在我国,乙型肝炎病毒(hepatitis B virus,HBV)在体内不断复制并由此导致的肝细胞免疫病理损伤是H B V感染后慢性化及病情加重的原因,因此,抗病毒是阻止病情进展的有效手段.在多种与宿主免疫调控异常有关的发病机制中,程序性死亡分子1(pr...在我国,乙型肝炎病毒(hepatitis B virus,HBV)在体内不断复制并由此导致的肝细胞免疫病理损伤是H B V感染后慢性化及病情加重的原因,因此,抗病毒是阻止病情进展的有效手段.在多种与宿主免疫调控异常有关的发病机制中,程序性死亡分子1(programmed death 1,PD-1)/程序性死亡分子1配体1(PD-1 ligand 1,PD-L1)通路被认为与HBV感染后结局相关,本文就慢性乙型肝炎(chronic hepatitis B,CHB)患者抗病毒治疗与免疫细胞上PD-1/PD-L1表达间关系进行综述.展开更多
AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathol...AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.展开更多
AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies be...AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two,independent,HCC-free,age/sex-matched control groups.The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation.The first control group comprised167 patients that were matched to the HCC cohort for the percentage of hepatitis B(HBV)and/or hepatitis C(HCV)infections.A second control group included192 virus-free,healthy individuals that were used to evaluate the generalizability of the identified predictive markers.All cases and controls were Caucasian.The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways.The study end-point was to assess the association between genetic variants and HCC onset. RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV.According to a dominant model,reduced HCC risk was associated with three polymorphisms:ERCC1rs3212986(OR=0.46,95%CI:0.30-0.71,P=0.0005),GST-P1 rs1138272(OR=0.41,95%CI:0.21-0.81,P=0.0097),and CYP17A1 rs743572(OR=0.50,95%CI:0.31-0.79,P=0.0032).Conversely,according to a recessive model,increased HCC risk was associated with two polymorphisms:XRCC3 rs1799794(OR=3.70,95%CI:1.02-13.39,P=0.0461)and ABCB1 rs1128503(OR=2.06,95%CI:1.18-3.61,P=0.0111).These associations remained significant in a subgroup analysis,where patients were stratified according to viral status(HBV-or HCV-positive serology).Two variants exhibited a serology-specific effect:ABCB1 rs1128503(OR=4.18,95%CI:1.55-11.29,P=0.0048)showed an effect in the HBV-positive subgroup;and ERCC1 rs3212986(OR=0.33,95%CI:0.18-0.60,P=0.0003)showed an effect in the HCV-positive subgroup.Among the five markers identified,ERCC1 rs3212986(OR=0.43,P<0.0001)and CYP17A1 rs743572(OR=0.73,P=0.0310)had a different distribution in patients with HCC compared to healthy individuals.With a recursive partitioning approach,we also demonstrated that significant gene-gene interactions between ERCC1rs3212986,CYP17A1 rs743572,GST-P1 rs1138272,and the previously described UGT1A7*3 predictive marker,played a role in the complex trait of HCC susceptibility.CONCLUSION We identified five polymorphisms and interactions that contributed crucially to predicting HCC risk.These findings represented an important step towards improving HCC diagnosis and management.展开更多
文摘在我国,乙型肝炎病毒(hepatitis B virus,HBV)在体内不断复制并由此导致的肝细胞免疫病理损伤是H B V感染后慢性化及病情加重的原因,因此,抗病毒是阻止病情进展的有效手段.在多种与宿主免疫调控异常有关的发病机制中,程序性死亡分子1(programmed death 1,PD-1)/程序性死亡分子1配体1(PD-1 ligand 1,PD-L1)通路被认为与HBV感染后结局相关,本文就慢性乙型肝炎(chronic hepatitis B,CHB)患者抗病毒治疗与免疫细胞上PD-1/PD-L1表达间关系进行综述.
基金Supported by National Natural Science Foundation of China,No.30970415
文摘AIM To investigate the utility of 1H magneticresonance spectroscopy （1H MRS） as a noninvasivetest for steatosis in patients infected with hepatitis Cvirus.METHODS： Ninety patients with chronic hepatitisC and pathology data underwent 3.0T 1H MRS, andthe results of MRS and pathological analysis werecompared.RESULTS： This group of patients included 26 peoplewith mild fatty liver （28.89%）, 16 people withmoderate fatty liver （17.78%）, 18 people with severefatty liver （20.0%）, and 30 people without fatty liver（33.33%）. The water peak was near 4.7 parts permillion （ppm）, and the lipid peak was near 1.3 ppm.Analysis of variance revealed that differences in thelipid peak, the area under the lipid peak, ratio of thelipid peak to the water peak, and ratio of the areaunder the lipid peak to the area under the waterpeak were statistically significant among the groups.Specifically, as the severity of fatty liver increased, thevalue of each index increased correspondingly. In thepairwise comparisons, the mean lipid peak, area underthe lipid peak, ratio of the lipid peak to the waterpeak, and ratio of the area under the lipid peak to thearea under the water peak were significantly differentbetween the no fatty liver and moderate fatty liver groups, whereas no differences were noted betweenthe severe fatty liver group and the mild or moderatefatty liver group. Area under the ROC curve （AUC） ofarea ratio in lipid and water and ratio in lipid and waterin the no fatty liver group to mild fatty liver group, mildfatty liver group to moderate fatty liver group, andmoderate fatty liver disease group to severe fatty livergroup, were 0.705, 0.900, and 0.975, respectively.CONCLUSION： 1H MRS is a noninvasive techniquethat can be used to provide information on the effectof liver steatosis on hepatic metabolic processes. Thisstudy indicates that the 1H MRS can be used as anindicator of steatosis in patients with chronic hepatitis C.
基金Supported by AIRC(Italian Association for Cancer Research) Regional Grant 2004
文摘AIM To uncover novel genetic markers that could contribute to predicting hepatocellular carcinoma(HCC)susceptibility in Caucasians. METHODS The present retrospective case-control study compared genotype frequencies between a cohort of HCC cases and two,independent,HCC-free,age/sex-matched control groups.The HCC cohort comprised 192 homogeneous patients that had undergone orthotopic liver transplantation.The first control group comprised167 patients that were matched to the HCC cohort for the percentage of hepatitis B(HBV)and/or hepatitis C(HCV)infections.A second control group included192 virus-free,healthy individuals that were used to evaluate the generalizability of the identified predictive markers.All cases and controls were Caucasian.The three study populations were characterized with a panel of 31 markers derived from 21 genes that encoded key proteins involved in hepatocarcinogenesis-related pathways.The study end-point was to assess the association between genetic variants and HCC onset. RESULTS Five genetic markers were identified as risk factors for HCC in high-risk patients infected with HBV/HCV.According to a dominant model,reduced HCC risk was associated with three polymorphisms:ERCC1rs3212986(OR=0.46,95%CI:0.30-0.71,P=0.0005),GST-P1 rs1138272(OR=0.41,95%CI:0.21-0.81,P=0.0097),and CYP17A1 rs743572(OR=0.50,95%CI:0.31-0.79,P=0.0032).Conversely,according to a recessive model,increased HCC risk was associated with two polymorphisms:XRCC3 rs1799794(OR=3.70,95%CI:1.02-13.39,P=0.0461)and ABCB1 rs1128503(OR=2.06,95%CI:1.18-3.61,P=0.0111).These associations remained significant in a subgroup analysis,where patients were stratified according to viral status(HBV-or HCV-positive serology).Two variants exhibited a serology-specific effect:ABCB1 rs1128503(OR=4.18,95%CI:1.55-11.29,P=0.0048)showed an effect in the HBV-positive subgroup;and ERCC1 rs3212986(OR=0.33,95%CI:0.18-0.60,P=0.0003)showed an effect in the HCV-positive subgroup.Among the five markers identified,ERCC1 rs3212986(OR=0.43,P<0.0001)and CYP17A1 rs743572(OR=0.73,P=0.0310)had a different distribution in patients with HCC compared to healthy individuals.With a recursive partitioning approach,we also demonstrated that significant gene-gene interactions between ERCC1rs3212986,CYP17A1 rs743572,GST-P1 rs1138272,and the previously described UGT1A7*3 predictive marker,played a role in the complex trait of HCC susceptibility.CONCLUSION We identified five polymorphisms and interactions that contributed crucially to predicting HCC risk.These findings represented an important step towards improving HCC diagnosis and management.
