounders. Conclusions Elevated ALT was associated with CKD regardless of GGT elevation. Moreover, low AST/ALT ratio was also associated with CKD independent of GGT elevation.

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Eribulin, Child-Pugh score, and liver-function tests: lessons from pivotal breast cancer studies 301 and 305

Breast Cancer Research ◽

10.1186/s13058-021-01407-w ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Iain R. Macpherson ◽

Yaohua He ◽

Carlo Palmieri

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Liver Function ◽

Liver Metastases ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Hepatic Impairment ◽

Metastatic Breast ◽

Dose Modifications ◽

Group D

Abstract Background The recommended starting dose of eribulin in patients with hepatic impairment is based on the Child-Pugh score, largely informed by a pharmacokinetic study of 18 patients. In the pivotal studies of eribulin in metastatic breast cancer (Study 301 and Study 305 [EMBRACE]), entry criteria and dose modifications were based on liver-function test (LFT) results rather than Child-Pugh score. In populations such as patients with metastatic breast cancer, in which metastatic infiltration is the predominant cause of hepatic impairment, using Child-Pugh score may be problematic; in clinical practice, it has been more common for oncologists to make dosing decisions based on LFTs. To address this, the effects of abnormal baseline LFT results on eribulin efficacy and safety were investigated. Methods In this pooled post hoc analysis, 1062 patients who were randomized to receive eribulin in Studies 301 and 305 were divided into 4 groups: (A) no elevated LFT results (no liver impairment); (B) increased levels of aspartate aminotransferase and/or alanine aminotransferase; (C) decreased albumin and/or increased levels of aspartate aminotransferase and/or alanine aminotransferase but not increased bilirubin; and (D) increased bilirubin. Patients were subcategorized by presence of liver metastasis. Drug exposure, dose intensity, and treatment-emergent adverse events (TEAEs) were analyzed. Results Eribulin mesylate mean dosage was 0.82 (group A)–0.65 mg/m2/week (group D). Group D had shorter treatment, more dose reductions/delays, more TEAEs leading to dose modifications, and numerically lower objective response rates and clinical benefit rates versus groups A–C. TEAE rates leading to dose modification were similar between group D (45.5%) and groups A–C (range, 43.5–54.9%) in the absence of liver metastases, but higher in group D (91.3%) compared with groups A–C (range, 41.7–54.3%) if liver metastases were present. Conclusions Mild elevations in bilirubin levels were associated with increased toxicity and a greater requirement for dose modifications. Based both on these study data and existing recommendations, we propose a novel scheme to guide initial dose selection in patients with metastatic breast cancer and hepatic impairment that is based on LFTs rather than Child-Pugh score.

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Production and certification of secondary enzyme reference materials (ERMs). Part 1: Preparation of the sera and some of their properties.

Clinical Chemistry ◽

10.1093/clinchem/32.10.1901 ◽

1986 ◽

Vol 32 (10) ◽

pp. 1901-1905 ◽

Cited By ~ 6

Author(s):

J C Koedam ◽

G M Steentjes ◽

S Buitenhuis ◽

E Schmidt ◽

R Klauke

Keyword(s):

Creatine Kinase ◽

Lactate Dehydrogenase ◽

Reference Material ◽

Human Serum ◽

Dehydrogenase Activity ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Glutamate Dehydrogenase Activity ◽

The Stability ◽

Clinical Enzymology

Abstract We produced three batches of a human-serum-based enzyme reference material (ERM) enriched with human aspartate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2), creatine kinase (EC 2.7.3.2), and lactate dehydrogenase (EC 1.1.1.27). The added enzymes were not exhaustively purified; thus the final ERMs contained some enzymes as contaminants, of which only glutamate dehydrogenase activity might interfere. The stability during storage and after reconstitution was good. The commutability of the four enzymes in the three ERM batches was also good, except when German or Scandinavian methods for aminotransferases were involved. The temperature-conversion factors for the ERMs were equivalent to those for patients' sera. Reactivation after reconstitution was complete within 5 min and was independent of the temperature of the reconstitution fluid. We believe that these secondary ERMs will aid in the transfer of accuracy between well-defined reference methods and daily working methods so that clinical enzymology results will become more comparable from laboratory to laboratory.

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