作者：Roxanne Nelson
出處：WebMD醫學新聞
October 3, 2008 - 研究者表示，過去暴露在B型肝炎病毒（HBV）可能與發生胰臟癌有關。除此之外，當病患接受化學治療時，HBV有再度活化的潛力。
研究者在10月1日臨床腫瘤學期刊上表示，這是第一項研究病毒肝炎與胰臟癌關聯的研究。他們發現過去暴露在HBV下的病患，發生胰臟癌的盛行率顯著地比健康人控制組高（7.6%比上3.2%）。然而，暴露在C型肝炎（HCV）下並不會顯著影響這個風險。
資深作者、德州大學安德森癌症中心腸胃道癌症部門主任與教授，同時也是休士頓腸胃道癌症中心副醫療主任的James Abbruzzese博士，推測這可能是因為HBV與HCV之間先天的差異。
他在一項訪談中向Medscape腫瘤學表示，HBV傾向是各全身的病毒，會在全身循環。HCV比較傾向待在肝臟，我們推測這可能是HCV病毒不會增加胰臟癌風險的原因之一。這也傾向是個低度的感染，且以長時間感染表現，因此這兩種病毒的自然史是相差很多的。
HBV與HCV顯著地與末期慢性肝臟疾病有關，包括肝細胞腫瘤、以及膽管惡性腫瘤，但是肝炎也是一種會有肝臟外表現的全身性疾病。肝炎病毒與肝臟外癌症之間的關係，目前為止只在非何杰金氏淋巴瘤病患身上研究；其他研究已經針對癌症病患接受細胞毒性或是免疫抑制療法，造成HBV感染重新活化進行研究。
作者寫道，胰臟是另一個肝炎病毒的潛在標的，因為這最接近肝臟，且因為這兩個器官共享相同的血管與管道。研究發現罹患急性或慢性HBV或HCV感染病患，大多數有胰臟酵素上升的情形，代表的是病毒性肝炎可能導致胰臟損傷的可能性。
【過去暴露在B型肝炎病毒下是顯著的】
Abbruzzese博士與同事收納了476位病理學確認罹患胰臟腺瘤，以及879位相對應的控制組。從這兩組受試者中抽血檢驗HCV抗體、HBV表面抗原（HBsAg）、與HBV核心抗原抗體（anti-HBc）、以及對抗HBsAg的抗體（anti-HBs）。
他們發現過去暴露在HBV的盛行率，以出現anti-HBc抗體來看，罹患胰臟癌病患顯著地比控制組高（7.6%比上3.2%）；暴露在HBV且有HBV復原證據或是免疫力也顯著地與胰臟癌風險增加有關（校正後的勝算比[AOR]為2.3），但是過去暴露但沒有HBV復原證據的風險更高（AOR為4.0）。
在校正危險因子後，糖尿病病史、吸菸以及有癌症家族史都顯著地與胰臟癌有關；有糖尿病也顯著地增加過去暴露在HBV病患胰臟癌風險。
研究者並未發現HCV與胰臟癌之間有顯著關係；胰臟癌病患有1.5%有HCV抗體，控制組有1%病患有HCV抗體。
【在化學治療時潛在感染再發】
這項研究引發的另一個重點是，所觀察到的anti-HBc陽性狀況的高盛行率，可能是潛在HBV感染的一個指標，這可能導致化學治療時HBV感染再發。HBV感染再發與接受化學治療的癌症病患發生肝臟衰竭有關，雖然病毒重新活化的機轉目前並不清楚。一個假設是，化學治療增加了HBV病毒複製。
Abbruzzese博士表示，有高風險行為或是在可能暴露到病毒工作環境下的工作人員，在開始進行化學治療前，都應該確認它們的HBV狀態。這是很簡單且很便宜的，只需要抽血檢驗，如果有需要的話，病患可以接受抗病毒藥物來減輕、甚至是消除病毒。
Abbruzzese博士解釋，他希望其他團隊可以開始檢驗這個病例控制研究，來看HBV是否是項議題。我們將可以看到確認我們這項研究的研究結果。如果HBV感染與胰臟癌之間的關係可以被其他研究確認，這些發現將提供胰臟癌成因更多的資訊。這可能使得我們可以找出胰臟癌一個可以很快地修飾的危險因子。
然而，在這個時候，Abbruzzese博士表示，要建議有HBV感染病史病患進行胰臟癌篩檢仍嫌太早。現在，該風險顯然是相當低的，我們希望試著去做結合糖尿病與其他危險因子，以及分子因子，合併成一個風險模式來確認出高風險病患。
這項研究由國家衛生研究院與Lockton研究基金會的經費贊助。研究者表示沒有相關資金上的往來。
Hepatitis B Virus Associated With Pancreatic Cancer
By Roxanne Nelson
Medscape Medical News
October 3, 2008 ?Past exposure to the hepatitis?B virus (HBV) might be associated with the development of pancreatic cancer, researchers report. In addition, there is a potential for HBV to be reactivated when patients undergo chemotherapy treatment.
This is the first study to investigate the association between viral hepatitis and pancreatic cancer, the researchers note in the October 1 issue of the Journal of Clinical Oncology. They found that the prevalence of past exposure to HBV was significantly higher in patients with pancreatic cancer than in healthy controls (7.6% vs 3.2%). However, exposure to hepatitis?C (HCV) was not significantly different in the 2 groups.
Senior author James Abbruzzese, MD, professor and chair of the department of gastrointestinal medical oncology at the University of Texas MD Anderson Cancer Center and associate medical director of the Gastrointestinal Center, in Houston, speculated that the reason for this might be due to the innate differences between HBV and HCV.
"HBV tends to be a systemic virus that circulates throughout the body," he told Medscape Oncology in an interview. "HCV is much more hepatotrophic, and we can speculate that it may be 1 of the reasons that it doesn't appear to increase the risk of pancreatic cancer. It also tends to be a lower-grade infection and manifests over a long period of time, so the natural history of these 2 viruses is quite different."
Both HBV and HCV are significantly associated with end-stage chronic liver diseases, including hepatocellular carcinoma and cholangiocarcinoma, but hepatitis is also a systemic disease with extrahepatic manifestations. The association between the hepatitis virus and extrahepatic cancers has only been studied in non-Hodgkin's lymphoma to date; other studies have investigated the reactivation of HBV infection in cancer patients undergoing cytotoxic or immunosuppressive therapy.
The pancreas could be another potential target for the hepatitis virus because of its proximity to the liver, and because the 2 organs share common blood vessels and ducts, the authors write. Studies have found elevated levels of pancreatic enzyme in a substantial percentage of patients with acute or chronic HBV or HCV infection, which supports thepossibility that viral hepatitis can lead to pancreatic damage.
Past Exposure to Hepatitis B Was Significant
Dr. Abbruzzese and colleagues recruited 476 patients with pathologically confirmed adenocarcinoma of the pancreas and 879 matched controls. Blood samples from both groups were tested for the presence of HCV antibodies, HBV surface antigen (HBsAg), antibodies against HBV core antigen (anti-HBc), and antibodies against HBsAg (anti-HBs).
They found that the prevalence of past exposure to HBV, which was indicated by the presence of anti-HBc, was significantly higher among patients with pancreatic cancer than among controls (7.6% vs 3.2%). Past exposure to HBV with evidence of HBV recovery or immunity was also significantly associated with an increased risk for pancreatic cancer (adjusted odds ratio [AOR], 2.3), but past exposure without evidence of HBV recovery was associated with an even greater risk (AOR, 4.0).
After adjustment for risk factors, a history of diabetes mellitus, cigarette smoking, and a positive family history of cancer were significantly associated with the development of pancreatic cancer. The presence of diabetes also significantly increased the risk for pancreatic cancer in patients with past exposure to HBV.
The researchers did not find a significant association between HCV and pancreatic cancer. The prevalence of HCV antibodies was 1.5% among pancreatic cancer patients and 1% among the control group.
Reactivation of Occult Infection During Chemotherapy
An important point raised by this study is that the observed high prevalence of anti-HBc-positive status might be an indication of an occult HBV infection, which might lead to the reactivation of HBV during chemotherapy. HBV reactivation is associated with hepatic failure among cancer patients who undergo chemotherapy, although the underlying mechanism of viral reactivation remains unclear. One hypothesis is that chemotherapy enhances the replication of HBV.
"In patients who have any history of high-risk behaviors or who work in settings where they may be exposed to the virus, it would be reasonable to check for HBV status before beginning chemotherapy," said Dr. Abbruzzese. "It is so easy and inexpensive to test the blood and, if needed, a patient can be put on antiviral medications that will lessen or even eliminate the virus."
Dr. Abbruzzese explained that he hoped that other groups would begin reviewing their caseontrol studies to see if HBV is an issue. "We would like to see validation of our study," he said. If the association between HBV infection and pancreatic cancer can be confirmed by other studies, these findings would offer additional insight into the cause of pancreatic cancer. They might even identify a readily modifiable risk factor for pancreatic cancer.
However, at this point, Dr. Abbruzzese said it would be a stretch to recommend screening patients with a history of HBV for pancreatic cancer. "Right now, the risk appears fairly low, and what we're trying to do is combine diabetes and other risk factors, along with molecular factors, into a risk profile that we can use to identify high-risk patients."
The study was supported by grants from the National Institutes of Health and a research grant from the Lockton Research Funds. The researchers have disclosed no relevant financial relationships.
J Clin Oncol. 2008:26:4557-4562. Abstract
[ 本帖最後由 goodcat1111 於 2008-10-16 22:40 編輯 ] |
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