Sofosbuvir-Based Antiviral Therapy Is Highly Effective In Recurrent Hepatitis C in Liver Transplant Recipients: Canadian Multicenter "Real-Life" Experience.

BACKGROUND: This study evaluates the efficacy, safety, and tolerability of regimens containing sofosbuvir (SOF) in the treatment of hepatitis C virus (HCV) recurrence in all genotypes in patients outside of clinical trials in all Canadian transplant centers. METHODS: One hundred twenty liver transplantation recipients from across Canada with HCV recurrence were started on SOF-based regimens (SOF + simeprevir ± ribavirin (RBV), n = 53; SOF + pegylated interferon + RBV, n = 25; SOF + RBV, n = 36; and SOF + ledipasvir, n = 6) between January and November 2014. Mean age 58 ± 6.85 years, majority (83%) were genotype 1, male (81%), and treatment experienced (82%). Twenty-seven percent had fibrosing cholestatic hepatitis/early aggressive HCV in the graft, and 48% had F3/4 fibrosis. The primary outcomes included patient and graft survival, on- and end-of-treatment response and sustained virological response at 12 weeks after treatment end (SVR12), and adverse events. RESULTS: One hundred thirteen of 120 (94%) patients were HCV RNA undetectable at end of treatment, and SVR12 was achieved in 102/120 (85%) patients, with 7 relapses, 1 nonresponder, and 10 deaths (liver-related complications). Sixty-three percent had HCV RNA levels below the lower limit of quantification at week 4. Serum creatinine levels remained stable throughout the treatment. Severe anemia occurred in 13% of patients, primarily in RBV-based regimens. CONCLUSIONS: Sofosbuvir-based antiviral therapy for HCV recurrence after liver transplantation was well tolerated, with an overall high SVR12 rate (85%) including patients with severe disease recurrence and F3-4 cirrhosis. The response rate was higher (91%) in mild HCV recurrence, suggesting earlier treatment might be beneficial.

Structural factors that promote stigmatization of drug users with hepatitis C in hospital emergency departments.

BACKGROUND: Interventions to mediate the stigmatization of people affected with HCV, particularly those who use illicit drugs, have been largely focused on changing health care practitioners' attitudes and knowledge regarding Hepatitis C and illicit drug use and these have had disappointing results. There is a need for research that examines factors beyond individual practitioners that explains why and how stigmatization of the population occurs within health care and informs interventions to mitigate these factors. METHODS: The research was intended to identify structural factors that contribute to the structural stigmatization of people within hospital Emergency Departments who are current users of illicit drugs and are HCV positive. The research had an interpretive description design and occurred in Nova Scotia, Canada. The year-long qualitative study entailed individual interviews of 50 service providers in hospital EDs or community organizations that served this population. RESULTS: The research findings generated a model of structural stigmatization that greatly expands the current understanding of stigmatization beyond individual practitioners' attitudes and knowledge and internal structures to incorporate structures external to hospitals, such as physician shortages within the community and the mandate of EDs to reduce wait times. CONCLUSIONS: The research reported herein has conceptualized stigmatization beyond an individualistic approach to incorporate the multifaceted ways that such stigmatization is fostered and supported by internal and external structures.

Future directions for investigation of fatigue in chronic hepatitis C viral infection.

Fatigue is a common and often debilitating symptom for people living with chronic hepatitis C viral infection. Numerous published reports in the past decade have attempted to address the nature and aetiology of fatigue in chronic hepatitis C; however, this field is plagued with lack of clarity about how hepatitis C virus (HCV)-related fatigue occurs and when it is experienced by the infected person. Consequently, both patients and clinicians alike are unclear about how to mediate or prevent the negative consequences of HCV-related fatigue. In the following article, the authors identify areas of ambiguity and incongruity that have evolved primarily from the underlying assumptions and methodological decisions of researchers in the field of HCV-related fatigue. Research related to fatigue in chronic illness is drawn upon to suggest future directions for investigations and interventions in the field of HCV-related fatigue. Future research needs to move beyond the subjective symptomatology of HCV-related fatigue and begin to account for the multidimensional and contextualised nature of the fatigue experience.

The 1F7 idiotype is selectively expressed on CD5+ B cells and elevated in chronic hepatitis C virus infection.

Antibodies against different chronic viruses, including hepatitis C virus (HCV), express a public cross-reactive idiotype (Id) designated as 1F7. The prominence of this Id may reflect selective engagement of B1 B cells by chronic pathogens. We investigated this by comparing 1F7 Id expression on CD5(+) and CD5(-) B cells, total IgG, total IgM and anti-HCV core antibodies in different HCV exposure settings. By flow cytometry, we observed a selective increase in 1F7 Id(+)CD5(+) B cells in chronic HCV infection. 1F7 Id levels in different immunoglobulin compartments were measured by enzyme-linked immunosorbent assay. 1F7 Id expression was prominent in anti-HCV core antibodies of approximately 90% of 141 HCV-exposed individuals tested. In the Canadian and Armenian study groups, participants who spontaneously cleared HCV infection had lower median 1F7 Id levels on total plasma IgG and anti-HCV core antibodies. Armenian spontaneous clearers, who were younger and more recently infected than their Canadian counterparts, also had had lower median 1F7 Id levels on total plasma IgM. Engagement by HCV of B-cell receptors within, or overlapping with the CD5(+) B1 B-cell repertoire is reflected in the production of 1F7 Id(+) anti-HCV antibodies and expansion of 1F7 Id(+)CD5(+) B cells. Higher 1F7 Id expression levels are associated with chronic infection.

Enhanced IL-10 production in response to hepatitis C virus proteins by peripheral blood mononuclear cells from human immunodeficiency virus-monoinfected individuals.

BACKGROUND: Multiple immune evasion strategies by which HCV establishes chronic infection have been proposed, including manipulation of cytokine responses. Prior infection with HIV increases the likelihood of chronic HCV infection and accelerates development of HCV-related morbidity. Therefore, we investigated in vitro cytokine responses to HCV structural and non-structural proteins in peripheral blood mononuclear cells (PBMC) from uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals. RESULTS: Intracellular flow cytometry was used to assess IL-2, IL-10, IL-12, and IFN-gamma production by freshly isolated PBMC incubated for 16 hours with recombinant HCV core, non-structural protein 3 (NS3), and NS4 proteins. Anti-HCV cellular responses were assessed in HIV/HCV-coinfected individuals by 3H-thymidine proliferation assay. Exposure to HCV antigens increased IL-10 production by PBMC, especially in uninfected and HIV-monoinfected individuals. This IL-10 response was attenuated in chronic HCV infection even with HCV/HIV-coinfection. The cells producing IL-10 in response to HCV proteins in vitro matched a PBMC subset recently shown to constitutively produce IL-10 in vivo. This subset was found at similar frequencies in uninfected, HIV-infected, HCV-infected and HIV/HCV-coinfected individuals before exposure to HCV proteins. HCV-specific T cell proliferation was detectable in only one HIV/HCV-coinfected individual who demonstrated no HCV-induced IL-10 response. CONCLUSION: This pattern suggests that selective induction of IL-10 in uninfected individuals and especially in HIV-monoinfected individuals plays a role in establishing chronic HCV infection and conversely, that attenuation of this response, once chronic infection is established, favours development of hepatic immunopathology.

The depiction of stigmatization in research about hepatitis C.

In the past decade, there has been an increasing emphasis by researchers regarding the stigmatization of people who are hepatitis C positive as they seek health care. Because the vast majority of people with hepatitis C have a history of injection drug use, they are frequently assumed by practitioners to be injection drug users (IDUs), blamed for acquiring the disease, and viewed as irresponsible, immoral, and unworthy. Such stigmatization may cause people who have hepatitis C to avoid testing, treatment and care, as well as to not disclose their hepatitis C or injection drug use to practitioners. The purpose of this paper is to critically examine the representation of stigmatization in 21 published research reports from 1995 to 2006, with a specific focus on how these depictions have shaped the current understanding of interventions to address stigmatization of people with hepatitis C by health care practitioners. We will identify two themes in this literature: (1) hepatitis C-related stigmatization in health care settings arises primarily from practitioners' negative views of injection drug use, and (2) practitioners' negative attitudes toward people with hepatitis C are the result of their lack of awareness and/or information about the disease and/or about injection drug use. We will illustrate that similar themes have informed anti-stigma initiatives in other diseases, notably HIV/AIDS and mental illness, which have had little sustained effect in changing practitioners' behaviour toward the stigmatized population. In conclusion, we will call for research that considers factors beyond the individual practitioner as contributing to the stigmatization of people with hepatitis C, such as social, structural and institutional forces that shape practitioners' interactions with people with hepatitis C in health care settings.

Choroidal neovascularization with interferon associated retinopathy: case report and review of literature.

We report a case of new interferon-associated ocular complication during treatment with combination of pegylated interferon plus ribavirin for chronic hepatitis C infection. Our patient developed choroidal neovascularization in addition to the classic interferon associated retinopathy. Choroidal neovascularization has not been reported before in association with interferon induced retinopathy. We describe our management to control the ocular symptoms and the retinal lesions with one year follow up. We also provide literature report on the natural history, the pathophysiology and the variable characteristics of interferon associated retinopathy versus hepatitis C related ophthalmopathy.