ABSTRACT
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.
Subject(s)
Necroptosis , Non-alcoholic Fatty Liver Disease , Humans , Female , Male , Mice , Animals , Epigenesis, Genetic , Non-alcoholic Fatty Liver Disease/genetics , Hepatocytes , Receptor-Interacting Protein Serine-Threonine Kinases/genetics , Protein Kinases/geneticsABSTRACT
BACKGROUND: A Mediterranean diet (MD) appears to be beneficial in non-alcoholic fatty liver disease (NAFLD) patients in Mediterranean countries; however, the acceptability of a MD in non-Mediterranean populations has not been thoroughly explored. The present study aimed to explore the acceptability through understanding the barriers and enablers of the MD and low-fat diet (LFD) interventions as perceived by participating Australian adults from multicultural backgrounds with NAFLD. METHODS: Semi-structured telephone interviews were performed with 23 NAFLD trial participants at the end of a 12-week dietary intervention in a multicentre, parallel, randomised clinical trial. Data were analysed using thematic analysis. RESULTS: Participants reported that they enjoyed taking part in the MD and LFD interventions and perceived that they had positive health benefits from their participation. Compared with the LFD, the MD group placed greater emphasis on enjoyment and intention to maintain dietary changes. Novelty, convenience and the ability to swap food/meals were key enablers for the successful implementation for both of the dietary interventions. Flavour and enjoyment of food, expressed more prominently by MD intervention participants, were fundamental components of the diets with regard to reported adherence and intention to maintain dietary change. CONCLUSIONS: Participants randomised to the MD reported greater acceptability of the diet than those randomised to the LFD, predominantly related to perceived novelty and palatability of the diet.
Subject(s)
Diet, Mediterranean , Non-alcoholic Fatty Liver Disease , Adult , Humans , Diet, Fat-Restricted , Australia , PatientsABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is predominantly managed by lifestyle intervention, in the absence of effective pharmacotherapies. Mediterranean diet (MedDiet) is the recommended diet, albeit with limited evidence. AIMS: To compare an ad libitum MedDiet to low-fat diet (LFD) in patients with NAFLD for reducing intrahepatic lipids (IHL) by proton magnetic resonance spectroscopy (1 H-MRS). Secondary outcomes include insulin resistance by homeostatic model of assessment (HOMA-IR), visceral fat by bioelectrical impedance analysis (BIA), liver stiffness measurement (LSM) and other metabolic outcomes. METHODS: In this parallel multicentre RCT, subjects were randomised (1:1) to MedDiet or LFD for 12 weeks. RESULTS: Forty-two participants (25 females [60%], mean age 52.3 ± 12.6 years) were included, 23 randomised to LFD and 19 to MedDiet.; 39 completed the study. Following 12 weeks, there were no between-group differences. IHL improved significantly within the LFD group (-17% [log scale]; p = .02) but not within the MedDiet group (-8%, p = .069). HOMA-IR reduced in the LFD group (6.5 ± 5.6 to 5.5 ± 5.5, p < .01) but not in the MedDiet group (4.4 ± 3.2 to 3.9 ± 2.3, p = .07). No differences were found for LSM (MedDiet 7.8 ± 4.0 to 7.6 ± 5.2, p = .429; LFD 11.8 ± 14.3 to 10.8 ± 10.2 p = .99). Visceral fat reduced significantly in both groups; LFD (-76% [log scale], p = <.0005), MedDiet (-61%, p = <.0005). CONCLUSIONS: There were no between-group differences for hepatic and metabolic outcomes when comparing MedDiet to LFD. LFD improved IHL and insulin resistance. Significant improvements in visceral fat were seen within both groups. This study highlights provision of dietary interventions in free-living adults with NAFLD is challenging.
Subject(s)
Diet, Mediterranean , Insulin Resistance , Non-alcoholic Fatty Liver Disease , Adult , Diet, Fat-Restricted , Female , Humans , Liver/pathology , Middle Aged , Non-alcoholic Fatty Liver Disease/pathologyABSTRACT
An estimated 18% of people living with chronic hepatitis B (CHB) in Australia were born in China. While guideline-based care, including regular clinical monitoring and timely treatment, prevent CHB-related cirrhosis, cancer and deaths, over three-quarters of people with CHB do not receive guideline-based care in Australia. This qualitative study aimed to identify enablers to engagement in CHB clinical management among ethnic Chinese people attending specialist care. Participants self-identified as of Chinese ethnicity and who attended specialist care for CHB clinical management were interviewed in Melbourne in 2019 (n = 30). Semi-structured interviews covered experiences of diagnosis and engagement in clinical management services, and advice for people living with CHB. Interviews were recorded with consent; data were transcribed verbatim and thematically analysed. Receiving clear information about the availability of treatment and/or the necessity of long-term clinical management were the main enablers for participants to engage in CHB clinical management. Additional enablers identified to maintain regular clinical monitoring included understanding CHB increases risks of cirrhosis and liver cancer, using viral load indicators to visualize disease status in patient-doctor communication; expectations from family, peer group and medical professionals; use of a patient recall system; availability of interpreters or multilingual doctors; and largely subsidized healthcare services. In conclusion, to support people attending clinical management for CHB, a holistic response from community, healthcare providers and the public health sector is required. There are needs for public health programmes directed to communicate (i) CHB-related complications; (ii) availability of effective and cheap treatment; and that (iii) long-term engagement with clinical management and its benefits.
Subject(s)
Hepatitis B, Chronic , Hepatitis B , Australia/epidemiology , China/epidemiology , Ethnicity , Hepatitis B, Chronic/drug therapy , HumansABSTRACT
BACKGROUND: Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion. METHOD: Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival. RESULTS: Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2-50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively. CONCLUSION: Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.
Subject(s)
Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/methods , Liver Neoplasms/therapy , Neoplasm Recurrence, Local/therapy , alpha-Fetoproteins/analysis , Aged , Australia/epidemiology , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Chemoembolization, Therapeutic/adverse effects , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Liver Neoplasms/blood , Liver Neoplasms/mortality , Male , Middle Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/mortality , Patient Selection , Prognosis , Retreatment/adverse effects , Retreatment/methods , Retrospective Studies , Treatment OutcomeABSTRACT
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.
Subject(s)
Communication , Health Knowledge, Attitudes, Practice , Hepatitis B, Chronic/epidemiology , Patient Education as Topic/methods , Adult , Australia/epidemiology , Female , Humans , Male , Middle Aged , Pilot Projects , Surveys and QuestionnairesABSTRACT
OBJECTIVES: To determine the factors associated with survival of patients with hepatocellular carcinoma (HCC) and the effect of HCC surveillance on survival. DESIGN, SETTING AND PARTICIPANTS: Prospective population-based cohort study of patients newly diagnosed with HCC in seven tertiary hospitals in Melbourne, 1 July 2012 - 30 June 2013. MAIN OUTCOME MEASURES: Overall survival (maximum follow-up, 24 months); factors associated with HCC surveillance participation and survival. RESULTS: 272 people were diagnosed with incident HCC during the study period; the most common risk factors were hepatitis C virus infection (41%), alcohol-related liver disease (39%), and hepatitis B virus infection (22%). Only 40% of patients participated in HCC surveillance at the time of diagnosis; participation was significantly higher among patients with smaller median tumour size (participants, 2.8 cm; non-participants, 6.0 cm; P < 0.001) and earlier Barcelona Clinic Liver Cancer (BCLC) stage disease (A/B, 59%; C/D, 25%; P < 0.001). Participation was higher among patients with compensated cirrhosis or hepatitis C infections; it was lower among those with alcohol-related liver disease or decompensated liver disease. Median overall survival time was 20.8 months; mean survival time was 18.1 months (95% CI, 16.6-19.6 months). Participation in HCC surveillance was associated with significantly lower mortality (adjusted hazard ratio [aHR], 0.60; 95% CI, 0.38-0.93; P = 0.021), as were curative therapies (aHR, 0.33; 95% CI, 0.19-0.58). Conversely, higher Child-Pugh class, alpha-fetoprotein levels over 400 kU/L, and later BCLC disease stages were each associated with higher mortality. CONCLUSIONS: Survival for patients with HCC is poor, but may be improved by surveillance, associated with the identification of earlier stage tumours, enabling curative therapies to be initiated.
Subject(s)
Carcinoma, Hepatocellular/mortality , Liver Neoplasms/mortality , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/therapy , Female , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/epidemiology , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/epidemiology , Humans , Incidence , Liver Diseases, Alcoholic/complications , Liver Diseases, Alcoholic/epidemiology , Liver Neoplasms/complications , Liver Neoplasms/epidemiology , Liver Neoplasms/therapy , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/epidemiology , Prospective Studies , Risk Factors , Survival Analysis , Victoria/epidemiologyABSTRACT
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.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Registries , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/therapy , Cohort Studies , Confidence Intervals , Female , Humans , Incidence , Liver Neoplasms/therapy , Male , Middle Aged , Needs Assessment , Neoplasm Invasiveness/pathology , Neoplasm Staging , Poisson Distribution , Prognosis , Sex Distribution , Statistics, Nonparametric , Victoria/epidemiologyABSTRACT
BACKGROUND/AIMS: Endoscopic screening for high-risk gastro-oesophageal varices (GOV) is recommended for compensated cirrhotic patients with transient elastography identifying increasing numbers of patients with cirrhosis without portal hypertension. Using liver stiffness measurement (LSM) ± platelet count, the aim was to develop a simple clinical rule to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis. METHODS: A retrospective analysis of 71 patients with Child-Pugh A cirrhosis diagnosed by transient elastography (LSM >13.6 kPa) who underwent screening gastroscopy was conducted. A predictive model using LSM ± platelet count was assessed to exclude the presence of high-risk GOV (diameter >5 mm and/or the presence of high-risk stigmata) and validated using a second cohort of 200 patients from two independent centres. RESULTS: High-risk GOV were present in 10 (15%) and 16 (8%) of the training and validation cohorts, respectively, which was associated with LSM and Pl count (P < 0.05). A combined model based on LSM and Pl count was more accurate for excluding the presence of high-risk GOV than either alone (training cohort AUROC: 0.87 [0.77-0.96] vs. 0.78 [0.65-0.92] for LSM and 0.71 [0.52-0.90] for platelets) with the combination of LSM ≤25 kPa and Pl ≥100 having a NPV of 100% in both the training and validation cohorts. A total of 107 (39%) patients meet this criterion. CONCLUSION: The combination of LSM ≤25 kPa and Pl ≥100 can be used in clinical practice to exclude the presence of high-risk GOV in patients with Child-Pugh A cirrhosis.
Subject(s)
Elasticity Imaging Techniques/methods , Esophageal and Gastric Varices , Liver Cirrhosis , Liver/pathology , Platelet Count/methods , Aged , Endoscopy, Digestive System/methods , Esophageal and Gastric Varices/diagnosis , Esophageal and Gastric Varices/etiology , Female , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/diagnosis , Male , Middle Aged , Reproducibility of Results , Risk Assessment/methodsABSTRACT
OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Subject(s)
Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/adverse effects , Protein Kinase Inhibitors/adverse effects , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/mortality , Cohort Studies , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/mortality , Male , Middle Aged , Multivariate Analysis , Niacinamide/adverse effects , Niacinamide/therapeutic use , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Sorafenib , Treatment Outcome , alpha-Fetoproteins/analysisABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease, the most prevalent liver disease in developed countries, remains difficult to manage with no proven safe and effective pharmacotherapy available. While weight reduction is the most commonly practiced treatment strategy, this is difficult to both achieve and/or maintain in the majority. Furthermore evidence-based dietary recommendations to guide the nutritional management of these patients are lacking. Using a randomised controlled trial design, this study compares the effectiveness of the Mediterranean diet to a standard low fat diet in terms of differences in insulin sensitivity, hepatic steatosis and metabolic outcomes in participants with non-alcoholic fatty liver disease. METHODS: Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant, will be randomised into either a Mediterranean or low fat diet group for a 3 month intervention period. Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy. Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian. The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The standard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines. Study recruitment will take place at four major metropolitan hospitals in Melbourne, Australia. Data collection will occur at all face to face reviews including baseline, 6, and 12 weeks. A follow up assessment to measure sustainability will take place at 6 and 12 months. The primary end point is improved insulin sensitivity scores at the 12 week time point. DISCUSSION: This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight loss can result in significant benefits in liver fat and insulin sensitivity and that these changes are sustained at 12 months. These metabolic changes would potentially lead to reductions in the risk of chronic liver disease, heart disease, type 2 diabetes and liver cancer. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register ACTRN: ACTRN12615001010583 .
Subject(s)
Diet, Fat-Restricted , Diet, Mediterranean , Non-alcoholic Fatty Liver Disease/diet therapy , Adiposity , Adult , Australia , Clinical Protocols , Female , Humans , Insulin/blood , Insulin Resistance , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Nutrition Policy , Young AdultSubject(s)
Diet, Mediterranean , Non-alcoholic Fatty Liver Disease , Diet, Fat-Restricted , Humans , LiverABSTRACT
The risk of depression and anxiety is higher in people with metabolic conditions, but whether dietary approaches, which are central to the management of metabolic conditions, can also improve depression and anxiety is uncertain. The primary aim of this systematic review and meta-analysis was to evaluate the effects of dietary interventions on depression and anxiety in adults with metabolic conditions. The secondary aim was to evaluate the effects of hypocaloric and isocaloric dietary interventions on these outcomes. Four databases (MEDLINE, PsychINFO, EMBASE, and CINAHL) were searched from inception to March 2023. Randomized controlled trials (RCTs) including dietary interventions in adults with metabolic conditions (type 2 diabetes mellitus, hyperlipidemia, hypertension, and/or overweight/obesity) that assessed depression and/or anxiety as outcomes were included. Overall, 13 RCTs were included in the systematic review, ≤13 of which were included in the meta-analysis. Estimates were pooled using random-effect meta-analysis for dietary interventions compared with controls. Improvements in depression scores were found in meta-analytic models including all dietary interventions [pooled estimate for the standardized mean difference (SMD) = -0.20 (95% CI: -0.35, -0.05); P = 0.007] and hypocaloric only diets [SMD = -0.27 (95% CI: -0.44, -0.10); P = 0.002]. There were no improvements in depression scores with isocaloric dietary interventions only [SMD = -0.14 (95% CI: -0.38, 0.10); P = 0.27]. In addition, there were no significant effects of any dietary interventions on anxiety scores. In adults with metabolic conditions, all dietary interventions and hypocaloric diets improved depression, but not anxiety. These findings suggest that dietary interventions including hypocaloric diets can play an important role in the management of depression in people with metabolic conditions. This systematic review and meta-analysis has been registered with PROSPERO (CRD42021252307).
Subject(s)
Anxiety , Depression , Adult , Humans , Obesity/complications , Overweight/complications , DietABSTRACT
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) presents a significant global health challenge, particularly among individuals with liver cirrhosis, with hepatitis C (HCV) a major cause. In people with HCV-related cirrhosis, an increased risk of HCC remains after cure. HCC surveillance with six monthly ultrasounds has been shown to improve survival. However, adherence to biannual screening is currently suboptimal. This study aimed to evaluate the effect of increased HCC surveillance uptake and improved ultrasound sensitivity on mortality among people with HCV-related cirrhosis post HCV cure. METHODS: This study utilized mathematical modelling to assess HCC progression, surveillance, diagnosis, and treatment among individuals with cirrhosis who had successfully been treated for HCV. The deterministic compartmental model incorporated Barcelona Clinic Liver Cancer (BCLC) stages to simulate disease progression and diagnosis probabilities in 100 people with cirrhosis who had successfully been treated for hepatitis C over 10 years. Four interventions were modelled to assess their potential for improving life expectancy: realistic improvements to surveillance adherence, optimistic improvements to surveillance adherence, diagnosis sensitivity enhancements, and improved treatment efficacy Results: Realistic adherence improvements resulted in 9.8 (95% CI 7.9, 11.6) life years gained per cohort of 100 over a 10-year intervention period; 17.2 (13.9, 20.3) life years were achieved in optimistic adherence improvements. Diagnosis sensitivity improvements led to a 7.0 (3.6, 13.8) year gain in life years, and treatment improvements improved life years by 9.0 (7.5, 10.3) years. CONCLUSIONS: Regular HCC ultrasound surveillance remains crucial to reduce mortality among people with cured hepatitis C and cirrhosis. Our study highlights that even minor enhancements to adherence to ultrasound surveillance can significantly boost life expectancy across populations more effectively than strategies that increase surveillance sensitivity or treatment efficacy.
ABSTRACT
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. METHODS: Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). RESULTS: At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). CONCLUSIONS: Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.
Subject(s)
Diet, Mediterranean , Fatty Liver/diet therapy , Fatty Liver/metabolism , Insulin Resistance , Adult , Aged , Cross-Over Studies , Fatty Liver/pathology , Female , Glucose Clamp Technique , Humans , Lipid Metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Non-alcoholic Fatty Liver Disease , Obesity, Abdominal/diet therapy , Obesity, Abdominal/metabolism , Obesity, Abdominal/pathology , Pilot ProjectsABSTRACT
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), encompassing both simple steatosis and non-alcoholic steato-hepatitis (NASH), is the most common cause of liver disease in Australia. Non-alcoholic fatty liver disease needs to be considered in the context of the metabolic syndrome, as cardiovascular disease will account for much of the mortality associated with NAFLD. OBJECTIVE: To provide an approach to the identification of NAFLD in general practice, the distinction between simple steatosis and NASH, and the management of these two conditions. DISCUSSION: Non-alcoholic steato-hepatitis is more common in the presence of diabetes, obesity, older age and increased inflammation, and is more likely to progress to cirrhosis. Cirrhosis may be complicated by hepatocellular carcinoma or liver failure. Hepatocellular carcinoma has also been described in NASH without cirrhosis. Assessment and treatment of features of the metabolic syndrome may reduce associated cardiovascular mortality. Numerous agents have been evaluated, but weight loss remains the only effective treatment for NAFLD.
Subject(s)
Fatty Liver/diagnosis , Liver/pathology , Australia , Fatty Liver/therapy , General Practice , General Practitioners , Humans , Non-alcoholic Fatty Liver DiseaseABSTRACT
Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of adults worldwide, with chronic low-grade inflammation being a key pathophysiological feature of progression. The Mediterranean diet (MedDiet) is recognized for improving metabolic and hepatic outcomes in people with diabetes and NAFLD, in part, via anti-inflammatory properties. The aim of this study was to determine the effect of an ad libitum MedDiet versus low-fat diet (LFD) on inflammatory markers in adults with NAFLD. It was hypothesized that the MedDiet, and its individual components, would improve inflammation. This multicenter, randomized controlled trial, randomized participants to a MedDiet or LFD intervention for 12 weeks. Primary outcomes included change from baseline to 12 weeks for serum high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, adiponectin, leptin, and resistin. Forty-two participants (60% female; age 52.3 ± 12.6 years; body mass index, 32.2 ± 6.2 kg/m²) were randomized to the MedDiet (n = 19) or low-fat diet (n = 23). At 12 weeks, the LFD showed a greater decrease in leptin compared with the MedDiet (-1.20 ± 3.9 ng/mL vs 0.64 ± 3.5 ng/mL, P = .010). Adiponectin significantly improved within the MedDiet (13.7 ± 9.2 µg/mL to 17.0 ± 12.5 µg/mL, P = .016), but not within the LFD group. No statistically significant changes were observed for other inflammatory markers following the MedDiet or LFD. Adherence to the MedDiet significantly improved in both study arms, although greater improvements were seen in the MedDiet group. Adiponectin significantly improved following a Mediterranean diet intervention, in the absence of weight loss. The low-fat diet did not elicit improvements in inflammatory markers. High-quality clinical trials appropriately powered to inflammatory markers are required in this population.
Subject(s)
Diet, Mediterranean , Non-alcoholic Fatty Liver Disease , Humans , Adult , Female , Middle Aged , Male , Adiponectin , Leptin , InflammationABSTRACT
Over 1.5 million preventable new hepatitis B infections continue to occur each year and there are an estimated 296 million people living with chronic hepatitis B infection worldwide, resulting in more than 820,000 deaths annually due to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B vaccination remains the cornerstone of public health policy to prevent HCC and a vital component of the global hepatitis B elimination response. The WHO has set a 90% vaccination target to achieve hepatitis B elimination by 2030; however, there is wide variability in reported birth dose coverage, with global coverage at only 42%. In this review, we outline the global trends in hepatitis B vaccination coverage and the impact of hepatitis B vaccination on HCC incidence and discuss the challenges and enabling factors for achieving WHO 2030 hepatitis B vaccination coverage targets.
ABSTRACT
Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34-97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00-1.02)), male (OR 1.37 (95% CI 1.17-1.59)), have ALT elevation (OR 3.21 (95% CI 2.59-3.99)), diabetes (OR 3.39 (95% CI 2.61-4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12-0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05-1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59-2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7-0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.