Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableEndoscopic features of buried Barrett's mucosa: visible to the trained eye?(Wiley, 2019-12-01)
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ItemFive-year efficacy and safety of tenofovir-based salvage therapy for patients with chronic hepatitis B who previously failed LAM/ADV therapy(WILEY, 2017-06)BACKGROUND: 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. METHODS: 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: 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. CONCLUSIONS: 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.
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ItemNovel Population-Based Study Finding Higher Than Reported Hepatocellular Carcinoma Incidence Suggests an Updated Approach Is Needed(WILEY, 2016-04)UNLABELLED: 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.
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Item"B in IT" - a community-based model for the management of hepatitis B patients in primary care clinics using a novel web-based clinical tool.(Springer Science and Business Media LLC, 2018)BACKGROUND: The current model of care for the treatment of chronic hepatitis B (CHB) in Australia is through specialist Hepatology or Infectious Diseases clinics, and limited accredited primary care practices. Capacity is limited, and less than 5% of Australians living with CHB currently access therapy. Increasing treatment uptake is an urgent area of clinical need. Nucleos(t)ide analogue therapy is safe and effective treatment for CHB that is suitable for community prescribing. We have evaluated the success of a community-based model for the management of CHB in primary care clinics using a novel web-based clinical tool. METHODS: Using guidelines set out by the Gastroenterological Society of Australia, we developed an interactive online clinical management tool for the shared care of patients with CHB in primary care clinics, with remote oversight from tertiary hospital-based hepatologists and a project officer. We call this model of care the "B in IT" program. Suitable patients were referred from the specialist liver clinic back to primary care for ongoing management. Compliance with recommended appointments, pathology tests and ultrasounds of patients enrolled in "B in IT" was assessed and compared to that of the same patients prior to community discharge, as well as a matched control group of CHB outpatients continuing to attend a specialist clinic. RESULTS: Thirty patients with CHB were enrolled in the "B in IT" program. Compliance with attending scheduled appointments within 1 month of the suggested date was 87% across all 115 visits scheduled. Compliance with completing recommended pathology within 1 month of the suggested date was 94% and compliance with completing recommended liver ultrasounds for cancer screening within 1 month of the suggested date was 89%. The compliance rates for visit attendance and ultrasound completion were significantly higher than the control patient group (p < 0.0001) and the "B in IT" patients prior to community discharge (p = 0.002 and p = 0.039, respectively). CONCLUSIONS: The "B in IT" program's novel web-based clinical tool supports primary care physicians to treat and monitor patients with CHB. This program promotes community-based care and increases system capacity for the clinical care of people living with CHB.
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ItemNo Preview AvailableRecurrent intestinal metaplasia at the gastroesophageal junction following endoscopic eradication of dysplastic Barrett's esophagus may not be benign(GEORG THIEME VERLAG KG, 2016-08)BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) combined with endoscopic mucosal resection (EMR) is effective for eradicating dysplastic Barrett's esophagus. The durability of response is reported to be variable. We aimed to determine the effectiveness and durability of RFA with or without EMR for patients with dysplastic Barrett's esophagus. PATIENTS AND METHODS: Patients with dysplastic Barrett's esophagus referred to two academic hospitals were assessed with high definition white-light endoscopy, narrow-band imaging, and Seattle protocol biopsies. EMR was performed in visible lesions. RFA was performed at 3-month intervals until complete remission of dysplasia (CR-D) and intestinal metaplasia (CR-IM) was achieved. RESULTS: In total, 137 patients received RFA (78 with EMR); 75 with over 12 months follow-up since commencing RFA. Pretreatment histology was intramucosal cancer (IMC) 21 %, high grade dysplasia (HGD) 54 %, low grade dysplasia (LGD) 25 %. CR-D rates were 88 %, 92 %, and 100 % at 1, 2, and 3 years; CR-IM rates were 69 %, 74 %, and 81 %. Kaplan-Meier analysis showed increasing probability of achieving CR-D/CR-IM over time. Of 26 patients maintaining CR-IM for > 12 months, five relapsed with intestinal metaplasia (19 %), and three with dysplasia (12 %). Recurrences occurred in patients with prior HGD/IMC, predominantly at the gastroesophageal junction (GEJ). None relapsed with cancer. Adverse events occurred in 4 % of RFA and 6.5 % of EMR procedures. CONCLUSIONS: RFA combined with EMR is effective in achieving CR-D/CR-IM in the majority of patients with dysplastic Barrett's esophagus, with an incremental response over time. While durable in the majority, recurrent intestinal metaplasia and dysplasia, frequently occurring at the GEJ, suggest long-term surveillance is warranted in high risk groups.
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ItemEfficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience(BAISHIDENG PUBLISHING GROUP INC, 2017-01-08)AIM: To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting. METHODS: We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent's Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time. RESULTS: Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of non-compliance. Tenofovir therapy was well tolerated. CONCLUSION: Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.
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ItemThe role of tumour necrosis factor in hepatitis B infection: Jekyll and Hyde(WILEY, 2016-12)Chronic hepatitis B (CHB) is a major health problem worldwide and is associated with significant long-term morbidity and mortality. The hepatitis B virus (HBV) is a hepatotropic virus that is capable of integrating in the host nucleus permanently resulting in lifelong infection. To date, there is no definitive cure for HBV, as our current treatments cannot eradicate the viral reservoir that has integrated in the liver. Elucidating the immunopathogenesis is key to finding a therapeutic target for HBV as the virus is not in itself cytopathic but the immune response to the virus causes the majority of the cellular injury. In most cases, the virus reaches a state of equilibrium with low viral replication constrained by host immunity. Multiple cytokines have been implicated in the pathogenesis of CHB. Tumor necrosis factor (TNF) has emerged as a key player; on one hand it can facilitate immune-mediated virological control but on the other hand it can cause collateral hepatocyte damage, cirrhosis and possibly promote hepatocellular carcinoma. In this review, we discuss the current understanding of the immunopathogenesis of HBV, focusing on TNF and whether it can be harnessed in therapeutic strategies to cure HBV infection.
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ItemSustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection(PUBLIC LIBRARY SCIENCE, 2017-10-24)BACKGROUND/AIMS: Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. METHODS: CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. RESULTS: 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p = 0.0001). SVR was independently associated with protection from liver fibrosis progression after adjustment for other variables including baseline ALT (p = 0.011), duration of HCV infection and mode of acquisition. CONCLUSION: HCV eradication is associated with lower rates of liver fibrosis progression. The data support early treatment to prevent long-term liver complications of HCV infection.
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ItemDiffuse endoscopically visible, predominantly low grade dysplasia in Barrett's esophagus (with video)(GEORG THIEME VERLAG KG, 2019-12)Background Low grade dysplasia (LGD) in Barrett's esophagus (BE) has generally been considered as undetectable endoscopically. Aim To describe a phenotype which consists of diffuse, endoscopically visible, predominantly low grade dysplasia in Barrett's esophagus (DEVLB), with often subtle but visible endoscopic changes seen with high definition white light (HDWL) and narrow-band imaging (NBI). Method A systematic search of a prospectively collected database for patients satisfying predefined criteria for DEVLB and a review of endoscopic and histological features of biopsies and endoscopic mucosal resection (EMR) specimens. Results Out of a total of 419 patients referred to our expert center for assessment of dysplastic Barrett's esophagus during the period January 2009 to March 2018, there were 7 patients (1.7 %) who satisfied the criteria defined for DEVLB, identified on their initial assessment endoscopy. All patients were treated by EMR of visible abnormal mucosa during their assessment endoscopy at our tertiary referral center. There was a total of 47 EMR specimens obtained, with a median of 6 (IQR 5-9) EMR resection pieces per patient, of which 36 (77 %) contained LGD, 8 (17 %) high grade dysplasia (HGD), 2 (4 %) non-dysplastic Barrett's esophagus (NDBE), and 1 (2 %) contained early esophageal adenocarcinoma (EAC). Conclusion DEVLB is a distinct phenotype seen in a small but significant proportion of individuals with dysplastic Barrett's esophagus. Patients with DEVLB have widespread LGD, with many having areas of focal HGD or early cancer within this area. We believe these patients are best treated with extensive EMR of the visibly abnormal area.
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Item'Teach-back' is a simple communication tool that improves disease knowledge in people with chronic hepatitis B - a pilot randomized controlled study(BMC, 2019-10-23)BACKGROUND: The low diagnosis rate and poor access to clinical care among people with CHB is a major barrier to reducing HBV-related morbidity and mortality in Australia. One explanation for this is a lack of disease-specific knowledge among people living with CHB. Health literacy has been shown to be important for maximising engagement with medical care and adherence to recommended management. The 'teach-back' communication strategy has been shown to improve patient understanding in other clinical areas. This study aims to assess disease-specific knowledge; and evaluate the efficacy of the teach-back strategy for improving HBV knowledge, compared to a standard medical consultation. METHOD: A randomized pilot study was conducted between February and June 2017. Participants were recruited from the liver clinic at an inner-city tertiary hospital. English-speaking patients aged ≥18 years and diagnosed with CHB were eligible for the study. Participants were randomised to a control group (medical specialist appointment) and intervention group (teach-back). Knowledge was assessed at baseline, immediately post-intervention and at one month using a validated questionnaire. Participants in the intervention group received a one-on-one teach-back session about CHB. The main outcome measure was a combined knowledge score of the domains assessed - transmission, natural history, epidemiology and prevention and clinical management. RESULTS: Seventy participants were recruited (control n = 32, teach-back n = 38). Mean baseline knowledge score was 19.1 out of 23 with 55 (79%) participants scoring ≥17.3 (defined as high knowledge) (7). Sub-analysis of CHB knowledge domains identified focal deficits concerning transmission and whether HBV is curable. Knowledge scores were found to be positively associated with English proficiency and antiviral treatment experience (p < 0.05). Teach-back was associated with a significant increase in CHB knowledge at early recall (22.5 vs 18.7, p < 0.001) and at 1-month follow-up (21.9 vs 18.7, p < 0.001); there was no improvement in CHB knowledge associated with standard clinical consultant (early recall: 19.6 vs 19.4, p = 0.49, one-month follow-up: 19.5 vs 19.4, p = 0.94). CONCLUSION: In a tertiary hospital liver clinic population, baseline knowledge about CHB was good, but there were focal deficits concerning transmission and potential for cure. Teach-back was associated with improvement in CHB knowledge and it is a simple communication tool suitable for incorporation into a standard medical consultation.