e抗原阴性慢性乙型肝炎合并非酒精性脂肪性肝病的病理特征

目的观察HBeAg阴性慢性乙型肝炎合并非酒精性脂肪性肝病患者肝组织病理特征。方法收集72例慢性乙型肝炎合并非酒精性脂肪性肝病患者的肝组织标本及临床相关资料,肝组织标本常规行HE、Masson三色及网状纤维染色,观察其病理改变特点,并进行分级、分期。结果HBeAg阴性慢性乙型肝炎合并非酒精性脂肪性肝病患者肝活检病理学改变以肝细胞脂肪变性为主,肝细胞脂肪变性主要位于腺泡Ⅲ带,呈弥漫分布,重度患者则可扩大至腺泡Ⅱ带甚至全腺泡,轻度患者汇管区炎及界面性炎均不明显,主要为小叶内点灶状坏死,大部分患者仅为血窦壁及中央静脉管壁及周围纤维组织增生,且多为纤细的网状纤维,汇管区纤维组织增生不明显,重度及肝硬化患者则汇管区纤维组织增生显著,彼此相连,破坏正常的肝小叶结构,形成假小叶。结论HBeAg阴性慢性乙型肝炎合并非酒精性脂肪性肝病患者肝组织病理改变具有一定病理学特征;其病理学特征应从炎症、纤维化程度与肝细胞脂肪变性范围、肝细胞损伤等方面综合分析,肝组织活检有助于早期明确诊断,从而指导临床合理治疗。     

高压氧治疗30例慢性淤胆型肝炎临床和病理的观察

目的 观察慢性淤胆型肝炎高压氧治疗前后患者的肝血流、肝功能、肝组织学、超微结构变化。方法随机选择30例住院的慢性淤胆型肝炎患者,用宁波产高压氧纯氧单仓治疗,剂量为2.5MPa,每天2小时,10天为一疗程,休息2天后再行下一疗程,共6个疗程。治疗前后用肝血流图仪和多普勒B超测定肝血流图收缩波和门静脉右支血流量;行肝穿刺活检术,取新鲜肝组织,常规透射电镜病理观察。结果 治疗后肝血流图收缩波和肝门静脉右支血流量明显升高;肝功能明显改善;治疗前后二次肝穿活检的10例患者中,9例患者肝组织汇管区淋巴细胞浸润和肝细胞淤胆减轻;8例患者肝细胞线粒体肿胀和Kupffer细胞增生减轻;7例患者肝细胞变性坏死,汇管区炎症、毛细胆管淤胆减轻和溶酶体数量减少;6例患者肝组织内毛细血管增生明显;3例患者肝细胞内内质网增生、间质纤维化程度减轻;2例患者肝细胞内高尔基体扩张、贮脂细胞增生、间质纤维增生减轻。结论 高压氧治疗慢性淤胆型肝炎,可增加肝动脉及门静脉右支血流量,改善患者肝脏功能和临床症状,有效地减轻肝细胞和毛细胆管淤胆及肝组织学和超微结构的损伤。     

肝移植术后急性排斥反应的病理诊断--200例次肝穿刺活检的病理组织学分析

目的观察同种异体肝移值术后急性排斥反应病理组织学表现,探讨相关的病理鉴别诊断。方法对136例(200例次)同种异体肝移植术后肝组织穿刺活检明确诊断为急性排斥反应的病理组织学资料进行回顾性分析。结果同种异体肝移植术后的急性排斥反应病理组织学表现为：汇管区内炎细胞浸润136例(200例次);小叶间静脉和(或)中央静脉内皮炎116例(170例次);小叶间胆管上皮变性和(或)炎细胞浸润136例(200例次);肝细胞和毛细胆管淤胆103例(151例次);肝细胞水肿和气球样变性83例(126例次);肝细胞嗜酸性变和点、灶性坏死76例(161例次)。结论同种异体肝移植术后肝组织穿刺活检的病理组织学变化对急性排斥反应的诊断及术后各种并发症的鉴别诊断具有重要价值。     

肝组织病理学检查在婴儿胆汁淤积症鉴别诊断中的价值

目的:对比胆道闭锁与淤胆性婴儿肝炎的肝组织病理学的异同点,探讨肝组织病理学检查在鉴别诊断中的实际应用价值.方法:将我院2002-04/2009-12经病理诊断的胆道闭锁65例与淤胆性婴儿肝炎病例24例进行回顾性分析.结果:胆道闭锁与淤胆性婴儿肝炎肝组织病理学均可表现为肝小叶结构变化、肝细胞变性坏死、汇管区炎症、胆汁淤积、汇管区纤维化、胆管增生、巨细胞样变和髓外造血.其中胆道闭锁以汇管区纤维化、胆管增生及汇管区炎症最常见(P<0.05),而淤胆性婴儿肝炎则以巨细胞样变及髓外造血最常见(P<0.05).结论:胆道闭锁与淤胆性婴儿肝炎肝组织病理学各有特点,但有一定的重叠性.在诊断时仍需结合临床,必要时行剖腹探查.     

熊去氧胆酸治疗酒精性肝炎伴胆汁淤积患者的临床观察

酒精性肝炎肝细胞呈气球样变和透明性变,细胞浆内可见Mallory 小体。有时可见巨大线粒体,肝细胞内淤胆、小胆管增生及铁颗粒沉积,炎症坏死灶内有中性白细胞浸润,易见凋亡小体,坏死可融合,可见不同程度的脂肪变性及纤维化。据炎症坏死灶范围和分布,可分为轻、中和重度。轻度：坏死灶主要见于3带;中度：炎症坏死灶明显增多,不限于3带,周围常见气球样变和透明变性肝细胞,胞浆内可见 Mallory 小体;重度：在慢性酒精性肝炎病变基础上,发生肝细胞弥漫变性、坏死和胆汁淤积。胆汁淤积性肝炎是由于肝细胞分泌受损使肝毒性胆汁酸在细胞内增多,虽然在胆汁淤积时肝细胞受损的机制是多因素的,但胆汁酸诱导的凋亡好像起了一个主要的作用,在体内外实验中,疏水性的胆汁酸被证实可以诱导肝细胞的凋亡。     

对病毒性淤胆型肝炎临床表现及其诊断问题的一些新认识

病毒性肝炎是引起肝内胆汁淤积的主要病因之一。临床上多数急性病毒性淤胆型肝炎为自限性疾病,预后良好。但慢性肝炎、肝硬化所致的慢性病毒性淤胆型肝炎及病程日久的急性病毒性淤胆型肝炎常有重度黄疸。黄疸持续不退或进行性加深,常可致胆汁性肝硬化或肝细胞发生液化和凝固性坏死而演变成重症肝炎。     

亚急性重症肝炎与淤胆性肝炎高胆红素血症黄疸成因的组织学差别

29例胆红素在9～28mg、亚急性重症肝炎,13例胆红素在10mg左右淤胆性肝炎的肝穿刺标本的光镜、电镜检查,测算了18例亚急性重症肝炎、9例淤胆性肝炎、肝细胞内淤胆的容积百分比,胆汁凝固性坏死的容积百分比与临床资料进行统计学处理。这两类肝炎都有肝细胞内淤胆、毛细胆管扩张,胆汁凝固性坏死。电镜示胞浆内及毛细胆管内电子致密的颗粒、斑块状胆色素物。毛细胆管微绒毛消失。但淤胆性肝炎光     

婴儿胆汁淤积性肝病肝组织病理学特征及其在病因诊断中的意义

目的 研究婴儿胆汁淤积性肝病肝活组织检查的病理及超微病理结构特征,并结合临床资料探讨其在诊断中的意义.方法 对2007-2008年在重庆医科大学儿童医院就诊的36例胆汁淤积型婴儿肝炎综合征患儿进行肝活组织检查并随访,分析其肝组织病理及超微病理特征.结果 36例婴儿胆汁淤积性肝病肝活组织检查的光镜结果显示,肝细胞肿胀、变性、坏死,多核巨细胞形成,胆管增生,纤维组织增生,肝小叶和汇管区炎性细胞浸润为主要病理表现.肝细胞淤胆,假腺腔形成、羽毛状变性和毛细胆管胆栓形成为胆汁淤积的特征.7例影像学检查除外胆道闭锁病例的肝组织呈现典型胆道梗阻征象.电镜下常见核改变、胞质溶解、炎症细胞浸润、胶原纤维增生和溶酶体增多.形态学改变结合临床表现诊断肝糖原累积病2例,尼曼皮克病1例,分类不明脂质沉积病1例.结论 婴儿胆汁淤积性肝病肝组织普通光镜和电镜下存在共同的病理改变,两者相结合增加了遗传代谢性疾病的检出率.部分影像学诊断困难的胆道闭锁患者,其肝组织形态学可提示胆道梗阻.     

186例药物性肝损伤组织病理学及临床特征分析

目的探讨药物性肝损伤的组织病理学特点及临床特征,为早期诊治提供帮助。方法回顾性分析186例经肝活组织穿刺病理学诊断的药物性肝损伤患者的用药史、病理特点、临床表现、生化、血清学标志以及治疗转归等。结果引起药物性肝损伤前3位的药物是中药91例（49％）、抗生素41例（22％）、解热镇痛药23例（12．4％）;临床分类：药物性肝功能衰竭8例（4．4％）、急性药物性肝损伤93例（50％）、慢性药物性肝损伤83例（44．6％）、药物性肝硬化2例（1．1％）;临床分型：肝细胞损伤型98例（52．7％）、胆汁淤积型35例（18．8％）、混合型55例（29．6％）。病理学特征主要表现为：肝细胞坏死、汇管区扩大、肝细胞脂肪变性、汇管区或窦周混合炎细胞浸润、嗜酸性粒细胞浸润、肝细胞胆汁淤积、肝细胞凋亡、可见吞噬色素的Kuffer细胞。治愈79例（42．5％）,好转102例（54．8％）,无效5例（2．7％）。无一例患者死亡或病情恶化。结论引起药物性肝损伤的首位药物为中药,临床表现无特异性,但组织病理学改变有一定特征。     

16例原发性胆汁性肝硬化临床及病理分析

目的总结原发性胆汁性肝硬化(PBC)患者的临床及肝组织病理特征,以提高对本病的认识。方法分析16例PBC患者的一般资料、临床表现、生化指标、免疫功能及肝组织病理特点。结果本组女性13例,男性3例,平均年龄(59.44±9.93)岁,临床表现以黄疸最为多见(13/16,占81.3%),其次为乏力(6/16,占37.5%)。肝功能改变以血清碱性磷酸酶(ALP)和γ-谷氨酰转肽酶(GGT)升高明显[分别为(288.56±162.10)IU/L和(314.13±179.08)IU/L],免疫功能检查抗核抗体(ANA)阳性12例(75%),抗线粒体抗体M2亚型(AMA-M2)阳性6例(37.5%),肝组织病理特点以小胆管改变最明显:消失5例,增生及坏死均2例,减少1例。胆管周围细胞浸润:淋巴细胞4例,嗜酸性粒细胞、浆细胞、中性粒细胞各1例。汇管区细胞浸润:淋巴细胞10例,部分有淋巴滤泡形成(3例),浆细胞4例,中性粒细胞3例。肝细胞改变:碎片状坏死和点状坏死各6例,灶状坏死5例,明显水肿8例,部分嗜酸变4例,淤胆6例。纤维化:纤维组织增生5例,假小叶形成6例。结论PBC患者的肝脏病理改变以小胆管改变最明显,周围有炎性细胞浸润;汇管区细胞浸润现象明显;肝细胞改变相对较轻,缺乏特异性;各期改变可相互混杂。肝组织病理检查对PBC诊断有重要意义。     

Prolonged jaundice following ketoconazole-induced hepatic injury

Two patients developed prolonged and progressive jaundice associated with ketoconazole-induced hepatic injury although the drug was discontinued before or shortly after the onset of symptoms of hepatic toxicity. One patient, who had been jaundiced for eight weeks and was not improving, showed prompt clinical improvement and progressive resolution of jaundice following therapy with prednisolone. Liver biopsy before therapy showed marked cholestasis in all acinar zones and moderately severe fibrosis in the space of Disse. The other patient, who was less severely jaundiced, showed spontaneous resolution although he remained jaundiced for 11 weeks. Liver biopsy performed three weeks after onset of symptoms showed a moderate degree of cholestasis in acinar zone 3 and collagen deposition about the terminal hepatic venules and within the space of Disse. These cases are reported because of the unique clinical course, documentation of the morphologic features, and experience with corticosteroid therapy.     

Eosinophil-induced chronic active hepatitis in the idiopathic hypereosinophilic syndrome

A 19-yr-old man had features of chronic hepatitis with piecemeal necrosis as the sole clinical feature of the idiopathic hypereosinophilic syndrome. Liver biopsy specimens demonstrated the presence of activated eosinophils and, by immunohistochemical staining, major basic protein in areas of hepatic cell damage. The case demonstrates the clinical presentation of the idiopathic hypereosinophilic syndrome as chronic hepatitis and the association between eosinophil infiltration and degranulation with the presence of hepatocyte necrosis.     

组织细胞坏死性淋巴结炎52例临床病理表现

目的探讨组织细胞坏死性淋巴结炎的临床和病理学特点。方法回顾性分析52例组织细胞坏死性淋巴结炎的临床表现、淋巴结活检病理学特点及其诊治。结果52例患者中女性41例（79％）,主要表现为持续发热（100％）,单发（23％）或多发（77％）淋巴结肿大（以颈部多见）,多形性皮疹（35％）,外周血白细胞计数降低（76％）,血沉增快（100％）,抗生素治疗无效（100％）,小剂量肾上腺糖皮质激素治疗有效（81％）等。26例患者（50％）肝酶升高,仅7例（13％）伴流感样上呼吸道症状。淋巴结活检病理学特点为不同程度的凝固性坏死伴多种形态的组织细胞、淋巴细胞浸润,无中性粒细胞浸润。免疫组化染色示组织细胞CD68及T细胞CD3、CD45,RO阳性,CD15、CD20及CD30均阴性。结论组织细胞坏死性淋巴结炎的临床表现无特异性,较易误诊,确诊主要依靠病理活检及免疫组化检查。     

Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities

BACKGROUND/AIMS: Liver lesions associated with primary hypogammaglobulinemia have been poorly described. We aimed to assess the clinical, histological and immune features and outcome of hepatic injury in patients with primary hypogammaglobulinemia. METHODS: The medical records of 51 patients (23 patients with liver biopsy) with primary hypogammaglobulinemia and liver abnormalities were retrospectively reviewed. Forty-three controls with primary hypogammaglobulinemia but with no hepatic manifestations were analyzed in parallel. RESULTS: Cholestasis (65%), mainly anicteric, and portal hypertension (50%) were the main hepatic manifestations. Histological analysis revealed non-fibrosing architectural abnormalities consistent with nodular regenerative hyperplasia (NRH) in 84% of CVID patients and in all HIGM and XLA patients. Intrasinusoidal lymphocytic infiltration, abnormalities of portal vessels and epithelioid granulomas were observed in 90%, 43% and 44% of patients, respectively. NRH was associated with portal hypertension in 75% of the cases. These patients more often presented with autoimmune diseases and peripheral lymphocytic abnormalities than control patients (p < 0.05). CONCLUSIONS: Liver involvement in primary hypogammaglobulinemia mainly consists of NRH leading to chronic cholestasis and portal hypertension. Association with intrasinusoidal T cell infiltration, portal vein endotheliitis, autoimmune diseases and peripheral lymphocytic abnormalities suggests an autoimmune mechanism.     

Relationship between apoptasis, tumour necrosis factor, cell proliferation in chronic cholestasis

BACKGROUND: Target of the immune response in chronic autoimmune cholestasis, is the bile duct epithelium. Lymphocytic infiltration and apoptosis have both been suggested to mediate the destruction of hepatocytes and biliary epithelium in primary biliary cirrhosis. AIMS: To further address this issue in two cholestatic liver diseases characterized by an autoimmune pathogenesis and, furthermore, evaluate the relationship between apoptosis and both tumour necrosis factor alpha and cell proliferation. METHODS: Liver tissue specimens from 16 patients with primary biliary cirrhosis, 15 with primary sclerosing cholangitis, and 16 with chronic hepatitis C (controls) were evaluated. DNA-fragmentation of apoptotic cells was ascertained by the TdT-mediated deoxyuridine triphosphate nick-end labelling method. Tumour necrosis factor alpha expression and cell proliferation (Ki-67 antigen) were assayed by immunohistochemistry. RESULTS: Hepatocytes with DNA fragmentation were observed in 75% of patients with primary biliary cirrhosis, in 66.6% with primary sclerosing cholangitis, and in 43.7% with chronic hepatitis C. Biliocytes showed apoptosis in only 3 cases of primary biliary cirrhosis. Biliocytes showed a strong cytoplasmic expression in 4 cases (1 primary biliary cirrhosis, 2 primary sclerosing cholangitis and 1 chronic hepatitis C). A few intralobular and portal inflammatory mononuclear cells expressing tumour necrosis factor alpha were observed in 62.5% of patients with primary biliary cirrhosis, 46.1% with primary sclerosing cholangitis, and 56.2% with hepatitis C virus chronic hepatitis. The amount of intraportal mononuclear cells expressing Ki-67 antigen was significantly higher in primary biliary cirrhosis specimens than in primary sclerosing cholangitis (p<0.001) or hepatitis C virus-related chronic hepatitis (p<0.03). No correlation was found within the 3 groups of patients between the Ki-67 histological score and the severity of liver disease. Moreover, no relationship was found between TdT-mediated deoxyuridine triphosphate nick-end labelling and either tumour necrosis factor alpha or Ki-67 staining. CONCLUSIONS: Apoptosis is a phenomenon which frequently involves hepatocytes in chronic autoimmune cholestasis. This process is apparently parallel, but unrelated to cell proliferation. Cell proliferation mainly involves mononuclear cells in portal tracts of primary biliary cirrhosis specimens. The finding of tumour necrosis factor alpha expression in biliocytes deserves further study to establish whether this cytokine is involved in triggering bile duct lesions.     

药物性肝损伤100例临床病理分析

目的探讨药物性肝损伤(DILI)患者的临床病理学特点,为临床诊治提供病理依据。方法选择行肝穿刺确诊DILI病例100例(男:女=48:52),年龄(33.04±14.00)岁,分为急性DILI组(39例)和慢性DILI组(61例)。肝组织行HE、组织化学染色和免疫组织化学染色,进行临床病理观察分析。结果致DILI的药物种类中,中药类占21%,激素类药物占11%。其中78%的患者出现血清ALT升高和(或)胆红素升高,急性DILI组ALT异常和高胆红素发生率均高于慢性DILI组(56.41%与34.43%,x2=4.69,P<0.05),且程度也明显较重(P<0.01)。急性DILI组和慢性DILI组病理改变,除纤维化和胆管增生外,其余差异无统计学意义。DILI的相对病理特点主要表现为:中央静脉周围为主的肝细胞坏死,富含中性粒细胞和嗜酸性粒细胞的炎性细胞浸润,肝细胞和(或)毛细胆管性淤胆,小泡性脂肪变性为主的混合性肝细胞脂肪变性,上皮样肉芽肿结构等。结论包括中药在内的DILI在中国大陆地区已非少见,中药应用需进一步规范。DILI有其相对临床病理特点,在临床诊治中要注意临床表现与病理特点的密切结合。     

Hepatic graft-versus-host disease presenting as an acute hepatitis after allogeneic peripheral blood stem cell transplantation.

Hepatic graft-versus-host disease (GVHD) generally presents as cholestatic jaundice, and increased serum alkaline phosphatase (ALP) is followed by hyperbilirubinemia and clinical jaundice. Currently accepted standards for evaluating the clinical severity of GVHD are based not on serum aminotransferase levels but on the serum bilirubin level. We describe a 17-year-old Japanese female who had increased aminotransferases without cholestasis on day 23 after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Liver biopsy revealed lymphocytic infiltration of the portal tracts and pericentral necrosis of the lobuli. The limiting plates were not clearly defined due to cellular infiltrates. There was periductal lymphocytic infiltration and vacuolization of the biliary epithelial cells with exocytosis, compatible with GVHD of cholangiohepatitic type. These findings indicate that acute hepatic GVHD may present as acute hepatitis and this should be included in the differential diagnosis for patients with increased aminotransferases after allogeneic stem cell transplantation.