Hepatic toxicity and prognosis in hepatitis C virus–infected patients with diffuse large B-cell lymphoma treated with rituximab-containing chemotherapy regimens: a Japanese multicenter analysis

Abstract

The influence of hepatitis C virus (HCV) infection on prognosis and hepatic toxicity in patients with diffuse large B-cell lymphoma in the rituximab era is unclear. Thus, we analyzed 553 patients, 131 of whom were HCV-positive and 422 of whom were HCV-negative, with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP)-like chemotherapy. Survival outcomes and hepatic toxicity were compared according to HCV infection. The median follow-up was 31 and 32 months for patients who were HCV-positive and HCV-negative, respectively. HCV infection was not a significant risk factor for prognosis (3-year progression-free survival, 69% vs 77%, P ‫؍‬ .22; overall survival, 75% vs 84%, P ‫؍‬ .07). Of 131 patients who were HCV-positive, 36 (27%) had severe hepatic toxicity (grade 3-4), compared with 13 of 422 (3%) patients who were HCV-negative. Multivariate analysis revealed that HCV infection was a significant risk factor for severe hepatic toxicity (hazard ratio: 14.72; 95% confidence interval, 6.37-34.03; P < .001). An exploratory analysis revealed that pretreatment transaminase was predictive of severe hepatic toxicity. HCV-RNA levels significantly increased during immunochemotherapy (P ‫؍‬ .006). These results suggest that careful monitoring of hepatic function and viral load is indicated during immunochemotherapy for HCV-positive patients. (Blood. 2010; 116(24):5119-5125)

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

“…DLBCL patients displayed a good prognosis with 80% of them achieving CR after front-line treatment and 73% of overall survival at 3-years. These results are consistent with those of Merli et al [26] and Ennishi et al [7]. This prognosis seems better than previously reported by our group in HCV positive patients with B-NHL treated in preRituximab era [5].…”

“…There is a two-to four-fold increased risk of developing B-NHL among HCV-positive patients [1][2][3][4]. In comparison to their negative counterparts, HCV-associated B-NHL (i) are more often marginal zone lymphomas (MZL) and diffuse large B-cell lymphomas (DLBCL) [4], (ii) often display extranodal localization [3], (iii) and have higher rates of liver toxicity after treatment by chemotherapy [5][6][7][8]. HCV-associated lymphomas have also been shown to be frequently associated with type II mixed cryoglobulinemia (MC) [9,10], which are immunoglobulin complexes containing both a polyclonal IgG and a monoclonal IgM rheumatoid factor (RF) directed against the IgG.…”

The NOTCH pathway is recurrently mutated in diffuse large B-cell lymphoma associated with hepatitis C virus infection

“…[9][10][11] These clinical and pathological features suggest that at least a fraction of HCV-positive DLBCL may represent the transformation of a pre-existent, though unrecognized MZL clone.…”

Diagnostic and Therapeutic Quandaries in a Patient with Primary Hepatic Lymphoma and Concurrent Hepatitis C Infection

“…In a study it was observed that addition of rituximab to chemotherapy posed a tenfold risk of severe hepatotoxicity (grade III/IV elevation of AST and ALT) when compared with chemotherapy alone. Despite that there was no significant increase in mortality rates in patients with HCV infection treated with rituximab [10]. Early antiviral therapy prevents worsening of hepatitis in B-cell NHL with co-existent HBV receiving rituximab and chemotherapy [11].…”