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Introduction: Hepatitis C virus (HCV) is a lymphotropic virus that promotes HCV-mediated B-cell proliferation and transformation to Non-Hodgkin Lymphoma (NHL). Here we present a case of reactivation of HCV presenting as an aggressive intra-abdominal B cell lymphoma. Case Description/Methods: A 68-years-old-male with history of eradicated HCV with recombinant interferon-alfa and resolved HBV infection presented with painless jaundice and pruritus. CT abdomen revealed a 9.6 x 11.5 x 9.5 cm heterogeneous mass causing CBD and intrahepatic biliary duct dilation. Labs revealed reactivation of HCV infection with worsening of liver function tests with total bilirubin of .40mg/dl. FNA biopsy confirmed mature B-cell lymphoma. Given persistent worsening jaundice despite biliary stent, trial of high dose steroid was initiated to improve lymphoma burden in order to get a window to initiate chemotherapy. After tumor board discussion, he received radiation therapy for tumor shrinkage for this aggressive lymphoma. Prior to initiation of planned R-CHOP chemotherapy, he developed severe sepsis with hepatic abscess. Patient and family opted for hospice care and comfort care was initiated. Discussion: Chronic HCV is a fast-growing epidemic in the U.S.A which carries an enormous threat to general population and healthcare. HCV becomes chronic in .70% of infected patients with risk for cirrhosis, hepatocellular carcinoma and lymphoma. HCV can cause NHL via lymphocyte proliferation from viral antigenic stimulation, HCV replication inside B-cell and mutation via B-cell damage. Among patient who achieve sustained viral response (SVR), reactivation occurs in 1%, 11% and 15% among low-risk monoinfected HCV, high-risk monoinfected HCV and HIV/HCV coinfected group respectively. Treatment of HCV with resolution of NHL has been reported and there is some literature with sequential chemotherapy followed by antiviral therapy (AVT) showing promising results in HCV-NHL cases. Concurrent use of AVT and chemotherapy is primarily discouraged due to hematological toxicity. More evidence and studies need to be explored for such aggressive HCV-NHL management. Patient with SVR should have at least an annual testing and periodic follow-up to access for HCV reactivation or reinfection. Hepatitis C education regarding risk factors reduction and transmission prevention should be encouraged at every healthcare level and in general community and only then we can achieve WHO aim of eradication by 2030.

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