Gudat F, Bianchi L, Stalder G A, Schmid M
Schweiz Med Wochenschr. 1976 Jun 12;106(24):812-24.
55 HBAg seropositive patients with chronic hepatitis B selected from a total of 217 liver biopsies were studied for the presence of HBcAg and HBsAg in the liver tissue and of Dane particles in blood by immunofluorescence and electron microscopy. Among 27 patients with non-aggressive chronic inflammation the following constellations were found: a) 19 patients (13 with nonspecific reactive hepatitis, 6 with chronic persistent hepatitis) had isolated HBsAg expression in the tissue (HBs type) and of these only 2 had rare Dane particles; b)4 patients (all with histologically very active chronic persistent hepatitis) with focal HBc- and HBsAg tissue expression (HBc+s type) and detectable Dane particles in blood; c)4 patients (1 with nonspecific reactive, 3 with chronic persistent hepatitis) with generalized HBcAg (and focal HBsAg) expression (HBc type) and multiple Dane particles in blood. Among 22 patients with aggressive inflammation (19 with chronic aggressive, 3 with "hippie"-hepatitis) focal HBcAg tissue expression (HBc+s type) was found in 17 cases and absence of HBcAg in 5 (3 with focal HBsAg, 2 completely negative by immunfluorescence), all 22 associated with Dane particles in blood, however. In a group of 6 immunosuppressed kidney transplant recipients exhibiting a high concentration of Dane particles in blood 5 patients had generalized HBcAg tissue expression (HBc type) in association with non-aggressive inflammation (1 nonspecific reactive and 4 chronic persistent hepatitis). One patient had chronic aggressive hepatitis in conjunction with focal HBcAg expression (HBc+s type). The consistent association of detectable HBcAg formation in the liver and presence of supposedly infectious Dane particles in blood has a bearing on the evaluation and classification of chronic hepatitis B. On the basis of a positive focal (HBc+s type) or generalized HBcAg tissue demonstration (HBc type and/or the direct identification of Dane particles in blood, discrimination of possibly highly infectious forms from those of low or even no infectivity has been rendered possible. This duality applies mainly to clinically and histologically benign non-aggressive forms of hepatitis presenting with a carrier state or chronic persistent hepatitis. On the basis of these and earlier findings a hypothetical concept of chronic hepatitis is presented which possesses proven diagnostic and prognostic applicability to routine liver biopsies. It is also capable of shedding new light on contradictory findings in the literature and serving as a basis for prospective epidemiologic studies.
从217例肝活检病例中选取55例乙肝表面抗原(HBAg)血清学阳性的慢性乙型肝炎患者,通过免疫荧光和电子显微镜检查研究肝组织中乙肝核心抗原(HBcAg)和乙肝表面抗原(HBsAg)以及血液中 Dane 颗粒的存在情况。在27例非侵袭性慢性炎症患者中发现了以下几种情况:a)19例患者(13例为非特异性反应性肝炎,6例为慢性持续性肝炎)在组织中仅有乙肝表面抗原表达(HBs型),其中只有2例有罕见的 Dane 颗粒;b)4例患者(均为组织学上非常活跃的慢性持续性肝炎)有局灶性乙肝核心抗原和乙肝表面抗原组织表达(HBc+s型)且血液中可检测到 Dane 颗粒;c)4例患者(1例为非特异性反应性肝炎,3例为慢性持续性肝炎)有广泛性乙肝核心抗原(和局灶性乙肝表面抗原)表达(HBc型)且血液中有多个 Dane 颗粒。在22例侵袭性炎症患者(19例为慢性侵袭性肝炎,3例为“嬉皮士”肝炎)中,17例发现局灶性乙肝核心抗原组织表达(HBc+s型),5例无乙肝核心抗原(3例有局灶性乙肝表面抗原,2例免疫荧光完全阴性),然而所有22例血液中均有 Dane 颗粒。在一组6例免疫抑制的肾移植受者中,血液中 Dane 颗粒浓度较高,5例有广泛性乙肝核心抗原组织表达(HBc型),伴有非侵袭性炎症(1例为非特异性反应性肝炎,4例为慢性持续性肝炎)。1例患者患有慢性侵袭性肝炎,伴有局灶性乙肝核心抗原表达(HBc+s型)。肝脏中可检测到的乙肝核心抗原形成与血液中可能具有传染性的 Dane 颗粒的一致关联,对慢性乙型肝炎的评估和分类具有重要意义。基于局灶性阳性(HBc+s型)或广泛性乙肝核心抗原组织显示阳性(HBc型)和/或血液中 Dane 颗粒的直接鉴定,有可能区分出可能具有高传染性的形式与低传染性甚至无传染性的形式。这种二元性主要适用于临床上和组织学上良性的非侵袭性肝炎形式,表现为携带状态或慢性持续性肝炎。基于这些及早期发现,提出了一个慢性肝炎的假设概念,该概念在常规肝活检中具有已证实的诊断和预后适用性。它还能够为文献中的矛盾发现提供新的线索,并作为前瞻性流行病学研究的基础。