Early development of de novo hepatocellular carcinoma after direct‐acting agent therapy: Comparison with pegylated interferon‐based therapy in chronic hepatitis C patients

Abstract

Patients with chronic hepatitis C who achieve a sustained viral response after pegylated interferon therapy have a reduced risk of hepatocellular carcinoma, but the risk after treatment with direct-acting antivirals is unclear. We compared the rates of early development of hepatocellular carcinoma after direct-acting antivirals and after pegylated interferon therapy. We retrospectively analysed 785 patients with chronic hepatitis C who had no history of hepatocellular carcinoma (211 treated with pegylated interferon, 574 with direct-acting antivirals) and were followed up for at least 24 weeks after antiviral treatment. De novo hepatocellular carcinoma developed in 6 of 574 patients receiving direct-acting antivirals and in 1 of 211 patients receiving pegylated interferon. The cumulative incidence of early hepatocellular carcinoma development did not differ between the treatment groups either for the whole cohort (1.05% vs 0.47%, P = .298) or for those patients with Child-Pugh Class A cirrhosis (3.73% vs 2.94%, P = .827). Multivariate analysis indicated that alpha-fetoprotein level >9.5 ng/mL at the time of end-of-treatment response was the only independent risk factor for early development of hepatocellular carcinoma in all patients (P < .0001, hazard ratio 176.174, 95% confidence interval 10.768-2882.473) and in patients treated with direct-acting agents (P < .0001, hazard ratio 128.402, 95% confidence interval 8.417-1958.680). In conclusion, the rate of early development of hepatocellular carcinoma did not differ between patients treated with pegylated interferon and those treated with direct-acting antivirals and was associated with the serum alpha-fetoprotein level at the time of end-of-treatment response.

Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea

“…Baseline AFP levels may increase because of viral activity, but patients with an increased AFP level at the end of treatment should be carefully monitored for HCC development or recurrence. We previously reported that the early development of HCC was associated with serum AFP level >9.5 mg/mL at the end of treatment in CHC patients treated with DAAs . The findings of the present study are consistent with this.…”

“…We previously reported that the early development of HCC was associated with serum AFP level >9.5 mg/ mL at the end of treatment in CHC patients treated with DAAs. 32 The findings of the present study are consistent with this.…”

The interplay between direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C

“…These features suggested that a more advanced liver disease, older age, and higher rates of comorbidities favor liver carcinogenesis. Yoo et al [22] published similar comparative data of de novo HCC occurrence in DAA group and IFN group. The cumulative incidence of HCC occurrence was not different between DAA group and IFN group (P = 0.827).…”

“…Yoo et al [22] Occurrence Alpha-fetoprotein level > 9.5 ng/mL Singer et al [23] Occurrence Older age, male gender, cirrhosis, thrombocytopenia, portal hypertension, diabetes, tobacco use, alcoholic liver disease Carrat et al [24] Occurrence Untreated, non-SVR Ide et al [25] Occurrence Age ≥ 62 years old, male gender, FIB-4 index ≥ 4.6, and GGTP level ≥ 44 IU/L Cabibbo et al [34] Recurrence Main tumor size > 2.5 cm, history of prior recurrence Nishibatake Kinoshita et al [35] Recurrence Higher lens culinaris agglutinin-reactive fraction of alpha-fetoprotein level, a history of multiple HCC treatments, and a shorter interval between HCC treatment and initiation of antiviral therapy Singal et al [37] Recurrence No associate factor HCC: hepatocellular carcinoma; SVR: sustained virological response; CPC: Child-Pugh Class; HCV: hepatitis C virus; IFN: interferon 95%CI: 1.01-1.39, P = 0.03) were significant factors prone to experience HCC recurrence [14] . A study from Japan reported on the impact of DAA on early recurrence of HCC and higher alpha-fetoprotein (AFP)-L3 level (HR: 1.47, 95%CI: 1.02-2.11, P = 0.04), larger number of HCC treatments (HR: 1.65, 95%CI: 1.16-2.35, P = 0.007), and shorter interval between the last HCC treatment and initiation of antiviral therapy (P = 0.007) were associated with the risk of HCC recurrence [35] .…”

“…There was no significant association between DAA use and risk of HCC. In our study, we compared the rates of HCC between DAA group and IFN group, and alpha-fetoprotein > 9.5 ng/mL at the time of end-of treatment response was the only significant risk factor for HCC occurrence [22] . Moreover, in a prospective study in France, exposure to DAA was strongly associated with a decrease in all-cause mortality (adjusted HR: 0.34, 95%CI: 0.22-0.55, P < 0.0001) and risk of HCC (adjusted HR: 0.57, 95%CI: 0.40-0.81 P = 0.016) [24] .…”