ORCID Profile
0000-0002-1821-4969
Current Organisations
Princess Alexandra Hospital
,
QIMR Berghofer Medical Research Institute
,
Royal Australasian College of Physicians
,
University of Queensland Greenslopes Clinical School
,
Blood Borne Virus and Sexual Health Service
,
Inala Indigenous Health Service
,
Mater Adult Hospital
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 12-2011
Publisher: Springer Science and Business Media LLC
Date: 19-06-2012
DOI: 10.1007/S11239-012-0760-4
Abstract: Budd-Chiari syndrome (BCS) or hepatic venous outflow obstruction, is a rare and complex clinical entity, with erse aetiology and a wide range of presentations. Its rarity and heterogeneity create significant challenges for evidence-based clinical decision-making, particularly in the even more infrequent setting of acute BCS presentation. Here we present the case of a young woman with acute, severe BCS, where treatment alternatives were limited due to a significant IVC thrombus burden. A clearly defined acute onset allowed the prompt use of systemic thrombolysis, conducted in consultation with a multi-disciplinary team of clinicians, with close monitoring for both treatment response and complications. Her treatment resulted in resolution of hepatic vein occlusion and prevention of the potentially significant clinical sequelae. We review the literature and discuss current opinion in the management of BCS.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2010
Abstract: As more pharmacogenomic insights into diseases and their treatments and toxicities are published each year, the challenge arises to incorporate such insights into clinical practice and drug development. For instance, recent genomic discoveries related to hepatitis C offer a challenge to clinicians, researchers,and health administrators to translate this information into knowledge in order to develop safer and more effective therapeutic strategies for all patients.
Publisher: Wiley
Date: 28-04-2016
DOI: 10.1111/JGH.13239
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
Publisher: Wiley
Date: 24-06-2001
DOI: 10.1111/JVH.12113
Abstract: Anaemia frequently complicates peginterferon/ribavirin therapy for chronic hepatitis C infection. Better prediction of anaemia, ribavirin dose reduction or erythropoietin (EPO) need, may enhance patient management. Inosine triphosphatase (ITPA) genetic variants are associated with ribavirin-induced anaemia and dose reduction however, their impact in real-life clinic patient cohorts remains to be defined. We studied 193 clinic patients with chronic hepatitis C infection of mixed viral genotype (genotype 1/4 n = 123, genotype 2/3, n = 70) treated with peginterferon/ribavirin. Patients were genotyped for ITPA polymorphisms rs1127354 and rs7270101 using Taqman primers. Hardy-Weinberg equilibrium was present. Estimated ITPA deficiency was graded on severity (0-3, no deficiency/mild/moderate/severe, n = 126/40/24/3, respectively). Multivariable models tested the association with anaemia at 4 weeks of treatment [including decline in haemoglobin (g/dL) haemoglobin 3 g/dL] ribavirin dose reduction and EPO use and explored sustained viral response (SVR) to peginterferon/ribavirin. More severe ITPA deficiency was associated with less reduction in haemoglobin level (P <0.001 R(2) = 0.34), less ribavirin dose reduction (OR 0.42 (95% CI = 0.23-0.77) P = 0.005) and less EPO use [OR 0.53 (0.30-0.94) P = 0.029]. ITPA deficiency was associated with SVR [OR: 1.70 (1.02-2.83) P = 0.041] independently of clinical covariates (adjusted R(2) = 0.31). In this clinical cohort, ITPA deficiency helped predict the risk of on-treatment anaemia, ribavirin dose reduction, need for EPO support and was associated with SVR. For patients on HCV regimens including peginterferon/ribavirin, testing for ITPA deficiency may have clinical utility.
Publisher: AMPCo
Date: 2014
DOI: 10.5694/MJA13.10654
Publisher: Elsevier BV
Date: 09-2007
Publisher: Springer Science and Business Media LLC
Date: 13-05-2023
DOI: 10.1007/S10620-022-07483-Y
Abstract: In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8% p 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.
Publisher: American Physiological Society
Date: 09-2018
DOI: 10.1152/AJPHEART.00417.2017
Abstract: Bilirubin, a potentially toxic catabolite of heme and indicator of hepatobiliary insufficiency, exhibits potent cardiac and vascular protective properties. In iduals with Gilbert’s syndrome (GS) may experience hyperbilirubinemia in response to stressors including reduced hepatic bilirubin excretion/increased red blood cell breakdown, with in iduals usually informed by their clinician that their condition is of little consequence. However, GS appears to protect from all-cause mortality, with progressively elevated total bilirubin associated with protection from ischemic heart and chronic obstructive pulmonary diseases. Bilirubin may protect against these diseases and associated mortality by reducing circulating cholesterol, oxidative lipid rotein modifications, and blood pressure. In addition, bilirubin inhibits platelet activation and protects the heart from ischemia-reperfusion injury. These effects attenuate multiple stages of the atherosclerotic process in addition to protecting the heart during resultant ischemic stress, likely underpinning the profound reduction in cardiovascular mortality in hyperbilirubinemic GS. This review outlines our current knowledge of and uses for bilirubin in clinical medicine and summarizes recent progress in revealing the physiological importance of this poorly understood molecule. We believe that this review will be of significant interest to clinicians, medical researchers, and in iduals who have GS.
Publisher: Springer Science and Business Media LLC
Date: 07-12-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 30-06-2010
DOI: 10.1002/HEP.23826
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-08-2011
DOI: 10.1002/HEP.24556
Publisher: Wiley
Date: 14-06-2011
DOI: 10.1111/J.1440-1746.2011.06722.X
Abstract: The role of insulin resistance (IR) and hepatic steatosis in fibrogenesis in chronic hepatitis C infection (CHC) has yielded conflicting data and few studies have been performed in Asian-region populations. We retrospectively investigated the relationship between host metabolic variables, including IR and hepatic steatosis, to hepatic fibrosis in Asian-region CHC genotype 2/3 patients. A total of 303 treatment-naïve Asian-region patients with CHC genotype 2/3 were enrolled in a multicenter phase 3 study of albinterferon alfa-2b plus ribavirin for 24 weeks. IR was defined as Homeostasis Model for Assessment of IR (HOMA-IR) > 2. Baseline liver biopsy was evaluated by a single expert histopathologist. Post hoc subgroup logistic regression modeling selected for independent variables associated with significant fibrosis (METAVIR stage F2-F4). Insulin resistance was available in 263 non-diabetic Asian-region patients (hepatitis C virus-2 [HCV-2] = 171, HCV-3 = 92), and 433 non-Asian region patients (407 "Caucasian") METAVIR fibrosis prevalence F0-F1 (minimal fibrosis)= 201 (77%) and F2-F4 (significant fibrosis) = 59 (23%), and steatosis prevalence of grade 0 = 169 (65%), grade 1 = 64 (25%), grade 2/3 = 27 (10%). Median HOMA-IR was 1.8 (interquartile range: 1.2-2.7) 100 (38%) patients had HOMA-IR > 2. Factors independently associated with significant fibrosis included HOMA-IR (odds ratio [OR]= 8.42), necro-inflammatory grade (OR = 3.17), age (OR = 1.07) and serum total cholesterol levels (OR = 0.008). This was similar to non-Asian region patients, but steatosis was not associated with significant fibrosis in either cohort. In this subgroup study of Asian-region HCV genotype 2 or 3 patients, insulin resistance, along with age, cholesterol levels and necro-inflammation, but not steatosis may be associated with significant hepatic fibrosis.
Publisher: Wiley
Date: 21-04-2023
DOI: 10.1111/JOCN.16302
Abstract: To explore the care experiences of Aboriginal and Torres Strait Islander Australians diagnosed with cirrhosis with a focus on support needed. Cirrhosis disproportionately affects Indigenous Australians, and liver diseases contribute to the mortality gap between Indigenous and other Australian adults. A qualitative study. Using yarning methods, Indigenous patients ( n = 13) and support persons ( n = 3) were interviewed by an Aboriginal researcher during April‐July, 2020. Thematic analysis was used to identify common themes using an inductive approach. Six themes emerged. (1) Experience of diagnosis . This theme included stories of delays in the system, self‐awareness of signs and symptoms and relief of being diagnosed. (2) ‘ Shame , shame , shame ’. Experiences of prejudices and discrimination from health professionals, the lack of understanding of cirrhosis among health professionals, and stories about alcohol cessation and counselling around alcohol cessation. (3) Health literacy . Participants’ understanding of cirrhosis was variable. While the importance of knowledge was recognised, ‘ what works for someone might not work for others’ . Several patients partnered with their support persons and clinicians to bridge the health literacy gap. (4) Sources of support included family and friends, transport facilities, health professionals and peers. (5) Positive and negative aspects of communication and patient consultation were discussed. (6) Psychosocial counselling to ‘look after the caring side’ . The need for more mental health care services was raised. Barriers related to poor health literacy, stigma and lack of practical and emotional support, and issues with communication and patient consultation, may lead to inequitable access to cirrhosis care and treatment for Indigenous Australians. Gaining knowledge of the experiences of Indigenous Australians with cirrhosis is important for providing patient‐centred and culturally appropriate care. Liver specialist nurses have an important role in bridging the health literacy gap and in supporting Indigenous patients and families.
Publisher: Elsevier BV
Date: 04-2016
Publisher: Future Medicine Ltd
Date: 07-2018
Abstract: Aim: To better understand the hepatocellular carcinoma (HCC) patient journey, we conducted a patient survey across 13 countries. Methods: The survey included closed- and open-ended questions developed using an iterative process to gather information on demographics, diagnosis and treatment. Patients self-selected or were directed to the online survey by their doctor. Results: A total of 256 patients completed the survey. More than two-thirds (68%) felt they did not receive enough information about HCC at diagnosis. Treatments included oral anticancer therapy, transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT). A total of 81% receiving sorafenib, 45% receiving SIRT and 32% receiving TACE reported impaired quality-of-life (QoL). A total of 42, 19 and 0% of patients using sorafenib rated their current QoL as ‘poor’, ‘good’ and ‘excellent’, respectively compared with SIRT (22, 33 and 6%) or TACE (11, 37 and 13%). Conclusion: Most patients with HCC require additional accessible information. People with incurable HCC require treatments that preserve QoL.
Publisher: Oxford University Press (OUP)
Date: 09-12-2011
Publisher: MDPI AG
Date: 25-04-2014
DOI: 10.3390/IJMS15057213
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 26-06-2014
DOI: 10.1002/HEP.27213
Publisher: Springer Science and Business Media LLC
Date: 25-04-2018
Publisher: Springer Science and Business Media LLC
Date: 29-04-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Publisher: Inishmore Laser Scientific Publishing Ltd
Date: 21-07-2021
DOI: 10.29392/001C.24940
Publisher: Wiley
Date: 22-05-2015
DOI: 10.1111/LIV.12853
Abstract: Incidence and mortality of hepatocellular carcinoma (HCC) is increasing globally, but varies between countries and regions. To target scarce resources to most need, clinical services must be informed by regional epidemiology. Using population-based data, we sought to document the incidence and mortality of HCC in Queensland, Australia, a state occupying a vast land area with erse at-risk subpopulations. Using population-based data from 1996 to 2011, the age-standardised incidence rate (ASR), annual percentage change (APC) and survival of HCC in Queensland were assessed with negative binomial regression, Kaplan-Meier and Cox survival analysis. Spatial patterns of HCC incidence and survival and relevant predictors were mapped. Thousand six hundred and twenty HCCs were diagnosed during this study period, with an overall ASR of 2.00-cases/1000 population. ASR increased by 3.5% per year, (95% CI: 2.1 to 5.0), P < 0.001) among males to 5.6/100,000 in 2011 and a non-significant increase of 2.6% per year, (95% CI = -0.7 to 6.0), P = 0.111) among females to 1.6/100,000 in 2011. Higher incidence was associated with male gender, older age, major city residence and proportionally higher area Indigenous population. Thousand and two hundred and eighty-seven patients died. Median survival was approximately 10 months. Five-year survival improved from 18% in 1996-2000 to 24% in 2006-2011 (P < 0.001). Poorer survival was associated with older age, less recent period of diagnosis, lower hepatitis B prevalence in country of origin and greater area-level social disadvantage. Over this study period, HCC incidence increased significantly. HCC survival improved but remains poor. Social determinants are critical to HCC epidemiology.
Publisher: Portland Press Ltd.
Date: 26-02-2014
DOI: 10.1042/CS20130473
Abstract: OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected cells. Hence we hypothesized that OPN directly promotes HCV replication, and that targeting OPN could be beneficial in HCV. In the present study, we compared the expression of OPN mRNA and protein in HCV (JFH1)-infected Huh7 and Huh7.5 cells, and evaluated whether modulating OPN levels using exogenous OPN ligands (up-regulate OPN) or OPN-specific RNA-aptamers (neutralize OPN) leads to changes in HCV expression. Sera and livers from patients with chronic HCV were analysed to determine whether OPN levels were associated with disease severity or response to therapy. Compared with Huh7 cells, Huh7.5 cells support higher levels of HCV replication (15-fold) and expressed significantly more OPN mRNA (30-fold) and protein. Treating Huh7 cells with OPN ligands led to a dose-related increase in HCV (15-fold) and OPN (8-fold) mRNA. Conversely, treating Huh7.5 cells with OPN-specific RNA aptamers inhibited HCV RNA and protein by & % and repressed OPN mRNA to basal levels. Liver OPN expression was significantly higher (3-fold) in patients with advanced fibrosis. Serum OPN positively correlated with fibrosis-stage (P=0.009), but negatively correlated with ETBCR (end-of-treatment biochemical response), ETVR (end-of-treatment virological response), SBCR (sustained biochemical response) and SVR (sustained virological response) (P=0.007). The OPN fibrosis score (serum OPN and presence of fibrosis ≥F2) may be a predictor of SVR. In conclusion, OPN is up-regulated in the liver and serum of patients with chronic hepatitis C, and supports increased viral replication. OPN neutralization may be a novel therapeutic strategy in chronic hepatitis C.
Publisher: Wiley
Date: 03-2018
DOI: 10.1111/IMJ.13718
Publisher: Wiley
Date: 24-11-2012
Publisher: Springer Science and Business Media LLC
Date: 12-07-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
DOI: 10.1002/CLD.565
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-08-2010
DOI: 10.1002/HEP.23853
Publisher: Elsevier BV
Date: 03-2012
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-06-2012
DOI: 10.1002/HEP.25631
Abstract: Hepatitis C virus (HCV) subverts host cholesterol metabolism for key processes in its lifecycle. How this interference results in the frequently observed, genotype-dependent clinical sequelae of hypocholesterolemia, hepatic steatosis, and insulin resistance (IR) remains incompletely understood. Hypocholesterolemia typically resolves after sustained viral response (SVR), implicating viral interference in host lipid metabolism. Using a targeted cholesterol metabolomic platform we evaluated paired HCV genotype 2 (G2) and G3 patient sera for changes in in vivo HCV sterol pathway metabolites. We compared HCV genotypic differences in baseline metabolites and following antiviral treatment to assess whether sterol perturbation resolved after HCV eradication. We linked these metabolites to IR and urine oxidative stress markers. In paired sera from HCV G2 (n = 13) and G3 (n = 20) patients, baseline sterol levels were lower in G3 than G2 for distal metabolites (7-dehyrocholesterol (7DHC) 0.017 versus 0.023 mg/dL P(adj) = 0.0524, cholesterol 140.9 versus 178.7 mg/dL P(adj) = 0.0242) but not the proximal metabolite lanosterol. In HCV G3, SVR resulted in increased levels of distal metabolites (cholesterol [Δ55.2 mg/dL P(adj) = 0.0015], 7DHC [Δ0.0075 mg/dL P(adj) = 0.0026], lathosterol [Δ0.0430 mg/dL P(adj) = 0.0405]). In contrast, lanosterol was unchanged after SVR (P = 0.9515). HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2012
DOI: 10.1002/HEP.25796
Publisher: Wiley
Date: 04-2017
DOI: 10.1111/IMJ.13380
Abstract: Many patients with cirrhosis follow complex medication and dietary regimens, and those with decompensated cirrhosis suffer debilitating complications. These factors impact activities of daily living and quality of life. To explore the concerns and challenges of people with cirrhosis and their use of support services and to also describe health professionals' (HP) perspectives of patients' concerns. This is a cross-sectional study at a tertiary liver clinic involving 50 patients and 54 HP. Data were collected using structured questionnaires. The study includes patients' report of their challenges roblems now that they have cirrhosis ('patient-volunteered concerns') and HP' report of patients' concerns. Both also ranked a list of 10 potential concerns. Patients were, on average, 58 years old (SD = 10.2), mostly male (78%), Caucasian (86%) and with compensated cirrhosis (60%). The patients' most common volunteered concerns related to managing symptoms, emotional issues and disease. Most ranked 'developing liver cancer' (79%), 'losing ability to do daily tasks for yourself' (76%), 'fear of dying' (64%) and 'fear of the unknown' (64%) as priority concerns. Regarding the use of support services, 24% of patients had accessed a dietician, 20% a pharmacist and 18% a psychologist. From the HP' perspective, the patients' most significant challenges related to managing disease (65%) and symptoms (48%), access to healthcare (56%) and information/knowledge (48%). Our findings demonstrate that cirrhosis (its symptoms, complications and treatment) is associated with significant concerns for patients. The discrepancies between the views of HP and patients suggest that we may not be measuring or addressing patients' needs appropriately.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-01-2011
DOI: 10.1002/HEP.24068
Publisher: Wiley
Date: 17-05-2016
DOI: 10.1111/APT.13657
Abstract: Liver-related mortality varies across developed nations. To assess the relative role of various risk factors in relation to liver-related mortality in an ecological study approach. Data for liver-related mortality, prevalence data for hepatitis B and C, human immunodeficiency virus (HIV), alcohol consumption per capita, Type 2 Diabetes mellitus (T2DM), overweight and obesity were extracted from peer-reviewed publications or WHO databases for different developed countries. As potential other risk-modifying factors, purchase power parity (PPP)-adjusted gross domestic product (GDP) per capita and health expenditure per capita were assessed. As an environmental 'hygiene factor', we also assessed the effect of the prevalence of Helicobacter pylori. Only countries with a PPP-adjusted GDP greater than $20 000 and valid information for at least 8 risk modifiers were included. Univariate and multivariate analyses were utilised to quantify the contribution to the variability in liver-related mortality. The proportion of chronic liver diseases (CLD)-related mortality ranged from 0.73-2.40% [mean 1.56%, 95% CI (1.43-1.69)] of all deaths. Univariately, CLD-related mortality was significantly associated with Hepatitis B prevalence, alcohol consumption, PPP-adjusted GDP (all P < 0.05) and potentially H. pylori prevalence (P = 0.055). Other investigated factors, including hepatitis C, did not yield significance. Backward elimination suggested hepatitis B, alcohol consumption and PPP-adjusted GDP as risk factors (explaining 66.3% of the variability). Hepatitis B infection, alcohol consumption and GDP, but not hepatitis C or other factors, explain most of the variance of liver-related mortality.
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1111/AJT.12684
Abstract: Determining risk for recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) is an important clinical need. We assessed consecutive patients who underwent LT for HCC following sequential transarterial chemoembolization (TACE). Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) categories: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Cox proportional hazard models were used to predict HCC recurrence. One hundred seventy-three patients underwent TACE and imaging to assess response prior to LT. TACE responses were: CR = 23.7%, PR = 24.3%, SD = 27.7% and PD = 24.3%. Five-year HCC recurrence rate was 5.3% in patients responding to TACE (CR/PR), versus 17.6%, among patients who did not respond (SD/PD, p = 0.014). In multivariate analysis, independent pre-LT predictors of recurrence were response to TACE and largest radiologic size of tumor (>3 cm vs. ≤3 cm). HCC recurrence rate for patients with tumor size >3 cm and no response to TACE was 35.8%, compared with 1.9% for patients with tumor size ≤3 cm and response to TACE (p = 0.0007). We conclude that mRECIST criteria and tumor size differentiate patients with high or low likelihood of HCC recurrence after LT. These findings raise the possibility of incorporating response to TACE and largest tumor size to identify patients at highest risk for HCC recurrence.
Publisher: BMJ
Date: 08-04-2015
Publisher: AMPCo
Date: 07-2017
DOI: 10.5694/MJA17.00323
Publisher: Massachusetts Medical Society
Date: 28-06-2012
DOI: 10.1056/NEJMP1202608
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JHEP.2015.08.027
Abstract: Hepatitis C virus (HCV) modulates host lipid metabolism for its replication and lifecycle. Our aims were to assess changes in the serum lipid and distal (post-squalene) cholesterol biosynthesis metabolite profile of HCV genotypes (GT) 2 and 3 patients treated with sofosbuvir+ribavirin. Serum s les [baseline, treatment week 12, 4weeks post-treatment] were analyzed for apolipoproteins B and E (apoB/E), total cholesterol, HDL, LDL, and 11 post-squalene sterol metabolites using a GC/MS platform. We selected 127 patients (GT2 n=50, GT3 n=77), 50% cirrhotic patients, and 42% who experienced a virological relapse. At baseline, GT3 patients had lower level of serum lipids, apoB/E, 7-dehydrocholesterol, desmosterol, lathosterol, compared to GT2 (p<0.006). Baseline lathosterol was lower in relapsers with cirrhosis compared to cirrhotic patients with SVR (p=0.003). From baseline to treatment week 12, serum lipids, apoB/E, and key sterol pathway metabolites (7-dehydrocholesterol, desmosterol, lathosterol, lanosterol) increased in GT3. In contrast, in GT2 patients, apoB/E and dihydrolanosterol decreased with viral suppression (p<0.025). At follow-up week 4, cirrhotic SVR patients showed substantially greater increases in apoB and total sterols compared to cirrhotic relapsers regardless of HCV genotype. After adjustment for genotype and gender, baseline lathosterol was independently associated with virologic response (p=0.04). HCV GT3 is associated with reduced circulation of lipids involved in the distal cholesterol biosynthesis pathway, resulting in relative hypocholesterolemia. HCV suppression during sofosbuvir+ribavirin restores distal sterol metabolites indicating viral interference with de novo lipogenesis or selective retention by hepatocytes.
Publisher: Elsevier
Date: 2014
Publisher: SAGE Publications
Date: 30-10-2016
Abstract: For regional and rural Queenslanders, chronic viral hepatitis treatment is a major unmet health need, with restricted access to specialists outside of tertiary, largely metropolitan hospitals. To increase treatment of chronic viral hepatitis in regional Queensland, a team-based telehealth model was expanded. This expansion embedded an initial nursing consultation prior to specialist telehealth consultation. We conducted a retrospective audit of the introduction and expansion of hepatology telehealth services. Activity from July 2014–June 2015 (pre-expansion) was compared with July 2015– June 2016 (post-expansion). Interviews were conducted with key staff to determine factors contributing to success of the service and identify ongoing challenges to the service model. A greater than four-fold increase in clinical consultation was observed (131 telehealth consultations pre-expansion vs 572 post-expansion p 0.001). The failure to attend rate decreased (13.0% vs 6.5%, pre vs post-expansion respectively p = 0.030), suggesting engagement with the service increased. Staff cited nurse-conducted primary assessment prior to specialist consultation and personalised patient treatment packs as key contributors to increased patient flow and engagement. This expanded team approach appears effective in delivering specialised treatment to an underserved area in regional Central Queensland. It may serve as a model to further expand telehealth management of chronic disease for regional Queenslanders.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.CANEP.2014.08.006
Abstract: Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer. DNA from WBCs of pancreatic cancer cases (n=559) and healthy unrelated controls (n=603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated s le compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated. The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit=1.37, 95%CI=1.16-1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend=0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p>0.1). We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2011
DOI: 10.1038/AJG.2010.370
Abstract: Genome-wide association studies (GWAS) have recently identified host genetic variation to be critical for predicting treatment response and spontaneous clearance in patients infected with hepatitis C virus (HCV). These important new studies are reviewed and their future clinical implications discussed. Single-nucleotide polymorphisms in the region of the IL28B gene on chromosome 19, coding for the interferon (IFN)-λ-3 or IL28B gene, are strongly associated with treatment response to pegylated IFN and ribavirin in patients infected with genotype 1 HCV. The good response variant is associated with a twofold increase in the rate of cure. Allele frequencies differ between ethnic groups, largely explaining the observed differences in response rates between Caucasians, African Americans and Asians. IL28B polymorphism is also strongly associated with spontaneous clearance of HCV. The biological mechanisms responsible for these genetic associations remain unknown and are the focus of ongoing research. Knowledge of a patient's IL28B genotype is likely to aid in clinical decision making with standard of care regimens. Future studies will investigate the possibility of in idualizing treatment duration and novel regimens according to IL28B type.
Publisher: Public Library of Science (PLoS)
Date: 05-07-2011
Publisher: Wiley
Date: 22-08-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 23-12-2017
DOI: 10.1002/HEP.29498
Publisher: Wiley
Date: 20-01-2012
DOI: 10.1111/J.1440-1746.2011.06918.X
Abstract: In 2009, an association between the interleukin-28B (IL28B) polymorphism and treatment outcome for genotype 1 (G1) hepatitis C virus (HCV) infection, as well as spontaneous clearance of HCV, was reported. Since the initial publications, over 100 articles have appeared in the peer-reviewed literature, with many more manuscripts in press and abstracts presented at scientific meetings. Despite the proliferation of data concerning the IL28B polymorphism and HCV infection, there remain many critical unanswered questions about clinical implications and the underlying biological mechanisms. In this review, we discuss the basic principles of genome-wide association study methodologies that are important for interpreting the results of genetic association studies. We then review the current literature concerning the association between IL28B variants and interferon (IFN) treatment response in patients with chronic HCV infection, as well as spontaneous HCV clearance. We consider the relevance of the IL28B polymorphism to non-G1 HCV, as well as the special treatment populations of HIV/HCV co-infection and recurrent HCV post-liver transplantation. We review current knowledge of the biological mechanisms underlying this genetic association, including the link to liver IFN-stimulated gene expression, and identify continuing gaps in our knowledge and key research priorities. Finally, pegylated-IFN and ribavirin is no longer the standard of care for the treatment of G1 HCV, and we conclude by considering the relevance of IL28B polymorphisms in the era of direct-acting antivirals.
Publisher: Wiley
Date: 31-03-2008
DOI: 10.1111/J.1445-5994.2008.01644.X
Abstract: Acute eosinophilic enteritis is a difficult diagnosis to make. Insufficient consideration of eosinophilia may commit patients to surgical treatment when medical therapy may be appropriate. The aim of the study was to determine whether the eosinophil count was considered in the diagnostic evaluation of patients presenting with acute abdominal pain who subsequently underwent appendectomy and whether eosinophilia was related to subsequent histology. The method used in the study was retrospective case-control. None of three patients with increased eosinophil counts had histologically proven appendicitis (Fisher's exact test 0.025) worm segments were seen in two patients. None of 39 patients who had histologically proven appendicitis had increased eosinophil counts. Eosinophilia may be underutilized and helminth infection may not be considered in the differential diagnosis of abdominal pain. A normal eosinophil count in the setting of clinically suspected appendicitis may make the diagnosis of eosinophilic enteritis less likely, but does not exclude it. Patients with abdominal pain and peripheral eosinophilia appear less likely to have acute appendicitis on subsequent histology however, further study is required to validate these findings. The decision to operate remains one of clinical judgement.
Location: Australia
Start Date: 2011
End Date: 2012
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
View Funded Activity