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作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　October 12, 2009 — B型肝炎基金會發表孩童感染慢性B型肝炎(HBV)之篩檢、監控與轉診指引。新版建議與臨床醫師計畫線上發表於10月5日的小兒科期刊。
　　
　　賓州兒童醫院的Barbara A. Haber醫師等人寫道，多數的兒童慢性HBV感染是沒有徵兆或症狀的，所以相當需要醫師的警覺性來加以辨識。對於開業醫師來說，重點在於瞭解和使用適當的監督、監控且及時轉診。在最近幾年，我們對於B型肝炎的瞭解以及整個可用的治療都逐漸成長，因此需更新臨床實務和方法。
　　
　　慢性HBV感染的定義為，有持續的陽性B型肝炎表面抗原(HBsAg)達6個月以上。雖然大多數的慢性HBV感染孩童沒有症狀，且通常不需要治療，實際上，他們在後來會面臨的肝病、肝癌和其他併發症風險更大，有時候甚至在30歲之前就發病。經母親傳染給小孩的HBV感染者，發生肝細胞腫瘤(hepatocellular carcinoma，HCC)的風險較高。
　　
　　在小兒科，HCC的盛行率低，但是其發病率和死亡率結果使執業者對於小兒風險有所警惕；重點在於這些小孩有關疾病惡化的終身監控。
　　
　　小孩一旦有HBV 感染診斷，後續的處置並沒有明確定義。在北美，專長於B型肝炎的小兒肝臟專家相對較少，以前也沒有針對小兒B型肝炎的處置指引。
　　
　　2008年11月11日，B型肝炎基金會這個支持研究和促進疾病相關建議的非營利組織，在北美組織一個小兒肝臟專家小組。根據他們的經驗和現有的證據，授權他們發展和建議小兒(18歲以下者)的HBV感染篩檢、監控、初步治療與轉診之建議策略。
　　
　　特別的是，這些指引傾向協助執業者確認是否須進行額外檢查、根據檢測結果確認監測頻率、何時應轉診給小兒肝臟專家。在開業醫師和肝臟專家之間建立夥伴關係，有助於孩童治療這個終身感染症。
　　
　　應進行慢性HBV感染篩檢的小孩包括：
　　* 出生於當地盛行HBV之國家的小孩，即使他們已經接受B型肝炎疫苗。這些盛行地區包括亞洲、非洲、南太平洋與中太平洋島嶼、東歐與歐洲之地中海地區、格陵蘭、俄羅斯、中東、亞馬遜河流域，以及加勒比海地區。
　　* 北極、澳洲和紐西蘭當地的原住民。
　　* 自盛行地區遷入美國之父母親所生的小孩。
　　* HbsAg陽性母親所生的小孩。
　　* 家中成員有HbsAg陽性者的孩童，包括出生後接受B型肝炎疫苗但是在接種前沒有篩檢的孩童。
　　
　　對於慢性HBV感染孩童之監控的特定建議包括：
　　* 任何小孩只要丙氨酸轉氨酶(ALT)或α胎兒蛋白值升高，或家族有HCC病史，或HbeAg陰性但是HBV DNA值高於2000 IU/mL，都需轉診給小兒肝臟專家。
　　* 開始時的評估需包括含ALT值之肝臟功能檢測，與包括白血球/血小板數量在內的全血球計數。
　　* ALT值升高的定義為大於正常檢測上限值或者大於40 IU/L，看哪一個較低。
　　* ALT與α胎兒蛋白值應每6至12個月檢測。
　　* HBeAg/Anti-HBe 與HBV DNA值應每12個月檢測。
　　* 根據許多小兒專家，家族有HCC病史、ALT或α胎兒蛋白值升高的小孩，每1到2年進行超音波檢測。
　　
　　孩童HBV感染的治療因為可能發生抗藥性與其他風險而益發複雜。目前獲得美國食品藥物管理局核准用於孩童慢性B型肝炎初步治療的抗病毒藥物，adefovir用於12歲以上者、entecavir用於16歲以上者、干擾素α-2b用於12個月以上者、lamivudine用於3歲以上者。
　　
　　指引之作者結論表示，對於HbeAg陽性和ALT值升高、代償性肝病的小孩，應考慮6至12個月的觀察期，以確認是否為發生自發性HbeAg血清轉化。有關抗病毒之初步治療決策與許多尚未解答的問題有關，就孩童有限的治療方式來說，最重要的是效果、治療期間、抗藥性風險。再次強調，一線開業醫師和小兒肝臟專家之間的成功夥伴關係，可以促進感染這終身感染之孩童的成功篩檢、初步處置與監控。
　　
　　發表這些指引的這項研討會，是由B型肝炎基金會召集與資助，該基金會主要接受聯邦、州與私人資金會和個人的捐助，以及Bristol-Myers Squibb、Gilead Sciences、Idenix、Merck和Novartis等藥廠的小額不限定用途教育資金。
　　
　　有些指引作者宣告與Bristol-Myers Squibb、Gilead、Roche、Novartis和/或Merc等藥廠有各種財務關係。
　　
　　Pediatrics. 線上發表2009年10月5日。

Hepatitis B Foundation Issues Guidelines for Pediatric Screening, Monitoring, and Referral

By Laurie Barclay, MD
Medscape Medical News

October 12, 2009 — The Hepatitis B Foundation has issued guidelines for the screening, monitoring, initial management, and referral of children with chronic hepatitis B virus (HBV) infection. The new recommendations, which target clinicians, are published online in the October 5 issue of Pediatrics.

"The majority of children with chronic...HBV infection have no signs or symptoms of chronic disease, [so] identification requires a heightened awareness on the part of physicians," write Barbara A. Haber, MD, from Children's Hospital of Philadelphia in Philadelphia, Pennsylvania, and colleagues. "It is important for practitioners to understand and use appropriate surveillance, monitoring, and timely referral. Our understanding of hepatitis B disease and the armamentarium of available therapies has grown substantially in recent years, calling for a fresh look at clinical practices and approaches."

Chronic HBV infection is defined as having persistently positive hepatitis B surface antigen (HBsAg) for longer than 6 months. Although most children with chronic HBV infection are asymptomatic and usually do not require treatment, they are at greater risk for advanced liver disease, liver cancer, and other severe complications later in life, sometimes even before age 30 years. The highest risk for hepatocellular carcinoma (HCC) occurs with HBV infection acquired via maternal-fetal transmission.

In the pediatric age group, the prevalence of HCC is low, but the morbidity and mortality of this outcome warrant vigilance among practitioners caring for at-risk children. It is crucial that these children have lifelong monitoring for progression of disease.

Once HBV infection is diagnosed in a child, subsequent management is not well defined. In North America, relatively few pediatric liver specialists concentrate on hepatitis B, and there have been no previous management guidelines specific for pediatric hepatitis B.

On November 11, 2008, the Hepatitis B Foundation, which is a nonprofit organization supporting research and promoting disease advocacy, assembled an expert panel of pediatric liver specialists nationally recognized in North America. Based on their expertise and on available evidence, their mandate was to develop and recommend strategies for screening, monitoring, initial management, and referral of children (< age 18 years) with chronic HBV infection.

Specifically, these guidelines were intended to help practitioners determine what additional tests to perform, how often to monitor based on test results, and when to refer to a pediatric liver specialist. Fostering a partnership between the practitioner and liver specialist should facilitate treatment of children with this lifelong infection.

Children who should be screened for chronic HBV infection include the following:

Children born in a country endemic for HBV, even if they received hepatitis B vaccine in their country of origin. Endemic regions are Asia, Africa, South- and mid-Pacific Islands, Eastern and Mediterranean Europe, Greenland, Russia, the Middle East, Amazon Basin, and Caribbean.
Indigenous populations from the Arctic, Australia, and New Zealand.
Children born in the United States to immigrant parents from endemic areas.
Infants born to HBsAg-positive mothers.
Children in the same household as someone who is HBsAg positive, including those children who received hepatitis B vaccine after birth who were not screened before vaccination.
Specific recommendations for monitoring children who have chronic HBV infection include the following:

Referral to a pediatric liver specialist is indicated for any child who has an elevated alanine aminotransferase (ALT) or alpha-fetoprotein level, who has a positive family history of HCC, or who is HBeAg negative but has an HBV DNA level of more than 2000 IU/mL.
The baseline evaluation should include a hepatic function panel with ALT level and complete blood count including white blood cell/platelet counts.
Definition of elevated ALT level is a level greater than the testing laboratory upper limits of normal or more than 40 IU/L, whichever is lower.
ALT and alpha-fetoprotein levels should be measured every 6 to 12 months.
HBeAg/Anti-HBe and HBV DNA levels should be measured every 12 months.
Especially for children with a family history positive for HCC or in whom ALT or alpha-fetoprotein level is elevated, ultrasound every 1 to 2 years may be indicated, according to many pediatric specialists.
Treatment of HBV infection in children is complicated by potential development of drug resistance and other risks. Antiviral drugs that are currently approved by the US Food and Drug Administration for use as initial therapy for chronic hepatitis B in children are adefovir for ages 12 years and older, entecavir for ages 16 years and older, interferon alfa-2b for children 12 months and older, and lamivudine for children 3 years and older.

"For children who are HBeAg-positive with elevated ALT levels and compensated liver disease, an observation period of 6 to 12 months should be considered to determine if spontaneous HBeAg seroconversion occurs," the guidelines authors conclude. "There are many unanswered questions that play into the decision to initiate treatment with antiviral therapy, not least of which are the potential efficacy, duration of therapy, and risk of drug resistance in view of the limited therapeutic options for children. Again, a successful partnership between the primary practitioner and pediatric liver specialist can enhance the success of screening, initial management, and monitoring of children with this lifelong infection."

The workshop leading to development of these guidelines was convened and funded by the Hepatitis B Foundation, which is supported primarily by federal, state, and private foundation grants and individual charitable donations, with small unrestricted educational grants from Bristol-Myers Squibb, Gilead Sciences, Idenix, Merck, and Novartis.

Some of the guidelines authors have disclosed various financial arrangements with Bristol-Myers Squibb, Gilead, Roche, Novartis, and/or Merck.

Pediatrics. Published online October 5, 2009.