慢性B型肝炎病毒及C型肝炎病毒感染與老年性黃斑部病變之相關性

Association of chronic hepatitis B and C virus infections with age-related macular degeneration

吳嘉敏(Chia-Min Wu)

指導教授 ： 葉志清

臺北醫學大學/公共衛生學院/公共衛生學系暨研究所/碩士(2017年)

摘要

前言: 老年性黃斑部病變(Age-related macular degeneration,AMD)在不論是開發中國家或已開發國家都是造成老年人視力受損的主因之一，隨著全球高齡化社會逐漸成形，老年性黃斑部病變不但成為備受重視的健康議題，也成為影響生活品質的重要因素之一。近年來有兩篇韓國大規模研究顯示B型肝炎病毒(hepatitis B virus,HBV)血清學表面抗原陽性為老年性黃斑部病變的可能危險因子。另外也有零星的病例報告顯示C型肝炎病毒(hepatitis C virus)感染與視網膜色素上皮細胞病變相關。台灣為慢性B型肝炎及C型肝炎病毒感染高度盛行的國家，本篇研究設法推斷慢性B型肝炎及C型肝炎病毒感染與老年性黃斑部病變間的因果關係。
研究方法:
本研究將採用台灣全民健康保險研究資料庫(National health insurance research database,NHIRD)之 2000年承保抽樣歸人檔(Longitudinal Health Insurance Database,LHID2000) ，由2000年承保檔中隨機抽取100萬人，擷取其各年度就醫資料建置而成。再由資料中經過年齡、性別及被選入時間的頻率配對後，篩選出(1)慢性B型肝炎病毒感染世代及非慢性B型肝炎病毒感染世代;(2)慢性C型肝炎病毒感染世代及非慢性C型肝炎病毒感染世代。分別進行其與老年性黃斑部病變之相關性分析還有其他相關因子的分析。本研究的統計分析皆採用SAS統計軟體作業。連續變項間的檢定使用T檢定，非連續變項間的檢定使用卡方檢定，危險因子與老年性黃斑部病變間風險比(Hazard Ratio,HR)及其95%信賴區間(Confidence Interval,CI)使用Cox比例風險模型分析，最後進行年齡和性別的分層分析。P<0.05視為統計上達顯著水準。
結果:
將有無慢性Ｂ型肝炎病毒感染世代經過多變項分析後發現，慢性Ｂ型肝炎感染者具有較高罹患老年性黃斑部病變的風險(HR=1.41,95% CI=1.23-1.63)，其他危險因子包括年齡[(50-64歲 (HR=2.92,95% CI=2.43-3.51), ≧65歲(HR= 5.53, 95% CI=4.46-6.85)、共病症中的高血壓(HR=1.25,95% CI=1.08-1.45)、糖尿病無合併糖尿病視網膜病變(HR=1.40,95% CI=1.20-1.64)、糖尿病合併糖尿病視網膜病變(HR=1.66,95% CI=1.11-2.48)及白內障(HR=2.61,95% CI=2.24-3.05)。保護因子為居住地理區域為中部地區(HR=0.67,95% CI=0.55-0.81)。將有無慢性Ｃ型肝炎病毒感染世代經過多變項分析後發現，慢性C型肝炎感染者具有較高罹患老年性黃斑部病變的風險(HR=1.42,95% CI=1.19-1.69)，其他危險因子包括年齡[50-64歲 (HR= 2.08,95% CI=1.49-2.91),≧65歲(HR=3.88, 95% CI=2.79-5.39)]、男性(HR=1.22,95% CI=1.05-1.43)、無職業(HR= 1.47,95% CI=1.55-1.89)、共病症中的高血壓(HR=1.28,95% CI=1.07-1.52)、糖尿病併糖尿病視網膜病變(HR= 2.34,95% CI=1.6-3.43)]、白內障(HR= 2.30,95% CI=1.57-3.36)及高血脂症未合併他汀類藥物使用(statin)( HR= 1.26,95% CI=1.05-1.51)。保護因子為居住地理區域為中部地區(HR= 0.77,95% CI=0.62-0.96)。在分層分析中發現慢性B型肝炎病毒感染者中，女性(HR=1.61,95%CI=1.32-1.96)相較於男性(HR=1.25,95% CI=1.02-1.53)傾向有更高風險得到老年性黃斑部病變，但交互作用未達顯著水準(P=0.104)。
結論: 慢性B型肝炎與慢性C型肝炎病毒感染為老年性黃斑部病變的危險因子且具有因果關係。

關鍵字

老年性黃斑部病變 ； 慢性B型肝炎感染 ； 慢性C型肝炎感染

並列摘要

Background:
Age-related macular degeneration (AMD) is one of the main causes of impairment in the elderly both in developing countries and in developed countries. As the global aging society gradually forms, AMD is not only a matter of great health , but also becomes one of the important factors affecting the quality of life. In recent years, two large-scale Korean census studies have shown that hepatitis B virus (HBV)serological surface antigen positive is a possible risk factor for AMD. There are also some case reports showing that hepatitis C virus (HCV) infection is associated with retinal pigment epithelial cell lesions. Taiwan is highly prevalent of chronic HBV and HCV infection. This study aim to analyze the causal relationship between chronic HBV and HCV infection with AMD.
Methods:
This study used the Longitudinal Health Insurance Database 2000 (LHID2000), which is derived from the Taiwan National Health Insurance Research Database(NHIRD) and maintained by the Taiwan National Health Research Institute, includes the registration files and original claims data for the reimbursement of 1,000,000 beneficiaries under the NHI program. These 1,000,000 beneficiaries were randomly selected from the year 2000 Registry of Beneficiaries (n=23.72 million) of the National Health Insurance (NHI) program. Using frequency matching by age, sex and index date, we defined two study groups (1) chronic HBV infection cohort and non-HBV infection cohort; (2) chronic HCV infection cohort and non-HCV infection cohort to analyze the association of chronic HBV infection and chronic HCV infection with AMD. All analyses were conducted using the SAS statistic package. T tests were used to compare differences in continuous variables. Chi-square tests were used to compare differences in categorical variables.
In addition, the relative risk of AMD (Hazard Ratio, HR),the 95% confidence interval(CI) and associated risk factors were analyzed using Cox proportional hazards models. Further, stratification by age and sex were done. The conventional p<0.05 was used to assess statistical significance.

Results:
After multivariate analysis of chronic HBV infection cohort and non-HBV infection cohort, chronic HBV infection cohort has a higher risk of suffering from AMD (HR=1.41,95% CI=1.23-1.63). Other associated risk factors include age(50-64 years HR=2.92, 95% CI=2.43-3.51,≧65 years HR=5.53,95% CI=4.46-6.85), the comorbidities of hypertension(HR=1.25,95% CI=1.08-1.45)、diabetes without diabetic retinopathy(HR=1.40,95% CI=1.20-1.64), diabetes with diabetic retinopathy(HR=1.66,95% CI=1.11-2.48) and cataract(HR=2.61,95% CI=2.24-3.05). The geographical region in the central area is a protective factor for AMD(HR=0.67,95% CI=0.55-0.81). After multivariate analysis of chronic HCV infection cohort and non-HCV infection cohort, chronic HCV cohort has a higher risk of suffering from AMD(HR=1.42,95% CI=1.19-1.69). Other associated risk factors include age(50-64 years HR=2.32,95% CI=1.69-3.18;≧65 years HR=3.88,95% CI=2.79-5.39), male(HR=1.22,95% CI=1.05-1.43), unemployed(HR=1.47,95% CI=1.15-1.89), the comorbidities of hypertension(HR=1.28,95% CI=1.07-1.52), diabetes with diabetic retinopathy(HR=2.30,95% CI=1.57-3.36), cataract(HR=2.34,95% CI=1.97-2.77) and hyperlipidemia without statin use(HR=1.26,95% CI=1.05-1.51). The geographical region in the central area is a protective factor for AMD(HR=0.77,95% CI=0.62-0.96). In patients with chronic HBV infection, women tend to have a higher risk than men of suffering from AMD(HR= 1.61,95% CI=1.32-1.96 versus HR=1.25, 95% CI=1.02-1.53; P=0.104).
Conclusions:
Chronic HBV and chronic HCV infection are risk factors for AMD.

並列關鍵字

age related macular degeneration ； HBV ； HCV

參考文獻

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