Hepatocellular carcinoma (HCC) is increasingly reported in patients with nonalcoholic fatty liver disease (NAFLD). Our aim was to assess the prevalence and mortality of patients with NAFLD-HCC. We examined Surveillance, Epidemiology and End Results (SEER) registries (2004)(2005)(2006)(2007)(2008)(2009)) with Medicare-linkage files for HCC, which was identified by the International Classification of Diseases for Oncology, third edition codes using topography and morphology codes 8170-8175. Medicare-linked data was used to identify NAFLD, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic liver disease (ALD), and other liver disease using International Classification of Diseases, Ninth Revision, Clinical Modification codes. NAFLD was also defined by clinical diagnosis (cryptogenic cirrhosis, obese-diabetics with cryptogenic liver disease). A logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of HCC. In addition, adjusted hazard ratios for 1-year mortality were estimated by Cox's proportional hazard regression. A total of 4,929 HCC cases and 14,937 controls without HCC were included. Of the HCC cases, 54.9% were related to HCV, 16.4% to ALD, 14.1% to NAFLD, and 9.5% to HBV. Across the 6-year period (2004 to 2009), the number of NAFLD-HCC showed a 9% annual increase. NAFLD-HCC were older, had shorter survival time, more heart disease, and were more likely to die from their primary liver cancer (all P < 0.0001). Of those who received a transplant after HCC (n 5 488), only 5% were related to NAFLD-HCC. In multivariate analysis, NAFLD increased the risk of 1-year mortality (OR, 1.21; 95% CI: 1.01-1.45). Additionally, older age, lower income, unstaged HCC increased risk of 1-year mortality while receiving a liver transplant (LT), and having localized tumor stage were protective (all P < 0.05). Conclusions: NAFLD is becoming a major cause of HCC in the United States. NAFLD HCC is associated with shorter survival time, more advanced tumor stage, and lower possibility of receiving a LT.

Background and Aims Chronic hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and alcohol‐associated liver disease (ALD) are main causes of chronic liver disease. We assessed the global incidence, mortality, and disability‐adjusted life‐years (DALYs) related to chronic liver disease (primary liver cancer [LC] and cirrhosis). Approach and Results We obtained data from the 2017 Global Burden of Disease study. In 2017, there were 2.14 million liver‐related deaths (2.06‐2.30 million), representing an 11.4% increase since 2012 (16.0% increase in LC deaths; 8.7% increase in cirrhosis deaths). LC and cirrhosis accounted for 38.3% and 61.7%, respectively, of liver deaths (LC and cirrhosis deaths were related to HBV [39% and 29%], HCV [29% and 26%], ALD [16% and 25%], and NAFLD [8% and 9%]). Between 2012 and 2017, age‐standardized incidence rate, age‐standardized death rate (ASDR), and age‐standardized DALY rate increased for LC from 11.1 to 11.8, 10.1 to 10.2, and 250.4 to 253.6 per 100,000, respectively. Although age‐standardized incidence rate for cirrhosis increased from 66.0 to 66.3, ASDR and age‐standardized DALY rate decreased from 17.1 to 16.5 and 532.9 to 510.7, respectively. The largest increase in ASDR for LC occurred in Eastern Europe (annual percent change [APC] = 2.18% [0.89%‐3.49%]), whereas the largest decrease occurred in high‐income Asia Pacific (APC = −2.88% [−3.58 to −2.18%]). ASDR for LC‐NAFLD and ALD increased annually by 1.42% (1.00%‐1.83%) and 0.53% (0.08‐0.89), respectively, whereas there were no increases for HBV (P = 0.224) and HCV (P = 0.054). ASDR for cirrhosis‐NAFLD increased (APC = 0.29% [0.01%‐0.59%]) but decreased for ALD (APC = −0.44% [−0.78% to −0.40%]), HCV (APC = −0.50% [−0.81% to −0.18%]), and HBV (APC = −1.43% [−1.71% to −0.40%]). Conclusions From 2012 to 2017, the global burden of LC and cirrhosis has increased. Viral hepatitis remains the most common cause of liver deaths, and NAFLD is the most rapidly growing contributor to liver mortality and morbidity.

ObjectiveGiven significant advances in treatment of viral hepatitis and the growing epidemic of obesity, the burden of the different types of liver diseases in the USA may be changing. Our aim was to assess the shift in the prevalence of different liver disease aetiologies in the USA over the past three decades.DesignNational Health and Nutrition Examination Surveys (NHANES; cross-sectional 1988–1994 and 1999–2016) were used.ResultsA total of 58 731 adults from NHANES (1988–2016) were included. Over the study period, the prevalence of chronic hepatitis B and alcoholic liver disease remained stable: 0.3%–0.4% and 0.8%–1.0%, respectively (p>0.05). The prevalence of chronic hepatitis C decreased nearly twofold: 1.6% in 1988–1994 to 0.9% in 2013–2016 (p=0.03). In contrast, the prevalence of non-alcoholic fatty liver disease (NAFLD; by US-Fatty Liver Index) increased from 20.0% (1988–1994) to 28.3% (1999–2004) to 33.2% (2009–2012) and 31.9% (2013–2016) (p<0.0001). Furthermore, steady increases were observed in the rates of obesity (22.2% in 1988–1994 to 31.0% in 1999–2004 to 38.9% in 2013–2016), type 2 diabetes mellitus (T2DM) (from 7.2% to 8.2% to 13.5% same years), insulin resistance and hypertension (all p<0.0001). Yearly trend analyses showed that the only LD with consistently increasing prevalence was NAFLD (trend p=0.01). Multivariable regression analysis showed that obesity (OR 10.4; 95% CI 9.5 to 11.3) and T2DM (OR 3.7; 95% CI 3.2 to 4.2) were the major independent predictors of NAFLD.ConclusionsOver the past 30 years in the USA, NAFLD is the only liver disease with growing prevalence, synchronous with the increasing rates of obesity and T2DM.

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