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Global Burden Of Liver Disease: A True Burden on Health Sciences and Economies!!

S. K. Sarin, MD, DM

S. K. Sarin, MD, DM
Department of Hepatology, Institute of Liver and Biliary Sciences
New Delhi, India

Rakhi Maiwall, MD, DM

Rakhi Maiwall, MD, DM
Department of Hepatology, Institute of Liver and Biliary Sciences
New Delhi, India

Chronic liver disease occurs throughout the world irrespective of age, sex, region or race. Cirrhosis is an end result of a variety of liver diseases characterized by fibrosis and architectural distortion of the liver with the formation of regenerative nodules and can have varied clinical manifestations and complications. According to WHO, about 46% of global diseases and 59% of the mortality is because of chronic diseases and almost 35 million people in the world die of chronic diseases 1. Liver disease rates are steadily increasing over the years. According to National statistics in the UK, liver diseases have been ranked as the fifth most common cause of death 2. Liver diseases are recognized as the second leading cause of mortality amongst all digestive diseases in the US 3.

Global Burden of Disease (GBD) Project was formed by WHO to provide a consistent estimate of mortality and morbidity which varies by age, sex and region 4. To understand the burden of a certain disease, it is important to know its incidence, prevalence, mortality and morbidity including, impairment of quality of life and the direct or indirect cost expenditures. Knowledge of burden of a disease helps in establishment of public health priorities and in guiding prevention programs.

Liver cirrhosis

Global prevalence of cirrhosis from autopsy studies ranges from 4.5% to 9.5% of the general population 5, 6, 7. Hence, we estimate that more than fifty million people in the world, taking the adult population, would be affected with chronic liver disease. Globally, alcohol, NASH and viral hepatitis currently are the most common causative factors. Prevalence of cirrhosis is likely to be underestimated as almost a third of the  patients remain asymptomatic. With the use of non-invasive tests like transient elastography, a more realistic picture could emerge in the near future. During 2001, the estimated worldwide mortality from cirrhosis was 771,000 people, ranking 14th and 10th as the leading cause of death in the world and in developed countries, respectively 8. Deaths from cirrhosis have been estimated to increase and would make it as the 12th leading cause of death in 2020 9.

Non-Viral Related Cirrhosis and Chronic Liver Diseases


According to the WHO, alcohol consumption accounts for 3.8% of the global mortality and 4.6% of DALYs. Liver disease represents 9.5% of alcohol-related DALY’s worldwide, while individual rates vary in different regions. Alcohol is the main cause of liver-related death in Europe with highest mortality rates reported from France and Spain (approximately 30 deaths per 100,000 per year). There is a possibility of underestimation of mortality due to legal issues of documenting alcohol as primary cause of death. The lack of specificity of the national survey questionnaires also fails to allow accurate classification of liver diseases. Today, even in Asian countries like India, alcohol is emerging as the commonest cause of chronic liver disease 11.


Fig 1: Alcohol-attributable deaths as proportion of all deaths by sex and alcohol-attributable disability adjusted life years (DALYs) as proportion of all DALYs by sex in Europe and World. Data from WHO Global Burden 2004 21


Non-Alcoholic Steato-Hepatitis (NASH)

The burden of obesity has been steadily increasing with an estimated 1 billion people reported as overweight, and over 300 million people as  obese (WHO 2005 report) with a predicted increase to 1.5 billion by 2015. Globally, the prevalence of NASH ranges from 6% to 35%, with a median of 20% 12. Prevalence rates from China, India and Japan have been reported as 5%, 5-28% and 14%, respectively. Prevalence in the US, using non-invasive tests is reported to be as high as 10-35% but only 3-5% using liver biopsy 10. The data from NASH Clinical Research Network demonstrated that individuals with NAFLD have reduced QOL which was more pronounced in patients who had underlying cirrhosis, diabetes and obesity 13.


Fig 2: Non-alcoholic fatty liver disease prevalence rates reported from Asia, Europe, Middle East, North America and South America 12


Fig 3: Non-alcoholic fatty liver disease incidence in the general population 12



Most of these patients have underlying diabetes and obesity similar to that of patients with NASH, and represents end-stage NASH. Also, a fraction of cryptogenic cirrhosis cases may represent Autoimmune Hepatitis (AIH) in a “burnt-out” stage. The reported prevalence of HCC in patients of cryptogenic cirrhosis has ranged from 6.9-29% by various studies, and is gradually increasing 14.

Cholestatic and autoimmune liver disease

In both Europe and the US, the incidence and prevalence of primary biliary cirrhosis (PBC) has been measured as 2-3 (peak incidence of 4-6 in women 40 years of age) and 21-40 (59-65 in adult women) per 100,000 persons per year, respectively, and mortality rate of 0.5 per 100,000 per year 15,16. Data from Norway showed an incidence and prevalence of primary sclerosing cholangitis (PSC) of 1.3 and 8.5 per 100,000 per year, respectively, and mortality rates were the same as that for PBC 16. In the Norwegian study, the reported incidence of AIH was 1.9 per  100,000 per year, and the prevalence was 17 per 100,000 16.

Metabolic Liver Diseases

Hereditary hemochromatosis

This is one of the most common genetic diseases among persons of Northern European descent with the highest reported allele frequency for the homozygous C282Y of 6.4%-9.5% 17.

Wilson’s disease (WD)

Globally, WD has been estimated to affect approximately 1 in 30,000 individuals, with higher incidence reported in parts of Asia, for instance India. Unfortunately, to date no community-based incidence and prevalence study has been reported from India. About 15-20 new cases of WD are registered annually at the WD specialty clinic in the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore 18.

Alpha-1-antitrypsin deficiency

This is the most common genetic liver disease in infants and children with reported prevalence of 1:1,600 to 1:2,800 babies born in the United States and Northern Europe. Given the low prevalence of these diseases, there are no national statistics available about mortality or economic burden associated with these conditions.

Hepatocellular carcinoma (HCC)

Cirrhosis is well recognized and the main cause of HCC, which has an annual global incidence of over half a million, and a 5 year survival of 10%. The incidence of this cancer has been steadily rising at an alarming rate, making HCC the 5th most common cancer in men and the 7th most common cancer in women in recent estimates. It is likely to contribute approximately 5.6% of all human cancers with a predicted increase in burden through 2020. Almost 85% of HCCs occur in the developing world. HCV-related HCC is the fastest rising cause of cancer related deaths in the developed countries 19. It accounts for 70% to 85% of primary liver cancers. With the rising incidence of NASH and metabolic syndrome, these are also becoming a major concern. Liver cancer was recognized as the 4th most common cancer in males and accounted for 37% of all infection-related cancers in females in a recent study from India 20. Data from 1992–2002 showed that combined liver and intrahepatic bile duct cancer ranked 12th in males and 18th in females with rates of 8.6 and 3.3 per 100,000 persons, respectively. The mortality rates for liver and intrahepatic bile duct cancers were still higher, ranking 10th for men and 13th for women.


Fig 4: Primary liver cancer: age-adjusted incidence rates (left axis) and 5-year survival rates (right axis), 1979 –2004. (Source: Surveillance, Epidemiology, and End Results [SEER] Program.)


Table 1: Cancer incidence (thousands) by site, by WHO region, 2004 21


Read Part II:  Global Burden Of Liver Disease: A True Burden on Health Sciences and Economies!!


  1. Murray CJ, Lopez AD. Evidence-based health policy – lessons from the Burden of Disease Study. Science 1996; 274: 740-743.
  2. UK national statistics,
  3. Everhart JE, Ruhl CE. Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas. Gastroenterology 2009; 136: 1134 –1144.
  4. Murray CJL, Lopez, AD, eds. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries and risk factors in 1990 and projected to 2020. Cambridge, Harvard University Press (Global Burden of disease and Injury Series, Vol. 1), 1996.
  5. Melato M, Sasso F, Zanconati F. Liver cirrhosis and liver cancer. A study of their relationship in 2563 autopsies. Zentralbl Pathol 1993; 139: 25–30.
  6. Graudal N, Leth P, Marbjerg L, Galloe AM. Characteristics of cirrhosis undiagnosed during life: a comparative analysis of 73 undiagnosed cases and 149 diagnosed cases of cirrhosis, detected in 4929 consecutive autopsies. J Intern Med 1991; 230:165–171.
  7. Lim YS, Kim WR. The global impact of hepatic fibrosis and end-stage liver disease. Clin Liver Dis 2008; 12: 733–746.
  8. Mathers C, Lopez A, Murray C. The burden of disease and mortality by condition: data, methods, and results for 2001. In: Lopez A, Mathers C, Ezzati M, et al, editors. Global burden of disease and risk factors. Washington (DC): Oxford University Press and the World Bank; 2006. p. 45–93.
  9. Murray CJ, Lopez AD. Alternative projections of mortality and disability by cause 1990–2020: Global Burden of Disease Study. Lancet 1997; 349: 1498–1504.
  10. Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011;34: 274–285.
  11. Garg V, Garg H, Khan A, Trehanpati N, Kumar A, Sharma BC, Sakhuja P, Sarin SK Granulocyte colony–stimulating factor mobilizes CD34+ cells and improves survival of patients with acute-on-chronic liver failure. Gastroenterology 2012; 142: 505–512.
  12. Amarapurkar DN, Hashimoto E, Lesmana LA, Sollano JD, Chen PJ, Goh KL; Asia-Pacific Working Party on NAFLD. How common is non-alcoholic fatty liver disease in the Asia–Pacific region and are there local differences? J Gastroenterol Hepatol 2007; 22: 788–793.
  13. David K, Kowdley KV, Unalp A, Kanwal F, Brunt EM, MD, Schwimmer JB, the NASH CRN Research Group. Quality of Life in Adults with Nonalcoholic Fatty Liver Disease: Baseline Data from the NASH CRN. Hepatology 2009; 49(6): 1904–1912.
  14. Starley BQ, Calcagno CJ, Harrison SA. Nonalcoholic fatty liver disease and hepatocellular carcinoma: A weighty connection. Hepatology 2010; 51: 1820–1832.
  15. Kim WR, Brown RS Jr, Terrault NA, El-Serag H. Burden of liver disease in the United States: summary of a workshop. Hepatology 2002; 36: 227–242.
  16. Boberg KM, Aadland E, Jahnsen J, Raknerud N, Stiris M, Bell H. Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population. Scand J Gastroenterol 1998; 33: 99-103.
  17. Merryweather-Clarke AT, Pointon JJ, Shearman JD, Robson KJ. Global prevalence of putative haemochromatosis mutations. J Med Genet 1997; 34: 275-278.
  18. Zhang Y, Wu ZY. Wilson’s disease in Asia. Neurology Asia 2011; 16 : 103–109.
  19. El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118-1127.
  20. Dikshit R, Gupta PC, Ramasundarahettige C, et al, for the Million Death Study Collaborators. Cancer mortality in India: a nationally representative survey. Lancet 2012; 379: 1807–1816.
  21. The global burden of disease, 2004 update. World Health Organization.