The oncogenic effect of hepatitis C lasts beyond the disease’s eradication Sofia Cerqueira 1 , Catarina Teixeira 2 , Nuno Afonso 2,3 , Rui Castro 1 , Teresa Morgado 1 , Rui Alves 2,3 1 Nephrology Department, Centro Hospitalar de Trás-os-Montes e Alto Douro 2 Nephrology Department, Centro Hospitalar e Universitário de Coimbra 3 Nephrology, Faculty of Medicine, Coimbra, Portugal CASE REPORT Port J Nephrol Hypert 2019; 33(3): 143-144 • Advance Access publication 5 September 2019  BACKGROUND Hepatitis C virus can induce B cell lymphocyte clonal proliferation that, in some cases, can lead to the development of a full‑blown lymphoma. It has been suggested that in these cases viral eradication would lead to lymphoma cure. Nonetheless, some clones can maintain proliferation despite elimination of the viral stimuli. Treatment of these patients is extremely difficult and hazardous.  CASE REPORT A 56‑year‑old male with no relevant clinical history, was admitted in March 2016 for a right‑sided pleural effusion. Subsequent clinical investigation revealed a lymphoproliferative disease. Myelogram revealed 0.5% clonal B cells for kappa chains, with non‑Hodgkin lymphoma phenotype. Hepatitis C virus infection, genotype 3a, METAVIR fibrosis score F4, was also detected. The patient was observed at a hematology consultation and a watchful‑waiting posi‑ tion was assumed. Eight months after that, he was admitted due to acute renal lesion. There was no context of nephrotoxic medication. At that time, his serum creatinine was 2.1 mg/dL; urine analysis was positive for hematuria and proteinuria (quantified at 2.9g/24h). Additional studies revealed diminished C3 and C4 and positive cryoglobulins with polyclonal IgG and monoclonal IgM; serum immune fixation was negative for a monoclonal component. Renal biopsy showed a membranoproliferative glomerulonephritis with immune complex deposition that was interpreted in association with the HCV infection. After discussion with the Hepatology department, the patient was started on sofosbuvir and ribavirin for 24 weeks; prednisolone 1mg/ kg was associated for treatment of the glomerulonephritis. During this 24‑week period he developed severe infections (ophthalmic CMV, herpes zoster, acute tracheobronchitis), and still maintained dimin‑ ished complement factors. HCV treatment was finished, with sustained viral response (SVR) and later cure. However, at that time the myelogram showed an increased number of clonal B cells staining for kappa chains, with a lymphoplasmacytic lymphoma phenotype; there was continued pro‑ duction of cryoglobulins with complement consumption and persistent renal involvement. After consulting with a hematologist, rituximab treatment was performed (two 1gr infusions, two weeks apart). Severe infectious episodes followed and there was persistent cryoglobulin production with complement consumption. Eventually, his chronic kidney disease progressed to end‑stage and he started hemodialysis, 14 months after the kidney biopsy was performed. Four months later he presented with necrotizing vasculitis in his lower limbs. Serum immune fixation then revealed a monoclonal IgM kappa gammopathy, and cryoglobulins showed only a monoclonal component. A new line of treatment with cyclophosphamide and corticosteroids was attempted and is now ongoing.  ABSTRACT Hepatitis C virus (HCV) is widely prevalent worldwide, with an estimated 180 million people infected. Its manifestations are not limited to hepatic disease, as it has widely known immunomodulator and oncogenic effects. Most HCV associated autoimmune and lymphoproliferative diseases have been shown to subside after successful antiviral treatment. However, viral eradication doesn’t always equal lymphoma cure. In some cases, the oncogenic effect lasts well beyond viral elimination. Although the new direct anti‑viral agents (DAA) have proved to be safe and effective in treating HCV (with sustained viral responses of 91–95%), this treatment has inherent toxicities. Further, immunologic manifestations of HCV‑associated diseases, when present, may require broad immunosuppression in association with the antiviral treatment. We present a case that illustrates the complexities of treating these viral mediated immunologic and lymphoproliferative diseases. Keywords: cryoglobulinemia; hepatitis C virus; lymphoma; onconephrology Received for publication: Mar 12, 2019 • Accepted in revised form: Aug 2, 2019 • http://doi.org/10.32932/pjnh.xxxx.xx.xxx