Composition of inflammatory infiltrate and its correlation with HBV/HCV antigen expression

AIM： To study the composition of liver inflammatory infiltrate in biopsy material from patients chronically infected with hepatotropic viruses and to evaluate the correlation of inflammatory infiltrate with hepatitis B virus （HBV） and hepatitis C virus （HCV） viral antigen expression in chronic B and C hepatitis.
METHODS： The phenotype of inflammatory cells was evaluated by the EnVision system, using a panel of monoclonal antibodies. HBV and HCV antigens were detected with the use of monoclonal anti-HBs, polyclonal anti-HBc and anti-HCV antibodies, respectively. RESULTS： The cellular composition of liver inflammatory infiltrate was similar in the patients with B and C hepatitis： ～50%-60% of cells were T helper lymphocytes. Approximately 25% were T cytotoxic lymphocytes; B lymphocytes comprised 15% of inflammatory infiltrate; other cells, including NK, totalled 10%. Expression of HLA antigens paralleled inflammatory activity. Portal lymphadenoplasia was found more often in hepatitis C （54.5%） than in hepatitis B （30.6%）. Expression of HB-cAg was found more often in chronic B hepatitis of moderate or severe activity. Overall inflammatory activity in HBV-infected cases did not correlate with the intensity of HBsAg expression in hepatocytes. Inflammatory infiltrates accompanied the focal expression of HCV antigens. A direct correlation between antigen expression and inflammatory reaction in situ was noted more often in hepatitis C than B.
CONCLUSION： Irrespective of the etiology and activity of hepatitis, components of the inflammatory infiltrate in liver were similar. Overall inflammatory activity did not correlate with the expression of HBsAg and HCVAg; HBcAg expression, however, accompanied chronic hepatitis 8 of moderate and severe activity.     

Significance of blood analysis in hemophiliacs co-infected with human immunodeficiency virus and hepatitis viruses

AIM： To study the effect of hepatitis virus infection on cirrhosis and liver function markers in HIV-infected hemophiliacs.
METHODS： We have analyzed the immunological, liver function and cirrhosis markers in a cohort of hemophiliacs co-infected with human immunodeficiency virus （HIV） and hepatitis viruses.
RESULTS： There was no difference in immunological markers among co-infected patients and patients infected with HIV only and those co-infected with one or more hepatitis virus. Although liver function and cirrhosis markers remained within a normal range, there was a worsening trend in all patients co-infected with hepatitis virus C （HCV）, which was further exacerbated in the presence of additional infection with hepatitis virus B （HBV）.
CONCLUSION： Co-infection with HIV, HBV and HCV leads to worsening of hyaluronic acid and liver function markers. Increases in serum hyaluronic acid may be suggestive of a predisposition to liver diseases.     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

Objective To study the liver histological changes in chronic hepaitits B (CHB) patients with normal serum alanine aminotransferase (ALT) levels and the related factors. Methods Six hundred and thirty-two CHB patients with normal ALT levels had undergone ultrasound guided percutaneous liver biopsies. All specimen were examined by HE staining, collagen fiber Masson staining and immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). The Knodell inflammation score and Ishak fibrosis score were both calculated and the relationship with age, serum levels of ALT and hepatitis B virus (HBV) DNA, hepatic expressions of HBsAg and HBcAg were analyzed. The means between two groups were compared by t test and those among groups were compared by one-factor analysis of variance and q test. Enumeration data were analyzed by x2 test. Results Among 632 CHB patients with normal ALT levels, 167 (26.4%) showed moderate necrotic inflammation in liver tissues and 26 (4.1%) showed severe necrotic inflammation; 217 (34. 3 % ) showed moderate fibrosis and 52 (8. 2 % ) showed severe fibrosis (cirrhosis). The Knodell inflammation score and Ishak fibrosis score in high ALT group were higher than low ALT group, those in female high ALT group were higher than male high ALT group and those in patients ＞ 40 years old were higher than ≤20 years old (q= 19.63, P＜0. 05). The liver injuries in patients with active HBV replication were more severe than those with undetectable HBV DNA levels (Knodell score, q=3.87, 2.87, 6.34; Ishak score, q=2.64,2. 64,5.54, all P＜0. 05),while there was no significant difference between patients with high levels and low levels of HBV DNA (F= 1.35, P＞0. 05). There was no significant difference between expressions of HBsAg (F= 1.65,0. 73,respectively; both P＞0. 05) and HBcAg in liver tissues and Knodell inflammation score and Ishak fibrosis score (F=0. 17, 1.29, respectively; both P＞0. 05). Conclusions Liver biopsies should be considered in CHB patients with normal ALT levels and detectable HBV DNA levels, especially those ＞ 40 years old and with ALT of (0.75-1.00) × upper limits of normal (ULN).     

丙氨酸转氨酶正常的慢性乙型肝炎病毒感染者的肝脏病理学分析

Objective To study the liver histological changes in chronic hepaitits B (CHB) patients with normal serum alanine aminotransferase (ALT) levels and the related factors. Methods Six hundred and thirty-two CHB patients with normal ALT levels had undergone ultrasound guided percutaneous liver biopsies. All specimen were examined by HE staining, collagen fiber Masson staining and immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg). The Knodell inflammation score and Ishak fibrosis score were both calculated and the relationship with age, serum levels of ALT and hepatitis B virus (HBV) DNA, hepatic expressions of HBsAg and HBcAg were analyzed. The means between two groups were compared by t test and those among groups were compared by one-factor analysis of variance and q test. Enumeration data were analyzed by x2 test. Results Among 632 CHB patients with normal ALT levels, 167 (26.4%) showed moderate necrotic inflammation in liver tissues and 26 (4.1%) showed severe necrotic inflammation; 217 (34. 3 % ) showed moderate fibrosis and 52 (8. 2 % ) showed severe fibrosis (cirrhosis). The Knodell inflammation score and Ishak fibrosis score in high ALT group were higher than low ALT group, those in female high ALT group were higher than male high ALT group and those in patients ＞ 40 years old were higher than ≤20 years old (q= 19.63, P＜0. 05). The liver injuries in patients with active HBV replication were more severe than those with undetectable HBV DNA levels (Knodell score, q=3.87, 2.87, 6.34; Ishak score, q=2.64,2. 64,5.54, all P＜0. 05),while there was no significant difference between patients with high levels and low levels of HBV DNA (F= 1.35, P＞0. 05). There was no significant difference between expressions of HBsAg (F= 1.65,0. 73,respectively; both P＞0. 05) and HBcAg in liver tissues and Knodell inflammation score and Ishak fibrosis score (F=0. 17, 1.29, respectively; both P＞0. 05). Conclusions Liver biopsies should be considered in CHB patients with normal ALT levels and detectable HBV DNA levels, especially those ＞ 40 years old and with ALT of (0.75-1.00) × upper limits of normal (ULN).     

Analysis of risk factors for susceptibility of abnormal liver function in male patients with gout

正Objective To investigate the risk factors for susceptibility of abnormal liver function in patients with gout.Methods A total of 5 044 cases of male gout patients in remission were selected and divided into normal liver function group with 3 693 patients and abnormal liver function group with 1 351 patients.The clinical information was collected and relevant biochemical indices were     

Fibrinogen-like protein 2 fibroleukin expression and its correlation with disease progression in murine hepatitis virus type 3-induced fulminant hepatitis and in patients with severe viral hepatitis B

AIM: To evaluate the expression of fibrinogen-like protein 2 (fgl2) and its correlation with disease progression in both mice and patients with severe viral hepatitis. METHODS: Balb/cJ or A/J mice were infected intraperitoneally (ip) with 100 PFU of murine hepatitis virus type 3 (MHV-3), liver and serum were harvested at 24, 48, and 72 h post infection for further use. Liver tissues were obtained from 23 patients with severe acute chronic (AOC) hepatitis B and 13 patients with mild chronic hepatitis B. Fourteen patients with mild chronic hepatitis B with cirrhosis and 4 liver donors served as normal controls. In addition, peripheral blood mononuclear cells (PBMC) were isolated from 30 patients (unpaired) with severe AOC hepatitis B and 10 healthy volunteers as controls. Procoagulant activity representing functional prothrombinase activity in PBMC and white blood cells was also assayed. A polyclonal antibody against fgl2 was used to detect the expression of both mouse and human fgl2 protein in liver samples as well as in PBMC by immunohistochemistry staining in a separate set of studies. Alanine aminotransferase (ALT) and total bilirubin (TBil) in serum were measured to assess the severity of liver injury. RESULTS: Histological changes were found in liver sections 12-24 h post MHV-3 infection in Balb/cJ mice. In association with changes in liver histology, marked elevations in serum ALT and TBil were observed. Mouse fgl2 (mfgl2) protein was detected in the endothelium of intrahepatic veins and hepatic sinusoids within the liver 24 h after MHV-3 infection. Liver tissues from the patients with severe AOC hepatitis B had classical pathological features of acute necroinflammation. Human fgl2 (hfgl2) was detected in 21 of 23 patients (91.30%) with severe AOC hepatitis B, while only 1 of 13 patients (7.69%) with mild chronic hepatitis B and cirrhosis had hfgl2 mRNA or protein expression. Twenty-eight of thirty patients (93.33%) with severe AOC hepatitis B and 1 of 10 with mild chronic hepatitis B had detectable hfgl2 expression in PBMC. No hfgl2 expression was found either in the liver tissue or in the PBMC from normal donors. There was a positive correlation between hfgl2 expression and the severity of the liver disease as indicated by the levels of TBil. PCA significantly increased in PBMC in patients with severe AOC hepatitis B. CONCLUSION: The molecular and cellular results reported here in both mice and patients with severe viral hepatitis suggest that virus-induced hfgl2 prothrombinase/fibroleukin expression and the coagulation activity associated with the encoded fgl2 protein play a pivotal role in initiating severe hepatitis. The measurement of hfgl2/fibroleukin expression in PBMC may serve as a useful marker to monitor the severity of AOC hepatitis B and a target for therapeutic intervention.     

Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection

Dual hepatitis C virus(HCV)/hepatitis B virus(HBV)infection is found in HBV or HCV endemic areas,and in specific populations exhibiting a high risk of parenteral viral transmission.Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients.The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations.Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections.Strikingly,approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV.The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined.Furthermore,approximately 30%of dually infected patients lost hepatitis B surface antigen(HBsAg)within 5 years after the start of peginterferonbased therapy,and 40%of them harbored occult HBV infection.The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations.Moreover,the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored.Finally,the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future,which warrants further clinical trials.     

白细胞介素-17肝内表达与慢性乙型肝炎病毒感染所致肝纤维化的相关性

Objective To explore the relationship between intrahepatic expression of interleukin-17 (IL-17) and liver fibrosis in patients with chronic hepatitis B virus infection. Methods IL-17 expressions in livers with different inflammation activity grades and hepatic fibrosis stages from patients with chronic hepatitis B virus carriers (n= 30), chronic hepatitis B (CHB, n = 55), liver cirrhosis (LC, n=20) were measured by immunohistochemistry. Serum IL-17 and liver fibrosis indices of haluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC Ⅲ ) and type Ⅳ collagen ( Ⅳ C) were determined by enzyme linked immunosorbent assay (ELISA). The differences between groups were compared by Kruskal-Wallis test, and the Mann-Whitney test, and the correlation analysis was done by Spearman test. Results Intrahepatic IL-17 expression in LC group was significantly higher than CHB group (x2 =25. 3982, P=0. 004), and that in CHB group was higher than chronic hepatitis B virus carriers group (x2 = 11. 5056, P= 0. 001). The inflammation activity grade and hepatic fibrosis stage were both positively correlated with IL-17 expression (r= 0.718, 0. 693, respectively; both P＜0.01). IL-17 mainly located in portal area and the expression was positively correlated with serum levels of HA, LN, PCⅢ and ⅣC (r=0. 793, 0. 834, 0. 722, 0. 883, respectively; all P＜0.01).Conclusion Intrahepatic IL-17 expression is closely correlated with liver inflammation activity grade and hepatic fibrosis stage.     

白细胞介素-17肝内表达与慢性乙型肝炎病毒感染所致肝纤维化的相关性

Objective To explore the relationship between intrahepatic expression of interleukin-17 (IL-17) and liver fibrosis in patients with chronic hepatitis B virus infection. Methods IL-17 expressions in livers with different inflammation activity grades and hepatic fibrosis stages from patients with chronic hepatitis B virus carriers (n= 30), chronic hepatitis B (CHB, n = 55), liver cirrhosis (LC, n=20) were measured by immunohistochemistry. Serum IL-17 and liver fibrosis indices of haluronic acid (HA), laminin (LN), type Ⅲ procollagen (PC Ⅲ ) and type Ⅳ collagen ( Ⅳ C) were determined by enzyme linked immunosorbent assay (ELISA). The differences between groups were compared by Kruskal-Wallis test, and the Mann-Whitney test, and the correlation analysis was done by Spearman test. Results Intrahepatic IL-17 expression in LC group was significantly higher than CHB group (x2 =25. 3982, P=0. 004), and that in CHB group was higher than chronic hepatitis B virus carriers group (x2 = 11. 5056, P= 0. 001). The inflammation activity grade and hepatic fibrosis stage were both positively correlated with IL-17 expression (r= 0.718, 0. 693, respectively; both P＜0.01). IL-17 mainly located in portal area and the expression was positively correlated with serum levels of HA, LN, PCⅢ and ⅣC (r=0. 793, 0. 834, 0. 722, 0. 883, respectively; all P＜0.01).Conclusion Intrahepatic IL-17 expression is closely correlated with liver inflammation activity grade and hepatic fibrosis stage.     

Inhibition of hepatitis B virus replication by APOBEC3G in vitro and in vivo

AIM: To investigate the effect of APOBEC3G mediated antiviral activity against hepatitis B virus (HBV) in cell cultures and replication competent HBV vector-based mouse model. METHODS: The mammalian hepatoma cells Huh7 and HepG2 were cotransfected with various amounts of CMV-driven expression vector encoding APOBEC3G and replication competent 1.3 fold over-length HBV. Levels of HBsAg and HBeAg in the media of the transfected cells were determined by ELISA. The expression of HBcAg in transfected cells was detected by western blot. HBV DNA and RNA from intracellular core particles were examined by Northern and Southern blot analyses. To assess activity of the APOBEC3G in vivo, an HBV vector-based model was used in which APOBEC3G and the HBV vector were co-delivered via high-volume tail vein injection. Levels of HBsAg and HBV DNA in the sera of mice as well as HBV core-associated RNA in the liver of mice were determined by ELISA and quantitative PCR analysis respectively. RESULTS: There was a dose dependent decrease in the levels of intracellular core-associated HBV DNA and extracellular production of HBsAg and HBeAg. The levels of intracellular core-associated viral RNA also decreased, but the expression of HBcAg in transfected cells showed almost no change. Consistent with In vitro results, levels of HBsAg in the sera of mice were dramatically decreased. More than 1.5 log 10 decrease in levels of serum HBV DNA and liver HBV RNA were observed in the APOBEC3G-treated groups compared with the control groups. CONCLUSION: These findings indicate that APOBEC3G could suppress HBV replication and antigen expression both in vivo and in vitro, promising an advance in treatment of HBV infection.     

隐匿性乙型肝炎病毒感染者临床特点和肝组织病理学检查

目的了解血清肝炎病毒标志物阴性、肝功能反复异常患者中HBV隐匿性感染的比例及其临床和病理学特点。方法对27例血清肝炎病毒标志物阴性、肝功能反复异常患者采用免疫组化法检测肝组织HBsAg、HBcAg和HCVAg，并进行常规的病理学检查。结果肝组织HBsAg和（或）HBcAg阳性9例（33．3％）；HBsAg和（或）HBcAg及HCVAg阳性10例（37．0％）；全阴性8例（29．6％）。在HBV隐匿性感染的19例患者中，慢性肝炎8例，肝硬化11例。结论HBV和HCV感染为血清肝炎病毒标志物阴性患者肝功能反复异常的主要原因之一，尤其是HBV感染。这种HBV隐匿性感染与慢性肝炎、肝硬化的发生关系密切，应引起重视。     

Differential distribution of hepatitis B surface antigen and hepatitis B core antigen in the liver of hepatitis B patients.

One hundred liver biopsies from 100 patients with clinical presumptive diagnosis of hepatitis were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBSAg) and hepatitis B core antigen (HBcAg). Of the 60 HBsAg-positive livers, 51 were diagnosed as chronic hepatitis on histological grounds, 6 as acute hepatitis, and 3 as "near-normal liver." From the 60 tissue-positive cases, 3 subjects were HBsAg seronegative. HBcAg was detected in 44 livers, all of which also had HBcAg in the localized in the cytoplasm and the membranes of the hepatocytes, and HBcAg in the nuclei and in 4 cases also in the cytoplasm. Predominant HBsAg expression in the cytoplasm was observed in near-normal liver, chronic persistent hepatitis, and cirrhosis with little activity. This correlated with the amount of ground glass hepatocytes in the biopsies. HBcAg and membrane-localized HBsAg were minimal in those conditions. HBcAg was most prevalent in patients with chronic aggressive hepatitis and active cirrhosis treated with immunosuppressive drugs, whereas the amounts of HBsAg and HBcAg in nontreated patients of those two groups and in acute hepatitis with signs of transition to chronicity were almost equal. HBsAg expression in liver cell membranes was most prominent in active forms of chronic hepatitis (chronic aggressive hepatitis and in active cirrhosis) and in acute hepatitis with signs of transition to chronicity. This observation correlated in the presence of HBcAg in the biopsies of those patients. In acute hepatitis both HBsAg and HBcAg were detected rarely and no membrane expression of HBsAg was observed. The over-all results show a significant relationship between the different degrees of accumulation of HBsAg and HBcAg in the liver and the various histological types of hepatitis and further suggest an interplay of both hepatitis B virus and host immune response in the development and pathogenesis of hepatitis B.     

细胞间粘附分子－1在乙型肝炎中的表达及意义

为观察细胞间粘附分子－１（ＩＣＡＭ－１）在乙型肝炎肝组织内的表达状况，探讨ＩＣＡＭ－１在乙型肝炎肝细胞免疫损伤中的作用。采用链菌素亲生物蛋白法（ＬＳＡＢ），以ＩＣＡＭ－１的单克隆抗体，检测１０４例急、慢性乙型肝炎，９例无症状携带者，１０例正常肝组织标本内ＩＣＡＭ－１抗原表达情况。结果发现：ＩＣＡＭ－１在正常肝细胞无表达，肝窦内皮细胞弱表达；ＨＢＶ感染后肝细胞呈不同程度的表达，肝窦内皮表达增强；中、重度慢性肝炎，活动性肝硬化肝细胞ＩＣＡＭ－１表达较急性肝炎，轻度慢性肝炎显著增强（Ｐ＜０．０１）；急性肝炎较轻度慢性肝炎显著增强（Ｐ＜０．０１）；轻度慢性肝炎较无症状携带者，正常肝组织显著增强（Ｐ＜０．０１）。表明ＩＣＡＭ－１在乙型肝炎肝细胞内表达与肝细胞损伤有关，对ＨＢＶ的清除可能起着重要作用，ＩＣＡＭ－１在肝窦内皮的表达有助于淋巴细胞向肝组织内浸润。     

非肝病及慢性乙型肝炎患者肝组织中巨细胞病毒的检测

目的：探讨巨细胞病毒（CMV）在非肝病患者及慢性乙型肝炎患者肝组织中的表达、分布特点及相关关系。方法：采用免疫组化方法以抗－CMV单克隆抗体对31例非肝病及76例慢性乙型肝炎肝组织进行检测，用抗－HBcAg多克隆抗体和抗－CMV单克隆抗体双标记技术在部分慢性乙型肝炎患者同一张肝组织切片上显示两种病毒分布特点。结果：31例非肝病肝组织中检出CMV Ag7例（22．6％），明显低于慢性乙型肝炎患者（43／76，56．6％），P＜0．01。在两组标本中CMV Ag均在肝细胞胞浆内表达。非肝病患者肝组织中阳性细胞数量较慢性乙型肝炎患者少，后者阳性细胞多近汇管区分布，数量多时，也可在肝小叶内弥漫分布。轻度和重度慢性乙型肝炎患者中CMV的检出率比较，差异无显著性，但慢性乙肝炎患者中CMV表达阳性细胞明显多于轻度慢性乙型肝炎（P＜0．05）。双标记染色显蒜CMV Ag和HBcAg多数可表达于肝小叶内同一区域肝细胞甚至同一肝细胞内，也可见于肝小叶中不同部位。结论：非肝病患者中CMV感染并不少见，慢性乙肝炎患者更易重叠CMV感染，并且其感染程度与肝组织的活动性病变密切相关。     

乙肝病毒感染对慢性乙肝肝硬化患者胃黏膜病变的影响

目的探讨乙肝病毒(HBV)感染对慢性乙肝、肝硬化患者胃黏膜病变的影响及其发病机制。方法2003-06～2004-02对河北医科大学第三医院感染科60例慢性乙肝、肝硬化患者同时行肝穿、胃镜、肝功能、血清肝炎病毒标志物检查,采用SP法检测肝及胃黏膜组织中HBsAg、HBcAg。结果(1)肝组织病理损害程度与胃黏膜病变程度成正比(r=0.483,P<0.01)。(2)56例中26例胃黏膜组织中可检测到HBsAg和(或)HBcAg,其病变以中重度为主。34例HBVM阴性患者中,病变以轻中度为主(P<0.01)。(3)肝组织与胃黏膜组织中HBsAg同时阳性17例;HBcAg同时阳性6例(P>0.05)。(4)血清及胃黏膜组织中HBsAg和(或)HBcAg同时阳性26例;HBVDNA同时阳性22例(P>0.05)。结论进一步证实了HBV可侵犯胃黏膜组织,并在其中复制,是导致慢性乙肝患者胃黏膜病变的重要因素。胃黏膜病变程度与胃黏膜组织HBV感染、肝组织病变程度密切相关;与血清及肝组织中HBV分布无关。     

Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers

Delta antigen is currently thought to reflect superinfection of the liver with a defective RNA virus (delta agent), requiring helper function from hepatitis B virus for its replication. To assess the influence of delta agent on hepatitis B virus replication in patients persistently infected with both viruses and showing chronic liver disease, we measured serum and liver hepatitis B virus DNA in HBsAg-positive chronic liver disease patients who were either positive or negative for delta antigen in the liver. Hepatitis B virus DNA was assayed in the serum of 21 patients with delta antigen-positive/HBsAg-positive chronic liver disease and in 21 patients with delta antigen-negative/HBsAg-positive chronic liver disease matched for HBeAg/anti-HBe status and underlying liver histology. HBcAg and delta antigen in liver was determined by immunofluorescence or immunoperoxidase staining. In delta antigen-positive/HBsAg-positive chronic liver disease, serum hepatitis B virus DNA was detected transiently in 4 of 21 cases (19%) and was present in these patients at low levels (trace to 2+). In contrast, 9 of 21 (43%) delta antigen-negative/HBsAg-positive chronic liver disease patients were serum hepatitis B virus DNA positive, and five of these had high serum hepatitis B virus DNA levels (3+ to 4+). Serum HBsAg and anti-HBc titers were significantly lower in delta antigen-positive cases and correlated with reduced amount of HBcAg in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

肾病综合征合并慢性乙型肝炎患者强的松长期治疗后肝组织学的初步观察

本文采用常规HE和免疫组织化学染色的方法观察了16例肾病综合征合并慢性乙型肝炎(CHB)患者长期使用强的松后肝组织病理变化和B7-1、HBcAg表达情况。结果显示:16例患者肝组织损害轻微,伴大量毛玻璃样细胞,均有HBcAg胞核强表达,仅1例B7-1弱表达;其中3例患者停药3个月后肝组织病变仍轻,无毛玻璃样细胞及B7-1表达,但仍有HBcAg胞核强表达。提示:肾上腺皮质激素有可能减轻肝细胞损害及纤维化,抑制细胞毒性T淋巴细胞(CTL)的活化、增殖过程;但停药后“免疫反跳”作用可疑。     

慢性乙型肝炎肝内浸润淋巴细胞功能相关抗原-1表达在肝细胞损伤及病毒清除中的意义

探讨淋巴细胞功能相关抗原—1(LFA-1）在慢性乙肝组织中浸润淋巴细胞的表达及意义。利用免疫组化技术，对51例不同类型的慢性HBV感染者肝组织内浸润淋巴细胞LFA-1的表达状况进行观察，并同时检测肝内HBcAg表达状况。慢性HBV感染者肝内浸润淋巴细胞存在不同程度的LFA-1表达，9例HBV感染的无症状携带者，肝内散在的淋巴细胞未见LFA-1表达，在42例慢性乙性肝炎中，其中38例肝组织浸润淋巴细胞LFA-1表达，阳性率为90．4％。阳性表达的淋巴细胞多位于肝组织病变明显区域及其周围肝组织，LFA-1表达强度与肝炎的程度有关，其中慢性重度乙型肝炎浸润淋巴细胞LFA—1表达较慢性中度乙型肝炎显著增强，慢性中度乙型肝炎LFA-1表达较慢性轻度乙型肝炎显著增强。肝内浸润淋巴细胞LFA-1表达阳性组、强阳性组较弱阳性及阴性组相比，肝内HBcAg阳性表达减少。慢性乙肝组织中浸润淋巴细胞LFA-1的表达参与了乙型肝炎的发病过程，不仅参与肝细胞的损害过程，同时亦有助于对肝细胞内HBV的清除。     

HLA class I antigen display on hepatocyte membrane in chronic hepatitis B virus infection: its role in the pathogenesis of chronic type B hepatitis

It has been suggested that cytotoxic T cells are involved in the recognition and lysis of the infected hepatocytes in chronic hepatitis B virus infection, and that the target antigen is probably HBcAg which is displayed on the hepatocyte membrane during active viral replication. However, studies in other viral infection have demonstrated that cytotoxic T cells recognize viral antigen on the infected cells only in the context of HLA class I antigens. To test whether this mechanism is also operative in chronic hepatitis B virus infection, we studied the expression of HLA class I antigens in livers from 35 patients with chronic hepatitis B virus infection by indirect immunofluorescence using monoclonal antibody against HLA class I antigens. The blocking effect of monoclonal antibody against HLA class I antigens on the in vitro T cell cytotoxicity to autologous hepatocytes was also studied. The results revealed that HLA class I antigen was undetectable on the hepatocyte membrane in all of 10 HBeAg-positive carriers with minor hepatitic activity, whereas it was demonstrated in 15 (88%) of the 17 HbeAg-positive patients with chronic active liver disease and in 7 (87%) of the 8 anti-HBe-positive "normal" carriers. The in vitro T cell cytotoxicity to autologous hepatocytes in six HBeAg-positive patients with chronic active liver disease was significantly inhibited by preincubation of hepatocytes with monoclonal antibody (10 to 40 micrograms per ml) against HLA class I antigen, but not by monoclonal antibody against HLA class II antigens and non-HLA-associated surface molecules (Leu 11).(ABSTRACT TRUNCATED AT 250 WORDS)     

HBV感染者肝细胞凋亡与乙型肝炎表面抗原双染色研究

目的探讨乙型肝炎肝细胞凋亡与病毒感染的关系。方法应用原位末端标记技术和免疫组化方法对一组乙肝患者肝细胞凋亡和乙肝表面抗原（ＨＢｓＡｇ）表达状况同时进行了检测。结果受检的８例乙型肝炎患者肝组织中均可检出凋亡细胞，阳性信号位于细胞核以及肝窦内之凋亡小体中；阳性细胞在肝细胞索多散在分布，在肝细胞坏死灶中亦可检出凋亡细胞；凋亡多发生于病毒抗原弱表达细胞，而大多数抗原阳性细胞未检测到凋亡信号，此外，少数凋亡细胞ＨＢｓＡｇ呈阴性。结论乙型肝炎患者感染和未感染病毒的肝细胞均可发生凋亡，但凋亡只在少数细胞发生。