| Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc |
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Original Article
Volume 18, Number 3, March 2026, pages 168-176
Uncommon Combination of Low Alanine Aminotransferase and High Fatty Liver Index Associated With High Charlson Comorbidity Index: Insights From the K7Ps-Study-7
Tables
| ALT (U/L) groups | 3–9 | 10–19 | 20–29 | 30–49 | 50–99 |
|---|---|---|---|---|---|
| Data are presented as mean ± standard deviation, median (interquartile range), or n (%). Normal FLI was defined as < 30. aChronic hepatitis and 27 other conditions as described in the Methods section. bDefined as consuming ≥ 69 g ethanol per drinking session. cDefined as not exercising for ≥ 30 min at least twice per week. dData are self-reported information. s-Age: substituted age; SBP: systolic blood pressure; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: γ-glutamyl transferase; HbA1c: glycated hemoglobin; CCI: Charlson Comorbidity Index; CVD: cardiovascular disease; NASH: non-alcoholic steatohepatitis; FLI: fatty liver index. | |||||
| N (% in total) | 268,498 (6.1) | 2,819,653 (63.8) | 1,027,124 (23.3) | 269,793 (6.1) | 33,555 (0.8) |
| s-Age | 52.1 ± 10.1 | 55.7 ± 10.3 | 56 ± 10.0 | 54.5 ± 9.8 | 53.6 ± 9.9 |
| Women, n (%) | 212,873 (79.3) | 1,794,092 (63.6) | 452,975 (44.1) | 95,569 (35.4) | 12,771 (38.1) |
| Body mass index (kg/m2) | 20.9 ± 2.3 | 21.3 ± 2.3 | 21.8 ± 2.3 | 22.1 ±2 .3 | 22.3 ± 2.3 |
| Waist circumference (cm) | 75.9 ± 7.0 | 77.5 ± 7.0 | 79.0 ± 6.7 | 79.7 ± 6.5 | 80 ± 6.4 |
| SBP (mm Hg) | 116 ± 16.8 | 119 ± 17.0 | 121 ± 16.6 | 122 ± 16.3 | 122 ± 16.4 |
| TG (mg/dL) | 67 (51–90) | 72 (55–97) | 77 (58–103) | 79 (60–105) | 80 (60.9–104) |
| HDL-C (mg/dL) | 69.8 ± 15.5 | 70.5 ± 16.5 | 68.3 ± 17.1 | 65.5 ± 17 | 62.7 ± 16.5 |
| AST (U/L) | 15.7 ± 3.0 | 19.4 ± 3.8 | 24.0 ± 4.9 | 29.6 ± 7.6 | 42 ± 12.9 |
| ALT (U/L) | 8.1 ± 1.1 | 14.5 ± 2.7 | 23.2 ± 2.7 | 35.5 ± 5.0 | 61.6 ± 11.4 |
| GGT (U/L) | 16.0 ± 7.7 | 21.1 ± 10.8 | 28.9 ± 15.3 | 35.4 ± 18.5 | 40.3 ± 19.7 |
| HbA1c (%) | 5.4 ± 0.4 | 5.5 ± 0.4 | 5.6 ± 0.5 | 5.6 ± 0.5 | 5.7 ± 0.6 |
| CCI | 0.5 ± 1.0 | 0.5 ± 1.0 | 0.6 ± 1.1 | 0.6 ± 1.1 | 0.8 ± 1.2 |
| FLI | 5 (3–10) | 8 (4–15) | 13 (7–21) | 17 (10–24) | 19 (12–25) |
| Hepatic diseases, n (%)a | 205 (0.08) | 2156 (0.08) | 909 (0.09) | 373 (0.14) | 103 (0.31) |
| NASH, n (%) | 11 (0.004) | 253 (0.01) | 277 (0.03) | 206 (0.08) | 129 (0.38) |
| Pharmacotherapyd | |||||
| Hypertension, n (%) | 25,778 (9.6) | 357,562 (12.7) | 151,667 (14.8) | 41,431 (15.4) | 5,567 (16.6) |
| Diabetes, n (%) | 5,378 (2.0) | 70,592 (2.5) | 35,727 (3.5) | 12,551 (4.7) | 2,102 (6.3) |
| Hyperlipidemia, n (%) | 12,647 (4.7) | 255,527 (9.1) | 138,764 (13.5) | 42,068 (15.6) | 5,364 (16.0) |
| History of CVD, n (%)d | 4,688 (1.8) | 62,143 (2.2) | 27,718 (2.7) | 7,743 (2.9) | 957 (2.9) |
| Unavailable, n (%)d | 16,265 (6.1) | 168,271 (6.0) | 63,219 (6.2) | 17,097 (6.3) | 2,048 (6.1) |
| History of stroke, n (%)d | 3,390 (1.3) | 36,169 (1.3) | 15,042 (1.5) | 4,126 (1.5) | 524 (1.6) |
| Unavailable, n (%)d | 16,284 (6.1) | 168,141 (6.0) | 63,232 (6.2) | 17,108 (6.3) | 2,044 (6.1) |
| Smokers, n (%)d | 49,284 (18.4) | 463,621 (16.4) | 182,141 (17.7) | 51,223 (19.0) | 6,026 (18.0) |
| Heavy drinkers, n (%)b, d | 4,456 (1.7) | 57,040 (2.0) | 27,390 (2.7) | 7,911 (2.9) | 845 (2.5) |
| Unavailable, n (%)d | 70,817 (26.4) | 698,311 (24.8) | 245,940 (23.9) | 66,097 (24.5) | 8,962 (26.7) |
| No regular exercise, n (%)c, d | 192,419 (71.7) | 1761,853 (62.5) | 612,925 (59.7) | 167,993 (62.3) | 22,249 (66.3) |
| Unavailable, n (%)d | 23,055 (8.6) | 249,813 (8.9) | 90,781 (8.849) | 23,668 (8.8) | 2,806 (8.4) |
| Slow gait, n (%)d | 131,571 (49.0) | 1177,599 (41.8) | 410,529 (40.0) | 112,079 (41.5) | 14,720 (43.9) |
| Unavailable, n (%)d | 26,026 (9.7) | 281,543 (10.0) | 102,354 (10.0) | 26,720 (9.9) | 3,184 (9.5) |
| ALT (U/L) groups | 2–9 | 10–19 | 20–29 | 30–49 | 50–99 |
|---|---|---|---|---|---|
| Data are presented as mean ± standard deviation, median (interquartile range), or n (%). High FLI were defined as ≥ 30. aChronic hepatitis and 27 other conditions as described in the Methods section. bDefined as consuming ≥ 69 g ethanol per drinking session. cDefined as not exercising for ≥ 30 min at least twice per week. dCounts of < 10 are not reported, in accordance with guidelines from the Japan Ministry of Health, Labor and Welfare to prevent individual identification. eData are self-reported information. s-Age: substituted age; SBP: systolic blood pressure; TG: triglycerides; HDL-C: high-density lipoprotein cholesterol; ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: γ-glutamyl transferase; HbA1c: glycated hemoglobin; CCI: Charlson Comorbidity Index; CVD: cardiovascular disease; NASH: non-alcoholic steatohepatitis; FLI: fatty liver index. | |||||
| N (% in total) | 17,261 (0.9) | 551,403 (27.6) | 690,221 (34.5) | 530,584 (26.5) | 210,123 (10.5) |
| s-Age | 58.9 ± 10.5 | 58.6 ± 10.0 | 56.6 ± 9.7 | 54.3 ± 9.4 | 52.4 ± 9.1 |
| Women, n (%) | 8,639 (50.1) | 221,916 (40.3) | 183,816 (26.6) | 103,129 (19.4) | 38,892 (18.5) |
| Body mass index (kg/m2) | 26.5 ± 3.2 | 26.2 ± 2.9 | 26.3 ± 3.0 | 27.0 ± 3.2 | 28.2 ± 3.6 |
| Waist circumference (cm) | 92.5 ± 7.3 | 91.4 ± 7.1 | 91.3 ± 7.3 | 92.6 ± 8.0 | 95.3 ± 8.7 |
| SBP (mm Hg) | 129.5 ± 16.8 | 129.4 ± 16.3 | 129.1 ± 15.9 | 129.1 ± 15.7 | 130 ± 15.6 |
| TG (mg/dL) | 135 (100–188) | 137 (102–187) | 140 (104–192) | 144 (107–200) | 146 (108–203) |
| HDL-C (mg/dL) | 55.6 ± 14.1 | 56.4 ± 13.6 | 55 ± 13.2 | 52.5 ± 12.2 | 49.8 ± 11 |
| AST (U/L) | 16.1 ± 3.8 | 19.1 ± 3.8 | 22.7 ± 4.5 | 28.1 ± 6.4 | 40.5 ± 11.3 |
| ALT (U/L) | 8.1 ± 1.2 | 15.7 ± 2.5 | 24.1 ± 2.8 | 37.2 ± 5.5 | 65 ± 12.8 |
| GGT (U/L) | 28.8 ± 17.4 | 34.7 ± 18.4 | 43 ± 20.3 | 49.6 ± 20.8 | 56.5 ± 20.1 |
| HbA1c (%) | 5.7 ± 0.6 | 5.7 ± 0.6 | 5.8 ± 0.6 | 5.9 ± 0.7 | 6.0 ± 0.8 |
| CCI | 1.1 ± 1.6 | 0.8 ± 1.3 | 0.7 ± 1.2 | 0.7 ± 1.2 | 0.8 ± 1.2 |
| FLI | 42 (35–54) | 43 (36–56) | 48 (38–63) | 56 (43–72) | 68 (51–82) |
| Hepatic diseases, n (%)a | 24 (0.14) | 534 (0.10) | 633 (0.09) | 513 (0.10) | 382 (0.18) |
| NASH, n (%) | –d | 201 (0.04) | 386 (0.06) | 742 (0.14) | 933 (0.44) |
| Pharmacotherapye | |||||
| Hypertension, n (%) | 6,440 (37.3) | 179,251 (32.5) | 207,594 (30.1) | 156,032 (29.4) | 64,268 (30.6) |
| Diabetes, n (%) | 1,882 (10.9) | 45,935 (8.3) | 53,811 (7.8) | 47,414 (8.9) | 22,905 (10.9) |
| Hyperlipidemia, n (%) | 3,357 (19.5) | 102,933 (18.7) | 135,581 (19.6) | 109,724 (20.7) | 42,882 (20.4) |
| History of CVD, n (%)e | 891 (5.2) | 23,576 (4.3) | 26,810 (3.9) | 18,721 (3.5) | 6,549 (3.1) |
| Unavailable, n (%)e | 1,005 (5.8) | 33,517 (6.1) | 44,447 (6.4) | 35,427 (6.7) | 14,205 (6.8) |
| History of stroke, n (%)e | 670 (3.9) | 13,739 (2.5) | 14,222 (2.1) | 9,599 (1.8) | 3,457 (1.7) |
| Unavailable, n (%)e | 998 (5.8) | 33,454 (6.1) | 44,432 (6.4) | 35,425 (6.7) | 14,219 (6.8) |
| Smokers, n (%)e | 4,884 (28.3) | 140,952 (25.6) | 183,182 (26.5) | 147,547 (27.8) | 56,578 (26.9) |
| Heavy drinkers, n (%)b, e | 656 (3.8) | 24,408 (4.4) | 35,061 (5.1) | 26,800 (5.1) | 9,645 (4.6) |
| Unavailable, n (%)e | 4,203 (24.3) | 123,277 (22.4) | 147,904 (21.4) | 119,973 (22.6) | 52,844 (25.1) |
| No regular exercise, n (%)c, e | 11,393 (66.0) | 346,861 (62.9) | 442,913 (64.2) | 361,026 (68.0) | 151,605 (72.2) |
| Unavailable, n (%)e | 1,639 (9.5) | 53,074 (9.6) | 64,758 (9.4) | 48,029 (9.1) | 19,184 (9.1) |
| Slow gait, n (%)e | 9,355 (54.2) | 263,270 (47.8) | 318,289 (46.1) | 253,117 (47.7) | 107,283 (51.1) |
| Unavailable, n (%)e | 1,907 (11.1) | 61,244 (11.1) | 74,513 (10.8) | 55,161 (10.4) | 21,878 (10.4) |
| Categorized ALT | ALT | ||||
|---|---|---|---|---|---|
| 3–9 U/L | 10–19 U/L | 20–29 U/L | 30–49 U/L | 50–99 U/L | |
| Normal and high FLI were defined as < 30 and ≥ 30, respectively. All associations were statistically significant (P < 0.0001). Model 1: adjustment for substituted age and sex. Model 2: model 1 plus adjustment for body mass index; systolic blood pressure; high-density lipoprotein cholesterol; triglycerides; HbA1c; pharmacotherapy for hypertension, diabetes, and dyslipidemia; smoking; heavy drinking; no regular exercise; slow gait; history of cardiovascular disease and stroke; hepatic diseases; aspartate aminotransferase; and γ-glutamyl transferase. ALT: alanine aminotransferase; β: coefficient; WCS: Wald Chi-square; FLI: fatty liver index; HbA1c: glycated hemoglobin; CCI: Charlson Comorbidity Index; CI: confidence interval; NFG: normal FLI group; HFG: high FLI group. | |||||
| Participants in NFG (n = 4,418,623) | |||||
| Model 1 | |||||
| β (95% CIs) | 0.062 (0.058–0.066) | 0 (reference) | 0.037 (0.034–0.039) | 0.1366 (0.133–0.141) | 0.353 (0.342–0.364) |
| WCS value | 930 | 983 | 4,484 | 4,100 | |
| Model 2 | |||||
| β (95% CIs) | 0.063 (0.058–0.067) | 0.014 (0.012–0.017) | 0 (reference) | 0.013 (0.009–0.017) | 0.094 (0.083–0.105) |
| WCS value | 766 | 132 | 37 | 275 | |
| Participants in HFG (n = 1,999,592) | |||||
| Model 1 | |||||
| β (95% CIs) | 0.266 (0.248–0.284) | 0.011 (0.007–0.015) | 0 (reference) | 0.089 (0.085–0.093) | 0.266 (0.260–0.272) |
| WCS value | 843 | 26 | 1,673 | 7,947 | |
| Model 2 | |||||
| β (95% CIs) | 0.251 (0.238–0.267) | 0.064 (0.058–0.068) | 0.012 (0.008–0.016) | 0 (reference) | 0.016 (0.010–0.022) |
| WCS value | 858 | 574 | 31 | 25 | |
| 2–9 U/L | 10–19 U/L | 20–29 U/L | 30–49 U/L | 50–99 U/L | |
|---|---|---|---|---|---|
| Normal and high FLI were defined as < 30 and ≥ 30, respectively. All associations were statistically significant (P < 0.0001). Model 1: adjustment for substituted age and sex. Model 2: model 1 plus adjustment for body mass index; systolic blood pressure; high-density lipoprotein cholesterol; triglycerides; HbA1c; pharmacotherapy for hypertension, diabetes, and dyslipidemia; smoking; heavy drinking; no regular exercise; slow gait; history of cardiovascular disease and stroke; hepatic diseases; ALT; AST; and GGT. ALT: alanine aminotransferase; AST: aspartate aminotransferase; GGT: γ-glutamyl transferase; HbA1c: glycated hemoglobin; CCI: Charlson Comorbidity Index; β: coefficient; WCS: Wald Chi-square; FLI: fatty liver index; CI: confidence interval. | |||||
| AST | |||||
| Participants with normal FLI | |||||
| Model 2 | |||||
| β (95% CIs) | 0.553 (0.517–0.588) | 0 (reference) | 0.022 (0.020–0.024) | 0.119 (0.114–0.123) | 0.305 (0.289–0.322) |
| WCS value | 933 | 421 | 2,604 | 1,329 | |
| Participants with high FLI | |||||
| Model 2 | |||||
| β (95% CIs) | 0.952 (0.876–1.028) | 0 (reference) | 0.018 (0.014–0.022) | 0.096 (0.089–0.102) | 0.220 (0.208–0.233) |
| WCS value | 602 | 70 | 899 | 1,152 | |
| GGT | |||||
| Participants with normal FLI | |||||
| Model 2 | |||||
| β (95% CIs) | 0.007 (0.00–0.014) | 0 (reference) | 0.009 (0.007–0.011) | 0.022 (0.020–0.025) | 0.060 (0.054–0.065) |
| WCS value | 4 | 68 | 268 | 437 | |
| Participants with high FLI | |||||
| Model 2 | |||||
| β (95% CIs) | 0.077 (0.013 -0.141) | 0 (reference) | 0.002 (–0.004 to 0.009) | 0.014 (0.008–0.020) | 0.043 (0.036–0.050) |
| WCS value | 6 | 1 | 21 | 152 | |