| Literature DB >> 34713990 |
In-Ae Song1, Eun Sun Jang2,3, Tak Kyu Oh1,4.
Abstract
The dynamic aspartate-to-alanine aminotransferase ratio (dAAR) was developed recently to predict the risk of incident chronic liver disease among the Nordic adult population; however, the dAAR has not been externally validated in other ethnic cohorts. Therefore, we aimed to examine the predictive ability of dAAR for liver disease mortality in the South Korean adult population. As a population-based cohort study, we used the National Health Screening Cohort database, which included adult individuals who underwent standardized medical examinations between 2002 and 2003 in South Korea. The primary endpoint was liver disease mortality, defined as death due to liver disease. Liver disease mortality was evaluated between 2004 and 2015 (12 years). Analysis of data from 512,749 adults showed that 4,052 (0.8%) individuals died due to liver disease. On receiver operating characteristic (ROC) analyses, the area under curve for alanine aminotransferase (ALT), aspartate-to-ALT ratio (AAR), and dAAR for liver disease mortality were 0.74, 0.55, and 0.81, respectively. The cutoff point of dAAR was determined to be 0.72 on ROC analysis, using the Youden index method. On competing risk analysis using the Fine and Gray model, the dAAR > 0.72 group demonstrated a 4.43-fold higher rate of liver disease mortality (subdistribution hazard ratio: 4.43, 95% confidence interval: 4.11, 4.77; P < 0.001) after adjustment for covariates.Entities:
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Year: 2021 PMID: 34713990 PMCID: PMC8948584 DOI: 10.1002/hep4.1844
Source DB: PubMed Journal: Hepatol Commun ISSN: 2471-254X
FIG. 1Flow chart depicting individual selection process.
Clinicopathological Characteristics of the Study Participants (n = 512,746)
| Variable | Number (%) | Mean (SD) |
|---|---|---|
| Age, year | 53.6 (9.6) | |
| Sex, male | 277,758 (54.2) | |
| Residence at diagnosis | ||
| Seoul (capital city) | 87,993 (17.2) | |
| Other metropolitan city | 140,239 (27.4) | |
| Other area | 284,514 (55.5) | |
| BMI, kg/m2 | ||
| 18.5‐24.9 (normal) | 320,852 (62.6) | |
| Below 18.5 (underweight) | 11,860 (2.3) | |
| 25.0‐29.9 (overweight) | 164,840 (32.1) | |
| Above 30.0 (obese) | 14,717 (2.9) | |
| Unknown | 477 (0.1) | |
| Annual income level | ||
| 0%‐20% (lowest) | 80,547 (15.7) | |
| 20%‐40% | 69,896 (13.6) | |
| 40%‐60% | 80,940 (15.8) | |
| 60%‐80% | 107,981 (21.1) | |
| 80%‐100% (highest) | 173,382 (33.8) | |
| Underlying disability | ||
| Mild to moderate | 2,052 (0.4) | |
| Severe | 1,245 (0.2) | |
| Smoking status | ||
| Never smoker | 331,264 (64.6) | |
| Previous smoker | 43,501 (8.5) | |
| Current smoker | 117,291 (22.9) | |
| Unknown | 20,690 (4.0) | |
| Alcohol consumption | ||
| No drink | 285,927 (55.8) | |
| Mild drink group | 188,598 (36.8) | |
| Heavy drink group | 26,398 (5.1) | |
| Unknown | 11,823 (2.3) | |
| Exercise frequency | ||
| No exercise | 285,668 (55.7) | |
| 1‐2 times per a week | 118,117 (23.0) | |
| 3‐4 times per a week | 47,073 (9.2) | |
| 5‐6 times per a week | 13,170 (2.6) | |
| Almost every day | 34,690 (6.8) | |
| Unknown | 14,028 (2.7) | |
| CCI | 1.3 (1.6) | |
| Alcohol‐associated liver disease | 17,806 (3.5) | |
| Toxic liver disease | 5,983 (1.2) | |
| Hepatic failure | 2,252 (0.4) | |
| Chronic hepatitis | 26,720 (5.2) | |
| Liver cirrhosis | 4,458 (0.9) | |
| Other inflammatory liver diseases | 7,134 (1.4) | |
| Other diseases of liver | 54,128 (10.6) | |
| Liver cancer | 26,720 (5.2) | |
| Chronic viral hepatitis | 7,512 (1.5) | |
| Carrier of viral hepatitis | 734 (0.1) | |
| Family history of liver disease | 15,459 (3.0) | |
| AST | 26.9 (17.7) | |
| ALT | 25.9 (21.0) | |
| AAR | 1.2 (0.9) | |
| dAAR | −0.04 (1.24) |
dAAR: median value (−0.18, interquartile range: −0.98, 0.79, range: −6.16, 6.49).
ROC Analysis for Liver Disease Mortality
| Variable | ROC Analysis |
|---|---|
| AUC (95% CI) | |
| Total cohort | |
| ALT | 0.74 (0.73, 0.75) |
| AAR | 0.55 (0.54, 0.56) |
| dAAR | 0.81 (0.81, 0.82) |
| Alcohol‐associated liver disease cohort | |
| ALT | 0.67 (0.64, 0.69) |
| AAR | 0.70 (0.68, 0.72) |
| dAAR | 0.81 (0.80, 0.83) |
| Toxic liver disease cohort | |
| ALT | 0.73 (0.69, 0.77) |
| AAR | 0.57 (0.52, 0.62) |
| dAAR | 0.82 (0.79, 0.86) |
| Hepatic failure cohort | |
| ALT | 0.71 (0.67, 0.75) |
| AAR | 0.69 (0.65, 0.73) |
| dAAR | 0.84 (0.80, 0.87) |
| Chronic hepatitis cohort | |
| ALT | 0.71 (0.69, 0.73) |
| AAR | 0.62 (0.60, 0.64) |
| dAAR | 0.82 (0.81, 0.84) |
| Liver cirrhosis cohort | |
| ALT | 0.63 (0.60, 0.65) |
| AAR | 0.63 (0.61, 0.65) |
| dAAR | 0.74 (0.73, 0.76) |
| Other inflammatory liver diseases cohort | |
| ALT | 0.68 (0.64, 0.72) |
| AAR | 0.63 (0.58, 0.67) |
| dAAR | 0.80 (0.76, 0.84) |
| Other diseases liver cohort | |
| ALT | 0.72 (0.70, 0.74) |
| AAR | 0.60 (0.58, 0.63) |
| dAAR | 0.82 (0.80, 0.84) |
| Liver cancer cohort | |
| ALT | 0.70 (0.68, 0.72) |
| AAR | 0.61 (0.59, 0.64) |
| dAAR | 0.81 (0.79, 0.83) |
| Chronic viral hepatitis cohort | |
| ALT | 0.72 (0.69, 0.75) |
| AAR | 0.58 (0.55, 0.62) |
| dAAR | 0.82 (0.80, 0.85) |
| Carrier of viral hepatitis cohort | |
| ALT | 0.71 (0.61, 0.80) |
| AAR | 0.53 (0.43, 0.64) |
| dAAR | 0.77 (0.68, 0.87) |
| Male cohort | |
| ALT | 0.70 (0.69, 0.71) |
| AAR | 0.60 (0.59, 0.61) |
| dAAR | 0.80 (0.80, 0.81) |
| Female cohort | |
| ALT | 0.74 (0.72, 0.76) |
| AAR | 0.52 (0.49, 0.54) |
| dAAR | 0.80 (0.79, 0.81) |
| Diabetes mellitus cohort | |
| ALT | 0.69 (0.66, 0.71) |
| AAR | 0.61 (0.59, 0.63) |
| dAAR | 0.78 (0.76, 0.80) |
FIG. 2ROC curves for liver disease mortality according to AAR, ALT, and dAAR.
FIG. 3Age (A), CCI (B), BMI (C), and alcohol consumption per week (D) specific AUC.
Fine and Gray Models for Liver Disease and Non‐liver Disease Mortality Among the Entire Cohort
| Variable | Liver Disease Mortality |
| Non‐liver Disease Mortality |
|
|---|---|---|---|---|
| HR (95% CI) | HR (95% CI) | |||
| ALT (model 1) | 1.01 (1.01, 1.01) | <0.001 | 1.00 (1.01, 1.00) | <0.001 |
| AAR (model 2) | 1.02 (1.01, 1.02) | <0.001 | 1.01 (1.01, 1.02) | <0.001 |
| dAAR, 1 increase (model 3) | 1.15 (1.15, 1.16) | <0.001 | 1.10 (1.07, 1.13) | <0.001 |
| dAAR using cutoff point (model 4) | ||||
| ≤0.72 (n = 376,099) | 1 | 1 | ||
| > 0.72 (n = 136,647) | 4.43 (4.11, 4.77) | <0.001 | 1.16 (1.14, 1.18) | <0.001 |
Age, sex, residence, BMI, annual income level, underlying disability, smoking status, alcohol consumption, exercise frequency, CCI, chronic liver disease, and family history of liver disease were included for adjustment shown in Supporting Table S3.
FIG. 4Aalen‐Johansen plots for liver mortality (A) and non‐liver mortality (B) in the dAAR score risk groups based on the cutoff value (0.72) from ROC analysis.