Prevention of hepatitis C virus-related liver cancer

(Hepatocellular carcinoma)

YOUR DOSE OF MEDICINE By Charles C. Chante, MD

The incidence of hepatocellular carcinoma (HCC) is increasing in North America, Europe, and Japan, caused largely by the high rates of chronic hepatitis C virus (HCV) infection. In such individuals, the risk factors for developing HCC are advancing age, male gender, worsening hepatic fibrosis (particularly cirrhosis), and greater degrees of hepatic inflammation. Additional, potentially modifiable risk factors include coinfection with hepatitis B, excessive alcohol use, iron overload, and diabetes/obesity. Thus, approaches to preventing HCC should focus on eradicating HCV infection, responsible for the inflammation and fibrosis, and also on treating or reducing the modifiable risks, such as through hepatitis B vaccination, decreasing alcohol use, phlebotomy for iron overload, and weight control and diabetes prevention. These approaches have yet to be proven effective; Meta-analyses of standard interferon monotherapy trials in patients with HCV-related cirrhosis suggest that interferon has a small but significant effect on reducing HCC risk, particularly in those who achieve a sustained response. Other studies indicate that the reduction in HCC is greatest if a response is achieved before cirrhosis develops. Secondary prevention when HCC has been ablated or resected may be partially effected with interferon treatment or oral polyprenoic acid. No long-term studies of the effect of the currently recommended regimen of peginterferon and ribavirin have been reported, and no current trials include untreated control groups. Studies of maintenance peginterferon therapy in virological nonresponders are under the way in the hope of proving that this approach is effective in decreasing the risk of HCC.

Recent reports from North America, Europe, and Japan show that the incidence of hepatocellular carcinoma (HCC) is increasing. This increase appears to be largely cause by chronic infection with the hepatitis C virus (HCV), the incidence of which increased in these areas of world several decades ago. The association of HCC with chronic hepatitis B virus (HBV) infection has been well recognized since the 1970s, but it was a decade later that the association of HCC with what was then called post-transfusion non-A, non-B hepatitis was established.

In chronic hepatitis B, HCC is most common in persons with cirrhosis but can occur in carriers of HBV with mild fibrosis without cirrhosis. In contrast, in chronic hepatitis C, HCC rarely occurs in persons without underlying cirrhosis or advanced fibrosis.

Risk factors for HCC in individuals with chronic hepatitis C

Risk factors for development of HCC in individuals with chronic hepatitis C include male gender, older age, hepatic fibrosis and cirrhosis, and hepatitis disease activity as indicated by elevations in serum aminotransferase levels and inflammation and necrosis on liver biopsy. Other potentially modifiable risk factors include coinfection with HBV, chronic alcohol use, smoking, iron overload, and diabetes and/or obesity.

Summary

Chronic hepatitis C is the major cause of HCC in North America, Europe, and Japan, and the incidence of this highly malignant cancer appears to be increasing. Risk factors for developing HCC in persons with chronic HCV infection include cirrhosis or advanced fibrosis, active liver disease, male gender, older age, alcohol abuse, smoking, iron overload, obesity, diabetes and coinfection with hepatitis B. Approaches to prevention of HCC in patients with chronic hepatitis C should focus on modifiable risk factors including use of HBV vaccine, recommendations for limiting alcohol intake, smoking cessation, assessment of iron status and iron depletion if necessary, education concerning weight management and diabetes, and finally appropriate recommendations for therapy. Multiple prospective and retrospective analyses have suggested that successful therapy of chronic hepatitis C will reduce the rate of HCC, and prevention appears to be most effective if therapy is given before the development of cirrhosis. Unfortunately, current optimal therapy of chronic hepatitis C is expensive, poorly tolerated, and effective in only 50 percent-60 percent of selected patients. Ultimately, satisfactory prevention of HCC in persons with chronic hepatitis C will depend on development of more effective and better tolerated therapies.