Surgery (Austin & Northern Health) - Research Publications
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ItemThe Hidden Epidemic: The Prevalence and Impact of Concurrent Liver Diseases in Patients Undergoing Liver Transplantation in Australia and New Zealand(LIPPINCOTT WILLIAMS & WILKINS, 2022-08)UNLABELLED: Prevalence of concurrent liver diseases among liver transplant recipients and impact on posttransplant outcomes are unknown. METHODS: This retrospective study included adult liver transplants between January 1' 1985' and December 31' 2019' from the Australian and New Zealand Liver and Intestinal Transplant Registry. Up to 4 liver disease causes were recorded for each transplant; concurrent liver diseases were defined as >1 liver disease indication for transplantation, excluding hepatocellular carcinoma. Impact on posttransplant survival was determined using Cox regression. RESULTS: A total of 840 (15%) of 5101 adult liver transplant recipients had concurrent liver diseases. Recipients with concurrent liver diseases were more likely male (78% versus 64%) and older (mean age 52 versus 50 y). A higher proportion of liver transplants for hepatitis B (12% versus 6%), hepatitis C (33% versus 20%), alcohol liver disease (23% versus 13%), and metabolic-associated fatty liver disease (11% versus 8%, all P < 0.001) were identified when all indications were included than with primary diagnosis only. The number and proportion of liver transplants performed for concurrent liver diseases have increased from 8 (6%) during Era 1 (1985-1989) to 302 (20%) during Era 7 (2015-2019; P < 0.001). Concurrent liver diseases were not associated with increased posttransplant mortality (adjusted hazard ratio, 0.98, 95% confidence interval, 0.84-1.14). CONCLUSIONS: Concurrent liver diseases are increasing among adult liver transplant recipients in Australia and New Zealand; however, they do not appear to impact posttransplant survival. Reporting all liver disease causes in the transplant registry reports provides more accurate estimates of liver disease burden.
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ItemNo Preview AvailableEpigenetic Silencing of RIPK3 in Hepatocytes Prevents MLKL -mediated Necroptosis From Contributing to Liver Pathologies(W B SAUNDERS CO-ELSEVIER INC, 2022-12)BACKGROUND & AIMS: Necroptosis is a highly inflammatory mode of cell death that has been implicated in causing hepatic injury including steatohepatitis/ nonalcoholic steatohepatitis (NASH); however, the evidence supporting these claims has been controversial. A comprehensive, fundamental understanding of cell death pathways involved in liver disease critically underpins rational strategies for therapeutic intervention. We sought to define the role and relevance of necroptosis in liver pathology. METHODS: Several animal models of human liver pathology, including diet-induced steatohepatitis in male mice and diverse infections in both male and female mice, were used to dissect the relevance of necroptosis in liver pathobiology. We applied necroptotic stimuli to primary mouse and human hepatocytes to measure their susceptibility to necroptosis. Paired liver biospecimens from patients with NASH, before and after intervention, were analyzed. DNA methylation sequencing was also performed to investigate the epigenetic regulation of RIPK3 expression in primary human and mouse hepatocytes. RESULTS: Identical infection kinetics and pathologic outcomes were observed in mice deficient in an essential necroptotic effector protein, MLKL, compared with control animals. Mice lacking MLKL were indistinguishable from wild-type mice when fed a high-fat diet to induce NASH. Under all conditions tested, we were unable to induce necroptosis in hepatocytes. We confirmed that a critical activator of necroptosis, RIPK3, was epigenetically silenced in mouse and human primary hepatocytes and rendered them unable to undergo necroptosis. CONCLUSIONS: We have provided compelling evidence that necroptosis is disabled in hepatocytes during homeostasis and in the pathologic conditions tested in this study.
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ItemAustralian recommendations for the management of hepatocellular carcinoma: a consensus statement(WILEY, 2021-06-06)Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths both globally and in Australia. Surveillance for HCC in at-risk populations allows diagnosis at an early stage, when potentially curable. However, most Australians diagnosed with HCC die of the cancer or of liver disease. In the changing landscape of HCC management, unique challenges may lead to clinical practice variation. As a result, there is a need to identify best practice management of HCC in an Australian context. This consensus statement has been developed for health professionals involved in the care of adult patients with HCC in Australia. It is applicable to specialists, general medical practitioners, nurses, health coordinators and hospital administrators.
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ItemTurning the Tide on Hepatitis C Virus-Related Liver Transplantation: The Return on Investment in Hepatitis C Virus Treatment in Australia and New Zealand(WILEY, 2022-02)Introduction of universal access to direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in Australia and New Zealand on March 1st , 2016, has had a major impact on the number of people with chronic HCV infection, but the impact on liver transplantation rates is unknown. We conducted a retrospective registry study including all adult liver transplantations from the Australia and New Zealand Liver and Intestinal Liver Transplant Registry (ANZLITR) data set. Interrupted time series analysis determined the impact of DAAs in 2016 on the number of HCV liver transplantations per year. Cox regression analysis was used to determine the impact of DAAs on post-liver transplantation survival. Between January 1, 1990, and December 31, 2019 5318 adult liver transplantations were performed, and 29% (1531) were for HCV infection. Prior to the introduction of DAAs, there was a mean increase of 3.5 adult liver transplantations performed for HCV per annum, but between 2016 and 2019 there was a mean decrease of 7.9 adult liver transplantations per annum (P < 0.001). Similarly, the proportion of liver transplantations performed for HCV increased from 9% (1990) to 33% in 2016 and then fell to 23% in 2019 (P < 0.001). The number and proportion of patients with HCV added to the liver transplantation waiting list also fell in 2016 (P < 0.001) when compared with other indications. The introduction of DAAs was associated with a 31% reduction in death after liver transplantation, adjusted for age at transplant and hepatocellular carcinoma (HCC; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.48-0.99; P = 0.047). The number of adult liver transplantations performed for HCV-related liver cirrhosis and HCC has reduced since the introduction of universal access to DAAs in 2016 in Australia and New Zealand.