家庭事务：家族史如何帮助围绕HBV治疗和监测的临床决策

StephenW

Family Affair: How Family History Helps Navigate Clinical Decisions Around HBV Treatment and Monitoring
delaCruz_AnnaChristina_100x100_Circle
       
Anna Christina L. dela Cruz, MD
Associate Professor
Division of Digestive Diseases and Nutrition
Department of Internal Medicine
University of Kentucky
Lexington, Kentucky
       
       


When managing patients with chronic hepatitis B, some clinical scenarios fall into the gray zones of current guidance. In this commentary, I discuss how I incorporate family history into treatment and monitoring decisions in certain clinical gray zones. In addition, I will walk through how to choose among recommended nucleos(t)ide analogues (NAs) once a decision has been made to initiate treatment.

Incorporation of Family History in the Management of Hepatitis B
Current hepatitis B management guidelines from the American Association for the Study of Liver Diseases (AASLD) recommend that in patients not meeting treatment thresholds for immune-active hepatitis B, either with alanine aminotransferase <2 x upper limit of normal or HBV DNA <2000 IU/mL for hepatitis B e antigen (HBeAg)–negative patients or <20,000 IU/mL for HBeAg-positive patients, a family history of hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC) or cirrhosis should be considered in deciding whether to initiate treatment for hepatitis B.

Multiple studies have corroborated the findings of increased risk of HCC in patients, including HBV carriers, with a family history of HBV-related HCC. Loomba and colleagues demonstrated that a family history of HCC multiplies the risk of HCC at each stage of HBV infection and reported a 40% increase in cumulative risk of HCC when both family history and HBeAg are present.

A family history of HBV-related HCC or cirrhosis should influence the decision not only to start treatment for hepatitis B, but also to initiate long-term screening for HCC. The AASLD recommends HCC screening in hepatitis B surface antigen (HBsAg)–positive patients with a first-degree family member with a history of HCC. The optimal age at which these patients start HCC screening is not yet established.

For patients in the gray zone or not meeting treatment criteria—including following the consideration of age, cirrhosis, degree of fibrosis and inflammation, extrahepatic manifestations, and quantitative HBsAg level—a family history of HBV-related HCC or cirrhosis would shift my decision toward starting treatment for hepatitis B and initiating HCC screening, based on AASLD guidelines and strong data associating family history and HCC risk.

Choosing Among NAs for Chronic Hepatitis B Treatment
Once you have decided to initiate treatment, how do you choose among the recommended NAs? Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are the recommended first-line NAs for patients with chronic hepatitis B, given their potent antiviral activity and high barrier to resistance. Older NAs such as lamivudine, telbivudine, and adefovir are not preferred due to their low barriers to resistance.

When selecting NA therapy, several factors should be considered:

    Presence of decompensated cirrhosis. TDF and ETV are preferred, as TAF has not been studied in these patients. The AASLD suggests that the “use of TAF would be reasonable in patients when TDF adverse effects are a concern and entecavir is not an option.”
    Prior HBV treatment. Tenofovir (TDF or TAF) is recommended over ETV for patients who have had prior antiviral exposure or resistance. ETV is not recommended for patients with lamivudine- or telbivudine-resistant HBV infection.  
    Patients with or at risk for osteopenia/osteoporosis or renal disease. ETV or TAF is preferred. TAF has lower rates of bone and renal abnormalities than TDF does. If a patient is on TDF, monitor renal function and switch to TAF or ETV if TDF-associated bone/renal dysfunction develops. The European Association for the Study of the Liver suggests the following indications in selecting ETV or TAF over TDF: age older than 60 years, bone disease (chronic steroid use, fragility fractures, osteoporosis), or renal alterations (glomerular filtration rate <60 mL/min, albuminuria, low phosphate, hemodialysis).
    Pregnancy. TDF is preferred due to the lack of sufficient data with ETV or TAF.
    Medication cost/insurance coverage. Not all NAs are covered by each patient’s insurance, and healthcare professionals should discuss the potential cost associated with the various treatments based on the patient’s insurance coverage.

StephenW

家庭事务：家族史如何帮助围绕HBV治疗和监测的临床决策
delaCruz_AnnaChristina_100x100_Circle

安娜·克里斯蒂娜·德拉·克鲁兹（MD）
副教授
消化系统疾病与营养学系
内科
肯塔基大学
肯塔基州列克星敦




在管理慢性乙型肝炎患者时，一些临床情况属于当前指南的灰色区域。在这篇评论中，我讨论了如何将家族史纳入某些临床灰色区域的治疗和监测决策中。此外，一旦决定开始治疗，我将逐步介绍建议的核苷酸类似物（NA）的选择方法。

将家族史纳入乙型肝炎的治疗
美国肝病研究协会（AASLD）现行的乙肝管理指南建议，丙氨酸转氨酶<2 x正常上限或HBV DNA上限> 2000 IU且未达到免疫活性乙肝治疗阈值的患者对于乙型肝炎e抗原（HBeAg）阴性的患者为/ mL，对于HBeAg阳性患者为<20,000 IU / mL，应考虑与乙肝病毒（HBV）相关的肝细胞癌（HCC）或肝硬化的家族史开始治疗乙型肝炎。

多项研究证实了具有HBV相关HCC家族史的患者（包括HBV携带者）的HCC风险增加的发现。 Loomba及其同事证明了家族史的HCC在HBV感染的每个阶段都增加了HCC的风险，并且当家族史和HBeAg同时存在时，HCC的累积风险增加了40％。

乙肝相关肝癌或肝硬化的家族史不仅会影响开始治疗乙肝的决定，而且还会影响对肝癌的长期筛查。 AASLD建议对具有一级家族成员且具有HCC病史的乙型肝炎表面抗原（HBsAg）阳性患者进行HCC筛查。这些患者开始进行HCC筛查的最佳年龄尚未确定。

对于处于灰色地带或不符合治疗标准的患者-包括考虑年龄，肝硬化，纤维化和炎症的程度，肝外表现和定量HBsAg水平-HBV相关HCC或肝硬化的家族史将使我的决定转向根据AASLD指南和将家族病史和HCC风险相关的强大数据，开始进行乙肝治疗并开始HCC筛查。

在慢性乙型肝炎的治疗中选择NAs
决定开始治疗后，如何选择推荐的NA？恩替卡韦（ETV），替诺福韦二富马酸富马酸酯（TDF）和替诺福韦阿拉芬酰胺（TAF）是慢性乙型肝炎患者的推荐一线NA，因为它们具有强大的抗病毒活性和高耐药性屏障。拉米夫定，替比夫定和阿德福韦等较老的NA由于抗药性较低，因此不受欢迎。

选择NA治疗时，应考虑以下几个因素：

    存在代偿性肝硬化。首选TDF和ETV，因为尚未在这些患者中研究TAF。 AASLD建议：“当需要考虑TDF的不良反应而不能选择恩替卡韦时，在患者中合理使用TAF”。
    事先进行乙肝病毒治疗。对于先前有抗病毒暴露或耐药性的患者，推荐将替诺福韦（TDF或TAF）优于ETV。不建议对拉米夫定或替比夫定耐药的HBV感染患者使用ETV。
    患有骨质疏松症/骨质疏松症或肾脏疾病或有此风险的患者。首选ETV或TAF。与TDF相比，TAF的骨和肾异常率更低。如果患者正在使用TDF，请监测肾脏功能，并在与TDF相关的骨/肾功能异常发展时切换至TAF或ETV。欧洲肝病研究协会建议在选择TDF之上的ETV或TAF时应考虑以下适应症：年龄超过60岁，骨病（长期使用类固醇，脆性骨折，骨质疏松）或肾功能改变（肾小球滤过率<60 mL / min，蛋白尿，低磷酸盐，血液透析）。
    怀孕。由于缺少ETV或TAF的足够数据，因此首选TDF。
    药物费用/保险范围。并非每个患者的保险都涵盖所有资产净值，因此医疗保健专业人员应根据患者的保险范围，讨论与各种治疗方法相关的潜在费用。

未济

To  StephenW          这篇文章中的“ Family History”（家族史），应该指的是“a first-degree family member” （一级家庭成员或称一级亲属）吧？

StephenW

回复 未济 的帖子

这不是发表的科学论文 , 这是一个治疗乙肝患者的医生的意见 . 她没有定义什么是“家族史” ,一般认为:

家庭病史中应包括哪些信息？ 如果可能，您的家庭病史至少应包括三代人。 汇编有关您的祖父母，父母，叔叔，阿姨，兄弟姐妹，堂兄弟姐妹，孩子，侄女，侄子和孙子的信息。
What information should be included in a family medical history? If possible, your family medical history should include at least three generations. Compile information about your grandparents, parents, uncles, aunts, siblings, cousins, children, nieces, nephews and grandchildren.

未济

回复 StephenW 的帖子

原文第四段“A family history of HBV-related HCC or cirrhosis should influence the decision not only to start treatment for hepatitis B, but also to initiate long-term screening for HCC. The AASLD recommends HCC screening in hepatitis B surface antigen (HBsAg)–positive patients with a first-degree family member with a history of HCC. ”
个人觉得这可视为该医生认可AASLD的观点，把family history 定义为“a first-degree family member”，至少在乙肝患者的监测和筛查方面。

StephenW

回复 未济 的帖子

作者是美国教授 , 因此，她遵循美国（AASLD)指南.

你是对的 , AASLD指南:
如果患者患有肝硬化，患有HCC的一级家庭成员或感染持续时间较长（从年轻开始已被HBV感染的男性为40岁以上，女性为50岁以上），则应继续进行hCC监测。
HCC surveillance should continue if the person has cirrhosis, a first-degree family member with HCC, or a long duration of infection (>40 years for males and>50years for females who have been infected with HBV from a young age).