Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma

Abstract

Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States. Most cases of hepatocellular carcinoma (HCC) are associated with cirrhosis related to chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Changes in the time trends of HCC and most variations in its age-, sex-, and race-specific rates among different regions are likely to be related to differences in hepatitis viruses that are most prevalent in a population, the timing of their spread, and the ages of the individuals the viruses infect. Environmental, host genetic, and viral factors can affect the risk of HCC in individuals with HBV or HCV infection. This review summarizes the risk factors for HCC among HBV- or HCV-infected individuals, based on findings from epidemiologic studies and meta-analyses, as well as determinants of patient outcome and the HCC disease burden, globally and in the United States. According to the International Agency for Research on Cancer, liver cancer is the fifth most common cancer in men worldwide (523,000 cases/y, 7.9% of all cancers) and the seventh most common cancer in women (226,000 cases/y, 6.5% of all cancers). Liver cancer has a high mortality rate; the geographic distribution of mortality is similar to that of incidence. Most of the burden of liver cancer is in developing countries, where almost 85% of the cases occur. Hepatocellular carcinoma (HCC) is the most common form of liver cancer; most cases of HCC (approximately 80%) are associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. Variations in the age-, sex-, and race-specific rates of HCC in different geographic regions are likely to be related to differences in the prevalence of hepatitis viruses in the populations, as well as the timing of the spread of the viral infection and the age of individuals at the time of the infection. Most cases of HCC (>80%) occur in sub-Saharan Africa and in Eastern Asia, with typical incidence rates of more than 20 per 100,000 individuals. Southern European countries (such as Spain, Italy, and Greece) tend to have mid-incidence levels (10.0–20.0 per 100,000 individuals), whereas North America, South America, Northern Europe, and Oceania have a low incidence of HCC (<5.0 per 100,000 individuals) (Figure 1). Recent decreases in the incidence of HCC were reported among Chinese populations in Hong Kong, Shanghai, and Singapore; the incidence in Japan also is decreasing. However, cases of HCC are increasing in low-incidence areas such as the United States and Canada. HCC rarely is seen during the first 4 decades of life, except in populations in which HBV infection is hyperendemic. The mean ages of diagnosis with HCC were 55–59 years in China and 63–65 years in Europe and North America. In low-risk populations, the highest incidence of HCC is among individuals aged 75 or older. However, in Qidong, China, where HCC burden is among the world's highest, the age-specific incidence rates among men increases until age 45 years and then plateaus; among women, the incidence rate increases until age 60 years and then plateaus. HCC is predominant among men, with the highest male:female ratios in areas of high incidence (Figure 1). HBV and HCV promote cirrhosis, which is found in 80%–90% of patients with HCC. The 5-year cumulative risk of developing HCC for patients with cirrhosis ranges between 5% and 30%, depending on etiology (it is highest in individuals with HCV infection), region or ethnicity (it is highest in Asians), and stage of cirrhosis (it is highest in individuals with decompensated disease).1Fattovich G. Stroffolini T. Zagni I. et al.Hepatocellular carcinoma in cirrhosis: incidence and risk factors.Gastroenterology. 2004; 127: S35-S50Abstract Full Text Full Text PDF PubMed Scopus (2061) Google Scholar Approximately 5% of the world population (350–400 million people) is chronically infected with HBV; 75% of infected people are Asian,2McMahon B.J. Alberts S.R. Wainwright R.B. et al.Hepatitis B-related sequelae Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers.Arch Intern Med. 1990; 150: 1051-1054Crossref PubMed Google Scholar with a lower prevalence (0.3%–1.5%) in Western countries. There is high ecologic correlation between areas of HBV prevalence and HCC incidence and mortality worldwide (Figure 2). Chronic HBV infection accounts for approximately 50% of the total cases and virtually all childhood HCC; it is the dominant risk factor in most areas of Asia and sub-Saharan Africa that have a high incidence of HCC, with the exception of Japan, where the major risk factor for HCC is chronic HCV infection. HB surface antigen (HBsAg) seroprevalence among persons with HCC varies widely: it is 3% in Sweden, 10% in the United States, 10%–15% in Japan, 19% in Italy, 55% in Greece, and 70% in South Korea. The global prevalence of HCV is estimated to be 2% (approximately 180 million people worldwide) and varies considerably among different regions (Figure 2). Phylogenetic studies of HCV diversity described the chronology of the spread of HCV epidemics in Japan, Europe, and the United States; these findings account for the geographic differences in the timing of the burden of HCV-related HCC.3Mizokami M. Orito E. 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