Interferon‐free therapy of chronic hepatitis C with direct‐acting antivirals does not change the short‐term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis

Mettke, F.; Schlevogt, Bernhard; Deterding, Katja; Wranke, A.; Smith, Andrea; Port, Kerstin; Manns, Michael P.; Vogel, Arndt; Cornberg, Markus; Wedemeyer, Heiner

doi:10.1111/apt.14427

Cited by 67 publications

(56 citation statements)

References 35 publications

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“…The occurrence of HCC during treatment with DAA does not appear to be associated with greater tumor aggressiveness, and, in this study, all the patients diagnosed during treatment were BCLC-A [40]. After EOT, 6 patients developed HCC, which represents an incidence rate of 11.6/1,000 person-years (a total incidence of 2.7%), similar to the results reported in other real-world studies [40][41][42][43][44]. Contrary to the initial reports about effects of DAA on the HCC incidence, recent data from larger cohorts, adjusted for confounding factors, linked DAA-induced HCV cure with a lower risk of HCC.…”

Section: Discussionsupporting

confidence: 89%

Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

Guedes

Fragoso

Lemos

et al. 2019

GE Port J Gastroenterol

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Background: Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficultto-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium-to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. Objectives: To report and analyze the long-term Seguimento a longo prazo da doença hepática avançada após cura do vírus C com antivíricos de ação direta: dados de uma coorte Portuguesa Palavras ChaveAgentes antivirais · Carcinoma hepatocelular · Cirrose hepática · Hepatite C · Resposta virológica sustentada Resumo Introdução: Os antivíricos de ação direta (AAD) revolucionaram o tratamento da hepatite C ao atingirem elevadas taxas de resposta virológica sustentada (RVS), mesmo em grupos historicamente difíceis de tratar. A RVS associa-se a uma diminuição do risco de carcinoma hepatocelular (CHC), necessidade de transplantação e mortalidade, global e de causa hepática. São ainda insuficientes de coortes reais na literatura dados que permitam avaliar a extensão dos benefícios clínicos a médio-longo prazo do atingimento de uma RVS com os AAD. Objetivos: Reportar e analisar o impacto a longo prazo da RVS numa coorte real de doentes com doença hepática avançada, tratados com AAD. Métodos: Estudo unicêntrico, retrospetivo, longitudinal com inclusão de doentes com hepatite C crónica com cirrose ou fibrose avançada, que iniciaram tratamento com AAD de fevereiro de 2015 a janeiro de 2017. Resultados: Foram incluídos 237 doentes. Verificou-se uma taxa de retenção no tratamento de 98.7% com uma taxa de RVS de 97.8% (intention to treat: 96.6%). Dos 229 doentes curados, 67.2% eram cirróticos (64.2% Child-Pugh A, 3.1% Child-Pugh B) e 32.8% F3, com um seguimento médio de 28 meses. A taxa de mortalidade global foi de 19/1,000 pessoas-ano e de mortalidade associada à doença hepática de 9.5/1,000 pessoasano. A incidência de eventos de descompensação hepática foi de 25/1,000 pessoas-ano e a de CHC foi de 11.6/1,000 pessoas-ano. Verificou-se um aumento sustentado dos valores séricos de plaquetas até 2 anos de seguimento. A história de eventos de descompensação hepática, concentração de plaquetas e albumina prétratamento encontrou-se significativamente associada a eventos adversos hepáticos durante o seguimento. Conclusões: A cura virológica após tratamento com AAD é sustentada no tempo, encontrando-se associada a um excelente prognóstico clínico em doentes com doença hepática avançada compensada, e a uma melhoria ou estabilização da doença em doentes descompensados. O atingimento de RVS associa-se a um baixo risco de CHC, não o eliminando, e de progressão da doença, sobretudo perante a presença de outros cofatores de agressão hepática, recomendando-se a manutenção do seguimento destes doentes.

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Section: Discussionsupporting

confidence: 89%

Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

Guedes

Fragoso

Lemos

et al. 2019

GE Port J Gastroenterol

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“…(4)(5)(6) Nevertheless, the impact of viral eradication after DAA treatment on disease progression, including the development of HCC, has been questioned. (7)(8)(9)(10)(11) Zinc is well known to be an active center of or coenzyme for >300 types of enzymes that are involved in numerous biological processes, including DNA synthesis, RNA transcription, cell growth and division, among others. As a result, zinc is considered to be an essential trace element for maintaining life.…”

mentioning

confidence: 99%

Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc

Ozeki

Nakajima

Suii

et al. 2020

J. Clin. Biochem. Nutr.

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The recently approved direct acting antivirals (DAA) agents are effective in terms of sustained virologic response (SVR) rates and are well tolerated in most hepatitis C virus (HCV) patients. This study aimed to analyze the association between serum zinc levels in patients who developed hepatocellular carcinoma (HCC) following HCV eradication after DAA treatment. The retrospective study included 769 HCV infected patients who achieved SVR after DAA treatment. We calculated the annual incidence rate of HCC and identified risk factors associated with HCC development. We also assessed serum zinc and clinical factors at both baseline and end of treatment (EOT). During follow up (median duration 35 months), HCC occurred in 18/769 (2.3%) patients. From the multivariate analysis, serum zinc <60 μg/dl [hazard ratio (HR) 5.936] and AFP ≥6.0 ng/dl (HR 5.862) at baseline, baseline zinc <60 μg/dl (HR 6.283), EOT serum zinc <63 μg/dl (HR 6.011), baseline AFP ≥6.0 ng/dl (HR 8.163), and EOT M2BPGi ≥2.5 (HR 12.194) at baseline and EOT were independently associated with increased HCC risk. In patients who achieved HCV eradication following DAA treatment, serum zinc levels before and at EOT could be a risk factor for developing HCC.

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“…Conversely, if patients are screened just before starting DAAs and those with suspicious lesions are excluded from follow-up analysis, the post-cure HCC incidence will be artificially lowered, causing an apparent treatment-related decrease that did not actually occur. As it stands, some HCC experts report that DAAs increase HCC risk in the short term, because they “prime” tumor growth (Mariño et al, 2019), others report “a considerable reduction in the risk of HCC” (Kanwal et al, 2017), and others report no short-term impact (Mettke et al, 2018). A recent investigation showed that the incidence of HCC remained constant for ten years after interferon-based treatment, but decreased between the first and fourth years after DAA treatment (Ioannou et al, 2019).…”

Section: Hepatitis C Virus (Hcv): Test Treat and Find A Way To Manage The Damage Left Behindmentioning

confidence: 99%

Escape from planned obsolescence: Hepatitis C, the cirrhotic liver, and clonal expansions

Branch

2020

Journal of Experimental Medicine

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Interferon‐free therapy of chronic hepatitis C with direct‐acting antivirals does not change the short‐term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis

Abstract: IFN-free direct-acting antiviral therapy of chronic hepatitis C does not alter the short-term risk for HCC in patients with liver cirrhosis. A reduced HCC incidence may become evident after more than 1.5 years of follow-up.

Cited by 67 publications

References 35 publications

Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

Predictors of hepatocellular carcinoma after hepatitis C virus eradication following direct-acting antiviral treatment: relationship with serum zinc

Escape from planned obsolescence: Hepatitis C, the cirrhotic liver, and clonal expansions

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