Clin Mol Hepatol > Volume 29(Suppl); 2023 > Article |
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Study | Country | Total population (number of NAFLD) | Diagnostic method | Average follow-up (years) | Outcomes | Confounder adjustment |
---|---|---|---|---|---|---|
Dam-Larsen et al. [19] (2004) | Denmark | 215 | Fatty liver: liver biopsy | NAFLD: 16.7 | Overall estimated survival in NAFLD was not different from general Danish population | None |
Alcoholic fatty liver: 9.2 | ||||||
Adams et al. [15] (2005) | USA | 420 NAFLD | NAFLD: ultrasonography, computed tomography, magnetic resonance imaging, liver biopsy, or cryptogenic cirrhosis + metabolic syndrome | 7.6 | Overall survival in NAFLD was lower than the expected survival for the general population (HR, 1.34; 95% CI, 1.003–1.76) | Age and sex |
Kim et al. [12] (2013) | USA | 11,154 (NAFLD: 34%) | NAFLD: ultrasonography | 14.5 | NAFLD had no association with all-cause mortality (HR, 0.89; 95% CI, 0.78–1.02). | Age, sex, race or ethnicity, education, income, diabetes, hypertension, history of cardiovascular disease, lipid-lowering medication, smoking status, waist circumference, alcohol consumption, caffeine consumption, total cholesterol, high-density lipoprotein cholesterol, transferrin saturation, and C-reactive protein |
Fibrosis: non-invasive panels | Advanced fibrosis had a 69% increase in all-cause mortality (HR, 1.69; 95% CI, 1.09–2.63) | |||||
Estes et al. [10] (2018) | USA | N/A | N/A | N/A | Total annual deaths in NAFLD patients were projected to reach 1.83 million in 2030, a 44% increase from a baseline of 1.27 million in 2015 | N/A |
Kim et al. [9] (2018) | USA | 25,379,768 (NAFLD: 30,091) | NAFLD: ICD-10 codes | 10 | Between 2007 and 2016, there was a linear increase in age-standardized all-cause mortality for NAFLD (APC, 7.8; 95% CI, 6.3–9.4). NAFLD-related mortality increased continuously in Hispanics and non-Hispanic whites from 2007 to 2016, while mortality remained stable in non-Hispanic black | Age |
Taylor et al. [21] (2020) | Multinational | 4,428 NAFLD | NAFLD: liver biopsy | 6.2 | Biopsy-confirmed fibrosis was associated with increased all-cause mortality in NAFLD, which increased incrementally with increasing fibrosis stage. | Variable |
Fibrosis: liver biopsy | Stage 1: HR 1.12 (95% CI, 0.91–1.38) | |||||
Stage 2: HR 1.50 (95% CI, 1.20–1.86) | ||||||
Stage 3: HR 2.13 (95% CI, 1.70–2.67) | ||||||
Stage 4: HR 3.42 (95% CI, 2.63–4.46) | ||||||
Alvarez et al. [22] (2020) | USA | 12,253 NAFLD | NAFLD: ultrasonography | 23.3 | The population attributable fraction for overall mortality associated with NAFLD was 7.5% (95% CI, 2.1–79.6) | Age, sex, race/ethnicity, years of education, physical activity score, cigarette smoking, moderate alcohol consumption, body mass index |
Kim et al. [13] (2021) | USA | 7,761 (NAFLD: 29.5% MAFLD: 25.9%) | NAFLD: ultrasonography | 23 | MAFLD(–)/NAFLD(+) had no association with all-cause mortality (HR, 0.94; 95% CI, 0.60–1.46). | Age, sex, race/ethnicity, education, marital status, smoking status, alanine aminotransferase, sedentary lifestyle, body mass index, diabetes, hypertension, fasting triglycerides, high-density lipoprotein cholesterol, waist circumference, and C-reactive protein |
MAFLD: criteria proposed by international panel | MAFLD(+)/NAFLD(–) (HR, 1.66; 95% CI, 1.19–2.32) and MAFLD(+)/NAFLD(+) (HR, 1.13; 95% CI, 1.00–1.26) were both associated with an increase in all-cause mortality | |||||
Simon et al. [20] (2021) | Sweden | 10,568 NAFLD | NAFLD: liver biopsy | 14.2 | NAFLD at all histological stages was associated with increased all-cause mortality when compared to the general population (HR, 1.93; 95% CI, 1.64–1.79). | Age at the index date, sex, county, calendar year, education level, cardiovascular disease, and the metabolic syndrome, defined as a composite categorical variable (ranging from 0 to 4) with 1 point given for each of the following conditions (i.e., diabetes, obesity, hypertension and/or dyslipidemia) |
Fibrosis: liver biopsy | Overall mortality increased with the worsening stage of fibrosis. | |||||
Simple steatosis: HR 1.71 (95% CI, 1.64–1.79) | ||||||
NASH without fibrosis: HR 2.14 (95% CI, 1.93–2.38) | ||||||
Non-cirrhotic fibrosis: HR 2.44 (95% CI, 2.22–2.69) | ||||||
Cirrhosis: HR 3.79 (95% CI, 3.34–4.30) | ||||||
P trend: <0.01 |
Study | Country | Total population (number of NAFLD) | Diagnostic method | Average follow-up (years) | Outcomes | Confounder adjustment |
---|---|---|---|---|---|---|
Adams et al. [15] (2005) | USA | 420 NAFLD | NAFLD: ultrasonography, computed tomography, magnetic resonance imaging, liver biopsy, or cryptogenic cirrhosis + metabolic syndrome | 7.6 | Cardiovascular disease was identified as the cause of death in 28% of participants. | Age and sex |
Kim et al. [12] (2013) | USA | 11,154 (NAFLD: 34%) | NAFLD: ultrasonography Fibrosis: non-invasive panels | 14.5 | Increased mortality in individuals with NAFLD and hepatic fibrosis was driven mostly by cardiovascular death. | Age, sex, race or ethnicity, education, income, diabetes, hypertension, history of cardiovascular disease, lipid-lowering medication, smoking status, waist circumference, alcohol consumption, caffeine consumption, total cholesterol, high- density lipoprotein cholesterol, transferrin saturation, and C-reactive protein |
NFS: HR 3.56 (95% CI, 1.91–6.25) | ||||||
APRI: HR 2.53 (95% CI, 1.33–4.83) | ||||||
FIB-4: HR 2.68 (95% CI, 1.44–4.99) | ||||||
Vilar-Gomez et al. [24] (2018) | Multinational | 458 NAFLD (Bridging fibrosis: 35%, Compensated cirrhosis: 65%) | NAFLD, fibrosis, or cirrhosis: liver biopsy | 5.5 | Cardiovascular deaths made up a higher proportion of overall mortality in patients with NAFLD and bridging fibrosis (5%) than in cirrhosis (1–2%). | Center, race/ethnicity, age, sex, calendar year of patients’ recruitment, baseline body mass index, hypertension, history of previous vascular events or malignant neoplasm, anti-diabetic, antihypertensive, and hypolipidemic drugs, aspirin, current smoking and diagnosis of type 2 diabetes as timevarying covariates. |
Annualized incidence of major vascular events in the entire cohort was 0.9 (95% CI, 0.5–1.8). | ||||||
Kim et al. [9] (2018) | USA | 25,379,768 (NAFLD: 30,091) | NAFLD: ICD-10 codes | 10 | Cardiovascular disease made up a higher proportion of overall mortality in individuals with NAFLD than those with other chronic liver diseases. | Age |
NAFLD-related cardiovascular mortality steadily decreased over the period. | ||||||
Kim et al. [11] (2019) | USA | 27,903,198 (NAFLD: 33,945) | NAFLD: ICD-10 codes | 11 | The cause of death in NAFLD was more likely to be cardiovascular disease (approximately 20%), which increased at a gradual rate (APC, 2.0%; 95% CI, 0.6–3.4), whereas liver-related mortality increased rapidly (APC, 12.6%; 95% CI, 11.7–13.5). | Age |
Mantovani et al. [23] (2021) | Multinational | 5,802,226 | NAFLD: liver biopsy, imaging techniques, or ICD-10 codes in the absence of significant alcohol consumption | 6.5 | Incidence of fatal or non-fatal cardiovascular events was higher in individuals with NALFD (HR: 1.45; 95% CI, 1.31–1.61). | Age, sex, adiposity measures, diabetes, and other common cardiometabolic risk factors |
Incidence increased with increasing severity of fibrosis (pooled randomeffects HR, 2.50; 95% CI, 1.68–3.72). |
Study | Country | Total population (number of NAFLD) | Diagnostic method | Average follow-up (years) | Outcomes | Confounder adjustment |
---|---|---|---|---|---|---|
Younossi et al. [37] (2015) | USA | 19,916 (NAFLD: 1,944) | NAFLD: ICD-9 codes | 10 | 14.1% of HCC cases were related to NAFLD. | Age, gender, cancer stage, residence region, education, median household income, modified Charlson comorbidity index, and date of diagnosis |
The proportion of HCC related to NAFLD had a 9% average annual increase between 2004–2009. | ||||||
NAFLD-related HCC was associated with increased risk of 1-year overall mortality (OR, 1.21; 95% CI, 1.01–1.45) | ||||||
Dulai et al. [32] (2017) | Multinational | 1,395 NAFLD | NAFLD: liver biopsy | 11.7 | Individuals with NAFLD and stage 2 fibrosis or higher had increased risk for liver-related mor tality when compared to individuals with NAFLD and stage 0 fibrosis (MRR, 9.57; 95% CI, 0.17-11.95) | None |
Liver-related mortality rates increased exponentially with increasing stage of fibrosis. Liver-related deaths made up 59% of all-cause mortality in individuals with stage 4 fibrosis. | ||||||
Kim et al. [33] (2019) | USA | 25,379,768 (NAFLD: 12,099) | NAFLD: ICD-10 codes | 10 | Age-standardized cirrhosis-related mortality rates in individuals with NAFLD increased linearly from 2007 and 2016 with an average annual percent change of 15.4% (95% CI, 14.1–16.7). | Age |
Age-standardized HCC-related mortality rates in individuals with NAFLD increased linearly from 2007 and 2016 with an average annual percent change of 19.1% (95% CI, 14.0–24.5). | ||||||
Taylor et al. [21] (2020) | Multinational | 4,428 NAFLD | NAFLD: liver biopsy | 6.2 | Biopsy-confirmed fibrosis was associated with increased liver-related mortality in NAFLD. This increased incrementally with increasing fibrosis stage, reaching significance at stage 3 fibrosis. | Variable |
Fibrosis: liver biopsy | Stage 1: HR 1.05 (95% CI, 0.35–3.16) | |||||
Stage 2: HR 2.53 (95% CI, 0.88–7.27) | ||||||
Stage 3: HR 6.65 (95% CI, 1.99–22.25) | ||||||
Stage 4: HR 11.13 (95% CI, 4.15–29.84) | ||||||
Kim et al. [41] (2020) | USA | 25,907,886 (NAFLD: 15,812) | NAFLD: ICD-10 codes | 10 | Age-standardized cirrhosis-related mortality rate in individuals with NAFLD increased linearly with an average annual percent change of 16.2% (95% CI, 15.4–17.0) between 2009–2018. | Age |
Age-standardized HCC-related mortality rate in individuals with NAFLD increased linearly with an average annual percent change of 21.1% (95% CI, 16.9–25.4) between 2009–2018. |
Donghee Kim
https://orcid.org/0000-0003-1919-6800
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