J Korean Neurosurg Soc.  2021 May;64(3):460-468. 10.3340/jkns.2020.0212.

Extremely Low Serum Alanine Transaminase Level Is Associated with All-Cause Mortality in the Elderly after Intracranial Hemorrhage

• Kim DY
• Cho KC

• KMID: 2515502
• DOI: http://doi.org/10.3340/jkns.2020.0212

Abstract

Objective
: Extremely low alanine transaminase (ALT) levels are associated with all-cause mortality in frail elderly individuals; the clinical significance of ALT as a reliable biomarker is now being considered. Predicting mortality with routine tests at the time of diagnosis is important for managing patients after intracranial hemorrhage. We aimed to investigate whether an extremely low ALT level is associated with mortality in the elderly after intracranial hemorrhage.
Methods
: A retrospective review was performed on 455 patients with intracranial hemorrhage admitted to a university-affiliated tertiary care hospital from February 2014 to May 2019. Multivariate Cox regression analysis was performed for all ages and for each age group to determine whether an extremely low ALT level is an independent predictor of mortality only in the elderly.
Results
: Overall, 294 patients were enrolled, and the mean age of the subjects was 59.1 years, with 99 (33.8%) aged ≥65 years. The variables associated with all-cause mortality in all subjects were age, C-reactive protein (CRP) levels, hemoglobin (Hb) levels (<11 g/dL), and initial Glasgow coma scale (GCS) scores. In young patients, CRP, low Hb levels, and initial GCS scores were significantly associated with all-cause mortality. However, in the elderly (≥65 years), the variables significantly associated with allcause mortality were extremely low levels of ALT (<10 U/L) (adjusted hazard ratio, 3.313; 95% confidence interval, 1.232–8.909; p=0.018) and initial GCS scores.
Conclusion
: Extremely low ALT level (<10 U/L) at the time of diagnosis is a significant risk factor for all-cause mortality in the elderly after intracranial hemorrhage.

Keyword

Alanine transaminase; Frail elderly; Frailty; Intracranial hemorrhages; Mortality

Figure

• 

  Fig. 1. Strengthening the reporting of observational studies in epidemiology diagram of the study population. From the 455 patients, 52, 14, and 20 patients were excluded because they had a history of previous stroke, tumor, or cardiac problems, respectively. Among the remaining 369 patients with intracranial hemorrhage, three patients under 18 years old, five patients with incomplete medical records and laboratory data, and 67 patients whose serum ALT levels greater than 40 were excluded. Finally, 294 subjects were enrolled in the study. ALT : alanine transaminase.

• 

  Fig. 2. Cumulative survival and log minus log curve in the elderly group. The Cox proportional model was constructed according to the ALT level, and it was found that there was a difference in survival rate in the elderly group, even though the confounders were controlled. Since the log minus log functions did not cross each other in this study, the application of the Cox proportional hazard model is appropriate. Elderly people with extremely low ALT levels (<10 U/L) at the time of intracranial hemorrhage had a higher mortality rate than those with reference ALT levels (10–40 U/L). ALT : alanine aminotransferase.

Reference

References

1. Alter G, Riley JC. Frailty, sickness, and death: models of morbidity and mortality in historical populations. Popul Stud (Camb). 43:25–45. 1989.

2. Ayis SA, Coker B, Rudd AG, Dennis MS, Wolfe CD. Predicting independent survival after stroke: a European study for the development and validation of standardised stroke scales and prediction models of outcome. J Neurol Neurosurg Psychiatry. 84:288–296. 2013.

3. Baztán JJ, Gálvez CP, Socorro A. Recovery of functional impairment after acute illness and mortality: one-year follow-up study. Gerontology. 55:269–274. 2009.

4. Bortz WM 2nd. A conceptual framework of frailty: a review. J Gerontol A Biol Sci Med Sci. 57:M283–M288. 2002.

5. Cameron ID, Kurrle SE. Frailty and rehabilitation. Interdiscip Top Gerontol Geriatr. 41:137–150. 2015.

6. Chang PE, Goh BG, Ekstrom V, Ong ML, Tan CK. Low serum albumin predicts early mortality in patients with severe hypoxic hepatitis. World J Hepatol. 9:959–966. 2017.

7. Corti MC, Guralnik JM, Salive ME, Sorkin JD. Serum albumin level and physical disability as predictors of mortality in older persons. JAMA. 272:1036–1042. 1994.

8. Dagan A, Sella T, Urban D, Onn A, Bar J, Segal G. Low alanine transaminase is not associated with increased rate of mortality in patients with advanced lung cancer. JCSM Clinical Reports. 2:1–5. 2017.

9. de Souza SP, Matos RS, Barros LL, Rocha PN. Inverse association between serum creatinine and mortality in acute kidney injury. J Bras Nefrol. 36:469–475. 2014.

10. Dziedzic T. Systemic inflammation as a therapeutic target in acute ischemic stroke. Expert Rev Neurother. 15:523–531. 2015.

11. Elinav E, Ackerman Z, Maaravi Y, Ben-Dov IZ, Ein-Mor E, Stessman J. Low alanine aminotransferase activity in older people is associated with greater long-term mortality. J Am Geriatr Soc. 54:1719–1724. 2006.

12. Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 59:M255–M263. 2004.

13. Fried LP, Tangen CM, Waltson J, Newman AB, Hirsch C, Gottdiener J, et al. Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 56:146–155. 2001.

14. Gilbertson DT, Ebben JP, Foley RN, Weinhandl ED, Bradbury BD, Collins AJ. Hemoglobin level variability: associations with mortality. Clin J Am Soc Nephrol. 3:133–138. 2008.

15. Kim WR, Flamm SL, Di Bisceglie AM, Bodenheimer HC, Public Policy Committee of the American Association for the Study of Liver Disease. Serum activity of alanine aminotransferase (ALT) as an indicator of health and disease. Hepatology. 47:1363–1370. 2008.

16. Le Couteur DG, Blyth FM, Creasey HM, Handelsman DJ, Naganathan V, Sambrook PN, et al. The association of alanine transaminase with aging, frailty, and mortality. J Gerontol A Biol Sci Med Sci. 65:712–717. 2010.

17. Lee TH, Kim WR, Benson JT, Therneau TM, Melton LJ 3rd. Serum aminotransferase activity and mortality risk in a United States community. Hepatology. 47:880–887. 2008.

18. Lee Y, Kim J, Han ES, Ryu M, Cho Y, Chae S. Frailty and body mass index as predictors of 3-year mortality in older adults living in the community. Gerontology. 60:475–482. 2014.

19. Liu Z, Ning H, Que S, Wang L, Qin X, Peng T. Complex association between alanine aminotransferase activity and mortality in general population: a systematic review and meta-analysis of prospective studies. PLoS One. 9:e91410. 2014.

20. Luengo-Fernandez R, Paul NL, Gray AM, Pendlebury ST, Bull LM, Welch SJ, et al. Population-based study of disability and institutionalization after transient ischemic attack and stroke: 10-year results of the Oxford Vascular Study. Stroke. 44:2854–2861. 2013.

21. Okamura T, Hayakawa T, Hozawa A, Kadowaki T, Murakami Y, Kita Y, et al. Lower levels of serum albumin and total cholesterol associated with decline in activities of daily living and excess mortality in a 12‐year cohort study of elderly Japanese. J Am Geriatr Soc. 56:529–535. 2008.

22. Pratt DS, Kaplan MM. Evaluation of abnormal liver-enzyme results in asymptomatic patients. N Engl J Med. 342:1266–1271. 2000.

23. Schmucker DL. Age-related changes in liver structure and function: implications for disease ? Exp Gerontol. 40:650–659. 2005.

24. Soud M, Alahdab F, Ho G, Kuku KO, Cejudo-Tejeda M, Hideo-Kajita A, et al. Usefulness of skeletal muscle area detected by computed tomography to predict mortality in patients undergoing transcatheter aortic valve replacement: a meta-analysis study. Int J Cardiovasc Imaging. 35:1141–1147. 2019.

25. Stahon KE, Bastian C, Griffith S, Kidd GJ, Brunet S, Baltan S. Agerelated changes in axonal and mitochondrial ultrastructure and function in white matter. J Neurosci. 36:9990–10001. 2016.

26. Thrift AG, Thayabaranathan T, Howard G, Howard VJ, Rothwell PM, Feigin VL, et al. Global stroke statistics. Int J Stroke. 12:13–32. 2017.

27. Towfighi A, Ovbiagele B. The impact of body mass index on mortality after stroke. Stroke. 40:2704–2708. 2009.

28. Tsivgoulis G, Katsanos AH, Patousi A, Pikilidou M, Birbilis T, Mantatzis M, et al. Stroke recurrence and mortality in northeastern Greece: the Evros Stroke Registry. J Neurol. 265:2379–2387. 2018.

29. Whiteley W, Chong WL, Sengupta A, Sandercock P. Blood markers for the prognosis of ischemic stroke: a systematic review. Stroke. 40:e380–e389. 2009.