Gastroenterology

Gastroenterology

Volume 142, Issue 6, May 2012, Pages 1264-1273.e1
Gastroenterology

Epidemiology and Pathophysiology
Review: Reviews and Perspectives
Epidemiology of Viral Hepatitis and Hepatocellular Carcinoma

https://doi.org/10.1053/j.gastro.2011.12.061Get rights and content

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.

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Global Epidemiology of HCC

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

The Role of HBV and HCV in HCC

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).1

Approximately 5% of the world population (350–400 million people) is chronically infected with HBV; 75% of infected

Risk of HCC From HBV Infection

Prospective cohort studies showed a 5- to 100-fold increase in the risk of developing HCC among persons chronically infected with HBV. Meta-analyses of case-control and cross-sectional studies indicated that the lifetime relative risk for HCC was 15–20 among HBsAg-positive individuals, compared with HBsAg-negative individuals. A systematic review of longitudinal (cohort) studies published through June 2007, by Fattovich et al,7 estimated the incidence rates of HCC in subjects with chronic HBV

Risk of HCC From HCV Infection

There is much evidence that HCV infection can cause HCC. Prospective studies have shown a significant increase in the incidence of HCC among HCV-infected cohorts, compared with HCV-negative cohorts.24 The rate of HCC among HCV-infected persons ranges from 1% to 3% over 30 years. Similarly, HCV infection is associated with a 15- to 20-fold increase in risk for HCC compared with HCV-negative subjects in cross-sectional and case-control studies.

HCV increases the risk for HCC by inducing fibrosis

Sex

Men are at increased risk for HCC partly because they have a greater incidence of viral hepatitis and alcoholic cirrhosis. However, their risk still is increased after adjusting for these confounders. Men have an increased risk of cirrhosis and HCC from different diseases, such as HBV and HCV infection. High serum levels of testosterone have been associated with HCC risk in nested case-control studies of HBV carriers in Taiwan and Shanghai.37 Male carriers of HBV usually have higher viral

Host Genetic Factors

Most individuals with HCV or HBV never develop cirrhosis or HCC. Family history of liver cancer has been associated with increased risk for HCC among HBV carriers (in cohort and case-control studies) and possibly among HCV-infected persons (in case-control studies), irrespective of viral hepatitis.57, 58 Host genetic factors might account for some of the variation in the risk of developing cirrhosis or HCC. Individual genetic association studies frequently are underpowered and often report

Using Epidemiologic Findings to Determine HCC Risk in the Clinic

Investigators from Taiwan examined the potential use of noninvasive clinical and laboratory measures, which have been shown in epidemiologic studies to be associated with HCC risk, to construct clinically usable nomograms to predict HCC risk in patients with chronic HBV infection.65 A number of risk factors, including sex, age, family history of HCC, heavy alcohol consumption, serum levels of ALT, HBeAg serostatus, serum levels of HBV DNA, and HBV genotype were used to create predictive models

HCC and Viral Hepatitis in the United States

In the United States, the age-adjusted incidence rates for HCC have tripled since the early 1980s. Incidence rates are 2- to 3-fold lower among Caucasians than African Americans, and 2- to 3-fold lower among African Americans than Asians, Pacific Islanders, or Native Americans. Asian men (Chinese, Korean, Filipino, and Japanese) have the highest age-adjusted incidence rates (as high as 23 per 100,000). However, the largest proportional increases have occurred among whites (Hispanic and

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    Conflicts of interest The authors disclose no conflicts.

    Funding This material is based on work supported in part by the Houston VA Health Services Research & Development Center of Excellence (HFP90-020) and support from NIH P30 DK58338.

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