scholarly journals The Role of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5560-5560
Author(s):  
Alba Rodríguez García ◽  
María Linares ◽  
Nicolas Mennesson ◽  
Alfredo Pérez-Revilla ◽  
Ricardo Sanchez ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Complete Remission ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Serum Samples ◽  
Monoclonal Gammopathies

INTRODUCTION: Recently, new understanding of monoclonal gammopathy pathogenesis highlighted possible disease initiation by viral infection in subsets of patients, notably by hepatitis C virus (HCV). If the infectious pathogen targeted by the monoclonal Ig could be eliminated at the monoclonal gammopathy of undetermined significance (MGUS) stage, chronic antigen-stimulation could disappear, leading in turn to the disappearance of the monoclonal Ig. Here we report a series of patients with monoclonal gammopathy and HCV infection, whose disease prognosis clearly improved, even reached complete remission, after antiviral treatment. METHODS: Nine patients diagnosed with MGUS (n=6) or multiple myeloma (MM) (n=3) after HCV infection were included in the study and classified into two groups: patients who received antiviral treatment, and patients who did not receive anti-viral treatment. Disease status was monitored by the quantification of the monoclonal immunoglobulin (mc Ig) level. The HCV burden was determined by RT-qPCR. Each patient's mc Ig was isolated from polyclonal immunoglobulins by agarose gel electrophoresis and mc Ig purity was evaluated by isoelectric focusing. The multiplex infectious antigen microarray (MIAA) was used to analyze the reactivity of serum immunoglobulins and of monoclonal Ig against commercially available antigens and/or lysates from different microorganisms. The INNO-LIA™ HCV Score assay (Fujirebio) was used to analyze the reactivity of monoclonal Ig to HCV proteins. RESULTS: Regarding patients treated with antiviral drugs (4 MGUS, 2 MM), mc Ig levels in serum decreased after antiviral treatment. MGUS patients remained in a stable status without disease progression. After antiviral treatment, one MM patient who was in third relapse achieved complete remission with minimal residual disease negativity. As expected, the HCV load decreased after antiviral therapy to undetectable levels. Serum samples from patients were reactive against antigens of various viruses and other microorganisms, but analysis of the specificity of recognition of the purified mc Ig of each patient revealed that it targeted HCV, either the core protein (C1, C2), NS3, or NS4. In contrast, for patients who did not receive antiviral treatment (2 MGUS, 1 MM), MGUS and MM disease progressed and the mc Ig level remained stable or increased. Serum samples from these patients were reactive against various viruses and other microorganisms, but their mc Ig did not recognize HCV proteins. CONCLUSION: In this study of monoclonal gammopathies where the mc Ig targeted HCV, successful HCV eradication with antivirals resulted in improvement of MGUS and MM disease as well as of hepatitis C. Our findings suggest that for HCV-positive individuals who were infected before being diagnosed with MGUS or MM, a causal relationship exists between HCV infection and the development of MGUS and MM, and both MGUS and MM patients infected with HCV may benefit from early anti-HCV therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Efficacy of Antiviral Treatment in Hepatitis C Virus (HCV)-Driven Monoclonal Gammopathies Including Myeloma

2022 ◽  
Vol 12 ◽  
Author(s):  
Alba Rodríguez-García ◽  
María Linares ◽  
María Luz Morales ◽  
Sophie Allain-Maillet ◽  
Nicolas Mennesson ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Plasma Cells ◽  
Residual Disease ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Antigen Specificity ◽  
Dot Blot ◽  
Monoclonal Immunoglobulin ◽  
Cell Malignancy

Multiple myeloma (MM) remains an incurable plasma cell malignancy. While its origin is enigmatic, an association with infectious pathogens including hepatitis C virus (HCV) has been suggested. Here we report nine patients with monoclonal gammopathy of undetermined significance (MGUS) or MM with previous HCV infection, six of whom received antiviral treatment. We studied the evolution of the gammopathy disease, according to anti-HCV treatment and antigen specificity of purified monoclonal immunoglobulin, determined using the INNO-LIA™ HCV Score assay, dot-blot assays, and a multiplex infectious antigen microarray. The monoclonal immunoglobulin from 6/9 patients reacted against HCV. Four of these patients received antiviral treatment and had a better evolution than untreated patients. Following antiviral treatment, one patient with MM in third relapse achieved complete remission with minimal residual disease negativity. For two patients who did not receive antiviral treatment, disease progressed. For the two patients whose monoclonal immunoglobulin did not react against HCV, antiviral treatment was not effective for MGUS or MM disease. Our results suggest a causal relationship between HCV infection and MGUS and MM progression. When HCV was eliminated, chronic antigen-stimulation disappeared, allowing control of clonal plasma cells. This opens new possibilities of treatment for MGUS and myeloma.

Clinico-Pathological Characteristics of B-Cell Non Hodgkins Lymphomas Associated with Hepatitis C Virus ANRS HC13 LYMPHO-C Observational Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1927-1927
Author(s):  
Caroline Besson ◽  
Danielle Canioni ◽  
Catherine Settegrana ◽  
Henda Driss ◽  
Laurent Alric ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Observational Study ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Antiviral Treatment ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Immune Stimulation

Abstract Abstract 1927 Poster Board I-950 Introduction: Hepatitis C virus (HCV) associated B-cell non-Hodgkin's lymphoma (B-NHL) is a rare entity that constitutes a model to study chronic immune stimulation related lymphomas. They are known to be preferentially Marginal Zone Lymphomas (MZL) and Diffuse Large B Cell Lymphoma (DLBCL) subtypes. Conflicting results are reported on the association between Follicular Lymphoma (FL) and HCV. In order to study the physiopathology of HCV-related B-NHL, we pursue a multicentric observational study in France. We present here the clinicopathological characteristics of the patients included. Patients and methods: Adult patients with a history of HCV associated B-NHL are included in the study. HCV infection is defined by a positive viral load at diagnosis of NHL. Patients with HIV infection are excluded from the study. Each patient is followed every 6 months during 5 years. At each follow-up, a blood sample is withdrawn allowing ancillary studies. Data collection concerns clinical presentation, treatment and evolution of NHL and HCV infection. Pathological and cytological materials are centralized in order to allow their review and a concerted analysis by a group of expert hematopathologists, haematologists and immunologists. Results: The data of the 54 consecutive patients included between november 2006 and april 2009 in 20 french centers are presented. Median age is 63 years (ranging from 39 to 87 years). There is a predominance of men: sex ratio (m/f) is 1.45 (32/22). Included women are older than men (p<0.01), median age being 71 among women and 60 years among men. HCV genotypic distribution does not differ from expected in a HCV infected population in France: 1: 51% (25/49), 2: 29% (14/49), 3: 8% (4/49), 4: 12% (6/49), 5 missing data. Transmission risk groups, known in 50% (27/54) of cases, are transfusion (18), drug abuse (5), endemic origin (2), and tattoo/acupuncture (2). Two patients are co-infected with HBV. Twenty-four patients out of 42 tested (57%) had positive cryoglobulinemia at diagnosis of NHL. This proportion did not differ with gender nor with genotype. Fifteen cases were included at diagnosis of B-NHL. The 39 other cases were included during follow-up of NHL. The median interval between NHL diagnosis and last follow-up is 15 months (range 0-13y). The histological subtype distribution is DLBCL 39% (21), MZL 35% (19), FL 13% (7), CLL 6% (3). Remarkably, there is a continuum between MZL and DLBCL, 6 cases with ongoing transformation. Four cases could not be classified due to small disease infiltration or lack of material. We confirm the link between cryoglobulinemia and MZL, 12+ out of 17 tested, 6+/12 in DLBCL versus 2+/5 in FL and 1+/2 in CLL. Nodal involvement is infrequent (5 out of 21 cases of DLBCL, 2/19 MZL, 4/7 FL). Extranodal involvements predominated in spleen (15 including 8 MZL), lung (6), digestive tract (4), liver (3), heart (1), skin (6) and bone marrow (4). The efficiency of antiviral treatment is confirmed in 5 cases with MZL, and remarkably, was followed by a good response in one case with FL. However, most patients in this observational study received treatment with Rituximab (R) either alone (5 cases with MZL), or combined with chemotherapy (including 15 cases with DLBCL and 4 with FL) or with antiviral treatment. This was associated with good clinical responses in most cases and low toxicity. Indeed, only 5 patients died during follow-up – two from disease progression - a 85 y man and a 40 y woman with liver DLBCL who was resistant to 3 lines of R-chemotherapy. The other patients died of sepsis (2), and cardiac ischemia (1). Conclusions: This study strengthens the heterogeneity of HCV-related lymphomas. The observation of cases with MZL and, remarkably, of one case with FL responding to antiviral treatment suggests that they are both linked to chronic immune stimulation. Therefore, the concept of antigen-driven lymphomagenesis seems more heterogeneous than initially anticipated: it could involve a T independent response in MZL, and a T dependent response in FL. The ongoing pathophysiological study will improve further understanding of the mechanisms by which antigen-driven lymphoproliferation arise. Disclosures: No relevant conflicts of interest to declare.

Genetic polymorphisms as the predictors of response to antiviral treatment in chronic hepatitis C virus infection

2011 ◽  
Vol 152 (22) ◽  
pp. 876-881
Author(s):  
Alajos Pár
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Genetic Polymorphisms ◽  
Chronic Hepatitis C ◽  
Genome Wide Association Study ◽  
Antiviral Treatment ◽  
Hcv Infection ◽  
Snp Analysis ◽  
Chronic Hcv

The review discusses the genetic polymorphisms involved in the pathogenesis of hepatitis C virus (HCV) infection, that may determine the outcome of disease. In this field earlier both certain major histocompatibility complex (MHC) alleles and some cytokine gene variants have also been studied. Recently, the genome-wide association study (GWAS) and targeted single nucleotide polymorphism (SNP) analysis have revealed that a variant in the promoter region of interleukin-28B (IL-28B) gene is strongly linked to viral clearance and it may be the strongest pretreatment predictor of treatment response in chronic hepatitis C. Last year it was shown that two genetic variants leading to inosine triphosphatase deficiency protect against haemolytic anemia in patients receiving ribavirin during antiviral treatment for chronic HCV infection. Orv. Hetil., 2011, 152, 876–881.

scholarly journals Hepatitis C Virus Prevalence and Risk Factors in a Village in Northeastern Romania—A Population-Based Screening—The First Step to Viral Micro-Elimination

Healthcare ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 651
Author(s):  
Laura Huiban ◽  
Carol Stanciu ◽  
Cristina Maria Muzica ◽  
Tudor Cuciureanu ◽  
Stefan Chiriac ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Treatment ◽  
Population Based ◽  
Hcv Infection ◽  
World Health ◽  
Hcv Rna ◽  
Virus Eradication ◽  
Tertiary Center

(1) Background: The World Health Organization adopted a strategy for the Global Health Sector on Viral Hepatitis in 2016, with the main objective of eliminating hepatitis C virus (HCV) by 2030. In this work, we aimed to evaluate the prevalence of HCV infection and risk factors in a Romanian village using population-based screening as part of the global C virus eradication program. (2) Methods: We conducted a prospective study from March 2019 to February 2020, based on a strategy as part of a project designed to educate, screen, treat and eliminate HCV infection in all adults in a village located in Northeastern Romania. (3) Results: In total, 3507 subjects were invited to be screened by rapid diagnostic orientation tests (RDOT). Overall, 2945 (84%) subjects were tested, out of whom 78 (2.64%) were found to have positive HCV antibodies and were scheduled for further evaluation in a tertiary center of gastroenterology/hepatology in order to be linked to care. In total, 66 (85%) subjects presented for evaluation and 55 (83%) had detectable HCV RNA. Of these, 54 (98%) completed antiviral treatment and 53 (99%) obtained a sustained virological response. (4) Conclusions: The elimination of hepatitis C worldwide has a higher chance of success if micro-elimination strategies based on mass screening are adopted.

Prospective study of hepatitis C virus infection in hemodialysis patients by monthly analysis of HCV RNA and antibodies

2003 ◽  
Vol 49 (8) ◽  
pp. 503-507 ◽  
Author(s):  
Regina Moreira ◽  
João Renato Rebello Pinho ◽  
Jorge Fares ◽  
Isabel Takano Oba ◽  
Maria Regina Cardoso ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Hemodialysis Patients ◽  
Hcv Infection ◽  
Hcv Rna ◽  
Hepatitis C Virus Infection ◽  
Serum Samples ◽  
Hcv Genotypes ◽  
High Prevalence ◽  
Time Required

The aims of this study were to (i) evaluate the prevalence and the incidence of hepatitis C virus (HCV) infection in hemodialysis patients in two different centers in São Paulo (Brazil), (ii) determine the time required to detect HCV infection among these patients by serology or PCR, (iii) establish the importance of alanine aminotransferase determination as a marker of HCV infection, and (iv) identify the HCV genotypes in this population. Serum samples were collected monthly for 1 year from 281 patients admitted to hospital for hemodialysis. Out of 281 patients, 41 patients (14.6%) were HCV positive; six patients seroconverted during this study (incidence = 3.1/1000 person-month). In 1.8% (5/281) of cases, RNA was detected before the appearance of antibodies (up to 5 months), and in 1.1% (3/281) of cases, RNA was the unique marker of HCV infection. The genotypes found were 1a, 1b, 3a, and 4a. The presence of genotype 4a is noteworthy, since it is a rare genotype in Brazil. These data pointed out the high prevalence and incidence of HCV infection at hemodialysis centers in Brazil and showed that routine PCR is fundamental for improving the detection of HCV carriers among patients undergoing hemodialysis.Key words: HCV genotypes, hemodialysis, hepatitis C, PCR, prevalence, incidence.

scholarly journals Contribution of insertions and deletions to the variability of hepatitis C virus populations

2007 ◽  
Vol 88 (8) ◽  
pp. 2198-2203 ◽  
Author(s):  
Manuela Torres-Puente ◽  
José M. Cuevas ◽  
Nuria Jiménez-Hernández ◽  
María A. Bracho ◽  
Inmaculada García-Robles ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Evolutionary Dynamics ◽  
Antiviral Treatment ◽  
Serum Samples ◽  
Frequency Distributions ◽  
Sequencing Project ◽  
Biologically Relevant ◽  
Insertions And Deletions ◽  
Hypervariable Regions

Little is known about the potential effects of insertions and deletions (indels) on the evolutionary dynamics of hepatitis C virus (HCV). In fact, the consequences of indels on antiviral treatment response are a field of investigation completely unexplored. Here, an extensive sequencing project was undertaken by cloning and sequencing serum samples from 25 patients infected with HCV subtype 1a and 48 patients with subtype 1b. For 23 patients, samples obtained after treatment with alpha interferon plus ribavirin were also available. Two genome fragments containing the hypervariable regions in the envelope 2 glycoprotein and the PKR-BD domain in NS5A were sequenced, yielding almost 16 000 sequences. Our results show that insertions are quite rare, but they are often present in biologically relevant domains of the HCV genome. Moreover, their frequency distributions between different time samples reflect the quasispecies dynamics of HCV populations. Deletions seem to be subject to negative selection.

Hepatitis C virus and B-cell non-Hodgkin lymphomas: an Italian multicenter case-control study

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 996-999 ◽  
Author(s):  
Alfonso Mele ◽  
Alessandro Pulsoni ◽  
Elvira Bianco ◽  
Pellegrino Musto ◽  
Andrè Szklo ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Case Control Study ◽  
Antiviral Treatment ◽  
Case Series ◽  
Positive Association ◽  
Case Control ◽  
Hcv Infection ◽  
Control Study

Abstract The existence of an association between infection with hepatitis C virus (HCV) and B-cell non-Hodgkin lymphoma (B-NHL) remains controversial, largely because previous studies were based on prevalent case series or comparisons with less than optimal control groups. This hospital-based case-control study was conducted from January 1998 through February 2001 to evaluate the association between HCV infection and B-NHL of different types. Cases were consecutive patients with a new diagnosis of B-NHL; controls were patients from other departments of the same hospitals. Both groups were interviewed using a standardized questionnaire. The prevalence of HCV infection was calculated by histologic type of B-NHL and clinical behavior (indolent or aggressive). Adjusted odds ratio (OR) and HCV-attributable risk (AR) were estimated. HCV prevalence was 17.5% among the 400 lymphoma patients and 5.6% among the 396 controls. The OR of B-NHL (patients vs controls), adjusted by age, sex, level of education, and place of birth, was 3.1 (95% confidence interval [CI], 1.8-5.2); an OR indicative of positive association was found for indolent and aggressive B-NHL. The estimated AR was 4.6%. This study confirms an association between HCV and B-NHL. In Italy, 1 of 20 instances of B-NHL may be attributable to HCV infection and may, thus, benefit from antiviral treatment.

Hepatitis C Virus Infection and B-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4668-4668
Author(s):  
Janet G. Grudeva
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Hcv Infection ◽  
Control Group ◽  
Cell Infection ◽  
Serum Samples ◽  
Pathogenetic Role ◽  
Significant Difference

Backgroud: An increasing number of bacterial and viral infections have been linked with specific subtypes of lymphoma. Preliminary evidence suggests that hepatitis C virus (HCV) might play a pathogenetic role in autoimmune-related, non-malignant B-cell lymphoproliferation, as well as a subset of B-cell non-Hodgkin, s lymphomas (B-NHL), often with extranodal localization. Design and methods: The study was conducted in the Department of Hematology and consisted 149 (86 male, 63 female) untreated patients with a new diagnosis of B-NHL for 5-years period (2000–2004). HCV infection was investigated by testing for HCV antibodies in serum samples. The controls were 587 patients (without intravenous drug users) in other departments of the same hospital. Results: HCV infection was documented in 13 cases (8,4%) with NHL. The infected patients were not clinically relevant cryoglobulinemic activity, increased rate of autoimmune disorders and extranodal localizations prevalence. There was statistically significant difference between the NHL and control group (p<0,01) and no statistically significant difference between man/women carriers (p>0,05) into the NHL group. Overall, the clinical outcome of HCV-positive NHL does not seem to be different from that of NHL patients without HCV infection. However, the evidence of a significant liver injury may predict a worse prognosis in these cases. Conclusions: Our date suggest that HCV infection may be associated with B-NHL. With regard to the mechanism(s) by which HCV might favor B-cell expansion and malignant transformation, most date support an indirect pathogenetic role of the virus as an exogenous trigger. A direct oncogenetic role of HCV by direct cell infection and deregulation has only been hypothesized on the basis of the lymphotropism of the virus.

scholarly journals Risk factors associated with hepatitis C virus infection in Taiwanese government employees

2001 ◽  
Vol 126 (2) ◽  
pp. 291-299 ◽  
Author(s):  
H. C. CHANG ◽  
M. W. YU ◽  
C. F. LU ◽  
Y. H. CHIU ◽  
C. J. CHEN
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Blood Transfusion ◽  
Hepatitis B Surface Antigen ◽  
Individual Characteristics ◽  
Hcv Infection ◽  
Serum Samples ◽  
Educational Levels ◽  
Previous Blood Transfusion ◽  
Positive Rate

This study evaluated the roles of multiple factors in hepatitis C virus (HCV) infection, with emphasis on the modification of various individual characteristics on the risk associated with percutaneous exposure to blood. Serum samples taken from 4869 men in Taiwan within a cohort study were tested for HCV antibody. The overall positive rate of anti-HCV was 1·6 %. In a logistic regression, factors positively associated with anti-HCV positivity were previous blood transfusion (odds ratio [OR] = 7·28; 95 % confidence interval [CI] = 4·26–12·45), a history of surgery (OR = 2·06; 95 % CI = 1·23–3·46), and lower educational levels (OR = 1·94; 95 % CI = 1·14–3·32). The anti-HCV positive rate was significantly lower in hepatitis B surface antigen (HBsAg) carriers than in non-carriers (OR = 0·60; 95 % CI = 0·37–0·95). Ageing, lower educational levels, O blood group, and Taiwanese ethnicity enhanced the likelihood of HCV infection through blood transfusion/surgery, whereas HBsAg status, cigarette smoking, and habitual alcohol drinking reduced it.

Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience

2005 ◽  
Vol 23 (3) ◽  
pp. 468-473 ◽  
Author(s):  
Daniele Vallisa ◽  
Patrizia Bernuzzi ◽  
Luca Arcaini ◽  
Stefano Sacchi ◽  
Vittorio Callea ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Antiviral Treatment ◽  
Complete Response ◽  
Hcv Infection ◽  
Low Grade ◽  
Hcv Treatment ◽  
Hematologic Response

Purpose Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Patients and Methods Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Results Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. Conclusion This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.

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