High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis

Cardoso, Hélder; Vale, Ana Maria Horta e; Rodrigues, Susana; Gonçalves, Regina; Albuquerque, Andreia; Pereira, Pedro; Lopes, Susana; Silva, Marco; Andrade, Patrícia; Morais, Rui; Coelho, Rosa; Macedo, Guilherme

doi:10.1016/j.jhep.2016.07.027

Cited by 144 publications

(148 citation statements)

References 6 publications

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“…This hypothesis is supported by reports of increased hepatocellular carcinoma recurrence in patients after interferon-free direct antiviral therapy [19,20,21,22], which is thought to occur from the mechanism exposed above. Nonetheless, studies on this matter are conflicting and still under debate.…”

Section: Discussionsupporting

confidence: 56%

Primary Liver Diffuse Large B-Cell Lymphoma following Complete Response for Hepatitis C Infection after Direct Antiviral Therapy

Andrade¹,

Paz²,

Nassar³

et al. 2018

Acta Haematol

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Introduction: Hepatitis C infection is highly prevalent worldwide and has a well-known association with B-cell lymphoid malignancies. Antiviral therapy has successfully decreased the rate of liver cirrhosis and improved the outcome in patients with hepatitis C-associated lymphomas. However, although there are a few case reports of aggressive lymphomas after successful hepatitis C therapy, the mechanism behind this association remains unclear. Case Presentation: We present the case of a 55-year-old man with chronic hepatitis C infection and liver cirrhosis who received antiviral therapy with sofosbuvir and ribavirin and achieved a sustained complete virological response. One year after successful therapy, there was an unexplained decline of his liver function and atypical liver nodularity, which led to the diagnosis of a primary liver diffuse large B-cell lymphoma. Discussion: We review the evidence supporting possible mechanisms of lymphomagenesis after successful hepatitis C therapy, particularly involving late “second-hit” mutations after viral-induced DNA damage and antiviral therapy facilitating the emergence of latent malignant B-cell clones by decreasing local inflammation and immune surveillance. More reports may help elucidate any association between hepatitis C antiviral therapy and late lymphoid malignancies.

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Section: Discussionsupporting

confidence: 56%

Primary Liver Diffuse Large B-Cell Lymphoma following Complete Response for Hepatitis C Infection after Direct Antiviral Therapy

Andrade¹,

Paz²,

Nassar³

et al. 2018

Acta Haematol

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“…Based only on this study, we can conclude that HCC occurrence remained probably higher than most expected, but there is definitely no increased risk. In another study, Cardoso et al [13] reported a higher occurrence, of 7.4%. There was no significant difference in the baseline variables that could be associated with an increased risk of HCC [13].…”

Section: The Impact Of Ifn-free Regimens On Hcc Occurrencementioning

confidence: 84%

“…In another study, Cardoso et al [13] reported a higher occurrence, of 7.4%. There was no significant difference in the baseline variables that could be associated with an increased risk of HCC [13]. A Letter to the Editor evidenced an incidence in the HCC rate of 6.6% [14].…”

Section: The Impact Of Ifn-free Regimens On Hcc Occurrencementioning

confidence: 84%

Hepatocellular Carcinoma Occurrence and Recurrence after Antiviral Treatment in HCV-Related Cirrhosis. Are Outcomes Different after Direct Antiviral Agents? A Review

Spârchez

Mocan²

2017

JGLD

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Hepatitis C virus (HCV) infection is one of the major causes of hepatocellular carcinoma (HCC) worldwide. In the last decades, several studies have showed a lower rate of HCC occurrence or recurrence in patients with HCV-related cirrhosis after interferon-based antiviral therapies compared to untreated controls, even without reaching viral clearance. Unfortunately, interferon regimens could only yield viral clearance in approximately half of the patients. The recent development of new all-oral regimens with direct-acting antivirals (DAAs) has radically improved the cure rate to above 90%. In respect to these findings, many would have thought that interferon-free regimens would decrease the development and recurrence of HCC. Literature data have unexpectedly reported high rates of both the occurrence and recurrence of HCC after therapy with DAAs. However, it is probably too early to express some concerns. More recent data showed that both occurrence and recurrence of HCC are decreased by the DAAs. Interferon-free therapy is definitely not without limits. Together with the initial thoughts of an increased risk of HCC, these may lead to an unwanted restricted access to interferon-free regimens in specific subpopulations. This issue should be settled as soon as possible because millions of hepatitis C patients are and will be using DAAs in the present and future. Our purpose is to review the existing literature and to offer a more precise and rational interpretation of the existing data.Key words: – – e – .Abreviations: AFP: alpha-fetoprotein; DAA: direct antiviral agent; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; HR: hazard ratio; IFN: interferon; LDV: Ledispavir; SMV: Simeprevir; SOF: Sofosbuvir; SVR: sustained virologic response.

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“…Ravi et al, observed an occurrence of de novo HCC in about 9% of the patients during or within six months of DAA therapy (39). DAA therapy seemed to increase the de novo occurrence of HCC among patients with HCV -related cirrhosis (40). However, other studies showed opposite conclusion (41)(42)(43).…”

Section: "De Novo Hcc" In Daa -Treated Patientsmentioning

confidence: 99%

Hepatitis C Virus - Related Hepatocellular Carcinoma in the Era of Direct - Acting Antiviral Agents

Gao

Niu

2018

Hepat Mon

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Context: The emergence of direct -acting antiviral agents (DAAs) with high sustained virological responses (SVR) is an epoch -making revolution. However, the value of antiviral agents in the field of hepatitis C -related hepatocellular carcinoma (HCC) is not clear. Further, the risk of tumor occurrence or recurrence following an antiviral regimen is not yet reached a consensus. Evidence Acquisition: All scientific evidence was collected through a systematic review of studies discussing DAA regimen and hepatitis C-related HCC, in PubMed, EMBASE, and Web of Science. The relevant articles were obtained and reviewed carefully before working on the paper. Results: The current review study aimed at discussing recent studies on hepatitis C -related HCC in the era of DAAs, including application of DAAs in the field of treatment of hepatitis C virus (HCV), efficacy of DAAs on HCV-associated HCC, and the effect of DAAs on occurrence and recurrence of HCC. Conclusions: It was shown that DAAs had a relatively poor therapeutic effect on HCV patients with HCC, based on the current studies. After analyzing the existing data, the conclusion cannot yet be reached that DAA treatment influences the risk of HCC in patients with HCV infection.

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High incidence of hepatocellular carcinoma following successful interferon-free antiviral therapy for hepatitis C associated cirrhosis

Cited by 144 publications

References 6 publications

Primary Liver Diffuse Large B-Cell Lymphoma following Complete Response for Hepatitis C Infection after Direct Antiviral Therapy

Primary Liver Diffuse Large B-Cell Lymphoma following Complete Response for Hepatitis C Infection after Direct Antiviral Therapy

Hepatocellular Carcinoma Occurrence and Recurrence after Antiviral Treatment in HCV-Related Cirrhosis. Are Outcomes Different after Direct Antiviral Agents? A Review

Hepatitis C Virus - Related Hepatocellular Carcinoma in the Era of Direct - Acting Antiviral Agents

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