Colorectal cancer screening participation in First Nations populations worldwide: a systematic review and data synthesis.

Background: First Nations populations have poorer colorectal cancer (CRC) survival compared to non-First Nations populations. Whilst First Nations populations across the world are distinct, shared experiences of discrimination and oppression contribute to persistent health inequities. CRC screening improves survival, however screening rates in First Nations populations are poorly described. This study seeks to define participation rates in CRC screening in First Nations populations worldwide. Methods: A systematic literature search was conducted of PubMed, Embase, Cochrane Library, CINAHL, MEDLINE, grey literature, national registries and ClinicalTrials.gov. All sources were searched from their inception date to 18 February 2024. Studies were included if they reported CRC screening rates in adult (≥18 years) First Nations populations. We aimed to undertake a meta-analysis if there were sufficient data. Quality of papers were assessed using the Joanna Briggs Institute (JBI) appraisal tool. The study was registered with PROSPERO, CRD42020210181. Findings: The literature search identified 1723 potentially eligible published studies. After review, 57 studies were included, 50 from the United States (US), with the remaining studies from Australia, Aotearoa New Zealand (NZ), Canada, Dominica and Guatemala. Additionally, eleven non-indexed reports from national programs in Australia and NZ were included. There were insufficient data to undertake meta-analysis, therefore a systematic review and narrative synthesis were conducted. CRC screening definitions varied, and included stool-based screening, sigmoidoscopy and colonoscopy. US First Nations screening rates ranged between 4.0 and 79.2%, Australia reported 10.6-35.2%, NZ 18.4-49%, Canada 22.4-53.4%, Guatemala 2.2% and Dominica 4.2%. Fifty-five studies were assessed as moderate or high quality and two as low quality. Interpretation: Our findings suggested that there is wide variation in CRC screening participation rates across First Nations populations. Screening data are lacking in direct comparator groups and longitudinal outcomes. Disaggregation of screening data are required to better understand and address First Nations CRC outcome inequities. Funding: None.

Joint association of drinking alcohol and obesity in relation to cancer risk: A systematic review and data synthesis.

BACKGROUND: Rates of alcohol consumption and obesity are increasing in many Western populations. For some cancer types, both heavy alcohol consumption and obesity are independently associated with increased risk. Whether combined exposure to both synergistically increases an individual's risk of cancer is unclear. We performed a systematic review to assess whether alcohol and obesity interact to confer higher risk for cancer than the additive sum of their effects. METHODS: A systematic literature search was conducted from the inception date to 13 February 2024 of PubMed, Embase, Cochrane Library and Web of Science to identify studies of alcohol, obesity, and cancer risk. We aimed to undertake a meta-analysis if there were sufficient data. RESULTS: The literature search identified 17,740 potentially eligible studies. After review, 24 studies were included. Eleven reported on the association between alcohol consumption and cancer risk in individuals according to their body mass index (BMI), nine reported on the association between BMI and cancer risk in individuals according to their alcohol consumption, and six studies examined potential synergistic interactions between alcohol consumption and obesity on cancer risk. However, there were insufficient data and significant heterogeneity in the cancers studied to undertake meta-analysis, therefore a systemic review and narrative synthesis was conducted. Overall, there was no consistent pattern of interaction between alcohol use and overweight/obesity on cancer risk across cancer types. CONCLUSIONS: While alcohol and obesity are prevalent and important risk factors for a range of cancers, data are lacking on whether their combined exposure may synergistically increase an individual's risk for cancer. Further study across more cancer types is required to better understand the nature of interactions between alcohol use and obesity on cancer risk.

Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress ß-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Hepatocellular and extrahepatic cancer risk in people with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Much of the recognised health-care burden occurs in the minority of people with NAFLD who progress towards cirrhosis and require specialist follow-up, including risk stratification and hepatocellular carcinoma surveillance. NAFLD is projected to become the leading global cause of cirrhosis and hepatocellular carcinoma, but the frequency of non-cirrhotic hepatocellular carcinoma provides a challenge to existing surveillance strategies. Deaths from extrahepatic cancers far exceed those from hepatocellular carcinoma in NAFLD. Unlike hepatocellular carcinoma, the increased extrahepatic cancer risk in NAFLD is not dependent on liver fibrosis stage. Given that almost 30% of the world's adult population has NAFLD, extrahepatic cancer could represent a substantial health and economic issue. In this Review, we discuss current knowledge and controversies regarding hepatocellular carcinoma risk stratification and surveillance practices in people with NAFLD. We also assess the associations of extrahepatic cancers with NAFLD and their relevance both in the clinic and the wider community.

Exercise in the Management of Metabolic-Associated Fatty Liver Disease (MAFLD) in Adults: A Position Statement from Exercise and Sport Science Australia.

Metabolic-associated fatty liver disease (MAFLD) is the most prevalent chronic liver disease worldwide, affecting 25% of people globally and up to 80% of people with obesity. MAFLD is characterised by fat accumulation in the liver (hepatic steatosis) with varying degrees of inflammation and fibrosis. MAFLD is strongly linked with cardiometabolic disease and lifestyle-related cancers, in addition to heightened liver-related morbidity and mortality. This position statement examines evidence for exercise in the management of MAFLD and describes the role of the exercise professional in the context of the multi-disciplinary care team. The purpose of these guidelines is to equip the exercise professional with a broad understanding of the pathophysiological underpinnings of MAFLD, how it is diagnosed and managed in clinical practice, and to provide evidence- and consensus-based recommendations for exercise therapy in MAFLD management. The majority of research evidence indicates that 150-240 min per week of at least moderate-intensity aerobic exercise can reduce hepatic steatosis by ~ 2-4% (absolute reduction), but as little as 135 min/week has been shown to be effective. While emerging evidence shows that high-intensity interval training (HIIT) approaches may provide comparable benefit on hepatic steatosis, there does not appear to be an intensity-dependent benefit, as long as the recommended exercise volume is achieved. This dose of exercise is likely to also reduce central adiposity, increase cardiorespiratory fitness and improve cardiometabolic health, irrespective of weight loss. Resistance training should be considered in addition to, and not instead of, aerobic exercise targets. The information in this statement is relevant and appropriate for people living with the condition historically termed non-alcoholic fatty liver disease (NAFLD), regardless of terminology.

High-Intensity Interval Training is Safe, Feasible and Efficacious in Nonalcoholic Steatohepatitis: A Randomized Controlled Trial.

BACKGROUND: High-Intensity Interval Training (HIIT) involves bursts of high-intensity exercise interspersed with lower-intensity exercise recovery. HIIT may benefit cardiometabolic health in people with nonalcoholic steatohepatitis (NASH). AIMS: We aimed to examine the safety, feasibility, and efficacy of 12-weeks of supervised HIIT compared with a sham-exercise control (CON) for improving aerobic fitness and peripheral insulin sensitivity in biopsy-proven NASH. METHODS: Participants based in the community [(n = 14, 56 ± 10 years, BMI 39.2 ± 6.7 kg/m2, 64% male), NAFLD Activity Score 5 (range 3-7)] were randomized to 12-weeks of supervised HIIT (n = 8, 4 × 4 min at 85-95% maximal heart rate, interspersed with 3 min active recovery; 3 days/week) or CON (n = 6, stretching; 3 days/week). Safety (adverse events) and feasibility determined as ≥ 70% program completion and ≥ 70% global adherence (including session attendance, interval intensity adherence, and duration adherence) were assessed. Changes in cardiorespiratory fitness (V̇O2peak), exercise capacity (time-on-test) and peripheral insulin sensitivity (euglycemic hyperinsulinemic clamp) were assessed. Data were analysed using ANCOVA with baseline value as the covariate. RESULTS: There were no HIIT-related adverse events and HIIT was globally feasible [program completion 75%, global adherence 100% (including adherence to session 95.4 ± 7.3%, interval intensity 95.3 ± 6.0% and duration 96.8 ± 2.4%)]. A large between-group effect was observed for exercise capacity [mean difference 134.2 s (95% CI 19.8, 248.6 s), ƞ2 0.44, p = 0.03], improving in HIIT (106.2 ± 97.5 s) but not CON (- 33.4 ± 43.3 s), and for peripheral insulin sensitivity [mean difference 3.4 mg/KgLegFFM/min (95% CI 0.9,6.8 mg/KgLegFFM/min), ƞ2 0.32, p = 0.046], improving in HIIT (1.0 ± 0.8 mg/KgLegFFM/min) but not CON (- 3.1 ± 1.2 mg/KgLegFFM/min). CONCLUSIONS: HIIT is safe, feasible and efficacious for improving exercise capacity and peripheral insulin sensitivity in people with NASH. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (anzctr.org.au) identifier ACTRN12616000305426 (09/03/2016).

Hepatocellular and extrahepatic cancers in non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND: Hepatocellular (HCC) and extrahepatic cancers have been associated with non-alcoholic fatty liver disease (NAFLD); however, the extent and nature of these relationships remain unclear. We aimed to estimate the absolute incidence rates of these cancers in adults with NAFLD with respect to key demographic and clinical factors. METHODS: We searched PubMed, Embase, Cochrane Library and Web of Science databases for studies reporting the incidence rates of any cancer in adults with NAFLD from inception to 31 August 2020. The main meta-analysis outcomes were pooled incidences of cancers in NAFLD using random-effects modelling. Subgroup analyses examined the effects of NAFLD disease stage. FINDINGS: In total, 64 studies were eligible for analysis of HCC and extrahepatic cancer incidence including 625,984 and 41,027 patients, respectively. The pooled HCC incidence rate was 1.25 per 1000 person-years (95% CI 1.01 to 1.49; I2 = 94.8%). In patients with NAFLD with advanced liver fibrosis or cirrhosis, the HCC incidence rate was 14.46 per 1000 person-years (95% CI 10.89 to 18.04; I2 = 91.3%). The pooled extrahepatic cancer incidence rate was 10.58 per 1000 person-years (95% CI 8.14 to 13.02; I2 = 97.1%). The most frequently occurring extrahepatic cancers were uterine, breast, prostate, colorectal, and lung. Extrahepatic cancer incidence rates were not higher in patients with NAFLD with advanced liver fibrosis or cirrhosis. INTERPRETATION: The rate of HCC development in patients with NAFLD who have progressed to advanced liver fibrosis or cirrhosis supports current HCC surveillance recommendations targeted for this group. Extrahepatic cancers are over eight-fold more frequent than HCC in NAFLD and not associated with liver fibrosis stage. As the global prevalence of NAFLD is approximately 25% and increasing, these findings support a focus on its prevention and the early detection of cancer in adults with NAFLD.

Expansion of Liver Transplantation Criteria for Hepatocellular Carcinoma from Milan to UCSF in Australia and New Zealand and Justification for Metroticket 2.0.

Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT within Milan versus UCSF criteria (to determine the true benefit of the expansion of criteria) and retrospectively validated the MT2 criteria. Methods: Retrospective analysis of ANZLITR (including all patients transplanted for HCC since July 1997). The entire cohort was divided based on criteria used at the time of listing, namely, Milan era (1997−2006) and the UCSF era (2007−July 2015). Results: The overall 5- and 10-year cumulative survival rates for the entire cohort of 691 patients were 78% and 69%, respectively. Patients transplanted in UCSF era had significantly higher 5- and 10-year survival rates than in the Milan era (80% vs. 73% and 72% vs. 65%, respectively; p = 0.016). In the UCSF era, the 5-year survival rate for patients transplanted within Milan criteria was significantly better than those transplanted outside Milan but within UCSF criteria (83% vs. 73%; p < 0.024). Patients transplanted within the MT2 criteria had a significantly better 5- and 10-year survival rate as compared to those outside the criteria (81% vs. 64% and 73% vs. 50%, respectively; p = 0.001). Conclusion: Overall survival following LT for HCC has significantly improved over time despite expanding criteria from Milan to UCSF. Patients fulfilling the MT2 criteria have a survival comparable to the UCSF cohort. Thus, expansion of criteria to MT2 is justifiable.

Duodenal bacterial load as determined by quantitative polymerase chain reaction in asymptomatic controls, functional gastrointestinal disorders and inflammatory bowel disease.

BACKGROUND: Small intestinal bacterial overgrowth may play a role in gastrointestinal and non-gastrointestinal diseases. AIMS: To use quantitative polymerase chain reaction (qPCR) to determine and compare bacterial loads of duodenal biopsies in asymptomatic controls, and patients with functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) including ulcerative colitis (UC) and Crohn's disease (CD). To define effects of gastric acid inhibition on bacterial load, explore links of bacterial load and gastrointestinal symptoms in response to a standardised nutrient challenge and compare bacterial load with glucose breath test results. METHODS: In 237 patients (63 controls, 84 FGID and 90 IBD), we collected mucosal samples under aseptic conditions during endoscopy extracted and total DNA. Bacterial load metric was calculated utilising qPCR measurements of the bacterial 16S rRNA gene, normalised to human beta-actin expression. Standard glucose breath test and nutrient challenge test were performed. RESULTS: The duodenal microbial load was higher in patients with FGID (0.22 ± 0.03) than controls (0.07 ± 0.05; P = 0.007) and patients with UC (0.01 ± 0.05) or CD (0.02 ± 0.09), (P = 0.0001). While patients treated with proton pump inhibitors (PPI) had significantly higher bacterial loads than non-users (P < 0.05), this did not explain differences between patient groups and controls. Bacterial load was significantly (r = 0.21, P < 0.016) associated with the symptom response to standardised nutrient challenge test. Methane, but not hydrogen values on glucose breath test were associated with bacterial load measured utilising qPCR. CONCLUSIONS: Utilising qPCR, a diagnosis of FGID and treatment with PPI were independently associated with increased bacterial loads. Increased bacterial loads are associated with an augmented symptom response to a standardised nutrient challenge.

Sex Differences in the Risk of Barrett's Esophagus Associated With the Metabolic Effects of Obesity.

GOAL: The goal of this study was to determine if there is an association between the insulin-insulin-like growth factor axis, the metabolic syndrome (MetS), type 2 diabetes mellitus and risk of Barrett's esophagus (BE), and if these associations are modified by sex. BACKGROUND: BE is more common in males. Gastroesophageal reflux disease, the major risk factor for BE occurs at similar frequencies in both sexes, suggesting that sex-related factors such as the metabolic effects of abdominal obesity may be important in the causation of BE. MATERIALS AND METHODS: A structured interview, anthropometric measures, and fasting blood were collected within a population-based case-control study. We recruited 227 BE cases (70% male) and 241 population controls, frequency matched by age and sex. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for association with BE using multivariable logistic regression models. RESULTS: Hyperinsulinemia (highest vs. lowest tertile, OR=1.9; 95% CI: 1.2-3.1), Homeostatic Model Assessment of Insulin Resistance (OR=1.9; 95% CI: 1.2-3.1) and the MetS (OR=1.8; 95% CI: 1.2-2.6) were independently associated with an increased risk of BE. With each additional MetS criterion, there was a 20% increased risk of BE (OR=1.2; 95% CI: 1.0-1.4). When stratified by sex, these associations were found in males but not females. We found no association with serum measures of insulin-like growth factors or interleukin-6 and risk of BE. CONCLUSION: Hyperinsulinemia, insulin resistance, and the MetS are associated with the risk of BE in males but not females, suggesting these factors may contribute to the higher prevalence of BE in males.

Management of Patients With Erythropoietic Protoporphyria-Related Progressive Liver Disease.

Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder of heme synthesis resulting from overproduction of protoporphyrin IX (PPIX), which can lead to progressive liver disease characterized by recurrent EPP crises and end-stage liver disease. We used the Australian Transplant Registry to identify 5 patients referred for liver transplantation between 2008 and 2017. A total of 4 patients had EPP secondary to ferrochelatase deficiency, and 1 patient had X-linked EPP. No patient had follow-up with a specialist prior to the diagnosis of progressive liver disease. There were 3 patients who underwent orthotopic liver transplantation, whereas 2 died while on the transplant waiting list. Parenteral PPIX-lowering therapy was used in 4 patients and was effective in 3 patients, although 2 of these had rebound porphyria and worsening liver function following a decrease in the intensity of therapy. Early disease recurrence in the allograft following transplantation occurred in 2 patients requiring red cell exchange (RCE) to successfully attain and maintain low PPIX levels, but RCE was associated with hemosiderosis in 1 patient. Allogeneic stem cell transplantation (AlloSCT) was performed in 2 patients. One failed engraftment twice, whereas the second rejected the first graft but achieved full donor chimerism with a second graft and increased immunosuppression. In conclusion, our observations suggest that progressive liver disease needs parenteral PPIX-lowering treatment with the intensity adjusted to achieve a target Erc-PPIX level. Because EPP liver disease is universally recurrent, AlloSCT should be considered in all patients with adequate immunosuppression to facilitate engraftment. RCE appears to be effective for recurrent EPP liver disease but is associated with an increased risk of iron overload.

Dysbiosis of the Duodenal Mucosal Microbiota Is Associated With Increased Small Intestinal Permeability in Chronic Liver Disease.

OBJECTIVES: Chronic liver disease (CLD) is associated with both alterations of the stool microbiota and increased small intestinal permeability. However, little is known about the role of the small intestinal mucosa-associated microbiota (MAM) in CLD. The aim of this study was to evaluate the relationship between the duodenal MAM and both small intestinal permeability and liver disease severity in CLD. METHODS: Subjects with CLD and a disease-free control group undergoing routine endoscopy underwent duodenal biopsy to assess duodenal MAM by 16S rRNA gene sequencing. Small intestinal permeability was assessed by a dual sugar (lactulose: rhamnose) assay. Other assessments included transient elastography, endotoxemia, serum markers of hepatic inflammation, dietary intake, and anthropometric measurements. RESULTS: Forty-six subjects (35 with CLD and 11 controls) were assessed. In subjects with CLD, the composition (P = 0.02) and diversity (P < 0.01) of the duodenal MAM differed to controls. Constrained multivariate analysis and linear discriminate effect size showed this was due to Streptococcus-affiliated lineages. Small intestinal permeability was significantly higher in CLD subjects compared to controls. In CLD, there were inverse correlations between microbial diversity and both increased small intestinal permeability (r = -0.41, P = 0.02) and serum alanine aminotransferase (r = -0.35, P = 0.04). Hepatic stiffness was not associated with the MAM. DISCUSSION: In CLD, there is dysbiosis of the duodenal MAM and an inverse correlation between microbial diversity and small intestinal permeability. TRANSLATIONAL IMPACT: Strategies to ameliorate duodenal MAM dysbiosis may ameliorate intestinal barrier dysfunction and liver injury in CLD.

'Back to Life'-Using knowledge exchange processes to enhance lifestyle interventions for liver transplant recipients: A qualitative study.

AIM: Interventions to prevent excessive weight gain after liver transplant are needed. The purpose of the present study was to enhance a specialist post-transplant well-being program through knowledge exchange with end-users. METHODS: The study used an interactive process of knowledge exchange between researchers, clinicians and health system users. Data were collected as focus groups or telephone interviews and underwent applied thematic analysis. RESULTS: There were 28 participants (age 24-68 years; 64% male). The results identified experiences that may influence decisions around health behaviours during the course of transplant recovery. Three over-arching themes were identified that impact on liver transplant recipients post-transplant health behaviours. These include (i) Finding a coping mechanism which highlighted the need to acknowledge the significant emotional burden of transplant prior to addressing long-term physical wellness; (ii) Back to Life encompassing the desire to return to employment and prioritise family, while co-ordinating the burden of ongoing medical monitoring and self-management and (iii) Tailored, Personalised Care with a preference for health care delivery by transplant specialists via a range of flexible eHealth modalities. CONCLUSIONS: This person-centred process of knowledge exchange incorporated experiences of recipients into service design and identified life priorities most likely to influence health behaviours post-transplant. Patient co-creation of services has the potential to improve the integration of knowledge into health systems and future directions will require evaluation of effectiveness and sustainability of patient-centred multidisciplinary service development.

Three-Dimensional Electromagnetic Torso Scanner.

A three-dimensional (3D) electromagnetic torso scanner system is presented. This system aims at providing a complimentary/auxiliary imaging modality to supplement conventional imaging devices, e.g., ultrasound, computerized tomography (CT) and magnetic resonance imaging (MRI), for pathologies in the chest and upper abdomen such as pulmonary abscess, fatty liver disease and renal cancer. The system is comprised of an array of 14 resonance-based reflector (RBR) antennas that operate from 0.83 to 1.9 GHz and are located on a movable flange. The system is able to scan different regions of the chest and upper abdomen by mechanically moving the antenna array to different positions along the long axis of the thorax with an accuracy of about 1 mm at each step. To verify the capability of the system, a three-dimensional imaging algorithm is proposed. This algorithm utilizes a fast frequency-based microwave imaging method in conjunction with a slice interpolation technique to generate three-dimensional images. To validate the system, pulmonary abscess was simulated within an artificial torso phantom. This was achieved by injecting an arbitrary amount of fluid (e.g., 30 mL of water), into the lungs regions of the torso phantom. The system could reliably and reproducibly determine the location and volume of the embedded target.

Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation.

BACKGROUND: Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease. METHODS: Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded. RESULTS: Eighty-two patients (aged 55.1 [50.6-59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7-13.4) mL·kg·min. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14-22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8-11.9]; no sepsis, 11.8 [10.5-13.8] mL·kg·min; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and ß-blocker use. CONCLUSIONS: Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.

Changes in dietary patterns and body composition within 12 months of liver transplantation.

BACKGROUND: Cardiometabolic risk factors are increasing in liver transplant recipients (LTR). Influencing dietary factors have not been assessed. The aim of this observational study was to assess changes in weight, metabolic function, dietary intake and eating behaviours in the first year after orthotopic liver transplantation (OLT). METHODS: Consecutive recruitment of 17 patients (14 males) awaiting OLT at a single tertiary hospital. Dietary intake, food behaviours and anthropometry were recorded at baseline, and 6 and 12 months post-transplant. RESULTS: By 12 months, patients had gained on average 7.3% of body weight. The prevalence of overweight or obesity increased from baseline 53% to 77% (P=0.001). By 6 months, 65% (n=11/17) of patients had altered glucose metabolism. Dietary intake was consistent with a Western-style dietary pattern with high saturated fat. Over half of the patients (69%, n=11/16) reported low to no depressive feelings and rated their self-esteem as good (53%, n=9/16). The Power of Food Scale increased between pre and post-transplant, indicating a stronger appetitive drive. CONCLUSIONS: Weight gain occurs early post-transplant, with significant metabolic dysfunction present within 6 months, however is not associated with significant psychological distress. Early dietary intervention designed to limit weight gain and target cardiometabolic health is recommended for this unique patient population.

Value of the 8-oxodG/dG ratio in chronic liver inflammation of patients with hepatocellular carcinoma.

The aim of this study was to examine the role of oxidative DNA damage in chronic liver inflammation in the evolution of hepatocellular carcinoma. The accumulated data demonstrated that oxidative DNA damage and chronic liver inflammation are involved in the transformation of normal hepatocytes and their evolution towards hepatocellular carcinoma. However, the levels of 8-oxy-2'-deoxy-guanosine (8-oxodG), a biomarker of oxidative DNA damage, were overestimated and underestimated in previous reports due to various technical limitations. The current techniques are not suitable to analyze the 8-oxodG levels in the non-malignant liver tissues and tumors of hepatocellular carcinoma patients unless they are modified. Therefore, in this study, the protocols for extraction and hydrolysis of DNA were optimized using 54 samples from hepatocellular carcinoma patients with various risk factors, and the 8-oxodG and 2'-deoxyguanosine (dG) levels were measured. The patients enrolled in the study include 23 from The Princess Alexandra Hospital and The Royal Brisbane and Women's Hospitals, Brisbane, Australia, and 31 from South Africa. This study revealed that the 8-oxodG/dG ratios tended to be higher in most non-malignant liver tissues compared to hepatocellular carcinoma tissue (p=0.2887). It also appeared that the ratio was higher in non-malignant liver tissue from Southern African patients (p=0.0479), but there was no difference in the 8-oxodG/dG ratios between non-malignant liver tissues and tumors of Australian hepatocellular carcinoma patients (p=0.7722). Additionally, this study also revealed a trend for a higher 8-oxodG/dG ratio in non-malignant liver tissues compared to tumoural tissues of patients with HBV. Significant differences were not observed in the 8-oxodG/dG ratios between non-cirrhotic and cirrhotic non-malignant liver tissues.

Additive impact of pre-liver transplant metabolic factors on survival post-liver transplant.

BACKGROUND AND AIM: Diabetes at time of liver transplantation is associated with reduced post-transplant survival. We aimed to assess whether additional metabolic conditions such as obesity or hypertension had additive prognostic impact on post-transplantation survival. METHODS: A multi-center cohort study of 617 adult subjects undergoing liver transplantation between 2003 and 2009 has been used. Dry body mass index was calculated following adjustment for ascites. RESULTS: After a median follow-up of 5.8 years (range 0-10.5), 112 (18.2%) patients died. Diabetes was associated with reduced post-transplant survival (hazard ratio 1.89, 95% confidence interval [CI] 1.25-2.86, P = 0.003), whereas obesity, hypertension, dyslipidemia, and the metabolic syndrome itself were not (P > 0.3 for all). Patients with concomitant diabetes and obesity had lower survival (adjusted Hazard Ratio [aHR] 2.40, 95%CI 1.32-4.38, P = 0.004), whereas obese non-diabetic patients or diabetic non-obese patients had similar survival compared with non-diabetic, non-obese individuals. The presence of hypertension or dyslipidemia did not impact on survival in patients with diabetes (P > 0.1 for both). Obese diabetic patients had longer intensive care and hospital stays than non-obese diabetic or obese, non-diabetic patients (P < 0.05). The impact of concomitant obesity and diabetes on survival was greater in subjects aged 50+ years (52.6% 5-year survival, aHR 3.04, 95% CI 1.54-5.98) or those transplanted with hepatocellular carcinoma (34.1% 5-year survival, aHR 3.35, 95% CI 1.31-5.57). Diabetes without obesity was not associated with an increased mortality rate in these sub-groups. CONCLUSIONS: Concomitant diabetes and obesity but not each condition in the absence of the other is associated with reduced post-liver transplant survival. The impact of diabetes and obesity is greater in older patients and those with hepatocellular carcinoma.

Symptoms of Obstructive Sleep Apnea, Gastroesophageal Reflux and the Risk of Barrett's Esophagus in a Population-Based Case-Control Study.

BACKGROUND: Gastroesophageal reflux is overrepresented in people with obstructive sleep apnea (OSA) and it has been suggested that OSA worsens gastroesophageal reflux symptoms. Aggravated reflux might lead to an increased risk of Barrett's esophagus. AIM: To assess the association between sleep apnea symptoms and Barrett's esophagus. METHODS: Included in a case-control study in Brisbane, Australia were 237 patients with histologically confirmed Barrett's esophagus and 247 population controls. The controls were randomly selected from the electoral roll and frequency-matched to the cases by age and sex. Information on OSA symptoms (excessive daytime sleepiness and sleep related apnea symptoms), gastroesophageal reflux symptoms and anthropometric measures were collected through interviews and written questionnaires. Multivariable logistic regression provided odds ratios (OR) and 95% confidence intervals (CI), adjusted for potential confounding by BMI and gastroesophageal reflux. RESULTS: The prevalence of Barrett's esophagus was higher among people with excessive daytime sleepiness than those without (24% vs. 18%; p-value 0.1142) and in participants with sleep-related apnea symptoms (20% vs. 13%; p-value 0.1730). However, there were non-significantly increased ORs of Barrett's esophagus among people with excessive daytime sleepiness (OR 1.42, 95% CI 0.90-2.34) and sleep related apnea symptoms (OR 1.32, 95% CI 0.74-2.36) when adjusting for age, sex and BMI. After further adjustment for gastroesophageal reflux symptoms, the point ORs were no longer increased (OR 1.02, 95% CI 0.61-1.70 for daytime sleepiness and OR 0.72, 95% CI 0.38-1.38 for sleep related apnea symptoms). CONCLUSIONS: Symptoms of OSA are possibly associated with an increased risk of Barrett's esophagus, an association that appears to be mediated entirely by gastroesophageal reflux.