Disease Burden of Non Alcoholic Fatty Liver Disease (NAFLD) Dr. H. Razavi May 31, 2017 First European NASH NAFLD Summit
Disclosure: This work with funded by a multi-sponsored research grant from Intercept, Gilead and Boehringer Ingelheim. The funders had no influence over the design, the implementation, or the outcomes of the study. H. Razavi has not received any personal remuneration for this or any other project. 2
This work would not be possible without the inputs of the following experts France Drs. Vlad Ratziu & Lawrence Serfaty Germany Drs. Andreas Geier, Michael Manns, Christian Trautwein & Stefan Zeuzem Italy Drs. Stefano Bellentani, Antonio Craxi, Giulio Marchesini & Salvatore Petta Spain Drs. Maria Arias-Loste, Joan Caballeria, Javier Crespo & Manuel Romero Gomez United Kingdom Drs. Quentin Anstee, Christopher Day, Jude Oben & Philip Newsome 3
Methodology Convened a panel of NAFLD experts in each country Collect published epidemiology data for NAFLD Gathered country specific rates for obesity and diabetes to estimate incidence Used published work to estimate progression rates for non-alcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) Modeled the disease progression Validates the forecasts against reported NASH related HCC cases 4
The disease progression model tracked the population over time, taking into consideration the reversible nature of the disease The outputs of the model were compared against empirical data at multiple stages New (Incident) Cases Incidence of Adult Obesity / Diabetes F0 NAFL/NASH F1 NASH F2 NASH F3 NASH Compensated Cirrhosis (F4) NASH Used to Calibrate the model Hepatocellular Carcinoma Decompensated Cirrhosis NASH % of population with NAFLD % of NASH with F3/F4 Incident HCC due to NASH Liver Related Death Liver Transplantation 5
NASH prevalence and obesity in the EU5 are lower than the US BMI 30 % of total population 15+ with NAFLD % of NAFLD with NASH % of total population 15+ with NASH US 28% 30% 20% 6.3% France 16% 25% 16% 4.2% Germany 19% 25% 18% 4.6% Italy 16% 28% 17% 4.9% Spain 18% 25% 17% 4.4% UK 21% 25% 18% 4.8% China 4% 20% 13% 2.8% Japan 4% 20% 16% 3.4% 6
Obesity has been increasing in the European countries NAFLD is accounting for more HCC cases in the UK Adult Obesity Rate 30% 25% 20% 15% 10% 5% 0% 1980 1990 2000 2010 2020 2030 UK Germany Spain France Italy Adult obesity have been increasing but the rate of increase has (and is projected to) slowed. UK The proportion of HCC attributable to NAFLD in Newcastle was 34.8% in 2010, a tenfold increase as compared to 2000 (Dyson 2014) Dyson J, Jaques B, Chattopadyhay D, Lochan R, Graham J, Das D, et al. Hepatocellular cancer: the impact of obesity, type 2 diabetes and a multidisciplinary team. J Hepatol. 2014;60(1):110-7. 7
Millions Millions Most individuals will remain as NAFL but the NASH population is expected to grow by 45% while cirrhotic cases will increase by 120% EU5, 2016 EU5, 2030 90.0 90.0 84.0 69.0 80.0 70.0 72.3 62.7 80.0 70.0 60.0 60.0 50.0 50.0 40.0 40.0 30.0 30.0 20.0 20.0 6.0 10.0 0.0 4.5 2.5 1.6 0.9 Total F0 F1 F2 F3 F4 10.0 0.0 4.0 3.0 2.0 Total F0 F1 F2 F3 F4 NASH NAFL 8
Although the increase in total NAFLD cases is slowing down, NASH, HCC, and liver related deaths is projected to continue to increase NAFLD & NASH Cases - EU5 90,000,000 80,000,000 70,000,000 60,000,000 50,000,000 40,000,000 30,000,000 20,000,000 10,000,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 NASH Cases - EU5 20,000,000 18,000,000 16,000,000 14,000,000 12,000,000 10,000,000 8,000,000 6,000,000 4,000,000 2,000,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 NAFLD Cases NASH Cases NASH Cases Annual Liver Related Deaths - EU5 50,000 45,000 40,000 35,000 30,000 25,000 20,000 15,000 10,000 5,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 NAFLD Annual HCC Incidence - EU5 9,000 8,000 7,000 6,000 5,000 4,000 3,000 2,000 1,000 0 1950 1960 1970 1980 1990 2000 2010 2020 2030 HCC Incidence 9
Conclusions In the absence of interventions, advance liver diseases associated with with NAFLD will more than double over the next 15 years while total NAFLD cases will increase by 16% NAFLD is reversible diet and exercise can reverse liver fibrosis Interventions are required to manage the increase in future disease burden The European Union should promote awareness of NAFLD and strategies to reduce the disease burden (including weight loss and diet) These same interventions will also have an impact on other noncommutable diseases including cardiovascular diseases and diabetes Better reporting systems are required to track NAFLD related disease burden to measure progress 10
US Model Transition Rates Model fibrosis progression as compared to Younossi 2016 and Singh 2015 20.0% Annual Fibrosis Progression Rates 15.0% 13.3% 13.3% 12% 13% 15% 14% 10.0% 5.0% 2.2% 9.9% 4.2% 4.2% 5.1% 6% 4% 4% 10% 5% 10% 7% 8% Model Max Model Min 0.0% 0.7% Younossi 2016-5.0% -3% Singh 2015-10.0% -15.0% -20.0% -25.0% -23% - Singh, S., et al., Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol, 2015. 13(4): p. 643-54.e1-9. - Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta- Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26707365 21
US Model Transition Rates Model liver related mortality as compared to Younossi 2016 Annual Liver Related Mortality Rates 1.40% 1.32% 1.20% 1.00% 1.18% 1.07% 0.80% 0.60% 0.54% Model 0.40% 0.20% 0.03% 0.17% 0.05% 0.07% 0.04% 0.03% 0.06% 0.03% 0.22% 0.04% 0.29% Younossi 2016 0.00% - Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta- Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26707365 22
US Model Transition Rates Model CVD mortality as compared to Younossi 2016 1.20% Annual CVD Mortality Rates 1.00% 0.98% 0.80% 0.60% 0.44% 0.49% 0.57% 0.47% Model 0.40% 0.20% 0.30% Younossi 2016 0.00% - Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta- Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26707365 23
US Model Transition Rates Model HCC incidence as compared to Younossi 2016 Annual HCC Incidence Rates 0.35% 0.3285% 0.30% 0.25% 0.20% Model 0.15% 0.10% 0.05% 0.00% 0.0003% 0.0093% 0.0189% 0.0380% 0.042% 0.044% 0.036% 0.063% Younossi 2016 - Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global Epidemiology of Non-Alcoholic Fatty Liver Disease-Meta- Analytic Assessment of Prevalence, Incidence and Outcomes. Hepatology. 2016. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26707365 24
US Model Transition Rates Other transition rates used in model: Miscellaneous Model Transition Rates 70.0% 60.0% 61.0% 50.0% 40.0% 30.0% 20.0% 16.2% Model 10.0% 3.8% 0.0% - Sanyal AJ, Banas C, Sargeant C, Luketic VA, Sterling RK, Stravitz RT, et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic steatohepatitis and hepatitis C. Hepatology. 2006;43(4):682-9. Available at: http://www.ncbi.nlm.nih.gov/pubmed/16502396 - Younossi ZM, Otgonsuren M, Henry L, Venkatesan C, Mishra A, Erario M, et al. Association of nonalcoholic fatty liver disease (NAFLD) with hepatocellular carcinoma (HCC) in the United States from 2004 to 2009. Hepatology. 2015;62(6):1723-30. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26274335 - Ries LAG, Young GL, Keel GE, Eisner MP, Lin YD, Horner M-J. SEER survival monograph: cancer survival among adults: U.S. SEER program, 1988-2001,patient and tumor characteristics. [NIH Pub.No.07-6215]. 2007. Bethesda, MD, National Cancer Institute, SEER Program. 25