scholarly journals Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis

2018 ◽  
Vol 8 (2) ◽  
pp. 161-170
Author(s):  
Ramy M. Hanna ◽  
Naomi So ◽  
Marian Kaldas ◽  
Jean Hou ◽  
Farid Arman ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Crescentic Glomerulonephritis ◽  
The United States ◽  
Cross Reactivity ◽  
Normal Serum ◽  
Hcv Infection ◽  
Low Grade ◽  
Glomerular Injury ◽  
Immune Assays

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN.

scholarly journals Differential reactivity of putative genotype 2 hepatitis C virus F protein between chronic and recovered infections

2008 ◽  
Vol 89 (8) ◽  
pp. 1890-1900 ◽  
Author(s):  
Wing Chia-Ming Chuang ◽  
Jean-Pierre Allain
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Core Protein ◽  
Cross Reactivity ◽  
Hcv Infection ◽  
Genotype 3 ◽  
F Protein ◽  
Genotype 2

To date, all studies regarding hepatitis C virus (HCV) F protein have been based on expression in vitro/in vivo of recombinant protein or monoclonal antibodies derived from genotype 1a or 1b sequences, but not from other genotypes. The objective of this study was to prepare a putative genotype 2 recombinant F protein and evaluate its reactivity in plasma from individuals with chronic HCV infection or who had recovered from infection. One genotype 2 strain was selected for F protein (F-2) and core expression in bacterial culture. An ELISA was developed and applied to samples from patients with chronic infection or recovered infection of various genotypes. The anti-F-2 response in 117 samples showed a significantly higher reactivity in chronic than in recovered HCV-infected blood donors (P<0.001), but no difference was found among genotypes. However, the correlation between anti-F and anti-core was more significant in genotypes 1 and 2 than in genotype 3. Anti-F-2 titres were also significantly higher in chronic than in recovered individuals (P<0.0001). Antibody titres to recombinant genotype 2 core protein or to genotype 1 multiple proteins used in commercial anti-HCV assays paralleled the anti-F-2 end-point antibody titre. This study thus demonstrated the antigenicity of genotype 2 HCV F protein, although the exact location of the natural frameshift position remains unknown. The difference in anti-F-2 response between chronic and recovered infection, the cross-reactivity irrespective of genotype and the correlation of antibody response with structural and non-structural antigens suggest that the immune response to F protein is an integral part of the natural HCV infection.

Testing for Hepatitis C Virus Infection Among Adults Aged ≥18 in the United States, 2013-2017

2021 ◽  
pp. 003335492110472
Author(s):  
Hope King ◽  
J. E. Soh ◽  
William W. Thompson ◽  
Jessica Rogers Brown ◽  
Karina Rapposelli ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Hepatitis C Virus ◽  
Liver Disease ◽  
Hepatitis C ◽  
The United States ◽  
Hcv Infection ◽  
High School Education ◽  
Related Risk ◽  
Hcv Testing

Objective Approximately 2.4 million people in the United States are living with hepatitis C virus (HCV) infection. The objective of our study was to describe demographic and socioeconomic characteristics, liver disease–related risk factors, and modifiable health behaviors associated with self-reported testing for HCV infection among adults. Methods Using data on adult respondents aged ≥18 from the 2013-2017 National Health Interview Survey, we summarized descriptive data on sociodemographic characteristics and liver disease–related risk factors and stratified data by educational attainment. We used weighted logistic regression to examine predictors of HCV testing. Results During the study period, 11.7% (95% CI, 11.5%-12.0%) of adults reported ever being tested for HCV infection. Testing was higher in 2017 than in 2013 (adjusted odds ratio [aOR] = 1.27; 95% CI, 1.18-1.36). Adults with ≥some college were significantly more likely to report being tested (aOR = 1.60; 95% CI, 1.52-1.69) than adults with ≤high school education. Among adults with ≤high school education (but not adults with ≥some college), those who did not have health insurance were less likely than those with private health insurance (aOR = 0.78; 95% CI, 0.68-0.89) to get tested, and non–US-born adults were less likely than US-born adults to get tested (aOR = 0.77; 95% CI, 0.68-0.87). Conclusions Rates of self-reported HCV testing increased from 2013 to 2017, but testing rates remained low. Demographic characteristics, health behaviors, and liver disease–related risk factors may affect HCV testing rates among adults. HCV testing must increase to achieve hepatitis C elimination targets.

scholarly journals In vitro hepatitis C virus infection and hepatic choline metabolism

2019 ◽  
Author(s):  
Kaelan Gobeil Odai ◽  
Conor O’Dwyer ◽  
Rineke Steenbergen ◽  
Tyler A. Shaw ◽  
Tyler M. Renner ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cultured Cells ◽  
Hcv Infection ◽  
Choline Uptake ◽  
Choline Transport ◽  
Choline Metabolism ◽  
Positive Strand Rna ◽  
Uptake And Metabolism

AbstractCholine is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC) and can enter one carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses can impact phospholipid metabolism. In the current study we sought to interrogate the link between choline transport and early HCV infection. Namely, we aimed to investigate how HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing how the inhibition of choline uptake and metabolism upon concurrent HCV infection may alter early viral replication. Finally, we assessed whether these parameters were consistent between cells cultured in fetal bovine serum (FBS) or human serum (HS), conditions known to differentially affect in vitro HCV infection. We observed that choline transport in FBS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter choline transporter-like family (CTL), and that CTL1 expression and the incorporation of choline into PC is diminished in 24 h infected FBS-cultured cells. Reciprocally, limiting the availability of choline for PC synthesis resulted in increased HCV replication at this early stage. In chronically HS-cultured Huh7.5 cells, there were no differences in the expression of choline transporters upon HCV infection or alterations to viral replication when choline transport was inhibited compared to control treatments. However, inhibiting choline uptake and metabolism in this system significantly impaired the production of infectious virions in HS-cultured cells. These results suggest that in addition to a known role of choline kinase, the transport of choline, potentially via CTL1, might also represent an important and regulated process during HCV infection.Abstract Figure

scholarly journals 293. Hepatitis C is now a Millennial Disease in Response to the Opioid Crisis: A Demographic Shift in Hepatitis C Infection

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S159-S159
Author(s):  
Michelle Rose ◽  
John Allen Myers ◽  
Nicholas Ryan ◽  
Alissa Prince ◽  
Morgan Talbot ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Baby Boomers ◽  
Infected Individual ◽  
The United States ◽  
Hcv Infection ◽  
Demographic Shift ◽  
Hepatitis C Infection ◽  
Opioid Crisis ◽  
Chronic Hcv ◽  
Over Time

Abstract Background Previous research has shown millennials represent the fastest growing generation for those infected with the hepatitis C virus (HCV). Millennials are also a key driver in the opioid crisis, particularly in states of the Appalachian region including Kentucky. Despite research demonstrating a change in prevalence from baby boomers (born 1945–1965) to millennials (born 1980–1995), large representative studies providing evidence of the magnitude of this demographic shift are lacking in the United States. Our objective was to assess trends of HCV infection since 2016 in a large healthcare system located in an area of high prevalence of opioid use and HCV infection. Methods All individuals were screened for HCV infection in 2016, 2017, and 2018 within Norton Healthcare per standard risk-based criteria (e.g., injection drug users, baby boomers, etc.) as recommended by CDC, except for pregnant women who were universally screened since 2016. We tested for demographic shifts over time using longitudinal and time series analyses techniques Results A total of 86,243 individuals were screened for HCV infection from 2016 to 2018. Of those, 2,615 (3.0%) individuals screened positive for chronic HCV. The average age of those infected significantly decreased by an average of 3.7 years annually (from 47.3 years in 2016 to 39.9 years in 2018, P < 0.001). We forecast a plateau near the age of 28 years will be observed in just over 7 years. In addition, the proportion of millennials increased over time (33.6% in 2016, 42.4% in 2017 and 51.4% in 2018, P < 0.001), while baby boomers significantly decreased over time (44.0% in 2016, 38.8% in 2017, and 29.3% in 2018, P < 0.001). Lastly, over time, those with chronic HCV were more likely to be male (increasing from 49.6% to 54.4%, P = 0.008) and Hispanic (increasing from 1.6% to 17.7%, P < 0.001) Conclusion Our results suggest that HCV infection has become a predominately millennial disease, skipping a generation. These results correlate with trends seen with the opioid epidemic, which is driven by millennials. We conclude that the opioid crisis has led to a drastic demographic shift, and currently the typical HCV-infected individual is a younger male. Without interventions, this trend will continue for over seven years, plateauing near the demarcation of millennials and generation Z Disclosures All authors: No reported disclosures.

Hepatitis C and HIV Co-Infection

2017 ◽  
Author(s):  
Jennifer Cohen Price ◽  
Priyanka Amin ◽  
Antoine Douaihy
Keyword(s):  
Hepatitis C ◽  
Natural History ◽  
The United States ◽  
Hcv Infection ◽  
Hepatic Decompensation ◽  
History Of ◽  
Chronic Hcv ◽  
Direct Acting ◽  
End Stage ◽  
Shared Risk

Chronic infection with hepatitis C virus (HCV) is a leading cause of end-stage liver disease and is the most common indication for liver transplantation in the United States. Because of shared risk factors, individuals living with HIV infection are disproportionately affected by HCV. Moreover, co-infection with HIV accelerates the natural history of chronic HCV infection, increasing the risk of cirrhosis, hepatocellular carcinoma, hepatic decompensation, and death. Highly effective medications such as direct-acting antivirals (DAA) to cure HCV are now available and have the potential to profoundly improve the health of HIV-HCV-co-infected individuals. However, addressing the many gaps in the HCV care cascade is necessary to fully achieve the benefits of these drugs. This chapter reviews the natural history of HIV-HCV co-infection, the psychiatric comorbidities associated with HCV infection, the evolution of HCV treatment, and the barriers to care that HIV-HCV-co-infected individuals continue to face.

scholarly journals In Vitro Hepatitis C Virus Infection and Hepatic Choline Metabolism

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 108 ◽  
Author(s):  
Kaelan Gobeil Odai ◽  
Conor O’Dwyer ◽  
Rineke Steenbergen ◽  
Tyler A. Shaw ◽  
Tyler M. Renner ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Post Infection ◽  
Cultured Cells ◽  
Hcv Infection ◽  
Choline Uptake ◽  
Choline Metabolism ◽  
Positive Strand Rna ◽  
Uptake And Metabolism

Choline is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC), and can enter one-carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses and can impact phospholipid metabolism. In the current study we sought to interrogate if HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing if the inhibition of choline uptake and metabolism upon concurrent HCV infection alters viral replication and infectivity. Additionally, we assessed whether these parameters were consistent between cells cultured in fetal bovine serum (FBS) or human serum (HS), conditions known to differentially affect in vitro HCV infection. We observed that choline transport in FBS- and HS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter, choline transporter-like family (CTL). HCV infection in FBS, but not HS-cultured cells diminished CTL1 transcript and protein expression at 24 h post-infection, which was associated with lower choline uptake and lower incorporation of choline into PC. No changes in other transporters were observed and at 96 h post-infection, all differences were normalized. Reciprocally, limiting the availability of choline for PC synthesis by use of a choline uptake inhibitor resulted in increased HCV replication at this early stage (24 h post-infection) in both FBS- and HS-cultured cells. Finally, in chronic infection (96 h post-infection), inhibiting choline uptake and metabolism significantly impaired the production of infectious virions. These results suggest that in addition to a known role of choline kinase, the transport of choline, potentially via CTL1, might also represent an important and regulated process during HCV infection.

scholarly journals Preclinical Characterization of the Novel Hepatitis C Virus NS3 Protease Inhibitor GS-9451

2013 ◽  
Vol 58 (2) ◽  
pp. 647-653 ◽  
Author(s):  
Huiling Yang ◽  
Margaret Robinson ◽  
Amoreena C. Corsa ◽  
Betty Peng ◽  
Guofeng Cheng ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Activity ◽  
Protease Inhibitor ◽  
Hcv Infection ◽  
Cross Resistance ◽  
Protease Gene ◽  
Ns5a Inhibitor ◽  
Ns3 Protease

ABSTRACTGS-9451 is a selective hepatitis C virus (HCV) NS3 protease inhibitor in development for the treatment of genotype 1 (GT1) HCV infection. Key preclinical properties of GS-9451, includingin vitroantiviral activity, selectivity, cross-resistance, and combination activity, as well as pharmacokinetic properties, were determined. In multiple GT1a and GT1b replicon cell lines, GS-9451 had mean 50% effective concentrations (EC50s) of 13 and 5.4 nM, respectively, with minimal cytotoxicity; similar potency was observed in chimeric replicons encoding the NS3 protease gene of GT1 clinical isolates. GS-9451 was less active in GT2a replicon cells (EC50= 316 nM). Additive to synergisticin vitroantiviral activity was observed when GS-9451 was combined with other agents, including alpha interferon, ribavirin, and the polymerase inhibitors GS-6620 and tegobuvir (GS-9190), as well as the NS5A inhibitor ledipasvir (GS-5885). GS-9451 retained wild-type activity against multiple classes of NS5B and NS5A inhibitor resistance mutations. GS-9451 was stable in hepatic microsomes and hepatocytes from human and three other tested species. Systemic clearance was low in dogs and monkeys but high in rats. GS-9451 showed good oral bioavailability in all three species tested. In rats, GS-9451 levels were ∼40-fold higher in liver than plasma after intravenous dosing, and elimination of GS-9451 was primarily through biliary excretion. Together, these results are consistent with the antiviral activity observed in a recent phase 1b study. The results ofin vitrocross-resistance and combination antiviral assays support the ongoing development of GS-9451 in combination with other agents for the treatment of chronic HCV infection.

Clinical Features and Outcome of 147 Patients with Diffuse Large B-Cell Lymphoma and Hepatitis C Virus Infection.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1921-1921
Author(s):  
Carlo Visco ◽  
Luca Arcaini ◽  
Michele Merli ◽  
Annalisa Andreoli ◽  
Sara Burcheri ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Hcv Infection ◽  
Low Grade ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Hepatitis C virus (HCV) has been implicated in the pathogenesis of a subset of low-grade non-Hodgkin lymphomas. Furthermore, diffuse large B-cell lymphoma (DLBCL) has been correlated to HCV infection in several series from our geographical area (north-east of Italy), but little is known about the characteristics of such high-grade tumors. We analyzed presentation features of 147 previously untreated HCV-positive patients with DLBCL who presented to the three participating centers between 1993 and 2004. All patients were provided with complete clinical information, were HIV negative, and had been tested at tumor onset for HCV antibodies by ELISA and RIBA. Median age at presentation was 64 years old (range 29–88), 47% were males, ECOG performance status was >1 in 20%, Ann Arbor stage was I in 20%, II in 27%, III in 26%, IV in 27%, and B-symptoms were present in 37% of patients. The International Prognostic Index (IPI) value at diagnosis was low in 18%, int/low in 23%, int/high in 32%, and high in 27% of patients. Surprisingly, DLBCL transformed from a low-grade histology represented only 7% of the whole population, while primary mediastinal DLBCL were extremely rare (1/147, <1%). Patients frequently presented as primary extranodal DLBCL (65/147, 44%). Most involved extranodal sites were skin, liver, stomach, and spleen, with the latter being the most represented syte (33% of patients). Remarkably, spleen was the only extranodal involved organ in 20% of patients. Treatment was delivered with cure-intent, and consisted of CHOP-like regimens +/− Rituximab for the large majority of patients, except for 16 (11%) patients with cirrhosis or severe hepatic dysfunction, who received mono-chemotherapy or radiotherapy. Only three (2%) HCV-positive patients had to discontinue chemotherapy due to liver function impairment. The addition of Rituximab to chemotherapy did not seem to affect patients’ tolerance to treatment. With a median follow-up of 48 months for survivors, 5-year overall survival (OS) was 75%, while 5-year failure-free survival (FFS) was 51%. In particular, the 65 patients with primary extranodal DLBCL shared a better 5-year OS (83% vs 71%, p=0.01) and FFS (75% vs 39%, p=0.009) than their nodal counterpart. Nodal origin of the tumor resulted the strongest independent adverse factor both in terms of OS and FFS in multivariate analysis. The peculiar clinical behavior shared by HCV-positive DLBCL may disclose relevant biological features of these tumors, and may be relevant for future studies aiming to clarify the link between HCV infection and aggressive lymphoproliferative disorders.

Hepatitis C Viral Infection Is Not Associated with Waldenstrom’s Macroglobulinemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4693-4693
Author(s):  
Xavier Leleu ◽  
Kelly O’Connor ◽  
Allen Ho ◽  
Daniel D. Santos ◽  
Robert Manning ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Hcv Infection ◽  
Antibody Detection ◽  
Low Grade ◽  
Waldenström’S Macroglobulinemia ◽  
Hcv Antibody ◽  
Pcr Assays ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Infection with hepatitis C virus (HCV) has previously been associated with the pathogenesis of low grade B-cell lymphoproliferative diseases including Waldenstrom’s macroglobulinemia (WM). Most of these studies have utilized HCV antibody detection assays, which may not accurately assess HCV presence in patients with impaired humoral responses. In patients with WM, pronounced IgA and IgG hypogammaglobulinemia is present, which remains persistant despite therapy (Blood 104:306b). As such, we investigated the incidence of HCV in 88 randomly selected, and previously untreated patients with the consensus panel diagnosis of WM utilizing both HCV antibody detection and qualitative PCR assays (Quest Diagnostics, Cambridge, MA, USA). The median age for these patients was 61 (38 – 83 years) and the male: female sex ratio was 1.44. No patient had a known history of liver disease, hepatitis B, HCV or HIV infection. Liver function tests obtained at time of serum collection showed normal range SGOT and and SGPT levels for 86/88 patients. In contrast to previous reports, we failed to demonstrate HCV infection by both HCV antibody detection and the PCR assays. These studies therefore show no association of WM with HCV infection.

Hepatitis C as a predictor of treatment outcome in patients with hepatocellular carcinoma treated with the retinoid derivative, TAC-101.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 200-200
Author(s):  
V. Khanijow ◽  
A. O. Kaseb ◽  
M. Hassan ◽  
V. I. Machicao ◽  
H. M. Hassabo ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Animal Studies ◽  
Cox Regression ◽  
Core Protein ◽  
The United States ◽  
Hcv Infection ◽  
Phase Iii ◽  
Cancer Center ◽  
Prognostic Impact ◽  
University Of Texas

200 Background: Most cases of HCC occur in the setting of cirrhosis secondary to alcohol abuse and hepatitis C, in the United States and Europe. Furthermore, recent data from phase III trials of sorafenib showed better survival in patients with HCV-related HCC. Animal studies suggested that TAC 101 regulates the transcription factor activated protein-1, which is constitutively activated by HCV core protein and contributes to hepatocarcinogenesis in persistent HCV infection. We hypothesized that prognostic impact of HCV-related HCC would be more pronounced in patients treated with TAC 101. Methods: This retrospective analysis included 105 patients treated in 3 clinical trials: TAC-101 (n=27), bevacizumab and erlotinib (n=48), and erlotinib alone (n=30) conducted at The University of Texas M. D. Anderson Cancer Center. Univariate and multivariate Cox regression was performed to estimate the adjusted hazard ratio (HR). Results: HCV was present in 35 (33%) patients. Multivariate survival analyses incorporating age, sex, HBV status, α-fetoprotein level, Child-Pugh classification, CLIP score, and BCLC staging did not identify a significant impact of HCV on OS or PFS. However, in patients who received TAC- 101, the presence of HCV was associated with a significantly reduced risk of disease progression (HR: 0.47, 95% CI:0.24-0.90, p= 0.024). Conclusions: These results indicate a possible beneficial interaction between HCV-related HCC and treatment with the retinoid derivative, TAC-101. HCV infection could be useful as a surrogate biomarker of the therapeutic efficacy of TAC-101. Further research is warranted to study the potential role of TAC 101 in HCV-related HCC patients. No significant financial relationships to disclose.

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