Association Between the Hepatitis B and C Viruses and Metabolic Diseases in Patients Stratified by Age
Wen-Cheng Li, Yi-Yen Lee, I-Chuan Chen, Cheng Sun, Feng-Hsiang Chiu, Chung-Hsun Chuang
Liver International. 2013;33(8):1194-1202.
Discussion Only
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In this multi-centre study including 26 305 subjects, the association between MS (including individual components of MS) and hepatitis B and C stratified by both age and gender was assessed. The results of this study showed that both females and males >45 years who were positive for anti-HCV had significantly higher levels of various individual components of MS, including WC, FBG, SBP and DBP than those who were 45 years. In addition, anti-HCV-positive subjects had lower TG, LDL and TC than those that were negative for anti-HCV.
HBV and HCV are important causes of both acute and chronic liver diseases. The severity of HBV- and HCV-related liver diseases and rate of disease progression are impacted by age, gender, host factors, exposure to alcohol, coinfections, viral genotype and MS.[11] In addition, the individual components of MS might also be independent predictors of morbidity/mortality in patients with liver diseases, such as those caused by HBV or HCV.[12] A multitude of other studies have also reported that HCV is a risk for MS and/or various individual components of MS, including IR as cited in Negro and, more recently, the review articles by Sheikh et al. and Del Campo and Romero-Gómez.[13–15] A myriad of other studies have noted the strong association between HCV and type 2 diabetes.[16–18] According to the Third National Health and Nutrition Examination Survey (NANHES-III), individuals ≥40 years infected with HCV have at least a three-fold increased chance of developing type 2 diabetes than those without HCV infection.[19] This study confirms the existence of various metabolic abnormalities, which from a clinical standpoint, support the contention that HCV-positive patients may have a decreased or even lack of SVR compared to individuals who are not infected with HCV.[20]
Fewer subjects positive for either HBV or HCV had elevations in both serum cholesterol and TGs. Instead, more subjects either had normal cholesterol and TGs or only one of the two was abnormally elevated. The difference between 'classic' (i.e. metabolic) MS and viral MS has been widely discussed and could potentially explain these findings. For example, Bugianesi et al. noted that a paradoxically favourable lipid profile in patients with HCV, especially those chronically infected with genotype 3. Specifically, total cholesterol and triglycerides are notably low, which is not typically observed in patients with MS.[8]
Finally, there was no association between HBV and MS (or the individual components) in any gender or age group in this study. This is in agreement with Persico et al. who reported that only 2/126 (1.72%) HBV subjects had MS whereas 76/726 (10.46%) of HCV subjects had MS.[21] Other studies have also noted that metabolic dysfunction (e.g. type 2 diabetes mellitus) is more common in HCV patients than other liver diseases, including patients infected with HBV. Jan et al. earlier confirmed those findings in a large (n = 53 528) population-based cross-sectional study.[22] Specifically, Jan and colleagues found that the likelihood of developing MS was lower in HBsAg-positive individuals compared with those who are HBsAg negative. Currently, it remains unclear why the two different hepatitis viruses so markedly differ in their role in MS (and its components), and more research is clearly necessary.
The overall prevalence of HBV and HCV in this study was 3448 (13.1%) and 1098 (4.2%) respectively. This is consistent with other studies that have reported that HBV and HCV infections are common in China. For example, a recent study by Li et al. reported a prevalence of HBsAg of 7.44% in Anhui province, China.[3] Risk factors for HBV included male gender and age.[3] The prevalence of HCV was similar to other reports indicating the prevalence of HCV in the general population in China is 3.2%.[23] The rate of anti-HCV positivity increased with age, and more women >45 years were positive than men.
Several limitations of this study are worth noting, including the fact that this was a cross-sectional study with no longitudinal follow-up. There was also a lack of data on diet and exercise to analyze their effect on metabolic disease in this population. Furthermore, because this was a cross-sectional study of retrospective nature, the authors did not have data regarding anti-HBsAb, HCV RNA, or follow-up data for HBsAg, anti-HBsAb or HCV RNA. Therefore, HBsAg (0.9–10) and anti-HCV [1-10] could only be classified as equivocal or 'weakly positive', and chronic infection status could neither be determined nor confirmed. Persistent anti-HCV positive status (× 2) or assaying HCV RNA is typically used to confirm chronic hepatitis; however, it was not possible to do that in this retrospective, cross-sectional study. The authors therefore attempted to minimize potential errors in HCV status by considering that in the nonacute infection phase, patients with past infection that were cured should have lower antibody titre while patients with chronic infection should be higher. Results for 'weakly positive' and 'positive' were analyzed separately. In addition, because Taiwan is endemic for HCV infection, subjects >45 years are anticipated to primarily have chronic infections compared with those <45 years old, which is why patients were categorized separately. Similarly, the authors did not have follow-up data (for >6 months), so information regarding 'chronicity' was not available. Instead, determination of chronic infection status was based on an HBsAg >10 and an anti-HCV >10 in an attempt to minimize diagnostic error. Despite these (and other) limitations, this was a large, population-based study conducted in an area with a high prevalence of both HCV and HBV. Key findings of this study were that both male and female subjects >45 years infected with HCV, but not HBV, were at increased risk for metabolic diseases, including MS and diabetes.
Overall, these findings corroborate previously published studies in this field and highlight the need for close patient monitoring and intervention in this age group, regardless of gender. The finding of favourable lipid profiles in HBV- and HCV-positive patients supports the theory that two 'types' of MS exist (i.e. metabolic and viral) that could potentially occur in concert in some patients. More specifically, the patients in this study were stratified by age. The patients >45 years could be construed as having long-term infections, while the patients <45 years could be considered as having short-term infections. It is presumed that HCADS requires a prolonged, chronic infection (likely many years) before reductions in TG and total cholesterol are noted, which was noted in this study, particularly considering that anti-HCV-negative patients >45 years did not have altered TG and cholesterol. That said, this study is limited by its cross-sectional nature, and longitudinal studies lasting >10 years are needed to confirm this finding/association. Furthermore, because this was a cross-sectional study, the effectiveness of treatment was not studied; however, this would have been an interesting and potentially beneficial addition to this project.
There were obvious metabolic derangements in patients infected with the hepatitis C virus who were also diagnosed with MS, particularly those >45 years of age. Considering that approximately 50% of CHC patients are not cured with the current standard of care, perhaps partly because of metabolic alterations, additional investigations focusing on the impact of viral and metabolic MS are warranted. Currently, no specific, evidence-based treatment strategies for managing patients with CHC that fail conventional therapy exist, despite the fact that such treatments are desperately needed.[10] In the meantime, the authors of this study recommend monitoring CHC subjects (especially those >45 years) to assess liver enzyme levels and AFP; routine hepatic ultrasound examinations, and tracking lipid profiles, fasting blood glucose, and waist circumference, regardless of baseline values. Patients with hepatosteatosis, hyperglycaemia, or increased waist circumference should be advised of their cardiovascular risks.
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