103 research outputs found
Hepatitis C-associated B-cell non-Hodgkin lymphomas: The emerging role of miRNA-26b
No full textthe authors described the emerging role of microRNA-26b in the field of HCV-related lymphoproliferation
MicroRNA expression in hepatitis C virus-related malignancies: A brief review
No full textNot only is chronic hepatitis C virus (HCV) infection a major public health problem, but also it can cause hepatocellular carcinoma and, more rarely, non-Hodgkin'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 post-transcriptional 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 malignancie
Hepatitis C virus-related mixed cryoglobulinemia: is genetics to blame?
No full textMixed 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 in 5%-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 HCV-related 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
Hepatitis C virus infection in the immunocompromised host: a complex scenario with variable clinical impact
No full textAbstract The relationship between Hepatitis C Virus (HCV) infection and immunosuppression is complex and multifaceted. Although HCV-related hepatocytolysis is classically interpreted as secondary to the attack by cytotoxic T lymphocytes against infected cells, the liver disease is usually exacerbated and more rapidly evolutive in immunosuppressed patients. This generally occurs during the immunosuppression state, and not at the reconstitution of the host response after immunosuppressive therapy discontinuation. The field of immunosuppression and HCV infection is complicated both by the different outcome observed in different situations and/or by contrasting data obtained in the same conditions, with several still unanswered questions, such as the opportunity to modify treatment schedules in the setting of post-transplant follow-up. The complexity of this field is further complicated by the intrinsic tendency of HCV infection in itself to lead to disorders of the immune system. This review will briefly outline the current knowledge about the pathogenesis of both hepatic and extrahepatic HCV-related disorders and the principal available data concerning HCV infection in a condition of impairment of the immune system. Attention will be especially focused on some conditions - liver or kidney transplantation, the use of biologic drugs and cancer chemotherapy - for which more abundant and interesting data exist.</p
Combined Treatment with Antiviral Therapy and Rituximab in Patients with Mixed Cryoglobulinemia: Review of the Literature and Report of a Case Using Direct Antiviral Agents-Based Antihepatitis C Virus Therapy
No full textMixed cryoglobulinemia (MC) is an autoimmune/B-cell lymphoproliferative disorder associated with Hepatitis C Virus (HCV) infection, manifesting as a systemic vasculitis. In the last decade, antiviral treatment (AT) with pegylated interferon (Peg-IFN) plus ribavirin (RBV) was considered the first therapeutic option for HCV-MC. In MC patients ineligible or not responsive to antivirals, the anti-CD20 monoclonal antibody rituximab (RTX) is effective. A combined AT plus RTX was also suggested. Since the introduction of direct acting antivirals (DAAs), few data were published about MC and no data about a combined schedule. Here, we report a complete remission of MC after a sustained virological response following a combined RTX/Peg-IFN+RBV+DAA (boceprevir) treatment and review the literature about the combined RTX/AT
Hepatitis C virus syndrome: A constellation of organ- and non-organ specific autoimmune disorders, B-cell non-Hodgkin's lymphoma, and cancer
No full textThe 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 clinico-epidemiological 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 non-Hodgkin's lymphomas. The same virus may be also involved in the pathogenesis of papillary thyroid cancer, a rare neoplastic condition that may complicate HCV-related 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
Virus-driven autoimmunity and lymphoproliferation: the example of HCV infection
No full textHCV chronic infection is characterized by possible development of both hepatic and extrahepatic manifestations. The infection by this both hepatotropic and lymphotropic virus is responsible for polyoligoclonal B-lymphocyte expansion, leading to several immune-mediated disorders. Mixed cryoglobulinemia syndrome that in some cases may evolve to frank B-cell non-Hodgkin's lymphoma is the prototype of HCV-driven autoimmune and lymphoproliferative disorders. The HCV oncogenic potential has been suggested by several clinicoepidemiological and laboratory studies; it includes hepatocellular carcinoma, B-cell non-Hodgkin's lymphoma and papillary thyroid cancer. The definition HCV syndrome refers to the complex of HCV-driven diseases; these latter are characterized by heterogeneous geographical distribution, suggesting a role of other important genetic and/or environmental cofactors. The natural history of HCV syndrome is the result of a multifactorial and multistep pathogenetic process, which may evolve from mild manifestations to systemic autoimmune disorders, and less frequently to malignant neoplasias. The present updated review analyzes the clinical and pathogenetic aspects of the main HCV-associated diseases
Long-term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open-label, cohort study
No full textLimited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC), especially concerning the long-term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long-term effects of viral eradication on MC. We prospectively enrolled 424 HCV+ patients belonging to the following groups: MCS-HCV (121 patients with symptomatic MC); MC-HCV (132 patients with asymptomatic MC); HCV group (158 patients without MC). Peg-IFN+RBV treatment was administered according to standard protocols. Post-treatment follow-up ranged from 35 to 124 months (mean: 92.5 months). A significant difference was observed in the rate of sustained virological response (SVR) between HCV and both MC-HCV (p=0.009) and MC-HCV+MCS-HCV (p=0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of non-response. The clinical-immunological response in MCS-HCV correlated with the virological one. All patients with SVR also experienced a sustained clinical response, either complete or partial. In the majority of SVR patients all MCS symptoms persistently disappeared (36 patients, 57%); in only 2 (3%) did definite MCS persist. All virological non-responders were also clinical non-responders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of IFN-based therapy on HCV patients with or without MC, and with or without symptoms, and the long-term effects of viral eradication on MC. MC was shown to be a negative prognostic factor of virological response. HCV clearance led to persistent resolution or improvement of MC syndrome, strongly suggesting the need for a next generation of highly effective antiviral drugs
HCV-related lymphatic and hepatic malignancies are associated with different microRNA expression patterns in PBMCs
No full textHCV infection leads to chronic liver damage often evolving to Hepatocellular Carcinoma (HCC), but also promotes lymphoproliferative disorders (LPDs) such as mixed cryoglobulinemia (MC) and Non Hodgkin Lymphomas (NHL).
Modified expression levels of specific microRNAs have been associated with different autoimmune/lymphoproliferative or neoplastic disorders.
We previously showed a downregulation of miR-26b in HCV-related MC and NHL.
In this study we analyzed the expression of a panel of microRNAs in peripheral blood mononuclear cells (PBMCs) from a large population of HCV patients with or without LPDs or HCC, in order to identify non-invasive markers of such evolutions of HCV infection.
PBMCs levels of miR-Let7d, miR-16, miR-21, miR-26b, miR-146a and miR-155 were evaluated by Real Time PCR in 187 HCV patients (75 with MC [HCV-MC], 11 with HCV-related NHL [HCV-NHL], 20 with HCV-related HCC [HCV-HCC], 81 without LPD or HCC [HCV]) and in 35 healthy blood donors (HS).
A significant increase of miR-21 (p< 0.001) expression was detected in PBMCs from only NHL patients, while miR-155 and miR-16 were upregulated both in NHL (p< 0.05) and HCC subjects (p<0.001), when compared to the other groups. A similar level for miR-146a was observed in all groups, except for the HCV-HCC patients, where miR-146a resulted upregulated (p<0.001).
A significant decrease of miR-26b was observed in both MC and NHL subjects (p<0.05) when compared to HS and HCV groups.
The upregulation of miR-16 and miR-155 is consistent with their reported role as “oncogenic microRNAs” in both HCC and lymphomas, while the upregulation of miR-21 only in the HCV-NHL group confirms its specific role in hematological malignancy. Interestingly, the downregulation of miR-26b in HCV-related LPDs, but not in HCC, suggests its pathogenetic relevance and its potential use as biomarker for evolution into LPDs. Furthermore, the upregulation of miR-146a in PBMC was shown as peculiar profile of HCC patients, suggesting that this could identify an evolution to a hepatic malignancy.
In conclusion, this study shows that microRNAs are differently modulated in PBMCs from HCV patients who developed LPDs, NHL or HCC and thus, they could represent clinically relevant tools, useful to discriminate between the two major HCV-related malignancies
- …
