Association Between CKD and Major Hemorrhage in Older Persons: Data From the Aspirin in Reducing Events in the Elderly Randomized Trial.

Introduction: Data on the association between chronic kidney disease (CKD) and major hemorrhage in older adults are lacking. Methods: We used data from a double-blind randomized controlled trial of aspirin in persons aged ≥ 70 years with prospective capture of bleeding events, including hemorrhagic stroke and clinically significant bleeding. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 and/or urinary albumin-to-creatinine ratio (UACR) ≥ 3 mg/mmol (26.6 mg/g). We compared bleeding rates in those with and without CKD, undertook multivariable analyses, and explored effect modification with aspirin. Results: Of 19,114 participants, 17,976 (94.0%) had CKD status recorded, of whom 4952 (27.5%) had CKD. Participants with CKD had an increased rate of major bleeding events compared with those without CKD (10.4/1000 vs. 6.3/1000 person-years [py], respectively) and increased bleeding risk (risk ratio [RR] 1.60; 95% confidence interval [CI]: 1.40, 1.90 for eGFR < 60 ml/min per 1.73 m2) and RR (2.10; 95% CI: 1.70, 2.50) for albuminuria. In adjusted analyses, CKD was associated with a 35% increased risk of bleeding (hazard ratio [HR] 1.37; 95% CI: 1.15, 1.62; P < 0.001). Other risk factors were older age, hypertension, smoking, and aspirin use. There was no differential effect of aspirin on bleeding by CKD status (test of interaction P = 0.65). Conclusion: CKD is independently associated with an increased risk of major hemorrhage in older adults. Increased awareness of modifiable risk factors such as discontinuation of unnecessary aspirin, blood pressure control, and smoking cessation in this group is warranted.

Incident Cancer Risk and Signatures Among Older MUTYH Carriers: Analysis of Population-Based and Genomic Cohorts.

MUTYH carriers have an increased colorectal cancer risk in case-control studies, with loss of heterozygosity (LOH) as the presumed mechanism. We evaluated cancer risk among carriers in a prospective, population-based cohort of older adults. In addition, we assessed if cancers from carriers demonstrated mutational signatures (G:C>T:A transversions) associated with early LOH. We calculated incident risk of cancer and colorectal cancer among 13,131 sequenced study participants of the ASPirin in Reducing Events in the Elderly cohort, stratified by sex and adjusting for age, smoking, alcohol use, BMI, polyp history, history of cancer, and aspirin use. MUTYH carriers were identified among 13,033 participants in The Cancer Genome Atlas and International Cancer Genome Consortium, and somatic signatures of cancers were analyzed. Male MUTYH carriers demonstrated an increased risk for overall cancer incidence [multivariable HR, 1.66; 95% confidence interval (CI), 1.03-2.68; P = 0.038] driven by increased colorectal cancer incidence (multivariable HR, 3.55; 95% CI, 1.42-8.78; P = 0.007), as opposed to extracolonic cancer incidence (multivariable HR, 1.40; 95% CI, 0.81-2.44; P = 0.229). Female carriers did not demonstrate increased risk of cancer, colorectal cancer, or extracolonic cancers. Analysis of mutation signatures from cancers of MUTYH carriers revealed no significant contribution toward early mutagenesis from widespread G:C>T:A transversions among gastrointestinal epithelial cancers. Among cancers from carriers, somatic transversions associated with base-excision repair deficiency are uncommon, suggestive of diverse mechanisms of carcinogenesis in carriers compared with those who inherit biallelic MUTYH mutations. PREVENTION RELEVANCE: Despite absence of loss of heterozygosity in colorectal cancers, elderly male MUTYH carriers appeared to be at increased of colorectal cancer.

Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial.

OBJECTIVE: There 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. DESIGN: Data 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. RESULTS: Over 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. CONCLUSION: Aspirin 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 NUMBER: ASPREE. NCT01038583.

Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease.

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.

Nonalcoholic fatty liver disease burden: Australia, 2019-2030.

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.

Trends in Colon and Rectal Cancer Incidence in Australia from 1982 to 2014: Analysis of Data on Over 375,000 Cases.

BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in Australia. Emerging evidence from several countries suggests increasing incidence in people aged <50 years. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 de facto and organized bowel cancer screening. IMPACT: 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.

Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly.

BACKGROUND: Aspirin is a well-established therapy for the secondary prevention of cardiovascular events. However, its role in the primary prevention of cardiovascular disease is unclear, especially in older persons, who have an increased risk. METHODS: From 2010 through 2014, we enrolled community-dwelling men and women in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or disability. Participants were randomly assigned to receive 100 mg of enteric-coated aspirin or placebo. The primary end point was a composite of death, dementia, or persistent physical disability; results for this end point are reported in another article in the Journal. Secondary end points included major hemorrhage and cardiovascular disease (defined as fatal coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal stroke, or hospitalization for heart failure). RESULTS: Of the 19,114 persons who were enrolled in the trial, 9525 were assigned to receive aspirin and 9589 to receive placebo. After a median of 4.7 years of follow-up, the rate of cardiovascular disease was 10.7 events per 1000 person-years in the aspirin group and 11.3 events per 1000 person-years in the placebo group (hazard ratio, 0.95; 95% confidence interval [CI], 0.83 to 1.08). The rate of major hemorrhage was 8.6 events per 1000 person-years and 6.2 events per 1000 person-years, respectively (hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001). CONCLUSIONS: The use of low-dose aspirin as a primary prevention strategy in older adults resulted in a significantly higher risk of major hemorrhage and did not result in a significantly lower risk of cardiovascular disease than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).

Development of a standardized definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial.

BACKGROUND: Bleeding is the major risk of aspirin treatment, especially in the elderly. A consensus definition for clinically significant bleeding (CSB) in aspirin primary prevention trials is lacking in the literature. METHODS: This paper details the development, modification, application, and quality control of a definition for clinically significant bleeding in the ASPirin in Reducing Events in the Elderly (ASPREE) trial, a primary prevention trial of aspirin in 19,114 community-dwelling elderly men and women. In ASPREE a confirmed bleeding event needed to meet criteria both for substantiated bleeding and clinical significance. Substantiated bleeding was defined as: 1) observed bleeding, 2) a reasonable report of symptoms of bleeding, 3) medical, nursing or paramedical report, or 4) imaging evidence. Bleeding was defined as clinically significant if it: 1) required transfusion of red blood cells, 2) required admission to the hospital for >24 h, or prolonged a hospitalization, with bleeding as the principal reason, 3) required surgery to stop the bleeding, or 4) resulted in death. Bleeding sites were subclassified as upper gastrointestinal, lower gastrointestinal, intracranial (hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, extradural hematoma, or other), or other sites. Potential events were retrieved from medical records, self-report or notification from treating doctors. Two reviewers adjudicated each event using electronic adjudication software, and discordant cases were reviewed by a third reviewer. Adjudication rules evolved to become more strictly defined as the trial progressed and decision rules were added to assist with frequent scenarios such as post-operative bleeding. CONCLUSIONS: This paper provides a detailed methodologic description of the development of a standardized definition for clinically significant bleeding and provides a benchmark for development of a consensus definition for future aspirin primary prevention trials. TRIAL REGISTRATION: ASPREE is registered on the International Standard Randomized Controlled Trial Number Register (ISRCTN83772183) and on clinicaltrials.gov (NCT01038583).

Burden of non-alcoholic fatty liver disease in Australia.

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.

Diagnostic Accuracy of Noninvasive Fibrosis Scores in a Population of Individuals With a Low Prevalence of Fibrosis.

BACKGROUND & AIMS: Noninvasive scoring systems for fibrosis are increasingly used in the clinic and in research because of their ease of use, accessibility, and low cost. However, test performance characteristics were established in groups of patients with a high prevalence of advanced fibrosis; little is known about diagnostic accuracy in low-risk populations. METHODS: In a cross-sectional study, 922 members of a general ambulatory population in Hong Kong (randomly selected; 18-70 years old) underwent clinical assessment from May 2008 through December 2010. All participants completed a standard questionnaire that collected information on age, sex, and history of smoking and alcohol use. Results of fasting blood tests and transient elastography were used as the reference standard to identify patients with advanced fibrosis. We assessed performance characteristics of 3 noninvasive fibrosis scoring systems: the nonalcoholic fatty liver disease fibrosis scoring system, the Fibrosis-4 scoring system, and aspartate transaminase to platelet ratio index, using standard thresholds. To calculate diagnostic test characteristics, we constructed a 2-by-2 table with the presence or absence of advanced fibrosis according to the transient elastography reading against the presence or absence of advanced fibrosis according to the scoring systems. Area under the receiver operating curve was calculated to assess overall diagnostic accuracy. RESULTS: Of the 922 individuals evaluated by transient elastography, 749 had a valid reading and 15 had advanced fibrosis (2%). The specificity of noninvasive scores in detection of advanced fibrosis approximated 100% (95% confidence interval [CI], 99%-100%), with a negative predictive value of 98% (95% CI, 97%-99%) for all systems. However, the scoring systems detected fibrosis with a low level of sensitivity, ranging from 7% (95% CI, 0%-32%) to 13% (95% CI, 2%-40%). Positive predictive values ranged from 50% (95% CI, 7%-93%) to 67% (95% CI, 9%-99%). Their negative likelihood ratios ranged from 0.87 (95% CI, 0.71%-1.06%) to 0.93 (95% CI, 0.82%-1.07%); positive likelihood ratios were uninformative because of the small number of people with positive scores. CONCLUSIONS: In low-risk populations, negative results from noninvasive scoring systems reliably exclude advanced fibrosis, without requirements for further tests. Positive test results are often a false-positive result and should prompt further testing.

Elevated Liver Enzymes and Mortality in Older Individuals: A Prospective Cohort Study.

AIM OF THE STUDY: The aim of the study was to determine the excess risk of all-cause and cardiovascular mortality in older people with elevated liver enzymes [alanine transaminase (ALT) and gamma glutamyltransferase (GGT)]. METHODS: We utilized data from a large, prospective, population based study of 2061 people aged 50 to 99 years with linkage to a National Death Registry. Participants were categorized as having elevated liver enzymes using standard thresholds (for males, GGT>51 and ALT>40 IU/L, and GGT>33 and ALT>31 IU/L for females). Adjusted Cox proportional hazards models assessed the association of elevated liver enzymes and mortality with long duration follow-up. RESULTS: Over a median follow-up of 10 years (20,145 person years), 701 people died, including 203 (34%) from cardiovascular disease. Cox regression models adjusted for sex, age, smoking, and alcohol intake indicated that people with elevated liver enzymes had an increased risk of all-cause mortality that was modified by age (test for interaction P=0.01). Age-stratified analyses demonstrated no increased risk at younger ages [age 59 y and below; hazard ratio (HR): 0.46; 95% confidence interval, 0.06-3.49], but increased risk with age; age 60 to 69, HR: 1.05 (0.53-2.07), age 70 to 79 years, HR: 1.54 (0.81 to 2.93), and age 80 years and above, HR: 3.53 (1.55 to 8.04). Similarly, the risk of cardiovascular mortality with elevated liver enzymes was also modified by, and increased with age (test for interaction P=0.02); age 70 to 79, HR: 3.15 (1.37 to 7.23), age 80 years and above, HR: 6.86 (2.44 to 19.30). CONCLUSIONS: In community-dwelling elderly persons, an elevation in both ALT and GGT are associated with an excess risk of all-cause and cardiovascular mortality which increases with age.

Prevalence of elevated alanine transaminase in Australia and its relationship to metabolic risk factors: A cross-sectional study of 9,447 people.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: 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.

Exercise and diet in the management of nonalcoholic fatty liver disease.

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.

Side effects are incompletely reported among systematic reviews in gastroenterology.

OBJECTIVES: Systematic reviews are an integral component of evidence-based health care. However, little is known on how well they report the potential harms of interventions. We assessed the reporting of harms in recently published systematic reviews of interventions relevant to clinical gastroenterology. STUDY DESIGN: We identified all systematic reviews of randomized trials of gastroenterology interventions published from 2008 to 2012 in highly cited gastroenterology and general medical journals. We adapted the Consolidated Standards of Reporting Trials guidelines for harms and assessed qualitative and quantitative parameters of harms reporting. Regression analyses determined predictors of more comprehensive harms reporting. RESULTS: In total, 78 systematic reviews were identified, with 72 published in gastroenterology journals and six in general medical journals. Overall, one in three systematic reviews (26/78, 33%) did not refer to harms of the intervention anywhere in the article. Less than half of the studies included adverse events as an outcome measure, and data on absolute rates of adverse events were only provided in 28%. Most (65%) did not include any figures or tables on adverse event; however, all included these on efficacy outcomes (mean, 3 and range, 1-7). Regression analyses indicated that the use of reporting guidelines was significantly associated with better harms reporting (P = 0.04). CONCLUSION: The reporting of harms in gastroenterology systematic reviews is largely inadequate and highly asymmetrical compared with the reporting of benefits. We suggest that review authors routinely assess both efficacy and harms outcomes of an intervention and that reporting guidelines specifically targeting harms reporting be developed.

Radiologists' perspectives about evidence-based medicine and their clinical practice: a semistructured interview study.

OBJECTIVES: To describe radiologist's attitudes and perspectives on evidence-based medicine (EBM) and their practice. DESIGN: Face-to-face semistructured interviews, thematic analysis. SETTING: 24 institutions across six Australian states and New Zealand. Transcripts were imported into HyperRESEARCH software and thematically analysed. PARTICIPANTS: 25 radiologists. RESULTS: Six themes were identified: legitimising decisions (validated justification, prioritising patient preferences, reinforcing protocols), optimising outcomes (ensuring patient safety, maximising efficiency), availability of access (requiring immediacy, inadequacy of evidence, time constraints, proximity of peer networks, grasping information dispersion), over-riding pragmatism (perceptibly applicability, preserving the art of medicine, technical demands), limited confidence (conceptual obscurity, reputation-based trust, demands constant practice, suspicion and cynicism), and competing powers (hierarchical conflict, prevailing commercial interests). CONCLUSIONS: Radiologists believe EBM can support clinical decision-making for optimal patient outcomes and service efficiency but feel limited in their capacities to assimilate and apply EBM in practice. Improving access to evidence, providing ongoing education and training supplemented with practical tools for appraising evidence; and developing evidence-based guidelines and protocols may enhance feasibility and promote the confidence and skills among radiologists in applying EBM in radiology practice for better patient care.

The future liver of the Asia pacific: fatter and firmer from more fructose and fortune?

The Asia Pacific region is the most diverse and the most populous region in the world. Recent socioeconomic changes have resulted in an emerging epidemic of non-communicable diseases such as type 2 diabetes and nonalcoholic fatty liver disease. The prevalence of nonalcoholic fatty liver disease in Asian Pacific countries now approximates that seen in Western countries. This increase is fueled by rising obesity, partly due to adoption of Western style diets and exposure to compounds such as high fructose corn syrup that are not included in traditional diets. Furthermore, South Asian populations may be more genetically susceptible via the inheritance of polymorphisms in apolipoprotein 3 that increase insulin resistance and nonalcoholic fatty liver disease. Importantly, there remains a substantial lack of data on the incidence and natural history of nonalcoholic steatohepatitis and subsequent complications such as hepatocellular carcinoma in Asian Pacific populations. This information gap prevents estimation of current and future disease burden and impedes efforts to lobby health policymakers to improve public health measures, as given the size of Asian Pacific populations, prevention rather than treatment of non-communicable diseases remains key. This review article addresses these issues and highlights research priorities for nonalcoholic fatty liver disease within the Asia Pacific region.

Management of nonalcoholic steatohepatitis: an evidence-based approach.

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.