Haley Bush

Clinical and Economic Burden of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with an increasing global prevalence associated with tremendous clinical, economic, and health-related quality-of-life burden. Clinically, NAFLD is considered the liver manifestation of metabolic syndrome. However, diagnosing NAFLD presents significant challenges due to the limited noninvasive and accurate diagnostic tools available to not only accurately diagnose nonalcoholic steatohepatitis but also to stage hepatic fibrosis, the major predictor of long-term outcomes, including mortality.

Non-alcoholic steatofibrosis (NASF) can independently predict mortality in patients with non-alcoholic fatty liver disease (NAFLD)

Background Hepatic fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) independently predicts mortality. Given liver biopsy’s invasive nature, non-invasive method to assess hepatic steatosis and fibrosis provides NAFLD risk stratification algorithm in clinical practice. NAFLD fibrosis score (NFS) is simple and non-invasive predictive model recommended by American Association for the Study of Liver Disease (AASLD) Guideline to identify patients with NAFLD with fibrosis risk. The aim of this study is to assess long-term outcomes of subjects with significant non-alcoholic steatofibrosis (NASF) as established by ultrasound (US) and NFS. Methods Used National Health and Nutrition Examination Survey (NHANES III) with National Death Index-linked Mortality Files. NAFLD diagnosis established by the presence of moderate to severe hepatic steatosis on US without other causes of chronic liver disease (alcohol consumption <20 gr/day,hepatitis B surface-antigen negative, anti-hepatitis C virus antibody negative, transferrin saturation <50%). Significant hepatic fibrosis was estimated by high NFS (>0.676) and calculated with previously published formula. Subjects with NAFLD and high NFS have significant NASF. Results NHANES III included 20 050 adult participants. 2515 participants complete data and NAFLD with 5.1% (n=129) meeting criteria for significant SF. Subjects with significant SF were older, had higher body mass index, waist circumference and the homeostasis model assessment (HOMA) scores and higher rates of comorbidities (diabetes, congestive heart failure (CHF), stroke; all p<0.001). After median of 207 months of follow-up, overall mortality in NAFLD cohort was 30.0% (n=754). Crude mortality higher in subjects with significant SF (67.4% vs 28.0%, p<0.001). In multivariate survival analysis, predictors of overall mortality included significant SF (adjusted HR (aHR): 1.37; 95% CI 1.07 to 1.76, p=0.01), older age (aHR:1.08; 95% CI 1.07 to 1.09 per year), male gender (aHR:1.44; 95% CI 1.24 to 1.67), black race (aHR:1.24; 95% CI 1.04 to 1.48)), history of hypertension (aHR:1.40; 95% CI 1.20 to 1.64), diabetes (aHR:1.69; 95% CI 1.43 to 2.00), CHF (aHR:1.77; 95% CI 1.38 to 2.261), stroke (aHR:1.84; 95% CI 1.38 to 2.48) and smoking (aHR:1.74; 95% CI 1.47 to 2.07) (all p<0.02). Sensitivity analysis showed that the best association of SF with mortality is higher at NFS threshold of 0.80 (aHR:1.41; 95% CI 1.09 to 1.83, p=0.01). Conclusions Significant NASF determined non-invasively is an independent predictor of mortality. These data should help clinicians to easily risk-stratify patients with NAFLD for close monitoring and treatment considerations in clinical trial setting.

Pediatric Non-Alcoholic Fatty Liver Disease

With the increase in the prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) has become among the leading causes of chronic liver disease in the pediatric age group. Once believed to be a “two-hit process”, it is now clear that the actual pathophysiology of NAFLD is complex and involves multiple pathways. Moreover, NAFLD is not always benign, and patients with non-alcoholic steatohepatitis (NASH) are at increased risk of developing advanced stages of liver disease. It has also been shown that NAFLD is not only a liver disease, but is also associated with multiple extrahepatic manifestations, including cardiovascular diseases, type 2 diabetes, and low bone mineral density. Although the data is scarce in the pediatric population, some studies have suggested that long-term mortality and the requirement of liver transplantation will continue to increase in patients with NAFLD. More studies are needed to better understand the natural history of NAFLD, especially in the pediatric age group.

Hospice care in Medicare patients with primary liver cancer: the impact on resource utilisation and mortality

Few studies have assessed the impact of hospice care in patients with primary liver cancer.

Among Patients With NAFLD, Treatment of Dyslipidemia Does Not Reduce Cardiovascular Mortality

Dyslipidemia is one of the common risk factors for NAFLD and is associated with cardiovascular (CV) mortality, which is the most common cause of death in NAFLD. Lipid‐lowering agents (LLAs) are used to reduce CV events in the general population. Our aim was to assess whether the use of LLAs in patients with NAFLD can reduce the risk of CV mortality. We used the third National Health and Nutrition Examination Survey mortality linked files. Mortality was determined from the National Death Index records through 2011. NAFLD was diagnosed by ultrasound after exclusion of other causes of liver disease. After inclusion and exclusion, the cohort consisted of 2,566 patients with NAFLD (45.8% < 45 years of age, 52.8% male, 75.4% white). Those who were taking LLAs were more likely to be older, non‐Hispanic white, and had significantly higher rates of diabetes mellitus (DM), hyperlipidemia, hypertension, metabolic syndrome, and history of CV disease (CVD) (all P< 0.01). In our multivariate analysis, DM was an independent predictor of overall mortality (adjusted hazard ratio [aHR]: 1.79 [95% confidence interval (CI): 1.40‐2.30]) and CV mortality (aHR: 1.89 [95% CI: 1.08‐3.30]). History of CVD was associated with both overall (aHR: 2.03 [95% CI: 1.57‐2.63]) and CV mortality (aHR: 3.69 [95% CI: 2.23‐6.08]). In contrast, the use of statins and other LLAs was not associated with reduction in overall (aHR = 0.95 [95% CI: 0.37‐2.44] and aHR = 1.43 [95% CI: 0.99‐2.07]) and CV mortality (aHR = 1.20 [95% CI: 0.26‐5.54] and aHR = 1.63 [95% CI: 0.70‐3.76]). Conclusion: The use of statins and other LLAs did not reduce the increased risk of overall or CV mortality in NAFLD.