ORCID Profile
0000-0002-1855-2757
Current Organisations
Eastern Health
,
Monash University
,
Melbourne Health
,
Royal Australasian College of Physicians
,
University of Melbourne
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Publisher: Wiley
Date: 09-06-2017
DOI: 10.1111/JVH.12717
Abstract: While HBV and HCV are risk factors for HCC, uncertainty exists as to whether these viral infections have prognostic significance in HCC. Thus, we compared the overall survival of patients with HBV, HCV and nonviral HCC, and evaluated whether the presence of HBV and HCV predicts patient outcomes. We conducted a multicentre study of HCC cases diagnosed at six Melbourne tertiary hospitals between Jan 2000-Dec 2014. Patient demographics, liver disease and tumour characteristics and patient outcomes were obtained from hospital databases, computer records and the Victorian Death Registry. Survival outcomes were compared between HBV, HCV and nonviral hepatitis cases and predictors of survival determined using Cox proportional hazards regression. There were 1436 new HCC cases identified including 776 due to viral hepatitis (HBV 235, HCV 511, HBV-HCV 30) and 660 from nonviral causes. The median survival of HBV, HCV and nonviral HCC patients was 59.1, 28.4 and 20.9 months, respectively (P<.0001). On multivariate analysis, independent risk factors for survival included HCC aetiology, gender, BCLC stage, serum AFP, total number and size of lesions, and serum creatinine and albumin. After adjusting for these and method of detection, HBV remained an independent predictor of improved overall survival when compared to both nonviral (HR 0.60%, 95% CI 0.35-0.98 P=.03) and HCV-related HCC (HR 0.51%, 95% CI 0.30-0.85 P=.01). In this large multicentre study, HBV is independently associated with improved overall survival compared with HCV and nonviral-related HCC. Further studies are needed to determine the underlying factor(s) responsible.
Publisher: Massachusetts Medical Society
Date: 17-01-2008
DOI: 10.1056/NEJMOA073286
Publisher: Wiley
Date: 16-03-2015
DOI: 10.1111/JGH.12804
Publisher: Wiley
Date: 12-04-2019
DOI: 10.1111/APT.15237
Publisher: MDPI AG
Date: 19-09-2022
DOI: 10.3390/NU14183875
Abstract: Background: Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent liver disease in Australia and is recognised to play a role in the development of hepatocellular carcinoma (HCC). There are no clear guidelines regarding screening for HCC in NAFLD. The aim of this retrospective study was to compare the characteristics and survival rates of NAFLD-HCC to patients with non-NAFLD-HCC to help guide future research in this area. Methods: A total of 152 HCC patients with either NAFLD (n = 36) or non-NAFLD (n = 116) were retrospectively analysed from the HCC database and medical records. Chi-square and independent t-test were used to compare baseline characteristics and Kaplan–Meier curves and Cox models were used for survival analysis. Results: Patients with NAFLD-HCC were more likely to be diagnosed due to symptoms rather than through screening, and at an older age, compared with non-NAFLD HCC. The median survival rates were lower in NAFLD-HCC (17.2 months) than in those with non-NAFLD-HCC (23.5 months). Conclusion: There is a rise in the number of HCC cases in patients with NAFLD, and this has significant implications for hepatologists as they are presented with more advanced diseases and have poorer outcomes. Future studies on HCC will need to identify this group earlier in order to have an impact on the HCC survival rate.
Publisher: Wiley
Date: 02-2023
DOI: 10.1111/IMJ.16010
Publisher: Wiley
Date: 10-05-2019
DOI: 10.1111/APT.15276
Publisher: MDPI AG
Date: 21-12-2023
DOI: 10.3390/CURRONCOL30010005
Abstract: Emerging evidence indicates an association between non-alcoholic fatty liver disease (NAFLD), cancer development and mortality. Cancer treatment-induced metabolic and hepatic dysfunction may be associated with increased rates of NAFLD. The review aims to investigate current evidence surrounding NAFLD in adults (≥18 years) with cancer including prevalence, effect of cancer treatments, metabolic co-morbidities, and mortality. Embase, Scopus, PubMed, and CINAHL were searched from inception to December 2021 including randomized controlled trials and observational studies. Twenty-three articles were included, comprising 142,218 participants. The overall risk of bias for observational studies was determined as low for 10 studies and neutral for 12 studies, and the RCT was determined as some concerns. The prevalence of NAFLD, based on imaging or histology, in adults with cancer ranged from 0.5 to 81.3%, with higher prevalence in breast, colorectal and gynecological cancers. Higher rates of NAFLD were also seen in patients who (i) underwent treatments—including chemotherapy and hormone therapy and/or who (ii) had higher BMI or other metabolic co-morbidities. NAFLD was associated with an increase in all-cause and cancer-related mortality. Based on review results, it is recommended that further assessment is carried out to determine whether liver screening in high-risk patients is cost effective and if interventions can be implemented to improve hepatic and health outcomes in adults with cancer.
Publisher: Wiley
Date: 28-12-2020
DOI: 10.1111/JGH.14924
Abstract: The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and in some parts of the world appears to be increasing. The aim of this study was to determine the 2013 prevalence of PBC in Victoria, Australia, and to determine the time trend by comparing it with previous studies undertaken in 1991 and 2002. Four case-finding methods were used to identify cases of PBC in Victoria: (1) physicians' survey (2) tertiary hospital search (3) liver transplant database search and (4) private pathology antimitochondrial antibody search. The prevalence of PBC in Victoria, Australia, is 189.0 per million using all four methods. The average annual increase in prevalence from 1991 to 2013 was 7.7 per million per year. Using the same case-finding methods as the 1991 Victorian prevalence study (methods 1 and 2), the prevalence of PBC increased from 19.1 per million in 1991 to 49.4 per million in 2002 (P < 0.001) and to 80.7 per million in 2013 (P < 0.001). The current prevalence of PBC in Victoria is significantly higher than previously reported. The use of private pathology-based case-finding methods is important in identifying the maximum number of PBC cases.
Publisher: Informa UK Limited
Date: 23-01-2015
DOI: 10.3109/00365521.2014.953572
Abstract: It remains unclear whether radiofrequency ablation (RFA) provides comparable outcomes to surgical resection (SR). We, therefore, compared survival outcomes of RFA to SR in patients with early stage and very early stage hepatocellular carcinoma (HCC). A multicenter retrospective analysis was performed in patients from five academic hospitals with Barcelona Cancer of the Liver Clinic (BCLC) stages 0-A HCC having RFA or SR as primary therapy. From 2000-2010, 146 patients who received treatment with RFA (n = 96) or SR (n = 52) were identified. In BCLC A patients with ≤5 cm HCC, there was a trend of lower overall survival after RFA compared with SR (3- and 5-year survival: 62% and 37% vs. 66% and 62% respectively p = 0.11). By multivariate analysis, RFA was an independent predictor of poor survival (hazard ratio = 2.26 95% confidence interval: 1.02-5.03 p = 0.04). In ≤3 cm HCC (n = 109), the 3- and 5-year survivals in RFA and SR groups were 66% and 39%, and 69% and 59%, respectively, with no difference in the median survival (p = 0.41). Local recurrence was significantly higher after RFA compared to SR in HCC ≤5 cm (p = 0.006) with a trend of lower recurrence-free survival (p = 0.06) after RFA in HCC ≤3 cm. There were fewer major complications after RFA (2% vs. 8%). While SR is superior to RFA for the management of early stage BCLC A disease with ≤5 cm HCC, both appear effective as first-line treatment options for Western patients with small ≤3 cm tumors. Although safer than SR, RFA is associated with higher rates of tumor recurrence and local disease progression. Further prospective randomized controlled trials are warranted to compare these two modalities.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2016
Publisher: Informa UK Limited
Date: 10-05-2016
DOI: 10.3109/00365521.2016.1166518
Abstract: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
Publisher: Wiley
Date: 21-06-2016
Abstract: The accuracy of Acoustic Radiation Force Impulse (ARFI) imaging has been validated in the setting of hepatitis C, however, the accuracy in the setting of fatty liver disease (FLD) has been less well-established. The aim of this study was to assess the accuracy of ARFI in the setting of hepatic steatosis. Patients with biopsy proven or sonographically diagnosed liver steatosis were assessed for ARFI trends including: inter-operator concordance, interquartile range, ARFI failure rate, relationship between ARFI velocity and steatosis severity, and concordance between biopsy and ARFI fibrosis scores. Three hundred and forty-nine patients were assessed (53 'biopsy' cohort and 296 'ultrasound' cohort), with 28 patients having biopsy on the same day as ARFI. Low stages of fibrosis (F0/1) were over-estimated by ARFI in 62% of cases with biopsy correlation (n = 16, P < 0.001), with ARFI offering increased accuracy in regard to higher-stage fibrosis (14/15 cases, 93%). In both the biopsy and ultrasound cohorts the failure rate and median inter-quartile range increased with increasing steatosis, and the inter-operator concordance remained good across all liver steatosis severities. In the setting of steatosis, ARFI is very sensitive in detecting, and accurate in diagnosing, higher stages of fibrosis regardless of steatosis severity. It tends to overestimate the fibrosis category in lower stages of fibrosis. The present study does not show conclusively if the presence of steatosis or its severity independently alters ARFI measurements.
Publisher: Wiley
Date: 05-2013
DOI: 10.1111/IMJ.12068
Abstract: Chronic hepatitis B (HBV) and cirrhosis are major risk factors for hepatocellular carcinoma (HCC). The proportion and characteristics of cases with cirrhosis are not well documented. Our aim was to compare demographic, viral and tumour characteristics of HBV-associated HCC in an Australian cohort, in patients with and without cirrhosis. Existing HCC databases at six Melbourne teaching hospitals were reviewed for cases associated with HBV. Patient demographics, HBV viral characteristics, presence of cirrhosis, serum alpha-fetoprotein and tumour size were assessed. Mode of diagnosis was recorded through surveillance or symptoms, and treatment was either palliative, percutaneous or surgical. We identified 197 cases of HBV-related HCC. The mean age was 57.9 ± 12.9 years 83% were male, and 55.3% and 35.3% were of Asian and European descent respectively. Of 168 patient with available data, 146 (87%) had cirrhosis versus 22 (13%) without. Patients with cirrhosis tended to be older (median 60 vs 52 years, P = 0.078). Asian patients were more likely to have HCC without cirrhosis than Europeans (17% vs 6%, P = 0.04). There were no other differences identified between cirrhotic and non-cirrhotic patients. Thirty-four per cent of patients had tumours greater than 5 cm at diagnosis, and 47% were diagnosed after presenting with symptoms. Twelve patients with HBV-HCC were outside current screening guidelines. Most patients in Melbourne with HBV-associated HCC have cirrhosis. HCC characteristics in non-cirrhotic and cirrhotic patients were similar. The large number of patients detected through symptoms and with large tumours reinforces the need for vigilance in screening.
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: 14-08-2019
DOI: 10.1111/APT.15426
Publisher: Wiley
Date: 29-03-2011
DOI: 10.1111/J.1440-0960.2011.00747.X
Abstract: A 35-year-old woman presented with skin fragility and photosensitivity with blisters affecting her face and hands. Other symptoms included intermittent headache, fatigue, abdominal pain and nausea. Porphyrin studies were markedly raised, with features consistent with hereditary coproporphyria (HCP). Despite strict precautions, symptoms remained significantly problematic. Regular haem arginate infusions of 3 mg/kg per day over 4 days on a monthly basis were commenced and resulted in significant improvement of the patient's symptoms and a reduction in urinary porphobilinogen. Although haem arginate infusion is known as a treatment for severe acute attacks of HCP, the effectiveness of regular infusions as maintenance therapy has not been established. This is the first report of effective symptom control correlating with normalization of biochemical markers in a patient receiving regular haem arginate infusions for the treatment of HCP.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-03-2009
DOI: 10.1002/HEP.22972
Publisher: Wiley
Date: 22-12-2016
DOI: 10.1111/LIV.13331
Abstract: Multidrug-resistant HBV continues to be an important clinical problem. The TDF-109 study demonstrated that TDF±LAM is an effective salvage therapy through 96 weeks for LAM-resistant patients who previously failed ADV add-on or switch therapy. We evaluated the 5-year efficacy and safety outcomes in patients receiving long-term TDF±LAM in the TDF-109 study. A total of 59 patients completed the first phase of the TDF-109 study and 54/59 were rolled over into a long-term prospective open-label study of TDF±LAM 300 mg daily. Results are reported at the end of year 5 of treatment. At year 5, 75% (45/59) had achieved viral suppression by intent-to-treat analysis. Per-protocol assessment revealed 83% (45/54) were HBV DNA undetectable. Nine patients remained HBV DNA detectable, however 8/9 had very low HBV DNA levels (<264IU/mL) and did not meet virological criteria for virological breakthrough (VBT). One patient experienced VBT, but this was in the setting of documented non-compliance. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. Four patients discontinued TDF, one patient was lost to follow-up and one died from hepatocellular carcinoma. Long-term TDF treatment appears to be safe and effective in patients with prior failure of LAM and a suboptimal response to ADV therapy. These findings confirm that TDF has a high genetic barrier to resistance is active against multidrug-resistant HBV, and should be the preferred oral anti-HBV agent in CHB patients who fail treatment with LAM and ADV.
Publisher: Wiley
Date: 24-03-2017
DOI: 10.1111/JGH.13621
Publisher: Elsevier BV
Date: 07-2015
Publisher: Wiley
Date: 13-02-2019
DOI: 10.1111/APT.15168
Abstract: Volatile anaesthetics are known to cause drug-induced liver injury, a hepatotoxic reaction characterised by antibodies to trifluoroacetylated lipid and protein adducts and cytochrome p450 2E1. The incidence of volatile anaesthetic drug-induced liver injury from older agents has been described, but modern agents have not been prospectively studied. To determine prospectively the incidence of volatile anaesthetic drug-induced liver injury from sevoflurane and desflurane. Adult surgical patients with a predicted post-operative stay of at least 4 days were recruited. If volatile anaesthetic was administered, liver biochemistry was performed regularly. Medications, observations and other investigations were documented. Patients with abnormal liver biochemistry were classified as likely volatile anaesthetic drug-induced liver injury or not based on clinical assessment, Roussel Uclaf Causality Assessment Method score, and the absence of other likely pathology. Some patients were also tested for antibodies to both trifluoroacetylated lipid and protein adducts, and cytochrome p450 2E1. A total of 209 patients were recruited, of which 121 were included for analysis. Post-operative liver biochemistry was abnormal in 62 patients (51.2%) further classified as not volatile anaesthetic drug-induced liver injury in 47 cases (38.8%), and likely volatile anaesthetic-drug induced liver injury in 15 cases (12.4%). Of the likely volatile anaesthetic drug-induced liver injury patients, only one had severe disease with alanine transaminase greater than five times the upper limit of normal, while four cases had moderate disease with alanine transaminase greater than three times the upper limit of normal. Thus, the incidence of clinically significant volatile anaesthetic drug-induced liver injury was 4.1%. No risk factors were identified. Volatile anaesthetic drug-induced liver injury from modern agents seems to be as common (4.1%) as previously reported with older agents (3%), and may identify patients at risk of severe acute liver injury with subsequent re-exposure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-02-2016
DOI: 10.1002/HEP.28267
Abstract: Hepatocellular carcinoma (HCC) incidence is rising rapidly in many developed countries. Primary epidemiological data have invariably been derived from cancer registries that are heterogeneous in data quality and registration methodology many registries have not adopted current clinical diagnostic criteria for HCC and still rely on histology for classification. We performed the first population‐based study in Australia using current diagnostic criteria, hypothesizing that HCC incidence may be higher than reported. Incident cases of HCC (defined by American Association for the Study of Liver Diseases diagnostic criteria or histology) were prospectively identified over a 12‐month period (2012‐2013) from the population of Melbourne, Australia. Cases were captured from multiple sources: admissions to any of Melbourne's seven tertiary hospitals attendances at outpatients and radiology, pathology, and pharmacy services. Our cohort was compared to the Victorian Cancer Registry (VCR) cohort (mandatory notified cases) for the same population and period, and incidence rates were compared for both cohorts. There were 272 incident cases (79% male median age: 65 years) identified. Cirrhosis was present in 83% of patients, with hepatitis C virus infection (41%), alcohol (39%), and hepatitis B virus infection (22%) the commonest etiologies present. Age‐standardized HCC incidence (per 100,000, Australian Standard Population) was 10.3 (95% confidence interval [CI]: 9.0‐11.7) for males and 2.3 (95% CI: 1.8 to 3.0) for females. The VCR reported significantly lower rates of HCC: 5.3 (95% CI: 4.4 to 6.4) and 1.0 (95% CI: 0.7 to 1.5) per 100,000 males and females respectively ( P 0.0001). Conclusions: HCC incidence in Melbourne is 2‐fold higher than reported by cancer registry data owing to under‐reporting of clinical diagnoses. Adoption of current diagnostic criteria and additional capture sources will improve registry completeness. Chronic viral hepatitis and alcohol remain leading causes of cirrhosis and HCC. (H epatology 2016 :1205–1212)
Publisher: BMJ
Date: 29-10-2010
Abstract: To determine the efficacy of tenofovir disoproxil fumarate (TDF) in adults with chronic hepatitis B virus (HBV) infection who had previously failed lamivudine (LAM) and had significant viral replication (HBV DNA >10⁵ copies/ml if HBeAg positive, > 10⁴ copies/ml if HBeAg negative) despite at least 24 weeks of treatment with adefovir dipivoxil (ADV). A prospective open-label study of TDF 300 mg daily. Patients receiving combination ADV/LAM prior to baseline were switched to TDF/LAM. Multiple tertiary referral centres. Sixty patients were enrolled. The median age was 48.5 years (range 21e80), 46 (77%) were male and 40 (67%) were HBeAg positive. Thirty-eight patients (63%) were switched from ADV to TDF, the remainder from ADV/LAM to TDF/LAM. At baseline, substitutions conferring resistance to LAM or ADV were present in 20 patients (33%) and 17 patients (28%), respectively. The median baseline viral load was 5.33 log₁₀ IU/ml (range 2.81-8.04). Patients initially treated with TDF monotherapy with persistent viral replication at or after 24 weeks were switched to TDF/LAM. The main outcome measures were change in HBV viral load from baseline and percentage of patients achieving an undetectable viral load (<15 IU/ml). Results are reported at 96 weeks of treatment. One patient discontinued TDF at 10 days due to rash. The time-weighted change in viral load from baseline to week 12 was -2.19 log10 IU/ml overall. The median change in HBV DNA from baseline to weeks 12, 24, 48 and 96 was -2.86, -3.23, -3.75 and -4.03 log₁₀ IU/ml, respectively. At 48 and 96 weeks, 27/59 (46%) and 38/59 (64%) patients achieved a HBV DNA <15 IU/ml. The response was independent of baseline LAM therapy or mutations conferring ADV resistance. In heavily pretreated patients with a high rate of genotypic resistance, TDF retains significant activity against HBV although this appears diminished in comparison with studies of naïve patients.
Publisher: BMJ
Date: 26-02-2013
Publisher: BMJ
Date: 08-2015
Publisher: Elsevier BV
Date: 12-2017
Start Date: 2004
End Date: 2007
Funder: National Institutes of Health
View Funded ActivityStart Date: 2002
End Date: 2004
Funder: University of Melbourne
View Funded ActivityStart Date: 1995
End Date: 1998
Funder: Gastroenterological Society of Australia
View Funded Activity