How Can We Tell if Patients are Still at Risk for HCC after HCV Therapy?

For patients with chronic Hepatitis C virus infection, high levels of α-fetoprotein after therapy can identify those at risk for hepatocellular carcinoma (HCC), researchers report in the July issue of Clinical Gastroenterology and Hepatology.

In persons with chronic HCV infection, lack of sustained virologic response (SVR) 24 weeks after the end of interferon therapy is a significant risk factor for HCC. Although many pretreatment factors certainly affect HCC incidence, little is known about post-treatment factors—many change during the course of interferon therapy.

Only 1.3% to 4.7% of patients who eradicate their HCV infection with interferon therapy develop HCC within 5 years. Conversely, patients who do not eradicate their HCV infection with interferon therapy have a high incidence of HCC, yet many remain cancer-free for long periods.

Tsugiko Oze et al. performed a prospective study to evaluate risk factors for HCC incidence separately between the 2 groups, which have distinct levels of risk for HCC.



Oze et al. knew that serum levels of alanine aminotransferase, α-fetoprotein, and liver fibrosis usually decrease with interferon therapy. Could these be factors that affect later risk for HCC?

Oze et al. collected specimens and data from 2659 patients with chronic hepatitis C without a history of HCC before and during treatment with interferon and ribavirin (48 to 72 weeks for HCV genotype 1 or 24 weeks for HCV genotype 2) in Japan.

HCC developed in 104 patients during a mean observation period of 40 months. Older age, being male, lower platelet counts, higher baseline levels of α-fetoprotein, and lack of an SVR were overall risk factors for HCC.

Among patients with SVRs, levels of α-fetoprotein and alanine aminotransferase significantly decreased after therapy. Post-treatment risk factors for HCC among patients with SVRs included higher levels of α-fetoprotein 24 weeks after the end of treatment and older age.

Among patients without SVRs, risk factors for HCC included higher levels of α-fetoprotein 24 weeks after the end of treatment, integrated level of alanine aminotransferase, older age, and being male.

Level of α-fetoprotein 24 weeks after the end of treatment (≥10 ng/mL, 10–5 ng/mL, or <5 ng/mL) was a better predictor of HCC incidence than pretreatment level among patients with and without SVRs.

Therefore, the level of α-fetoprotein 24 weeks after the end of treatment was associated strongly with HCC incidence irrespective of SVR.

Oze et al. would like to investigate whether the results obtained from this study apply to patients with cirrhosis, who are at greatest risk for HCC. Also, it will be important to determine whether the level of α-fetoprotein reduces HCC incidence in patients treated with interferon-free regimens (direct-acting antivirals).

Although level of α-fetoprotein can be a comprehensive surrogate marker for HCC risk in relation to various factors, such as liver inflammation and fibrosis, Oze et al. propose that α-fetoprotein is a marker for HCC, independent of liver inflammation.

Oze et al. conclude that, in clinical practice, even if HCV and eradicated and serum level of alanine aminotransferase is normal, careful surveillance for HCC was needed for patients with levels of α-fetoprotein of 5 ng/mL or greater.

Patients who do not achieve SVRs and have high levels of α-fetoprotein and alanine aminotransferase should be carefully monitored.

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