慢性乙型肝炎病毒(HBV)感染的诊断需要将血清学、病毒学、生化学和病理学标记联合考虑。乙肝病毒感染的自然史可以分为四个阶段:免疫耐受、免疫清除( 慢性乙肝病毒e抗原阳性)、不活跃的乙肝病毒表面抗原携带、再次复发(慢性乙肝病毒e抗原阴性)。处于免疫清除和再次复发阶段的患者,谷丙转氨酶(ALT)和乙肝病毒DNA水平都有所升高,需要进行抗病毒药物治疗。
治疗慢性乙肝的首要目的是抑制病毒的复制,以减少肝坏死和延缓进展性肝纤维化的发生。长期抑制血清乙肝病毒DNA很可能会减缓肝硬化和肝失代偿的进程,降低发展为肝癌的风险。目前慢性乙肝的抗病毒治疗包括干扰素、聚乙二醇干扰素α2a、拉米夫定、阿德福韦、恩替卡韦等。
对于乙肝e抗原阳性患者来说,当血清乙肝病毒DNA水平等于或大于105 copies/mL (2,000 IU/mL)、且谷丙转氨酶水平升高的情况下,就需要采用抗病毒疗法,。而对于e抗原阴性的患者,在较低水平就可以采用抗病毒疗法,例如血清乙肝病毒DNA水平等于或大于104 copies/mL (2,000 IU/mL),同时伴随谷丙转氨酶水平升高。
肝脏活检时,至少中度坏死性炎症和肝纤维化的存在对决定采用初始疗法是很有帮助的,尤其是对于丙谷转氨酶水平正常的患者(治疗前是可选的而不是强制的)。在进行治疗时,如果服用口服制剂,患者需要接受每3至6个月一次的监测,以确保能够使用该药,并检测耐药性的发展情况。
但是,对于是否需要制定肝脏活检基线值、乙肝病毒DNA和丙谷转氨酶处于何种水平时需要进行抗病毒疗法、抗病毒疗法要持续多久、用何种药最合适、以及是否需要几种药物联合使用,目前国际上仍然存在争议,还需要进一步的研究来证明。
PMID: 17415343 [PubMed - indexed for MEDLINE]
The diagnosis of chronic hepatitis B virus (HBV) infection
The diagnosis of chronic hepatitis B virus (HBV) infection is made using a combination of serological, virologic, biochemical, and histologic markers. The natural history of HBV infection can be divided into four phases: immune tolerance, immune clearance (HBeAg-positive chronic hepatitis 8), inactive HBsAg carrier, and reactivation (HBeAg-negative chronic hepatitis 8). Patients in the immune clearance and reactivation phases, with elevated alanine aminotransferase (ALT) and HBV DNA levels, are candidates for antiviral therapy.
The primary goal of therapy for chronic hepatitis B is suppression of viral replication, which has been shown to reduce hepatic necroinflammation and retard progression of hepatic fibrosis. Long-term suppression of serum HBV DNA is likely to reduce progression to cirrhosis and hepatic decompensation and decrease the risk of hepatocellular carcinoma. Current antiviral therapy for chronic hepatitis B includes interferon alfa, peginterferon alfa-2a, lamivudine, adefovir, entecavir, and telbivudine.
In patients with HBeAg-positive chronic hepatitis B, antiviral treatment is indicated when the serum HBV DNA level is = or > 10(5) copies/mL (20,000 IU/mL) and the ALT level is elevated. For HBeAg-negative patients, the threshold for initiation of therapy is lower, i.e., a serum HBV DNA level = or > 10(4) copies/mL (2,000 IU/mL) in association with an elevated ALT level.
The presence of at least moderate necroinflammation and the presence of fibrosis on liver biopsy, which is optional and not mandatory before therapy, may be useful in supporting the decision to initiate therapy, particularly in patients with normal ALT levels. While undergoing therapy, patients require monitoring every 3 to 6 months to ensure compliance and to test for the development of resistance if an oral agent is used.
Issues that remain controversial or need to be studied further are the necessity of a baseline liver biopsy, the HBV DNA and ALT thresholds for initiation of therapy, the optimal duration of antiviral therapy, selection of one agent over another, and the role of combination therapy.
PMID: 17415343 [PubMed - indexed for MEDLINE]
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