Nonalcoholic fatty liver disease(NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, ...excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis(NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma(HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type Ⅱ diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear toexperience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis.
Background and Aims
In general, physical activity (PA) and nonalcoholic fatty liver disease (NAFLD) have an inverse association. However, studies assessing the impact of the widely accepted Physical ...Activity Guidelines for Americans (PA Guidelines) on NAFLD are lacking.
Approach and Results
We performed a serial, cross‐sectional analysis among adults by using the 2007‐2016 US National Health and Nutrition Examination Survey. NAFLD and advanced fibrosis were defined by using various noninvasive panels. A PA questionnaire assessed the leisure‐time PA, occupation‐related PA, transportation‐related PA, and total sitting time as sedentary behavior. PA was categorized according to the PA Guidelines. Of the 24,588 individuals (mean age, 47.4 years; 47.9% males), leisure‐time PA (≥150 minutes per week) demonstrated 40% lower odds of NAFLD, whereas transportation‐related PA was associated with a 33% risk reduction in NAFLD. Analysis of total PA and sitting times simultaneously showed a dose‐response association between sitting time and NAFLD (P for trend < 0.001). Compliance with the PA Guidelines was lower in individuals with NAFLD versus those without NAFLD. The trends in compliance with the PA Guidelines for any type of PA remained stable in individuals with NAFLD except for a downtrend in transportation‐related PA. In contrast, an improvement in compliance with the PA Guidelines for leisure time was noted in the cohort without NAFLD. Although PA demonstrated a 10% stronger association with risk reduction of NAFLD in women, women showed a lower tendency of meeting the PA Guidelines. Trends in total sitting time increased significantly regardless of NAFLD status.
Conclusions
Sedentary behavior emerged as an independent predictor of NAFLD. Overall compliance with the PA Guidelines was lower in the cohort with NAFLD, with sex‐ and ethnicity‐based differences. Implementation of these observations in clinical practice may improve our understanding as well as clinical outcomes.
With recent improvements in the treatment of end‐stage liver disease (ESLD), a better understanding of the burden of cirrhosis and hepatocellular carcinoma (HCC) is needed in the United States. A ...population‐based study using the US Census and national mortality database was performed. We identified the age‐standardized etiology‐specific mortality rates for cirrhosis and HCC among US adults ages 20 years or older from 2007 to 2016. We determined temporal mortality rate patterns by joinpoint analysis with estimates of annual percentage change (APC). Age‐standardized cirrhosis‐related mortality rates increased from 19.77/100,000 persons in 2007 to 23.67 in 2016 with an annual increase of 2.3% (95% confidence interval CI 2.0‐2.7). The APC in mortality rates for hepatitis C virus (HCV)‐cirrhosis shifted from a 2.9% increase per year during 2007 to 2014 to a 6.5% decline per year during 2014 to 2016. Meanwhile, mortality for cirrhosis from alcoholic liver disease (ALD, APC 4.5%) and NAFLD (APC 15.4%) increased over the same period, whereas mortality for hepatitis B virus (HBV)‐cirrhosis decreased with an average APC of −1.1%. HCC‐related mortality increased from 3.48/100,000 persons in 2007 to 4.41 in 2016 at an annual rate of 2.0% (95% CI 1.3‐2.6). Etiology‐specific mortality rates of HCC were largely consistent with cirrhosis‐related mortality. Minority populations had a higher burden of HCC‐related mortality. Conclusion: Cirrhosis‐related and HCC‐related mortality rates increased between 2007 and 2016 in the United States. However, mortality rates in HCV‐cirrhosis demonstrated a significant decline from 2014 to 2016, during the direct‐acting antiviral era. Mortality rates for ALD/NAFLD‐cirrhosis and HCC have continued to increase, whereas HBV‐cirrhosis‐related mortality declined during the 10‐year period. Importantly, minorities had a disproportionately higher burden of ESLD‐related mortality.
Background & Aims
Nonalcoholic fatty liver disease (NAFLD) has been associated with sarcopenia. However, mortality in the setting of NAFLD‐related sarcopenia remains undefined. We aim to determine ...the all‐cause and cause‐specific mortality from sarcopenia among adults with NAFLD in the USA.
Methods
11 065 individuals in the Third National Health and Nutrition Examination Survey were studied and linked mortality through 2015 was analysed. NAFLD was diagnosed based on presence of ultrasonographic hepatic steatosis without other known liver diseases. Sarcopenia was defined as skeletal muscle index determined by bioelectrical impedance analysis. The Cox proportional hazard model was used to assess all‐cause mortality and cause‐specific mortality, and hazard ratio (HR) adjusted for known risk factors.
Results
During a median follow‐up of 23 years or more, sarcopenia was associated with increased all‐cause mortality (HR 1.27, 95% confidence interval CI 1.11‐1.44). Only in individuals with NAFLD, sarcopenia was associated with a higher risk for all‐cause mortality, while this association was absent in those without NAFLD. Individuals with both sarcopenia and NAFLD had a higher risk for all‐cause mortality (HR 1.28 95% CI 1.06‐1.55) compared with those without sarcopenia and NAFLD. Furthermore, sarcopenia was associated with a higher risk for cancer‐ and diabetes‐related mortality among those with NAFLD. This association was not noted in those without NAFLD.
Conclusion
In this nationally representative sample of US adults, sarcopenia was associated with a higher risk for all‐cause, cancer‐ and diabetes‐related mortality in individuals with NAFLD.
Background and Aims
Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in ...the US were studied.
Methods
A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003–2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan–Meier methods and multivariate Cox proportional hazards models.
Results
Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH −77.81%, 95% CI 76.37–79.25 vs. HCV −72.15%, 95% CI 71.37–72.93,
P
< .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71–0.79,
P
< .001).
Conclusions
Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.
With the prevalence of hepatitis C virus expected to decline, the proportion of hepatocellular carcinoma (HCC) related to non-alcoholic steatohepatitis (NASH) is anticipated to increase exponentially ...due to the growing epidemic of obesity and diabetes. The annual incidence rate of developing HCC in patients with NASH-related cirrhosis is not clearly understood with rates ranging from 2.6%-12.8%. While multiple new mechanisms have been implicated in the development of HCC in NASH; further prospective long-term studies are needed to validate these findings. Recent evidence has shown a significant proportion of patients with non-alcoholic fatty liver disease and NASH progress to HCC in the absence of cirrhosis. Liver resection and transplantation represent curative therapeutic options in select NASH-related HCC patients but have placed a significant burden to our healthcare resources and utilization. Currently NASH-related HCC is the fastest growing indication for liver transplant in HCC candidates. Increased efforts to implement effective screening and preventative strategies, particularly in non-cirrhotic NASH patients, are needed to reduce the future impact imposed by NASH-related HCC.
Statins may improve outcomes in patients with chronic liver disease (CLD). We conducted a systematic review and meta-analysis to evaluate the impact of statins in the setting of CLD.
We searched ...several databases from inception to 17 October 2016 to identify comparative studies evaluating the role of statins in CLD. Outcomes of interest were the associations between statin use and progression of fibrosis, development of hepatic decompensation in cirrhosis, and mortality in CLD. Adjusted hazard ratios (HRs) were pooled and analyzed using a random effects model. Subgroup analyses were performed based on the method of detection for progression of hepatic fibrosis and quality of studies.
We included 10 studies (1 randomized controlled trial and 9 observational) with 259,453 patients (54,441 statin users and 205,012 nonusers). For progression of hepatic fibrosis, pooled HR (95% confidence interval) was 0.49 (0.39-0.62). On subgroup analysis of studies using ICD-9 (The International Classification of Diseases, Ninth Revision) coding and a second method to detect cirrhosis, pooled HR was 0.58 (0.51-0.65); pooled HR for studies using ICD-9 coding only was 0.36 (0.29-0.44). For progression of fibrosis in patients with hepatitis C virus (HCV) infection, pooled HR was 0.52 (0.37-0.73). For hepatic decompensation in cirrhosis, pooled HR was 0.54 (0.46-0.65). For mortality, pooled HR based on observational studies was 0.67 (0.46-0.98); in the randomized controlled trial, HR was 0.39 (0.15-0.99). However, the quality of evidence for these associations is low as most included studies were retrospective in nature and limited by residual confounding.
Statins may retard the progression of hepatic fibrosis, may prevent hepatic decompensation in cirrhosis, and may reduce all-cause mortality in patients with CLD. As the quality (certainty) of evidence is low, further studies are needed before statins can be routinely recommended.
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