Background/Aims
End-stage liver disease accounts for one in forty deaths worldwide. Chronic infections
with hepatitis B virus (HBV) and hepatitis C virus (HCV) are well-recognized risk
factors for cirrhosis and liver cancer, but estimates of their contributions to worldwide
disease burden have been lacking.
Methods
The prevalence of serologic markers of HBV and HCV infections among patients diagnosed
with cirrhosis or hepatocellular carcinoma (HCC) was obtained from representative
samples of published reports. Attributable fractions of cirrhosis and HCC due to these
infections were estimated for 11 WHO-based regions.
Results
Globally, 57% of cirrhosis was attributable to either HBV (30%) or HCV (27%) and 78%
of HCC was attributable to HBV (53%) or HCV (25%). Regionally, these infections usually
accounted for >50% of HCC and cirrhosis. Applied to 2002 worldwide mortality estimates,
these fractions represent 929,000 deaths due to chronic HBV and HCV infections, including
446,000 cirrhosis deaths (HBV: n = 235,000; HCV: n = 211,000) and 483,000 liver cancer deaths (HBV: n = 328,000; HCV: n = 155,000).
Conclusions
HBV and HCV infections account for the majority of cirrhosis and primary liver cancer
throughout most of the world, highlighting the need for programs to prevent new infections
and provide medical management and treatment for those already infected.
Abbreviations:
HBV (hepatitis B virus), HCV (hepatitis C virus), HCC (hepatocellular carcinoma), WHO (World Health Organization), GBD (Global Burden of Disease)Keywords
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References
World Health Organization. The World Health Report 2003: shaping the future. Geneva: World Health Organization, 2003. Available at: <http://www.who.int/whr/2003/en/whr03_en.pdf/>.
- Epidemiology of hepatocellular carcinoma.Clin Liver Dis. 2001; 5 (vi): 87-107
- Clinical presentation and natural course of hepatocellular carcinoma.Eur J Gastroenterol Hepatol. 2005; 17: 485-489
- Pathogenesis of hepatocellular carcinoma.Eur J Gastroenterol Hepatol. 2005; 17: 477-483
- Hepatocellular carcinoma in cirrhosis: incidence and risk factors.Gastroenterology. 2004; 127: S35-S50
- Alcohol and hepatocellular carcinoma: the effect of lifetime intake and hepatitis virus infections in men and women.Am J Epidemiol. 2002; 155: 323-331
- Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus.Hepatology. 2002; 36: 1206-1213
- The epidemiology and prevention of hepatocellular carcinoma.Semin Oncol. 2001; 28: 441-449
- Epidemiology of hepatocellular carcinoma.Clin Liver Dis. 2005; 9: 191-211
- Global epidemiology and burden of hepatitis C.Microbes Infect. 2002; 4: 1219-1225
The Global Burden Of Hepatitis C Working Group. Global burden of disease (GBD) for hepatitis C. J Clin Pharmacol 2004;44:20–9.
- Selected major risk factors and global and regional burden of disease.Lancet. 2002; 360: 1347-1360
- The relationship of average volume of alcohol consumption and patterns of drinking to burden of disease: an overview.Addiction. 2003; 98: 1209-1228
- Cancer and infection: estimates of the attributable fraction in 1990.Cancer Epidemiol Biomarkers Prev. 1997; 6: 387-400
- Proportion of disease caused or prevented by a given exposure, trait, or intervention.Am J Epidemiol. 1974; 99: 325-332
- Interaction between alcohol consumption and positivity for antibodies to hepatitis C virus on the risk of liver cirrhosis: a case-control study. Provincial Group for the Study of Chronic Liver Disease.Eur J Epidemiol. 1992; 8: 634-639
- Habitual betel quid chewing as a risk factor for cirrhosis: a case-control study.Medicine. 2003; 82: 365-372
- The relationships of chronic hepatitis and cirrhosis to alcohol intake, hepatitis B and C, and delta virus infection: a case-control study in Albania.Epidemiol Infect. 1998; 121: 391-395
- A meta-analysis of epidemiological studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma.Int J Cancer. 1998; 75: 347-354
- Hepatitis C virus infection and chronic liver disease in Ethiopia where hepatitis B infection is hyperendemic.Trans R Soc Trop Med Hyg. 1995; 89: 171-174
- [HBs Ag and antibodies to hepatitis C virus in complicated chronic liver disease in Gabon. A case control study].Gastroenterol Clin Biol. 2002; 26: 131-135
- The prevalence of hepatitis C virus antibodies in renal patients, blood donors and patients with chronic liver disease in Kenya.East Afr Med J. 1995; 72: 362-364
- [Study of antigen HBs and antivirus antibodies of hepatitis C during hepatopathies in Mali].Bull Soc Pathol Exot. 2004; 97: 161-164
- Hepatitis B virus markers, hepatitis D virus antigen and hepatitis C virus antibodies in Nigerian patients with chronic liver disease.East Afr Med J. 1995; 72: 719-721
- [Hepatitis C virus and chronic hepatopathies in Dakar: case-control study].Med Trop. 2000; 60: 47-52
- Hepatitis C virus infection in chronic liver disease in Natal.S Afr Med J. 1996; 86: 80-83
- Risk factors for hepatocellular carcinoma in patients with cirrhosis.Dig Dis Sci. 2004; 49: 850-853
- Screening for hepatocellular carcinoma in patients with advanced cirrhosis.Am J Gastroenterol. 1999; 94: 2988-2993
- Chronic liver disease among U.S. military patients: the role of hepatitis C and G virus infection.Mil Med. 2000; 165: 178-179
- Chronic liver disease in central Harlem: the role of alcohol and viral hepatitis.Hepatology. 1999; 29: 883-888
- Etiology of liver cirrhosis in Mexico.Ann Hepatol. 2004; 3: 30-33
- Chronic liver disease in Peru: role of viral hepatitis.J Med Virol. 1994; 42: 129-132
- Hepatitis C virus infection in chronic liver disease and hepatocellular carcinoma in Saudi Arabia.J Gastroenterol Hepatol. 1992; 7: 237-239
- Serodiagnosis of hepatitis C in acute and chronic liver disease in southwestern Saudi Arabia.J Trop Med Hyg. 1992; 95: 428-431
- Hepatitis C core antibody detection in acute hepatitis and cirrhosis patients from Tunisia.Pathol Biol. 1992; 40: 646-648
- [Epidemiology of hepatitis B virus, hepatitis C virus and Delta virus in the general population and in liver cirrhosis in Tunisia].Archives de l Institut Pasteur de Tunis. 1994; 71: 403-406
- High prevalence of hepatitis C in Egyptian patients with chronic liver disease.Gut. 1995; 37: 105-107
- Hepatitis C and cirrhotic liver disease in the Nile delta of Egypt: a community-based study.Am J Trop Med Hyg. 2001; 64: 147-153
- Hepatitis B and C single and co-infection in chronic liver disease and their effect on the disease pattern.J Pak Med Assoc. 2003; 53: 136-140
- The spectrum of chronic liver disease in Balochistan.J Coll Physicians Surg Pak. 2001; 11: 95-97
- Hepatitis C virus infection in chronic liver disease in Somalia.Am J Trop Med Hyg. 1993; 48: 581-584
- Surveillance for hepatocellular carcinoma: compliance and results according to the aetiology of cirrhosis in a cohort of 141 patients.Acta Gastroenterologica Belgica. 2000; 63: 5-9
- Prevalence of anti-HCV antibodies in chronic liver disease in the Czech Republic.Infection. 1997; 25: 49-50
- Characteristics of liver cirrhosis in Italy: results from a multicenter national study.Dig Liver Dis. 2004; 36: 56-60
- Epidemiological and clinical aspects of hepatitis C virus infection in the Russian Republic of Daghestan.Eur J Epidemiol. 1998; 14: 549-553
- [Current problems of viral and alcohol diseases of the liver].Klin Med (Mosk). 2002; 80: 14-19
- Clinicopathologic features and risk factors for hepatocellular carcinoma: results from a single center in southern Turkey.Turk J Gastroenterol. 2003; 14: 85-90
- Hepatitis B and C virus infection in Ujung Pandang, Indonesia.Gastroenterol Jpn. 1991; 26: 184-188
- Hepatitis B virus subtypes and hepatitis C virus genotypes in patients with chronic liver disease or on maintenance hemodialysis in Indonesia.J Med Virol. 1994; 43: 182-186
- Hepatitis C virus infection in patients with chronic liver disease or chronic renal failure and blood donors in Thailand.J Med Virol. 1994; 44: 287-292
- Hepatitis viruses and chronic liver disease.Southeast Asian J Trop Med Public Health. 1999; 30: 489-495
- Hepatitis B subtypes and hepatitis C genotypes in cirrhosis in western India: results of a pilot study.J Assoc Physicians India. 1999; 47: 580-583
- Association of hepatitis C virus & hepatitis B virus in chronic liver disease.Indian J Med Res. 1998; 108: 255-299
- Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity.Indian J Gastroenterol. 2003; 22: 127-131
- Hepatitis B virus subtypes and hepatitis C virus genotypes in patients with chronic liver disease in Nepal.Hepatology. 1994; 19: 805-809
- Viral Hepatitis in Japan.Viral Hepatitis And Liver Disease: Proceedings. 1994; : 426-428
- Risk factors for infections in cirrhotic patients with and without hepatocellular carcinoma.J Gastroenterol. 2002; 37: 1028-1034
- Hepatitis C virus infection in patients with chronic liver diseases.Gastroenterologia Jpn. 1991; 26: 202-205
- Hepatitis C virus infections and genotypes in China.Hepatobiliary Pancreat Dis Int. 2002; 1: 194-201
- High prevalence of dual or triple infection of hepatitis B, C, and delta viruses among patients with chronic liver disease in Mongolia.J Med Virol. 2005; 77: 491-499
- [The change of the etiology, complications and cause of death of the liver cirrhosis in 1990s].Korean J Hepatol. 2000; 6: 328-339
- The Gambia Liver Cancer Study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa.Hepatology. 2004; 39: 211-219
- Hepatitis B and C virus and hepatocellular carcinoma.Trans R Soc Trop Med Hyg. 1997; 91: 38-41
- Hepatitis C virus and HIV antibodies in patients with hepatocellular carcinoma in Zimbabwe: a pilot study.Trans R Soc Trop Med Hyg. 1997; 91: 570-572
- Rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States.J Clin Gastroenterol. 2002; 35: 266-269
- Hepatitis C-related hepatocellular carcinoma in the United States: influence of ethnic status.Am J Gastroenterol. 2003; 98: 2060-2063
- Hepatocellular carcinoma in Brazil: report of a national survey (Florianopolis, SC, 1995).Rev Inst Med Trop Sao Paulo. 1997; 39: 165-170
- [Hepatitis B and C virus infection and the hepatocellular carcinoma in the East Amazon, Brazil].Rev Soc Bras Med Trop. 2004; 37: 47-51
- Hepatocellular carcinoma and hepatitis C in Mexico.Hepatogastroenterology. 2005; 52: 1159-1162
- [Hepatitis B and C Virus Infection as Risk Factors for Hepatocarcinoma in Peru: Case and Control Study].Rev Gastroenterol Peru. 1998; 18: 199-212
- Risk factors for hepatocellular carcinoma in Southern Iran.Saudi Med J. 2005; 26: 974-977
- Hepatocellular carcinoma in Saudi Arabia: role of hepatitis B and C infection.J Gastroenterol Hepatol. 2004; 19: 665-669
- Prevalence of hepatitis C infection and schistosomiasis in Egyptian patients with hepatocellular carcinoma.Dis Markers. 1997; 13: 177-182
- The role of hepatitis C in hepatocellular carcinoma: a case control study among Egyptian patients.J Clin Gastroenterol. 2001; 33: 123-126
- Spectrum of chronic liver disease in a tertiary care hospital.J Pak Med Assoc. 2002; 52: 56-58
- The role of hepatitis B and hepatitis C viral infections in the incidence of hepatocellular carcinoma in Sudan.Trans R Soc Trop Med Hyg. 2001; 95: 487-491
- Hepatocellular carcinoma in Germany: a retrospective epidemiological study from a low-endemic area.Liver. 2000; 20: 312-318
- Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors.Dig Dis. 2001; 19: 345-351
- Hepatitis B and C viruses in the etiology of hepatocellular carcinoma; a study in Greece using third-generation assays.Cancer Causes Control. 2000; 11: 171-175
- Trends of aetiological factors of hepatocellular carcinoma in Italy.Dig Liver Dis. 2005; 37: 985-986
- The importance of HCV on the burden of chronic liver disease in Italy: a multicenter prevalence study of 9,997 cases.J Med Virol. 2005; 75: 522-527
- Incidence and epidemiological factors of hepatocellular carcinoma in Valencia during the year 2000.Rev Esp Enferm Dig. 2003; 95: 385-388
- Risk factors for hepatocellular carcinoma in patients with liver cirrhosis.Rev Esp Enferm Dig. 2000; 92: 458-469
- [Liver cirrhosis and liver cancer associated with viral hepatitis B and C in republic of Tatarstan].Zh Mikrobiol Epidemiol Immunobiol. 2003; : 26-28
- Risk factors for hepatocellular carcinoma in Turkey.Dig Dis Sci. 2001; 46: 1022-1028
- Hepatitis B virus and hepatitis C virus infections in Turkish patients with hepatocellular carcinoma.Am J Gastroenterol. 1996; 91: 1479-1480
- Demographic, clinical, and virological characteristics of hepatocellular carcinoma in Asia: survey of 414 patients from four countries.J Med Virol. 2002; 67: 394-400
- Association of hepatitis viruses with hepatocellular carcinoma in Thailand.J Gastroenterol. 1999; 34: 227-233
- Primary hepatocellular carcinoma and viral hepatitis B and C infection in Bangladeshi subjects.J Trop Med Hyg. 1995; 98: 64-68
- Profile of hepatocellular carcinoma in India: an insight into the possible etiologic associations.J Gastroenterol Hepatol. 2001; 16: 666-673
- High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar (Burma).Acta Med Okayama. 2000; 54: 137-138
- Trends in clinical characteristics, treatment and prognosis of hepatocellular carcinoma.Hepatogastroenterology. 2003; 50: 1872-1877
- High prevalence of infection with hepatitis B and C viruses in patients with hepatocellular carcinoma in Japan.Hepatogastroenterology. 1999; 46: 357-359
- Clinical features of patients with HCC who are negative for both HBV and HCV markers.Hepatogastroenterology. 2003; 50: 2157-2160
- Seroprevalence of hepatitis B and C viral markers in patients with primary hepatocellular carcinoma in Singapore.Singapore Med J. 1996; 37: 492-496
- A meta-analysis of case-control studies on the combined effect of hepatitis B and C virus infections in causing hepatocellular carcinoma in China.Br J Cancer. 2005; 92: 607-612
- Clinical features of HBsAg-negative but anti-HBc-positive hepatocellular carcinoma in a hepatitis B virus endemic area.J Gastroenterol Hepatol. 2005; 20: 746-751
- Age, gender, and local geographic variations of viral etiology of hepatocellular carcinoma in a hyperendemic area for hepatitis B virus infection.Cancer. 1999; 86: 1143-1150
- Global epidemiology of hepatitis B virus.J Clin Gastroenterol. 2004; 38: S158-S168
- Epidemiology of hepatitis C: geographic differences and temporal trends.Semin Liver Dis. 2000; 20: 1-16
- The global health burden of infection-associated cancers in the year 2002.Int J Cancer. 2006; 118: 3030-3044
- Viral hepatitis and hepatocellular carcinoma.World J Surg Oncol. 2005; 3: 27
- Primary liver cancer: worldwide incidence and trends.Gastroenterology. 2004; 127: S5-S16
- Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures.J Viral Hepat. 2004; 11: 97-107
- Global epidemiology of hepatitis C virus infection.Lancet Infect Dis. 2005; 5: 558-567
World Health Organization WHO Vaccine Preventable Diseases Monitoring System, 2004 Global Summary. Geneva: World Health Organization, 2004. Available at: <http://www.who.int/vaccines-documents/GlobalSummary/GlobalSummary.pdf/>.
- Global control of hepatitis B virus infection.Lancet Infect Dis. 2002; 2: 395-403
- A mathematical model to estimate global hepatitis B disease burden and vaccination impact.Int J Epidemiol. 2005; 34: 1329-1339
- Epidemiology and prevention of hepatitis B.Semin Liver Dis. 2003; 23: 39-46
- Hepatocellular carcinoma: paradigm of preventive oncology.Cancer J. 2004; 10: 67-73
- The maze of treatments for hepatitis B.N Engl J Med. 2005; 352: 2743-2746
- Treatment of hepatitis C.J Viral Hepat. 2005; 12: 223-235
- Treatment of chronic hepatitis B.J Viral Hepat. 2005; 12: 333-345
- The coming wave of HCV-related liver disease: dilemmas and challenges.J Hepatol. 2006; 44: 441-443
- Commentary: modelling the epidemiology of hepatitis C and its complications.Int J Epidemiol. 2003; 32: 725-726
- Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C.J Hepatol. 2005; 42: 639-645
Article info
Publication history
Published online: June 23, 2006
Accepted:
May 16,
2006
Received in revised form:
May 3,
2006
Received:
January 9,
2006
Footnotes
☆The authors who have taken part in this study declared that they have no relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research.
Identification
Copyright
© 2006 European Association for the Study of the Liver. Published by Elsevier Inc. All rights reserved.
