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

Abstract

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.

Development of diffuse large B‑cell lymphoma after sofosbuvir‑ledipasvir treatment for chronic hepatitis C: A case report and literature review

“…Moreover, acute or chronic HCV infections are known to be associated with increased frequencies of BCL-6 and p53 gene mutations in B-cells in vitro ; mutations in these genes have been linked to DLBCL ( 31 ). Accordingly, HCV-related lymphomagenesis may be attributed to either chronic viral antigen stimulation or genetic mutations that lead to the clonal expansion and malignant transformation of B-cells, as previously reported ( 7 , 5 , 25 ).…”

“…However, several possible mechanisms have been proposed in recent publications. Andrade et al ( 25 ) suggested that HCV-induced genetic damage produced a survival signal in B-cells, which may lead to late transformation, even years after successful HCV therapy. Indeed, genetic mutations derived from either acute or chronic HCV infection are known to persist, even after HCV clearance ( 31 ).…”

Primary hepatic large B-cell lymphoma following direct-acting antiviral treatment for hepatitis C

“…There are even few available data on PHL occurring after DAA therapy, and to the best of our knowledge, there are only two cases reporting this association in the literature. 1 2 The issues raised about HCC following DAA therapy, which led to an avalanche of studies with contradictory findings, make these anecdotal observations more disquieting.…”

Transformation of A Marginal Lymphoma in Hepatitis C Virus-Infected Patient After Clearance of HCV Viral Load

“…Interestingly, the development of lymphoma occurs in the context of clearance of chronic HCV infection. There are few reports [17,18] to support the development of HCV-associated B-cell lymphoma after clearance of HCV viral load. Andrade et al [17] hypothesize that HCV clearance may restore host T-cell and B-cell mediated immunity facilitating a previously suppressed lymphoid malignant clone to proliferate.…”