‘It’s been a long haul, a big haul, but we’ve made it’: hepatitis C virus treatment in post-transplant patients with virus recurrence: An interpretative phenomenological analysis

The lived experience of both interferon-based and new interferon-free treatments in patients with hepatitis C virus remains understudied. To explore their journey through hepatitis C virus treatment, we interviewed seven post-transplant patients with recurrent hepatitis C virus. Three themes were identified using interpretative phenomenological analysis. Participants reported an ongoing sense of ontological uncertainty characterized by lack of control over their condition and treatment. Furthermore, an apposition of scepticism and hope accompanying each stage of hepatitis C virus treatment was described. A staged approach to psychological intervention tailored to the needs of the patient and their associated ‘stage’ of hepatitis C virus treatment was recommended

Experiences of diagnosis, stigma, culpability, and disclosure in male patients with hepatitis C virus: an interpretative phenomenological analysis

The current study aimed to explore the lived experience of patients with hepatitis C virus infection. Semi-structured interviews were conducted with seven male participants living with hepatitis C virus and were analysed using interpretative phenomenological analysis. Two master themes were identified: (1) diagnosis and the search for meaning and (2) impact of stigma on disclosure. Participants reported fears of contaminating others, feelings of stigma and concerns of disclosing the condition to others. Response to diagnosis, stigma and disclosure among the participants appeared to be interrelated and directly related to locus of blame for virus contraction. More specifically, hepatitis C virus transmission via medical routes led to an externalisation of culpability and an openness to disclosure. Transmission of hepatitis C virus as a direct result of intravenous drug use led to internalised blame and a fear of disclosure. The inter- and intra-personal consequences of hepatitis C virus explored in the current study have potential implications for tailoring future psychological therapy and psychoeducation to the specific needs of the hepatitis C virus population

Hepatitis C and ageing: a community brief

Executive summary: An estimated 226,700 people in Australia are living with chronic hepatitis C. While the numbers of people estimated to have been infected with hepatitis C has reduced over the past 15 years, the number of people with hepatitis C-related liver disease is increasing. Growing older and duration of infection are significant determinants in the progression to cirrhosis amongst people with hepatitis C. There is a lack of social research describing the experiences of people with hepatitis C as they grow older. Australia’s population is ageing with an increasing number and proportion of people over 65. Government programmatic responses to the ageing population are of a health promotion approach focussing on maintaining older people’s health and independence. Less than five percent of older people in Australia live or will live in aged care facilities with a greater emphasis from government policy on keeping people at home: home based aged care services will have an increasingly important role into the future. This qualitative, interview-based research conducted with key clinical, community and bureaucratic stakeholders in the Australian hepatitis C sector aimed to identify key issues and challenges relating to ageing and hepatitis C to inform future research directions. While all participants recognised ageing and hepatitis C as a significant issue for Australia, they acknowledged that there was a lack of specific services (clinical and/or community-based) targeting older people with hepatitis C. The lack of services resulted from the limited contact participants had with older people with hepatitis C, and participants expressed concern of their limited understanding of the needs of older people with hepatitis C. The lack of services is compounded by the variety of definitions of ageing between the research literature, national policy and stakeholder perspectives. For example, the Australia government considers people over 65 years to be “older”, whereas in the context of people with hepatitis C, participants described ageing as older than 55 years. An Australian Injecting & Illicit Drug Users League investigation into ageing in 2010 describes people who inject drugs who are over 40 years as ageing. During interviews, significant attention was directed towards discussing whether “age” is a proxy for “severity of liver disease” or whether there are specific-age related issues associated with mild liver disease. Participants acknowledged that older people with hepatitis C often experience co-morbidities related to ageing, in addition to extrahepatic manifestations of hepatitis C infection, which often complicate the management and treatment of hepatitis C. While the clinical management of hepatitis C is changing and new treatments promise a shorter treatment course with fewer side effects, several clinicians expressed guilt in advising older people to wait for interferon-free regimes because of concern about pre-existing comorbidities, while being concerned that advising older people to wait for three to five years for the new treatments may be too late. Older people with hepatitis C are not identified as a priority population nor are their needs discussed in the National Hepatitis C Strategy 2010-2013. Therefore, it is not surprising that hepatitis C and ageing are not identified as a priority in either the national or state health agenda of the aged care sector. In order to articulate the impact and issues associated with hepatitis C and ageing, the issue of ageing in Australia needs to be examined broadly and the impact of hepatitis C considered in the current context. Exploring the needs of people with hepatitis C as they age needs to occur as a matter of urgency, as older people with hepatitis C are a hidden population. A comprehensive, strategic approach to hepatitis C and ageing is needed to ensure that the needs of older people with hepatitis C do not continue to go unrecognised

Era of direct acting anti-viral agents for the treatment of hepatitis C.

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents (DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article

Risk factors and outcome among a large patient cohort with community-acquired acute hepatitis C in Italy

BACKGROUND: The epidemiology of acute hepatitis C has changed during the past decade in Western countries. Acute HCV infection has a high rate of chronicity, but it is unclear when patients with acute infection should be treated. METHODS: To evaluate current sources of hepatitis C virus (HCV) transmission in Italy and to assess the rate of and factors associated with chronic infection, we enrolled 214 consecutive patients with newly acquired hepatitis C during 1999-2004. The patients were from 12 health care centers throughout the country, and they were followed up for a mean (+/- SD) period of 14+/-15.8 months. Biochemical liver tests were performed, and HCV RNA levels were monitored. RESULTS: A total of 146 patients (68%) had symptomatic disease. The most common risk factors for acquiring hepatitis C that were reported were intravenous drug use and medical procedures. The proportion of subjects with spontaneous resolution of infection was 36%. The average timespan from disease onset to HCV RNA clearance was 71 days (range, 27-173 days). In fact, 58 (80%) of 73 patients with self-limiting hepatitis experienced HCV RNA clearance within 3 months of disease onset. Multiple logistic regression analyses showed that none of the variables considered (including asymptomatic disease) were associated with increased risk of developing chronic hepatitis C. CONCLUSIONS: These findings underscore the importance of medical procedures as risk factors in the current spread of HCV infection in Italy. Because nearly all patients with acute, self-limiting hepatitis C - both symptomatic and asymptomatic - have spontaneous viral clearance within 3 months of disease onset, it seems reasonable to start treatment after this time period ends to avoid costly and useless treatment

The impact of illicit drug use on Spontaneous Hepatitis C Clearance: Experience from a large cohort population study

Background and Aims: Acute hepatitis C infection usually ends in chronic infection, while in a minority of patients it is spontaneously cleared. The current population-based study is performed on a large cohort in Golestan province of Iran to examine the demographic correlates of Spontaneous Hepatitis C Clearance. Methods: Serum samples used in this study had been stored in biorepository of Golestan Cohort Study. These samples were evaluated for anti hepatitis C Virus by third generation Enzyme-linked immunosorbent assay (ELISA). Subjects who tested positive were then invited and tested by Recombinant Immunoblot Assay (RIBA) and Ribonucleic Acid Polymerase Chain Reaction test (PCR). If tested positive for RIBA, subjects were recalled and the two tests were re-done after 6 months. Those subjects who again tested positive for RIBA but negative for PCR were marked as cases of spontaneous clearance. Results: 49,338 serum samples were evaluated. The prevalence of Chronic Hepatitis C Virus (CHCV) infection based on PCR results was 0.31. Among those who had acquired hepatitis C, the rate of SC was 38. In multivariate analysis, illicit drug use both Injecting Use (OR = 3.271, 95 CI: 1.784-6.000, p-value<0.001) and Non-Injecting Use (OR = 1.901, 95 CI: 1.068-3.386, p-value = 0.029) were significant correlates of CHCV infection versus SC. Conclusions: Illicit drug use whether intravenous or non-intravenous is the only significant correlate of CHCV, for which several underlying mechanisms can be postulated including repeated contacts with hepatitis C antigen. © 2011 Poustchi et al

Hepatitis C Screening in the Homeless Population of Philadelphia

Hepatitis C is a viral infectious disease that is a major cause of liver disease around the world. By the 1970s, it was recognized that many hepatitis cases were not due to the known hepatitis A or hepatitis B viruses. It was not until 1989 when the virus, then known as non--‐A, non--‐B hepatitis, was identified as a new distinct virus, hepatitis C. The virus has seven major genotypes, with genotype 1 causing about 75% of cases in the United States. By 1990, a screening test for the virus was developed, and within a year, the first treatment for the virus was approved.1 Research through the 1990s and into the early 2000s improved treatment options. Before 2011, the standard of care treatment for hepatitis C consisted of pegylated interferon and ribavirin, which successfully cured between 45% and 80% of individuals, depending on the specific genotype of HCV. In recent years, new treatments consisting of a combination of ledpiasivir, sofosbuvir, ribavirin, and pegylated interferon have improved the cure rate to up to 99% in some genotypes.2 These drugs work without the many severe side effects of older classes of drugs, which had a relatively high risk of causing life threatening hemolytic anemia.3 However, the cost of these new treatments can approach $100,000 for a twelve--‐week therapy, making the cost of treatment prohibitively expensive for many Americans. 4https://jdc.jefferson.edu/cwicposters/1027/thumbnail.jp

Distinct cytokine patterns in Occult Hepatitis C and Chronic Hepatitis C Virus Infection

Background &#x26; Aim: &#xd;&#xa;The immunopathogenesis of chronic hepatitis C virus (HCV) infection is a matter of great controversy. The imbalance of T-helper lymphocyte cell cytokine production was believed to play an important pathogenic role in chronic viral hepatitis. Occult hepatitis C infection is regarded as a new entity that should be considered when diagnosing patients with a liver disease of unknown origin. The aim of this study was to determine serum T-helper 1 and T-helper 2 cytokine production in patients with occult HCV infection and its role in pathogenesis versus chronic viral hepatitis C infection.&#xd;&#xa;&#xd;&#xa;Methods: &#xd;&#xa;Serum levels of cytokines of T-helper 1 (IL-2, IFN-[gamma]) and T-helper 2 (IL-4) were measured in 27 patients with occult HCV infection and 50 patients with chronic hepatitis C infection.&#xd;&#xa;&#xd;&#xa;Results: &#xd;&#xa;The levels of the T-helper 1 cytokines, IL-2 and IFN-[gamma], were highly and significantly increased in patients with chronic HCV infection as compared with occult HCV infection (p&#x3c;0.001). The T-helper 2 cytokine IL-4 was highly and significantly increased in occult HCV infection as compared with chronic HCV infection (p&#x3c;0.001). Necroinflammation (P&#x3c;0.001) fibrosis (P&#x3c;0.001) and cirrhosis (P =0.03) were significantly increased in chronic HCV than occult HCV. &#xd;&#xa;&#xd;&#xa;Conclusion: &#xd;&#xa;Patients with occult HCV infection exhibited distinct immunoregulatory cytokine patterns, favoring viral persistence in the liver in spite of its absence from peripheral blood and explaining the less aggressive course of this disease entity than chronic hepatitis C virus infection

Baseline anti-NS4a antibodies in combination with on-treatment quantitative HCV-RNA reliably identifies nonresponders to pegylated interferon-ribavirin combination therapy after 4 weeks of treatment

Background Early detection of nonresponders to hepatitis C therapy limits unnecessary exposure to treatment and its side-effects. A recent algorithm combining baseline anti-NS4a antibodies and on-treatment quantitative PCR identified nonresponders to a combination of interferon and ribavirin after 1 week of treatment. Aim To validate a stopping rule based on baseline anti-NS4a antibody levels and early on-treatment virological response in treatment-naive genotype 1 chronic hepatitis C patients treated with the current standard pegylated interferon and ribavirin combination therapy. Methods Eighty-nine genotype 1 patients from the Dynamically Individualized Treatment of hepatitis C Infection and Correlates of Viral/Host dynamics Study treated for 48 weeks with standard 180 mu g pegylated interferon (PEG-IFN)-alpha-2a (weekly) and ribavirin 1000-1200mg (daily) were analysed. Baseline anti-NS4a antibody enzyme-linked immunosorbent assay (NS4a AA 1687-1718) was performed on pretreatment serum. Hepatitis C virus-RNA was assessed at days 0, 1, 4, 7, 8, 15, 22, 29, weeks 6, 7, 8, 10, 12 and 6 weekly thereafter until end of treatment. Multiple regression logistic analysis was performed. Results Overall 54 of 89 (61%) patients achieved sustained virological response. A baseline anti-NS4a antibody titre less than 1/1250 correlated with absence of favourable initial viral decline according to variable response types (P=0.015). The optimal algorithm was developed using the combination of the absence of anti-NS4a Ab (= 100.000 IU/ml at week 4. This algorithm has a specificity of 43% and negative predictive value of 100% to detect nonresponse to standard PEG-IFN-alpha-2a and ribavirin therapy at fourth week of therapy (intention-to-treat analysis). Conclusion The decision to stop the therapy in genotype 1 chronic hepatitis C patients treated with PEG-IFN-alpha-2a and ribavirin can be confidently made after 4 weeks of treatment based on the absence of baseline anti-NS4a Ab and a week-4 hepatitis C virus-RNA above 100.000 IU/ml. Eur J Gastroenterol Hepatol 22:1443-1448 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome