Sci Rep. 2018;8(1):13651.

Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality.

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제1저자 이윤빈,남준열 · 교신저자 이정훈

PMID 30209336 PMC6135856 DOI 10.1038/s41598-018-31839-y IF 4.9 소화기내과

소속 (5)

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea. pindra@empal.com.
Department of Internal Medicine and Liver Center, Ewha Womans University School of Medicine, Seoul, Korea.
Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.

Abstract

Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. We investigated the differential effect of SVR on the risk of outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised using FIB-4: <1.45, low-probability of significant fibrosis; 1.45-3.25, intermediate-probability; and ≥3.25, high-probability. Primary and secondary endpoints were hepatocellular carcinoma (HCC) occurrence and death, respectively. Among 1,373 included chronic hepatitis C patients, 744 patients were treated with interferon-based or -free regimens and 622 (83.6%) achieved SVR. SVR was independently associated with lower risk of HCC (vs. untreated: adjusted hazard ratio [aHR], 0.165; 95% confidence interval [CI], 0.077-0.350; P < 0.001) and overall death (vs. untreated; aHR, 0.146; 95% CI, 0.050-0.424; P < 0.001) during the median observation of 3.5 (interquartile range, 1.9-6.6) years. The SVR group had significantly lower risk of HCC than the untreated group among patients with intermediate-probability (n = 492: aHR, 0.171; 95% CI, 0.051-0.578; P = 0.004) and high-probability (n = 446: aHR, 0.243; 95% CI, 0.107-0.551; P < 0.001) of significant fibrosis. HRs were maintained after balancing with inverse probability weighting. SVR was associated with reduced risk of HCC development and all-cause mortality in patients with chronic hepatitis C.

Figures

**Figure 1** Incidence of HCC by group. (A) In the entire study population. (B) In patients with low-probability of significant fibrosis (FIB-4 < 1.45). (C) In patients with intermediate-probability of significant fibrosis (FIB-4 1.45–3.25). (D) In patients with high-probability of significant fibrosis (FIB-4 ≥ 3.25).

**Figure 2** The risk of HCC in the subgroups stratified according to baseline characteristics. The graph shows the estimates of the HR for each subgroup as a *square* (which is sized proportionally to the amount of information per subgroup) and the *horizontal lines* indicate 95% CIs, those were calculated using the Cox proportional hazards model. The *vertical solid line* at the HR of unity corresponds to the line of no effect, the HR values less than unity mean a reduced risk of developing HCC by antiviral treatment. The *diamond* indicates HR with 95% CI for all study subjects and the *vertical dashed line* depicts the overall effect. Patients who received antiviral treatment were included in the treated group regardless of SVR achievement.

**Figure 3** Incidence of all-cause mortality by group. (A) In the entire study population. (B) In patients with low-probability of significant fibrosis (FIB-4 < 1.45). (C) In patients with intermediate-probability of significant fibrosis (FIB-4 1.45–3.25). (D) In patients with high-probability of significant fibrosis (FIB-4 ≥ 3.25).

**Figure 4** The risk of all-cause mortality in the subgroups stratified according to baseline characteristics. The graph shows the estimates of the HR for each subgroup as a *square* (which is sized proportionally to the amount of information per subgroup) and the *horizontal lines* indicate 95% CIs, those were calculated using the Cox proportional hazards model. The *vertical solid line* at the HR of unity corresponds to the line of no effect, the HR values less than unity mean a reduced risk of all-cause mortality by antiviral treatment. The *diamond* indicates HR with 95% CI for all study subjects and the *vertical dashed line* depicts the overall effect. Patients who received antiviral treatment were included in the treated group regardless of SVR achievement.

그림 출처: PubMed Central 공개 논문 (PMC6135856)

Comment · 정정

Erratum in Sci Rep. 2019 Aug 16;9(1):12146. doi: 10.1038/s41598-019-48367-y.

Conflict of interest statement

These authors disclose the following: Dr. Jung-Hwan Yoon reports receiving research grants from Bayer HealthCare Pharmaceuticals, Daewoong Pharmaceuticals, and Bukwang Pharmaceuticals; Dr. Yoon Jun Kim, research grants from Bristol-Myers Squibb, Roche, JW Creagene, Bukwang Pharmaceuticals, Handok Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Samjin Pharmaceuticals, and Pharmaking, and lecture fees from Bayer HealthCare Pharmaceuticals, Gilead Science, MSD Korea, Yuhan Pharmaceuticals, Samil Pharmaceuticals, CJ Pharmaceuticals, Bukwang Pharmaceuticals, and Handok Pharmaceuticals; Dr. Seong Gyu Hwang, research grants from Gilead Science and Dong-A ST; and Dr. Su Jong Yu, lecture fee from Bayer HealthCare Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. Dr. Yun Bin Lee, Dr. Joon Yeul Nam, Dr. Jeong-Hoon Lee, Dr. Young Chang, Dr. Hyeki Cho, Dr. Young Youn Cho, Dr. Eun Ju Cho, Dr. Hwi Young Kim, Dr. Dong Ho Lee, and Dr. Jeong Min Lee report no conflict of interest.

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