Andreas Kyvernitakis

Concomitant use of direct-acting antivirals and chemotherapy in hepatitis C virus-infected patients with cancer.

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.

Prevalence and association of hepatitis C virus infection with different types of lymphoma

To the Editor, Hepatitis C virus (HCV) is the most common blood-borne infection in the United States, affecting about 4.1 million people (1.6%) of the US population. Chronic HCV infection has been associated with extrahepatic hematological manifestations such as mixed cryoglobulinemia and lymphoma. Several reports support an association of HCV infection with the development of non-Hodgkin lymphomas (NHLs). Furthermore, eradication of the chronic HCV infection has been correlated with regression of certain NHLs. However, studies of patients with HCV infection and specific histological types of NHL and Hodgkin lymphoma (HL) are limited. We thus sought to determine the prevalence of HCV seropositivity in patients with different subtypes of NHL and HL and its association with these subtypes. We conducted a case–control study, abstracting data from the electronic medical records of cancer patients screened for HCV antibodies (anti-HCV) at The University of Texas MD Anderson Cancer Center from June 2004 to May 2014. HCV cases were defined as patients who tested positive for antiHCV. Among this group, patients with available information on detectable HCV-RNA or history of HCV infection treatment were considered to be chronically infected with HCV. NHL and HL cases were classified for subtype-specific analysis using the International Classification of Diseases, Ninth Revision, Clinical Modification codes and nested classification by the International Lymphoma Epidemiology Consortium Pathology Working Group. Controls were cancer patients without lymphoma and hepatocellular carcinoma who were screened for anti-HCV during the same period. The v test was used to calculate prevalence of HCV-seropositivity and the odds ratio (OR) as a measure of association with lymphoma. Bonferroni correction was performed to adjust p values, reducing false-positive rates owing to multiple testing. Hence, the p value for statistical significance was 0.0036. All hypothesis testing was two-sided. Statistical analyses were conducted using the Stata/IC software program (version 11.0; StataCorp, College Station, TX). The study was approved by the MD Anderson Institutional Review Board. Of 34,545 patients tested for anti-HCV during the study period, 8,310 (24.1%) had lymphoma (NHL, 7,030 [84.6%]; HL, 1,280 [15.4%]). Of these patients, 198 (2.4%) were positive for anti-HCV and considered cases, consisting of 173 with NHLs and 25 with HLs. We confirmed chronic HCV infection in 114 of the 173 (65.9%) NHL cases and 11 of the 25 (44.0%) HL cases. The overall prevalence of HCV-seropositivity was higher in the NHL patients (2.5%) than in the HL patients (1.9%) or controls (1.7%). HCV-seropositivity was significantly associated with NHL (OR, 1.5 [95% confidence interval (CI), 1.2–1.8]; p5 0.0030) but not HL (Table 1). Of the 173 patients with NHL, 153 (88.4%) had B-cell NHL, 16 (9.2%) had T-cell NHL and 4 (2.3%) had other lymphomas. When compared with that in the controls, HCV prevalence was higher in patients with B-cell NHLs (2.6%), with a significant association between HCV-seropositivity and B-cell NHL (OR, 1.6 [95% CI, 1.3–1.9]; p< 0.0001). The HCV prevalence in the T-cell NHL cases was similar to that in the controls (1.7%). In a subtype-specific analysis, the most common B-cell NHLs in the patients were diffuse large B-cell lymphoma (DLBCL; 43.9%), marginal zone (MZ) lymphoma (11.6%) and follicular lymphoma (10.6%). The prevalence of HCV-seropositivity was greater in the cases than in the controls for all B-cell NHL subtypes except follicular lymphoma, with the highest prevalence noted for MZ lymphoma (3.9%), Burkitt lymphoma (3.8%) and DLBCL (3.7%) (Table 1). Compared with controls, DLBCL had a 2.2-fold greater association with HCV-seropositivity (95% CI, 1.7–2.8; p< 0.0001), and MZ lymphoma had a 2.3-fold greater association with it (95% CI, 1.4–3.5; p5 0.0006). The most prevalent T-cell NHL was mycosis fungoides/S ezary syndrome, and patients with it had a slightly higher HCV infection prevalence (1.9%) than did the controls (1.7%). The predominant HL subtype was nodular sclerosis, and patients with it had an HCV infection prevalence of 2.2%. The association between HCV-seropositivity and either T-cell NHL or HL subtypes was not statistically significant. This is one of the largest studies to systematically evaluate the association of anti-HCV with different subtypes of NHL and HL. We found that HCV-seropositivity was associated with some but not all B-cell NHL subtypes. This finding enabled us to better define the subset of non-liver cancers linked with chronic HCV infection. The association of HCV-seropositivity with B-cell NHL but not T-cell NHL or HL can be supported by a proposed mechanism of chronic antigenic stimulation by HCV in specific B-cell clones, which induces malignant lymphoproliferation. In addition to generalized binding of HCV E2 protein to CD81, the HCV NS3/IgG antigen binds with a B-cell receptor, explaining selective proliferation of B-cell subtypes analogous to B-cell receptor segments, such as DLBCL and MZ lymphoma. Le tt er to th e E di to r

Impact of hepatitis E virus seropositivity on chronic liver disease in cancer patients with hepatitis C virus infection

Immunocompromised patients can develop chronic hepatitis E virus (HEV) infection and progress to cirrhosis. Hepatitis C virus (HCV)‐infected cancer patients who have received chemotherapeutic agents experience accelerated liver fibrosis progression. Our aim was to investigate the prevalence and impact of HEV seropositivity on liver‐related outcomes in HCV‐infected cancer patients.

Management of Multiple Myeloma Complicated by Hepatitis C Virus Reactivation: The Role of New Antiviral Therapy

Reactivation of chronic hepatitis C virus (HCV) infection has been reported in cancer patients receiving chemotherapy. In this study, we report the first case, to our knowledge, of thalidomide-induced acute exacerbation and reactivation of chronic HCV infection complicating management of multiple myeloma. Sofosbuvir-based antiviral therapy helped achieve viral clearance and normalization of liver enzymes, thus allowing access to future potentially life-saving chemotherapy agents.

Leukopenia and lack of ribavirin predict poor outcomes in patients with haematological malignancies and respiratory syncytial virus infection

Objectives Respiratory syncytial virus (RSV) infection causes morbidity and mortality in cancer patients. However, studies describing this infection in patients with haematological malignancies are scarce. We sought to evaluate the clinical impact of RSV infection on this patient population. Methods We reviewed the records of patients with haematological malignancies and RSV infections cared for at our institution between January 2000 and March 2013. Results Of the 181 patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%) had multiple myeloma. Most patients [117 (65%)] presented with an upper respiratory tract infection (URTI) and 15 (13%) had a subsequent lower respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day mortality rate was 15%. Multivariable regression analysis showed that having both neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P < 0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR = 0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI. Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI = 1.24-15.0, P = 0.021). Conclusions Patients with haematological malignancies and RSV infections, especially those with immunodeficiency, may be at risk of LRTI and death; treatment with ribavirin during RSV URTI may prevent these outcomes.

Mixed Mycobacterium Avium-Intracellulare and Serratia Marcescens Cellulitis of the Breast in an HIV-Negative Patient with Breast Cancer: A Case Report

Mycobacterium avium-intracellulare (MAI) causes pulmonary infection in patients with chronic lung diseases or severe T-cell deficiency. Cutaneous manifestations caused by MAI are rare and the few cases reported describe mostly patients with hematologic malignancies who were treated with highly immunosuppressive agents. Herein, we report a case of a breast cancer survivor who developed chronic breast cellulitis due to MAI, following localized breast cancer treatment.

Sustained Virologic Response After 6 Weeks of Therapy With a First-Generation Hepatitis C Virus Protease Inhibitor

To the Editor—Patients with hepatitis C virus (HCV) genotype 1 infection should receive 12 weeks of triple combination therapy with the first-generation HCV protease inhibitor telaprevir, pegylated interferon (peg-IFN) alfa-2a or alfa-2b, and ribavirin (RBV), followed by 12 or 36 weeks of double therapy with peg-IFN and RBV [1]. We report a case of sustained virologic response (SVR) achieved after only 6 weeks of triple combination treatment. A 53-year-old white woman with history of breast cancer was treated with surgery, adjuvant chemotherapy, and radiation in 2010, followed by hormonal therapy with letrozole. During a routine follow-up at another facility, elevated transaminases were detected and further investigation led to the diagnosis of chronic HCV infection that was probably acquired 30 years before current presentation. She was infected with HCV genotype 1b, and host genotyping revealed the IL28B CC allele. Liver biopsy showed bridging fibrosis. The patient was initiated on telaprevir, peg-IFN alfa-2a, and RBV. Concurrent medications included hydrochlorothiazide and lisinopril for hypertension. Letrozole was discontinued a few weeks before antiviral treatment initiation, to avoid potential drug interactions. On week 4 of treatment, the HCV load was undetectable (rapid virological response [RVR]). Two weeks later, the patient presented with shortness of breath, anemia, thrombocytopenia, rash, and acute renal failure. HCV treatment was discontinued because of severe renal dysfunction. During the first 2 weeks off therapy, the hematologic toxic effects worsened, necessitating hospital admission, use of hematopoietic growth factors, and red blood cell transfusion (Figure ​(Figure11). Figure 1. Outcome and laboratory abnormalities in a patient successfully treated with 6 weeks of telaprevir-based therapy. aHepatitis C virus was measured with the transcription-mediated amplification method. Abbreviations: HCV, hepatitis C virus; Rx, treatment; ... The patient was referred to our institution for investigation of possible myelodysplastic syndrome. Bone marrow biopsy revealed no evidence of malignancy, and the abnormal laboratory parameters were attributed to HCV treatment. In the following weeks, the patient improved and all laboratory parameters normalized. The HCV load remained undetectable at 24 weeks after cessation of HCV treatment (SVR24). Telaprevir-containing therapy is very effective, but is often associated with the development of severe side effects [1]. This treatment combination is also associated with renal impairment, which leads to more pronounced anemia from decreased RBV elimination [2]. The half-life of RBV ranges from 100 hours normally to 500 hours in patients with decreased renal function [3]. The renal impairment our patient developed might have contributed to her severe anemia by prolonging RBV exposure after treatment cessation. The fact that the anemia worsened even after treatment discontinuation supports this hypothesis. On the other hand, extended RBV exposure might have led to the patients favorable virologic outcome. In regard to positive predictors of response to HCV treatment, our patient had several: female sex, white race, HCV-1b genotype infection, IL28B CC allele, low baseline viral load, no cirrhosis or steatosis, and RVR [4]. We found 2 reports of patients with SVR after shortened duration of telaprevir-based therapy (Table ​(Table1)1) [5, 6]. The common characteristics of these patients and our patient include non–African American race, HCV-1b genotype, and absence of cirrhosis. Table 1. Reported Cases of Sustained Virologic Response After Short-Duration Telaprevir-Based Therapy The interim analysis of an exploratory multicenter study designed to evaluate the efficacy of 12-week-total telaprevir-based therapy in patients with HCV genotype 1, either treatment-naive or with relapse after treatment, showed an SVR of 87% (74 of 85 subjects) among noncirrhotic patients with the IL28B CC genotype who had achieved RVR [7]. In conclusion, the addition of first-generation protease inhibitors to the anti-HCV treatment armamentarium has improved outcomes of patients infected with genotype 1 HCV [1]. Unfortunately, these regimens are frequently associated with serious adverse events. The present report describes the common characteristics of patients successfully treated after short-duration telaprevir-based therapy.