The clinical course of chronic hepatitis C virus(HCV)infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several i...The clinical course of chronic hepatitis C virus(HCV)infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinicoepidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells nonHodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCVrelated thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.展开更多
Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the on...Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.展开更多
Mixed cryoglobulinemia(MC)is the extrahepatic manifestation most strictly correlated with hepatitis C virus(HCV)infection;it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in5%-10%of ...Mixed cryoglobulinemia(MC)is the extrahepatic manifestation most strictly correlated with hepatitis C virus(HCV)infection;it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in5%-10%of cases.MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood.It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms(MC syndrome).Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown.Here,we try to clarify the complex relationship between HCVrelated MC and the host’s genetic background.The data that we report are heterogeneous and sometimes even conflicting.Therefore,large,multicenter studies are clearly needed.The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care.The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.展开更多
AIM:To evaluate the association between liver stiffness(LS) prior to the initiation of dual/triple therapy and viral response.METHODS:LS was measured in all patients before treatment was administered.The therapeutic a...AIM:To evaluate the association between liver stiffness(LS) prior to the initiation of dual/triple therapy and viral response.METHODS:LS was measured in all patients before treatment was administered.The therapeutic approach was based on hepatic,virological,and immunological evaluations and considered the fact that patients with severe fibrosis(F3)or compensated cirrhosis(F4)in Child-Pugh class A are the primary candidates for triple therapy.In total,65 hepatitis C virus(HCV)patients were treated with Peg-interferon/ribavirin(Peg-IFN/RBV);24patients were classified as genotypes 1/4(36.92%),and41 patients were classified as genotypes 2/3(63.08%)(dual therapy).In addition,20 HCV treatment-experienced genotype 1 patients were treated with Peg IFN-RBV and boceprevir(triple therapy).Wilcoxon rank-sum tests were used to compare the groups.RESULTS:LS significantly differed between dual therapy and triple therapy(P=0.002).The mean LS value before dual therapy treatment was 8.61±5.79k Pa and was significantly different between patients achieving a sustained virologic response(SVR)24weeks after therapy and those who did not(7.23±5.18 k Pa vs 11.72±5.99 k Pa,respectively,P=0.0003).The relative risk of non-response to therapy was 4.45(95%CI:2.32-8.55).The attributable risk of non-response to therapy was 49%.The mean LSvalue before triple therapy treatment was 13.29±8.57k Pa and was significantly different between patients achieving and not achieving SVR24(9.41±5.05 vs19.11±9.74,respectively;P=0.008).The relative risk of non-response to therapy was 5.57%(95%CI:1.50-20.65).The attributable risk of non-response to therapy(70%)was increased compared with dual therapy patients.Pre-treatment stiffness>12 k Pa was significantly associated with non-SVR(P<0.025)in both groups.CONCLUSION:Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy.展开更多
文摘The clinical course of chronic hepatitis C virus(HCV)infection is characterized by possible development of both liver and extrahepatic disorders. The tropism of HCV for the lymphoid tissue is responsible for several immune-mediated disorders; a poly-oligoclonal B-lymphocyte expansion, commonly observed in a high proportion of patients with HCV infection, are responsible for the production of different autoantibodies and immune-complexes, such as mixed cryoglobulins. These serological alterations may characterize a variety of autoimmune or neoplastic diseases. Cryoglobulinemic vasculitis due to small-vessel deposition of circulating mixed cryoglobulins is the prototype of HCV-driven immune-mediated and lymphoproliferative disorders; interestingly, in some cases the disease may evolve to frank malignant lymphoma. In addition, HCV shows an oncogenic potential as suggested by several clinicoepidemiological and laboratory studies; in addition to hepatocellular carcinoma that represents the most frequent HCV-related malignancy, a causative role of HCV has been largely demonstrated in a significant percentage of patients with isolated B-cells nonHodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCVrelated thyroid involvement. Patients with HCV infection are frequently asymptomatic or may develop only hepatic alteration, while a limited but clinically relevant number can develop one or more autoimmune and/or neoplastic disorders. Given the large variability of their prevalence among patients' populations from different countries, it is possible to hypothesize a potential role of other co-factors, i.e., genetic and/or environmental, in the pathogenesis of HCV-related extra-hepatic diseases.
基金Supported by Grants from 2015 Post-Doc fellowship "Fondazione Umberto Veronesi"(to Gragnani L)2015 AIRC fellowship(to Fognani E)FIRE(to Piluso A)
文摘Not only is chronic hepatitis C virus(HCV) infection a major public health problem,but also it can cause hepatocellular carcinoma and,more rarely,nonHodgkin's lymphoma.These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers.The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear.In the last decade,it has been shown that microRNAs(miRNAs),a class of 21-23-nucleotide molecules modulating posttranscriptional gene expression,make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers.Here,we briefly describe the current knowledge about microRNAs' involvement in HCV-related molecular oncogenesis.We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology,and on cultured cell lines partially or completely expressing the HCV genome.Some of the results reported in this review are controversial,possibly because of methodological issues,differences in sampling size and features,and ethnicity of patients.What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection.A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies.
基金Supported by Grants from the"Associazione Italiana per la Ricerca sul Cancro"Investigator Grant,No.1461‘‘Istituto Toscano Tumori’’+1 种基金"Fondazione Istituto di Ricerche Virologiche Oretta Bartolomei Corsi""Ente Cassa di Risparmio di Firenze"
文摘Mixed cryoglobulinemia(MC)is the extrahepatic manifestation most strictly correlated with hepatitis C virus(HCV)infection;it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in5%-10%of cases.MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood.It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms(MC syndrome).Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown.Here,we try to clarify the complex relationship between HCVrelated MC and the host’s genetic background.The data that we report are heterogeneous and sometimes even conflicting.Therefore,large,multicenter studies are clearly needed.The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care.The new wide-ranging genomics technologies will hopefully help to resolve these complex issues.
文摘AIM:To evaluate the association between liver stiffness(LS) prior to the initiation of dual/triple therapy and viral response.METHODS:LS was measured in all patients before treatment was administered.The therapeutic approach was based on hepatic,virological,and immunological evaluations and considered the fact that patients with severe fibrosis(F3)or compensated cirrhosis(F4)in Child-Pugh class A are the primary candidates for triple therapy.In total,65 hepatitis C virus(HCV)patients were treated with Peg-interferon/ribavirin(Peg-IFN/RBV);24patients were classified as genotypes 1/4(36.92%),and41 patients were classified as genotypes 2/3(63.08%)(dual therapy).In addition,20 HCV treatment-experienced genotype 1 patients were treated with Peg IFN-RBV and boceprevir(triple therapy).Wilcoxon rank-sum tests were used to compare the groups.RESULTS:LS significantly differed between dual therapy and triple therapy(P=0.002).The mean LS value before dual therapy treatment was 8.61±5.79k Pa and was significantly different between patients achieving a sustained virologic response(SVR)24weeks after therapy and those who did not(7.23±5.18 k Pa vs 11.72±5.99 k Pa,respectively,P=0.0003).The relative risk of non-response to therapy was 4.45(95%CI:2.32-8.55).The attributable risk of non-response to therapy was 49%.The mean LSvalue before triple therapy treatment was 13.29±8.57k Pa and was significantly different between patients achieving and not achieving SVR24(9.41±5.05 vs19.11±9.74,respectively;P=0.008).The relative risk of non-response to therapy was 5.57%(95%CI:1.50-20.65).The attributable risk of non-response to therapy(70%)was increased compared with dual therapy patients.Pre-treatment stiffness>12 k Pa was significantly associated with non-SVR(P<0.025)in both groups.CONCLUSION:Pre-treatment liver stiffness may be useful for predicting the response to treatment in patients treated with either dual or triple anti-HCV therapy.
