Abstract
Background
Metabolic syndrome has clinical implications for chronic liver disease, but the relationship between chronic hepatitis B and metabolic syndrome remains unclear. The aim of this study was to determine whether hepatitis B surface antigen (HBsAg) positivity is associated with metabolic syndrome.
Methods
Data were obtained from the Third Korean National Health and Nutrition Examination Survey (KNHANES). Participant sera were tested for HBsAg. Metabolic syndrome was defined according to the modified National Cholesterol Education Program Adult Treatment Panel III guidelines for Koreans.
Results
Of the 5108 participants, 209 (4.1%) tested positive for HBsAg, and 1364 (26.7%) were diagnosed with metabolic syndrome. The prevalence of metabolic syndrome was 23.4% in HBsAg-positive men, 31.5% in HBsAg-negative men, 18.6% in HBsAg-positive women, and 23.7% in HBsAg-negative women. After adjusting for multiple factors, male participants who tested positive for serum HBsAg had an odds ratio of 0.612 (95% confidence interval [CI] 0.375–0.998) for metabolic syndrome and an odds ratio of 0.631 (95% CI 0.404–0.986) for elevated triglycerides. Women who tested positive for serum HBsAg had an odds ratio of 0.343 (95% CI 0.170–0.693) for elevated triglycerides.
Conclusions
Positive results for serum HBsAg are inversely associated with metabolic syndrome in men and with elevated triglycerides in men and women. This suggests that elevated triglycerides may contribute to the inverse association between HBsAg and metabolic syndrome.
Key words: chronic hepatitis B, metabolic syndrome, survey, triglycerides
INTRODUCTION
Chronic hepatitis B, which results from hepatitis B virus (HBV) infection, is widespread in Korea. In 2009, the prevalence of hepatitis B surface antigen (HBsAg), a marker of HBV infection, was 3.2% in Korea.1 Chronic HBV infection can lead to the development of liver cirrhosis and/or hepatocellular carcinoma.2 The majority of chronic HBV infections in Korea are acquired in the perinatal period, though some HBV infections are acquired via horizontal transmission.
Metabolic syndrome, also known as insulin resistance syndrome, is a constellation of metabolic disorders, including increased waist circumference, hyperglycemia, elevated blood pressure, and an abnormal lipid profile. In Korea, the prevalence of metabolic syndrome has increased markedly in recent years, from 24.9% in 1998 to 31.3% in 2007.3 Metabolic syndrome is associated with liver diseases, including non-alcoholic fatty liver disease, chronic hepatitis C virus (HCV) infection, and hepatocellular carcinoma. Non-alcoholic fatty liver disease is a hepatic manifestation of metabolic syndrome.4 In chronic hepatitis C, metabolic syndrome is a potential independent predictor of liver-related mortality.5 Insulin resistance reduces the response to anti-HCV treatment.6 Metabolic syndrome is a possible risk factor for hepatocellular carcinoma, independent of the hepatitis virus.4,7 However, to the best of our knowledge, there are few existing studies on the association between metabolic syndrome and chronic hepatitis B. Three studies conducted in Asian populations reported that chronic hepatitis B is associated with a low prevalence of metabolic syndrome.8–10 However, the study populations were limited to small geographic areas, which may have led to selection bias. In addition, the statistical models used in these three studies were not adjusted for all potentially confounding factors.
The Third Korean National Health and Nutrition Examination Survey (KNHANES III) is a population-based examination survey conducted in 2005 by the Korean Centers for Disease Control and Prevention and the Korean Ministry of Health and Welfare.11 KNHANES III was designed to yield data representative of the Korean population. Thus, use of KNHANES III data will hopefully prevent selection bias that may have been unavoidable in the aforementioned studies focused on smaller geographic areas.8–10
HBV is endemic to Korea, and the prevalence of metabolic syndrome is also increasing in Korea.1,3 The aim of this study was to use representative data from KNHANES III to investigate the possible association between HBsAg and metabolic syndrome and to determine if there are correlations between HBsAg and components of metabolic syndrome, including elevated blood pressure, elevated blood glucose, elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, or increased waist circumference.
METHODS
Study population and data
The KNHANES III data used in this study included anthropometric measurements, questionnaire responses, and blood chemistry tests. Enrolled participants were ≥20 years of age and underwent an examination including a test for serum HBsAg, which was detected using an electrochemiluminescence immunoassay. A total of 5108 participants were selected and their data analyzed. Approval of this study was obtained from the Institutional Review Board of Myongji Hospital, Goyang, Korea, complying with the Treaty of Helsinki.
Parameters and definitions
Metabolic syndrome was defined based on the modified criteria for Koreans from the National Cholesterol Education Program Adult Treatment Panel III.12 Participants were categorized into three groups by Korean districts according to the population: large city, small-medium city, or rural area. Subjects with a body mass index ≥25 kg/m2 were considered obese. Increased waist circumference was defined as a waist circumference ≥90 cm in Korean men and ≥85 cm in Korean women.13 Subjects were considered to have hypertension when systolic blood pressure was ≥140 mm Hg, diastolic blood pressure was ≥90 mm Hg, or they had a medical history of antihypertensive drug use. Type 2 diabetes mellitus was defined as a fasting blood glucose ≥126 mg/dL or a medical history of hypoglycemia or insulin use. Subjects who had smoked more than 100 cigarettes in their life were categorized as smokers, while current alcohol consumption was defined as consumption of more than one glass of alcohol in the last year. Planned, systematic, and repeated physical activity to improve or maintain physical strength was considered regular exercise. Income status was classified into five categories: <1 000 000 Korean Won/month, ≥1 000 000 and <2 000 000, ≥2 000 000 and <3 000 000, ≥3 000 000 and <4 000 000, and ≥4 000 000. Education level was classified into five categories: none (did not complete elementary school), only through elementary school, only through middle school, only through high school, and through college.
Statistical analysis
Chi-square tests and t-tests were used to assess differences in anthropometric features, laboratory test results, personal medical history, and health behaviors between participants with and without chronic hepatitis B. Logistic regression analysis was used to investigate the association between chronic hepatitis B and metabolic syndrome. Logistic regression analysis was also used to investigate the associations between chronic hepatitis B and the five components of metabolic syndrome, including elevated triglycerides, elevated blood pressure, elevated blood glucose, low HDL cholesterol, and increased waist circumference. SPSS software version 11.0 (SPSS, Inc., Chicago, IL, USA) was used for analysis. P-values <0.05 were considered statistically significant.
RESULTS
Baseline characteristics of participants
A total of 5108 participants were analyzed, consisting of 2144 men and 2964 women (Table 1). Mean ± standard deviation age was 47.1 ± 15.1 years. The prevalences of HBsAg positivity and metabolic syndrome were 4.1% and 26.7%, respectively. Of the 107 men participants who were HBsAg-positive, 23.4% also had metabolic syndrome. Of the 2037 men participants who were HBsAg-negative, 31.5% had metabolic syndrome. There was no significant difference in the prevalence of metabolic syndrome between HBsAg-positive and HBsAg-negative men (P = 0.077). Of the five components of metabolic syndrome, only prevalence of elevated triglycerides was significantly lower in HBsAg-positive men than in HBsAg-negative men (29.0% vs. 38.5%, P = 0.047). Of the 102 woman participants who were HBsAg-positive, 18.6% had metabolic syndrome. Of the 2862 woman participants who were HBsAg-negative, 23.7% had metabolic syndrome. There was no significant difference in the prevalence of metabolic syndrome between HBsAg-positive and HBsAg-negative women (P = 0.233). Of the five components of metabolic syndrome, only prevalence of elevated triglycerides was significantly lower in HBsAg-positive women than in HBsAg-negative women (8.8% vs. 20.7%, P = 0.003).
Table 1. Baseline characteristics of all participants (n = 5108).
| Variable | All (n = 5108) |
Men | Women | ||||
| HBsAg Positive (n = 107) |
HBsAg Negative (n = 2037) |
P | HBsAg Positive (n = 102) |
HBsAg Negative (n = 2862) |
P | ||
| Age (year)a | 47.1 (15.1) | 45.4 (12.5) | 47.4 (14.6) | 0.112 | 46.6 (13.5) | 46.9 (15.5) | 0.855 |
| Gender (men), n (%) | 2144 (42.0%) | — | — | — | — | ||
| Location (large city), n (%) | 2201 (43.1%) | 42 (39.3%) | 696 (34.2%) | 0.313 | 34 (33.3%) | 963 (33.6%) | 0.710 |
| BMI (kg/m2)a | 23.7 (3.3) | 24.2 (3.0) | 24.0 (3.1) | 0.466 | 24.0 (3.7) | 23.5 (3.4) | 0.170 |
| Systolic pressure (mm Hg)a | 119.1 (17.8) | 119.6 (13.0) | 123.0 (16.2) | 0.011 | 118.7 (19.6) | 116.3 (18.5) | 0.201 |
| Diastolic pressure (mm Hg)a | 77.3 (10.7) | 79.2 (9.5) | 80.9 (10.4) | 0.106 | 75.7 (10.1) | 74.7 (10.3) | 0.328 |
| Waist circumference (cm)a | 81.0 (9.7) | 84.6 (8.4) | 84.3 (8.8) | 0.790 | 79.5 (9.3) | 78.5 (9.6) | 0.263 |
| AST (IU/L)b | 22.0 [19.0–27.0] | 27.0 [22.0–39.0] | 24.0 [20.0–29.0] | 0.000d | 23.0 [20.8–29.0] | 20.0 [17.0–24.0] | <0.0001d |
| ALT (IU/L)b | 18.0 [13.0–25.0] | 30.0 [21.0–47.0] | 22.0 [17.0–31.0] | <0.0001d | 18.0 [15.0–23.3] | 15.0 [12.0–20.0] | <0.0001d |
| Fasting blood glucose (mg/dL)b | 90.0 [85.0–98.0] | 91.0 [85.0–99.0] | 92.0 [86.5–101.0] | 0.331d | 88.0 [83.0–96.3] | 89.0 [84.0–96.0] | 0.600d |
| Total cholesterol (mg/dL)b | 183.0 [160.0–206.0] | 179.0 [153.0–199.0] | 184.0 [161.0–206.0] | 0.050d | 181.5 [156.0–201.3] | 182.0 [160.0–206.0] | 0.320d |
| HDL cholesterol (mg/dL)a | 45.1 (10.8) | 43.2 (10.3) | 42.2 (10.1) | 0.337 | 47.9 (10.6) | 47.1 (10.9) | 0.443 |
| Triglyceride (mg/dL)b | 105.0 [75.0–157.0] | 106.0 [76.0–158.0] | 126.0 [88.0–188.5] | 0.011d | 84.5 [65.0–109.3] | 94.0 [68.0–136.0] | 0.014d |
| Metabolic syndrome, n (%) | 1364 (26.7%) | 25 (23.4%) | 641 (31.5%) | 0.077 | 19 (18.6%) | 679 (23.7%) | 0.233 |
| Elevated triglyceride, n (%) | 1418 (27.8%) | 31 (29.0%) | 785 (38.5%) | 0.047 | 9 (8.8%) | 593 (20.7%) | 0.003 |
| Elevated blood pressure, n (%) | 1860 (36.4%) | 44 (41.4%) | 938 (46.0%) | 0.319 | 30 (29.4%) | 848 (29.6%) | 0.962 |
| Elevated blood glucose, n (%) | 1130 (22.1%) | 25 (23.4%) | 577 (28.3%) | 0.266 | 16 (15.7%) | 512 (17.9%) | 0.568 |
| Low HDL cholesterol, n (%) | 2875 (56.3%) | 48 (44.9%) | 933 (45.8%) | 0.849 | 63 (61.8%) | 1831 (64.0%) | 0.648 |
| Abdominal obesity, n (%) | 1306 (25.6%) | 29 (27.1%) | 539 (26.5%) | 0.883 | 26 (25.5%) | 712 (24.9%) | 0.888 |
| Hypertension, n (%) | 1361 (26.6%) | 30 (28.0%) | 638 (31.3%) | 0.475 | 23 (22.5%) | 670 (23.4%) | 0.840 |
| Diabetes mellitus, n (%) | 437 (8.6%) | 9 (8.4%) | 225 (11.0%) | 0.394 | 7 (6.9%) | 196 (6.8%) | 0.995 |
| Obesityc, n (%) | 1665 (32.6%) | 43 (40.2%) | 728 (35.7%) | 0.350 | 33 (32.4%) | 861 (30.1%) | 0.624 |
| Smoking, n (%) | 1934 (37.9%) | 83 (77.6%) | 1636 (80.3%) | 0.488 | 3 (2.9%) | 212 (7.4%) | 0.087 |
| Alcohol, n (%) | 3287 (74.9%) | 83 (77.6%) | 1743 (85.6%) | 0.023 | 63 (61.8%) | 1938 (67.7%) | 0.207 |
| Exercise, n (%) | 2432 (47.6%) | 56 (52.3%) | 1051 (51.6%) | 0.881 | 43 (42.2%) | 1282 (44.8%) | 0.599 |
| Income status, n (%) | n = 5022 | n = 103 | n = 1999 | 0.315 | n = 102 | n = 2818 | 0.336 |
| <1 000 000 Won | 1269 (25.3%) | 17 (16.5%) | 472 (23.6%) | 20 (19.6%) | 760 (27.0%) | ||
| ≥1 000 000 but <2 000 000 Won | 1462 (29.1%) | 34 (33.0%) | 605 (30.3%) | 36 (35.3%) | 787 (27.0%) | ||
| ≥2 000 000 but <3 000 000 Won | 1196 (23.8%) | 23 (22.3%) | 480 (24.0%) | 22 (21.6%) | 671 (23.8%) | ||
| ≥3 000 000 but <4 000 000 Won | 517 (10.3%) | 16 (15.5%) | 213 (10.7%) | 10 (9.8%) | 278 (9.9%) | ||
| ≥4 000 000 Won | 578 (11.5%) | 13 (12.6%) | 229 (11.5%) | 14 (13.7%) | 322 (11.4%) | ||
| Education level, n (%) | n = 5065 | n = 107 | n = 2018 | 0.089 | 99 | 2841 | 0.004 |
| none | 500 (9.9%) | 2 (1.9%) | 88 (4.4%) | 11 (11.1%) | 399 (14.0%) | ||
| only through elementary school | 776 (15.3%) | 6 (5.6%) | 268 (13.3%) | 15 (15.2%) | 487 (17.1%) | ||
| only through middle school | 590 (11.6%) | 15 (14.0%) | 239 (11.8%) | 23 (23.2%) | 313 (11.0%) | ||
| only through high school | 1891 (37.3%) | 43 (40.2%) | 789 (39.1%) | 35 (35.4%) | 1024 (36.0%) | ||
| through college | 1308 (25.8%) | 41 (38.3%) | 634 (31.4%) | 15 (15.2%) | 618 (21.8%) | ||
ALT, alanine aminotransferase; AST, aspartate aminotransferase.
aData are expressed as mean (SD).
bData are expressed as median [25–75 percentiles].
cObesity was defined as body mass index ≥25 kg/m2.
dP values were obtained using Mann-Whitney U test for skewed variables: AST, ALT, fasting glucose, total cholesterol, and triglyceride.
Serum HBsAg and metabolic syndrome
In a multivariate analysis, the odds ratio of a positive result for HBsAg was 0.612 (95% confidence interval [CI] 0.375–0.998) in men with metabolic syndrome and 0.695 (95% CI 0.400–1.208) in women with metabolic syndrome, after adjusting for age, location, smoking habits, alcohol consumption, exercise habits, income status, and education level (Table 2).
Table 2. Multivariate analysis of the association between positive HBsAg and metabolic syndrome.
| Model | Men (n = 2144) | Women (n = 2964) | ||||
| Odds ratio | 95% CI | P value | Odds ratio | 95% CI | P value | |
| Unadjusted | 0.664 | 0.420–1.049 | 0.079 | 0.736 | 0.444–1.221 | 0.235 |
| Model 1a | 0.659 | 0.412–1.054 | 0.082 | 0.721 | 0.416–1.249 | 0.243 |
| Model 2b | 0.656 | 0.410–1.049 | 0.079 | 0.715 | 0.413–1.239 | 0.232 |
| Model 3c | 0.612 | 0.375–0.998 | 0.049 | 0.695 | 0.400–1.208 | 0.197 |
CI, confidence interval.
aAdjusted for age.
bAdjusted for age, location and exercise habits.
cAdjusted for age, location, smoking habits, alcohol consumption, exercise habits, income status, and education levels.
Multivariable analyses were performed to explore the associations between a positive result for HBsAg and the five components of metabolic syndrome. The odds ratio for elevated triglycerides was 0.631 in HBsAg-positive men (95% CI 0.404–0.986) and 0.343 in HBsAg-positive women (95% CI 0.170–0.693; Table 3). Elevated triglycerides were inversely associated with HBsAg positivity.
Table 3. Multivariate analysis of the association between positive HBsAg and metabolic abnormalities.
| Dependent variables | |||||
| Elevated triglyceride |
Elevated blood pressure |
Elevated blood glucose |
Low HDL cholesterol |
Increased waist circumference |
|
| Men (n = 2144) | |||||
| Positive HBsAga | |||||
| Odds ratio | 0.631 | 0.856 | 0.803 | 0.915 | 1.042 |
| 95% CI | 0.404–0.986 | 0.558–1.314 | 0.491–1.314 | 0.608–1.376 | 0.660–1.645 |
| P value | 0.043 | 0.477 | 0.382 | 0.670 | 0.860 |
| Women (n = 2964) | |||||
| Positive HBsAga | |||||
| Odds ratio | 0.343 | 1.037 | 0.840 | 0.862 | 1.014 |
| 95% CI | 0.170–0.693 | 0.623–1.725 | 0.476–1.483 | 0.569–1.305 | 0.624–1.648 |
| P value | 0.003 | 0.890 | 0.548 | 0.482 | 0.955 |
CI, confidence interval.
aAdjusted for age, location, smoking habits, alcohol consumption, exercise habits, income status, and education level.
DISCUSSION
Our study shows that serum HBsAg positivity is inversely correlated with prevalence of metabolic syndrome in Korean men but not in women. This is consistent with findings from other Asian studies.8–10 A Taiwanese study reported that the prevalence of metabolic syndrome was 8.0% in HBsAg-positive subjects and 10.9% in HBsAg-negative subjects.8 Another study performed in China reported that the prevalence of metabolic syndrome was 5.9% in HBsAg-positive participants and 8.8% in HBsAg-negative participants.10 In both of these studies, this inverse association remained even after adjusting for age and sex. A study performed in Hong Kong reported that the prevalence of metabolic syndrome was 11.0% in patients with chronic hepatitis B and 20.2% in controls without chronic hepatitis B.9 However, these three studies did not stratify subjects by sex, as our study did. The definition of metabolic syndrome differs according to sex, and analysis should be performed separately for men and women.12,13 Our study conducted separate analysis according to sex and found that only HBsAg-positive males had a lower prevalence of metabolic syndrome than their HBsAg-negative counterparts. In addition, our study used a nationally representative population, while the other studies did not.
In the present study, a positive result for serum HBsAg was associated with a low prevalence of elevated triglycerides. This low prevalence might be an important contributor to the inverse association between HBsAg positivity and metabolic syndrome, which would be consistent with findings in other studies.9 Chen et al. reported that HBsAg positivity is associated with lower prevalence of hypertriglyceridemia,14 while Su et al. reported that chronic hepatitis B is associated with low serum levels of triglycerides.15 However, the exact mechanism causing the low levels of triglycerides in HBsAg-positive patients remains unclear. One study suggested that the hepatitis B virus X protein is a contributor to low serum triglycerides.16 The role of HBV in lipid metabolism should be further explored.
Metabolic syndrome is related to liver fibrosis. A cross-sectional study in Taiwan reported that metabolic syndrome increases the risk of liver cirrhosis in patients with chronic hepatitis B.17 Metabolic syndrome has been linked to increased risk and severity of liver fibrosis through activation of hepatic stellate cells.18 However, liver cirrhosis itself can cause metabolic disturbances.19 These observations suggest a relationship between HBV infection and diabetes mellitus; development of diabetes mellitus may contribute to secondary changes due to HBV infection but not to HBV infection itself.20 In addition, hepatic fibrosis in an HBV-infected liver is caused by virus-induced liver injury rather than insulin resistance.21 Thus, the cause and effect relationship between metabolic syndrome and liver cirrhosis in patients with chronic hepatitis B remains unclear.22
Chronic hepatitis C is associated with insulin resistance, but the association between chronic hepatitis B and insulin resistance is not well-established. Huang et al. reported that chronic hepatitis B without cirrhosis is not associated with type 2 diabetes mellitus.20 Kumar et al. reported that chronic hepatitis B is not correlated with insulin resistance.23 On the other hand, a study using NHANES III data reported that type 2 diabetes mellitus and insulin resistance are independent predictors of overall mortality in chronic hepatitis B, although only 66 participants in the study had chronic hepatitis B.5
Our study had several limitations. First, various conditions associated with HBsAg were not considered because the KNHANES tested only for the presence of HBsAg and hepatitis B surface antibody. An individual who is HBsAg-positive may be a healthy carrier, have chronic active hepatitis, or have liver cirrhosis. In terms of serology, HBsAg positivity is associated with various levels of HBV DNA concentration and two states of hepatitis B e antigen. Further stratification of HBsAg states should be performed to determine the exact role of HBsAg in the development of metabolic syndrome.
Second, the KNHANES did not differentiate between liver cirrhosis and chronic hepatitis. Liver cirrhosis is closely related to glucose intolerance, regardless of its cause.19 Diabetes may develop as a complication of cirrhosis, which is called hepatogenous diabetes.24 Therefore, liver cirrhosis may have contributed to the metabolic derangement observed in our study. In addition, two recent studies reported conflicting results on the association between metabolic syndrome and liver cirrhosis in chronic hepatitis B patients.17,21 One of these studies reported that metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B patients.17 However, the other reported that hepatic fibrosis in HBV-infected liver is caused by virus-induced liver injury, rather than by insulin resistance.21 The data suggest that metabolic syndrome is not a risk factor for liver cirrhosis but an outcome of liver cirrhosis.21 Therefore, liver cirrhosis must be excluded when clarifying the effect of HBsAg on metabolic syndrome.
Third, our study was a cross-sectional study, and therefore it was not possible to explore a causal relationship between chronic HBV infection and metabolic syndrome. It is unclear whether chronic HBV infection suppresses development of metabolic syndrome. In addition, horizontal transmission could not be completely excluded from subjects with chronic infection resulting from vertical transmission; in this situation, chronic hepatitis B infection could have been followed by development of metabolic syndrome.
In conclusion, data from KNHANES III indicate that HBsAg positivity is associated with a low prevalence of metabolic syndrome in men, and this association may be partly attributed to low prevalence of elevated triglycerides.
ACKNOWLEDGMENTS
This research was supported by the Clinical Research Program (11-067) of the Bukwang Pharm Company, Seoul, Korea.
Conflicts of interest: None declared.
REFERENCES
- 1.Park B, Choi KS, Lee HY, Jun JK, Park EC. Socioeconomic inequalities in completion of hepatitis B vaccine series among Korean women: results from a nationwide interview survey. Vaccine. 2012;30:5844–8. 10.1016/j.vaccine.2012.07.022 [DOI] [PubMed] [Google Scholar]
- 2.Chan HL, Wong GL, Wong VW. A review of the natural history of chronic hepatitis B in the era of transient elastography. Antivir Ther. 2009;14:489–99. [PubMed] [Google Scholar]
- 3.Lim S, Shin H, Song JH, Kwak SH, Kang SM, Won Yoon J, et al. Increasing prevalence of metabolic syndrome in Korea: the Korean National Health and Nutrition Examination Survey for 1998–2007. Diabetes Care. 2011;34:1323–8. 10.2337/dc10-2109 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Siegel AB, Zhu AX. Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. Cancer. 2009;115:5651–61. 10.1002/cncr.24687 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Stepanova M, Rafiq N, Younossi ZM. Components of metabolic syndrome are independent predictors of mortality in patients with chronic liver disease: a population-based study. Gut. 2010;59:1410–5. 10.1136/gut.2010.213553 [DOI] [PubMed] [Google Scholar]
- 6.Negro F, Clément S. Impact of obesity, steatosis and insulin resistance on progression and response to therapy of hepatitis C. J Viral Hepat. 2009;16:681–8. 10.1111/j.1365-2893.2009.01186.x [DOI] [PubMed] [Google Scholar]
- 7.Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology. 2011;54:463–71. 10.1002/hep.24397 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Jan CF, Chen CJ, Chiu YH, Chen LS, Wu HM, Huang CC, et al. A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung Community-based Integrated Screening study No. 10). Int J Obes (Lond). 2006;30:794–9. 10.1038/sj.ijo.0803204 [DOI] [PubMed] [Google Scholar]
- 9.Wong VW, Wong GL, Chu WC, Chim AM, Ong A, Yeung DK, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56:533–40. 10.1016/j.jhep.2011.09.013 [DOI] [PubMed] [Google Scholar]
- 10.Luo B, Wang Y, Wang K. Association of metabolic syndrome and hepatitis B infection in a Chinese population. Clin Chim Acta. 2007;380:238–40. 10.1016/j.cca.2007.01.012 [DOI] [PubMed] [Google Scholar]
- 11.The Third Korean National Health and Nutrition Examination Survey. Further Analysis, Korea Centers for Disease Control and Prevention and the Korea Ministry of Health and Welfare. 2005 (in Korean).
- 12.National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) . Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421. [PubMed] [Google Scholar]
- 13.Lee SY, Park HS, Kim DJ, Han JH, Kim SM, Cho GJ, et al. Appropriate waist circumference cutoff points for central obesity in Korean adults. Diabetes Res Clin Pract. 2007;75:72–80. 10.1016/j.diabres.2006.04.013 [DOI] [PubMed] [Google Scholar]
- 14.Chen JY, Wang JH, Lin CY, Chen PF, Tseng PL, Chen CH, et al. Lower prevalence of hypercholesterolemia and hyperglyceridemia found in subjects with seropositivity for both Hepatitis B and C strains independently. J Gastroenterol Hepatol. 2010;25:1763–8. 10.1111/j.1440-1746.2010.06300.x [DOI] [PubMed] [Google Scholar]
- 15.Su TC, Lee YT, Cheng TJ, Chien HP, Wang JD. Chronic hepatitis B virus infection and dyslipidemia. J Formos Med Assoc. 2004;103:286–91. [PubMed] [Google Scholar]
- 16.Kang SK, Chung TW, Lee JY, Lee YC, Morton RE, Kim CH. The hepatitis B virus X protein inhibits secretion of apolipoprotein B by enhancing the expression of N-acetylglucosaminyltransferase. J Biol Chem. 2004;279:28106–12. 10.1074/jbc.M403176200 [DOI] [PubMed] [Google Scholar]
- 17.Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58:111–7. 10.1136/gut.2008.157735 [DOI] [PubMed] [Google Scholar]
- 18.Lanthier N, Horsmans Y, Leclercq IA. The metabolic syndrome: how it may influence hepatic stellate cell activation and hepatic fibrosis. Curr Opin Clin Nutr Metab Care. 2009;12:404–11. 10.1097/MCO.0b013e32832c7819 [DOI] [PubMed] [Google Scholar]
- 19.Garcia-Compean D, Jaquez-Quintana JO, Gonzalez-Gonzalez JA, Maldonado-Garza H. Liver cirrhosis and diabetes: risk factors, pathophysiology, clinical implications and management. World J Gastroenterol. 2009;15:280–8. 10.3748/wjg.15.280 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Huang ZS, Huang TS, Wu TH, Chen MF, Hsu CS, Kao JH. Asymptomatic chronic hepatitis B virus infection does not increase the risk of diabetes mellitus: A ten-year observation. J Gastroenterol Hepatol. 2010;25:1420–5. 10.1111/j.1440-1746.2010.06268.x [DOI] [PubMed] [Google Scholar]
- 21.Park SH, Kim DJ, Lee HY. Insulin resistance is not associated with histologic severity in nondiabetic, noncirrhotic patients with chronic hepatitis B virus infection. Am J Gastroenterol. 2009;104:1135–9. 10.1038/ajg.2009.6 [DOI] [PubMed] [Google Scholar]
- 22.Chang LC, Chung CS, Liu CJ, Kao JH. Metabolic syndrome on top of chronic hepatitis B: the more, the worse? Gut. 2010;59:276–7. 10.1136/gut.2009.183855 [DOI] [PubMed] [Google Scholar]
- 23.Kumar M, Choudhury A, Manglik N, Hissar S, Rastogi A, Sakhuja P, et al. Insulin resistance in chronic hepatitis B virus infection. Am J Gastroenterol. 2009;104:76–82. 10.1038/ajg.2008.9 [DOI] [PubMed] [Google Scholar]
- 24.Holstein A, Hinze S, Thiessen E, Plaschke A, Egberts EH. Clinical implications of hepatogenous diabetes in liver cirrhosis. J Gastroenterol Hepatol. 2002;17:677–81. 10.1046/j.1440-1746.2002.02755.x [DOI] [PubMed] [Google Scholar]