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| 1 | Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist显示文摘AIM To investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist.METHODS Cirrhotics listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios(IRR). RESULTS Of 587 cirrhotics, 64% were male, median age(interquartile range) was 60(53-64) years and MELD score was 15(12-18). Median Fried Frailty Index was 2(1-3); 31.6% were classified as frail(fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1hospitalisation; 38% of which involved major infection.107/184(58%) frail and 142/399(36%) non-frail patients were hospitalised at least once(P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year(IRR = 1.51,95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender(IRR for frailty of 1.21,95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty.CONCLUSION In cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity. | Marie Sinclair Eduard Poltavskiy Jennifer L Dodge Jennifer C Lai | 2017 | World Journal of Gastroenterology2017，23，5： | 11 |
| 2 | Malnutrition in cirrhosis:More food for thought显示文摘Malnutrition is highly prevalent in liver cirrhosis and its presence carries important prognostic implications.The clinical conditions and pathophysiological mechanisms that cause malnutrition in cirrhosis are multiple and interrelated.Anorexia and liver decompensation symptoms lead to poor dietary intake;metabolic changes characterised by elevated energy expenditure,reduced glycogen storage,an accelerated starvation response and protein catabolism result in muscle and fat wasting;and,malabsorption renders the cirrhotic patient unable to fully absorb or utilise food that has been consumed.Malnutrition is therefore a considerable challenge to manage effectively,particularly as liver disease progresses.A high energy,high protein diet is recognised as standard of care,yet patients struggle to follow this recommendation and there is limited evidence to guide malnutrition interventions in cirrhosis and liver transplantation.In this review,we seek to detail the factors which contribute to poor nutritional status in liver disease,and highlight complexities far greater than“poor appetite”or“reduced oral intake”leading to malnutrition.We also discuss management strategies to optimise nutritional status in this patient group,which target the inter-related mechanisms unique to advanced liver disease.Finally,future research requirements are suggested,to develop effective treatments for one of the most common and debilitating complications afflicting cirrhotic patients. | Brooke Chapman Marie Sinclair Paul J Gow Adam G Testro | 2020 | World Journal of Hepatology2020，12，11： | 8 |
| 3 | Epidemiology and outcomes of acute liver failure in Australia显示文摘BACKGROUND Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988- 2001. RESULTS Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF. | Penelope Hey Timothy P Hanrahan Marie Sinclair Adam G Testro Peter W Angus Adam Peterson Stephen Warrillow Rinaldo Bellomo Marcos V Perini Graham Starkey Robert M Jones Michael Fink Tess McClure Paul Gow | 2019 | World Journal of Hepatology2019，11，7： | 1 |
| 4 | Dropout Prevention for Youth with Disabil- ities : Efficacy of a Sustained School Engagement Procedure 显示文摘 | Sinclair Mary F | 1998 | Exceptional Children1998，65，1： | 1 |
| 5 | SIRT1 mRNA Expression May Be Associated With Energy Expenditure and Insulin Sensitivity显示文摘 | Rutanen Jarno Yaluri Nagendra Modi Shalem Pihlajam?ki Jussi V?nttinen Markku Itkonen Paula Kainulainen Sakari Yamamoto Hiroyasu Lagouge Marie Sinclair David A Elliott Peter Westphal Christoph Auwerx Johan Laakso Markku | 2010 | Diabetes2010，，4： | 1 |
| 6 | Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations显示文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in people with diabetes with no available treatment.AIM To explore the effect of testosterone treatment on liver.Testosterone therapy improves insulin resistance and reduces total body fat,but its impact on the liver remains poorly studied.METHODS This secondary analysis of a 40 wk,randomised,double-blinded,placebocontrolled trial of intramuscular testosterone undecanoate in men with type 2 diabetes and lowered serum testosterone concentrations evaluated the change in hepatic steatosis as measured by liver fat fraction on magnetic resonance imaging(MRI).RESULTS Of 88 patients enrolled in the index study,39 had liver MRIs of whom 20 received testosterone therapy and 19 received placebo.All patients had>5%hepatic steatosis at baseline and 38 of 39 patients met diagnostic criteria for NAFLD.Median liver fat at baseline was 15.0%(IQR 11.5%-21.1%)in the testosterone and 18.4%(15.0%-28.9%)in the placebo group.Median ALT was 34units/L(26-38)in the testosterone and 32units/L(25-52)in the placebo group.At week 40,patients receiving testosterone had a median reduction in absolute liver fat of 3.5%(IQR 2.9%-6.4%)compared with an increase of 1.2%in the placebo arm(between-group difference 4.7%P<0.001).After controlling for baseline liver fat,testosterone therapy was associated with a relative reduction in liver fat of 38.3%(95%confidence interval 25.4%-49.0%,P<0.001).CONCLUSION Testosterone therapy was associated with a reduction in hepatic steatosis in men with diabetes and low serum testosterone.Future randomised studies of testosterone therapy in men with NAFLD focusing on liver-related endpoints are therefore justified. | Ross Apostolov Emily Gianatti Darren Wong Numan Kutaiba Paul Gow Mathis Grossmann Marie Sinclair | 2022 | World Journal of Hepatology2022，14，4： | 0 |
| 7 | Women on the liver transplantation waitlist are at increased risk of hospitalization compared to men显示文摘BACKGROUND Hospital admissions are common among patients with cirrhosis,but patient factors associated with hospitalization have not been well characterized.Given recent data suggesting increased liver transplant waitlist dropout among women,we hypothesized that women on the liver transplant waitlist would have increased rates of hospitalization compared with men.AIM To evaluate the role of gender on risk of hospitalization for patients on the liver transplant waitlist,in order to help explain gender disparities in waitlist outcomes.METHODS Patients listed for liver transplant at a single center in the United States were prospectively enrolled in the Functional Assessment in Liver Transplantation Study.Patients included in this retrospective analysis included those enrolled between March 2012 and December 2014 with at least 12 mo of follow up and without hepatocellular carcinoma.The primary and secondary outcomes were hospitalization and total inpatient days within 12 mo,respectively.Logistic and negative binomial regression associated baseline factors with outcomes.RESULTS Of the 392 patients,41%were female,with median(interquartile range)age 58 years(52-63)and model for end-stage liver disease 18(15-22).Within 12 mo,186(47%)patients were hospitalized≥1 time;48%were readmitted,with a median of 8(4-15)inpatient days.More women than men were hospitalized(54%vs 43%;P=0.03).In univariable analysis,female sex was associated with an increased risk of hospitalization[odds ratios(OR)1.6,95%confidence interval(CI)1.0-2.4;P=0.03],which remained significant on adjusted multivariable analysis(OR 1.6,95%CI:1.1-2.6;P=0.03).Female gender was also associated with an increased number of inpatient days within 12 mo in both univariable and multivariable regression.CONCLUSION Women with cirrhosis on the liver transplant waitlist have more hospitalizations and inpatient days in one year compared with men,suggesting that the experience of cirrhosis differs between men and women,despite similar baseline illness severity.Future studies should explore gender-specific vulnerabilities to help explain waitlist disparities. | Jessica B Rubin Marie Sinclair Robert S Rahimi Elliot B Tapper Jennifer C Lai | 2019 | World Journal of Gastroenterology2019，25，8： | 0 |
| 8 | Clinical outcomes of patients with two small hepatocellular carcinomas显示文摘BACKGROUND Management of single small hepatocellular carcinoma(HCC)is straightforward with curative outcomes achieved by locoregional therapy or resection.Liver transplantation is often considered for multiple small or single large HCC.Management of two small HCC whether presenting synchronously or sequentially is less clear.AIM To define the outcomes of patients presenting with two small HCC.METHODS Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC≤3 cm between January 2000 and March 2018.Primary outcomes were overall survival(OS)and transplant-free survival(TFS).RESULTS 104 patients were identified(male n=89).Median age was 63 years(interquartile range 58-67.75)and the most common aetiology of liver disease was hepatitis C(40.4%).59(56.7%)had synchronous HCC and 45(43.3%)had sequential.36 patients died(34.6%)and 25 were transplanted(24.0%).1,3 and 5-year OS was 93.0%,66.1% and 62.3% and 5-year post-transplant survival was 95.8%.1,3 and 5-year TFS was 82.1%,45.85% and 37.8%.When synchronous and sequential groups were compared,OS(1,3 and 5 year synchronous 91.3%,63.8%,61.1%,sequential 95.3%,69.5%,64.6%,P=0.41)was similar but TFS was higher in the sequential group(1,3 and 5 year synchronous 68.5%,37.3% and 29.7%,sequential 93.2%,56.6%,48.5%,P=0.02)though this difference did not remain during multivariate analysis.CONCLUSION TFS in patients presenting with two HCC≤3 cm is poor regardless of the timing of the second tumor.All patients presenting with two small HCC should be considered for transplantation. | Anh Duy Pham Karl Vaz Zaid S Ardalan Marie Sinclair Ross Apostolov Sarah Gardner Ammar Majeed Gauri Mishra Ning Mao Kam Kurvi Patwala Numan Kutaiba Niranjan Arachchi Sally Bell Anouk T Dev John S Lubel Amanda J Nicoll Siddharth Sood William Kemp Stuart K Roberts Michael Fink Adam G Testro Peter W Angus Paul J Gow | 2021 | World Journal of Hepatology2021，13，10： | 0 |
| 9 | Reduced upper limb lean mass on dual energy X-ray absorptiometry predicts adverse outcomes in male liver transplant recipients显示文摘BACKGROUND Pre-transplant muscle wasting measured by computed tomography has been associated with adverse clinical outcomes after liver transplantation including increased rates of sepsis and hospitalisation days.Upper limb lean mass(LM)measured by dual-energy X-ray absorptiometry(DEXA)was recently identified as a novel predictor of sarcopenia-associated mortality in men waitlisted for transplantation.AIM To investigate the use of DEXA LM in predicting gender-stratified early posttransplant outcomes.METHODS Liver transplant recipients who underwent pre-transplant DEXA body composition imaging between 2002 and 2017 were included.Endpoints included posttransplant mortality and graft failure,bacterial infections,acute cellular rejection(ACR)and intensive care and total hospital length of stay.RESULTS Four hundred and sixty-nine patients met inclusion criteria of which 338 were male(72%).Median age was 55.0 years(interquartile range 47.4,59.7)and model for end-stage liver disease(MELD)score 16.Median time from assessment to transplantation was 7 mo(3.5,12).Upper limb LM was inversely associated with bacterial infections at 180 d post-transplant(hazard ratio=0.42;95%confidence interval:0.20-0.89;P=0.024)in males only.There was a negative correlation between upper limb LM and intensive care(τb=-0.090,P=0.015)and total hospital length of stay(τb=-0.10,P=0.0078)in men.In women,neither MELD nor body composition parameters were associated with post-transplant adverse outcomes or increased length of stay.Body composition parameters,MELD and age were not associated with 90-d mortality or graft failure in either gender.There were no significant predictors of early ACR.CONCLUSION Sarcopenia is an independent and potentially modifiable predictor of increased post-transplant bacterial infections and hospital length of stay in men with cirrhosis.DEXA upper limb LM provides a novel measure of muscle wasting that has prognostic value in this cohort.The lack of association in women requires further investigation. | Penelope Hey Rudolf Hoermann Paul Gow Timothy P Hanrahan Adam G Testro Ross Apostolov Marie Sinclair | 2022 | World Journal of Transplantation2022，12，6： | 0 |
| 10 | Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients显示文摘BACKGROUND While clinical guidelines recommend hepatocellular carcinoma(HCC)surveillance for at-risk individuals,reported surveillance rates in the United States and Europe remain disappointingly low.AIM To quantify HCC surveillance in an Australian cohort,and assess for factors associated with surveillance underutilisation.METHODS All patients undergoing HCC surveillance liver ultrasounds between January 1,2018 to June 30,2018 at a tertiary hospital in Melbourne,Australia,were followed until July 31,2020,or when surveillance was no longer required.The primary outcome was the percentage of time up-to-date with HCC surveillance(PTUDS).Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation.RESULTS Among 775 at-risk patients followed up for a median of 27.5 months,the median PTUDS was 84.2%(IQR:66.3%-96.3%).85.0%of patients were followed up by specialist gastroenterologists.Amongst those receiving specialist care,quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors.Older age at the 25th quantile(estimate 0.002 per percent,P=0.03),and cirrhotic status at the 75th quantile(estimate 0.021,P=0.017),were significantly associated with greater percentage of time up-to-date.African ethnicity(estimate-0.089,P=0.048)and a culturally and linguistically diverse(CALD)background(estimate-0.063,P=0.01)were significantly associated with lower PTUDS at the 50th quantile,and again for CALD at the 75th quantile(estimate-0.026,P=0.045).CONCLUSION While median PTUDS in this Australian cohort study was 84.2%,awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance. | Elizabeth SL Low Ross Apostolov Darren Wong Sandra Lin Numan Kutaiba Josephine A Grace Marie Sinclair | 2021 | World Journal of Gastrointestinal Oncology2021，13，12： | 0 |
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