Inhibition of hepatocellular carcinoma by PegIFNα-2a in patients with chronic hepatitis C: a nationwide multicenter cooperative study

Abstract

BackgroundWe investigated whether the administration of maintenance doses of interferon prevented hepatocellular carcinoma (HCC) in patients with chronic hepatitis C.MethodsStudy 1: A multicenter, retrospective, cooperative study was carried out to determine whether long-term administration of low-dose peginterferon alpha-2a (PegIFNα-2a) prevented HCC development in patients with chronic hepatitis C. In total, 594 chronic hepatitis C patients without a history of HCC were enrolled and treated with 90 μg PegIFNα-2a administered weekly or bi-weekly for at least 1 year. Study 2: HCC developed in 16 of 99 additional patients without PegIFNα-2a treatment during 3.8 years of observation. A propensity-matched control study was then carried out to compare the incidence of HCC between the 59 patients who received low-dose PegIFNα-2a (PegIFNα-2a group) and 59 patients who did not receive PegIFNα-2a treatment (control group), matched for sex, age, platelet count, and total bilirubin levels.ResultsStudy 1: HCC developed in 49 patients. The risk of HCC was lower in patients with undetectable hepatitis C virus RNA, ≤40 IU/L alanine aminotransferase (ALT), or ≤10 ng/L alpha-fetoprotein (AFP) 24 weeks after the start of therapy. Study 2: The incidence of HCC was significantly lower in the PegIFNα-2a group than in the control group.ConclusionsLow-dose and long-term maintenance administration of PegIFNα-2a decreased the incidence of HCC in patients with normalized ALT and AFP levels at 24 weeks compared with patients without normal ALT and AFP levels.

Guidelines for the Management of Hepatitis C Virus Infection

“…The reduction in risk of HCC was particularly marked in patients with advanced fibrosis (F3–4) (RR, 0.0847; P = 0.0036). Even in patients who failed to eradicate HCV RNA, the HCC rate was significantly lower in those who achieved either an ALT level <40 IU/L or AFP <10 ng/mL at treatment week 24 . Improvement in ALT and AFP levels with Peg‐IFN‐α‐2a monotherapy has been reported in other Japanese studies …”

“…Strict control of the ALT level is particularly necessary in the group at high risk of developing HCC. Low‐dose Peg‐IFN therapy should be discontinued if no improvement is seen within 6 months in the ALT level (to ≤40 IU/L) or the α‐fetoprotein (AFP) level (to ≤10 ng/mL) …”

Reduced Organic Anion Transporter Expression Is a Risk Factor for Hepatocellular Carcinoma in Chronic Hepatitis C Patients: A Propensity Score Matching Study

“…Subsequently, we revealed a significant association between SLC22A7 expression in hepatitis tissue and the risk of future HCC in chronic HCV patients. Indeed, previous studies show several risk factors for HCC in these patients, including failure to achieve SVR, older age, male gender, obesity and advanced fibrosis and steatosis of the liver [20,21,22]. According to current data, assessments of transporter function in liver biopsies contribute an additional valuable predictor.…”

Efficacy and HCC development after DAA therapy for patients with chronic hepatitis C: a single center retrospective cohort study

“…In Italy, Bruno et al [15] reported that the SVR to IFN-α was associated with improved outcomes in HCV-related cirrhosis. Moreover, IFN itself has an anti-tumor effect [16] , and low-dose and long-term maintenance administration of PEG-IFNα-2α decreased the incidence of HCC in non-SVR patients [17] . On the other hand, DAA has no direct anti-tumor effect, and the suppressive effect of DAA on HCC occurrence remains controversial in western countries [18][19][20][21] .…”