- 學位論文
台灣偏遠地區居民及原住民B型肝炎之研究
Investigation of Hepatitis B in Residents of Rural Areas and Aborigines in Taiwan
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摘要
一、研究背景及目的 B型肝炎是台灣引起肝癌的最主要原因，然而根據統計，台灣原住民之慢性肝病及肝硬化死亡率雖然遠高於非原住民族群，但肝癌死亡率卻略低於非原住民。此外，偏遠地區之肝癌存活率也較一般都會地區為低。台灣B型肝炎病毒基因型主要為B型及C型，其中基因型B盛行率高達80%，一但隨著肝炎、肝硬化及肝癌的進展，基因型B型之盛行率也逐漸下降；另外，B型肝炎之病毒量偏高與e抗原陽性者，其未來罹患肝癌風險也較高。本研究以台灣偏遠地區居民及原住民為對象，探討一般社區族群之B型肝炎患者，其影響未來罹患肝癌之因子與病毒基因型分佈，是否存在地區性與不同族群間之差異。 二、研究方法 針對台灣偏遠地區成年B型肝炎患者，進行基本資料收集、問卷、抽血檢查（包括：AST、ALT、AFP、e抗原及抗體、病毒量、基因型）及腹部超音波檢查。以即時聚合酶鏈反應法（Real-Time polymerase chain reaction）技術先進行B型肝炎病毒量（HBV DNA level）檢測，以巢式聚合酶鏈反應法(nested polymerase chain reaction) 和多重聚合酵素鏈鎖反應（multiplex-polymerase chain reaction）技術檢定病毒基因型，再來分析病毒全長基因體定序以確定基因型之正確性。最後以不同的統計方法分析所收集之資料結果。 三、研究結果 研究中招募3,488位（1,527位原住民與1,961位非原住民）來自台灣各地偏遠社區的B型肝炎患者，原住民相較於非原住民族群之下，兩者平均年齡約50歲且平均ALT為39 U/L，統計上並無明顯差異；而統計上顯著發現者為：其e抗原陽性率較低（5.3% vs. 10.2%，p-value<0.0001）、HBV DNA>2, 000 IU/ml比率也較低（27.4% vs. 36.7%，p-value<0.0001）、有經常飲酒習慣者比率則較高（40.0% vs. 19.3%，p-value<0.0001）。取其中有基因型分析結果之1,178人，發現任何年齡層之原住民基因型B/C盛行率皆偏高（92.7% vs. 72.7%，p-value<0.05）且以鄒族語系與排灣語系為最高（97%）。而離島地區（澎湖縣與連江縣）非原住民的B型肝炎患者以基因型C為主（60%），本島地區以基因型B為主（89%）。此外，研究中發現13位在台灣相當罕見的基因型D，主要集中於屏東縣，以當地排灣族居多，其病毒量較高（HBV DNA >2,000 IU/ml），且問卷資料顯示雖有部分病患曾經接受輸血、開刀、刺青或穿體洞，但無人曾共用針頭。 四、結論 本研究發現影響罹患肝癌風險的因子，如：B型肝炎病毒之病毒量、e抗原陽性率及基因型C盛行率等，屬於南島語族的原住民都較非原住民族群為低。由此可知B型肝炎並非主要造成原住民慢性肝病死亡率較高的原因，可能是酒精性肝炎或其他原因所導致。另外，某些地區群聚台灣較為罕見之B型肝炎病毒基因型D，其感染途徑與傳播方式，未來都值得進一步研究與調查。
並列摘要
Background: Hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC) in Taiwan. The standardized mortality rates of chronic liver diseases and liver cirrhosis are higher in Taiwanese aborigines than non-aborigines. However, the standardized mortality rate of HCC is slightly lower in Taiwanese aborigines. High HBV DNA, positive HBeAg and genotype C have been shown be the risks for the HBV-related HCC. Therefore, in this study we further investigated the distributions of HCC related risk factors in HBV patients and HBV genotype among different regional areas and ethnic groups. Materials and methods: A total of 3,488 patients (1,527 aborigines and 1,961 non-aborigines) with HBV infection were recruited from various regions in Taiwan. Basic background information and blood samples were collected and abdominal ultrasound examinations were done. The blood samples were checked for AST, ALT, AFP, HBeAg, anti-HBe, HBV DNA by Real-Time PCR (polymerase chain reaction, PCR) and genotype by nested PCR (nested polymerase chain reaction) and multiplex-PCR (multiplex-polymerase chain reaction). The accuracy of HBV genotypes was validated with full length sequence. Results: There were no differences in the mean age (50 years old) and mean ALT levels (39 U/L) between aborigines and non-aborigines. However, lower HBeAg-positive rate (5.3% vs. 10.2%, p<0.0001), lower rate of HBV DNA > 2,000 IU/ml (27.4% vs. 36.7%, p<0.0001), higher rate of drinking habit（40.0% vs. 19.3%, p<0.0001）were noted in aborigines than non-aborigines. Among 1,178 patients with complete data of genotype and HBeAg, the prevalence of genotype B in aborigine group was higher (92.7%) than that in non-aborigine group (72.7%) in any age group (p<0.05), especially in Tsou (97%). The dominant genotype was C in non-aborigines in Penghu County and Lienchiang County (60%) and was genotype B in the countries of Taiwan island (89%). Besides, our research found 13 patients with genotype D, a very rare genotype in Taiwan. Patients with genotype D were clustered in the local Paiwan tribe of Pingtung County. These subjects had higher HBV DNA (greater than 2,000 IU/ml) without the experience of sharing needles with others and some of them had received blood transfusion or surgeries or tattoo or piercings. Conclusion: We found Taiwanese aborigines who belong to Austronesian language populations have lower HBV DNA viral load, lower HBeAg-positive rate and higher prevalence of HBV genotype B when compared with non-aborigines. Therefore, HBV infection is not the major cause of the death of chronic liver diseases in Taiwanese aborigines. A cluster of patients with HBV genotype D was found in the local area of southern Taiwan.
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延伸閱讀
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