Association between alanine aminotransferase within the normal range and all-cause and cause-specific mortality: A nationwide cohort study

Abstract

Background and aim We sought to determine the association between alanine aminotransferase (ALT) in the normal range and mortality in the absence of liver dysfunction to better understand ALT’s clinical significance beyond liver injury and inflammation. Methods A cohort of 2,708 male and 3,461 female adults aged 20–75 years without liver dysfunction (ALT<30 in males & <19 in females, negative viral serologies, negative ultrasound-based steatosis, no excess alcohol consumption) from the National Health and Nutrition Examination Survey (NHANES)-III (1988–1994) were linked to the National Death Index through December 31, 2015. Serum ALT levels were categorized into sex-specific quartiles (Females: <9, 9–11, 11–14, ≥14 IU/L, Male: <12, 12–15, 15–20, ≥20 U/L). The primary outcome was all-cause mortality. Hazard ratios (HRs) were estimated, adjusting for covariates and accounting for the complex survey design. Results Relative to males in the lowest quartile (Q1), males in the highest quartile (Q4) had 44% decreased risk of all-cause mortality (aHR [95% CI]: 0.56 [0.42, 0.74]). Females in Q4 had 45% decreased risk of all-cause mortality (aHR [95% CI]: 0.55 [0.40, 0.77]). Males with BMI <25 kg/m2 in Q4 had significantly lower risk of all-cause mortality than Q1; however, this association did not exist in males with BMI ≥25 (BMI<25: 0.36 [0.20, 0.64], BMI≥25: 0.77 [0.49, 1.22]). Risk of all-cause mortality was lower in males ≥50 years than in males<50 (age≥50: 0.55 [0.39, 0.77], age<50: 0.81 [0.39, 1.69]). These age- and BMI-related differences were not seen in females. Conclusion ALT within the normal range was inversely associated with all-cause mortality in U.S. adults.

High Aspartate Aminotransferase/Alanine Aminotransferase Ratio is the Conventional Biochemical Biomarker that is Most Closely Associated with All-Cause Mortality in Older People

“…However, the contribution of serum AST to mortality was lower (the tenth greatest contributor) than those of other parameters, including serum ALT activity alone (seventh greatest contributor) in the present AI analysis (Table 2). Although many studies have shown associations between low serum ALT activity and mortality [1][2][3][4][5][6]9,11,12], few have shown that high serum AST activity is a risk factor for mortality [18,19]. Therefore, the present findings are consistent with those of the majority of the previous studies concerning serum ALT and AST.…”

“…As also shown in previous studies [1][2][3][4][5][6]9,11,12], we found that people with low serum ALT activity are at a higher risk of mortality. However, the ranges of serum ALT activity that made positive and negative contributions to mortality overlapped (Figure 1 and Figure 3), which may have reduced the overall contribution calculated for serum ALT activity in the present study.…”

“…It can be difficult to identify older members of the community who are at a high risk of mortality, particularly using the conventional biochemical parameters measured in clinical practice. During the past two decades, many studies have shown that low serum alanine aminotransferase (ALT) activity and high aspartate transaminase (AST)/ALT ratio are associated with high mortality in older people [1][2][3][4][5][6][7][8][9][10][11][12][13]. However, the mechanisms involved remain to be conclusively established [14][15][16][17].…”

Association between alanine aminotransferase and all‐cause mortality rate: Findings from a study on Japanese community‐dwelling individuals

“…ALT, and gamma glutamyl transferase [GGT]), and similar associations were found for non-liver disease mortality. 10 Elevated serum ALT within the normal range is initially associated with lower mortality, 11 although this effect is not observed at ≥17 U/L. Older adult populations tend to exhibit significantly less mortality with elevated ALT levels than do younger populations.…”

“…On the other hand, significantly depleted ALT within normal range at the time of diagnosis is an independent risk factor contributing to increased mortality in elderly adults who have suffered an ischemic stroke 14 and those with stable coronary heart disease 15,16 . Some researchers have reported a positive association between the ALT, even within normal range, and mortality from liver disease, 17 although with inconsistent directions and magnitudes, which can be attributed to the varying ranges of ALT levels that were examined, inclusion of confounders, and differences in study populations 11 …”