ORCID Profile
0000-0002-3411-9267
Current Organisation
Royal Brisbane and Women's Hospital
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Publisher: Springer Science and Business Media LLC
Date: 29-07-2009
Publisher: Baishideng Publishing Group Inc.
Date: 2012
Publisher: Wiley
Date: 11-04-2019
DOI: 10.1111/APT.15248
Abstract: Mycophenolate mofetil is a commonly used salvage therapy for patients with autoimmune hepatitis (AIH). To evaluate the predictors of response to mycophenolate rescue therapy to facilitate clinical decision making. We performed a retrospective observational cohort study of AIH patients managed in 17 major Australian liver centres who received mycophenolate after an inadequate response or intolerance to corticosteroids with/without thiopurine(s). Baseline demographic, clinical and laboratory variables were compared between responders and nonresponders. A multivariable logistic regression model was developed using forward selection to identify independent predictors of treatment response. A total of 105 patients received mycophenolate rescue therapy of whom 63 (60%) achieved biochemical remission. On univariable analysis, older age (P = 0.003), INR < 1.1 (P = 0.02), and lower immunoglobulin gamma (IgG P < 0.002) levels were associated with treatment response, while no association was found with cirrhosis status (P = 0.07) or treatment indication (P = 0.63). On multivariable analysis, lower pre-treatment serum IgG level (P = 0.01), higher age at commencing mycophenolate (P = 0.01) and higher INR (P = 0.03) were the only significant independent predictors. An IgG level <17 g/L had a positive and negative predictive value for response of 71% and 60% respectively, while age ≥54 years when commencing mycophenolate had a positive and negative predictive value for response of 80% and 59% respectively. Mycophenolate remains an excellent treatment option for patients with AIH refractory to or intolerant of standard therapy with those most likely to benefit being older and/or having lower pre-treatment IgG levels.
Publisher: Wiley
Date: 27-02-2013
DOI: 10.1111/J.1445-5994.2012.02848.X
Abstract: Subjects with metabolic risk factors for non-alcoholic fatty liver disease (NAFLD) are commonly seen by hospital specialists other than gastroenterologists/hepatologists. The aim of this study was to assess the awareness of NAFLD and opinions regarding management among non-hepatologists at two major tertiary hospitals in Brisbane. A face-to-face questionnaire assessing current beliefs and practices regarding NAFLD was administered to specialists and specialists-in-training across six specialties (internal medicine, cardiology/cardiac surgery, endocrinology, thoracic medicine, rheumatology and nephrology). One hundred clinicians were surveyed with 99% returning completed questionnaires (>89% questions answered). The majority of respondents (75%) believe the prevalence of NAFLD in the general population to be ≤ 10%, although two-thirds feel that its incidence will rise markedly. The vast majority (>90%) appreciate that traditional cardiovascular risk factors (obesity, hypertriglyceridaemia and diabetes) are risk factors for NAFLD and acknowledge that these are common in non-hepatology patients. Despite this, most believe that NAFLD is uncommon in their own patients (89% indicated a prevalence ≤ 30%). The vast majority (93%) agree that non-alcoholic steatohepatitis (NASH) is associated with increased overall mortality, but 60% also believe that simple steatosis confers increased liver-related mortality. Most (74%) agree that a diagnosis of NASH cannot be made using liver enzymes, but 67% support 6-monthly liver function tests as the most effective way to monitor progression of NAFLD. Most respondents (71%) make no referrals to hepatology for suspected NAFLD. Non-hepatologists appreciate the seriousness of NAFLD but appear to underestimate its prevalence, especially among their own patients despite known risk factors. Attitudes regarding simple steatosis versus NASH and appropriate monitoring of suspected NAFLD suggest that more can be done to improve the understanding of this disease among non-hepatologists. This has implications for targeting 'at-risk' populations and appropriate referral of patients to hepatology clinics.
Publisher: Baishideng Publishing Group Inc.
Date: 21-12-2014
Publisher: Wiley
Date: 29-01-2013
DOI: 10.1111/LIV.12100
Abstract: Adult non-alcoholic fatty liver disease (NAFLD) involves lobular necroinflammatory activity and fibrosis is typically centrilobular, whereas paediatric NAFLD has predominantly portal fibrosis. The reasons for these differences are unclear. We aimed to determine (a) how centrilobular and portal fibrosis in children relate to histological parameters and (b) whether atypical fibrosis patterns exist in adults that are unexplained by current fibrogenesis models. Histological features of paediatric (n = 38) and adult (n = 56) NAFLD were assessed using conventional scoring systems. Keratin-7 immunostaining was used to assess hepatic progenitor cell numbers and the ductular reaction. Centrilobular and portal components of fibrosis were independently scored and fibrosis patterns were classified according to accepted types. Post-treatment (rosiglitazone/gastric banding) biopsies were also examined in adults. Twenty-six children (68.4%) had portal-predominant fibrosis, although the typical "adult" pattern was seen in 11 (28.9%). Portal fibrosis was associated with a ductular reaction (P = 0.021) and hepatic progenitor cell expansion (P < 0.001), whereas centrilobular fibrosis was associated with lobular inflammation (P = 0.026) and ballooning (P = 0.001). Before intervention, six adults (10.7%) had atypical fibrosis including 3 (5.4%) with a previously unrecognized pattern of very fine, non-zonal sinusoidal fibrosis. Despite improvements in steatosis and inflammation, more patients developed this unusual pattern after intervention with most having had surgery (9 of 10 adults P < 0.001). Differing associations with portal and centrilobular fibrosis in children and atypical fibrosis patterns in adults suggest that multiple fibrogenic pathways exist in NAFLD. This has implications for therapy and understanding pathogenesis.
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/AH12162
Abstract: Objectives. To determine the spectrum of disease among non-urgent referrals to a tertiary hospital hepatology outpatient clinic, assess the adequacy of referral information in terms of risk stratification and determine whether a specifically designed referral template altered urgency for specialist assessment. Methods. A snapshot of the waiting list of a hepatology clinic at a tertiary hospital was taken from the scheduling database. Information was retrieved from referrals and attached investigations. Updated information was requested from subjects and their current general practitioner. Results. Hepatitis C virus accounted for 68.7% of the 1223 reviewed referrals. Clinical information provided by referring clinicians was often incomplete. Provision of updated information identified the presence of comorbidities (obesity, ‘heavy’ alcohol consumption, mental health issues) and altered the need or urgency for specialist assessment in 22% of cases. Conclusions. Hepatitis C virus accounts for the majority of non-urgent referrals waiting to access hepatology outpatient consultations. Using a standardised assessment form as part of the referral process provides more information on comorbidities and risk factors and facilitates more accurate triaging of clinical urgency. Wider adoption of this strategy may increase appropriate access to hepatology services and reduce the future burden of cirrhosis and hepatocellular cancer. What is known about the topic? Little published data are available that describe the content and standard of hepatology referrals, or the urgency with which these patients need to be reviewed. Inadequate clinical information impairs the ability to accurately triage referrals and may lead to delays in access. What does the paper add? Almost 70% of reviewed referrals were for management of patients with hepatitis C virus infection, confirming this condition remains a major priority area in liver disease. Clinical information provided by referring clinicians was often incomplete, impairing the ability to accurately triage referrals. Only a minority of referrals provided information about relevant comorbidities (alcohol intake, injecting drug use, mental health issues and obesity) that negatively impact on the progression of liver disease or the response to antiviral treatment. What are the implications for practitioners? Hepatitis C virus remains a major health priority area in liver disease, increasing the future burden of cirrhosis and hepatocellular cancer. Many referred patients have comorbidities that increase their risk of progressive liver disease and related complications. Strategies to increase recognition and management of liver disease and its comorbidities in the community are required. The use of a standardised assessment form in referrals to hepatology outpatient services may assist with triaging of patients and improve access to appropriate care.
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: Wiley
Date: 10-12-2021
DOI: 10.1002/JGH3.12462
Abstract: Health‐related quality‐of‐life measurements are important to understand lived experiences of patients who have cirrhosis. These measures also inform economic evaluations by modelling quality‐adjusted life years (QALYs). We aimed to describe health‐related quality of life, specifically multiattribute utility (scale anchors of death = 0.00 and full health = 1.00), across various stages and etiologies of cirrhosis. Face‐to‐face interviews were used to collect Short Form 36 (SF‐36) questionnaire responses from CirCare study participants with cirrhosis (June 2017 to December 2018). The severity of cirrhosis was assessed using the Child‐Pugh score classified as class A (5–6 points), B (7–9), or C (10–15) and by the absence (“compensated”) versus presence (“decompensated”) of cirrhosis‐related complications. Patients ( n = 562, average 59.8 years [SD = 11.0], male 69.9%) had a range of primary etiologies (alcohol‐related 35.2%, chronic hepatitis C 25.4%, non‐alcoholic fatty liver disease (NAFLD) 25.1%, chronic hepatitis B 5.9%, “other” 8.4%). Significantly lower (all P 0.001) mean multiattribute utility was observed in the health states of patients with decompensated (mean = 0.62, SD = 0.15) versus compensated cirrhosis (mean = 0.68, SD = 0.12), Child‐Pugh class C (mean = 0.59, SD = 0.15) or B (mean = 0.63, SD = 0.15) versus A (mean = 0.68, SD = 0.16), and between those of working age (18–64 years mean = 0.64, SD = 0.16) versus those aged 65+ years (mean = 0.70, SD = 0.16). The greatest decrements in health‐related quality of life relative to Australian population norms were observed across physical SF‐36 domains. Persons with more advanced cirrhosis report greater life impacts. Estimates from this study are suitable for informing economic evaluations, particularly cost‐utility modelling, which captures the benefits of effective prevention, surveillance, and treatments on both the quality and quantity of patients' lives.
Publisher: MDPI AG
Date: 14-05-2014
DOI: 10.3390/IJMS15058591
Publisher: Humana Press
Date: 24-11-2012
Publisher: Elsevier BV
Date: 12-2019
Publisher: MDPI AG
Date: 17-02-2019
DOI: 10.3390/IJMS20040864
Abstract: Early diagnosis of cirrhosis and hepatocellular carcinoma (HCC) due to chronic Hepatitis C (CHC) remain clinical priorities. In this pilot study, we assessed serum microRNA (miRNA) expression to distinguish cirrhosis and HCC, alone and in combination with the aminotransferase-to-platelet ratio (APRI), Fibrosis 4 (FIB-4), and alpha-fetoprotein (AFP). Sixty CHC patients were sub ided into 3 cohorts: Mild disease (fibrosis stage F0-2 n = 20) cirrhosis (n = 20) and cirrhosis with HCC (n = 20). Circulating miRNA signatures were determined using a liver-specific real-time quantitative reverse transcription PCR (qRT-PCR) microarray assessing 372 miRNAs simultaneously. Differentially-expressed miRNA candidates were independently validated using qRT-PCR. Serum miRNA-409-3p was increased in cirrhosis versus mild disease. In HCC versus cirrhosis, miRNA-486-5p was increased, whereas miRNA-122-5p and miRNA-151a-5p were decreased. A logistic regression model-generated panel, consisting of miRNA-122-5p + miRNA-409-3p, distinguished cirrhosis from mild disease (area under the curve, AUC = 0.80 sensitivity = 85%, specificity = 70% p 0.001). When combined with FIB-4 or APRI, performance was improved with AUC = 0.89 (p 0.001) and 0.87 (p 0.001), respectively. A panel consisting of miRNA-122-5p + miRNA-486-5p + miRNA-142-3p distinguished HCC from cirrhosis (AUC = 0.94 sensitivity = 80%, specificity = 95% p 0.001), outperforming AFP (AUC = 0.64, p = 0.065). Serum miRNAs are differentially expressed across the spectrum of disease severity in CHC. MicroRNAs have great potential as diagnostic biomarkers in CHC, particularly in HCC where they outperform the only currently-used biomarker, AFP.
Publisher: Wiley
Date: 24-04-2015
DOI: 10.1111/ANS.13118
Publisher: CSIRO Publishing
Date: 2012
DOI: 10.1071/AH11111
Abstract: Background. Appropriate and uniform prioritisation (‘triaging’) of outpatient referrals is critical to good patient outcomes, equity of access to services and efficient use of resources. Objective. To determine whether there is uniformity in the allocation of triage categories for hepatology outpatient referrals at public hospitals in Queensland. Methods. A series of 10 recent hepatology referrals were de-identified for both patient and referring clinician details and sent to nine gastroenterology or hepatology centres throughout Queensland. Consultant gastroenterologists and hepatologists (n = 25) were asked to triage the referrals using the process in place in their centre. Responses were de-identified and analysed. Each case was reviewed and allocated an ‘agreed triage category’ based upon the majority view of respondents. Results. Nineteen responses were received. There was substantial variation amongst consultants in the allocation of triage categories. Although almost two-thirds of respondents agreed with the majority view in 60–80% of cases, none agreed with the majority for every case and some agreed in as few as 50% cases. Disagreement with the majority view of an appropriate triage category was not associated with geography or specialist experience. Conclusions. Variability in triage categorisation suggests that similar cases may be allocated different priorities by those responsible for determining the urgency of outpatient review. This has implications for equity of access to treatment. The development of triage guidelines and formal training in their implementation, along with periodic audits of triage practices in different centres, may reduce variability. What is known about the topic? Outpatient clinic appointments are allocated within categories according to ‘agreed’ clinical urgency. The process of triaging referrals seeks to prioritise referrals based on the severity of patients’ conditions and the potential for improving outcomes. At present there are no statewide guidelines or training for the triaging process in hepatology and no recommendations for who should take responsibility for prioritising referrals. What does the paper add? In Queensland, gastroenterologists (including hepatologists) triage hepatology cases differently and most likely interpret and weight clinical information provided in the referral differently. Disagreement with the majority view of an appropriate triage category is not associated with geography or specialist experience. What are the implications for practitioners? Variability in triage categorisation suggests that similar cases may be allocated different priorities by those responsible for determining the urgency of outpatient review. This has implications for equity of access to treatment. The development of triage guidelines and formal training in their implementation, along with periodic audits of triage practices in different centres, may reduce variability.
Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.JHEP.2015.08.015
Abstract: Telaprevir plus pegylated interferon/ribavirin (TPV+PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir aritaprevir/ritonavir and dasabuvir±ribavirin (OBV/PTV/r+DSV±RBV) and TPV+PegIFN/RBV. Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r+DSV+weight-based RBV, OBV/PTV/r+DSV (treatment-naïve, GT1b-infected patients only), or 12weeks of TPV+PegIFN+weight-based RBV and 12-36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies. Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV-treated GT1a-infected patients SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r+DSV+RBV, OBV/PTV/r+DSV, and TPV+PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r+DSV+RBV and TPV+PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Rates of discontinuation due to adverse events (0-1% and 8-11%, respectively, p<0.05) and rates of hemoglobin decline to <10g/dl (0-4% and 34-47%, respectively, p<0.05) were lower for OBV/PTV/r+DSV±RBV than TPV+PegIFN/RBV. Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97-99% with 12week, multi-targeted OBV/PTV/r+DSV±RBV regimens and 66-82% with 24-48 total weeks of TPV+PegIFN/RBV. OBV/PTV/r+DSV±RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.2147/PPA.S236818
Publisher: Elsevier BV
Date: 05-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2014
DOI: 10.1002/HEP.26937
Abstract: Although nonalcoholic fatty liver disease (NAFLD) is conventionally assessed histologically for lobular features of inflammation, development of portal fibrosis appears to be associated with disease progression. We investigated the composition of the portal inflammatory infiltrate and its relationship to the ductular reaction (DR), a second portal phenomenon implicated in fibrogenesis. The portal inflammatory infiltrate may contribute directly to fibrogenesis as well as influence the fate of the DR hepatic progenitor cells (HPCs), regulating the balance between liver repair and fibrosis. The presence of portal inflammation in NAFLD was strongly correlated with disease severity (fibrosis stage) and the DR. The portal infiltrate was characterized by immunostaining NAFLD liver biopsy sections (n = 33) for broad leukocyte subset markers (CD68, CD3, CD8, CD4, CD20, and neutrophil elastase) and selected inflammatory markers (matrix metalloproteinase 9 and interleukin [IL]-17). Cells expressing all markers examined were identified throughout the liver lobules and in portal tracts, although portal tracts were more densely populated (P < 0.01), and dominated by CD68(+) macrophages and CD8(+) lymphocytes, at all stages of disease. An increase in portal macrophages in NAFLD patients with steatosis alone (P < 0.01) was the earliest change detected, even before elevated expression of the proinflammatory cytokines, IL1B and TNF, in patients with early NASH (P < 0.05). Portal and periductal accumulation of all other cell types examined occurred in progressed NASH (all P < 0.05). Knowledge of the complex cellular composition of the portal inflammatory infiltrate and HPC/DR niche in NAFLD will shape future functional studies to elucidate the contribution of portal inflammation to HPC differentiation and NAFLD pathogenesis.
No related grants have been discovered for Richard Skoien.