Immune Checkpoint Inhibitors Suppress Hepatitis C Virus Replication in Infected Patients With Solid Tumors.

INTRODUCTION: Data are scarce regarding the virologic impact and safety of immune checkpoint inhibitors (ICI) in patients with chronic hepatitis C virus (HCV) infection. We examined the virologic impact of ICI in HCV-infected patients with solid tumors and their safety. METHODS: HCV-infected patients with solid tumor treated with ICI at our institution between April 26, 2016, and January 5, 2022, were enrolled in a prospective observational study. The primary outcomes were ICI-induced changes in HCV viremia (HCV inhibition and HCV reactivation) and safety of ICI. RESULTS: We enrolled 52 consecutive patients with solid tumors treated with ICI. Most were men (41; 79%), White (31; 59%), without cirrhosis (34; 65%), and with HCV genotype 1 (40; 77%). Four patients (7.7%) experienced HCV inhibition while receiving ICI including 1 patient who developed undetectable viremia for 6 months in the absence of direct-acting antivirals (DAA). Two patients (4%) developed HCV reactivation, both while receiving immunosuppressive therapy for ICI-related toxic effects. Adverse events occurred in 36 patients (69%), and 39 of the 47 adverse events (83%) were grade 1-2. Grade 3-4 adverse events occurred in 8 patients (15%), and in all cases, they were related to ICI, not to HCV. No HCV-associated liver failure or death occurred. DISCUSSION: Inhibition of HCV replication with virologic cure can develop in patients receiving ICI without DAA. HCV reactivation occurs primarily in patients receiving immunosuppressants for ICI-related toxic effects. ICI are safe in HCV-infected patients with solid tumors. Chronic HCV infection should not be considered a contraindication for ICI therapy.

The Clinical Value of Methicillin-Resistant Staphylococcus aureus Nasal Screening in the Management of Diabetic Foot Infections.

Nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) remains an important risk factor for diabetic foot infections (DFIs). We explored herein the clinical value of MRSA-nasal screening in the management of DFIs. In this retrospective case-control study, patients admitted with a DFI between 1/1/2014-6/30/2020 were studied and divided into cases (positive MRSA-nasal screening) and controls (negative MRSA-nasal). We included 171 patients (22 cases and 149 controls). MRSA nasal screening had a negative predictive value (NPV) of 86%. Compared to controls, cases were treated with intravenous vancomycin for a longer duration: (median [IQR], 5[3,11] vs 2[2,6]) days, P = .037). In multivariate analysis, a negative MRSA nasal screening was associated with a 74% decreased risk of AKI (OR = 0.26, 95% CI = 0.07-0.89). MRSA nasal screening in patients admitted with DFI has a high NPV. Obtained early, it can shorten the duration of intravenous vancomycin, consequently preventing AKI.

High sustained virologic response rate after 8 weeks of direct-acting antivirals in cancer patients with chronic hepatitis C virus.

OBJECTIVE: There is no prospective data on 8 weeks of direct-acting antivirals (DAA) therapy with glecaprevir/pibrentasvir (GLE/PIB) or ledipasvir/sofosbuvir (LDV/SOF) in hepatitis C virus (HCV)-infected patients with different types of malignancies. This study evaluated the efficacy and safety with 8 weeks of DAA therapy in cancer patients with chronic HCV infection. METHODS: Patients treated with DAAs at our center during 2014-2021 were included in a prospective observational study. Efficacy (sustained virologic response at 12 weeks; SVR12) and safety [adverse events and clinically significant drug-drug interactions (DDIs)] were assessed. RESULTS: We included 47 patients. Most were men (29; 62%), white (33; 70%), non-cirrhotic (45; 96%), and with HCV genotype 1 (38; 85%). None of the patients had HCC. The SVR12 rate was 96% (45/47; 95% CI: 86-99%) for the entire study cohort, 100% [17/17; 95% CI: 82-100%] for the patients treated with GLE/PIB and 93% [28/30; 95% CI: 79-98%] for the patients treated with LDV/SOF. Fisher's exact test showed no significant difference in SVR12 rates between the regimens (P = 0.53). No patients had serious adverse events (grade 3-4) or treatment discontinuation. Among the 17 patients who received concomitant cancer therapy, no DDIs occurred. CONCLUSION: Eight weeks of DAA therapy is highly effective and safe in HCV-infected patients with different types of malignancies and may grant access to investigational cancer therapy, broadening treatment options.

Insulin use in type II diabetic patients: a predictive of mortality in covid-19 infection.

INTRODUCTION: Starting December 2019, the world has been devastated by the rapid spread of coronavirus disease 2019 (Covid-19). Many risk factors have been associated with worse outcomes and death from Covid-19 pneumonia including having diabetes mellitus. To date, it is not clear if all group of diabetics share the same risk of complications with COVID-19 infection. This study aims to compare disease severity and mortality rate in insulin users versus non-insulin users. METHODS: In this retrospective case-control study conducted at the largest health care network in New York state, we included adult, diabetic patients admitted from March 2020 to October 2020 with Covid-19 pneumonia. We compared the baseline characteristics in addition to outcomes of diabetic patients on home insulin (cases) and non-insulin user diabetics (controls). In addition, to determine if home insulin use is associated with an increased mortality, we conducted a cox regression analysis. RESULTS: We included 696 patients in the study period with a median age of 57 years, interquartile range [IQR] 51-62, and median body mass index 29.9 (IQR: 26-34.7). The majority (476 [68%]) were males. We identified 227 cases (33%) and 469 controls (67%). More cases than controls were hypertensive (74% vs 67%, p = 0.03), on ACE/ARB (50% vs 42%, p = 0.05), and had a hemoglobin A1c > 8.1 (71% vs 44%, p < 0.001). More cases had AKI (52% vs 38%, p < 0.001), however no significant differences were found in intubation rates (26% vs 24%, p = 0.54), detection of pulmonary embolism (4% vs 6%, p = 0.19) or death rate (15% vs 11%, p = 0.22) comparing cases and controls. In a multivariate analysis, we found that home insulin use was independently associated with increased risk of death: Hazard ratio: 1.92, 95% confidence interval (1.13-3.23). CONCLUSION: We showed herein that diabetic patients on home insulin with COVID-19 pneumonia, have worse outcomes and increased mortality compared to diabetics on oral antihyperglycemic agents. Close monitoring of insulin-dependent type II diabetic patients is needed in the current pandemic.

The Prognostic Significance of Peripheral Blood Biomarkers in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab: A Clinical Study.

Systemic inflammation has long been associated with poor outcomes in many types of solid tumors. Peripheral blood biomarkers, such as absolute lymphocyte count (ALC) and the ratio of absolute neutrophil count to absolute lymphocyte count (ANC/ALC), have been shown to be immune-inflammatory parameters highlighting an individual's immune status. The prognostic role of ALC and ANC/ALC on overall survival (OS) was examined in patients with advanced non-small cell lung carcinoma (NSCLC) receiving pembrolizumab. Of a total of 239 patients, 52% were male, with a median age of 67 years (interquartile range [IQR], 59-73). Most patients had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PD-L1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.8 months (IQR, 2.9-12.7). An ANC/ALC <5 was associated with improved OS at initiation of pembrolizumab (P = .002), whereas an ALC >1.4 deciliter (dL) trended toward improved OS compared with ALC <1.4 dL (P = .053). After adjusting for potential cofounders with a multivariate analysis, a baseline ANC/ALC of 5 or higher was associated with a significantly increased risk of death (HR, 1.93; 95% CI, 1.27-2.93; P = .002). An ANC/ALC <5 at the time of initiation of treatment with pembrolizumab was associated with improved OS in patients with advanced NSCLC. The median ALC and ANC/ALC were significantly lower after 6 weeks of treatment with pembrolizumab.

Beyond Pain Relief: Is Opioids Use Safe in Clostridium difficile Infection?

BACKGROUND: Clostridium difficile infection (CDI) is a common condition in hospitalized patients. In the USA, there has been an alarming rise in the use of opioids for analgesia during hospitalization. Due to their antiperistalsis effect, opioids can increase absorption of bacterial toxins. Our study aimed to highlight any correlation between opioids use in CDI and morbidity, mortality, and duration of hospitalization. METHODS: A retrospective study was performed, and data were collected from 321 hospitalized patients with CDI. The dosage of opioids received in the first 4 days following diagnosis was calculated. Patients were divided into two groups (control group vs. opioid group). Reassessment of severity of disease on day 4 was performed. Complications, hospital mortality, readmissions for CDI within 3 months, length of stay, and disposition at discharge were compared. RESULTS: The opioid arm consisted of 169 patients, and 152 patients served as controls. On day 4, the number of patients with severe disease was significantly higher in the opioid group versus controls (78 (46.1%) vs. 37 (24%), respectively, P < 0.01), and complications including ileus, high white blood cell count, and need for vasopressors were significantly higher in the opioid group (27.8% versus 16.4%, P = 0.01). Control group patients were more likely to be discharged home (47% vs. 33%, P = 0.04), while opioid group required predominantly long-term facilities care after discharge. CONCLUSION: Opioid usage for analgesia in CDI increases the risk for severe disease, complications, longer hospitalization, readmission rates, hospital mortality and discharge to a long-term facility.

Is the Use of Proton Pump Inhibitors a Predisposing Factor for Pyogenic Liver Abscesses?

BACKGROUND: Proton pump inhibitors (PPIs) increase gastric pH by reducing acid production. The resulting alkaline milieu in the stomach increases the risk of bacterial translocation. This study aimed to investigate if there is a correlation between PPI use and developing pyogenic liver abscesses. METHODS: In this retrospective case-control analysis, we studied adult patients diagnosed with cryptogenic liver abscess at Northwell hospitals between 2015 and 2019. Adult patients with the diagnosis of liver abscess were included. We excluded patients with history of liver abscess prior to admission, biliary disease, hepatobiliary malignancy, or intra-abdominal infections. A group of randomly selected patients without liver abscess from the same hospitals' database were enrolled as the control group. A multivariate logistic regression analysis was performed to adjust for potential confounding factors. RESULTS: We identified 277 patients diagnosed with first episode of pyogenic liver abscess. Cases were compared to 554 controls. Klebsiella pneumonia was the most common pathogen. PPI use was associated with an increased risk of developing a first episode of pyogenic liver abscess in univariate (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.70 - 3.27), and multivariate analysis (adjusted OR: 2.27, 95% CI: 1.55 - 3.32). CONCLUSION: This study is the first US population-based analysis to demonstrate that PPI use is associated with increased risk of developing pyogenic liver abscesses. Further prospective studies are needed to shed more light on this association and better evaluate the impact of dose and duration of PPI exposure.

Gender-related Disparities of Percutaneous Coronary Interventions in ST-elevation Myocardial Infarction: A Retrospective Chart Review of 500 Patients.

Door-to-balloon (DTB) time of primary percutaneous coronary intervention in ST-elevation myocardial infarction (STEMI) is a predictive indicator of outcomes and mortality. Traditional gender-related differences that existed in the provision of DTB in STEMI had been allegedly improving until recent controversial data showed re-emergence of longer DTB in females. The objective of our study was to compare circadian disparities in percutaneous coronary intervention for STEMI according to gender in our institution. We compared DTB and symptom-to-balloon (STB) as well as mortality outcomes in a registry of 514 patients. We studied 117 females and 397 males. Baseline characteristics and cardiovascular risk factors were similar among both populations. Men used more self-transportation (51% vs. 38%) compared with women. Both had similar DTB median times: males, 63 (47-79) min; and females, 61 (44-76) min. In addition, STB median times were also similar: males, 155 (116-264) min; and females, 165 (115-261) min. Mortality outcomes at 1 month were comparable at 3% in males versus 0.9% in females (P = 0.164). In a review of a tertiary care center in New York, we observed no gender differences in DTB and STB, endorsing the role of emergency medical service transportation in eliminating disparities.

Salvage therapy in cancer patients with hepatitis C without sustained virologic response after direct-acting antivirals-A prospective study.

BACKGROUND AND AIM: No information exists regarding direct-acting antivirals (DAAs) salvage therapy for Hepatitis C (HCV)-infected patients with any type of cancer. We prospectively evaluated the safety and efficacy (SVR12) of salvage therapy in these patients. METHODS: Patients who failed initial DAAs (01/2015-01/2018) were analyzed. Resistance-associated substitutions to NS5A and NS3 were investigated by population sequencing. RESULTS: Of 164 patients enrolled, 16 (10%) experienced treatment failure. Of these, 11 patients received salvage therapy. The majority (91%) were men; 55% had genotype 1a, 45% had cirrhosis, and 45% had hepatocellular carcinoma. Four patients failed the first salvage therapy, and two of them required a second salvage therapy. Overall, 9 of 11 (82%) patients achieved SVR12. All four patients treated with sofosbuvir/velpatasvir/voxilaprevir (+/- ribavirin) achieved SVR12. The presence of resistance-associated substitutions did not impact response. Seven patients developed grade 1/2 adverse events. No patient had grade 3/4 adverse events. No patient required interruption of DAA therapy because of clinical or laboratory abnormalities. CONCLUSIONS: This is the first prospective study in HCV-infected cancer patients failing DAAs. The efficacy of salvage therapy in this group appears to be lower than previously reported in non-cancer patients, but better response rates are observed with newer regimens. Salvage therapy is associated with minimal toxicity.

Clinicopathologic characteristics of follicular lymphoma in hepatitis C virus-infected patients.

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.

Sofosbuvir-Based Therapy in Hepatitis C Virus-Infected Cancer Patients: A Prospective Observational Study.

BACKGROUND: Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients. METHODS: Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed. RESULTS: We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%). CONCLUSIONS: SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.

Clinicopathologic characteristics and outcomes of transformed diffuse large B-cell lymphoma in hepatitis C virus-infected patients.

Hepatitis C virus (HCV) causes a chronic but curable infection associated with the development of marginal zone lymphoma (MZL) and diffuse large B-cell lymphoma (DLBCL). Preliminary data have shown frequent transformation of indolent lymphoma to DLBCL in HCV-infected patients. To compare their clinicopathologic characteristics and oncologic outcomes, we reviewed the medical records and pathology reports of HCV-infected and uninfected patients with DLBCL that transformed from indolent lymphoma seen at The University of Texas MD Anderson Cancer Center (June 2004 to May 2015). To identify predictors of DLBCL relapse, patients with relapse after first-line chemotherapy were compared with those without it using univariate and logistic regression analyses. Compared with the uninfected patients (n = 63), HCV-infected patients (n = 21) were younger (median age =54 years [interquartile range= 49-62 years] vs. 62 years [53-66 years]; p = 0.01) and more often had advanced DLBCL (Ann Arbor stage 3-4; 95% vs. 76%; p = 0.05). Immunophenotypically, more HCV-infected than uninfected patients had CD10-negative B cells (76% vs. 43%; p = 0.008), CD5-positive B cells (39% vs. 7%; p = 0.004) and activated B-cell phenotypes (57% vs. 31%; p = 0.07). Comparison of the patients who had relapse after first-line chemotherapy (n = 42) and those who did not (n = 40) revealed that having CD5-positive B cells was the only factor associated with DLBCL relapse in multivariate analysis (odds ratio= 10.7; p = 0.02). HCV-infected patients with transformed DLBCL have unique clinicopathologic characteristics that make their lymphoma difficult to treat, potentially leading to unfavorable outcome. The impact of HCV eradication should be explored in such patients.

Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

Hepatitis C virus reactivation in patients receiving cancer treatment: A prospective observational study.

Hepatitis C virus (HCV) reactivation in patients receiving cancer treatment has been reported in retrospective studies. We sought to determine prospectively the incidence, predictors, and clinical significance of HCV reactivation during cancer treatment. HCV-infected patients receiving cancer treatment at our institution between November 2012 and July 2016 were studied. Reactivation was defined as an increase in HCV-RNA ≥1 log10 IU/mL over baseline and hepatitis flare as an increase in alanine aminotransferase to ≥3 times the upper limit of normal. One hundred patients were studied, 50 with hematologic malignancies and 50 with solid tumors. Reactivation occurred in 23 (23%) patients, including 18 (36%) patients with hematologic malignancies and 5 (10%) patients with solid tumors. In univariate analysis, patients with reactivation were more likely than those without reactivation to have prolonged lymphopenia (median, 95 versus 22 days; P = 0.01) and to have received rituximab (44% versus 9%; P < 0.0001), bendamustine (22% versus 0%; P < 0.001), high-dose steroids (57% versus 21%; P = 0.001), or purine analogs (22% versus 5%; P = 0.02). Rituximab (odds ratio = 9.52; P = 0.001), and high-dose steroids (odds ratio = 5.05; P = 0.01) retained significance in multivariable analysis. Of the 23 patients with reactivation, 10 (43%) had hepatitis flare. No patient with reactivation experienced liver failure or liver-related death within 36 weeks after initiation of cancer treatment. Fourteen patients with hepatitis flare, six of whom had reactivation, required discontinuation or dose reduction of cancer treatment. CONCLUSION: HCV reactivation occurred in 23% of HCV-infected patients receiving cancer treatment, and most had an unremarkable clinical course. However, reactivation can affect the cancer treatment plan. Our findings suggest that HCV infection should not contraindicate cancer therapy and infected patients should have access to multiple cancer treatments with close monitoring while receiving regimens associated with HCV reactivation. (Hepatology 2018;67:36-47).

Impact of chronic hepatitis C virus infection on the survival of patients with oropharyngeal cancer.

BACKGROUND: Although an association between hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported, to the authors' knowledge the clinical significance of this epidemiological finding remains unknown. Therefore, the authors analyzed the oncologic outcomes of HCV-infected patients with OPCs. METHODS: In this retrospective cohort study, all patients with OPCs who were seen at The University of Texas MD Anderson Cancer Center between January 2004 and December 2015 were reviewed. HCV infection was defined as detectable HCV RNA in the serum. Five-year overall survival and progression-free survival rates were compared between patients infected with HCV and those not infected. RESULTS: A total of 161 patients were examined. The majority of the patients were white (141 patients; 88%) and male (132 patients; 82%) and had TNM stage III or IV disease (147 patients; 91%). The OPC involved the tonsils (83 patients; 52%), base of the tongue (67patients; 42%), or the soft palate (11 patients; 7%). The median follow-up after an OPC diagnosis was 3 years (range, 1-13 years). HCV-infected patients (25 patients) and HCV-uninfected patients (136 patients) were comparable with regard to smoking and alcohol status. In multivariate analysis, HCV was associated with increased cancer-specific mortality (hazard ratio, 2.15; 95% confidence interval, 1.08-6.85 [P = .02]) and risk of OPC progression (hazard ratio, 5.42; 95% confidence interval, 2.64-11.14 [P = .0008]) independent of age and cirrhosis status. Antivirals were administered after the diagnosis of OPC in 8 of the 25 HCV-infected patients (32%). HCV-infected patients who received antivirals were found to have better 5-year overall survival (70% vs 12%; P = .005) and progression-free survival (72% vs 19%; P = .005) compared with patients who did not. CONCLUSIONS: The early detection of HCV is important in patients with OPC because this infection may affect their oncologic outcomes. Cancer 2018;124:960-5. © 2017 American Cancer Society.

Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma.

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non-Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV-infected patients with diffuse large B-cell lymphoma (DLBCL) is unclear. We therefore analyzed AVT's impact on oncologic outcomes of HCV-infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004-May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon-based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first-line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5-year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01-5.3]; p = 0.04). Furthermore, AVT improved 5-year OS rates among cases in both univariate (median [Interquartile range]: 39 [26-56] vs. 16 [6-41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06-0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5-year OS.

Hepatitis C Virus Infection in Patients Undergoing Hematopoietic Cell Transplantation in the Era of Direct-Acting Antiviral Agents.

There is paucity of literature regarding hepatitis C virus (HCV) infection in hematopoietic cell transplant (HCT) recipients. In the study described herein we evaluated several aspects of HCV infection in HCT recipients, including the impact of this infection on cancer status, liver-related outcomes, mortality, and the role of antiviral treatment (AVT), including direct-acting antivirals (DAAs). The medical records of HCV-infected allogeneic and autologous HCT recipients, seen at The University of Texas MD Anderson Cancer Center from August 2009 to November 2015, were reviewed. Patients seen from August 1, 2009 to October 30, 2012 were reviewed retrospectively, whereas those seen from November 1, 2012 to November 30, 2015 were analyzed prospectively in an observational study. Of 434 HCV-infected cancer patients evaluated, 64 underwent 69 HCTs. Most (78%) underwent autologous transplantation. Thirteen percent of patients became HCV-seronegative post-HCT. Compared with patients who did not receive AVT, treated patients had fewer relapses of HCV-associated non-Hodgkin lymphomas (20% versus 86%; P = .015), higher 5-year survival rates (75% versus 39%; P = .02), and a trend toward lower rate of progression to cirrhosis (5% versus 21%; P = .06). AVT discontinuation rate post-HCT was 71% in those receiving IFN-containing regimens and 0% in those receiving DAAs (P < .01). AVT was effective in 12 of 37 patients (32%) and 11 of 13 patients (85%) receiving IFN-based and DAA regimens, respectively (P = .003). HCV is an important cause of morbidity and mortality in this population. HCV seropositivity can be lost post-HCT, posing a diagnostic challenge. Treatment of HCV infection in HCT recipients improves both oncologic and hepatic outcomes. These patients can be successfully treated with DAAs.