Mary E. Rinella

Background & Aims: Non‐alcoholic fatty liver disease is an epidemic. Identifying modifiable risk factors for non‐alcoholic fatty liver disease development is essential to design effective prevention programmes. We tested whether 25‐year patterns of body mass index change are associated with midlife non‐alcoholic fatty liver disease.Methods: In all, 4423 participants from Coronary Artery Risk Development in Young Adults, a prospective population‐based biracial cohort (age 18‐30), underwent body mass index measurement at baseline (1985‐1986) and 3 or more times over 25 years. At Year 25, 3115 had liver fat assessed by non‐contrast computed tomography. Non‐alcoholic fatty liver disease was defined as liver attenuation ≤40 Hounsfield Units after exclusions. Latent mixture modelling identified 25‐year trajectories in body mass index per cent change (%Δ) from baseline.Results: We identified four distinct trajectories of BMI%Δ: stable (26.2% of cohort, 25‐year BMI %Δ = 3.1%), moderate increase (46.0%, BMI%Δ = 21.7%), high increase (20.9%, BMI%Δ = 41.9%) and extreme increase (6.9%, BMI%Δ = 65.9%). Y25 non‐alcoholic fatty liver disease prevalence was higher in groups with greater BMI %Δ: 4.1%, 9.3%, 13.0%, and 17.6%, respectively (P‐trend <.0001). In multivariable analyses, participants with increasing BMI%Δ had increasingly greater odds of non‐alcoholic fatty liver disease compared to the stable group: OR: 3.35 (95% CI: 2.07‐5.42), 7.80 (4.60‐13.23) and 12.68 (6.68‐24.09) for moderate, high and extreme body mass index increase, respectively. Associations were only moderately attenuated when adjusted for baseline or Y25 body mass index.Conclusions: Trajectories of weight gain during young adulthood are associated with greater non‐alcoholic fatty liver disease prevalence in midlife independent of metabolic covariates and baseline or concurrent body mass index highlighting the importance of weight maintenance throughout adulthood as a target for primary non‐alcoholic fatty liver disease prevention.

Background: Management guidelines from the American Association for the Study of Liver Diseases/American College of Gastroenterology/American Gastroenterology Association published in 2012 for nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) recommend weight loss, vitamin E and pioglitazone as effective therapies for the treatment of biopsy-confirmed NASH. However, little is known about how physicians in the US diagnose NASH or whether published guidelines are being followed. Methods: We assessed current diagnostic and treatment patterns of the management of NAFLD and NASH among academic gastroenterologists and hepatologists in the US using a standardized survey developed to collect information regarding respondents’ practice environments, diagnostic techniques, and medication usage in patients with NAFLD/NASH. Results: We invited 482 gastroenterologists and hepatologists, predominantly from academic centers, of whom 163 completed the survey. Only 24% of providers routinely perform liver biopsy, predominantly among patients with elevated serum aminotransferases. Vitamin E is prescribed regularly by 70% while only 14% routinely prescribe pioglitazone. Despite recommendations to the contrary, ~25% prescribe pioglitazone or vitamin E without biopsy confirmation of NASH. Metformin is used as frequently as pioglitazone despite its proven lack of efficacy in NASH. Overall, 40–73% adhere to published guidelines, depending on the specific question. There was no significant difference seen in adherence to guidelines between gastroenterologists and hepatologists. Conclusion: This survey suggests that clinical practice patterns among gastroenterologists and hepatologists for the management of NASH frequently diverge from published practice guidelines. Although liver biopsy remains the gold standard to diagnose NASH, less than 25% of respondents routinely require it to make the diagnosis of NASH. We conclude that NASH is underdiagnosed in gastroenterology and hepatology practices, highlighting the need to refine noninvasive diagnostic tools.

Background & Aims: Non‐alcoholic steatohepatitis (NASH) is an independent risk factor for cardiovascular disease (CVD) morbidity after liver transplantation, but its impact on CVD mortality is unknown. We sought to assess the impact of NASH on CVD mortality after liver transplantation and to predict which NASH recipients are at highest risk of a CVD‐related death following a liver transplant.Methods: Using the Organ Procurement and Transplantation Network database, we examined associations between NASH and post‐liver transplant CVD mortality, defined as primary cause of death from thromboembolism, arrhythmia, heart failure, myocardial infarction or stroke. A physician panel reviewed cause of death.Results: Of 48 360 liver transplants (2/2002–12/2011), 5057 (10.5%) were performed for NASH cirrhosis. NASH recipients were more likely to be older, female, obese, diabetic and have history of renal failure or prior CVD vs. non‐NASH (P < 0.001 for all). Although there was no difference in overall all‐cause mortality (log‐rank P = 0.96), both early (30‐day) and long‐term CVD‐specific mortality was increased among NASH recipients (Odds ratio = 1.30, 95% Confidence interval (CI): 1.02–1.66; Hazard ratio = 1.42, 95% CI: 1.07–1.41 respectively). These associations were no longer significant after adjustment for pre‐transplant diabetes, renal impairment or CVD. A risk score comprising age ≥55, male sex, diabetes and renal impairment was developed for prediction of post‐liver transplant CVD mortality (c‐statistic 0.60).Conclusion: NASH recipients have an increased risk of CVD mortality after liver transplantation explained by a high prevalence of comorbid cardiometabolic risk factors that in aggregate identify those at highest risk of post‐transplant CVD mortality.

Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are obesity‐related conditions with high cardiovascular mortality. Whether NAFLD is independently associated with subclinical myocardial remodeling or dysfunction among the general population is unknown. We performed a cross‐sectional analysis of 2,713 participants from the multicenter, community‐based Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent concurrent computed tomography (CT) quantification of liver fat and comprehensive echocardiography with myocardial strain measured by speckle tracking during the Year‐25 examination (age, 43‐55 years; 58.8% female and 48.0% black). NAFLD was defined as liver attenuation ≤40 Hounsfield units after excluding other causes of liver fat. Subclinical left ventricular (LV) systolic dysfunction was defined using values of absolute peak global longitudinal strain (GLS). Diastolic dysfunction was defined using Doppler and tissue Doppler imaging markers. Prevalence of NAFLD was 10.0%. Participants with NAFLD had lower early diastolic relaxation (e’) velocity (10.8 ± 2.6 vs. 11.9 ± 2.8 cm/s), higher LV filling pressure (E/e’ ratio: 7.7 ± 2.6 vs. 7.0 ± 2.3), and worse absolute GLS (14.2 ± 2.4% vs. 15.2 ± 2.4%) than non‐NAFLD (P < 0.0001 for all). When adjusted for HF risk factors or body mass index, NAFLD remained associated with subclinical myocardial remodeling and dysfunction (P < 0.01). The association of NAFLD with e’ velocity (β = −0.36 [standard error = 0.15] cm/s;P = 0.02), E/e’ ratio (β = 0.35 [0.16];P = 0.03), and GLS (β = −0.42 [0.18]%;P = 0.02) was attenuated after controlling for visceral adipose tissue. Effect modification by race and sex was not observed.Conclusions:NAFLD is independently associated with subclinical myocardial remodeling and dysfunction and provides further insight into a possible link between NAFLD and HF. (Hepatology2015;62:773–783)

Nonalcoholic fatty liver disease (NAFLD) is recognized as the most common cause of chronic liver disease in the United States. Nonalcoholic steatohepatitis (NASH) occurs in a subset of patients with NAFLD and is characterized by the presence of hepa-tocellular injury, which is progressive in a substantial proportion of cases and can lead to cirrhosis and all of its complications. Although the diagnosis of NAFLD can be made through imaging studies or liver biopsy, the diagnosis of NASH still requires histologic confirmation. Liver biopsy should be performed in the presence of risk factors for advanced disease. Measures aimed at promoting weight loss, a healthier lifestyle, and optimization of metabolic risk factors remain the cornerstone of management of NAFLD. Therapeutic agents that are presently considered the most promising in NAFLD are effective in less than 50% of patients. Among patients with biopsy-proven NASH, treatment with pharmacologic agents should be considered; however, the role of specific agents in NASH still needs further study. Despite a wealth of research over the past 15 years, many controversies remain with respect to the diagnosis and management of NAFLD and NASH as well as the influence of alcohol on liver disease progression in these patients.