肝性脑病的病因和防治探讨

肝性脑病至今仍以血液检查所见的生化代谢异常来解释，因不能圆满解释全面情况，需进一步探讨。不加选择收集70例肝硬化死亡者脑组织，分别作HE和免疫组化检查，观察病理改变和HBsAg、HBcAg表达。在70例脑组织标本中免疫组化染色HBsAg、HBcAg阳性者计30例，阳性率42.3%，临床上有肝性脑病表现者阳性率明显高于无表现者，脑组织病理改变较明显者，阳性率亦明显高于较轻者。肝硬化脑组织内出现HBsAg和HBcAg表达，而且阳性率与脑组织病理改变和是否出现临床表现密切有关。提示HBV侵及脑组织，导致病理形态改变可能是肝性脑病的病理基础，生化代谢异常可能仅是肝衰的表现。     

慢性乙型肝炎患者血清HBV复制标志物与肝组织HBsAg和HBcAg抗原表达的相关性研究

目的探讨血清HBV复制标志物与肝组织HBsAg和HBcAg抗原表达的相关性。方法用免疫组化法检测肝组织HBsAg、HBcAg,与血清HBeAg和/或HBV DNA进行相关性比较。结果血清HBeAg阳性与阴性组中肝组织HBsAg阳性率无显著性差异,而血清HBeAg阳性者肝组织HBcAg阳性率显著高于HBeAg阴性者;血清HBV DNA阳性与阴性组中肝组织HBsAg阳性率无显著性差异,但血清HBV DNA阳性者肝组织HBcAg阳性率显著高于HBV DNA阴性者。结论血清HBeAg和HBV DNA水平与肝组织HBcAg阳性率呈正相关。     

肝性脑病脑组织病理形态观察

我们于九十年代初起不加选择收集肝硬变死亡者肝、脑组织,对照临床表现和血液检查,探讨肝性脑病(HE)的病理基础,共观察70例,现总结报道如下。 资料和方法 一、一般资料 70例患者的临床表现和实验室检查均符合肝硬变诊断,肝组织病理切片检查,均可见典型肝硬变的病理特点。男51例,女19例,年龄7岁～71岁,平均48.7岁。临床显示HE,死于肝衰者41例,     

慢性HBsAg阳性携带者肝组织病理学改变及其与临床相关指标的关系

目的了解慢性HBsAg阳性携带者肝组织病理改变及其临床指标之间的关系。方法对500例慢性HBsAg阳性携带者进行肝穿病理检查结果与临床血清生化指标及血浆PT值进行对照分析。结果随着炎症程度加重CHE逐渐下降,PT逐渐延长,且各组间比较差异有统计学意义（P〈0.05）。同时发现HBeAg阴性患者的炎症分级与纤维化分期都较HBeAg阳性患者重,病理诊断G4,S4级所占比例高达34.8%;HBeAg阳性者HBVDNA阳性率和拷贝数高于HBeAg阴性者,二组比较有统计学意义,P〈0.05。结论CHE、PT等指标是反映慢性HBsAg阳性携带者病理损害良好的实验室指标,临床定期检测对判断肝组织病理分级与调整治疗方案有重要意义。     

慢性HBV携带者病毒抗原表达类型与抗病毒治疗效果相关性研究

目的观察肝脏病理改变和肝细胞内病毒抗原的表达类型与抗病毒治疗疗效的关系。方法选择79例慢性HBV携带者,通过肝组织病理检测,观察肝脏病理改变程度、肝细胞内病毒抗原的表达类型和抗病毒治疗后血清HBeAg、HBVDNA转阴之间的关系。结果HBsAg表达类型与疗效无显著相关性,HBcAg浆型表达的疗效明显优于核型表达,肝组织病理病变大于4分,血清HBV标志物阴转率高。结论肝组织HBcAg浆型表达和肝组织病理改变与慢性HBV携带者抗病毒治疗疗效均呈正相关。     

HBsAg及AFP在肝细胞癌组织中的表达及其相关性

目的进一步探讨HBV感染在肝细胞癌（HCC）发病中的作用。方法选择40份HCC、癌旁肝组织标本及6份正常肝组织标本,用免疫组化SP法检测其HBsAg与甲胎蛋白（AFP）表达。结果正常肝组织中HBsAg及AFP表达均为阴性;HCC和癌旁肝组织中HBsAg及AFP表达阳性率分别为70%、90%（P〈0.05）,HCC和癌旁肝组织AFP表达阳性率分别为87.5%、82.5%（P〉0.05）;HCC及癌旁肝组织中HBsAg阳性者AFP表达阳性率明显高于HBsAg阴性者（P〈0.05）。结论 HBV感染可能通过诱发肝细胞产生AFP参与HCC发病,具体机制有待进一步研究。     

HBeAg阳性和阴性的慢性乙型肝炎患者组织病理学及免疫组化学研究

目的探讨HBeAg阴性和阳性慢性乙型肝炎（CHB）患者组织病理学及免疫组化学的特点。方法对156例HBeAg阴性和阳性CHB患者肝组织炎症分级（G）及纤维化分期（S）的结果进行对比分析,并分别探讨两组CHB患者HBVDNA与ALT、G及S的关系,检测CHB患者肝组织HBsAg和HBcAg阳性表达率。结果HBeAg阴性CHB患者HBVDNA含量明显低于HBeAg阳性者,肝组织炎症程度高于后者,HBVDNA水平与ALT、G和S呈正相关,HBeAg阳性CHB血清HBVDNA与ALT、G无相关性。CHB患者肝组织HBcAg阳性率随炎症程度升高而升高。结论与HBeAg阳性CHB相比,HBeAg阴性者HBVDNA水平低,炎症程度高,HBVDNA水平与ALT、G、S正相关。CHB患者肝组织HBcAg阳性率随炎症程度增高而升高。     

慢性乙型肝炎中医辨证分型的论证

应用分子生物学和免疫组化等技术,对131例慢性乙型肝炎中医辨证分型进行了论证,发现肝郁脾虚型临床符合慢性迁延型肝炎(CPH)者占4.6％,肝组织病理呈CPH改变者为69.2％,血清HBeAg和(或)HBV DNA阳性占61.5％,肝组织HBsAg阳性率为69.2％,其中呈弥漫型者占44.4％,HBV DNA阳性率为33.3％。肝肾阴虚型临床符合慢性活动性肝炎(CAH)者占75.5％,     

HBeAg阴性慢性乙肝病毒携带者临床、肝脏病理、血清学检查五年回访

目的了解HBeAg阴性慢性乙肝病毒携带者的转归。方法对52例HBeAg阴性慢性乙肝病毒携带者进行了为期5年的临床症状、肝活检及血清学检查的动态观察研究。结果5年间,52例HBeAg阴性慢性乙肝病毒携带者中有12例出现临床显性发病,约占总数的23．1％。其中13例行2次肝活检,原肝组织正常者几年内相对稳定,病理很少变化,原有病理改变者不易恢复。HBsAg年转阴率为1．2％。结论HBeAg阴性慢性乙肝病毒携带者肝脏病理极大多数有异常,临床是否发病与肝脏炎症分级密切相关。     

肝硬变和肝性脑病时的低氧血症与碱中毒

本文测定52例失代偿期肝硬变(其中17例并发肝性脑病)患者的动脉血气分析、血酸碱度。结果发现动脉低氧血症者34例占65.4％;发生呼吸性碱中毒者41例占78.8％,重度低氧血症者均为并发肝性脑病者。并发肝性脑病组低氧血症发生率94.1％,呼吸性碱中毒发生率88.2％,较无肝性脑病组的PaO_2、PaCO_2的减低及血PH值的增高为明显(P值均<0.05)。结果表明随肝硬变加重尤其在并发肝性脑病时,动脉低氧血症、碱中毒更为明显,两者在肝性脑病的发展中可能具有互为因果的关系。     

Identification of hepatitis B antigens in hepatic tissue in various forms of acute hepatitis

Presence of HBsAg and HBcAg have been tested by immunohistochemical technique (peroxidase-antiperoxidase complex, PAP) in liver tissue of 223 patients with acute viral hepatitis using formalin fixed and paraffin embedded pieces of tissue. Histologic picture in usual acute viral hepatitis in 203 cases, submassive hepatic necrosis in 16, massive hepatic necrosis in four. HBsAg was positive in the serum of 85 of the 223 patients. In seven cases HBsAg and/or HBcAg was detected in liver tissue. In five of them only HBcAg was present; in one case only HBsAg and in one other HBsAg and HBcAg were detected. All but one of this seven cases had HBsAg positive in the blood. Three of seven cases with antigens in liver tissue went into chronic active hepatitis, one of them died with cirrhosis. The low incidence of detection of HBsAg or HBcAg in liver tissue was explained by the clearing of virus during the acute phase. The presence of this viral marks during this phase could be correlated with a bad evolution.     

肝组织免疫组化病人104例远期随访调查

目的　为了解病毒性肝炎患者肝组织不同免疫组化与远期预后关系。方法　采用回顾性前瞻性方法随访 6～ 8年前经肝穿病理组织学、免疫组化诊断的 132例肝病住院患者远期转归与肝组织免疫组化的关系。内容包括症状、体征、肝功能、HBVM、肝脾B超等指标。结果　随访到 10 4例中有 4例已死于肝硬化 ,病死率为 3 85 % ;存活 10 0例中 2例 (2 0 0 % )B超显示典型肝硬化改变 ,16例 (16 0 % )B超显示早期肝硬化改变 ,2 6例 (2 6 % )B超显示肝表面欠光滑 ,肝内实质呈弥漫性改变。肝组织HBsAg、HBcAg阳性者 ,ALT较易波动。结论　肝组织中HBsAg、HBcAg阳性者病情易波动 ,对预后影响不明显。     

Hepatitis B core and surface antigen expression in HBeAg and HBV DNA positive chronic hepatitis B: correlation with clinical and histological parameters

The interrelationship between hepatitis B virus (HBV) infection, hepatic injury and clinical activity in chronic HBV infection is incompletely understood. We have scored histologic activity, the expression of hepatitis B core (HBcAg) and hepatitis B surface antigen (HBsAg) and assessed HBV replication to correlate HBV antigen expression with histologic disease. Forty-seven formalin-fixed, percutaneous liver biopsies from HBeAg carriers were studied. Twenty-nine were Black, 16 Caucasian and two Oriental. Fifty-nine percent had chronic active, 35% chronic persistent hepatitis and 14% cirrhosis. None were positive for antibodies to Human Immunodeficiency Virus (HIV). HBsAg and HBcAg in tissue were detected by immunochemical staining. Diffuse HBsAg staining was observed in 10/15 patients with CPH, but there was no correlation between histologic score and HBsAg expression. Intracytoplasmic HBcAg was observed in patients seroconverting to anti-HBe, but was also detected in patients with minimal hepatitis. An inverse correlation between histologic score and HBcAg expression was observed. HBcAg expression was more widespread in patients with CPH (mean 37%) than in CAH (mean 18%). A positive correlation was observed between serum aminotransferase concentrations and histologic score. Although no consistent pattern can be discerned, HBcAg expression and hepatic injury are frequently dissociated in patients with chronic HBV infection; complex host responses may determine the variable degree of disease activity and hepatic injury.     

儿童慢性乙型肝炎肝组织HBsAg、HBcAg的表达与抗病毒疗效的关系

目的探索性研究慢性乙型肝炎(CHB)儿童肝组织HBsAg和HBcAg不同表达与抗病毒疗效的关系。方法收集2014年1月—2017年12月在解放军总医院第五医学中心青少年肝病科住院并明确诊断为CHB的276例6月~16岁儿童患者的病例资料,比较肝组织HBsAg和HBcAg免疫组化染色阳性和阴性组(HBsAg阳性组249例,HBsAg阴性组27例;HBcAg阳性组163例,HBcAg阴性组113例)患者的临床特点,以及肝组织HBsAg和HBcAg不同表达模式下抗病毒疗效的差异。计量资料组间比较采用Mann-Whitney U检验;计数资料组间比较采用χ2检验或Fisher精确检验。以肝组织HBsAg和HBcAg染色阳性和阴性为应变量,以可能影响其表达强度有意义的相关因素为自变量,进行logistic回归分析。结果276例患者年龄0.5~16岁,男性占60.51%(167例)。HBeAg阴性14例(5.07%)。肝脏炎症程度分级(G):2级52.54%,2~3级6.88%,3级7.61%。肝纤维化分期(S):3期7.25%,3~4期1.45%,4期3.62%。肝组织HBsAg阳性组儿童年龄及血清HBsAg定量高于阴性组(Z值分别为1.854、2.447,P值均<0.05)。肝组织HBcAg阳性组HBeAg阳性率高于阴性组(χ^2=2.650),ALT(Z=2.473)、AST(Z=1.813)、肝组织纤维化分期S≥3期的比例(χ^2=2.086)均低于阴性组(P值均<0.05)。logistic回归分析显示,影响肝组织HBsAg染色阳性的因素为血清HBsAg定量(P<0.05),影响肝组织HBcAg染色阳性的因素为HBeAg阴性或阳性(P<0.05)。276患者中186例完成IFNα或单用拉米夫定抗病毒治疗停药后6个月的随访,155例(83.33%)获得HBeAg血清学转换,其中76例(40.86%)HBsAg阴转。肝组织的HBsAg阳性表达强度越高,血清HBsAg阴转率越低。肝组织的HBcAg阳性表达强度越高,HBeAg血清学转换率越低。肝组织HBsAg及HBcAg均阴性表达模式的儿童HBsAg阴转率最高(100%),HBsAg阳性及HBcAg阴性的儿童HBsAg阴转率(32.31%)最低。结论肝组织HBsAg及HBcAg阴性的CHB儿童抗病毒治疗HBsAg阴转率最高。     

Brain metabolism of 13N-ammonia during acute hepatic encephalopathy in cirrhosis measured by positron emission tomography

Animal studies and results from 13N-ammonia positron emission tomography (PET) in patients with cirrhosis and minimal hepatic encephalopathy suggest that a disturbed brain ammonia metabolism plays a pivotal role in the pathogenesis of hepatic encephalopathy (HE). We studied brain ammonia kinetics in 8 patients with cirrhosis with an acute episode of clinically overt HE (I-IV), 7 patients with cirrhosis without HE, and 5 healthy subjects, using contemporary dynamic 13N-ammonia PET. Time courses were obtained of 13N-concentrations in cerebral cortex, basal ganglia, and cerebellum (PET-scans) as well as arterial 13N-ammonia, 13N-urea, and 13N-glutamine concentrations (blood samples) after 13N-ammonia injection. Regional 13N-ammonia kinetics was calculated by non-linear fitting of a physiological model of brain ammonia metabolism to the data. Mean permeability-surface area product of 13N-ammonia transfer across blood-brain barrier in cortex, PS(BBB), was 0.21 mL blood/min/mL tissue in patients with HE, 0.31 in patients without HE, and 0.34 in healthy controls; similar differences were seen in basal ganglia and cerebellum. Metabolic trapping of blood 13N-ammonia in the brain showed neither regional, nor patient group differences. Mean net metabolic flux of ammonia from blood into intracellular glutamine in the cortex was 13.4 micromol/min/L tissue in patients with cirrhosis with HE, 7.4 in patients without HE, and 2.6 in healthy controls, significantly correlated to blood ammonia. In conclusion, increased cerebral trapping of ammonia in patients with cirrhosis with acute HE was primarily attributable to increased blood ammonia and to a minor extent to changed ammonia kinetics in the brain.     

Glomerular nephropathies and B virus: apropos of 4 cases in adults, with an immunofluorescence study and review of the literature

The association of glomerulonephritis and persistent HBs antigenemia is reported in 4 adults with nephrotic syndrome: 2 cases of membranous glomerulonephritis associated with chronic persistent hepatitis and 2 cases of membrano-proliferative glomerulonephritis associated with active cirrhosis. In 3 patients, all positive for HBsAg, anti-HBc and HBeAg by radioimmunoassay, indirect immunofluorescent study was performed on kidney and liver biopsies. Glomerular deposit of HBcAg was detected in two cases. HBsAg and HBcAg were not found in the liver. The pathogenesis of such glomerulonephritis remains uncertain and the role of HBs antigen-antibody circulating immune complexes is not clearly proved. Two patients were treated with vidarabine intravenously. Vidarabine produced a transitory decrease of HBsAg concentration in 2 cases and a transitory loss of DNA-polymerase activity associated with a decrease of HBeAg concentration in one case. Neither seroconversion nor improvement of the glomerular disease were ascertained.     

拉米夫定治疗慢性乙型肝炎的临床观察及病理学研究

目的观察拉米夫定治疗慢性乙型肝炎患者的临床疗效、肝组织学改变及肝组织内乙型肝炎病毒(HBV)标志物的变化。方法随机选择70例慢性乙型肝炎患者予口服拉米夫定100mg／d，连用1年。观察HBVDNA、血清HBeAg／抗-HBe、肝功能以及血清肝纤维化指标的变化；对其中35例患者行治疗前后肝穿刺活检，行Knodell病理学评分，检测肝细胞内HBsAg、HBcAg、α平滑肌肌动蛋白(α-SMA)。结果治疗结束时，完全应答率为23．73％，部分应答率为69．49％，无应答率为6．78％。发生HBeAg血清学转换的患者治疗前血清ALT水平明显高于未发生血清HBeAg转换的患者。41．18％患者肝组织学活动指数得以改善，汇管区坏死、门静脉炎症及纤维化明显改善。血清HBeAg转换组肝组织内HBcAg、α-SMA的表达明显减少．HBsAg的表达无显著性改变。治疗期间不良反应轻，安全性良好。结论拉米夫定100mg／d可以迅速降低血清HBvDNA和ALT的水平，促进HBeAg血清转换，减轻肝脏炎症坏死活动度，延缓肝纤维化的进展。     

HBsAg阳性患者HBcAg表达与肝组织淋巴细胞数量变化的关系

目的研究HBsAg阳性患者HBcAg表达与肝组织中T、B淋巴细胞、NK细胞、Kupffer细胞数量等临床指标变化的关系。方法选取50例HBsAg阳性表达的患者肝组织及23例肝血管瘤患者瘤旁正常肝组织,分别进行CD3、CD57、CD20、CD68及HBcAg免疫组织化学染色;用病理图像分析仪测量每例患者肝组织和正常肝组织每平方微米面积阳性细胞数。结果HBsAg阳性表达的患者肝组织中T淋巴细胞、B淋巴细胞、NK细胞和Kupffer细胞数量明显多于正常肝组织,以T淋巴细胞数量增加最为显著（P〈0．05）,HBcAg阳性表达组与HBcAg阴性表达组肝组织中T淋巴细胞、B淋巴细胞、NK细胞和Kupffer细胞数量变化无统计学意义（P〉0．05）。HBcAg阳性表达组比HBcAg阴性表达组外周血的AFP、ALT含量高（P均〈0．05）,AST、GGT、ALP、白蛋白减少（P均〈0．05）,A／G比例降低（P〈0．01）。结论各免疫细胞数量变化与膜型HBsAg的表达有关,与核型HBcAg表达无关;但核型HBcAg的表达与各临床指标的改变密切相关。     

Hepatitis B virus markers in peripheral blood mononuclear cells]

Recent studies have shown tropism of the hepatitis B virus (HBV) by peripheral blood mononuclear cells (PBMC). The consequences of this phenomenon and their clinical use are not yet clear, however. Seventy-nine patients were studied between March 1989 and October 1990. Sixty-nine patients had chronic liver disease with histological evaluations, and 10 were vaccinated for HBV. The following markers were determined: serum: HBsAg, HBeAg, anti-HBe, antitotal-HBc, anti-HBs, anti-HCV, HBV-DNA; lysated PMBC cells: HBsAg, HBeAg. Hepatic tissue: HBsAg, HBcAg. Four groups were formed according to serology. Group I--positive HBsAg patients (n = 25) HBsAg was observed in the lysated of PBMC in 19 (76%) of the patients. HBeAg in PBMC was detected in 8 (32%), all of them showed evidence of viral replication (presence of HBcAg and/or HBV-DNA in the serum HBcAg in the tissue). Group II--antitotal HBc/anti-HBs positive (n = 14), HBsAg in PBMC was found in 5 (36%) and HBeAg in 1 (7.0%). In this patient replication markers in the serum and in the tissue (HBV-DNA, HBcAg) was also present. Three patients out of 9 anti-HBs positive had HBsAg in PBMC. Group III--seronegative patients for HBV. HBsAg was present in PBMC in 2 (6.6%) of the patients, but was absent in all of them. There was concomitant presence of HBsAg in MN and the hepatic tissue in 1 patient. Replication markers were not observed in the group. Group IV--10 asymptomatic individuals vaccinated for HBV. Except anti-HBs in serum, no other HBV marker could be identified in serum or in PBMC.(ABSTRACT TRUNCATED AT 250 WORDS)