庚型肝炎——庚型肝炎病毒感染对慢性肝炎发生发展的影响

目的：探讨庚型肝炎病毒（GBvirusC）感染对慢性肝炎发生发展的影响及临床意义。方法：采用免疫组化方法对143例慢性肝炎患者肝组织标本进行GBvirusC非结构蛋白5（NSS）抗原的检测，结合组织学改变进行分析。结果：慢性肝炎肝组织中GBvirusC总检出率为24．5％，其中单纯GbvirusC感染占11．9％；单纯GBvirusC感染和病原不明组炎症活动度程度较轻，只有8．9％达到3—4级，显著低于HBV／HCV感染病例和GBviru SC＆HBV／HCV混合感染组（26．5％）。结论：GBvirusC的致病性值得怀疑或者仅具有较弱的致病性，GBvirusC可能不是慢性肝炎的主要致病因子，它和HBV／HCV混合感染并不加重肝损害程度，不影响慢性肝炎的发生发展。     

乙型肝炎病毒前C区变异与慢性乙型肝炎病理改变的相关性

目的 探讨慢性乙型肝炎中乙型肝炎病毒（HBV）前C区1896突变与肝组织病理的关系。方法 对173例慢性乙型肝炎患者进行肝活检,观察肝组织病理分级（G）和分期（S）情况,同时检测乙型肝炎病毒的e系统状态和HBV前c区1896阳性患者（20％）;随着肝组织炎症活动度和纤维化程度的进展,变异株检出率似乎有增加趋势,但无统计学意义（P＝0．98和P=0．052)。结论 HBV前C区变异在HBeAg阴性组高于HBeAg阳性组;未发现HBV前C1896变异与慢性乙型肝炎的炎症分级和纤维化分期有相关关系。     

Fas、FasL在慢性乙型肝炎患者肝细胞和外周血淋巴细胞上的表达

探讨慢性乙型肝炎患者肝细胞及外周血淋巴细胞上Fas、FasL的表达与乙型肝炎病毒（HBV）复制水平及肝组织炎症程度的关系。对30例慢性乙型肝炎患者进行肝穿刺肝组织病理检查及免疫组化SP法检测肝细胞中Fas、FasL表达强度。并采用单克隆抗体经流式细胞仪检测外周血淋巴细胞上Fas、FasL表达阳性百分率;同时,采用荧光实时标记法测定血清中病毒复制指标HBV DNA水平;采用Beckman全自动生化分析仪检测肝功能并研究其相关性。慢性乙型肝炎患者肝细胞中Fas、FasL表达强度随肝组织炎症活动度加重而增强（P均〈0．001）,与白蛋白及丙氨酸转移酶（ALT）呈负相关（P〈0．005,P〈0．001）,与球蛋白、总胆红质无明显相关性（P均〉0．05）。外周血淋巴细胞上Fas、FasL的表达阳性率与血清中肝炎病毒复制指标HBV DNA水平呈正相关;与慢性肝炎分度无明显的相关性。乙型肝炎病毒感染可诱导肝细胞及外周血淋巴细胞上Fas、FasL的表达。肝细胞Fas、FasL的表达随炎症活动度加重而表达增强,但其介导的凋亡并不引起肝细胞炎症损伤即ALT活性并不升高,相反减少;同时在某种程度上影响白蛋白的合成。提示Fas—FasL介导的肝细胞凋亡是以非细胞损伤方式参与慢性乙型肝炎的发病过程。同时,随血清HBV DNA水平增高,外周血淋巴细胞上Fas、FasL的表达亦增强,淋巴细胞的凋亡因而增多,是导致乙型肝炎慢性化的原因之一。由此可见,Fas、FasL介导的凋亡参与了慢性乙型肝炎的发病机制,且在慢性乙型肝炎的发生发展中起重要作用。     

352例ALT<2ULN慢性乙型肝炎患者肝活检病理分析

目的对比丙氨酸氨基转移酶(ALT)2倍正常值上限(ULN)的慢性乙型肝炎病毒(HBV)感染者中,乙型肝炎E抗原(HBeAg)阳性患者与HBeAg阴性患者肝组织病理学炎症活动度及纤维化程度的差异,病理改变与年龄的关系。方法回顾性分析352例ALT2 ULN慢性HBV感染者,分为HBeAg阳性与HBeAg阴性组,对比两组患者肝脏炎症活动度、纤维化程度的差异;并分析所有患者病理改变与年龄关系。结果 (1)HBeAg阳性组患者144例,肝脏炎症改变在G1~G3级,纤维化程度在S0~S4期,其中达G2及以上、达S4者分别为121例(84.03%)、14例(9.72%);HBeAg阴性组患者208例,肝脏炎症改变在G1~G4级,纤维化程度在S0~S4期,其中G2及以上、达S4者分别为164例(78.85%)、67例(32.21%)。HBeAg阳性组与HBeAg阴性组患者炎症活动度无明显差异;HBeAg阴性组患者的肝脏纤维化程度明显高于HBeAg阳性组患者,差异有统计学意义(P0.05)。(2)352例慢性乙型肝炎患者炎症活动度及纤维化程度随着年龄增长,炎症活动度无明显差异,但纤维化程度逐渐加重,差异有统计学意义(P0.05)。结论ALT2ULN的慢性HBV感染者中,HBeAg阴性组患者的肝脏纤维化程度明显高于HBeAg阳性组患者,而两组患者炎症活动度无明显差异;随着年龄增长,慢性乙型肝炎患者纤维化程度则在加重。     

纤维淤胆性肝炎

纤维淤胆性肝炎(fibrosing cholestatic hepatitis,FCH)是一类新的临床病种,它发生于各种原因引起的严重免疫抑制状态下,特别是器官移植后大量使用免疫抑制剂的肝炎病毒感染者。其肝脏病理组织学改变主要表现为:(1)自门管区向肝窦周围延伸的纤维化条带,并包绕胆管上皮的基板;(2)显著肝内淤胆;(3)肝细胞气球样变性伴细胞丢失;(4)可见大量的毛玻璃样肝细胞、胞浆内有大量病毒抗原(包括HBsAg)堆积;(5)仅有轻度混合性炎症反应。     

肝功能正常的慢性乙型肝炎病毒感染者血清HBeAg及HBV DNA与肝组织病理改变的关系

目的了解肝功能正常的慢性乙型肝炎病毒（HBV）感染者肝组织病理改变特征,并分析血清HBeAg及HBV DNA定量与肝组织病理改变的关系。方法选取肝功能正常的慢性HBV感染者90例,行肝穿刺病理检查,依据血清HBeAg及HBV DNA将患者分组,分别比较HBeAg阳性和阴性组及HBV DNA阳性和阴性组患者肝组织炎症分级和纤维化分期结果。结果90例患者100%存在肝组织损伤,其中肝硬化8例（8.9%）;慢性乙型肝炎轻度62例（68.9%）,中度8例（8.9%）,重度12例（13.3%）。82例病理诊断慢性乙型肝炎的患者中,炎症分级G≥2者30例（36.6%）;纤维化分期S≥2者28例（34.15%）。HBeAg阴性组病理炎症分级及纤维化分期均明显重于阳性组（P值均〈0.05）。HBV DNA阴性和阳性组肝组织炎症分级和纤维化分期差异均无统计学意义。结论肝功能正常的慢性HBV感染者,肝组织病理皆非＂正常＂;血清HBeAg、HBV DNA均不能反映肝脏损伤情况;对此类患者制定治疗方案时应考虑肝组织病理检查结果。     

肾移植后纤维化淤胆性肝炎的临床病理特点

目的 探讨纤维化淤胆性肝炎（fibrosing cholestatic hepatitis,FCH)临床病理特点和拉米夫定的防治效果。方法 回顾性分析我院794例肾移植后发生的17例重度黄疸性肝炎，其中6例经肝活检证实，2例有发病前后组织病理对比。结果 肾移植者中慢性HBV感染者为9.3%，其中FCH发生率为22.9%，肝活检证实的6例发病时间在移植后的1.5-22个月中，2例经拉米夫定治疗后缓解，4例慢性乙肝患者移植前后服用拉米夫定未发生纤维化淤胆性肝炎，移植后应用极大剂量多种免疫抑制剂，逐渐发生淤胆性肝炎和迅速进展肝功能衰竭，血清HBVDNA达极高水平；组织学表现独特的病变组合；肝细胞广范围气球样变性，毛玻璃样肝细胞不少见，区域性肝细胞溶解消失，淤胆，而炎症浸润轻微，并由汇管区发展的广范围纤维化。结论 肾移植后可发生纤维化淤胆性肝炎，拉米夫定对FCH有明显的即时治疗效应。     

慢性乙型肝炎肝组织内HBsAg、HBcAg的表达及临床研究进展

一直以来临床将血清乙型肝炎e抗原(HBeAg)、乙肝病毒DNA(HBV DNA)阳性作为乙肝病毒复制的标志,随着肝穿活检及抗病毒治疗的研究进展,肝活检组织中乙肝表面抗原(HBsAg)和乙肝核心抗原(HBcAg)的表达模式与血清乙型肝炎病毒(HBV)DNA定量、肝组织炎症活动度分级及纤维化分期之间关系的临床研究日益增多,本文就HBsAg和HBcAg在肝组织的表达模式及临床研究进展综述如下.     

乙型和丙型肝炎病毒对MAPKK信号转导的影响

0 引言乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)的感染,不仅引起急、慢性病毒性肝炎,而且与肝纤维化、肝细胞癌的发生密切相关。虽然HBV和HCV感染与肝细胞癌之间的关系已经得到确定,但是具体的分子生物     

庚型肝炎患者肝组织中HGV表达的免疫组化研究

目的探讨庚型肝炎病毒（ＨＧＶ）在庚型肝炎肝组织中的表达状况与临床意义．方法应用免疫组织化学ＰＡＰ方法以鼠抗ＨＧＶＮＳ５单克隆抗体对庚型肝炎患者２０例（急性肝炎２例，慢性肝炎８例，肝硬变１０例，血清ＨＧＶＲＮＡ皆阳性）肝组织中ＨＧＶ抗原进行检测．结果庚型肝炎患者２０例中，８例（４０％）肝组织中检出ＨＧＶ抗原；不同病期检出率分别为：急性肝炎０／２（０％），慢性肝炎２／８（２５％），肝硬变６／１０（６０％），各组间差异无显著意义；阳性信号位于肝细胞胞质；阳性细胞可位于炎症坏死灶周围；抗原阳性与阴性组间肝组织炎症活动度及血清谷丙转氨酶水平无明显差别，但阳性组纤维化指数较高．结论ＨＧＶ感染及其在肝组织中表达可能与肝组织纤维化有一定关系     

Histomorphological characteristics of liver tissue in patients with chronic viral hepatitis

OBJECTIVE : Chronic viral hepatitis and cirrhosis caused by hepatitis B virus (HBV), hepatitis C virus (HBC) or both constitute the majority of cases of liver diseases in China. Pathologists often need to differentiate between the morphological features of HBV and HCV. The aim of this study was to explore the differences in inflammatory activity, fibrosis and morphological characteristics in various types of chronic viral hepatitis. METHODS : Inflammatory activity and degree of fibrosis in liver biopsies taken from 224 patients with chronic hepatitis were determined according to the Diagnostic Criteria of Chronic Hepatitis, China, 1995. Each of hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg) and the hepatitis C virus nuclear core protein (CP₁₀) were detected on paraffin sections of the biopsies by using immunohistochemical methods. Patients were divided into HBV, HCV and HBV + HCV infection groups and the differences among these groups were assessed on the basis of histopathological characteristics including inflammatory activity, fibrosis, steatosis, intrahepatic cholestasis, Councilman bodies and ground‐glass hepatocytes. RESULTS : The HCV infection group had more severe inflammatory activity, fibrosis and intrahepatic cholestasis than did the HBV infection group. The degree of inflammatory activity and fibrosis in the HBV + HCV infection group was moderate, but the degree of intrahepatic cholestasis was the most severe of the three study groups. Ground‐glass hepatocytes were only noted in HBV‐infected specimens. There was no difference in the occurrences of steatosis and Councilman bodies among the three study groups. CONCLUSIONS : The degree of inflammatory activity and fibrosis induced by HCV in hepatocytes is more severe than that induced by HBV. The histological changes observed in liver infected by both HBV and HCV are no more severe than those observed in liver infected with either HBV or HCV. Intrahepatic cholestasis may play an important role in aggravating damage to hepatocytes.     

Insulin resistance and steatosis in HBV-HCV co-infected patients: Role of PNPLA3 polymorphisms and impact on liver fibrosis progression

AIM:To evaluate steatosis,insulin resistance(IR)and patatin-like phospholipase domain-containing 3(PNPLA3) and their relation to disease progression in hepatitis B and C viruses(HCV-HBV) coinfected patients.METHODS:Three hundred and thirty patients with biopsy proven chronic hepatitis were enrolled:66 had HBV-HCV,66 HBV and 198 HCV infection.Prevalence of steatosis,IR and PNPLA3 polymorphisms and their relation to anthropometric,biochemical,virological and histological parameters were evaluated.RESULTS:Prevalence of steatosis in group HBV-HCV was similar to that in HCV(47.0% vs 49.5%,respec-tively);group HBV showed the lowest steatosis(33.3%).Group HBV-HCV had a lesser degree of steatosis than HCV(P = 0.016),lower HCV RNA levels(P = 0.025) and lower prevalence and degree of IR(P = 0.01).PNPLA3 polymorphisms were associated with steatosis.Group HBV-HCV showed higher levels of liver fibrosis than group HCV(P = 0.001),but similar to that ob-served in HBV group.In HBV-HCV group,liver fibrosis was not associated with steatosis,IR or PNPLA3.HBV infection was the independent predictor of advanced liver fibrosis.CONCLUSION:HBV-HCV co-infected patients have lower degree of hepatic steatosis,IR and HCV RNA than HCV mono-infected;co-infected patients showed a more rapid liver fibrosis progression that seems to be due to the double infection and/or HBV dominance.     

慢性肝病者乙型和丙型肝炎病毒重叠感染的研究

对２１３例老年慢性肝病患者的乙型肝炎病毒（ＨＢＶ）和丙型肝炎病毒（ＨＣＶ）血清标志物检测发现：ＨＢＶ感染占７３．２４％、ＨＢＶ和ＨＣＶ重叠感染占重叠感染点１５．４９％、ＨＣＶ感染占７．０４％、其它占４．２６％；ＨＢＶ阴性者ＨＣＶ检出率高于ＨＢＶ阳性者，肝癌和肝硬化患者较慢性肝炎患者高；ＨＢＶ和ＨＣＶ重叠感染患者的血清血蛋白下降显著，γ－球蛋白升高明显，肝硬化并腹水和上消化道出血者了多。结果表明，老     

Liver damage in Italian patients with hereditary hemochromatosis is highly influenced by hepatitis B and C virus infection

We evaluated the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in 78 Italian patients with hereditary hemochromatosis as well as the relation between HCV antibody (anti-HCV) status, hepatitis B surface antigen (HBsAg) and liver histology. None of the patients had been transfused or ever consumed more than 60 g of alcohol per day. Eighteen showed histological signs of chronic hepatitis, active cirrhosis was present in 12, chronic active hepatitis in 4 and chronic persistent hepatitis in 2. Liver fibrosis or cirrhosis without inflammatory activity was observed in 31 subjects, whereas liver histology was normal except for iron overload in 18. The prevalence of HBsAg in the whole series was 5% and of anti-HCV was 20.5%. The prevalence of HBsAg and anti-HCV was significantly higher in the chronic hepatitis group than in the fibrosis/cirrhosis (p = 0.01) and the normal groups (p < 0.01). Fourteen of 18 hereditary hemochromatosis patients with chronic hepatitis were HBsAg (4) or anti-HCV (10) positive and all the latter subgroup had HCV-RNA in their serum as shown by the polymerase chain reaction. Although most of the patients with associated chronic hepatitis had cirrhosis, their serum ferritin levels and amount of mobilizable iron were significantly lower than those of the fibrosis/cirrhosis group (p < 0.01). This indicates that hepatitis viral infection acts synergistically with iron in accelerating the development of liver damage.     

Changes to hepatocyte ploidy and binuclearity profiles during human chronic viral hepatitis

BACKGROUND AND AIMS: The importance of the hepatocyte ploidisation pattern to the control of cell proliferation and differentiation has been well established. However, there are no data that have characterised hepatocyte ploidy at various stages of chronic liver inflammation and fibrosis in vivo. METHODS: We therefore investigated hepatocyte ploidy/binuclearity patterns in 57 patients with chronic hepatitis, using a recently developed methodology which allows simultaneous hepatocyte ploidy and binuclearity analyses on the same liver section. RESULTS: The percentage of mononuclear diploid hepatocytes was significantly reduced in patients with high hepatitis activity and marked fibrosis (low activity: 75.1 (18.8)% v high activity: 61.8 (21.6)%, p=0.0111, and low fibrosis: 77.3 (13.8)% v high fibrosis: 57.4 (23.3)%, p=0.0002). Accordingly, the percentage of mononuclear polyploid hepatocytes increased in patients with high hepatitis activity and marked fibrosis (low activity: 11.9 (15.5)% v high activity: 22.2 (20.1)%, p=0.0166, and low fibrosis: 9.4 (10.7)% v high fibrosis: 26.4 (21.6)%, p=0.0001). In addition, the fraction of binuclear hepatocytes was significantly higher in patients with hepatitis B virus (HBV) than in those with hepatitis C virus (HCV) infections (HBV: 18.2 (7.6)% v HCV: 12.0 (4.8)%; p=0.0020). Under multivariate analysis, HBV infection was an independent factor accounting for the larger binuclear hepatocyte fraction (p=0.0294). CONCLUSION: Our results revealed an increase in the polyploid hepatocyte fraction which correlates with the severity of chronic hepatitis; moreover, we demonstrated that HBV and HCV related chronic hepatitis exhibited distinctive hepatocyte ploidy patterns, thus allowing the suggestion that these two viral infections may modulate liver ploidy through different mechanisms.     

Adiponectin and Its Receptors in Chronic Hepatitis B Patients With Steatosis in China

Background

HBV infection is a serious public health problem worldwide, which can contribute to the incidence of chronic hepatitis B (CHB), cirrhosis, and hepatocellular carcinoma (HCC).

Objectives

In the present report, we assessed the association between adiponectin, its receptors and hepatic steatosis, fibrosis, and inflammation with hepatitis B virus.

Patients and Methods

Liver biopsies from 89 patients with untreated chronic hepatitis B (34 steatosis vs. 55 without steatosis) were analyzed; liver biopsies from 50 healthy adults were used as control. The liver biopsies were subjected to routine histological examination, and stained immunohistochemically for adiponectin and adiponectin receptor2 (adipoR2).

Results

The two groups were found to be comparable with respect to demographic, biochemical, metabolic, histological, and viral characteristics. BMI, γ-GT, FPG, insulin, and insulin sensitivity estimated by the HOMA index were significantly higher in patients with steatosis. The viral load of HBV and HBeAg positivity was higher in patients with steatosis than those without steatosis. High serum adiponectin levels were significantly correlated with abnormal serum ALT level (vs. normal ALT, P = 0.000), and HBV genotype C (vs. genotype B, P = 0.018). In patients with chronic HBV, the insulin sensitizing adipokine adiponectin, and its receptor AdipoR2were associated with steatosis. While adiponectin may becorrelated with inflammation, adiponectin, and its receptors were not associated with viral factors.

Conclusions

Our results suggest that the role of adiponectin might be impaired in chronic hepatitis B with steatosis. Reduced hepatic expression of adiponectin and adipoR2 might be of pathophysiological relevance in CHB patients with steatosis. These findings indicated that reduced liver adiponectin expression may play an important role in the pathogenesis, and progression of CHB patients with steatosis. However, hepatic expression of adiponectin, and adipoR2 was not associated with various measures of HBV infection.     

肝癌和癌旁组织中乙型肝炎表面抗原及丙型肝炎抗原表达与肝纤维化标志物的相关性

目的研究肝癌组织、癌旁组织中乙型肝炎表面抗原(HBsAg)、丙型肝炎抗原表达与血清肝纤维化标志物的相关性。方法采用免疫组织化学法对肝癌组织及癌旁组织中的HBsAg、丙型肝炎抗原表达进行了标记和分析,同时检测其血清肝纤维化标志物水平,并研究它们的相关性。结果肝癌血清肝纤维化标志物水平在乙型、丙型肝炎病毒混合感染组中最高,单独乙型、丙型肝炎病毒感染组次之,无病毒感染组最低,肝癌组织、癌旁组织中HBsAg、丙型肝炎抗原表达与透明质酸、层黏连蛋白、Ⅳ型胶原蛋白呈正相关,相关系数分别为0.60、0.45、0.46,P值均<0.01。结论肝癌遵循慢性病毒性肝炎、肝硬化、肝癌的发展趋势,有病毒感染的肝癌组织,其血清肝纤维化水平明显高于无病毒感染者。一方面病毒的感染是肝癌发生的原因,另一方面长期的病毒血症会加重肝脏组织病变,所以病毒性肝炎的抗病毒干预治疗对肝癌的预后有着积极的意义。     

Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C

BACKGROUND/AIMS: Hepatitis B virus (HBV) DNA has been detected in HBsAg-negative patients with hepatitis C. We determined the rate and explored the clinical significance of HBsAg negative HBV coinfections in Austrian patients with chronic hepatitis C. METHODS: Sera (n=82, group I) or liver tissue (n=16, group II) from 98 HBsAg negative Austrian patients with chronic hepatitis C were examined for HBV DNA by nested polymerase chain reaction (PCR). For control purposes, sera from 15 patients with chronic HBV infection (8 HBsAg positive, 7 HBsAg negative, all HBV PCR positive) were examined. RESULTS: HBV DNA was detected in 22% of sera and 19% of liver tissue specimens of patients with chronic hepatitis C. No significant difference in mean aminotransferase values, markers of HBV infection, inflammatory disease activity, or degree of hepatic fibrosis was observed in patients with or without HBV DNA. Anti-HBc alone as a marker of past HBV infection was more frequent in chronic hepatitis C patients compared to control individuals. Negative HCV PCR was more common (p=0.009) among patients with positive HBV PCR in serum. When examining repeat sera for HBV DNA, positive results were obtained in previously negative, but also negative results in previously positive patients. CONCLUSIONS: Coinfection with HBV can be demonstrated by PCR in a considerable number of HBsAg negative Austrian patients with chronic hepatitis C. HBV infection seems to suppress HCV replication even in HBsAg negative patients with dual infection. HBV coinfection in HCV infected patients cannot be excluded by negative HBsAg status alone. Repeat PCR examinations are needed to exclude dual infections.     

Aspartate aminotransferase (AST) more than alanine aminotransferase (ALT) levels predict the progression of liver fibrosis in chronic HCV infection

The development and severity of liver fibrosis in patients with chronic HCV infection can be evaluated best according to the staging of fibrosis in blind liver biopsy. So far there is however no biochemical indicator suggesting advanced fibrosis or progression of fibrosis in chronic HCV infection. In 1997 - 1999 60 adult out-patients (32 women) with chronic HCV infection were examined by blind liver biopsy. The grading of hepatitis was scored according to Knodell and staging of fibrosis according to Desmet. All patients were anti-HCV positive, assessed by the ELISA-3 method and 48/60 had positive HCV RNA in serum. The main risk factor of HCV infection was blood transfusion (67%). Of 27 examined patients 20 (74%) had serotype HCV 1. Staging of fibrosis: histologically confirmed fibrosis was not recorded in 11 patients (18.3%), mild and medium fibrosis was recorded in 25 (42%), severe fibrosis in 14 (23%) and cirrhosis in 10 (17%). With confirmed fibrosis correlated more closely AST serum activity (p < 0.002) than ALT activity (p < 0.03). Steatosis of the liver was found in 25 (42%) patients. The mean age of patients with steatosis was significantly higher than that of patients without steatosis (p < 0.0008). Steatosis was more frequent in patients with fibrosis (p < 0.04), in particularin the age group above 60 years. The development of fibrosis in patients with chronic HCV infection is suggested by permanently elevated activity of both transaminases whereby AST has a higher predictive value than ALT activity. A total of 40% histologically tested patients had the highest staging of fibrosis (3 - 4). Steatosis is in chronic HCV infection a very frequent finding (42%), in particular in patients above 60 years and those with serious fibrosis. The finding of fibrosis should stimulate the initiation of antiviral treatment which can lead to regression of fibrosis and improvement of the histological finding.