Hepatocellular carcinoma in cirrhosis: Incidence and risk factors

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Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non-HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.

Section snippets

The burden of HCC in cirrhosis

HCC is a common cause of death among patients with compensated cirrhosis. European cohort studies have reported that, among persons who died of a liver-related cause, HCC was the responsible cause in 54%6 to 70%7 of patients with compensated cirrhosis of different etiologies and in 50% of patients with HCV-related cirrhosis.8 Data from one of the longitudinal studies, which involved 112 cirrhotic patients with HCC detected during ultrasound surveillance, showed that tumor progression was the

HCC with and without underlying cirrhosis

Patients at risk for HCC include those with chronic HBV or HCV infection, certain metabolic liver disease, such as hereditary hemochromatosis and porphyria cutanea tarda, and those with cirrhosis, regardless of its etiology. The prevalence of cirrhosis in persons with HCC is about 80%–90% in autopsied series worldwide, and, therefore, approximately 10% to 20% of cases of HCC develop in persons without cirrhosis.1 Differences of geographic area, method of recruitment of the HCC cases (medical or

Incidence and risk factors for HCC according to etiology of cirrhosis

Although there have been several published studies on the risk of developing HCC in patients with cirrhosis, a comprehensive analysis is hampered by the different study designs (case control, cross-sectional, longitudinal), the heterogeneity of the patient populations relative to the severity of the cirrhosis stage at enrollment, and the lack of a focused analysis of HCC based on etiology. Furthermore, in studies involving subjects with HCV or HBV infection treated with interferon-α, separate

Age and gender

Older age and male sex have been found in longitudinal studies to be associated with an increased risk of HCC among persons with cirrhosis of different etiologies.6, 40, 133, 134 Older age may reflect a longer duration of cirrhosis. The higher risk of HCC among male cirrhotic patients could be explained by either the higher prevalence of other risk factors, such as alcohol abuse, or by a tumorigenic effect of androgens.

Stage of cirrhosis

In a surveillance program of a cohort of 313 Italian cirrhotic patients of

Summary

The following conclusions can be drawn: (1) Mortality from HCC is rising in some developed countries, whereas mortality from cirrhosis is either decreasing or is stable, possibly because of improved medical management of non-HCC complications of cirrhosis, leading to longer survival of cirrhotic patients. (2) Cohort studies indicate that HCC currently represents the major cause of liver-related death in patients with compensated cirrhosis. (3) Cirrhosis underlies HCC in approximately 80%–90% of

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