This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by...This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.展开更多
AIM:To determine the seroprevalence of hepatitis C virus(HCV) and its co-infection with hepatitis B virus(HBV),hepatitis delta agent(HDV) and human immunodeficiency virus(HIV) among liver disease patients of south Tam...AIM:To determine the seroprevalence of hepatitis C virus(HCV) and its co-infection with hepatitis B virus(HBV),hepatitis delta agent(HDV) and human immunodeficiency virus(HIV) among liver disease patients of south Tamil Nadu. METHODS:A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus(anti HCV and HCV RNA) ,Hepatitis B virus(HBsAg),Hepatitis delta agent(anti HDV) and Human immuno virus(antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits.HCV RNA wasdetected by RT-PCR.Liver function tests like ALT,AST,GGT,ALP,bilirubin and albumin were also studied. RESULTS:The seroprevalence of HCV was found to be 5.6%among liver disease patients by ELISA.27/512,49/512 and 12/512 patients were positive for HIV,HBV &HDV respectively.Co-infection of HCV&HBV was found in 8 patients,with 6 for HCV&HIV and 4 for HCV,HBV&HIV co-infections.Sex-wise analysis showed that HIV,HCV&HBV and HCV&HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1±8.3 and 49±10.1.In people co-infected with HCV&HBV or HCV&HIV or HCV,HBV&HIV the mean ALT of 58.0±03.16,56.78±4.401 and 64.37±4.01 respectively. CONCLUSION:We strongly recommend routine test of the blood for HCV in addition to HBV and HIV.We also recommend individualized counseling to identify those at risk and testing for those who want it.Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.展开更多
目的了解癌症患者乙型肝炎病毒(hepatitis B virus,HBV)的感染状态和感染特点。方法回顾性分析2017年7月26日至2023年9月18日于广西医科大学附属肿瘤医院确诊的92031例癌症患者的HBV血清标志物检测结果,以肝癌、非肝癌进行分组,比较未感...目的了解癌症患者乙型肝炎病毒(hepatitis B virus,HBV)的感染状态和感染特点。方法回顾性分析2017年7月26日至2023年9月18日于广西医科大学附属肿瘤医院确诊的92031例癌症患者的HBV血清标志物检测结果,以肝癌、非肝癌进行分组,比较未感染(全阴或Anti-HBs阳性)、感染(除外Anti-HBs任何一项阳性)、隐性感染(occult hepatitis B virus infection,OBI;HBsAg阴性、血清或肝组织HBV DNA阳性)的占比。结果92031例癌症患者的HBV总感染率为73.75%(67876/92031),其中肝癌患者的HBV总感染率为97.65%(8922/9137),非肝癌患者的HBV总感染率为71.12%(58954/82894),肝癌组的普通感染率和OBI率均显著高于非肝癌组(均P<0.001)。肝癌组HBV血清标志物中HBsAg、HBeAg、Anti-HBe、Anti-HBc的阳性率明显高于非肝癌组(均P<0.001),但Anti-HBs的阳性率低于非肝癌组(P<0.001)。肝癌组和非肝癌组分别有20种和27种血清标志物组合模式,其中14种模式构成比在两组间差异有统计学意义(均P<0.001);两组均有7种OBI血清组合模式,其中5种模式构成比在两组间的差异有统计学意义(均P<0.05)。结论癌症患者HBV感染状态和血清学组合模式复杂,区分肝癌与非肝癌进行HBV感染统计更利于癌症患者的HBV感染评估。展开更多
目的观察结肠癌患者乙肝病毒感染状态及表面抗原/抗体水平,分析其与结肠癌分期的关联,从而间接评估结肠癌患者合并乙型肝炎对其预后的影响。方法收集福建省立医院收治的85例结肠癌患者,采用SPSS16.0统计软件回顾性分析乙肝病毒感染状态...目的观察结肠癌患者乙肝病毒感染状态及表面抗原/抗体水平,分析其与结肠癌分期的关联,从而间接评估结肠癌患者合并乙型肝炎对其预后的影响。方法收集福建省立医院收治的85例结肠癌患者,采用SPSS16.0统计软件回顾性分析乙肝病毒感染状态对结肠癌浸润深度、区域淋巴结转移和远处转移的影响。结果乙肝病毒感染状态对结肠癌原发灶浸润深度(T)(P=0.331)和结肠癌区域淋巴结转移(N)的影响差异无统计学意义(P=0.098)。合并乙肝病毒阳性的结肠癌患者其区域淋巴结转移度明显低于乙肝病毒阴性的亚组(8.1%vs.17.8%),且无区域淋巴结转移的结肠癌患者血清中Hbs Ab水平较发生淋巴结转移的亚组患者明显升高(240.111 m IU/ml vs.178.161 m IU/ml)。乙肝病毒感染状态对结肠癌患者发生远处转移(M)以及肝转移的影响差异均具有统计学意义(均P<0.001)。不论是乙肝病毒感染还是乙肝疫苗相关的乙肝病毒阳性患者,肝转移发生率均显著低于乙肝病毒阴性的患者(P=0.039,P<0.001)。结论结肠癌合并乙肝病毒表面抗体水平高表达对区域淋巴结转移可能具有潜在的抑制作用。乙肝病毒阳性对结肠癌发生远处转移(尤其对肝转移)呈显著性负相关。乙肝病毒感染状态以及表面抗原/抗体水平显著性影响结肠癌患者的分期及预后。展开更多
目的探讨乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义。方法前瞻性纳入内蒙古医科大学附属医院2014年1月至2016年1月收治的乙型肝炎(HBV)性肝癌患者40例作为研究组,同期收集非肝炎性肝癌患者40例作为对照组。观察两组...目的探讨乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义。方法前瞻性纳入内蒙古医科大学附属医院2014年1月至2016年1月收治的乙型肝炎(HBV)性肝癌患者40例作为研究组,同期收集非肝炎性肝癌患者40例作为对照组。观察两组患者肿瘤微环境中CD4^+T细胞、CD8^+T细胞、Treg细胞水平,以及外周血中IL-2、IL-10、TGF-β水平。同时观察HBV DNA病毒载量与免疫指标的相关性。结果与对照组比较,研究组患者CD4+T细胞水平显著升高[(21.08±3.12)%vs(19.72±2.89)%,P=0.047],CD8+T细胞水平显著降低[(28.83±2.52)%vs(30.07±2.41)%,P=0.027],Treg细胞水平显著升高[(8.12±1.47)%vs(6.62±1.42)%,P<0.001];IL-2水平显著降低[(15.48±4.30)pg/m L vs(27.28±5.95)pg/m L,P<0.001),IL-10水平显著升高[(36.39±7.69)pg/m L vs(29.82±6.17)pg/m L,P<0.001),TGF-β水平显著升高[(31.95±3.72)pg/m L vs(23.49±3.83)pg/m L,P<0.001)。Pearson线性相关性分析显示,HBV DNA病毒载量与CD8+T细胞及IL-2水平负相关,与CD4+T细胞、Treg和TGF-β水平正相关(P<0.05)。结论乙型肝炎性肝癌患者肿瘤组织微环境中淋巴细胞失衡,且与HBV DNA病毒载量有关。展开更多
文摘This review describes woodchucks chronically infected with the woodchuck hepatitis virus(WHV)as an animal model for hepatocarcinogenesis and treatment of primary liver cancer or hepatocellular carcinoma(HCC)induced by the hepatitis B virus(HBV).Since laboratory animal models susceptible to HBV infection are limited,woodchucks experimentally infected with WHV,a hepatitis virus closely related to HBV,are increasingly used to enhance our understanding of virus-host interactions,immune response,and liver disease progression.A correlation of severe liver pathogenesis with high-level viral replication and deficient antiviral immunity has been established,which are present during chronic infection after WHV inoculation of neonatal woodchucks for modeling vertical HBV transmission in humans.HCC in chronic carrier woodchucks develops 17 to 36 mo after neonatal WHV infection and involves liver tumors that are comparable in size,morphology,and molecular gene signature to those of HBV-infected patients.Accordingly,woodchucks with WHV-induced liver tumors have been used for the improvement of imaging and ablation techniques of human HCC.In addition,drug efficacy studies in woodchucks with chronic WHV infection have revealed that prolonged treatment with nucleos(t)ide analogs,alone or in combination with other compounds,minimizes the risk of liver disease progression to HCC.More recently,woodchucks have been utilized in the delineation of mechanisms involved in innate and adaptive immune responses against WHV during acute,self-limited and chronic infections.Therapeutic interventions based on modulating the deficient host antiviral immunity have been explored in woodchucks for inducing functional cure in HBV-infected patients and for reducing or even delaying associated liver disease sequelae,including the onset of HCC.Therefore,woodchucks with chronic WHV infection constitute a well-characterized,fully immunocompetent animal model for HBV-induced liver cancer and for preclinical evaluation of the safety and efficacy of new modalities,which are based on chemo,gene,and immune therapy,for the prevention and treatment of HCC in patients for which current treatment options are dismal.
文摘AIM:To determine the seroprevalence of hepatitis C virus(HCV) and its co-infection with hepatitis B virus(HBV),hepatitis delta agent(HDV) and human immunodeficiency virus(HIV) among liver disease patients of south Tamil Nadu. METHODS:A total of 1012 samples comprising 512 clinically diagnosed cases of liver disease patients and 500 apparently healthy age and sex matched individuals were screened for Hepatitis C virus(anti HCV and HCV RNA) ,Hepatitis B virus(HBsAg),Hepatitis delta agent(anti HDV) and Human immuno virus(antibodies to HIV-1 and HIV-2) using commercially available enzyme linked immunosorbent assay kits.HCV RNA wasdetected by RT-PCR.Liver function tests like ALT,AST,GGT,ALP,bilirubin and albumin were also studied. RESULTS:The seroprevalence of HCV was found to be 5.6%among liver disease patients by ELISA.27/512,49/512 and 12/512 patients were positive for HIV,HBV &HDV respectively.Co-infection of HCV&HBV was found in 8 patients,with 6 for HCV&HIV and 4 for HCV,HBV&HIV co-infections.Sex-wise analysis showed that HIV,HCV&HBV and HCV&HIV co-infection was high among females whereas for HBV it was high in males. The mean ALT and AST in HCV positive cases were 42.1±8.3 and 49±10.1.In people co-infected with HCV&HBV or HCV&HIV or HCV,HBV&HIV the mean ALT of 58.0±03.16,56.78±4.401 and 64.37±4.01 respectively. CONCLUSION:We strongly recommend routine test of the blood for HCV in addition to HBV and HIV.We also recommend individualized counseling to identify those at risk and testing for those who want it.Improved surveillance and periodic epidemiological studies will have to be undertaken to monitor and prevent these blood-borne viruses.
文摘目的了解癌症患者乙型肝炎病毒(hepatitis B virus,HBV)的感染状态和感染特点。方法回顾性分析2017年7月26日至2023年9月18日于广西医科大学附属肿瘤医院确诊的92031例癌症患者的HBV血清标志物检测结果,以肝癌、非肝癌进行分组,比较未感染(全阴或Anti-HBs阳性)、感染(除外Anti-HBs任何一项阳性)、隐性感染(occult hepatitis B virus infection,OBI;HBsAg阴性、血清或肝组织HBV DNA阳性)的占比。结果92031例癌症患者的HBV总感染率为73.75%(67876/92031),其中肝癌患者的HBV总感染率为97.65%(8922/9137),非肝癌患者的HBV总感染率为71.12%(58954/82894),肝癌组的普通感染率和OBI率均显著高于非肝癌组(均P<0.001)。肝癌组HBV血清标志物中HBsAg、HBeAg、Anti-HBe、Anti-HBc的阳性率明显高于非肝癌组(均P<0.001),但Anti-HBs的阳性率低于非肝癌组(P<0.001)。肝癌组和非肝癌组分别有20种和27种血清标志物组合模式,其中14种模式构成比在两组间差异有统计学意义(均P<0.001);两组均有7种OBI血清组合模式,其中5种模式构成比在两组间的差异有统计学意义(均P<0.05)。结论癌症患者HBV感染状态和血清学组合模式复杂,区分肝癌与非肝癌进行HBV感染统计更利于癌症患者的HBV感染评估。
文摘目的观察结肠癌患者乙肝病毒感染状态及表面抗原/抗体水平,分析其与结肠癌分期的关联,从而间接评估结肠癌患者合并乙型肝炎对其预后的影响。方法收集福建省立医院收治的85例结肠癌患者,采用SPSS16.0统计软件回顾性分析乙肝病毒感染状态对结肠癌浸润深度、区域淋巴结转移和远处转移的影响。结果乙肝病毒感染状态对结肠癌原发灶浸润深度(T)(P=0.331)和结肠癌区域淋巴结转移(N)的影响差异无统计学意义(P=0.098)。合并乙肝病毒阳性的结肠癌患者其区域淋巴结转移度明显低于乙肝病毒阴性的亚组(8.1%vs.17.8%),且无区域淋巴结转移的结肠癌患者血清中Hbs Ab水平较发生淋巴结转移的亚组患者明显升高(240.111 m IU/ml vs.178.161 m IU/ml)。乙肝病毒感染状态对结肠癌患者发生远处转移(M)以及肝转移的影响差异均具有统计学意义(均P<0.001)。不论是乙肝病毒感染还是乙肝疫苗相关的乙肝病毒阳性患者,肝转移发生率均显著低于乙肝病毒阴性的患者(P=0.039,P<0.001)。结论结肠癌合并乙肝病毒表面抗体水平高表达对区域淋巴结转移可能具有潜在的抑制作用。乙肝病毒阳性对结肠癌发生远处转移(尤其对肝转移)呈显著性负相关。乙肝病毒感染状态以及表面抗原/抗体水平显著性影响结肠癌患者的分期及预后。
文摘目的探讨乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义。方法前瞻性纳入内蒙古医科大学附属医院2014年1月至2016年1月收治的乙型肝炎(HBV)性肝癌患者40例作为研究组,同期收集非肝炎性肝癌患者40例作为对照组。观察两组患者肿瘤微环境中CD4^+T细胞、CD8^+T细胞、Treg细胞水平,以及外周血中IL-2、IL-10、TGF-β水平。同时观察HBV DNA病毒载量与免疫指标的相关性。结果与对照组比较,研究组患者CD4+T细胞水平显著升高[(21.08±3.12)%vs(19.72±2.89)%,P=0.047],CD8+T细胞水平显著降低[(28.83±2.52)%vs(30.07±2.41)%,P=0.027],Treg细胞水平显著升高[(8.12±1.47)%vs(6.62±1.42)%,P<0.001];IL-2水平显著降低[(15.48±4.30)pg/m L vs(27.28±5.95)pg/m L,P<0.001),IL-10水平显著升高[(36.39±7.69)pg/m L vs(29.82±6.17)pg/m L,P<0.001),TGF-β水平显著升高[(31.95±3.72)pg/m L vs(23.49±3.83)pg/m L,P<0.001)。Pearson线性相关性分析显示,HBV DNA病毒载量与CD8+T细胞及IL-2水平负相关,与CD4+T细胞、Treg和TGF-β水平正相关(P<0.05)。结论乙型肝炎性肝癌患者肿瘤组织微环境中淋巴细胞失衡,且与HBV DNA病毒载量有关。
