慢性肝炎高盛行率之台灣地區巨紅血球症的評估

Evaluation of Macrocytosis in Taiwan, an Area with High Prevalence of Chronic Viral Hepatitis

Macrocytosis, defined as a mean corpuscular volume (MCV) over 100fL, is a frequent erythrocyte abnormality of routine automated complete blood count (CBC) in hospital central hematology laboratories. The etiologies of macrocytosis in different populations have been reported including vitamin B12/folate deficiency, chronic alcoholism, hypothyroidism, liver disease and medicine intervention, such as with chemotherapeutic agents, hydroxyurea and antiretroviral drugs. However, evaluation of macrocytosis not yet been performed in Taiwan, an endemic area with chronic liver disease mostly caused by the infections of hepatitis B and C viruses (HBV and HCV). In this study, a retrospective survey with an objective to characterize macrocytosis from CBC data warehouse was conducted in the central Hematology Laboratory of National Cheng Kung University Hospital, Tainan, Taiwan. During April 1 to May 31, 2013, 637 (male=447, female=190) cases displaying MCV>105fL were recruited. The CBC hemograms, biochemical data and serological markers for HBV and HCV were recorded. The increment of MCV values were stratified into 3 groups (105-110fL, 110-115fL and >115fL). Among the 637 macrocytotic cases, 439 (68.9%) had an anemic hemoglobin (Hb) level (male<13g/dL, female<12g/dL), and the rates for macrocytic anemia were constant among the 3 stratified MCV groups. The increment of MCV was associated with decreased rates of abnormal total bilirubin (p=0.039), and with increased HBV surface antigen (HBsAg) positive (p=0.002). Furthermore, the group with HBsAg positive had higher values of MCV (p=0.002), mean corpuscular hemoglobin (MCH) (p=0.031) and red blood cell distribution width (p<0.001), but a lower platelet count (p<0.001) in the CBC hemograms than did the group with negative HBsAg. Additionally, the MCV values negatively correlated with RBC count but positive correlated with MCH in either the presence or the absence of HBV infection. On contrary, a differential correlation of MCV values with mean corpuscular hemoglobin concentration (p<0.001) was revealed only in the HBsAg-negative cases and with Hb (p=0.023) and hematocrit (p=0.004) in HBsAg-positive cases. In conclusion, our study suggests that the macrocytic phenotypes might display distinct hemograms in patients who were infected with HBV, and checking the laboratory parameters in association with hepatitis B diseases and treatments are highly encouraged for macrocytic cases in an area with high prevalence of chronic hepatitis B.

巨紅血球症（macrocytosis）是醫院血液實驗室常規自動化全血球計數，常見的紅血球異常，其定義為平均紅血球體積大於100fL。不同族群的巨紅血球症病因已有報導，包括維生素B12或葉酸缺乏、慢性酒精中毒、甲狀腺機能低下症、肝臟疾病以及藥物介入，如化療藥物、羥基脲及抗反轉錄病毒藥物等。但是，在台灣這個B型與C型肝炎病毒感染所導致的慢性肝炎高盛行地區，則仍未對巨紅血球症進行評估。本篇研究即於台灣台南的成大醫院血液實驗室，從全血球計數的數據資料庫實施回溯性的巨紅血球症特性調查。收樣2013年4月1日至5月31日間平均紅血球體積超過105fL的637個案（男性為447人，女性為190人），紀錄其全血球計數數據、生化數據及B型與C型肝炎病毒血清標記結果，隨著平均紅血球體積的數值增加，將之分層為105-110fL、110-115fL及＞115fL三組。在637個案中，439（68.9％）其血紅素達貧血標準（男性＜13g/Dl；女性＜12g/dL），且平均紅血球體積數值三組間，其巨紅血球性貧血之比率相同。平均紅血球體積數值增加與不正常的總膽紅素數值的比率減少（p=0.039）及B型肝炎病毒血清標記陽性比率增加（p=0.002）相關。B型肝炎病毒表面抗原陽性組別相較於陰性組別，具有較高的平均紅血球體積（p=0.002）、平均血球血紅素（p=0.031）及紅血球分佈寬度（p＜0.001），但具較低的血小板數（p＜0.001）。同時，無論是否受到B型肝炎病毒感染，平均紅血球體積數值與紅血球數量呈現負相關，但與平均血球血紅素呈現正相關；然而，平均紅血球體積數值與平均血紅素濃度，僅於B型肝炎病毒表面抗原陰性組呈現相關；平均紅血球體積數值與血紅素及血球容積比，則僅於B型肝炎病毒表面抗原陽性組呈現相關。綜合以上研究，我們認為巨紅血球症在B型肝炎病毒感染病患具特別的血球相變化，在慢性B型肝炎高盛行地區，醫院血液實驗室檢查發現巨紅血球症，應增加考慮是否與B型肝炎病毒感染與治療相關。