Expert opinion on managing chronic HCV in patients with mixed cryoglobulinaemia vasculitis

International audienceMixed cryoglobulinaemia vasculitis (CryoVas) is a small-vessel systemic vasculitis caused by deposition of mixed cryoglobulins and is characterized by a wide range of clinical symptoms. HCV is the primary cause of CryoVas, which is associated with significant morbidity and mortality. The mortality rate among patients with HCV-associated CryoVas is 3× that of the general population, with a 63% 10-year survival rate. First-line treatment for CryoVas is anti-HCV therapy because viral clearance is associated with clinical improvement. The introduction of highly effective, interferon-free, direct-acting antiviral regimens provides additional treatment options for these patients. Here, we review recent studies investigating the effect of antiviral therapy on HCV-associated CryoVas and provide expert opinion for health-care professionals managing these patients

Sustained response after a 2-year course of lamivudine treatment of hepatitis B e antigen-negative chronic hepatitis B

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72882/1/j.1365-2893.2004.00556.x.pd

Sequencing of the Hepatitis C Virus: A Systematic Review

Since the identification of hepatitis C virus (HCV), viral sequencing has been important in understanding HCV classification, epidemiology, evolution, transmission clustering, treatment response and natural history. The length and diversity of the HCV genome has resulted in analysis of certain regions of the virus, however there has been little standardisation of protocols. This systematic review was undertaken to map the location and frequency of sequencing on the HCV genome in peer reviewed publications, with the aim to produce a database of sequencing primers and amplicons to inform future research. Medline and Scopus databases were searched for English language publications based on keyword/MeSH terms related to sequence analysis (9 terms) or HCV (3 terms), plus "primer" as a general search term. Exclusion criteria included non-HCV research, review articles, duplicate records, and incomplete description of HCV sequencing methods. The PCR primer locations of accepted publications were noted, and purpose of sequencing was determined. A total of 450 studies were accepted from the 2099 identified, with 629 HCV sequencing amplicons identified and mapped on the HCV genome. The most commonly sequenced region was the HVR-1 region, often utilised for studies of natural history, clustering/transmission, evolution and treatment response. Studies related to genotyping/classification or epidemiology of HCV genotype generally targeted the 5'UTR, Core and NS5B regions, while treatment response/resistance was assessed mainly in the NS3-NS5B region with emphasis on the Interferon sensitivity determining region (ISDR) region of NS5A. While the sequencing of HCV is generally constricted to certain regions of the HCV genome there is little consistency in the positioning of sequencing primers, with the exception of a few highly referenced manuscripts. This study demonstrates the heterogeneity of HCV sequencing, providing a comprehensive database of previously published primer sets to be utilised in future sequencing studies

Hepatitis C virus genotype frequency in Isfahan province of Iran: a descriptive cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Hepatitis C is an infectious disease affecting the liver, caused by the hepatitis C virus (HCV). The hepatitis C virus is a small, enveloped, single-stranded, positive sense RNA virus with a large genetic heterogeneity. Isolates have been classified into at least eleven major genotypes, based on a nucleotide sequence divergence of 30-35%. Genotypes 1, 2 and 3 circulate around the world, while other genotypes are mainly restricted to determined geographical areas. Genotype determination of HCV is clinically valuable as it provides important information which can be used to determine the type and duration of therapy and to predict the outcome of the disease.</p> <p>Results</p> <p>Plasma samples were collected from ninety seven HCV RNA positive patients admitted to two large medical laboratory centers in Isfahan province (Iran) from the years 2007 to 2009. Samples from patients were subjected to HCV genotype determination using a PCR based genotyping kit. The frequency of HCV genotypes was determined as follows: genotype 3a (61.2%), genotype 1a (29.5%), genotype 1b (5.1%), genotype 2 (2%) and mixed genotypes of 1a+3a (2%).</p> <p>Conclusion</p> <p>Genotype 3a is the most frequent followed by the genotype 1a, genotype 1b and genotype 2 in Isfahan province, Iran.</p

'HepCheck Dublin': An Intensified Hepatitis C Screening Programme in a Homeless Population Demonstrates the Need for Alternative Models of Care

Background: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. Prevalence of HCV in homeless populations ranges from 3.9% to 36.2%. The HepCheck study sought to investigate and establish the characterisation of HCV burden among individuals who attended an intensified screening programme for HCV in homeless services in Dublin, Ireland. Methods: The HepCheck study was conducted as part of a larger European wide initiative called HepCare Europe. The study consisted of three phases; 1) all subjects completed a short survey and were offered a rapid oral HCV test; 2) a convenience sample of HCV positive participants from phase 1 were selected to complete a survey on health and social risk factors and 3) subjects were tracked along the referral pathway to identify whether they were referred to a specialist clinic, attended the specialist clinic, were assessed for cirrhosis by transient elastography (Fibroscan) and were treated for HCV. Results: 597 individuals were offered HCV screening, 73% were male and 63% reported having had a previous HCV screening. We screened 538 (90%) of those offered screening, with 37% testing positive. Among those who tested positive, 112 (56%) were ‘new positives’ and 44% were ‘known positives’. Undiagnosed HCV was prevalent in 19% of the study sample. Active past 30-day drug use was common, along with attendance for drug treatment. Unstable accommodation was the most common barrier to attending specialist appointments and accessing treatment. Depression and anxiety, dental problems and respiratory conditions were common reported health problems. 46 subjects were referred to specialised services and two subjects completed HCV treatment. Conclusions: This study demonstrates that the current hospital-based model of care is inadequate in addressing the specific needs of a homeless population and emphasises the need for a community-based treatment approach. Findings are intended to inform HepCare Europe in their development of a community-based model of care in order to engage with homeless individuals with multiple co-morbidities including substance abuse, who are affected by or infected with HCV

Autoimmune hemolytic anemia occurred prior to evident nephropathy in a patient with chronic hepatitis C virus infection: case report

BACKGROUND: Renal involvement in patients with chronic hepatitis C virus infection has been suggested to be due to a variety of immunological processes. However, the precise mechanism by which the kidneys are damaged in these patients is still unclear. CASE PRESENTATION: A 66 year old man presented with the sudden onset of autoimmune hemolytic anemia. Concomitant with a worsening of hemolysis, his initially mild proteinuria and hemoglobinuria progressed. On admission, laboratory tests revealed that he was positive for hepatitis C virus in his blood, though his liver function tests were all normal. The patient displayed cryoglobulinemia and hypocomplementemia with cold activation, and exhibited a biological false positive of syphilic test. Renal biopsy specimens showed signs of immune complex type nephropathy with hemosiderin deposition in the tubular epithelial cells. CONCLUSIONS: The renal histological findings in this case are consistent with the deposition of immune complexes and hemolytic products, which might have occurred as a result of the patient's underlying autoimmune imbalance, autoimmune hemolytic anemia, and chronic hepatitis C virus infection

The mode and tempo of hepatitis C virus evolution within and among hosts

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) is a rapidly-evolving RNA virus that establishes chronic infections in humans. Despite the virus' public health importance and a wealth of sequence data, basic aspects of HCV molecular evolution remain poorly understood. Here we investigate three sets of whole HCV genomes in order to directly compare the evolution of whole HCV genomes at different biological levels: within- and among-hosts. We use a powerful Bayesian inference framework that incorporates both among-lineage rate heterogeneity and phylogenetic uncertainty into estimates of evolutionary parameters.</p> <p>Results</p> <p>Most of the HCV genome evolves at ~0.001 substitutions/site/year, a rate typical of RNA viruses. The antigenically-important <it>E1/E2 </it>genome region evolves particularly quickly, with correspondingly high rates of positive selection, as inferred using two related measures. Crucially, in this region an exceptionally higher rate was observed for within-host evolution compared to among-host evolution. Conversely, higher rates of evolution were seen among-hosts for functionally relevant parts of the <it>NS5A </it>gene. There was also evidence for slightly higher evolutionary rate for HCV subtype 1a compared to subtype 1b.</p> <p>Conclusions</p> <p>Using new statistical methods and comparable whole genome datasets we have quantified, for the first time, the variation in HCV evolutionary dynamics at different scales of organisation. This confirms that differences in molecular evolution between biological scales are not restricted to HIV and may represent a common feature of chronic RNA viral infection. We conclude that the elevated rate observed in the <it>E1/E2 </it>region during within-host evolution more likely results from the reversion of host-specific adaptations (resulting in slower long-term among-host evolution) than from the preferential transmission of slowly-evolving lineages.</p

The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

BACKGROUND: The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. METHODS: We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. RESULTS: Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. CONCLUSION: Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found