< Presentation of Case >
A 61-year-old woman was seen because of nausea, vomting, and tea-colored urine for 3 weeks.
The patient had a history of hypertension, for which she received oral antihypertensives; and right breast cancer, invasive ductal carcinoma, pT2N1aM0, stage II b that was diagnosed in September 2012, for which she had undergone right lumpectomy, dissection of the axillary lymph nodes, and breast reconstruction with tissue expander on 7 September, 2012. Chemotherapy with the regimen of cyclophosphamide and Toxotere was initiated in October 2012. and she received follow-up as an outpatient in the Department of Surgery at this hospital. On 8 November, 2012, the fouth day of the third cycle of chemotherapy, she developed grade 2 nausea and vomiting, general malaise and tea-colored urine. There were no abdominal pain or clay-colored stool. Follow-up liver function tests showed elevated aminotransferases and hyperbilirubinemia. Tests for coagulation were within normal limits and those for viral hepatitis serologies showed negative results for hepatitis B virus (HBV) and hepatitis C virus (HCV). She did not take other medications than hypnotics and antihypertensives. She did not report a history travel abroard or to the countryside. A diagnosis of chemotherapy-related hepatitis was made and she was admitted to the hospital for further evaluation.
On admission, follow-up laboratory tests showed elevated levels of aminotransferases, total bilirubin and prolonged prothromin time. The abdominal ultrasound showed parenchymal liver disease and minimal ascites, and no biliary tract dilatation was noted. Serologic tests showed no findings suggestive of acute infection with hepatitis A virus (HAV), HBV, HCV, cytomegalovirus (CMV), or Epstein-Barr virus (EBV). A serum sample was submitted to the Taiwan Centers for Disease Contrl (CDC) for hepatitis E virus (HEV) serologies. Tests for autoimmune profiles showed negative findings. A positive direct Coomb's test with a low hepatoglobin level was found, and a diagnosis of immune-related hemolysis (due to drug or autoimmunity) was made.
She underwent liver biopsy on 7 December, 2012. The pathology showed acute hepatitis with intra-hepatic cholestasis, which was sugegstive of drug-related hepatitis. On 14 December, 2012, we were informed of the results of the serologic tests for HEV, which showed positive for anti-HEV IgM and IgG. A diagnosis of acute hepatitis E was made. The hyperbilirubinemia and elevated aminotransferases improved gradually with supportive treatment.
The results of laboratory studies on admission are as follows.
CBC:
Hb
g/dl |
WBC
K/μl |
Plt
K/μl |
MCV
fL |
11.1 |
5.24 |
165 |
87.2 |
Biochemistry:
Alb
g/dL |
T-bil
mg/dL |
D-bil
mg/dL |
AST
U/L |
ALT
U/L |
ALP
U/L |
GGT
U/L |
BUN
mg/dL |
Cre
mg/dL |
Na
mmol/L |
K
mmol/L |
3.1 |
5.8 |
3.05 |
420 |
567 |
82 |
230 |
7.6 |
0.6 |
136 |
4.4 |
PT
sec |
INT |
PTT
Sec |
11.4 |
1.08 |
25.7 |
Virology:
IgM anti-HAV |
HBsAg |
Anti-HBs |
Anti-HCV Ab |
IgM/IgG anti-HEV |
Negative |
negative |
Positive |
negative |
positive/positive |
< 討論 >
肝炎是一種因肝臟細胞的發炎，導致肝細胞損傷的肝臟疾病。引起肝炎的原因很多，如果是由E型肝炎病毒感染所造成的肝炎，就叫做E型肝炎。
E型肝炎病毒為一種球形、無套膜、單股RNA病毒。在感染急性期的初期可在患者糞便中發現32至34 nm大小類似病毒狀的粒子。根據資料顯示E型肝炎病毒至少有四種以上的基因型，中國大陸東南的廣州和台灣分離出的屬於第四基因型，隨著分子流行病學更廣泛的研究，未來可能會有更多基因型的發現。
E型肝炎病毒流行區通常發生於環境衛生較不好的開發中國家包括印度、緬甸、尼泊爾、巴基斯坦、蘇聯、阿爾及利亞、利比亞、索馬利亞、墨西哥及中國大陸。通常E型肝炎流行多因水污染引起，但散發性病例及與水污染感染似乎無關連之爆發流行事件亦曾報告。另根據國外研究資料顯示，在豬血及豬糞中可以分離出基因序列相當近似人類E型肝炎病毒的病毒，這也顯示豬隻所攜帶的HEV可能會經過接觸或食用到未煮熟的豬內臟（生吃豬肝、生吃豬肉…）而傳播給人，但豬隻及其他動物是否扮演病毒儲存庫的角色仍是值得研究的議題。而E型肝炎侵襲率以年輕人及中年人最高，通常男性感染率較高。兒童及老年人發生E型肝炎的情形較不常見。
臺灣急性病毒性E型肝炎病例概況：依據全國法定傳染病通報資料顯示，各項急性肝炎確定病例及境外移入個案數如下，其中急性病毒性E型肝炎，2007-2009年每十萬人口發生率分別為0.05、0.06、0.04。
E型肝炎主要借由糞口途徑傳染，藉由受污染的水傳播最常見，另人與人之間的糞口途徑感染亦可能發生，雖然在爆發流行時家戶內的二次感染不高，最近研究顯示E型肝炎可能為人畜共通傳染病。
E型肝炎與A型肝炎類似，發病情況通常為突然出現發燒，全身倦怠不適，食慾不振，嘔吐及腹部不舒服，數天之後發生黃疸。除孕婦外，其他人口感染E型肝炎的致死率與A型肝炎類似（約千分之一），懷孕第三期的孕婦感染E型肝炎時，其致死率有報告達20％。
E型肝炎潛伏期為15~64天，平均潛伏期從26～42天。
E型肝炎的診斷是借由臨床及流行病學上的資料並經由血清學方法除去其他肝炎致病原。在研究實驗室已可使用數種檢驗方法，包括偵測IgM及IgG的enzyme immunoassays及Western blot assays偵測血清及糞便中RNA的PCR；及偵測抗體的immunofluorescent antibody blocking assays。
在治療照護方面,患者多數被感染後都能自癒，少數患者演變成較嚴重的急性肝炎，甚至猛爆性肝炎，在治療上並無特殊治療，一般給予支持性療法即可。在接種預防方面，根據大陸在2010年於Lancet的發表，目前大陸已研發出E型肝炎疫苗，且能有效預防E型肝炎的感染。
< 參考資料 >
- 衛生署疾病管制局：傳染病介紹 - 急性病毒性Ｅ型肝炎
- N Engl J Med 2012;367:1237-44
- Lancet Infect Dis 2008;8:698-709.
- Lancet 2010;376:895-902.
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Case Discussion
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