HCV基因分型和不同型HCV重叠HBV感染临床分析

ＨＣＶ基因分型和不同型ＨＣＶ重叠ＨＢＶ感染临床分析颜学兵魏来吴文漪徐州医学院附属医院传染科江苏省徐州市２２１００２Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｇｅｎｏｔｙｐｅ；ｈｅｐａｔｉｔｉｓＣｖｉｒｕｓｅｓ／ｇｅｎｅｔｉｃｓ；ｈｅｐａｔｉｔｉｓＣ／ｃｏｍｐ...     

HBV,HCV及其重叠感染的临床观察

作者检测３９６例各类肝病患者ＨＢＶ－Ｍ及抗－ＨＣＶ，结果表明ＨＢＶ感染最多；单纯ＨＣＶ感染少；ＨＣＶ感染多与ＨＢＶ感染同时存在。重叠感染病情重，易发生重症肝炎。ＨＣＶ未干扰ＨＢＶ复制。     

HBV/HCV重叠感染的研究进展

HBV是一种嗜肝DNA病毒,HBV DNA和HBV特异P蛋白由核壳包裹成为核心颗粒,再由脂蛋白外膜包裹成完整的病毒颗粒。HCV是黄病毒科病毒,为单股正链RNA。HBV和HCV均由肠道外途径传播,2种病毒常可由相同途径发生感染。归纳了HBV/HCV重叠感染的发病机制、与隐匿性HBV感染和肝细胞癌以及器官移植、HBV疫苗之间的关系,同时介绍了重叠感染的治疗。指出存在于患者体内的HBV和HCV在病毒学方面相互干扰,在病变方面相互叠加。     

HBV/HCV重叠感染的现状与研究进展

乙型肝炎病毒(HBV)与丙型肝炎病毒(HCV)具有共同的传播途径,因此HBV/HCV重叠感染较为常见。HBV/HCV重叠感染时,两种病毒间存在相互抑制或干扰现象,加速了肝脏疾病的进展,预后不佳。为防止更严重的肝脏损伤,除了进行有效的预防外,应先针对优势病毒株及时进行有效的抗病毒治疗,并注意关注优势病毒株的转换,针对不同病毒模式的特点,及时调整治疗方案。     

上海慢性乙型肝炎患者HCV重叠感染及其与日本所见的差异

上海慢性乙型肝炎患者ＨＣＶ重叠感染及其与日本所见的差异王裕发１巫协宁１徐萍１邵力２易苗英１温文倩１ＳｕｂｊｅｃｔｈｅａｄｉｎｇｓｈｅｐａｔｉｔｉｓＢ／ｅｐｉｄｅｍｉｏｌｏｇｙ；ｈｅｐａｔｉｔｉｓＣ／ｅｐｉｄｅｍｉｏｌｏｇｙ；ｓｕｐｅｒｉｎｆｅｃｔｉ...     

献血员HIV感染者合并感染HCV、HBV的调查分析

献血员ＨＩＶ感染者合并感染ＨＣＶＨＢＶ的调查分析张华林１姚国科２尹玉忠１李安玲１刘荣花１郭丽梅１Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｂｌｏｏｄｄｏｎｏｒｓ；ＨＩＶｉｎｆｅｃｔｉｏｎｓ／ｃｏｍｐｌｉｃａｔｉｏｎｓ；ｈｅｐａｔｉｔｉｓＣ／ｃｏｍｐｌｉｃａｔ...     

HBV和HCV重叠感染的研究进展

乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染是目前全球慢性肝病的主要原因。据世界卫生组织（WHO）估计全球HBV和HCV慢性感染者分别超过3．5亿和1．7亿。由于具有共同的传播途径,所以HBV和HCV重叠感染现象的发生相当普遍,特别是在两种病毒都流行的地区,可达1％～15％。2004年东欧一项研究显示,在随机选择的2200健康个体中发现HBV／HCV重叠感染率为0．68％。     

HBV/HCV重叠感染的抗病毒治疗

从全球范围看,乙型肝炎病毒(hepatitis B virus,HBV)和丙型肝炎病毒(hepatitis C virus,HCV)重叠感染估计约有700-2000万人口感染.重叠感染和单一HBV或HCV感染比较,更易发展为肝硬化、肝细胞癌甚至肝衰竭的比例也高,HBV和HCV重叠感染可有四种不同的临床模式,即HCV活动...     

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     

HCV与HBV重叠感染与单纯慢性乙、丙型肝炎对照研究

乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）重叠感染比较常见，其对肝病的慢性化、严重化及癌变有着不可忽视的作用，为探讨HBV、HCV重叠感染相互关系及对病情转归的影响，我们对32例HBV、HCV重叠感染病例与单纯慢性乙、丙型肝炎病例进行对照分析，报道如下：     

Profound suppression of chronic hepatitis C following superinfection with hepatitis B virus.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) share similar transmission routes; thus, coinfection is frequent. The consequences of acute HBV infection in patients with chronic hepatitis C are unknown. METHODS: We describe a 47-year-old male with chronic hepatitis C who acquired HBV and then spontaneously and apparently completely cleared HCV but developed chronic hepatitis B. Five serum samples collected over 14 months and lymphoid cells obtained after acquiring HBV were tested for HCV and HBV by both standard assays and ultra-sensitive polymerase chain reaction/nucleic acid hybridization (PCR/NAH) (sensitivity approximately 2 IU/ml). RESULTS: After superinfection with HBV, HBV surface antigen-positive chronic hepatitis developed with readily detectable HBV DNA. All sera collected after acquisition of HBV, which tested negative for HCV RNA by standard laboratory assay, were positive for HCV genomes when analysed by PCR/NAH. Peripheral lymphoid cells carried HBV DNA and covalently closed circular DNA, but were negative for HCV. CONCLUSIONS: This is the first reported case of profound suppression of chronic hepatitis C after superinfection with HBV and establishment of chronic hepatitis B. It is hypothesized that HBV infection precipitated generalized and/or virus-specific cellular immune responses that profoundly suppressed HCV replication and yet failed to inhibit progression to chronic hepatitis B.     

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.     

HDV重叠感染可增加慢性乙型肝炎患者的肝细胞癌风险

HDV的重叠感染可加速慢性乙型肝炎患者的肝病进程,尤其肝细胞癌(HCC)的发生风险明显增高。但HDV的致癌机制有待进一步探索,治疗方式及效果也亟待突破。综述了HDV相关HCC流行病学新特点、致病机制的新认识和诊疗进展等,对推进研发更精准的HDV检测手段、更有效的治疗药物及减少HDV相关HCC具有重要意义。     

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.     

Detection of hepatitis C virus antibody in patients with autoimmune hepatitis and other chronic liver diseases

To clarify the relationship between autoimmune hepatitis (AIH) and the hepatitis C virus (HCV), we investigated the prevalence of antibodies to HCV (anti-HCV) by an enzyme-linked immunosorbent assay in patients with AIH, primary biliary cirrhosis (PBC), rheumatoid arthritis and multiple myeloma. The antibody was detected in 9 out of 18 patients with AIH (50%), in 3 out of 23 with PBC (23%), in 2 out of 10 with rheumatoid arthritis (20% ), and in 5 out of 9 with multiple myeloma (56% ). However, the optical density values in these patients were lower than those observed in non-A, non-B hepatitis (NANBH). Anti-HCV became negative immediately after the initiation of glucocorticoid therapy in all four antibodypositive AIH patients tested. The extracted immunoglobulin G fraction from sera of 5 anti-HCV negative AIH patients became positive for the antibody. This phenomenon was not observed in 5 normal volunteer sera. The 9 family members of three anti-HCV positive AIH patients showed no anti-HCV positivity. These results suggest that autoantibodies in AIH patients may cross-react with the HCV -related antigen. Direct association of the HCV influencing the development of AIH is unlikely. Therefore, care should be taken in the evaluation of anti-HCV positivity in patients with autoimmune diseases and multiple myeloma. This study was supported by the Ministry of Health, Science and Welfare of Japan.     

Clinical and histological impact of previous hepatitis B virus infection in patients with chronic hepatitis C

Background: Recent reports suggest that hepatitis C virus (HCV) carriers with serological markers of prior hepatitis B virus (HBV) infection have more advanced liver fibrosis, irrespective of HBV‐DNA detection. Aims: We sought to assess the prevalence and impact of previous HBV infection in patients with HCV chronic infection. Methods: This cross‐sectional study included hepatitis B surface antigen‐ and human immunodeficiency virus‐negative subjects with positive HCV‐RNA. All patients had prior parenteral exposure as the probable source of HCV infection. Serum samples were tested for HBV‐DNA using a commercial assay. The METAVIR system was used for histological analysis. Results: One‐hundred and eleven patients were evaluated. Thirty‐one out of 111 patients (28%) tested positive for antihepatitis B core antigen (anti‐HBc). HBV‐DNA was not detected in any sample. Anti‐HBc‐positive patients showed higher histological grading, staging and a higher fibrosis progression rate. By multivariate analysis, anti‐HBc‐positivity was predictive of moderate to severe activity [odds ratio (OR)=3.532; P=0.032] and significant hepatic fibrosis (OR=3.364; P=0.017). After approximately 20 years of infection, advanced liver fibrosis (F3/F4) can be expected in 13% of anti‐HBc‐negative subjects who acquired HCV before the age of 30 and in 57% of those anti‐HBc‐positive patients who were infected by HCV after 30 years of age (P<0.001). Conclusion: Previous HBV infection is common among HCV carriers and may exert a negative impact on the natural history of HCV infection, independently of the presence of significant HBV replication.     

Impact of acute hepatitis C virus superinfection in patients with chronic hepatitis B virus infection

BACKGROUND & AIMS: Superinfection in patients with chronic hepatitis B virus (HBV) infection is not uncommon. Acute hepatitis delta virus (HDV) superinfection is associated with severe and/or progressive liver disease. The natural course following acute hepatitis C virus (HCV) superinfection has not been well studied. The aim of this study was to investigate the impact of acute HCV superinfection. METHODS: The clinical features during acute phase and long-term outcomes of acute HCV superinfection were studied and compared with a cohort of acute HDV superinfection and a matched control group of active chronic hepatitis B. RESULTS: Acute HCV superinfection typically occurs as acute icteric hepatitis. The severity is similar to acute HDV superinfection in that hepatic decompensation developed in 34% of patients, hepatitis failure occurred in 11%, and 10% died. During a follow-up period of 1-21 years, patients with acute HCV superinfection had a significantly higher cumulated incidence of cirrhosis (48% at 10 years) and hepatocellular carcinoma (14% at 10 years, 21% at 15 years, and 32% at 20 years) than acute HDV superinfection or active chronic hepatitis B. Hepatitis B surface antigen (HBsAg) seroclearance occurred earlier in HCV superinfected patients. Continuing hepatitis after HBsAg seroclearance was observed only in HCV superinfected patients. CONCLUSIONS: Acute HCV superinfection in patients with chronic HBV infection is clinically severe during its acute phase. The long-term prognosis following acute HCV superinfection is much worse than that following HDV superinfection or active hepatitis B in terms of continuing hepatitis activity after HBsAg loss and the development of cirrhosis or hepatocellular carcinoma.     

Characteristics of regulatory T‐cell function in patients with chronic hepatitis B and C coinfection

Regulatory T cells (Tregs) affect the pathogenesis and disease progression of chronic viral hepatitis. This study evaluated the frequency and function of Tregs in patients with chronic HBV/HCV coinfection. Seventy‐four untreated HBV/HCV co‐infected patients were enrolled in this study. These subjects were divided into four subgroups: HBV‐active/HCV‐active (BACA), HBV‐inactive/HCV‐active (BICA), HBV‐active/HCV‐inactive (BACI) and HBV‐inactive/HCV‐inactive (BICI). Treg frequency was calculated as the fraction of CD4⁺Foxp3⁺T cells among CD4⁺T cells. Treg‐mediated inhibition was measured as percent of inhibition of T‐cell proliferation. The expression of interferon (IFN)‐γ, tumour necrosis factor (TNF)‐α and interleukin (IL)‐10 with/without Treg inhibition was also studied. Among the patients, there were 8 cases of BACA (10.8%), 38 of BICA (51.4%), 14 of BACI (18.9%) and 14 of BICI (18.9%). The frequency of CD4⁺Foxp3⁺T cells was comparable between the four groups. The inhibitory function of Tregs among the patients in the BACA and BICA was higher than that in the BICI (BACA vs BICI, P = .0210; BICA vs BICI, P = .0301). Patients in the BACA and BICA had higher fibrosis‐4 (FIB‐4) scores and serum ALT levels and lower serum albumin levels than those of the other groups. ALT abnormality was significantly and independently associated with a higher Treg immunosuppressive ability. The IFN‐γ expression of the effector T cells in the BACA was higher than that of the other groups. In conclusion, the inhibitory function of Tregs is higher among the HBV/HCV co‐infected patients with active HCV infection. ALT abnormality plays a dominant role in Treg function.     

Anti-hepatitis a virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.