In older persons without known cardiovascular disease, the use of low-dose aspirin resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of ...cardiovascular disease than placebo.
Abstract Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition worldwide, and is projected to become the leading cause for liver transplantation in the United States ...as early as 2020. The mainstay of treatment remains lifestyle modification with diet and exercise recommendations, as although some pharmacological treatments such as glitazones and Vitamin E have shown benefit, there are concerns regarding long term safety. The evidence base for dietary interventions in NAFLD such as the Mediterranean diet, omega-3 polyunsaturated fatty acids and coffee is mainly derived from observational data with questionable validity. Where trials exist, they have shown benefit for surrogate outcomes such as hepatic steatosis and insulin resistance, but no trials have been conducted with salient clinical outcomes such as reduction in progression to chronic liver disease. Benefit in surrogate outcomes has also been seen for aerobic, anaerobic and combined modality exercise but it remains unclear if one type is superior. Furthermore, a reduction in sedentary time appears equally important. To provide a sound evidence base for lifestyle recommendations to people with NAFLD, longer duration trials of standardized dietary or exercise interventions, and testing various doses, types and with liver related outcomes, are essential.
Background and Aim
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) account for a large and growing proportion of liver disease burden globally. The burden of ...NAFLD/NASH manifests in increasing levels of advanced liver disease and primary liver cancer in Australia. A Markov model was used to forecast NAFLD burden in Australia through 2030.
Methods
A model was used to estimate fibrosis progression, primary liver cancer, and liver deaths among the Australian NAFLD population, with changes in incident NAFLD cases based on long‐term trends for changes in the prevalence of obesity. Published estimates and surveillance data were applied to build and validate the model projections, including surveillance data for the incidence of liver cancer.
Results
Prevalent NAFLD cases were projected to increase 25% from the current burden (5 551 000 4 748 000–6 306 000 cases in 2019) to 7 024 000 5 838 000–7 886 000 cases in 2030. The projected increase in the number of NASH cases (40%) was greater than that of NAFLD cases. Incident cases of advanced liver disease are projected to increase up to 85% by 2030, and incident NAFLD liver deaths are estimated to increase 85% from 1900 (1100–3300) deaths in 2019 to 3500 (2100–6100) deaths in 2030.
Conclusions
Restraining growth of the obese and diabetic populations, along with potential therapeutic options, will be essential for mitigating disease burden.
While the prevalence of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) continues to rise, with both conditions increasingly recognized in primary care and ...specialist practice, quantifying future disease burden has always been challenging. Accurate prevalence data is essential to inform modeling studies of NAFLD disease burden, which in turn is needed to support healthcare policy and planning. Here, Mahady and George discuss a study by Estes and colleagues which offered a creative approach to approximating NAFLD prevalence. By utilizing population based, epidemiological data on obesity and type 2 diabetes from national health surveys, Estes et al were able to apply the expected prevalence of NAFLD and NASH in these conditions to provide estimates of prevalence at a population level.
Non‐alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease in the Australian population, although precise estimates of prevalence are lacking. NAFLD may progress to ...liver fibrosis, cirrhosis, decompensated liver disease, and liver cancer and is becoming an increasingly common indication for liver transplantation in Australia and New Zealand. There is an extrahepatic burden of NAFLD extending beyond the liver, which is manifested by an increased risk of developing cardiovascular disease, diabetes, and chronic renal impairment, all of which are common causes of morbidity in the Australian population. Early recognition of those patients at high risk of developing advanced liver disease is essential in order to target those who will benefit from intensive lifestyle modification. In this review, we present data on the epidemiology of NAFLD within Australia, its associated health burden in terms of hepatic and extrahepatic complications, common clinical presentations, and indications for treatment. We also propose a research agenda that highlights knowledge needed to improve diagnosis and management specific to the Australian context.
Background & Aims Non alcoholic steatohepatitis (NASH) has no approved pharmacological therapy. Insulin sensitisers such as thiazolidinediones ameliorate insulin resistance and are a potential ...therapeutic option. We performed a systematic review and meta-analysis of the effect of thiazolidinediones on histological and biochemical variables in NASH. Methods Two reviewers searched Medline, Embase, Cochrane Central, international meeting abstracts, reference lists, and contacted experts. Inclusion criteria were randomized trials of people with NASH receiving thiazolidinediones, compared with placebo or other treatments. Methodological quality was assessed in domains suggested by the Cochrane Collaboration. The primary outcome was histological improvement (fibrosis, steatosis, inflammation, hepatocellular ballooning, and NAS score). Secondary outcomes included change in alanine transaminase, insulin resistance, body mass index, weight, and adverse events. Meta-analysis used random effects with dichotomous outcomes as relative risk (RR) and continuous outcomes as mean difference (MD), both with 95% confidence intervals (CI). Results Of seven randomized trials (n = 489) with histological outcomes, four were placebo controlled (n = 355). Methodological quality was variable although better for placebo controlled studies. Treated participants showed improvement in fibrosis (RR 1.38, CI 1.01–1.89), steatosis (RR 2.03, CI 1.57–2.62), inflammation (RR 1.71, CI 1.32–2.21), and hepatocellular ballooning (RR 1.62, CI 1.15–2.28). Treatment increased weight by an average of 4.4 kg (CI 2.6–5.2 kg). Adverse event reporting was inconsistent and only one trial assessed quality of life. Conclusions Thiazolidinediones modestly improve histological variables including fibrosis and hepatocellular ballooning, but at the cost of significant weight gain. Trials of longer duration and reporting of patient oriented outcomes would be informative.
Colorectal cancer is the third most commonly diagnosed cancer in Australia. Emerging evidence from several countries suggests increasing incidence in people aged <50 years.
We assessed colon and ...rectal cancer incidence trends in people aged 20+ in Australia from 1982 to 2014. We used data on 375,008 incident cases (248,162 colon and 126,846 rectal). We quantified the annual percentage change (APC) in rates by age group using Joinpoint regression.
For people aged <50 years, colon cancer rates increased from the mid-2000s, with the increase in APCs ranging from 1.7% to 9.3% per annum (depending on specific age group); rectal cancer rates increased from the early 1990s, with APCs ranging from 0.9% to 7.1% per annum. For people aged 50 to 69 years, colon and rectal cancer rates decreased from the mid-1990s, with the decrease in APCs in specific age groups ranging from 0.8% to 4.8% per annum (except for colon cancer in those ages 65 to 69 years, where similar rate decreases were observed from 2007). An overall reduction in older persons (>70 years) was estimated at 1.9% to 4.9% per annum for colon cancer from 2010 onward and 1.1% to 1.8% per annum in rectal cancer from the early 2000s onward.
Colon and rectal cancer incidence has increased in people aged <50 years in Australia over the last two decades. However, colon and rectal cancer rates decreased in people aged 50+, likely due to
and organized bowel cancer screening.
Further research is needed to examine the cause of the increase and to quantify the impact of future trends on the cost-effectiveness of population-based screening for those <50 years.
ObjectiveThere is a lack of robust data on significant gastrointestinal bleeding in older people using aspirin. We calculated the incidence, risk factors and absolute risk using data from a large ...randomised, controlled trial.DesignData were extracted from an aspirin versus placebo primary prevention trial conducted throughout 2010–2017 (‘ASPirin in Reducing Events in the Elderly (ASPREE)’, n=19 114) in community-dwelling persons aged ≥70 years. Clinical characteristics were collected at baseline and annually. The endpoint was major GI bleeding that resulted in transfusion, hospitalisation, surgery or death, adjudicated independently by two physicians blinded to trial arm.ResultsOver a median follow-up of 4.7 years (88 389 person years), there were 137 upper GI bleeds (89 in aspirin arm and 48 in placebo arm, HR 1.87, 95% CI 1.32 to 2.66, p<0.01) and 127 lower GI bleeds (73 in aspirin and 54 in placebo arm, HR 1.36, 95% CI 0.96 to 1.94, p=0.08) reflecting a 60% increase in bleeding overall. There were two fatal bleeds in the placebo arm. Multivariable analyses indicated age, smoking, hypertension, chronic kidney disease and obesity increased bleeding risk. The absolute 5-year risk of bleeding was 0.25% (95% CI 0.16% to 0.37%) for a 70 year old not on aspirin and up to 5.03% (2.56% to 8.73%) for an 80 year old taking aspirin with additional risk factors.ConclusionAspirin increases overall GI bleeding risk by 60%; however, the 5-year absolute risk of serious bleeding is modest in younger, well individuals. These data may assist patients and their clinicians to make informed decisions about prophylactic use of aspirin.Trial registration numberASPREE. NCT01038583.
Nonalcoholic fatty liver disease (NAFLD) and its progressive form, nonalcoholic steatohepatitis (NASH), are an increasingly common cause of chronic liver disease in the developed world, with NASH ...projected to be the leading cause of liver transplantation in the United States by 2020. This review of NASH management addresses current data from the perspective of levels of evidence for therapeutic options in NASH, including lifestyle modification, drug therapies, and bariatric surgery. In particular, behavioral therapies to assist patients in adopting lifestyle changes are highlighted and a research agenda for future NASH management is presented.
Elevated alanine transaminase (ALT) is a strong predictor of metabolic syndrome, but there are few data from the Australian population. We aimed to determine the prevalence of elevated ALT and ...association with metabolic risk factors.
In this cross-sectional study including adult participants (N = 9,447) from a nationwide, population-based survey, we assessed the prevalence of elevated ALT defined as ≥ 40 IU/L (men) and ≥ 30 IU/L (women) as baseline, and ALT as ≥ 30 IU/L (men) and ≥ 19 IU/L (women) as lower threshold, distribution of metabolic risk factors, and independent predictors of elevated ALT in logistic regression models. Analyses were weighted to the population with population weights.
Elevated ALT levels were found in 11.2% of the Australian population. People with elevated ALT were younger (43 vs 46 yrs) with more truncal adiposity (100 vs 91 cm), higher pro-atherogenic lipids and glucose and exercised less (120 vs 160 min per week, P < 0.05 for all analyses). Regression analyses indicated that younger age, male sex, diabetes, triglycerides, apolipoprotein B, and waist circumference were independent predictors of elevated ALT. The population attributable fraction of elevated ALT due to truncal obesity was estimated at 47%.
These data demonstrate a high prevalence of elevated ALT in the general population that is closely associated with metabolic risk factors. Individuals with elevated ALT should be evaluated for co-existent metabolic disorders.
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