Sex difference in the development of hepatocellular carcinoma after direct‐acting antiviral therapy in patients with HCV infection

Watanabe, Takao; Terada, Yoshio; Joko, Kouji; Michitaka, Kojiro; Horiike, Norio; Tanaka, Yoshinori; Tada, Fujimasa; Kisaka, Yoshiyasu; Nakanishi, Seiji; Yamauchi, Kazuhiko; Yukimoto, Atsushi; Nakamura, Yoshiko; Hirooka, Masashi; Abe, Masanori; Hiasa, Yoichi

doi:10.1002/jmv.25984

Cited by 11 publications

(15 citation statements)

References 30 publications

(59 reference statements)

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“…Several studies have reported that males are at high risk of developing HCC after IFN-based therapy [ 23 , 24 ]. In the present results, sex difference also affected HCC recurrence after IFN-free DAA regimens [ 25 ]. As in some previous reports, in the present study, absence of SVR was strongly associated with recurrence after DAA therapy.…”

Section: Discussionmentioning

confidence: 69%

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

et al. 2021

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Background An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment. Methods Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated. Results Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase. Conclusion Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.

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Section: Discussionmentioning

confidence: 69%

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

et al. 2021

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“…Results from another two recently published studies are consistent with those reported by this second study by Kanwal et al [ 39 ] In a retrospective study, Tani et al [ 40 ] demonstrated that the 12- and 36-mo cumulative incidences of HCC were 1.88 and 6.00%, respectively. Similarly, Watanabe et al [ 41 ] reported 1- and 2-year cumulative incidences of HCC of 1.9 and 4.1%, respectively.…”

Section: Hcc Occurrence After Daa Therapymentioning

confidence: 80%

“…Despite using different inclusion criteria and study methods, these three cohort studies demonstrated that the presence of cirrhosis and the absence of SVR were the major risk factors of HCC occurrence in HCV patients[ 34 , 35 , 37 ]. A high FIB-4 index and posttreatment AFP were identified as independent factors that contributed to HCC occurrence in two recent studies[ 39 , 41 ].…”

Section: Risk Factors For De Novo and Recurrent Hcmentioning

confidence: 99%

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end

Muzîca

Stanciu

Huiban

et al. 2020

WJG

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Direct acting antivirals (DAAs) have revolutionized the treatment of hepatitis C virus (HCV) infection, achieving high rates (≥ 95%) of sustained virological response, with a good safety profile and high compliance rates. Consequently, it had been expected that viral clearance will reduce morbidity and mortality rates, as well as the risk of hepatocellular carcinoma (HCC). However, since 2016, concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy, which led to an avalanche of studies with contradictory results. We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

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“…In 5 studies, baseline FIB-4 was reported to be an independent risk factor for HCC occurrence. 34 , 40 , 47 , 50 , 59 Risk thresholds varied according to each study: Kanwal et al used the standard 3.25 cut-off, 34 whereas Iio et al used the 2.67 cut-off. 47 In the study by Watanabe et al, baseline FIB-4 predicted HCC in females, only.…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

“… 47 In the study by Watanabe et al, baseline FIB-4 predicted HCC in females, only. 59 In addition, three Japanese studies reported that post-SVR FIB-4 (at EOT and at SVR12) and changes in FIB-4 independently predicted de-novo HCC. 50 , 55 , 60 Among investigated serological biomarkers of fibrosis was Wisteria floribunda agglutinin positive Mac-2 (WFA*M2BP), which was tested in the study by Nagata et al, reporting that WFA*M2BP assessed 24 weeks after EOT independently predicted de-novo HCC 55 ( Tables 5 and 6 ).…”

Section: Predictors Of De-novo Hccmentioning

confidence: 99%

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

D’Ambrosio¹,

Degasperi²,

Lampertico³

2021

JHC

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Chronic infection with hepatitis C virus (HCV) may complicate with hepatocellular carcinoma (HCC), especially in patients with cirrhosis. Although the achievement of a sustained virological response (SVR) had been associated with a reduction in the risk of HCC already in the Interferon era, some concerns initially raised following the use of direct-acting antivirals (DAA), as their use was associated with increased risk of HCC development and aggressiveness. However, studies demonstrated that the risk of HCC was strongly influenced by pre-treatment fibrosis stage and, eventually, prior HCC history more than the type of antiviral therapy. According to published studies, rates of de-novo HCC ranged between 1.4% and 13.6% in patients with cirrhosis or advanced fibrosis vs 0.9% and 5.9% in those with chronic hepatitis C (CHC). Conversely, rates of recurrent HCC were higher, ranging between 3.2% and 49% in cirrhotics vs 0% and 40% in CHC patients. Most studies tried to identify predictors of HCC development, either de-novo or recurrent, and some authors were also able to build predictive scores for HCC risk stratification, which however still need prospective validation. Whereas some clinical features, such as age, gender, presence of comorbidities and fibrosis stage, may influence both de-novo and recurrent HCC, previous tumour burden before DAA seems to prevail over these features in recurrent HCC risk prediction.

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Sex difference in the development of hepatocellular carcinoma after direct‐acting antiviral therapy in patients with HCV infection

Cited by 11 publications

References 30 publications

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy: A debate near the end

Predicting Hepatocellular Carcinoma Risk in Patients with Chronic HCV Infection and a Sustained Virological Response to Direct-Acting Antivirals

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