Global Epidemiology of Chronic Liver Disease

Watch a video presentation of this article Cirrhosis is a leading cause of mortality and morbidity across the world. It is the 11th leading cause of death and 15th leading cause of morbidity, accounting for 2.2% of deaths and 1.5% of disability-adjusted life years worldwide in 2016.1 CLD caused 1.32 million deaths in 2017, approximately two-thirds among men and one-third among women.2 Historically, viral hepatitis has been the leading etiology for CLD. However, improved prevention strategies (in the case of hepatitis B) and treatment (in the case of hepatitis C) have led to improving CLD trends. This is reflected in global declines that have been observed in liver disease mortality rates over the past 30 years. Specifically, the age-adjusted death rate (AADR) from CLD has declined from 21 to 16.5 per 100,000 population from 1990 to 2017.2, 3 As depicted in Fig. 1, these declines have been most marked for liver disease from hepatitis B infection. Meanwhile, obesity and alcohol consumption, which are common and increasing in many parts of the world, have become key liver disease risk factors. They are anticipated to drive CLD epidemiology going forward and to account for increasing proportions of death in the future, although mortality trends have not yet reflected their impact (Fig. 2). Reductions in CLD mortality rates vary across regions and reflect country-specific approaches to viral hepatitis prevention and treatment, as well as trends in IVDU, alcohol consumption, and obesity rates. From 1980 to 2010, mortality significantly declined in countries as varied as China (66% AADR reduction from 43 to 16 per 100,000) and the United States (24% reduction from 15 to 11 per 100,000), largely because of HBV prevention efforts.3 Meanwhile, other countries have experienced significant mortality reductions but still face persistently high liver disease mortality rates: an example is Egypt with a 26% AADR decline from 98 to 72 per 100,000 largely a result of massive efforts targeting chronic hepatitis C infection and schistosomiasis.3 Finally, there are regions that have experienced increases in mortality rates. For example, AADR increased by 24% in Mongolia (44-55 per 100,000) and by 18% in India (17-20 per 100,000), largely driven by viral hepatitis and in part by increasing alcohol consumption and obesity rates; AADR increased by 64% in Russia (11-19 per 100,000) and 31% in the United Kingdom (7-9 per 100,000) largely because of alcohol-related liver disease.3 The absolute number of CLD cases (inclusive of any stage of disease severity) is estimated at 1.5 billion worldwide.4 The most common causes of prevalent disease are NAFLD (59%), followed by HBV (29%), HCV (9%), and ALD (2%) (Table 1).2, 5 Other liver diseases, including primary biliary cholangitis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, Wilson’s disease, and autoimmune hepatitis, account for 1% of cases. An important caveat to these data is that alcohol most likely accounts for a larger proportion of liver disease prevalence and mortality but is underreported by persons and countries because of cultural concerns and is often a secondary (and unreported) liver disease etiology that coexists with viral hepatitis or NAFLD. There are 257 million people worldwide who are living with chronic HBV. Without proper management, approximately 20% will die early of liver failure or hepatocellular carcinoma.6 It is estimated that only 11% of infected persons are aware of their infection, and 17% of those receive treatment.7 Vertical transmission, IVDU, sexual transmission, and nosocomial transmission (use of contaminated medical equipment or blood products) are the main modes of spread.6 Childhood acquisition represents the highest risk for chronic HBV infection: 80% to 90% of infections acquired within the first year of life and 50% to 60% of infections before age 6 years lead to chronic HBV.6 In contrast, 50%. In 2016, Russia was among the highest alcohol-consuming countries (12 L/year), followed by the United States (8-10 L/year) and moderate use in India and China (4-6 L/year). The Middle East has the lowest consumption rates; Egypt, for instance, consumes 30% in the Middle East and South America.27 Up to 59% of NAFLD cases are of the nonalcoholic steatohepatitis (NASH) phenotype, the main disease subtype with risk for fibrotic progression to cirrhosis.28 Although direct markers of NASH do not exist, obesity and type 2 diabetes are strong clinical risk factors for fibrotic progression, and their population-level trends provide insight into disease trends.29-32 Obesity has increased in nearly all regions of the world since 1975. Obesity rates in the United States are among the highest, estimated at >30%. However, despite obesity prevalence rates <5%, China and India account for a very large proportion of global obesity because of their large populations. Russia, Mexico, and Egypt also have the highest absolute numbers of adults with obesity.33, 34 Mathematical modeling studies using current estimates of NAFLD, obesity, and diabetes forecast that the burden of NASH will increase over the next 10 years. These models estimate that the United States will have a 168% increase in decompensated cirrhosis and 178% increase in death related to NAFLD,35 and that China will have the largest absolute number of NAFLD-related deaths.36 Also important to consider is that the simultaneous increase in alcohol consumption in the population potentially has implications for obesity-related liver disease. Alcohol consumption, even at low-to-moderate quantities, has been noted to increase the risk for CLD among obese individuals and also may exacerbate NAFLD progression.37 CLD is a significant public health concern. NAFLD and ALD are expected to increase given that most of the world is experiencing increasing obesity rates, and many areas are experiencing increasing alcohol consumption. HBV’s burden will most likely decline with greater childhood vaccination coverage; however, it will take time to see its impact, and in the meantime improved diagnosis and better access to treatment are key. Finally, despite the availability of effective treatments, increasing IVDU and breaks in the cascade of care are concerning for an increasing HCV burden. Reducing the impact of CLD requires region-specific interventions tailored according to local epidemiological trends and specific risk factors.