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Cancer patients with haematological malignancies are at risk for chronic hepatitis E virus infection following chimeric antigen receptor (CAR) T-cell therapy. Strong clinical suspicion is essential for the early diagnosis and prompt treatment of this difficult-to-treat type of viral hepatitis. Commentary on: Schwarz et al. Chronic hepatitis E in a patient after CAR-T cell treatment for diffuse large B-cell lymphoma and rapid progression towards decompensated liver cirrhosis. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19892., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin lymphoma. It has been hypothesized that chronic hepatitis C virus (HCV) infection stimulates IGH-BCL2 clone proliferation, leading to development of FL. Furthermore, regression of FL after antiviral treatment without chemotherapy has been reported in HCV-infected patients. To clarify the relationship between HCV and FL, we compared the prevalence of IGH-BCL2 translocation and other clinicopathologic characteristics between HCV-infected and HCV-uninfected FL patients and determined the impact of HCV eradication on the oncologic outcomes of HCV-infected FL patients. The study included HCV-infected patients (cases) with FL seen at our institution during 2004-2018. Cases were matched with HCV-uninfected FL patients (controls) according to year of lymphoma diagnosis, sex, and hepatitis B serology. We studied 19 cases and 57 controls. More cases than controls had splenic involvement of FL (26% vs 5%, P = 0.02), higher histologic grade (grade 3 in 56% vs 24%, P = 0.01), absent or weak CD10 expression (42% vs 11%, P = 0.005), and absent BCL2 expression (33% vs 4%, P = 0.004). Compared to controls, cases had a lower rate of detection of IGH-BCL2 translocation (31% vs 68%, P = 0.02). Finally, cases with a sustained virologic response (virologic cure of HCV) had a better 10-year overall survival rate than did cases not treated with antivirals or controls (P = 0.001). In conclusion, HCV-infected patients with FL have unique clinicopathologic characteristics including improved overall survival with HCV eradication. The pathogenesis of FL in HCV-infected patients seems unrelated to antiapoptotic effect of IGH-BCL2 rearrangement., (© 2020 John Wiley & Sons Ltd.)

Background: Antiviral therapy improves hepatic outcomes in hepatitis C virus (HCV)-infected cancer patients. However, such patients are not treated simultaneously with antivirals and chemotherapy, owing to overlapping toxicities with previous standard of care treatment of pegylated interferon and ribavirin., Aim: To examine the safety and clinically-significant drug-drug interactions observed in patients who received simultaneous treatment with direct-acting antivirals (DAAs) and chemotherapy., Methods: Safety was determined by the presence of adverse events which were graded according to the division of AIDS Table (version 2.0). Adverse events were monitored throughout antiviral treatment and up to 3 months after its completion. Drug-drug interactions were assessed using current online databases. Sustained virological response (SVR) was defined as absence of serum HCV RNA 12 weeks after end of DAA treatment. Cirrhosis was diagnosed via imaging, biopsy or with the use of non-invasive fibrosis markers., Results: Twenty-one patients received concomitant treatment with DAAs and chemotherapy between January 2013 and September 2016. Concomitant treatment was started either for virological (14; 67%) or oncologic (7; 33%) reasons. DAAs used were sofosbuvir, ledipasvir, simeprevir, daclatasvir ± ribavirin. The adverse events observed were mainly constitutional (12; 57%), hematological and gastrointestinal (7; 33% each). Physicians changed the DAA regimens in two patients (10%) in anticipation of drug-drug interactions with daclatasvir and dexamethasone. The overall SVR rate was 95% (20/21)., Conclusions: Hepatitis C virus-targeted antiviral therapy can be used concomitantly with selected anti-neoplastic agents under close monitoring for drug-drug interactions. This therapeutic intervention may prevent delay in the administration of chemotherapy in HCV-infected cancer patients., Competing Interests: Statement of interests Disclosures: Dr. Torres is or has been the principal investigator for research grants from Gilead Sciences, Merck & Co., Inc., and Vertex Pharmaceuticals, with all funds paid to MD Anderson. He also is or has been a paid scientific advisor for Gilead Sciences, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Vertex Pharmaceuticals, Genentech, Novartis, Astellas Pharma, Pfizer Inc., and Theravance Biopharma, Inc.; the terms of these arrangements are being managed by MD Anderson in accordance with its conflict of interest policies. The other authors have no conflicts to disclose., (© 2016 John Wiley & Sons Ltd.)

Background & Aims: Hepatitis C virus (HCV) is associated with development of B-cell non-Hodgkin lymphoma (HCV-NHL). Antiviral therapy (AVT) is prioritized in HCV-infected patients with significant fibrosis/cirrhosis. It is unknown whether current recommendations based on liver parameters cover the risk of HCV-NHL development. We aimed to evaluate the liver disease stages of patients with HCV-NHL., Methods: Hepatitis C virus-NHL patients seen at MD Anderson Cancer Center between 2008 and 2014 were evaluated for underlying liver disease within a year of HCV-NHL diagnosis by non-invasive fibrosis markers, radiology or liver biopsy. Included patients were observed retrospectively (2008-2012) or prospectively (2012-2014)., Results: Eighty nine patients with HCV-NHL were evaluated. Most patients had genotype 1 (62%) infection, had diffuse large B cell lymphomas (62%), and detectable HCV RNA (90%) at NHL diagnosis. Notably, advanced liver disease (Metavir stage ≥ 3) was present in only 18% of the patients at the time of HCV-NHL diagnosis. All 53 patients with chronic HCV infection documented before lymphoma diagnosis were seen by HCV-treating physicians. Providers did not recommend AVT in almost one half of cases (44%), mostly because of the lack of advanced liver disease at HCV diagnosis (38%)., Conclusions: Most patients with HCV-NHL have mild liver disease at cancer diagnosis. Our findings suggest the need for early initiation of AVT in infected patients to eradicate HCV infection and its extra-hepatic manifestations. Treatment prioritization and cost must be weighed against the potential benefits of preventing NHL., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)