Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related Chronic Liver Disease

Ogata, Fumihiro; Kobayashi, Masahiro; Akuta, Norio; Osawa, Mitutaka; Fujiyama, Shunichiro; Kawamura, Yusuke; Sezaki, Hitomi; Hosaka, Tetsuya; Kobayashi, Mariko; Saitoh, Satoshi; Suzuki, Yoshiyuki; Suzuki, Fumitaka; Arase, Yasuji; Ikeda, Kenji; Kumada, Hiromitsu

doi:10.1159/000470910

Cited by 45 publications

(39 citation statements)

References 24 publications

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“…However, it is well documented that treatment with interferon‐based therapies resulted in a reduced incidence of HCC . Furthermore, a recent study by Ogata et al demonstrated through multivariate analysis of 1170 Japanese patients that SVR with DAA therapy, including that of daclatasvir + asunaprevir, sofosbuvir/ledipasvir, and ombitasvir + paritaprevir+ritonavir, was significantly associated with a reduction in the development of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…At present within Japan, all types of treatment for hepatitis C covered by national insurance are subsidized including interferon‐based and interferon‐free regimens . With this in mind, it has become increasingly essential for patients to seek treatment with DAA's as the cost to patients is quite low; with hepatitis patients generally pay only ¥10 000‐20 000 per month due to heavy subsidies .…”

Section: Discussionmentioning

confidence: 99%

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Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan

Younossi

Tanaka

Eguchi

et al. 2018

Journal of Viral Hepatitis

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Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision-analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state-transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all-oral direct-acting anti-virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan-specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality-adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness-to-pay threshold of ¥4-to-¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment-related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness-to-pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness-to-pay thresholds. In conclusion treatment of HCV GT1b with all-oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan

Younossi

Tanaka

Eguchi

et al. 2018

Journal of Viral Hepatitis

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“…Our previous study found that the risk factors of hepatocarcinogenesis after elimination of HCV RNA by direct‐acting antiviral combinations were hypoalbuminemia and high α‐fetoprotein . In the present study, including HCV‐2a/2b patients, multivariate analysis identified an HCV subgroup (HCV‐1b with Gln70(His70)) and age (>65 years) as determinants of hepatocarcinogenesis.…”

Section: Discussionmentioning

confidence: 49%

“…Our previous study found that the risk factors of hepatocarcinogenesis after elimination of HCV RNA by direct-acting antiviral combinations were hypoalbuminemia and high α-fetoprotein. 26 In the present study, including HCV-2a/2b patients, multivariate analysis identified an HCV subgroup (HCV-1b with Gln70(His70)) and age (>65 years) as determinants of hepatocarcinogenesis. The present study is, to our knowledge, the first report to indicate that aa substitution in the core region also has an association with hepatocarcinogenesis following indirect role in the pathogenesis of HCC.…”

Section: Discussionmentioning

confidence: 64%

“…[3][4][5][6][7][8] Treatment with direct-acting antiviral regimens is often effective in HCV eradication, has been associated with high tolerance and adherence rates even in elderly patients and those with advanced-stage disease, and has a favorable safety profile. 7 Furthermore, eradication of HCV RNA by direct-acting antiviral regimens reduces the risk of HCC 26,32 However, hepatocarcinogenesis still occurs even after eradication of HCV RNA by direct-acting antivirals: a large number of patients might still develop HCC under these conditions. To address this issue, the results | 1091 of this study indicated that aa substitutions in the core region of HCV-1b should be detected before using direct-acting antivirals to eradicate HCV RNA.…”

Section: Discussionmentioning

confidence: 99%

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Amino acid substitutions in the hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by all‐oral direct‐acting antiviral regimens

Ogata

Akuta

Kobayashi

et al. 2018

Journal of Medical Virology

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Impact of substitution of aa70 in the core region (Core aa70) in HCV genotype 1b (HCV-1b) on hepatocarcinogenesis following eradication of HCV RNA by direct-acting antiviral therapy is not clear. In a retrospective study, 533 patients with HCV-related chronic liver disease, with sustained virological response defined as negative HCV RNA at 12 weeks after cessation of direct-acting antiviral therapy, were examined to evaluate the relationship between Core aa70 substitution and hepatocarcinogenesis. Twelve patients developed hepatocellular carcinoma during the follow-up period. The cumulative hepatocarcinogenesis rates were 1.7% and 2.4% at the end of 1 and 2 years, respectively. Overall, multivariate analysis identified HCV subgroup (HCV-1b with Gln70(His70); P = 0.003) and age (>65 years; P = 0.049), as pretreatment predictors of hepatocarcinogenesis. In HCV-1b patients, multivariate analysis identified post-treatment Wisteria floribunda agglutinin positive Mac-2 binding protein (>1.8 COI; P = 0.042) and HCV subgroup (HCV-1b with Gln70(His70); P = 0.071), as predictors of hepatocarcinogenesis, including post-treatment parameter. In conclusion, Core aa70 substitution in HCV-1b at the start of direct-acting antiviral therapy is an important predictor of hepatocarcinogenesis following eradication of HCV RNA. This study emphasizes the importance of detection of Core aa70 substitution before initiating antiviral therapy.

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Impact of hepatitis C virus eradication on hepatocellular carcinoma rates

Zamor

Russo

2017

Clinical Liver Disease

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Among individuals with hepatocellular carcinoma (HCC) in the United States, 50% to 70% occur in hepatitis C virus (HCV) patients with cirrhosis. 1 Although the risk for HCC is highest in HCV patients with cirrhosis, HCC can occur in HCV patients who do not have cirrhosis. In the interferon era, studies demonstrated the risk for HCC is substantially reduced after successful treatment, but despite virological cure, HCV patients with advanced fibrosis remain at risk for HCC. Although it would stand to reason that virological cure after direct-acting antiviral (DAA) therapy would also be associated with a reduced risk for HCC, reports have emerged that challenge this assumption. In individuals with HCC and HCV, the efficacy of DAA therapy may be lower than in individuals with only HCV. DE NOVO HCC AND THE NEED FOR SCREENINGPatients with HCV and cirrhosis or bridging fibrosis have an increased risk for HCC, with an estimated incidence rate of 1% to 4% per year, and the risk is highest among patients with cirrhosis. Among 1048 subjects with HCV followed in the Hepatitis C Antiviral Long term Treatment against Cirrhosis (HALT-C) trial for a median of 6.1 years, HCC developed in 88 (8.3%) patients. 2 The cumulative 7-year risk rate for HCC in untreated subjects with cirrhosis and bridging fibrosis was 24.2%. Because there is a high incidence of HCC in HCV patients with cirrhosis, the American Association for the Study of Liver Diseases guidelines recommend ultrasound every 6 months in individuals with HCV cirrhosis. 3 The role of alpha-fetoprotein is controversial because the 6% to 8% gain in detection rates is outweighed by an increase in false-positive results and an increase in cost. The utility of screening for HCC in HCV patients who have bridging fibrosis is controversial. 4 Viral-associated risk factors for HCC in subjects with HCV are listed in Table 1.Sustained viral response (SVR) or virological cure after interferon-based therapy for HCV is associated with a Abbreviations: CI, confidence interval; DAA, direct-acting antiviral; HALT-C, hepatitis C antiviral long term treatment against cir-

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Outcome of All-Oral Direct-Acting Antiviral Regimens on the Rate of Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Genotype 1-Related Chronic Liver Disease

Cited by 45 publications

References 24 publications

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan

Treatment of hepatitis C virus leads to economic gains related to reduction in cases of hepatocellular carcinoma and decompensated cirrhosis in Japan

Amino acid substitutions in the hepatitis C virus core region predict hepatocarcinogenesis following eradication of HCV RNA by all‐oral direct‐acting antiviral regimens

Impact of hepatitis C virus eradication on hepatocellular carcinoma rates

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