Association of liver stiffness and steatosis with hepatocellular carcinoma development in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response

Toshifumi Tada; Takashi Nishimura; Tomomitsu Matono; Masahiro Yoshida; Minako Yuri; Aoi Fujiwara; Yukihisa Yuri; Tomoyuki Takashima; Nobuhiro Aizawa; Naoto Ikeda; Hirayuki Enomoto; Takashi Kumada; Hiroko Iijima

doi:10.1111/hepr.13677

Association of liver stiffness and steatosis with hepatocellular carcinoma development in patients with hepatitis C virus infection who received direct-acting antiviral therapy and achieved sustained virological response

Hepatol Res. 2021 Aug;51(8):860-869. doi: 10.1111/hepr.13677. Epub 2021 Jun 7.

Authors

Toshifumi Tada^{1

2

3}, Takashi Nishimura^{2

3}, Tomomitsu Matono^{2

3

4}, Masahiro Yoshida³, Minako Yuri², Aoi Fujiwara², Yukihisa Yuri², Tomoyuki Takashima², Nobuhiro Aizawa², Naoto Ikeda², Hirayuki Enomoto², Takashi Kumada⁵, Hiroko Iijima^{2

3}

Affiliations

¹ Department of Internal Medicine, Japanese Red Cross Society Himeji Hospital, Himeji, Hyogo, Japan.
² Department of Internal Medicine, Division of Gastroenterology and Hepatology, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
³ Ultrasound Imaging Center, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
⁴ Department of Internal Medicine, Himeji St. Mary's Hospital, Himeji, Hyogo, Japan.
⁵ Faculty of Nursing, Gifu Kyoritsu University, Ogaki, Japan.

PMID: 34046970
DOI: 10.1111/hepr.13677

Abstract

Aim: The pathogenic process underlying the development of hepatocellular carcinoma (HCC) is not yet clear in patients with chronic hepatitis C virus who receive direct-acting antiviral therapy and achieve sustained virological response. This study investigated two risk factors for HCC in these patients; specifically, hepatic fibrosis and steatosis.

Methods: A total of 355 patients in whom hepatitis C virus was eradicated by direct-acting antiviral were evaluated. Fibrosis and steatosis were assessed using transient elastography (TE) and the controlled attenuation parameter (CAP). Inverse probability weighting was applied to patient age, sex, albumin-bilirubin, α-fetoprotein, history of HCC, TE, or CAP.

Results: The 12-, 24-, and 36-month cumulative incidence rates of HCC were 0.9%, 2.4%, and 4.1%, respectively. Univariate analysis with the Cox proportional hazards model showed that whereas a high TE value (≥10 kPa) was significantly associated with HCC development (HR 7.861, 95% CI 2.126-29.070; p = 0.002), CAP was not. Additionally, univariate analysis with the Cox proportional hazards model adjusted by inverse probability weighting showed that a high TE value was significantly associated with HCC development (HR 3.980, 95% CI, 1.036-15.290; p = 0.044), whereas CAP was not. The cumulative inverse probability weighting-adjusted incidence of HCC rates at 12, 24, and 36 months were 0.0%, 0.5%, and 1.7%, respectively, in patients with a low TE value, and 2.5%, 5.1%, and 7.6%, respectively, in those with a high TE value.

Conclusion: A high TE value was a risk factor for HCC in hepatitis C virus patients who received direct-acting antiviral therapy and achieved sustained virological response.

Keywords: controlled attenuation parameter; direct-acting antiviral; hepatitis C virus; hepatocellular carcinoma; sustained virological response; transient elastography.