How Do Direct-Acting Antivirals for Hepatitis C Affect the Risk for Hepatocellular Carcinoma?

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Hepatocellular carcinoma (HCC), which has an annual incidence rate of 1%-4%, is a potential complication of hepatitis C virus (HCV) cirrhosis owing to a multistep carcinogenesis pathway. Previous HCV treatment with interferon was associated with poor cure rates and was limited to individuals with early fibrosis or well-compensated cirrhosis. Such therapy, however, also led to a decrease in HCC after a sustained viral response (SVR). Although remarkable progress has occurred in curing HCV in the current direct-acting antiviral (DAA) era, there is controversy regarding the associated risk of patients developing either incident (new, de novo) or recurrent HCC after DAA treatment. Additional data also suggest a lower SVR rate in patients with HCC.

Collectively, these emerging data suggest several key points.

  • The strongest risk for HCC development is advanced liver disease.
  • Robust data support a decreased incident (new, de novo) HCC rate in patients with HCV cirrhosis after SVR with DAA treatment.
  • Clinical research suggests that when individuals develop HCC after DAA therapy, tumors demonstrate a more aggressive phenotype, which appears to be an immunologic phenomenon.
  • Patients with active HCC show lower SVR rates.

On the basis of the data, in patients without HCC, HCV treatment with DAA therapy should not be withheld due to the risk for HCC. A thorough evaluation for HCC immediately before and 3 months after initiating DAA therapy should be completed. This evaluation may include an ultrasound and alpha-fetoprotein (AFP) levels for those without HCC, and axial imaging (CT or MRI) and AFP levels for those with a history of HCC.

If a patient has HCC, providers should treat HCC first and wait 3-6 months after complete response before initiating DAA therapy. Individuals with HCV cirrhosis and HCC awaiting liver transplant should be considered for delay of HCV treatment until after transplant[26] due to the decreased rate of SVR with HCC, the potential risk for aggressive recurrence, and access to HCV-positive donors.

Patients with advanced fibrosis without HCC should have ongoing monitoring for HCC after SVR with DAA therapy.

Read complete article here: http://www.medscape.com/viewarticle/884003