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Cody C Allison,
Jonathan Ferrand,
Louise McLeod,
Mohammad Hassan,
Maria Kaparakis-Liaskos,
Alexandra Grubman,
Prithi S Bhathal, Anouk Dev,
William Sievert,
Brendan J Jenkins,
Richard L Ferrero
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ABSTRACT: Virulent Helicobacter pylori strains that specifically activate signaling in epithelial cells via the innate immune molecule, nucleotide oligomerization domain 1 (NOD1), are more frequently associated with IFN-γ-dependent inflammation and with severe clinical outcomes (i.e., gastric cancer and peptic ulceration). In cell culture models, we showed that H. pylori activation of the NOD1 pathway caused enhanced proinflammatory signaling in epithelial cells in response to IFN-γ stimulation through the direct effects of H. pylori on two components of the IFN-γ signaling pathway, STAT1 and IFN regulatory factor 1 (IRF1). Specifically, H. pylori activation of the NOD1 pathway was shown to increase the levels of STAT1-Tyr701/Ser727 phosphorylation and IRF1 expression/synthesis in cells, resulting in enhanced production of the NOD1- and IFN-γ-regulated chemokines, IL-8- and IFN-γ-induced protein 10, respectively. Consistent with the notion that heightened proinflammatory signaling in epithelial cells may have an impact on disease severity, we observed significantly increased expression levels of NOD1, CXCL8, IRF1, and CXCL10 in human gastric biopsies displaying severe gastritis, when compared with those without gastritis (p < 0.05, p < 0.001, p < 0.01, and p < 0.05, respectively). Interestingly, NOD1, CXCL8, and IRF1 expression levels were also significantly upregulated in gastric tumor tissues, when compared with paired nontumor samples (p < 0.0001, p < 0.05, and p < 0.05, respectively). Thus, we propose that cross-talk between NOD1 and IFN-γ signaling pathways contribute to H. pylori-induced inflammatory responses, potentially revealing a novel mechanism whereby virulent H. pylori strains promote more severe disease.
The Journal of Immunology 03/2013; · 5.79 Impact Factor
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Jacinta A Holmes,
Tin Nguyen,
Dilip Ratnam,
Neel M Heerasing,
Jane V Tehan,
Sara Bonanzinga, Anouk Dev,
Sally Bell,
Stephen Pianko,
Robert Chen,
Kumar Visvanathan,
Rachel Hammond,
David Iser,
Ferry Rusli,
William Sievert,
Paul V Desmond,
D Scott Bowden,
Alexander J Thompson
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ABSTRACT: BACKGROUND AND AIM: IL28B genotype predicts response to pegylated-interferon (peg-IFN)-based therapy in chronic hepatitis C. However, the utility of IL28B genotyping in chronic hepatitis B (CHB) cohorts treated with peg-IFN is unclear. We investigated whether IL28B genotype is associated with peg-IFN treatment outcomes in a predominantly Asian CHB cohort. METHODS: This was a retrospective analysis of CHB patients treated with 48-weeks of peg-IFN monotherapy. IL28B genotype (rs12979860) was determined (TaqMan allelic discrimination kit). Baseline HBV DNA, ALT, and liver histology were available. The primary endpoints were HBeAg seroconversion with HBV DNA <2,000 IU/mL 24-weeks post-therapy (HBeAg-positive patients), and HBV DNA <2,000 IU/mL 24-weeks after peg-IFN (HBeAg-negative patients). We analysed the association between IL28B genotype and peg-IFN outcomes. RESULTS: IL28B genotype was determined for 96 patients. 88% were Asian, 62% were HBeAg-positive and 13% were METAVIR stage F3-4. Median follow-up time was 39.3 months. The majority of patients carried the CC IL28B genotype (84%). IL28B genotype did not differ according to HBeAg status. The primary endpoints were achieved in 27% of HBeAg-positive and 61% of HBeAg-negative patients. There was no association between IL28B genotype and the primary endpoint in either group. Furthermore, there was no difference in HBeAg loss alone, HBsAg loss, ALT normalisation or on-treatment HBV DNA levels according to IL28B genotype. CONCLUSIONS: In the context of a small possible effect size, and high frequency in Asian populations, IL28B genotyping is likely to have, at best, limited clinical utility for predicting peg-IFN treatment outcome for CHB patients in the Asian-Pacific region.
Journal of Gastroenterology and Hepatology 01/2013; · 2.87 Impact Factor
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Hazel Tye,
Catherine L Kennedy,
Meri Najdovska,
Louise McLeod,
William McCormack,
Norman Hughes, Anouk Dev,
William Sievert,
Chia Huey Ooi,
Tomo-O Ishikawa,
Hiroko Oshima,
Prithi S Bhathal,
Andrew E Parker,
Masanobu Oshima,
Patrick Tan,
Brendan J Jenkins
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ABSTRACT: Gastric cancer (GC) is associated with chronic inflammation; however, the molecular mechanisms promoting tumorigenesis remain ill defined. Using a GC mouse model driven by hyperactivation of the signal transducer and activator of transcription (STAT)3 oncogene, we show that STAT3 directly upregulates the epithelial expression of the inflammatory mediator Toll-like receptor (TLR)2 in gastric tumors. Genetic and therapeutic targeting of TLR2 inhibited gastric tumorigenesis, but not inflammation, characterized by reduced proliferation and increased apoptosis of the gastric epithelium. Increased STAT3 pathway activation and TLR2 expression were also associated with poor GC patient survival. Collectively, our data reveal an unexpected role for TLR2 in the oncogenic function of STAT3 that may represent a therapeutic target in GC.
Cancer cell 10/2012; 22(4):466-78. · 25.29 Impact Factor
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Dilip Ratnam, Anouk Dev,
Tin Nguyen,
Vijaya Sundararajan,
Hugh Harley,
Wendy Cheng,
Alice Lee,
Ferry Rusli,
Robert Chen,
Sally Bell,
Stephen Pianko,
William Sievert
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ABSTRACT: Pegylated interferon-α (PEG-IFN) provides potential advantages over nucleos(t)ide analogues in the treatment of chronic hepatitis B (CHB) given its finite course, durability and lack of drug resistance. Much of the evidence is derived from controlled studies and it is unclear whether these results can be replicated in an everyday, non-controlled setting. The aim of this study was to examine the efficacy and tolerability of PEG-IFN-α2A in CHB patients in a clinical setting.
Chronic hepatitis B patients treated with PEG-IFN-α2A (180µg/week, 48 weeks) at five tertiary hospitals were retrospectively identified. Baseline demographic and clinical data, on-treatment virological and serological responses and adverse events (AE) were recorded. Treatment outcomes were defined as alanine aminotransferase (ALT) normalization, hepatitis B virus DNA <351 IU/mL and hepatitis B e antigen (HBeAg) seroconversion.
Sixty three HBeAg positive patients were identified (65% male, 80% born in Asia, 84% with viral loads > 6log IU/mL, 9.5% advanced fibrosis). Six months after therapy 46% achieved normalization of ALT, 16% had viral loads < 351 IU/mL and 32% achieved HBeAg seroconversion. 29 HBeAg negative patients were treated (75% male, 86% born in Asia, 48% had viral loads > 6log IU/mL, 24% advanced fibrosis). Six months post-treatment, 55% and 36% maintained a normalized ALT and HBV DNA < 351 IU/mL, respectively. Optimal viral suppression was maintained in 50-75% of patients over 2 years of follow up. 6.5% of all patients discontinued therapy due to AEs.
In everyday clinical practice PEG-IFN therapy in CHB is well tolerated and can achieve a similar efficacy to that seen in large controlled trials.
Journal of Gastroenterology and Hepatology 12/2011; 27(9):1447-53. · 2.87 Impact Factor
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ABSTRACT: Hepatitis B virus (HBV) infection represents a growing health burden in Australia. This clinical audit aimed to enhance general practitioner awareness of the recommended management for patients with chronic hepatitis B.
This article describes a clinical two-phase audit of 119 Australian GPs who contributed records retrospectively of patients with chronic hepatitis B.
Patient records were examined for compliance with prevailing guidelines and GPs received education on guidelines. At completion of the audit 29% of patients were monitored at recommended intervals and 47% were managed according to the current guidelines. Recording of hepatitis B virus DNA results increased from 24% in phase 1 to 63% in phase 2. General practitioners reported increased knowledge of appropriate management and referral. Twenty-five percent of patients audited in both phases had been referred to a specialist. Participating GPs improved their management of patients with chronic hepatitis B. However, there remains considerable scope for enhancing GP understanding of hepatitis B virus and applying current guidelines to clinical practice.
Australian family physician 07/2011; 40(7):533-8. · 0.73 Impact Factor
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Catherine L Kennedy,
Meri Najdovska,
Gareth W Jones,
Louise McLeod,
Norman R Hughes,
Cody Allison,
Chia Huey Ooi,
Patrick Tan,
Richard L Ferrero,
Simon A Jones, Anouk Dev,
William Sievert,
Prithi S Bhathal,
Brendan J Jenkins
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ABSTRACT: Chronic activation of the gastric mucosal adaptive immune response is a characteristic trait of gastric cancer. It has recently emerged that a new class of T helper (Th) cells, defined by their ability to produce interleukin (IL)-17A (Th17), is associated with a host of inflammatory responses, including gastritis. However, the role of these Th17 cells in the pathogenesis of gastric cancer is less clear. To formally address this, we employed gp130(F/F) mice, which spontaneously develop gastric inflammation-associated tumours akin to human intestinal-type gastric cancer. At the molecular level, these tumours demonstrate hyper-activation of the latent transcription factor signal transducer and activator of transcription (STAT)3 via the IL-6 cytokine family member, IL-11. In gp130(F/F) mice, the generation of Th17 cells, as well as the gastric expression of IL-17a and other Th17-related factors (Rorγt, IL-23), were augmented compared to wild-type gp130(+/+) mice. Consistent with a role for IL-6 and STAT3 in regulating IL-17A, increased Th17 generation and gastric expression of Th17-related factors in gp130(F/F) mice were reduced to wild-type levels in gp130(F/F) :Stat3(-/+) mice displaying normalized STAT3 activity, and also in gp130(F/F) :IL-6(-/-) mice. Importantly, genetic ablation of IL-17A in gp130(F/F) :IL-17a(-/-) mice did not suppress the initiation and growth of gastric tumours. Furthermore, IL-17A and RORC gene expression was strongly increased in human gastric biopsies from patients with gastritis, but not gastric cancer. Collectively, our data suggest that increased expression of Th17-related factors does not correlate with the molecular pathogenesis of gastric tumourigenesis.
The Journal of Pathology 05/2011; 225(2):255-64. · 6.32 Impact Factor
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ABSTRACT: Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.
We surveyed 1050 members of the American Association for the Study of Liver Diseases regarding their participation in clinical research. We compared the survey responses by specialty and level of clinical trial experience.
A majority of the respondents (71.6%) reported involvement in research activities. Factors most influential in clinical trial participation included funding and compensation (88.3%) and intellectual pursuit (87.8%). Barriers to participation were similar between gastroenterologists (n = 160) and hepatologists (n = 189) and between highly experienced (n = 62) and less experienced (n = 159) clinical researchers. These barriers included uncompensated research costs and lack of specialized support. Industry marketing was a greater influence among respondents with less trial experience, compared to those with extensive experience (15.7% vs 1.6%; P < .01). Hepatologists and respondents with extensive clinical trial experience tended to be more interested in phase 1 and 2 studies, whereas gastroenterologists and less experienced investigators were more interested in phase 4 studies.
This study suggests that the greatest barrier to participation in clinical research is lack of adequate resources. Respondents also favored industry-sponsored research with less complex trial protocols and studies of relatively short duration.
BMC Health Services Research 10/2008; 8:208. · 1.66 Impact Factor
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ABSTRACT: To conduct a multicentre retrospective review of virological response rates in Asians infected with genotype 1 chronic hepatitis C (CHC) treated with combination interferon and ribavirin and then to compare their responses to that among Caucasians.
Asian patients infected with genotype 1 CHC treated at 4 Australian centres between 2001 to 2005 were identified through hospital databases. Baseline demographic characteristics, biochemical, virological and histological data and details of treatment were collected. Sustained virological responses (SVR) in this cohort were then compared to that in Caucasian subjects, matched by genotype, age, gender and the stage of hepatic fibrosis.
A total of 108 Asians with genotype 1 CHC were identified. The end of treatment response (ETR) for the cohort was 79% while the SVR was 67%. Due to the relatively advanced age of the Asian cohort, only sixty-four subjects could be matched with Caucasians. The ETR among matched Asians and Caucasians was 81% and 56% respectively (P = 0.003), while the SVR rates were 73% and 36% (P < 0.001) respectively. This difference remained significant after adjusting for other predictive variables.
Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians.
World Journal of Gastroenterology 06/2008; 14(21):3416-20. · 2.47 Impact Factor
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Keyur Patel,
David R Nelson,
Don C Rockey,
Nezam H Afdhal,
Katie M Smith,
Esther Oh,
Keith Hettinger,
Marc Vallée, Anouk Dev,
Margaret Smith-Riggs,
John G McHutchison
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ABSTRACT: Accurate disease staging in chronic hepatitis C (CHC) infection helps guide treatment and may provide prognostic information. Liver biopsies are invasive, costly, and associated with morbidity. We hypothesized that a noninvasive test of liver fibrosis can accurately stage liver fibrosis. We prospectively evaluated the FIBROSpect II (FSII) biomarker panel versus pathology assessment and a quantitative measure of fibrosis.
Liver biopsy specimens and serum were obtained from 252 CHC patients, including 50 posttransplant, from 3 tertiary centers. Biopsy specimens were scored centrally and independently at each site, along with central quantification of fibrosis by digitized morphometry. Serum tests were performed blinded to clinical or histologic evaluation.
The mean biopsy specimen length was 1.95 +/- 0.87 cm; prevalence of stage F2 through F4 fibrosis was 77%. Agreement between central and site readings for individual stages was modest (k = 0.674), with concordant readings in 106 of 248 (43%) biopsy specimens. The area under the receiver operating characteristic curve for FSII and morphometry for stages F2 through F4 for concordant biopsy specimens were 0.823 and 0.728, respectively. Sensitivity and specificity for FSII were 83.5% and 66.7%, respectively, with an accuracy of 80.2%. The aspartate aminotransferase to platelet ratio index sensitivity and specificity for predicting F2 through F4 were 30.4% and 100%, respectively, the indeterminate rate was 40.4%, and the accuracy rate was 48.4%. The accuracy of FSII in concordant biopsy specimens in the posttransplant cohort was 73%.
Serum biomarkers can differentiate mild from moderate-to-severe fibrosis. This prospective study validates the performance characteristics of FSII in CHC patients and a posttransplant cohort. Assessing the diagnostic utility of biomarkers is limited by variability in methods to quantify fibrosis and poor interobserver agreement for histologic staging.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 02/2008; 6(2):242-7. · 5.64 Impact Factor
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Ian R White,
Keyur Patel,
William T Symonds, Anouk Dev,
Philip Griffin,
Nikos Tsokanas,
Mark Skehel,
Chiang Liu,
Amany Zekry,
Paul Cutler,
Mahanandeeshwar Gattu,
Don C Rockey,
Michelle M Berrey,
John G McHutchison
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ABSTRACT: Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.
Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.
Seven individual protein spots were identified as either significantly increased (alpha2-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and alpha2-macroglobulin, are included in existing non-invasive serum marker panels.
Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.
Journal of Translational Medicine 02/2007; 5:33. · 3.41 Impact Factor
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Ian White,
Keyur Patel,
William Symonds, Anouk Dev,
Philip Griffin,
Nikos Tsokanas,
Mark Skehel,
Chiang Liu,
Amany Zekry,
Paul Cutler,
Mahanandeeshwar Gattu,
Don Rockey,
Michelle Berrey,
John McHutchison
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ABSTRACT: Abstract
Background
Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis.
Methods
Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups.
Results
Seven individual protein spots were identified as either significantly increased (α<sub>2</sub>-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α<sub>2</sub>-macroglobulin, are included in existing non-invasive serum marker panels.
Conclusion
Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.
Journal of Translational Medicine. 01/2007;
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ABSTRACT: Preliminary studies have suggested that in patients with chronic hepatitis C (CHC), cigarette smoking increases the risk for developing liver fibrosis. Hypoxia caused by smoking may induce expression of the cytokines' vascular endothelial growth factor (VEGF) and VEGF-D and their corresponding soluble tyrosine kinase receptors fms-like tyrosine kinase receptor (s-Flt) and kinase insert domain receptor (s-KDR). These cytokine levels are increased in animals with cirrhosis and in human beings with CHC. We studied whether the concentrations of VEGF, VEGF-D, s-Flt, and s-KDR were increased in CHC smokers with and without hepatic fibrosis.
A total of 170 CHC patients were identified retrospectively from a single center's database. In 59 patients, serum levels of VEGF, VEGF-D, s-Flt, and s-KDR were measured using an enzyme-linked immunosorbent assay.
All 170 patients were hepatitis C virus RNA positive, 117 (69%) were men, 43 (25%) were smokers, and their mean (+/-SD) age was 47 (+/-6) years. Overall, 21% of smokers had Metavir fibrosis scores of 3 and 4 compared with 14% of nonsmokers (P < .01). In an age-weighted multivariate model using step-wise logistic regression, smoking, infection with hepatitis C virus genotype 1, male sex, and increased VEGF-D concentration all were significant independent predictors of more severe liver fibrosis (P < .05 for all observations).
These data suggest that CHC patients who smoke may have more hepatic fibrosis. The data also suggest that increased VEGF and VEGF-D concentrations are associated with smoking and may be involved in the molecular mechanisms of fibrogenesis.
Clinical Gastroenterology and Hepatology 07/2006; 4(6):797-801. · 5.63 Impact Factor
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ABSTRACT: Chronic hepatitis C virus (HCV) infection is the most common indication for orthotopic liver transplantation (OLT) in the United States. Recent studies from selected centers have suggested that older donor age is associated with worse outcomes after transplantation for HCV.
We analyzed the United Network for Organ Sharing Liver Transplant Registry database from April 1987 to March 2003 to examine predictors of death or retransplantation in patients with HCV. Univariate models for each predictor were evaluated. Factors significant in the univariate model were used to develop a multivariable model.
Of 6,956 patients meeting the inclusion/exclusion criteria, 1,527 (22.0%) died or received retransplants during the first year after transplant. Recipients with graft failure were older, had greater serum creatinine levels, and were more likely to require mechanical ventilation and hemodialysis before transplant. Donors of patients with graft failure were older and more likely to have diabetes mellitus. In the multivariable regression model, predictors of graft failure at 1 year were donor age, recipient age, recipient creatinine greater than 2 mg/dL, and the requirement for mechanical ventilation for the recipient.
Both older donor age and older recipient age plus markers of severity of disease, including requirement for mechanical ventilation and renal insufficiency, are negatively associated with survival after liver transplantation. These factors should be considered when assessing OLT recipient and donor candidacy in patients with HCV.
Transplantation 08/2005; 80(1):145-8. · 4.00 Impact Factor
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ABSTRACT: Measuring hepatitis C virus (HCV) RNA in serum or plasma may underestimate the true HCV burden. Extracting viral RNA from whole blood (WB) with a cationic surfactant (Catrimox-14) has resulted in HCV RNA concentrations up to 1000-fold higher than from serum or plasma in some studies, but not others. We compared the Catrimox-14 WB assay with a standard serum assay.
Seventy-two chronic HCV patients received 48 weeks of standard or pegylated interferon alpha-2b and ribavirin therapy. Catrimox-14-treated WB and corresponding serum samples were obtained at baseline and weeks 12, 24, 48 and 72. HCV RNA concentrations from WB and serum were quantified by a previously validated RT-PCR assay.
Overall mean (+/- SD) baseline serum log10 HCV RNA concentration was 6.5 ((+/- 0.58) copies/ml. Out of 72 patients, 33 had no detectable virus at 72 weeks. Neither assay detected virus in these patients at 12 weeks and neither WB nor serum assays detected virus at end-of-treatment in the 10 patients who subsequently relapsed at 72 weeks. HCV RNA concentrations from WB and serum assays were linearly correlated (R2 = 0.73; P < 0.001), although mean serum HCV RNA concentrations were 0.5 log10, copies/ml higher in serum than in WB [6.0 (+/- 0.82) vs 5.5 ((+/- 0.84), respectively, P = 0.12].
Catrimox-14-treated WB assays detect changes in HCV RNA, but do not offer clinical advantage over a conventional serum RT-PCR based assay.
Antiviral therapy 01/2005; 10(4):535-41. · 3.16 Impact Factor
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ABSTRACT: Steatosis is a common finding in patients with chronic hepatitis C (CHC) due to a combination of the direct steatogenic effect of hepatitis C virus (HCV) and the prevalence of metabolic risk factors in the HCV population. Steatosis is now established as a risk factor for disease progression in CHC and significantly impacts therapeutic response. Research efforts should continue to focus on defining the complex viral and host interactions involved in the pathogenesis of HCV-related steatosis so that future therapeutic strategies may be accurately and appropriately targeted.
Clinics in Liver Disease 12/2004; 8(4):881-92, ix. · 3.18 Impact Factor
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ABSTRACT: In the developed world hepatitis C virus (HCV) infection is predominantly associated with sharing contaminated equipment between injecting drug users (IDU). In developing countries inadequately sterilized medical equipment, transmission of infected blood and cultural practices have been implicated. Accurate risk factor assessment is essential for education targeted at risk reduction in culturally diverse populations.
Ninety Australian-born Caucasians and 72 South-east Asian (SEA) HCV patients attending a Melbourne hospital liver clinic completed a questionnaire which assessed risk factor profile, perceived risk factors, knowledge of risk factors and methods to minimize transmission. Medical records were audited to identify doctor assessment of risk factors.
Risk factors in Caucasians were IDU, body piercing and tattooing (89%, 47% and 32%, respectively). Risk factors in SEA patients were injection therapy, dental therapy and surgery (89%, 70% and 38%, respectively). Most Caucasian patients (94%) correctly identified their mode of acquisition compared with 33% of SEA patients (P < 0.0001). Accurate risk factor documentation in medical records was more common in Caucasians (96 vs 32%; P < 0.0001). The majority of patients identified blood-to-blood and sexual/vertical transmission as important modes of acquisition. However, 33% of SEA patients believed transmission occurred through food, water and poor hygiene and 80% did not identify therapeutic injection or traditional medical practices as risk factors. Education provided to SEA patients did not address less well established routes of transmission.
Ethnicity influences perception and knowledge of risk factors. Improved assessment of risk factors in high-risk ethnic groups is needed. Education should be culturally appropriate and address the concerns of all populations with HCV.
Journal of Gastroenterology and Hepatology 08/2004; 19(7):792-8. · 2.87 Impact Factor
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ABSTRACT: Chronic hepatitis C infection is associated with significant morbidity and mortality in addition to substantial social and health-related costs. Since the identification of the virus and determination of the HCV genome over a decade ago, considerable progress has been made in the treatment of chronic hepatitis C infection. However, the current standard combination of interferon-based therapies and ribavirin is effective in only 50% of patients. In addition, this combination is expensive, requires lengthy periods of administration, and is associated with significant side effects. Furthermore, no effective preventive measure, such as vaccination, is currently available. A number of newer therapies, including protease and helicase inhibitors, ribozymes, antisense therapies, and therapeutic vaccines, are in preclinical and clinical development and may significantly enhance existing therapeutic options for the future.
Current Gastroenterology Reports 03/2004; 6(1):77-86.
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The American Journal of Gastroenterology 12/2003; 98(11):2344-7. · 7.28 Impact Factor
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Hepatology 08/2003; 38(1):21-4. · 11.66 Impact Factor
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ABSTRACT: Australia receives many migrants from countries with a high prevalence of hepatitis C infection. General practitioners, who are often the first health professionals consulted, need to be aware of risk factors and complications associated with hepatitis C in this group.
Four hundred and forty-seven general practitioners, obtained from registries at two Melbourne teaching hospitals serving large non-English-speaking migrant populations, were sent a questionnaire. Two hundred and forty-one returned a completed questionnaire. The survey attempted to assess knowledge of risk factors, complications, currently recommended antiviral therapy, referral practice to specialists and difficulties encountered by practitioners and patients in accessing information about HCV.
Sexual and vertical transmission were listed as more common risk factors than iatrogenic causes or injecting drug use. Most respondents interpreted basic diagnostic tests correctly but there was a range of estimates regarding progression to cirrhosis and hepatocellular carcinoma with many seriously overestimating these aspects of natural history. Interferon and ribavirin were commonly listed as optimal therapy, but both interferon monotherapy and lamivudine, a treatment for hepatitis B, were stated as optimal therapy by 25% of respondents. Considerable frustration was expressed regarding access to reliable information about treatment outcomes and to linguistically and culturally appropriate patient information.
The wide response range regarding modes of acquisition of HCV in patients from non-English-speaking backgrounds, rates of progression to cirrhosis and hepatocellular carcinoma and optimal antiviral therapy suggests a need to improve provision of appropriate educational resources that will facilitate general practice management of a common and important public health problem.
Journal of Gastroenterology and Hepatology 04/2002; 17(3):295-300. · 2.87 Impact Factor
