Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study

Ide, Tatsuya; Koga, Hironori; Nakano, Masahito; Hashimoto, Satoru; Yatsuhashi, Hiroshi; Higuchi, Nobito; Nakamuta, Makoto; Oeda, Satoshi; Eguchi, Yuichiro; Shakado, Satoshi; Sakisaka, Shotaro; Yoshimaru, Yoko; Sasaki, Yutaka; Honma, Yuichi; Harada, Masaru; Seike, Masataka; Maeshiro, Tatsuji; Miuma, Satoshi; Nakao, Kazuwa; Mawatari, Seiichi; Ido, Akio; Nagata, Kenji; Matsumoto, Shuichi; Takami, Yuko; Sohda, Tetsuo; Kakuma, Tatsuyuki; Torimura, Takuji

doi:10.1007/s12072-019-09939-2

Cited by 51 publications

(79 citation statements)

References 22 publications

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“…Similar risk factors were also reported by several studies . Interestingly diabetes mellitus is not reported as a risk factor for development of HCC in our study or the other studies in patients who achieved SVR after DAAs, but it was reported as a risk factor in CHC patients treated with IFN …”

Section: Discussionsupporting

confidence: 91%

“…HCC incidence rates were 2.28/100 person‐years for 1160 DAA treated patients compared with 2.12 for 463 IFN treated patients and 4.53 per 100 person‐years in untreated patients with cirrhosis (n = 1236) and concluded that DAAs decrease the incidence of HCC in CHC patients who achieved SVR . The same conclusion was recently reached by Carrat et al and Ide et al…”

Section: Introductionsupporting

confidence: 62%

“…The reduced incidence of HCC after DAAs was also confirmed by Ide et al, who prospectively investigated the incidence and risk factors of HCC after DAA treatment in a large multicenter cohort in Japan with mean follow‐up period was 22.6 ± 8.3 months; most of the Japanese patients (78%) were genotype 1 …”

Section: Discussionmentioning

confidence: 57%

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Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Shiha

Mousa

Soliman

et al. 2020

Journal of Viral Hepatitis

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Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%‐8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long‐term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis‐related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow‐up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow‐up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow‐up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942‐2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407‐3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333‐1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionsupporting

confidence: 62%

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Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Shiha

Mousa

Soliman

et al. 2020

Journal of Viral Hepatitis

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“…However, careful follow-up is important not only in patients with virological failure or with known risk factors (i.e., decompensation of liver cirrhosis prior to antiviral treatment or a "cured" HCC), but also in patients with F4 fibrosis stage/liver cirrhosis prior to viral eradication. The cumulative incidence reported in this study is similar with previously reported incidence of newly diagnosed HCC at 1 year after exposure to DAA [9,[24][25][26]. In patients with advanced hepatitis C receiving DAA, the residual HCC risk might be lower than that of untreated patients and declines progressively with time after a sustained virological response [26].…”

Section: Discussionsupporting

confidence: 87%

“…After successful DAA treatment, preliminary data have shown an improvement in Child-Pugh class (observed in 85% of coinfected and in 65.9% of monoinfected patients, with no significant difference between the two groups), suggesting that viral eradication helps liver function recovery in the majority of patients with liver cirrhosis (data not shown). As previously reported, HCV cured after DAA therapy induce a reduction of the risk of HCC occurrence compared with non-responders; however, a residual risk still persists even after viral eradication [23][24][25][26]. In particular, regarding the HCC occurrence following viral eradication, the cumulative incidence was 2.2% in coinfected and 3.9% in monoinfected patients, significantly lower compared to the cumulative incidence of HCC (13.8%) reported in patients who experienced treatment failure in the PITER cohort [23].…”

Section: Discussionmentioning

confidence: 62%

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

et al. 2020

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Background Liver disease progression after Hepatitis C Virus (HCV) eradication following direct-acting antiviral (DAA) treatment in the real-life setting according to Human Immunodeficiency Virus (HIV) coinfection was evaluated. Methods Patients consecutively enrolled in PITER between April 2014 and June 2019 and with at least 12-weeks follow-up following treatment were analysed. Cox regression analysis were used to evaluate HIV coinfection and factors independently associated with liver disease outcomes following viral eradication in DAA treated patients with pre-treatment liver cirrhosis. Results 93 HIV/HCV coinfected and 1109 HCV monoinfected patients were evaluated during a median follow-up of 26.7 (range 6-44.6) and 24.6 (range 6.8-47.3) months, respectively. No difference in the cumulative HCC incidence and hepatic decompensation was observed between coinfected and monoinfected patients. Age (Hazard Ratio [HR] = 1.08; 95% CI 1.04-1.13), male sex (HR = 2.76; 95% CI 1.28-5.96), lower albumin levels (HR = 3.94; 95% CI 1.81-8.58), genotype 3 (HR = 5.05; 95% CI 1.75-14.57) and serum anti-HBc positivity (HR = 1.99, 95% CI 1.01-3.95) were independently associated with HCC incidence. Older age (HR = 1.03; 95% CI 1.00-1.07), male sex (HR = 2.13; 95% CI 1.06-4.26) and lower albumin levels (HR = 3.75; 95% CI 1.89-7.46) were independently associated with the appearance of a decompensating event after viral eradication. Conclusion Different demographic, clinical and genotype distribution between HIV coinfected vs those monoinfected, was observed in a representative cohort of HCV infected patients in Italy. Once liver cirrhosis is established the disease progression is decreased, but still persists regardless of viral eradication in both coinfected and monoinfected patients. In patients with cirrhosis, HIV coinfection was not associated with a higher probability of liver complications, after viral eradication.

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Characterization of circulatingmiRNAsin the treatment of primary liver tumors

Umezu,

Tanaka,

Kubo

et al. 2023

Cancer Reports

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Background and AimCirculating micro RNAs (miRNAs) indicate clinical pathologies such as inflammation and carcinogenesis. In this study, we aimed to investigate whether miRNA expression level patterns in could be used to diagnose hepatocellular carcinoma (HCC) and biliary tract cancer (BTC), and the relationship miRNA expression patterns and cancer etiology.MethodsPatients with HCC and BTC with indications for surgery were selected for the study. Total RNA was extracted from the extracellular vesicle (EV)‐rich fraction of the serum and analyzed using Toray miRNA microarray. Samples were divided into two cohorts in order of collection, the first 85 HCC were analyzed using a microarray based on miRBase ver.2.0 (hereafter v20 cohort), and the second 177 HCC and 43 BTC were analyzed using a microarray based on miRBase ver.21 (hereafter v21 cohort).ResultsUsing miRNA expression patterns, we found that HCC and BTC could be identified with an area under curve (AUC) 0.754 (v21 cohort). Patients with anti‐hepatitis C virus (HCV) treatment (SVR‐HCC) and without antiviral treatment (HCV‐HCC) could be distinguished by an AUC 0.811 (v20 cohort) and AUC 0.798 (v21 cohort), respectively.ConclusionsIn this study, we could diagnose primary hepatic malignant tumor using miRNA expression patterns. Moreover, the difference of miRNA expression in SVR‐HCC and HCV‐HCC can be important information for enclosing cases that are prone to carcinogenesis after being cured with antiviral agents, but also for uncovering the mechanism for some carcinogenic potential remains even after persistent virus infection has disappeared.

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Direct-acting antiviral agents do not increase the incidence of hepatocellular carcinoma development: a prospective, multicenter study

Cited by 51 publications

References 22 publications

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study

Advanced liver disease outcomes after hepatitis C eradication by human immunodeficiency virus infection in PITER cohort

Characterization of circulatingmiRNAsin the treatment of primary liver tumors

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