Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023;101(2):79-88.
doi: 10.1159/000527633. Epub 2022 Oct 21.

Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals

Norio Akuta  1 , Hitomi Sezaki  1 , Shunichiro Fujiyama  1 , Yusuke Kawamura  1 , Tetsuya Hosaka  1 , Mariko Kobayashi  2 , Satoshi Saitoh  1 , Yasuji Arase  1 , Kenji Ikeda  1 , Yoshiyuki Suzuki  1 , Fumitaka Suzuki  1 , Hiromitsu Kumada  1
Affiliations

Simple Predictive Markers and Clinicopathological Features of Primary Liver Cancer following HCV Clearance with Direct-Acting Antivirals

Norio Akuta et al. Oncology. 2023.

Abstract

Introduction: Simple predictive markers enabling even nonspecialized medical doctors and clinicopathological features of primary liver cancer (PLC) following HCV clearance with direct-acting antivirals (DAAs) are unclear.

Methods: The subjects of this retrospective study were 2,476 patients following HCV clearance with DAAs. All patients were confirmed to be PLC-free before and during DAAs.

Results: PLC was diagnosed in 73 patients during the follow-up, with an incidence rate per 1 000 person-years of 5.9. The annual rate of PLC during the first 6 years was 0.6%. Multivariate analysis identified gender, GGT, and FIB-4 index as the significant determinants of PLC. According to a combination of these risk factors, the cumulative PLC incidence rates were significantly different among the five subgroups based on the number of PLC risk scores. In 73 patients with PLC, the rates of abnormal AFP, PIVKAII, and serum TERT C228T positive were 37.0, 32.4, and 22.2%. PIVKAII levels in BCLC stage A and B were significantly higher than those in stage 0. In 41 patients, who underwent surgical resection for PLC, maximum tumor diameters of abnormal PIVKAII were significantly larger than those of normal PIVKAII. PLC of abnormal PIVKAII significantly indicated presence of vp more than that of normal PIVKAII, and did not contain well-differentiated HCC.

Conclusions: Combination of simple markers, enabling even nonspecialized medical doctors, is useful for the evaluation of PLC risk following HCV clearance with DAAs. However, imaging studies are regularly recommended for the early detection of PLC.

Keywords: Clinicopathology; Direct-acting antivirals; Fibrosis-4 index; Gamma glutamyl transpeptidase; Gender; HCV; Primary liver cancer; Sustained virological response; TERT.

PubMed Disclaimer

Conflict of interest statement

(1) Hiromitsu Kumada has received honoraria from Gilead Sciences and AbbVie Inc. (2) Yusuke Kawamura has received honoraria from Eisai Co., Ltd. All other authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Primary liver cancer rates after SVR. The cumulative primary liver cancer rates were 1.1, 1.9, 2.4, 2.8, 3.4, and 3.5% at the end of 1, 2, 3, 4, 5, and 6 years, respectively. The annual incidence of PLC during the first 6 years was 0.6%.
Fig. 2
Fig. 2
Primary liver cancer rates, according to subgroups of gender, GGT, and FIB-4 index. The cumulative primary liver cancer rates were shown, according to subgroups of gender (p = 0.002), GGT (p = 0.002), and FIB-4 index (p < 0.001), based on the log-rank test. ULN, upper limit of normal.
Fig. 3
Fig. 3
Primary liver cancer (PLC) rates, according to PLC risk scores. Incidence rates of PLC according to PLC risk scores were shown. PLC risk scores were evaluated based on the sum of gender, GGT, and FIB-4 index scores. Gender scores of 0 and 1 corresponded to female and male, respectively. GGT scores of 0, 1, and 2 corresponded to <0.5, 0.5–0.9, and ≥1.0 × ULN. FIB-4 index scores of 0, 1, 2, and 3 corresponded to <2.00, 2.00–2.66, 2.67–3.24, and ≥3.25, respectively. ULN, upper limit of normal.
See this image and copyright information in PMC

References

    1. Kanwal F, Kramer J, Asch SM, Chayanupatkul M, Cao Y, El-Serag HB. Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents. Gastroenterology. 2017;153((4)):996.e1–1005.e1. - PubMed
    1. Ioannou GN, Green PK, Berry K. HCV eradication induced by direct-acting antiviral agents reduces the risk of hepatocellular carcinoma. J Hepatol. 2018;68((1)):25–32. - PMC - PubMed
    1. Calvaruso V, Cabibbo G, Cacciola I, Petta S, Madonia S, Bellia A, et al. Incidence of hepatocellular carcinoma in patients with HCV-associated cirrhosis treated with direct-acting antiviral agents. Gastroenterology. 2018;155((2)):411.e4–421.e4. - PubMed
    1. Nahon P, Layese R, Bourcier V, Cagnot C, Marcellin P, Guyader D, et al. Incidence of hepatocellular carcinoma after direct antiviral therapy for HCV in patients with cirrhosis included in surveillance programs. Gastroenterology. 2018;155((5)):1436.e6–1450.e6. - PubMed
    1. Kumada T, Toyoda H, Yasuda S, Ito T, Tsuji K, Fujioka S, et al. Factors linked to hepatocellular carcinoma development beyond 10 years after viral eradication in patients with hepatitis C virus. J Viral Hepat. 2022 Jul 5;29:919–929. Online ahead of print. - PubMed

MeSH terms

Substances