Hepatitis C

Computational identification of interplay between phosphorylation and O-β-glycosylation of human occludin as potential mechanism to impair hepatitis C virus entry

by Azeem Butt

Published in "Infection, Genetics and Evolution"

Hepatitis C virus (HCV) is one of the leading causes of liver diseases. Several host factors that facilitate the... more Hepatitis C virus (HCV) is one of the leading causes of liver diseases. Several host factors that facilitate the attachment and entry of HCV have been discovered, of which human occludin seems to be the most promising. Studies have shown that activity of occludin is dependent upon its phosphorylation status, and that during HCV infection deregulation of phosphorylated occludin collectively leads to a reduction in tight junction (TJ) integrity of hepatocytes and favors HCV entry. However, detailed information of the posttranslational modifications (PTMs) of occludin still remains largely unknown. In addition to phosphorylation, serine/threonine residues of several proteins are also regulated by a unique type of modification known as O-β-glycosylation and this crosstalk serves as a functional switch. To identify the O-β-glycosylation potential and how interplay between phosphorylation and O-β-glycosylation can be exploited for the inhibition of HCV entry, here we report a computational analysis of PTMs of human occludin. Several conserved phosphorylation residues and kinases that can alter the ability of occludin to regulate the integrity of TJs were identified. In addition to previously reported Tyr residues, two additional Tyr residues (Tyr29 and Tyr287) were identified as target sites of Src kinase. To our knowledge, this is the first study to report the O-β-GlcNAc potential of occludin and target sites of ERK (Ser8, Ser310, and Thr345), GSK-3 (Ser8, Ser341) and Cdk5 (Thr376). Furthermore, based on findings from this study, a potential novel interplay between phosphorylation and O-β-glycosylation at the two Yin Yang sites (Ser408 and Ser490) is also proposed.

Venous access and care: Harnessing pragmatics in harm reduction for people who inject drugs

by Magdalena Harris

Addiction, 2012, co-authored with Tim Rhodes

Aim: To explore the facilitators of long-term hepatitis C avoidance among people who inject drugs.
Design: We... more Aim: To explore the facilitators of long-term hepatitis C avoidance among people who inject drugs.
Design: We employed a qualitative life history design. Two interviews were conducted with each participant, with the second interview incorporating reference to a computer constructed
life history time line. Interview accounts were audio-recorded, transcribed verbatim and analysed thematically.
Setting: Recruitment took place through low threshold drug services and drug user networks in South East and North London. Participants were interviewed at the recruitment services or in their homes.
Participants: The sample comprised 35 people who inject drugs, 20 of whom were hepatitis C antibody negative. Participants’ average injecting trajectory was 19 years (6 – 33), with 66%
primarily injecting heroin, and 34% a crack and heroin mix. Nine (26%) of the sample were female and the average age was 39 years (23 – 53).
Findings: Hepatitis C risk awareness was recent and de-prioritised by the majority of participants. The facilitation of venous access and care was an initial and enduring rationale
for safe injecting practices. Difficult venous access resulted in increased contamination of injecting environments and transitions to femoral injecting. Participants expressed an unmet
desire for non-judgemental venous access information and advice.
Conclusions: Harm reduction interventions which attend to the immediate priorities of people who inject drugs, such as venous access and care, have the potential to re-engage individuals
who are jaded or confused by hepatitis C prevention messages.

Oral lichen planus and lichenoid reactions: etiopathogenesis, diagnosis, management and malignant transformation

by Rosnah Binti Zain

Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides... more Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.

Effects of Host and virus related factors on Interferon-alpha+ ribavirin and Pegylated-interferon+ ribavirin treatment outcomes in Chronic Hepatitis C patients

by Azeem Butt

Hepatitis Associated Aplastic Anemia: A review

by Azeem Butt

An 'Elephant In the Room'? Stigma and Hepatitis C Transmission Among HIV-Positive 'Serosorting'Gay Men

by Gareth J. Owen

Abstract
Recent research has highlighted concerns about sexually transmitted infection with hepatitis C virus... more Abstract
Recent research has highlighted concerns about sexually transmitted infection with hepatitis C virus
(HCV) in populations of HIV-positive men who have sex with men. This paper presents results from
a qualitative pilot study exploring the experience of stigma in HIV/HCV co-infected men. The
preliminary findings suggest that HCV infection can be experienced as more stigmatising than HIV
among gay and other men who have sex with men. This hierarchical stigmatisation complicates the
disclosure of HCV infection, threatening the ‘safety’ of HIV serosorted unprotected sexual practice.
Further research is required to explore the effect of stigma on HIV/HCV co-infected men, but these
preliminary findings suggest that heath promotion initiatives are needed to counter hepatitis C stigma
by raisin

Antioxidant and hepatoprotective effect of the roots of Hibiscus esculentus Linn.

by Dr Syam Mohan

Staying Safe From Hepatitis C: Engaging With Multiple Priorities

by Magdalena Harris

Qualitative Health Research, 2011

Hepatitis C virus (HCV) infection is a significant global public health problem. In developed countries, 90% of new... more Hepatitis C virus (HCV) infection is a significant global public health problem. In developed countries, 90% of new infections occur among people who inject drugs (PWID), with seroprevalence increasing rapidly among new injectors. Staying Safe is an international, qualitative, social research project, the aim of which is to draw on the experiences of longterm PWID to inform a new generation of HCV prevention strategies. The Sydney project team employed life history interviews and computer-generated timelines to elicit detailed data about unexposed participants’ (n =13) injecting practices, circumstances, and social networks over time. The motivations and strategies that enabled participants to avoid risk situations, and which might have helped them to “stay safe,” appeared not to be directly related to harm reduction messages or HCV avoidance. These included the ability and inclination to maintain social and structural resources, to mainly inject alone, to manage withdrawal, and to avoid injecting-related scars. These findings point to the multiple priorities that facilitate viral avoidance among PWID and the potential efficacy of nonspecific HCV harm reduction interventions for HCV prevention.

Integrated HCV Treatment: Addressing Co-morbid Substance Use Disorders, Psychiatric Disorders, and HIV Infection

by Aaron Blackwell

Huckans, MS, Blackwell, AD, Harms, TA, Indest, DW, Hauser, P. 2005

Objectives: To examine hepatitis C virus (HCV) and HIV testing patterns within the Northwest Veterans Integrated... more Objectives: To examine hepatitis C virus (HCV) and HIV testing patterns within the Northwest Veterans Integrated Service Network (VISN 20).

Methods: Using a comprehensive VISN 20 database, we retrospectively reviewed medical records of 293 445 veterans.

Results: 32.8% of patients were tested for HCV, 5.5% were tested for HIV, and 4.3% were co-tested. Of those tested, 12.3% were HCV positive, 5.4% were HIV positive, and 1.6% were co-infected. 79.1% of HIV-positive patients were tested for HCV, 29.2% of whom tested positive. 34.8% of HCV-positive patients were tested for HIV, 4.9% of whom tested positive. Of those tested, HCV-positive patients were significantly more likely than HCV-negative patients to test positive for HIV; HIV-positive patients were no more likely to test positive for HCV than HIV-negative patients. HIV-positive patients with substance use disorders (SUD) were significantly more likely to test HCV positive than those without. Within the total sample, veterans with SUD were significantly more likely to be tested for both diseases and to test positive for HCV but not HIV. After controlling for other categories of SUD, veterans with a history of cocaine abuse compared with those without were at an increased risk of HIV infection and co-infection.

Conclusion: 79.1% of HIV-positive but only 34.8% of HCV-positive veterans were co-tested, suggesting barriers to HIV testing may exist in VISN 20. Results also indicate that HCV-positive patients are at increased risk for HIV infection and that HIV-positive patients with SUD are at increased risk of HCV infection; routine co-testing for these patients is therefore warranted. Given significant co-infection rates, HCV and HIV screening and testing should be increasingly integrated. Increased infection rates among patients with SUD also warrant integration of HCV and HIV screening and testing into mental health and addiction programmes.

Management of hepatitis C disease among VA patients with schizophrenia and substance use disorders

by Aaron Blackwell

Huckans, MS, Blackwell, AD, Harms, TA and Hauser, P. 2006.

OBJECTIVE: Rates of hepatitis C (HCV) infection, testing, and treatment were compared among patients with... more OBJECTIVE: Rates of hepatitis C (HCV) infection, testing, and treatment were compared among patients with schizophrenia, a substance use disorder, or co-occurring schizophrenia or schizoaffective disorder and a substance use disorder and a control group. METHODS: Information about 293,445 patients of the Northwest Veterans Healthcare Administration was obtained. RESULTS: The substance use disorder group constituted 13.6 percent of the sample; the schizophrenia group, 1.6 percent; and the co-occurring-disorders group, 1.4 percent. Respectively, these groups were approximately four, two, and six times as likely as the control group to receive HCV testing and about seven, two, and eight times as likely to be infected. The rate of interferon (IFN) therapy was significantly lower for the substance use group and the group with co-occurring disorders. However, the magnitude of the differences was not substantial, suggesting that these high-risk groups were not excluded from IFN therapy.

Hepatitis C testing and infection rates in bipolar patients with and without co-morbid substance use disorders

by Aaron Blackwell

Matthews, A, Huckans, MS, Blackwell, AD, and Hauser, P. 2008. Bipolar Disorders

Objectives:  To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i)... more Objectives:  To determine and compare hepatitis C (HCV) screening and testing rates among four groups: those with (i) bipolar disorder [BD group (history of BD but no substance use disorder)]; (ii) substance use disorders [SUD group (history of SUD but no BD)]; (iii) co-occurring disorders [DD group (history of both BD and an SUD)]; and (iv) a control group (no history of either bipolar disorder or substance use disorder). Our hypothesis was that HCV antibody testing rates and HCV prevalence would be higher in the BD, SUD, and DD groups than the control group.

Methods:  Data were retrospectively collected on 325,410 patients seen between 1998 and 2004 within facilities and clinics of the Veterans Integrated Service Network (VISN) 20 Northwest Veterans Health Care Administration from electronic medical records. HCV screening and prevalence rates were compared between the BD, SUD, DD, and control groups. Odds ratios and relative risks were determined and compared between groups.

Results:  Patients in the BD, SUD, and DD groups had been tested at a higher rate than controls and were at increased risk for HCV infection compared with controls. These high-risk groups had a 1.31-fold, 4.86-fold, and 5.46-fold increase in the relative risk of HCV infection, respectively. Overall, compared to the control group, the relative risk of a patient having HCV if he or she had BD (with or without an SUD) was 3.6.

Conclusions:  Patients with BD and comorbid SUD had an over fourfold increase in relative risk for HCV than our control group and a similar risk as patients in our SUD group. Furthermore, even if bipolar patients did not have a comorbid SUD (the BD group), their relative risk of HCV was significantly higher than that of the control group. This suggests that patients with BD, particularly those with a comorbid SUD, should be screened and tested for HCV.

Drug use, hepatitis C and exposure to injecting among young people in New South Wales

by Yvonna Lavis

Illness-related stigma, mood and adjustment to illness in persons with hepatitis C.

by Ronan Conroy

Golden, J., R. M. Conroy, et al. (2006). "Illness-related stigma, mood and adjustment to illness in persons with hepatitis C." Soc Sci Med.

We examined stigma in persons with hepatitis C and its relationship with mood and adjustment to illness. We studied 87... more We examined stigma in persons with hepatitis C and its relationship with mood and adjustment to illness. We studied 87 persons awaiting interferon treatment for hepatitis C at St James's Hospital, Dublin. Stigma was assessed using Fife's Experience of Illness scale. A structured clinical interview was used to establish DSM-IV diagnosis. The Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI) were also used as measures of mood. Factor analysis and clustering around latent variables analysis were used to assess scale structure and reliability. The stigma scale had an overall reliability of 0.94. A strong dimension of fear of disclosure emerged, from item analysis, together with dimensions of social isolation and social rejection. Stigma was higher in those in manual occupations and the unemployed than in those in non-manual occupation. There were high levels in those with disease associated with injecting drug use and iatrogenic disease caused by transfusion or anti-D blood products, and low levels in those who had been treated for haemophilia with contaminated products or whose hepatitis was of unknown origin. Adjusted for confounders, a 1-decile increase in stigma score had an odds ratio of 1.4 for DSM-IV depression and similar associations with depression on the HADS and BDI. Stigma was also associated with poorer work and social adjustment, lower acceptance of illness, higher subjective levels of symptoms and greater subjective impairment of memory and concentration. These associations were replicated in the non-depressed subsample. The results underline the strong link between stigma and well-being in hepatitis C. However, they also suggest that stigma is a complex construct that will require further research to elucidate.

Golden, J., M. O'Dwyer A, et al. (2005). "Depression and anxiety in patients with hepatitis C: prevalence, detection rates and risk factors." Gen Hosp Psychiatry 27(6): 431-8.

by Ronan Conroy

OBJECTIVE: We examined a group of patients awaiting interferon treatment for hepatitis C to estimate the prevalence... more OBJECTIVE: We examined a group of patients awaiting interferon treatment for hepatitis C to estimate the prevalence and detection rates of and risk factors for mood disorders. METHODS: The Structured Clinical Interview for DSM-IV Axis I Disorders: Clinician Version was used to detect psychiatric disorder. Self-completion instruments were used to rate symptom severity, subjective cognitive function, work and social adjustment, stigma, acceptance of illness and treatment satisfaction. RESULTS: The 90 participants included 23 women (26%); 33 (37%) had contracted hepatitis C iatrogenically, 42 (47%) through injecting drug use and the remainder (17%) were of unknown origin. There was a 28% 1-month prevalence of depressive disorders, 72% of whom were previously undiagnosed, and a 24% prevalence of anxiety disorders, 86% previously undiagnosed. Current methadone maintenance was strongly associated with risk of depression (odds ratio, 5.0; 95% CI, 1.08-23.0). After adjustment for age and sex, depression was associated with poorer work and social adjustment, lower acceptance of illness, higher illness stigma, poorer reported thinking and concentration, and higher levels of subjective physical symptoms (all P<.05). Anxiety disorders were uncorrelated with any risk factor. CONCLUSIONS: Depression and anxiety have high prevalences in hepatitis C, and are largely undetected and treated. Depression, but not anxiety, is associated with adverse experiences of illness.

Living With Hepatitis C: The Medical Encounter

by Magdalena Harris

New Zealand Sociology, 2005.

This paper is based on interviews with twenty individuals with
hepatitis C living in the Auckland region. A... more This paper is based on interviews with twenty individuals with
hepatitis C living in the Auckland region. A primary theme that arose from these interviews was that of the participants’ interaction with medical professionals. The stigmatised and ambiguous nature of hepatitis C often made for an unsatisfactory and harrowing encounter. I argue that the biomedical model is flawed in its attitude towards chronic illness. Instead of a one‑dimensional focus on treatment and cure there needs to be renewed focus on helping patients “live a good life while being ill”. Necessary for the attainment of this goal are ongoing models of care that take into account the experiential nature of illness and the social context of the individual.

Living With Hepatitis C In New Zealand: Narratives of Chaos and Quest

by Magdalena Harris

Polare, 2009

http://www.gendercentre.org.au/76article5.htm

Relapse to injecting drug use: A hepatitis C treatment concern

by Magdalena Harris

Contemporary Drug Problems, 2009.

In light of current initiatives to increase hepatitis C treatment uptake amongst current and former injectors, this... more In light of current initiatives to increase hepatitis C treatment uptake amongst current and former injectors, this paper aims to explore the barriers and facilitators to treatment uptake from the patient’s perspective. Semi-structured interviews were conducted with people living with hepatitis C in Auckland, New Zealand and Sydney, Australia in 2004 and 2006.  This paper explores in detail one significant issue, which has not so far been addressed in the social research literature about decision-making for hepatitis C treatment. This is the concern expressed by a quarter of the 34 ex-injecting participants regarding the potential for hepatitis C treatment to cause a relapse to injecting drug use. The connection between hepatitis C treatment and relapse to injecting drug use is supported by a substantial clinical literature. Thus the proposed expansion of hepatitis C treatment into alcohol and other drug settings needs to be undertaken with caution.

Troubling biographical disruption: Narratives of unconcern about hepatitis C diagnosis

by Magdalena Harris

Sociology of Health and Illness, 2009.

This paper explores the impact of hepatitis C diagnosis among participants of a recent qualitative study based in New... more This paper explores the impact of hepatitis C diagnosis among participants of a recent qualitative study based in New Zealand and Australia. The findings of this research were unique with regard to the small amount of existing literature on the topic. Whilst most social research indicates that diagnosis with hepatitis C is a disruptive or distressing experience, study participants were almost evenly divided between those who reported being distressed by diagnosis and those who described contracting hepatitis C as ‘no big deal’. The varied nature of participants’ narratives about their hepatitis C diagnosis indicates that the experience of biographical disruption is contextual: dependent upon previous experiences of illness, marginalisation or hardship, and the extent to which hepatitis C is an unknown entity or normalised within community networks. This paper draws on the theoretical frameworks of biographical disruption, normalisation and dys appearance to illuminate these and other contextual issues informing participants’ narratives of unconcern about hepatitis C diagnosis.

Pleasure and guilt: Alcohol use and hepatitis C

by Magdalena Harris

Qualitative Health Research, 2010

One hundred and seventy million people worldwide live with chronic hepatitis C. Heavy alcohol use plays a key role in... more One hundred and seventy million people worldwide live with chronic hepatitis C. Heavy alcohol use plays a key role in progression of the illness and is a contraindication to hepatitis C treatment. Despite the ubiquity of alcohol in Western society as a marker of celebration and sociability, there has been little research addressing the meanings of alcohol use and the dilemmas involved in ceasing or limiting consumption for affected people. This article fills a gap in the literature by addressing the meanings and practices of alcohol use for people with hepatitis C. Data are drawn from a qualitative study exploring the experiences of 40 people living with hepatitis C in New Zealand and Australia. Participants described a number of tensions and dilemmas involved in their relationship with alcohol, illustrating a complex and under-researched interplay of factors that inform drinking practice.

Injecting, infection, illness: Abjection and hepatitis C stigma

by Magdalena Harris

Body & Society, 2009

While social research has documented the prevalence and ill effects of hepatitis C related stigma, there has been... more While social research has documented the prevalence and ill effects of hepatitis C related stigma, there has been little analysis of the ways in which this stigma is constituted. This article addresses this gap in the literature by providing a phenomenologically informed account of the ways in which societal attitudes and regulations draw from and feed back into corporeal processes and experiences of embodiment in the creation of hepatitis C related stigma. The case is made that three components are central to hepatitis C stigma: associations with illicit drug injecting, infectiousness and societal aversion to chronic illness. The article draws upon qualitative interviews with 40 people living with chronic hepatitis C in New Zealand and Australia, as well as the researcher’s embodied experience of living with the virus. The works of Julia Kristeva and Mary Douglas are utilized to provide an analysis that moves beyond acknowledgement of societal reinforcers of stigma, such as prohibitory drug laws, to address underlying notions of boundary crossing in the production of stigma and exclusionary practices.