Alcoholic fatty liver disease elevates estimated coronary heart disease risk to levels comparable with those of nonalcoholic fatty liver disease in the Korean population: a cross-sectional study

Study design

This is a cross-sectional study of the association between AFLD and CHD risk. We performed the retrospective analysis of the data collected in 2010, at a single center of a region, Konkuk University Health Care Center in Seoul. The recruitment period of the individuals who visited Konkuk University Health Care Center for general health check-up was from January 2010 to December 2010. The individuals visited the hospital and took the medical examination on just one day. They completed the self-administered questionnaire that had been sent by mail several days before and submitted it on the visiting day. The results of the examinations were noticed to the individuals by mailing or phone calls. The health care program included several different types of examinations upon the individuals' requests. Study data included laboratory, physical examination, liver US finding and information of the questionnaire.

Study samples

Patients were considered eligible if the three following inclusion criteria were fulfilled: (a) age 18 years or older, (b) subjects who visited Konkuk University Hospital health care center between January 2010 and December 2010 and who had undergone liver US, (c) individuals who had fulfilled the self-administered questionnaire. The study participants reached 11,469 individuals. Out of them, we excluded 167 participants with at least one potential cause of chronic liver disease: 98 subjects with hepatitis B virus, 25 subjects with hepatitis C virus, 9 subjects with some other history of hepatitis. In addition we excluded 35 participants with history of CHD. Altogether, 10,710 individuals were included in the study. Study protocol was approved by the Institutional Review Board of Konkuk University Hospital at Seoul and conformed to the ethical guidelines of the 1975 Declaration of Helsinki.

Clinical and laboratory evaluations

We reviewed all the medical records performed at health check-up, including anthropometric, laboratory and imaging study. The anthropometric data included systolic and diastolic blood pressure, height, weight, waist circumference. There was also information about participants' past history, family history, drug history and alcohol, smoking history, all collected by self-administered questionnaire. We abstracted all this information including the questionnaire from the medical record. Regarding to alcohol history, the self-administered questionnaire included the following two questions: (a) How often do you have a drink containing alcohol, during an average week (b) How many units of alcohol have you drunk during a typical occasion over the past 12 months The weekly frequency was evaluated using a closed question comprising six subcategories where patients were to choose one of the following answers: (a) once daily (b) 5-6 times per week (c) 3-4 times per week (d) 1-2 times per week (e) 2-3 times per month (f) less than once a month. The standard number of drinks consumed on an average occasion was measured by an open question. We defined significant alcohol consumption based on the threshold of ≥210 g/week (men) and ≥140 g/week (women) and discriminated between NAFLD and AFLD accordingly (15). A standard drink was defined as having 10 g of ethanol, which comprises 150 mL of wine, 200 mL of beer, 50 mL of spirit, or 50 mL of Soju, the most popular alcoholic beverage among Koreans.14 The total amount of alcohol consumed per week on average was obtained by multiplying the weekly frequency ((a) 7 for once daily (b) 5.5 for 5-6 times per week (c) 3.5 for 3-4 times per week (d) 1.5 for 1-2 times per week (e) 0.75 for 2-3 times per month (f) 0.25 for less than once a month) by the consumption amount on a single occasion, at 10 g per drink. The amount of alcohol consumption is expressed in gram/week.

Laboratory data included aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (rGT), serum total cholesterol, triglyceride, HDL-C, fasting plasma glucose, C-reactive protein and ferritin.

Diagnosis of NAFLD and AFLD

Hepatic steatosis was diagnosed if he/she had the following components at liver US: Ultrasound beam attenuation and poor visualization of intra-hepatic vessel borders and diaphragm, evidence of diffuse hyper-echogenicity of liver relative to kidneys. Liver US was performed in all patients by two experienced radiologists. The intra-observer variability for the ultrasound diagnosis of hepatic steatosis was within 3%.15 We diagnosed NAFLD by relying on the presence of hepatic steatosis as confirmed by liver US when the following criteria were absent: a) excess alcohol consumption defined as >210 g/week in men and >140 g/week in women based on the KASL definition, b) causes for secondary hepatic fat accumulation such as steatogenic medications or hereditary disorders c) positivity for hepatitis B surface antigen or antibody to hepatitis C virus. AFLD was diagnosed based on a combination of features including ongoing or recent excessive alcohol consumption with hepatic steatosis confirmed by liver US. Two radiologists performed US scanning using the Philips model (iU22x MATRIX Ultrasound System, Philips). Definition of metabolic syndrome was based on the World Health Organization-West Pacific Region Guideline16 and Insulin resistance was estimated by homeostasis model assessment of insulin resistance.17

CHD risk assessment

Among various Framingham-based tools, we used the conventional Framingham risk score (FRS) from Wilson et al 199818 to estimate total CHD risk at 10-year. For hard CHD risk estimation, we used the revised FRS form, where ATP III risk factor scoring is incorporated into the 10-year risk assessment tool.19 The FRS was calculated based on six coronary risk factors: gender, age, total cholesterol, HDL-C, systolic BP and smoking habit. Among these factors, age, BP, and cholesterol levels were categorized according to their values and smoking status was classified as either "current smoker" or "non-smoker". Finally, the corresponding point was assigned to each individual and the total score was used as the individual's CHD risk level.19

Statistical analysis

Quantitative data was expressed as mean±standard deviation (SD), and categorical data as percentages. We used chi-square tests or the Mann-Whitney test and analysis of variance or Kruskal-Wallis test for continuous variables. One-way analysis of covariance (ANCOVA) was used to compare the means of FRS and 10-year risk for total and hard CHD between the control and fatty liver group, and between the NAFLD and AFLD group after adjustment for the main differences between the groups (age, sex, metabolic syndrome, smoking and family history of CHD). All statistical tests were two-sided, and a P value of less than 0.05 was considered to be significant. Statistical analysis of the data was performed using SPSS version 17.0 (SPSS Inc., Chicago, Ill, USA).

Baseline characteristics

Out of 11,469 individuals, 10,710 subjects met the inclusion criteria. The characteristics of the study population are shown in Table 1. Of 10,710 individuals, 59.4% were men with an average age of 44.5 and a BMI of 23.8 kg/m², for whom the prevalence of metabolic syndrome was 24.1%. Relying on liver US, we discriminated 4,142 fatty liver subjects (38.7%), with the remaining 6,568 (61.3%) constituting the control group. The majority of overall group comparisons showed significant differences, with higher mean values in the population with fatty liver as compared to the control group, except for waist-to-hip ratio (P=0.08) and HDL-C which was higher in the control group (P<0.001).

Table 1.

Baseline characteristics of the study population with and without fatty liver

NAFLD vs. AFLD

Of the 4,142 subjects with fatty liver, 71.3% (2,953) had NAFLD and 28.7% (1,189) had AFLD. Table 2 shows the comparisons of the baseline characteristics between NAFLD and AFLD. Subjects with AFLD were more likely to be younger (46.2 vs. 44.3 years, P<0.001), men (62.4 vs. 92.3%, P<0.001), and were also more likely to be smokers (36.8 vs.74.6%, P<0.001), with all these variables showing significant differences compared to the NAFLD group. Subjects with NAFLD and AFLD showed comparable results for HOMA-IR, plasma level of HDL-C, low-density lipoprotein cholesterol (LDL-C), serum high-sensitive C-reactive protein (hsCRP) and daily physical activity. There were statistical differences in mean blood pressure, fasting plasma glucose, serum AST, ALT, and ferritin between the two groups.

Table 2.

Baseline characteristics of the study population with NAFLD and AFLD

Comparison of CHD risk between groups

Table 3 shows comparisons of mean 10-year estimated total risk between the control and fatty liver group, and the NAFLD and AFLD group. The mean 10-year risk for total CHD was higher in the fatty liver group than the matched control group. Individuals with AFLD had a higher 10-year estimated CHD risk compared to the control group (6.72±0.12 vs 5.50±0.04 P<0.001) and a comparable risk to those with NAFLD (6.72±0.12 vs 7.32±0.07, P=0.02). The prevalence of total CHD risk over 10% (more than moderate risk) and over 20% (high risk) were significantly higher in the fatty liver group as compared to the control. However, between NAFLD and AFLD, we obtained inconsistent results showing a higher prevalence of total CHD events greater than 10% in the AFLD group, whereas total CHD over 20% showed no unidirectional tendency (Table 4).

Table 3.

Comparisons of mean estimated 10-year total CHD risk in fatty liver vs. control group and NAFLD vs AFLD group

Table 4.

Prevalence of of estimated total CHD risk over 10% and 20% in control vs. fatty liver group and NAFLD vs. AFLD group