隐匿性乙型肝炎79例临床与病理分析

目的：探讨隐匿性乙型肝炎的临床与病理特征。方法：应用荧光定量PCR及免疫组织化学方法，对79例不同HBV抗体阳性而肝功能反复异常者的临床与肝组织病理进行分析。结果：79例患者中，血清HBV DNA阳性27例（34．2％），肝组织中HBV DNA阳性59例（74．7％），差异具有显著性意义（X^2=26．1，P〈0．01）；肝组织病理检查结果显示慢性肝炎77例，其中大多数为轻中度损害，肝硬化早期2例；免疫组化检测结果显示肝组织中HBsAg阳性11例，HBcAg阳性32例。结论：①隐匿性乙型肝炎患者肝组织中HBV DNA阳性率明显高于血清；②隐匿性乙型肝炎患者大多数存在不同程度肝损害，需要及时治疗。     

31例HBsAg阴性慢性乙型肝炎患者的临床及病理分析

目的了解HBsAg阴性慢性乙型肝炎(隐匿性乙型肝炎)患者的发病情况、临床和病理特点以及可能的发病机制。方法对31例反复肝功能异常、HBsAg阴性HBV感染患者进行临床、肝组织病理及免疫组化分析;采用荧光定量PCR方法对血清HBVDNA进行定量分析,以免疫组化法检测肝组织内HbsAg和HBcAg的表达,按慢性肝炎病理诊断标准进行分级(G)及分期(S)。结果31例HBsAg阴性慢性乙型肝炎患者中,18例肝组织病理和免疫组化检测证实为慢性乙型肝炎,其中7例诊断为肝炎后肝硬化;18例肝组织学检查HBsAg阳性2例,HBcAg阳性16例;病理分级、分期G4S4有7例,G1-3、S2-3有11例。结论HBsAg阴性HBV感染仍是我国原因不明肝病的主要原因之一,低水平HBV感染可导致慢性肝炎,甚至肝硬化或肝癌。     

隐匿性乙型肝炎病毒感染289例临床分析

HBsAg阴性不能排除乙型肝炎病毒（HBV）感染已经成为共识,尤其在HBV感染的高发地区。HBsAg阴性的HBV感染通常称为隐匿性HBV感染,是指血清HBsAg阴性,而应用荧光定量PCR技术检测血清和（或）肝组织中HBVDNA阳性。我们对可疑人群的HBVDNA进行检测,以观察本地区隐匿性HBV感染的流行情况,同时对隐匿性HBV感染患者进行跟踪观察,并对隐匿性HBV感染的肝炎（肝功能异常）患者进行治疗。     

HBsAg阴性慢性乙型病毒性肝炎患者的临床与病理分析

目的研究HBsAg阴性慢性乙型病毒性肝炎患者的临床和病理特点,探讨其在不明原因肝病中的发病情况及临床意义。方法对62例HBsAg阴性不明原因反复肝功能异常的慢性肝炎患者用巢式PCR方法检测患者血清HBV—DNA,并行肝组织活检,免疫组化检测肝组织中HB—sAg和HBcAg,排除常见嗜肝病毒感染及其它原因的肝损害。结果62例HBsAg阴性不明原因肝炎患者中血清HBV—DNA阳性11例,其中2例荧光定量PCR阳性（2／62）,9例巢式PCR阳性（9／60）,阳性率为17．74％（11／62）,肝组织病理及免疫组化亦证实为慢性乙型病毒性肝炎。对照组2例阳性（2／25,8％）,两组比较差异有显著性（P〈0．05）。结论HBsAg阴性慢性HBV感染是不明原冈肝病的主要原因之一。     

HCV/HBV重叠感染重症肝炎患者的临床与病理

探讨HCV／HBV重叠感染重症肝炎的发病机制。用直接酶标法检测肝组织内HCVAg，用PAP法检测肝组织内HBsAg、HBcAg。在264例肝病肝组织中共检出15例HCVAg阳性患者(5．7％)，肝内HCVAg阳性细胞表现为脑浆型9例、核浆型2例、核型4型。脑浆型HCVAg阳性患者肝组织内还检出HBsAg阳性5例、HBcAg阳性3例，脑浆型HCVAg阳性肝细胞疏松水肿，并可见淋巴细胞围绕。HCV／HBV重叠感染重症肝炎组与单纯HBV阳性重症肝炎组相比较，前者肝损害程度严重，结果提示HCV与HBV二者有相互促进作用，从而加重肝脏的损害。     

隐匿性慢性乙型肝炎5例

隐匿性乙型肝炎病毒（hepatitis B virus,HBV）感染是指血清学检测HBsAg阴性,而血清和（或）肝组织HBV DNA阳性的一种HBV感染状况[1],这种感染状态可发生于抗-HBc和（或）抗-HBs阳性的患者,也可见于HBV血清标志物均阴性的个体[2]。     

血清学阴笥病毒性肝炎的临床特点及免疫组化分析

目的 对60例血清学阴性（非甲0非庚型）的病毒性肝炎患者进行临床特点及肝组织免疫组化分析。方法 用Menghini法穿刺取肝组织，10％福尔马林固定标本，石蜡包埋，切片。采用生物素标记的第二抗体及链霉菌抗生物素连接的过氧化物酶及底物色素（S－P法）测定肝组织HBsAg、HBcAg、HCVAg。结果 HBVAg阳性30例，HCVAg阳性5例，HBV、HCV重叠感染6例，全阴性19例。结论 HBV、HCV为血清学全部了有性肝炎的主要病原，对血清学病原阴性病毒性肝炎应重视肝组织病理学及病原学的检查。     

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。     

乙、丙型肝炎病毒及幽门螺杆菌在慢性肝炎、肝硬化患者胃黏膜的表达

目的 探讨乙、丙型肝炎病毒(HBV、HCV)的泛嗜性及幽门螺杆菌(Helicobacter pylori)感染的关系。方法 选择慢性乙型肝炎(慢肝)28例、乙型肝炎后肝硬化(肝硬化)44例,共72例作为观察组,无肝病的胃病患者30例作为对照组。受检者常规胃镜检查,取胃窦幽门周围3cm以内活体组织3块,除普通病理检查外,分别做乙型肝炎病毒表面抗原(HBsAg)、乙型肝炎病毒核心抗原(HBcAg)、丙型肝炎病毒抗原(HCVAg)检测及快速尿素酶、品红染色和免疫组化法检测H.pylori抗原(HPAg)。结果 慢肝组有不同程度的胃黏膜慢性炎症者达92.9％(26/28)、肝硬化组为95.5％(42/44)。排除年龄影响因素外,慢肝组以单纯慢性炎症为多,而肝硬化组以伴萎缩和肠化者多。72例慢性肝病者中有51例胃黏膜HBVAg阳性,其中HBsAg、HBcAg双阳性31例。肝硬化组HBsAg或HBcAg表达及HBsAg、HBcAg双阳性者均高于慢肝组(P均<0.05)。51例慢性肝病胃黏膜中有33例占64.7％有HCVAg表达;其中22例占52.4％与HBsAg或(和)HBcAg同时表达。在慢肝和肝硬化组有炎症的胃黏膜中H.pylori阳性率分别为67.9％(20/26)、69.0％(29/42),与对照组相比无显著差别。慢性肝病H.Pylori阳性、阴性者胃黏膜HBV抗原表达率分别为69.8％(37/53)、73.7％(14/19),亦无统计学差异(P>0.05)。结论 (1)HBV、H     

单项抗-HBs阳性肝炎的临床与病理分析

目的 分析单项抗-HBs阳性肝炎的临床与病理特征,提高对单项抗-HBs阳性肝炎的认识。方法 对72例单项抗-HBs阳性肝炎患者进行肝炎病毒血清学检测、肝功能检查、血清HBV DNA检测及肝穿刺活组织病理和免疫组化检查。结果 72例患者除去4例脂肪肝和3例Dubin-Johnson综合征外,另65例中89.2％为慢性肝炎(58/65),其中慢性肝炎轻度占慢性肝炎79.3％(46/58)。与病理诊断比较临床诊断的正确率为61.1％,在慢性肝炎轻度则较高为71.7％。临床表现和肝功能变化与肝组织炎症活动度密切相关。3.2％的患者示肝内HBsAg或/和HBcAg阳性,而血清HBV DNA检测7.9％阳性。结论 单项抗-HBs阳性肝炎多为慢性肝炎,临床表现轻,炎症活动度和纤维化程度较轻,但体内仍可有HBV复制,仍可发展为肝硬化。肝穿刺病理及免疫组化检测有助于明确诊断。     

Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection in liver specimens and in serum samples

Prevalence and impact of occult HBV infection in HIV positive patients is controversial. The aims of this study were to determine the prevalence of occult HBV infection and its impact on histological and virological parameters. 52 HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied. DNA was extracted from frozen biopsies and amplified with primers for S, C and X regions, and for (ccc) HBV-DNA. Sera were tested for HBV-DNA with two quantitative assays (Cobas Amplicor HBV Monitor, and the real-time COBAS (r) Taqman HBV Test, Roche Diagnostics, UK). Occult HBV infection was detected in 7 (13.4%) liver biopsies of the study group, and in none case of the non viral chronic hepatitis group (p=0.04). All serum samples were HBV-DNA negative with Cobas Amplicor HBV monitor assay, while 3 cases were found positive with real time PCR. Statistical analysis didn't show any impact of occult HBV infection on liver histology, CD4+ cells count, HIV and HCV load, and ALT levels. Occult B infection is relatively frequent in HIV/HCV co-infected patients, and is underestimated by common HBV-DNA serological assays. However, it doesn't seem to exert a relevant impact.     

Occult hepatitis B virus infection in Greek patients with chronic hepatitis C and in patients with diverse nonviral hepatic diseases

Occult hepatitis B virus (HBV) infection has been reported in patients with chronic hepatitis C who are negative for HBV surface antigen (HBsAg). However, the significance of 'silent' HBV in hepatitis C virus (HCV) infection is unknown. We investigated 540 subjects for the presence of occult HBV in Greek HCV patients, patients with nonviral liver diseases and healthy donors in an attempt to determine the frequency and importance of this phenomenon. One hundred and eighty-seven anti-HCV(+)/HBsAg(-) patients' sera were investigated for the presence of HBV-DNA by polymerase chain reaction. Two hundred and eighty-two selected blood donors (positive for antibodies to HBV core antigen) and 71 patients with various nonviral hepatic diseases consisted the control groups [both controls were anti-HCV(-)/HBsAg(-)]. HBV-DNA was detected in 26.2% of HCV-infected patients vs 8.5% of patients with nonviral diseases (P = 0.003) and 0/282 of donors (P = 0.0000). HBV-DNA was neither associated with HBV markers, nor with the clinical status of HCV and nonHCV patients. Neither epidemiological, histologic and virologic data nor the response to therapy were associated with the HBV-DNA detection. Hence one quarter of HCV-infected patients had occult HBV infection. Similar findings were not found in both control groups. Occult HBV infection in Greek patients with chronic hepatitis C does not seem to modify the progression of chronic liver disease. Further studies of longer duration are needed in order to clarify the role of 'silent' HBV infection in HCV-infected patients.     

Seroprevalence of occult hepatitis B among Egyptian paediatric hepatitis C cancer patients

Occult hepatitis B infection is characterized by the presence of hepatitis B virus (HBV) DNA in the serum in the absence of hepatitis B surface antigen (HBsAg). Prevalence of hepatitis C virus (HCV) infections in Egypt is among the highest in the world. In this study, we aim at analysing the rates of occult HBV infections among HCV paediatric cancer patients in Egypt. The prevalence of occult HBV was assessed in two groups of paediatric cancer patients (HCV positive and HCV negative), in addition to a third group of paediatric noncancer patients, which was used as a general control. All groups were negative for HBsAg and positive for HCV antibody. HBV DNA was detected by nested PCR and real‐time PCR. HCV was detected by real‐time PCR. Sequencing was carried out in order to determine HBV genotypes to all HBV patients as well as to detect any mutation that might be responsible for the occult phenotype. Occult hepatitis B infection was observed in neither the non‐HCV paediatric cancer patients nor the paediatric noncancer patients but was found in 31% of the HCV‐positive paediatric cancer patients. All the detected HBV patients belonged to HBV genotype D, and mutations were found in the surface genome of HBV leading to occult HBV. Occult HBV infection seems to be relatively frequent in HCV‐positive paediatric cancer patients, indicating that HBsAg negativity is not sufficient to completely exclude HBV infection. These findings emphasize the importance of considering occult HBV infection in HCV‐positive paediatric cancer patients especially in endemic areas as Egypt.     

45例HBsAg阴性乙型肝炎的临床分析

目的研究HBsAg阴性乙型肝炎的临床特点、血清HBV标志物、HBVDNA水平、肝脏病理变化及肝组织HBsAg和HBcAg的表达情况。方法回顾性分析45例HBsAg阴性乙型肝炎患者的临床资料,所有患者均进行了肝组织活检和病理免疫组化检测。结果在45例患者中,23例(51.1%)感染途径不明,25例(55.5%)无任何自觉症状,肝功能异常和病理损害均为轻度,但8例(17.8%)肝脏病理诊断为早期肝硬化;45例患者肝组织HBsAg和(或)HB-cAg均有至少一项阳性;43例(95.6%)患者血清抗-HBs、抗-HBe和抗-HBc出现单独或联合阳性,而仅4例(8.9%)血清HBVDNA阳性。结论HBsAg阴性乙型肝炎起病隐匿,临床症状、肝功能变化和病理损害相对较轻,但其危害不容忽视,明确诊断需检测血清HBVDNA和(或)肝组织HBsAg和HBcAg。     

慢性乙型肝炎病毒感染者家族隐匿性乙型肝炎病毒感染的调查

目的 了解慢性HBV感染者家族隐匿性HBV感染的发生率及其与HBV标志物、年龄和性别等的关系.方法 ELISA方法检测慢性HBV感染者家族成员的HBV血清学标志物,套式PCR法检测136例HBsAg阴性家族成员的血清HBV DNA,并将隐匿性HBV感染者和HBsAg、HBV DNA均阴性者分别作为试验组和对照组进行HBV标志物、年龄、性别和生物化学检测结果的比较.两组均数比较采用t检验.率的比较采用χ~2检验或Fisher确切概率法检验.结果 在52个慢性HBV感染者家族中共检测到92例HBsAg阳性者和136例HBsAg阴性者,其中15例为隐匿性HBV感染者,慢性HBV感染者家族HBsAg阳性率和隐匿性HBV感染的发生率分别为40.4%和11.0%,15例隐匿性HBV感染者中有7例抗-HBc阳性(χ~2=5.341,P=0.02),但隐匿性HBV感染的存在与年龄、性别等无关.结论 HBV感染存在家庭聚集现象,且在其家族中存在隐匿性HBV感染,并在抗-HBc阳性者中发生率较高.     

Analysis of occult hepatitis B virus infection in liver tissue of HIV patients with chronic hepatitis C

OBJECTIVE: Current data on the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals conflict. As occult HBV infection could have an impact on the outcome of liver disease in HIV-positive patients, we investigated a large number of HIV-positive/HBV-surface-antigen (HBsAg) negative subjects with hepatitis C virus (HCV) infection by using the 'gold standard' approach for occult HBV detection--analysis of liver DNA extracts. METHODS: The presence or absence of HBV DNA was determined by PCR testing of four different viral genomic regions in DNA extracts of needle liver biopsy specimens of 101 HBsAg negative individuals with HIV/HCV co-infection. HBV genotyping was performed by sequencing analysis of the preS-S gene in occult HBV isolates from 18 cases. RESULTS: Occult HBV infection was diagnosed in 42 of the 101 cases (41%). No clinically relevant difference was found between occult HBV-positive and -negative patients. HBV genotype D and A were detected, respectively, in 11 (61%) and 7 (39%) of 18 cases analysed. CONCLUSIONS: Occult HBV infection frequently occurs in HIV/HCV co-infected patients indicating the importance of performing prospective studies able to clarify its clinical impact in these patients. HBV genotype A is highly prevalent in HIV-infected subjects with occult HBV infection in a similar way to HBsAg/HIV-positive individuals.     

Occult hepatitis B virus infection in patients with chronic liver disease due to hepatitis C virus and hepatocellular carcinoma in Brazil

BACKGROUND: The prevalence and consequences of occult HBV infection in patients with chronic liver disease by HCV remain unknown. AIMS: To evaluate the prevalence of occult HBV infection in a population of HCV-infected patients with hepatocellular carcinoma. METHODS: The serum samples were tested for HBV DNA by nested PCR and liver tissue analysis was carried out using the immunohistochemical technique of 66 HBsAg-negative patients: 26 patients with chronic hepatitis by HCV (group 1), 20 with hepatocellular carcinoma related to chronic infection by HCV (group 2) and 20 with negative viral markers for hepatitis B and C (control group). RESULTS: Occult HBV infection was diagnosed in the liver tissue of 9/46 (19.5%) HCV-infected patients. Prevalence of occult B infection was evaluated in the HCV-infected patients with and without hepatocellular carcinoma, and there were seven (77.7%) of whom from group 2, conferring a 35% prevalence of this group. No serum sample was positive for HBV DNA in the three groups. CONCLUSION: Occult infection B is frequently detected in liver tissue of HCV-infected patients, especially in cases of hepatocellular carcinoma. However large studies are needed to confirm that co-infection could determine a worse progress of chronic liver disease in this population.     

Role of occult hepatitis B virus in chronic hepatitis C patients with flare of liver enzymes

Background

Occult HBV infection is defined by detection of HBV DNA in the serum or liver tissue of patients who test negative for HBsAg. The prevalence of occult HBV is higher in hepatitis C virus (HCV) positive patients than HCV negative patients and may have an impact on their clinical outcome. In this study, we evaluated the role of occult hepatitis B virus infection in chronic hepatitis C patients with ALT flare.

Methods

Sixty HBsAg negative patients with chronic hepatitis C virus infection were included. Patients were divided into 2 groups according to their ALT level: 30 patients with normal or slightly high ALT and 30 patients with ALT flare (≥ 5 times normal values). Patients in both groups were examined for the detection of anti-HBs, anti-HBc IgM, and anti-HBc IgG. HBV DNA was detected using semi-nested PCR technique.

Results

In patients with normal or slightly high ALT, HBV DNA was detected in 4 (13.3%) patients, while in those with ALT flare, HBV DNA was detected in 19 (63.3%) patients (p < 0.001). No association was found between the presence of HBV DNA and various serology markers of HBV infection.

Conclusion

Presence of occult hepatitis B, with its added deleterious effect, must always be considered in chronic hepatitis C patients especially those with flare in liver enzymes; HBsAg should not be used alone for the diagnosis of HBV infection.     

Serological assessment of HBcAg and HBV DNA: its prognostic relevance in acute hepatitis B

Treatment of serum precipitates with sodium thiocyanate in patients with hepatitis B virus (HBV) replication results in liberation of circulating hepatitis core antigen (HBcAg) which can be demonstrated radioimmunologically. Follow-up investigations were performed in 80 patients with acute hepatitis B. Sera were examined for HBcAg. HBV DNA and conventional HBV markers. At the time of admission to hospital 34 of 80 (42%) patients were HBeAg positive. Twenty-six (76%) of the 34 HBcAg positive patients were HBV DNA positive, and circulating HBcAg was detectable in 25 of 34 (73%) HBcAg positive cases. In patients with uncomplicated courses of acute hepatitis B the serological HBcAg assay and HBV DNA became negative 1 to 8 weeks before elimination of HBeAg and up to 12 weeks earlier than the sera became negative for HBsAg. Five patients (6%) showed transition to chronic hepatitis B with persistence of HBsAg, HBeAg, HBV DNA and HBcAg in serum. One patient with acute hepatitis B and development of chronic hepatitis suffered from acquired immunodeficiency syndrome and showed delayed formation of anti-HBc. In this case uncomplexed HBcAg was demonstrable during the acute phase of hepatitis B. With the appearance of anti-HBc HBcAg circulated in a complexed form. The data indicate that serological determinations of HBcAg and HBV DNA can serve as prognostic markers in the early phase of acute hepatitis B. The demonstration of uncomplexed HBcAg in serum of a patient with inadequate formation of anti-HBc supports the hypothesis that circulating HBcAg is usually complexed by specific antibodies.     

Occult hepatitis B virus infection in HIV-infected Lebanese patients with isolated antibodies to hepatitis B core antigen

The presence of hepatitis B virus (HBV) serological markers have been investigated in 101 Lebanese patients (69 men, 32 women; mean age 32.7 +/- 1.7 years) infected with human immunodeficiency virus type 1 (HIV-1). Seven patients (6.9%) were HBsAg carriers compared with 54 patients (53.5%) who had no evidence of exposure to HBV infection. Twenty-four patients (23.8%) had anti-HBc alone as a serological marker compared with four patients who were positive for anti-HBs alone and 12 patients (11.9%) who were anti-HBc and anti-HBs-positive. Occult HBV infection (presence of HBV DNA in the absence of HBsAg) is found to be relatively high (28.7%) in HIV-infected Lebanese patients and the overwhelming majority (83.3%) of those who were positive for anti-HBc alone had a detectable HBV DNA in their serum. However, none of our HIV-positive patients with occult HBV infection had abnormal alanine aminotransferase level, which also raises the question as to whether occult HBV plays a role in the aetiology of liver disease in HIV-infected patients. Further, studies on the association between HBV DNA levels and markers of liver function in addition to data on liver biopsy would help in answering this question.