Alanine Aminotransferase, Metabolic Syndrome, and Cardiovascular Disease: A Missing Link?

Chia-Chi Wang MD1 and Jia-Horng Kao MD, PhD2

1Department of Hepatology, Buddhist Tzu Chi General Hospital, Taipei Branch and School of Medicine, Tzu Chi University, Hualien, Taiwan
2Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan

published to the editor:
We read with great interest the article by Olynyk et al. (1). In this population-based cohort study, whether elevated alanine aminotransferase (ALT) concentration could predict metabolic syndrome (MS) or cardiovascular disease (CVD) was investigated. Olynyk et al. found a strong association between baseline ALT concentration and MS, independent of insulin resistance. However, serum ALT levels did not seem to contribute to the risk of CVD. Although their results provided additional data to this area of active investigation, several issues deserve further discussion.

First, previous studies have shown similar findings regarding the relationship between serum ALT activity and MS. However, the lack of association of serum ALT levels with the risk of CVD was contradictory to recent reports. In the Hoorn study on an elderly population, a positive association between serum ALT and coronary heart disease events was observed even after adjustment for the components of MS and traditional risk factors (2). In another 20-year follow-up study, higher ALT levels were significantly associated with incident CVD in age-/gender-adjusted models, but this association was attenuated on multivariable adjustment (3). These discrepant findings may be attributed to the more stringent definition of incident CVD, younger participants, or to shorter follow-up period. In this study by Olynyk et al., incident CVD events were ascertained only from hospital admission or death records. However, CVD such as angina pectoris could possibly have been diagnosed and treated by primary care physicians without admission. Therefore, incident CVD events might be underestimated in this study.

Second, nonalcoholic fatty liver disease has been recognized as the hepatic manifestation of MS, by which the risk of CVD could be predicted. On the basis of time to development, CVD may be a later manifestation of MS compared with nonalcoholic fatty liver disease. Therefore, it is possible to show positive results among these parameters in case larger or elderly populations, longer follow-up periods, or more sensitive tests to define the risk of CVD could be adopted in future studies. In a cross-sectional analysis using the Framingham risk score to estimate the 10-year risk of coronary heart disease (4), elevated serum ALT activity in the absence of viral hepatitis or excessive alcohol consumption was found to be associated with increased calculated risk of coronary heart disease.

In summary, serum ALT activity in the absence of viral hepatitis or excessive alcohol consumption serves not only as a marker of nonalcoholic fatty liver disease but also as a possible predictor of MS and CVD (5).

1.Olynyk JK, Knuiman MW, Divitini ML et al. Serum alanine aminotransferase, metabolic syndrome, and cardiovascular disease in an Australian population. Am J Gastroenterol 2009;104:1715–1722. | Article | PubMed | ChemPort |
2.Schindhelm RK, Dekker JM, Nijpels G et al. Alanine aminotransferase predicts coronary heart disease events: a 10-year follow-up of the Hoorn Study. Atherosclerosis 2007;191:391–396. | Article | PubMed | ChemPort |
3.Goessling W, Massaro JM, Vasan RS et al. Aminotransferase levels and 20-year risk of metabolic syndrome, diabetes, and cardiovascular disease. Gastroenterology 2008;135:1935–1944. | Article | PubMed | ChemPort |
4.Ioannou GN, Weiss NS, Boyko EJ et al. Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. Hepatology 2006;43:1145–1151. | Article | PubMed | ChemPort |
5.Wang CC, Lin SK, Tseng YF et al. Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2009;24:1411–1416. | Article | PubMed | ChemPort |

Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma

Injury, Volume 40, Issue 9, Pages 978-983
K. Tan, S. Bang, A. Vijayan, M. Chiu

Introduction: Delayed diagnosis of patients with severe liver injuries is associated with an adverse outcome. As computed tomographic (CT) scan is not always available in the management of blunt abdominal trauma worldwide, the present study was undertaken to determine the accuracy of selected haematological markers in predicting the presence of hepatic injury and its severity after blunt abdominal trauma.

Methods: A retrospective review of all patients with blunt abdominal trauma presented to our institution over a 3-year period was performed. Patients were excluded if they suffered penetrating injuries, died in the emergency department or if the required blood tests were not performed within 24h of the accident. The grading of the hepatic injury was verified using CT scans or surgical findings.

ResultsNinety-nine patients with blunt abdominal trauma had the required blood tests performed and were included in the study. The median injury severity score was 24 (range 4–75). Fifty-five patients had hepatic injuries, of which 47.3% were minor (Grades I and II) while 52.7% had major hepatic injuries (Grades III–V). There were no patients with Grade VI injuries.

A raised Alanine Transaminase (ALT)(sGPT) was strongly associated with presence of hepatic injuries (OR, 109.8; 95% CI, 25.81–466.9). This relation was also seen in patients with raised AST>2 times (OR, 21.33; 95% CI, 7.27–62.65). This difference was not seen in both bilirubin and ALP.

Alanine Transaminase ALT>2 times normal was associated with major hepatic injuries (OR, 7.15; 95% CI, 1.38–37.14; p=0.012) while patients with simultaneous raised AST>2 times and ALT>2 times had a stronger association for major hepatic injuries (OR, 8.44; 95% CI, 1.64–43.47).

Conclusion: Abnormal transaminases levels are associated with hepatic injuries after blunt abdominal trauma. Patients with (GPT) ALT and (GOT) AST>2 times normal should be assumed to possess major hepatic trauma and managed accordingly. Patients with normal ALT, AST and LDH are unlikely to have major liver injuries.