Table 1. Characteristics of enrolled cohort prospective studies included in meta-analysis.
| First author and publication year | Country | Population characteristic | Definition of normal ALT level (U/L) | Enrolled subjects (M/F) | Age (range, mean±SD, years) | Outcome (events number) gender/age (years) | Follow up (years) | Comparison (U/L) | HR (95%CI)a | Adjusted covariates |
| Arndt et al [8] | Germany | Construction | Not | 7858 | 42.8 | All-cause (163) | 5 | >22/≤22 | 1.3(0.9–1.9) | Age, nationality, |
| (1998) | workers | referred | (7858/0) | (25-64) | occupational group, | |||||
| smoking status, BMI, | ||||||||||
| alcohol consumption | ||||||||||
| Kim et al [3] | Korea | Insured | 35–40 | 142055 | M: | All-cause(3392)M | 8 | M:≥100/<20 | 5.2(4.2–6.4) | Age, BMI, smoking |
| (2004) | workers in | 93.5% of | (94533 | 44.8±6.7 | All-cause(394)F | F: ≥50/<20 | 1.2(0.5–3) | status, alcohol | ||
| Korea Medical | subjects | /47522) | F: | CV-disease(624)M | M:≥100/<20 | 2.9(1.5–5.6) | consumption, plasma | |||
| Insurance | within | 42.0±6.0 | CV-disease(52)F | F: 30–39/<20 | 1.3(0.4–4.1) | glucose, serum total | ||||
| Corporation | normal | Cancer(1514)M | M:≥100/<20 | 6.2(4.2–8.3) | cholesterol, blood | |||||
| range | Cancer(235)F | F: > = 100/<20 | 0.9(0.2–3.5) | pressure, family | ||||||
| Liver disease(501)M | M:≥100/<20 | 59(43.4–80.1) | history of liver | |||||||
| Liver disease(23)F | F: ≥50/<20 | 21.5(5.3–81.6) | disease | |||||||
| Elinav et al [15] | Israel | Community | < 40 for | 455 | 70 | All-cause(146) | 12 | >median | 0.67 | Sex, physical activity, |
| (2006) | residents | men, | (245/210) | /≤median | (0.46–0.93) | health perception, | ||||
| <30 for | Median:13 in | diabetes mellitus, | ||||||||
| women, | men/11 in | IHD, malignancy, CRF, | ||||||||
| 96% of the | women | anemia, smoking | ||||||||
| subjects | ||||||||||
| within | ||||||||||
| normal | ||||||||||
| range | ||||||||||
| Nalamura et al [4] | Japan | Community | Not | 4524 | 40–69 | All-cause (214) | 10 | Below median | 8.11 | Age, sex, BMI, |
| (2006) | residents | referred | (1531/2593) | 54.3±8.1 | BMIb: ≥50/<20 | (3.16–20.82) | smoking habit, | |||
| Up than | drinking habit, SBP, | |||||||||
| median BMI: | 1.38 | medication for | ||||||||
| ≥50/<20 | (0.34–5.63) | hypertension, serum | ||||||||
| Whole | total cholesterol, | |||||||||
| population: | 3.72 | history of diabetes | ||||||||
| (including | (1.95–7.10) | mellitus | ||||||||
| people with | ||||||||||
| lower and | ||||||||||
| higher BMI) | ||||||||||
| Schindhelm et al | Nether- | Community | Not | 1439 | 50–75 | All-cause (174) | 10 | T3/T1 | 1.10 | Age, sex, |
| [9] (2007) | lands | residents | referred | (788/651) | 60.9±7.2 | T3:26(21–143) | (0.77–1.61) | alcohol-intake, | ||
| T1:12(1-14) | smoking, physical | |||||||||
| activity, waist, | ||||||||||
| triglycerides, SBP, | ||||||||||
| fasting glucose, | ||||||||||
| HDL-C | ||||||||||
| Ruhl et al [11] | USA | Community | ≤30 for | 14950 | Normal | All-cause(1205)M | 8.8 | Elevated ALT | 1.1(0.62–1.9) | Age, sex, |
| (2009) | residents with | men, | (6953/7997) | ALT | All-cause(984)F | /normal ALT | 1.2(0.82–1.8) | race-ethnicity, BMI, | ||
| exclusion of | ≤19 for | group: | CV-disease(379)M | (Normal ALT | 0.38(0.12–1.2) | waist-to-hip ratio, | ||||
| HBV and HCV | women, | 45.3±0.50 | CV-disease(286)F | definition: | 1.2(0.64–2.2) | glucose status, total | ||||
| infectors | 85.6% of | elevated | Cancer(291)M | M≤30, F≤19) | 1.3(0.66–2.6) | cholesterol, HDL-C, | ||||
| subjects | ALT group: | Cancer(208)F | 0.9(0.43–1.9) | SBP, DBP, smoking, | ||||||
| within | 42.1±0.60 | Liver disease (22)M | 8.8(2.0–38.7) | alcohol, caffeine, | ||||||
| normal | Liver disease (12)F | 8.7(1.03–74) | physical activity, CRP, | |||||||
| range | transferrin | |||||||||
| saturation, education | ||||||||||
| Hovinen et al [17] | Finland | Community | Not | 397 | M: 75–91 | All-cause (127) | 5.8 | M:≥21/<21 | 0.45 | M: BMI, charlson |
| (2010) | residents | referred | (138/259) | (0.24–0.86) | comorbidity index, | |||||
| mini-mental state | ||||||||||
| examination, peak | ||||||||||
| expiratory flow, | ||||||||||
| smoking, alcohol use, | ||||||||||
| hemoglobin, glucose | ||||||||||
| F: 75–90 | F: ≥19/<19 | 0.62 (0.39–1) | F: Charlson | |||||||
| comorbidity index, | ||||||||||
| statin use, diabetes | ||||||||||
| mellitus, DBP, | ||||||||||
| heoglobin, LDL-C, | ||||||||||
| HDL-C | ||||||||||
| Ford et al- | Scotland | Participants in a | ≤55 largely | 6595 | 45–64 | All-cause(1293) | 4.9 | Q4/Q1 | 0.86 | Treatment allocation, |
| WOSCOPS | clinical trail of | within | (6595/0) | 55.24–90 | (>27/≤17) | (0.73–1.01) | age, history of | |||
| [13](2011) | pravastatin | normal | angina, history of | |||||||
| with exclusion | range | CV-disease (377) | 0.87 | diabetes and | ||||||
| of ALT outlier | (0.64–1.18) | hypertension, | ||||||||
| (≥165 IU/L) | smoking status, BMI, | |||||||||
| Cancer (532) | 0.82 | SBP, DBP, HDL-C, | ||||||||
| (0.63–1.07) | LDL-C, | |||||||||
| log(triglycerides), | ||||||||||
| glucose, nitrate use, | ||||||||||
| socioeconomic | ||||||||||
| deprivation, alcohol | ||||||||||
| use | ||||||||||
| Ford et al- | Scotland, | Participants in a | ≤55 largely | 5804 | 70–82 | All-cause (604) | 3.2 | Q4/Q1 | 0.64 | Country, treatment |
| PROSPER [13] | Ireland, | clinical trail of | within | (2803/3001) | 75.3±3.3 | (>22/≤14) | (0.5–0.81) | allocation, age, sex, | ||
| (2011) | Netherland | pravastatin | normal | current smoker and | ||||||
| with exclusion | range | CV-disease (216) | 0.58 | histories of diabetes, | ||||||
| of ALT outlier | (0.39–0.87) | hypertension | ||||||||
| (≥165 IU/L) | (components of | |||||||||
| Cancer (206) | 0.68 | vascular disease, | ||||||||
| (0.45–1.03) | BMI, SBP, DBP, | |||||||||
| HDL-C, LDL-C, | ||||||||||
| log(triglycerides), | ||||||||||
| glucose, alcohol | ||||||||||
| consumption | ||||||||||
| Ford et al- | Nether- | Community | ≤45 largely | 561 | 85 | All-cause (451) | 2 | Q4/Q1 | 0.66 | Sex, BMI, |
| Leiden 85-plus | lands | residents | within | (188/373) | (>27/≤17) | (0.5–0.87) | hypertension, SBP, | |||
| [13] (2011) | normal | DBP, HDL-C, LDL-C, | ||||||||
| range | CV-disease (48) | 0.8 | triglycerides, CRP, | |||||||
| (0.34–1.88) | diabetes, HbA1c, | |||||||||
| history of vascular | ||||||||||
| Cancer (78) | 0.63 | disease | ||||||||
| (0.32–1.21) | ||||||||||
| Schooling et al | USA | Community | Not | 16854 | T1c: | All-cause(2199)M | 13.2 | M:T3/T1 | 0.89(0.70–1.12) | Age, gender, |
| [14] (2012) | residents | referred | (7888/8966) | 49.8±22.9 | All-cause(1906)F | F:T3/T1 | 0.99(0.85–1.14) | race/ethnicity, | ||
| T2d: | All-cause(266)<50 yr | <50 yr: T3/T1 | 1.15(0.67–1.99) | education, smoking | ||||||
| 46.9±20.1 | All-cause(1110)50–75 yr | 50–75 yr:T3/T1 | 0.96(0.76–1.22) | status, alcohol use | ||||||
| T3e: | All-cause(2729)>75 yr | >75 yr: T3/T1 | 0.87(0.75–1.01) | |||||||
| 43.5±17.1 | CV-disease(974)M | M:T3/T1 | 0.86(0.66–1.11) | |||||||
| CV-disease(889)F | F:T3/T1 | 0.93(0.73–1.17) | ||||||||
| CV-disease(58)<50 yr | <50 yr: T3/T1 | 1.66(0.64–4.31) | ||||||||
| CV-disease(436)50–75 yr | 50–75 yr:T3/T1 | 1.02(0.68–1.53) | ||||||||
| CV-disease(1369)>75 yr | >75 yr: T3/T1 | 0.81(0.68–0.96) | ||||||||
| Koehler et al [18] | Nether- | Community | < 40 for | 5186 | 70.3 ± 9.1 | All-cause (2997) | 14 | P95/P25 | 0.92 | Age, sex, education, |
| (2013) | land | residents | men, | (3195/1991) | (0.76–1.11) | smoking status, | ||||
| <30 for | alcohol intake, | |||||||||
| women, | CV-disease (672) | 0.87 | hypertension, | |||||||
| 94.8% of | (0.57–1.29) | diabetes mellitus, | ||||||||
| subjects | BMI, total | |||||||||
| within | Cancer (703) | 1.05 | cholesterol levels | |||||||
| normal | (0.74–1.50) | |||||||||
| range |
a
two studies [3], [8] only provided RR as observational indicator. RR was treated as HR unless specific notification.
b
the median BMI in study was 22.7 kg/m2.
c
T1 represented the subjects with lowest category of ALT value (≤13 U/l for men and ≤9 U/l for women)
d
T2 represented the subjects with middle category of ALT value (13–21 U/l for men and 9–15 U/l for women)
e
T3 represented the subjects with highest category of ALT value (≥21 U/l for men and ≥15 U/l for women)
Abbreviations: ALT: alanine aminotransferase; BMI: body mass index; CI: confidence interval; CRF: chronic renal failure; CRP: C-reactive protein; CV: cardiovascular; DBP: diastolic blood pressure; F: female; HbA1c: glycated haemoglobin; HBV: hepatitis B virus; HCV: hepatitis B virus; HDL-C: high-density lipoprotein cholesterol; HR: hazard ratio; IHD: ischemic heart disease; LDL-C: low density lipoprotein cholesterol; M: male; P: percentile; Q: quartile; SBP: systolic blood pressure; SD: Standard deviation; T: tertile; U/l: units per liter; yr: year.