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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.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.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.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.

Background Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment. Materials and Methods We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019. Results Of the 1076 patients screened, we identified 33 with concurrent hepatitis. All 10 patients with HBV underwent concomitant antiviral therapy during ICI treatment. Sixteen of the 23 patients with HCV received it before the initiation of ICI. The median follow-up time was 33 months (95% CI, 23-45) and the median duration of ICI therapy was 3 months (IQR, 1.9-6.6). Of the 33 patients, 12 (39%) experienced irAEs (immune-related adverse events) of any grade, with 2 (6%) having grade 3 or higher. None of the patients developed hepatitis toxicities. Conclusion ICIs may be a therapeutic option with an acceptable safety profile in patients with cancer and advanced liver disease.

Direct-acting antivirals (DAAs) against hepatitis C virus (HCV) infection can cause hepatitis B virus (HBV) reactivation in HBV/HCV co-infected patients. Cancer patients undergoing immunosuppressant treatment or chemotherapy are at risk for HBV reactivation. To our knowledge, no prospective studies have examined the risk of HBV reactivation during DAA treatment for HCV infection in cancer patients with HBV/HCV co-infection. Here, we report the results of one such study. In a prospective observational study, we enrolled HCV-infected cancer patients undergoing DAA treatment at The University of Texas MD Anderson Cancer Center between January 2015 and March 2018. Data regarding demographics, cancer history, and prior HCV treatment history were collected. Patients were assessed for HBV status before DAA treatment and for HBV-related outcomes, including HBV reactivation, hepatitis flare, and HBV-associated hepatitis, during DAA treatment. Demographic and treatment variables were analyzed using descriptive statistics. One hundred sixty-six patients were analyzed. Forty-eight patients received systemic chemotherapy within 6 months before to 6 months after treatment with DAAs. Ledipasvir plus sofosbuvir was the most common DAA regimen, administered to 88 patients (53%). Fifty-one patients (31%) had past HBV infection, and 4 (2.4%) had chronic HBV infection. No patient experienced HBV reactivation, hepatitis flare, or HBV-associated hepatitis induced by DAA treatment. In HCV-infected cancer patients, DAA treatment is safe regardless of whether patients have past or chronic HBV infection. However, HBV screening is still recommended before the initiation of and during DAA treatment, as is anti-HBV prophylactic treatment in selected cases.

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.

Bruton’s tyrosine kinase (BTK) plays a pivotal role in B-cell proliferation and survival of leukemic cells. Ibrutinib, a molecule targeting BTK, was approved by the U.S. Food and Drug Administration in 2013 for treatment of mantle cell lymphoma and has since been approved for treatment of several other hematologic malignancies, including chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia, and marginal zone lymphoma (MZL) (1). Recently, Ibrutinib plus venetoclax have been found to be effective as first line treatment for high risk and older patients with CLL (2). Patients receiving ibrutinib are at increased risk for serious bacterial, fungal, and viral reactivation (3). In this report, we describe the first case, to our knowledge, of HBV-associated liver failure after ibrutinib therapy in a patient with B-cell non-Hodgkin lymphoma. Additionally, we review the previously reported cases of HBV reactivation after ibrutinib therapy (3–7). We analyzed our patient reported below together with 5 of the 6 previously described patients for whom sufficient data about HBV reactivation were available. HBV-related outcomes were defined according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidance (8), and included past or chronic HBV infection, HBV reactivation, HBV-associated hepatitis, and HBV-associated liver failure

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., This is the first prospective study in HCV‐infected cancer patients failing direct‐acting antivirals. The efficacy of salvage therapy in this group appears to be lower than the previously reported in non‐cancer patients but better response rates are observed with newer regimens. Salvage therapy is associated with minimal toxicity.

Chronic hepatitis C virus (HCV) infection increases the risk for several types of cancer, including hepatocellular carcinoma (HCC) and B-cell non-Hodgkin lymphoma, as primary and second primary malignancies. HCV-infected patients with cancer, particularly those undergoing anticancer therapy, are at risk for development of enhanced HCV replication, which can lead to hepatitis flare and progression of liver fibrosis or cirrhosis. Risk factors for HCV infection include injection drug use, blood transfusion, or solid organ transplantation before 1992, receipt of clotting factor concentrates before 1987, long-term hemodialysis, chronic liver disease, HIV positivity, and occupational exposure. Widely available direct-acting antivirals are highly effective against HCV and well tolerated. Identification of HCV-infected individuals is the essential first step in treatment and eradication of the infection. One-time screening is recommended for persons born from 1945 to 1965; screening is also recommended for persons with risk factors. Recently, a public health recommendation has been drafted to screen all adults age 18 to 79 years. Two oncology organizations recommend screening all patients with hematologic malignancies and hematopoietic cell transplant recipients, and a recently published multicenter prospective study supports universal HCV screening for all patients with cancer. HCV screening entails testing for anti-HCV antibodies in serum and, when results are positive, HCV RNA quantitation to confirm infection. Direct-acting antiviral therapy eradicates HCV in almost all cases. Virologic cure of HCV prevents chronic hepatitis and progression to liver fibrosis or cirrhosis. HCV eradication also decreases the risk of developing HCV-associated primary and second primary malignancies, and it may allow HCV-infected patients access to important cancer clinical trials. Patients with HCV-related cirrhosis require lifelong surveillance for HCC, even after viral eradication.

Testing for antibody against hepatitis C virus (anti-HCV) is a low-cost diagnostic method worldwide; however, an optimal screening test for HCV in patients with cancer has not been established. We sought to identify an appropriate screening test for HCV infection in patients with hematologic malignancies and/or hematopoietic cell transplants (HCT). Patients in our center were simultaneously screened using serological (anti-HCV) and molecular (HCV RNA) assays (February 2019-November 2019). In total, 214 patients were enrolled in this study. Three patients (1.4%) were positive for anti-HCV, and 2 (0.9%) were positive for HCV RNA. The overall percentage agreement was 99.5% (95% CI: 97.4-99.9). There were no cases of seronegative HCV virus infection. The positive percentage agreement was 66.7% (95% CI: 20.8-93.9), and the negative percentage agreement was 100.0% (95% CI: 98.2-100.0). Cohen kappa coefficient was 0.80 (95% CI: 0.41-1.00, P.0001). The diagnostic yield of screening for chronic HCV infection in patients with cancer is similar for serologic and molecular testing.

Limited data are available on the use of CD4+ T-cell count and percentage to predict response to direct-acting antiviral (DAA) treatment outside the hepatitis C virus (HCV)-HIV coinfected population. We sought to determine the impact of CD4+ T-cell count and percentage on response to DAAs in cancer patients with HCV monoinfection. Patients treated with DAAs were enrolled in a prospective observational study. CD4+ T-cell count and percentage was measured at baseline, end of treatment (EOT), and 12 weeks after the EOT (SVR12). A total of 174 patients were enrolled. Most patients (155/174, 89%) achieved an SVR12. A multivariate logistic regression model found that patients with hepatocellular carcinoma, HCV-3 and previous DAA treatment were more likely to develop treatment failure. Neither univariate analysis nor multivariate logistic regression analysis did show any association between CD4+ T-cell count or percentage and SVR12. CD4 T-cell count or percentage does not appear to impact SVR rates in cancer patients with HCV monoinfection receiving DAAs.

Chronic Hepatitis C virus (HCV) infection has been associated with extrahepatic cancers. Few studies have reported associations between HCV and genitourinary cancers such as kidney and prostate cancers with inconsistent findings. We sought to study associations between HCV and the most common genitourinary cancers including kidney, prostate and urinary bladder.This case-control study included adult (≥18 years at diagnosis) cancer patients who were screened for HCV antibody (anti-HCV) at MD Anderson Cancer Center from June 2004 through January 2018. Cases had incident primary genitourinary cancers (cancers of the kidney, prostate, renal pelvis and ureter, or urinary bladder). Controls had smoking-associated cancers (esophagus, lung and pancreas). Multivariate logistic regression models were used.Among 42,244 patients screened for anti-HCV, 1,493 cases (527 kidney, 691 prostate, 58 renal pelvis and ureter, and 217 urinary bladder cancer) and 1,187 controls (242 esophagus, 709 lung, and 236 pancreas cancer) were studied. In the univariate analysis, the prevalence of anti-HCV positivity did not differ significantly between the controls and the cases with cancers of the renal pelvis and ureter (8% v9%, P = .81), prostate (10% v8%, P = .34), or urinary bladder (8% v 6%, P = .18). In contrast, the prevalence of anti-HCV positivity was lower among the cases with kidney cancer than among the controls (4% v 8%, P.001). However, in the multivariate analyses after adjustment for cofounders, no significant association between anti-HCV positivity and any genitourinary cancer we evaluated.Our results do not support an association between chronic HCV and common genitourinary cancers.

BACKGROUND. Optimal hepatitis C virus (HCV) screening strategies for cancer patients have not been established. We compared the performance of selective HCV screening strategies. METHODS. We surveyed patients presenting for first systemic anticancer therapy during 2013–2014 for HCV risk factors. We estimated the prevalence of positivity for HCV antibody (anti-HCV) and examined factors associated with anti-HCV status using Fisher’s exact test or Student’s t-test. Sensitivity was calculated for screening patients born during 1945–1965, patients with ≥1 other risk factor, or both cohorts (“combined screening”). RESULTS. We enrolled 2,122 participants. Median age was 59 years (range, 18–91); 1,138 participants were women. Race/ethnicity distribution was white non-Hispanic, 76% (n=1616); Hispanic, 11% (n=233); black non-Hispanic, 8% (n=160); Asian, 4% (n=78); other, 2% (n=35). Primary cancer distribution was non-liver solid tumor, 78% (n=1,664); hematologic cancer, 20% (n=422); liver cancer, 1% (n=28). Prevalence of anti-HCV was 1.93% (95% CI, 1.39%–2.61%). Over 28% of patients with detectable HCV RNA were unaware of infection. Factors significantly associated with anti-HCV positivity included less than a bachelor’s degree, birth in 1945–1965, chronic liver disease, injection drug use, and blood transfusion or organ transplant before 1992. A total of 1,315 participants (62%), including 39 of 41 with anti-HCV, reported ≥1 risk factor. Sensitivity was 80% (95% CI, 65–91%) for birth-cohort-based, 68% (95% CI, 52–82%) for other-risk-factor-based, and 95% (95% 83–99%) for combined screening. CONCLUSION. Combined screening still missed 5% of patients with anti-HCV. These findings favor universal HCV screening to identify all HCV-infected cancer patients.

Summary Background Patients previously infected with hepatitis B virus (HBV; indicated by positivity for anti-HBc) can experience HBV reactivation during cancer chemotherapy. Intravenous immunoglobulin infusion, which is frequently used in supportive care, might facilitate passive transfer of anti-HBc. We aimed to estimate the probability of passive transfer of anti-HBc after intravenous immunoglobulin infusion in patients with cancer. Methods We reviewed institutional databases to identify adult patients who received outpatient chemotherapy between Jan 1, 2004, and Dec 31, 2011, at the University of Texas MD Anderson Cancer Center, Houston, TX, USA. Eligible patients had received intravenous immunoglobulin therapy, had tested negative for both anti-HBc and HBsAg before infusion, and had been tested for anti-HBc after infusion. The primary endpoint was the proportion of patients who became positive for anti-HBc after intravenous immunoglobulin infusion. Findings 950 of 18 874 patients who underwent chemotherapy within the study time frame received intravenous immunoglobulin, of whom 870 had been tested for anti-HBc before infusion. 199 patients who were negative for anti-HBc before receiving intravenous immunoglobulin were retested after infusion, of whom 29 (15% [95% CI 10–20]) became positive for anti-HBc. The probability of anti-HBc conversion at 1 week after intravenous immunoglobulin infusion was 34% (95% CI 22–48) and at 12 weeks was 4% (2–7). Interpretation Conversion of patients from anti-HBc negativity to anti-HBc positivity was common after intravenous immunoglobulin administration. However, the probability of a positive test decreased with time since infusion. Positive anti-HBc tests done shortly after intravenous immunoglobulin infusion should be interpreted with caution because they might indicate passive transfer instead of true infection. Funding None.

Introduction Chronic hepatitis C virus (HCV) infection is one of the leading causes of hepatocellular carcinoma (HCC) worldwide. Antiviral therapy in patients with HCV infection reduces the risk of primary HCC development by 71%–75%. HCV-infected patients with different primary cancers are also at risk for HCC development as a second primary malignancy (HCC-SPM). Limited information is available on the occurrence and characteristics of HCC-SPM. Herein, we determine the prevalence and clinical features of HCV-associated HCC-SPM when compared to primary HCC. Materials and methods Patients with HCV-associated HCC seen at MD Anderson Cancer Center (2011–2017) were enrolled in a prospective observational study. Patients with multiple cancers diagnosed simultaneously or with hepatitis B virus or HIV coinfections were excluded. At enrollment, patients completed a questionnaire on medical history and HCC risk factors. Information on demographics, comorbidities, HCV treatment, tumor characteristics, treatment modalities, and virologic and oncologic outcomes were extracted from the medical records. Results Among 171 consecutive patients with HCV-associated HCC enrolled, 26 (15%) had HCC-SPM. Most of the underlying primary cancers were solid tumors (85%). In 12 (46%) of these patients, the diagnosis was made incidentally while undergoing surveillance for primary malignancies, and the majority (81%) had their primary cancer in remission. Most patients (72%) with documented HCV viral load had chronic viremia due to lack of diagnosis, lack of treatment, or prior unsuccessful treatment of HCV infection and only 28% had undetectable viral load following successful antiviral therapy. The overall median survival for both groups was 29 months (95% CI: 23–35) without difference between groups (p=0.2). Conclusion Cancer patients with any malignancies must be screened for HCV as HCC-SPM can develop in 15% of infected patients. Early HCV diagnosis and treatment should be attempted to prevent the development of HCC-SPM, a condition associated with high mortality in cancer survivors., Video abstract

The incidence rate of hepatocellular carcinoma (HCC) is rising. It is one of the most common cancers worldwide and accounts for substantial morbidity and mortality. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, and nonalcoholic fatty liver disease (NAFLD) are the most important etiologies of HCC, and effective screening and management strategies are crucial to reduce the HCC risk. For HBV, which accounts for the majority of HCC cases, most infections were acquired via perinatal and early horizontal transmission. Universal vaccination of newborns has led to a decline in HCC incidence compared with the pre-vaccination era. Effective antiviral therapies with nucleos(t)ide analogues or pegylated interferon reduced the incidence of HCC. For HCV, the emergence of effective direct-acting antiviral (DAA) agents has substantially improved cure rates; therefore all patients with HCV should be considered for DAA treatment. The most important obstacle in eliminating HCV is access to therapy. For NAFLD, the global incidence is increasing rapidly, thus its impact on HCC incidence may be explosive. Progression to HCC in NAFLD happens particularly in those with nonalcoholic steatohepatitis (NASH) and exacerbated by metabolic syndrome, or PNPLA3 gene polymorphism. Lifestyle changes are imperative while drug therapy has yet to demonstrate substantive protective effects on HCC prevention. For management of HCC, early diagnosis via imaging surveillance among persons with HCC risk factors remains the most important strategy to identify early-stage disease appropriate for resection or transplantation.

Background Data on the efficacy and tolerability of latent tuberculosis infection (LTBI) treatment in cancer patients receiving checkpoint inhibitor immunotherapy (CPI) is limited. We sought to assess LTBI therapy and its adverse events and outcomes in patients treated with CPI. Methods We performed a retrospective cohort study at MD Anderson Cancer Center of adult patients, between April 2016 and May 2021, who were receiving CPI and were diagnosed with LTBI based on positive T-SPOT TB test. We then compared those patients treated with isoniazid (INH) 5mg/kg daily versus those that did not receive INH therapy. Results We identified 35 patients treated with CPI who had a diagnosis of LTBI. Patients were divided into 2 groups: CPI alone (23 patients, 65.7%) and CPI+INH (12 patients, 34.3%). The majority of patients in both groups had renal cell carcinoma (34.3%) and melanoma (17.1%). Nivolumab as monotherapy was the most commonly used CPI agent in both groups (37.1%), whereas nivolumab and ipilimumab combination was mainly used in the CPI group (34.7%) compared to CPI+INH group (8.3%). In the CPI+INH group, 7 patients (58.3%) developed moderate to severe hepatoxicity that led to discontinuation of INH and CPI therapy versus none in the CPI group (p= 0.001). There was no statistically significant difference in the alanine aminotransferase (ALT) at baseline between both groups (p=0.117), whereas the median ALT level was significantly higher during CPI+INH therapy compared to CPI alone (135 U/L vs 24 U/L respectively, p=0.025. Furthermore, immune-related adverse events were reported in a total of 12 of 35 patients (34.2%). None of the patients in either group developed tuberculosis reactivation during a follow up period of up to 1148 days. Conclusion Our data suggest that latent tuberculosis reactivation is rare in cancer patients on CPI immunotherapy. Hepatotoxicity remains a concern in this patient population with LTBI treated with CPI and INH. With the widespread use of CPI, close laboratory and clinical monitoring is required to avoid life-threatening drug-induced liver injury and interruption of LTBI therapy and immunotherapy. Further clinical studies are warranted to determine the optimal management of LTBI during CPI therapy. Disclosures Pablo C. Okhuysen, MD, FACP, FIDSA, Deinove Pharmaceuticals (Grant/Research Support)Ferring Pharmaceuticals (Consultant)Melinta Therapeutics (Grant/Research Support)Merck & Co. (Grant/Research Support)Napo Pharmaceuticals (Consultant, Scientific Research Study Investigator, Research Grant or Support)Singulex (Consultant)Summit Therapeutics (Grant/Research Support) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Background The prevalence of chronic hepatitis C virus (HCV) infection in patients with cancer in the U.S. has been reported to be 1.5% overall and up to 10.6% in specific subgroups. Testing for antibody to HCV (anti-HCV) is a low-cost diagnostic method in widespread use worldwide; however, the optimal screening test for HCV in cancer patients has not been established. We sought to identify the optimal screening test for HCV in patients with hematologic malignancies and/or prior hematopoietic cell transplant (HCT). Methods New patients who were seen at the Lymphoma/Myeloma, Leukemia, and Stem Cell Transplant clinics at MD Anderson Cancer Center (02/11/2019-11/5/2019) were simultaneously screened for HCV with serologic (antibody to HCV [anti-HCV]) and molecular (HCV RNA) assays. Anti-HCV testing was performed by using the ARCHITECT Anti-HCV assay and HCV RNA testing was performed by using the Cobas HCV test. The agreement between the two tests was evaluated using Cohen’s kappa statistic and McNemar’s test. All tests were two-sided with a significance level of 0.05. Results A total of 214 patients were enrolled in the study, of whom 127 (59%) were men (Table), One hundred forty-nine patients (70%) had a lymphoid neoplasm, 65 (30%) had a myeloid neoplasm, and 15 (7%) underwent HCT. Ninety-three patients (43%) had progressive disease. Three patients (1.4%) had positive anti-HCV, and two (0.9%) had positive HCV RNA. The overall percentage agreement was 99.5% (95% CI, 97.4% to 99.9%). Of the 3 patients with positive anti-HCV, 2 had positive and 1 had negative HCV RNA. There were no cases of seronegative HCV infection. The positive percentage agreement was 66.7% (95 CI, 20.8% to 93.9%), and the negative percentage agreement was 100.0% (95% CI, 98.2% to 100.0%). Cohen’s Kappa coefficient was 0·80 (95% CI, 0.41 to 1.00, p < 0·0001), indicating substantial agreement between anti-HCV and HCV RNA tests for diagnosis of HCV infection. Conclusion The diagnostic yield for screening for chronic HCV infection in heavily immunocompromised cancer patients is similar for serologic and molecular testing. The use of anti-HCV, a diagnostic method with low cost, in patients with cancer would contribute to the World Health Organization’s goal of HCV elimination worldwide. Table. Characteristics of the study population (n=214) Disclosures Harrys A. Torres, MD, Merck & Co., Inc. (Grant/Research Support) Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

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 2017. © 2017 American Cancer Society.

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 (11/2012-07/2016) were studied. Reactivation was defined as an increase in HCV-RNA ≥1 log10 IU/mL over baseline and hepatitis flare as alanine aminotransferase (ALT) increase 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 patients (23%), including 18 patients (36%) with hematologic malignancies and 5 (10%) with solid tumors. In univariate analysis, patients with reactivation were more likely than those without, to have prolonged lymphopenia (median, 95 vs 22 days, P=0.01) and to have received rituximab (44% vs 9%, P

Answer questions and earn CME/CNE Chronic hepatitis C virus (HCV) infection affects millions of people worldwide and is associated with cancer. Direct-acting antivirals (DAAs) have changed HCV treatment paradigms, but little is known about the management of HCV infection in patients with cancer. The substantial burden of HCV infection and the inconclusive evidence regarding its detection and management in patients with cancer prompted the authors to review the literature and formulate recommendations. Patients for whom HCV screening is recommended included all patients with hematologic malignancies, hematopoietic cell transplantation candidates, and patients with liver cancer. There is a lack of consensus-based recommendations for the identification of HCV-infected patients with other types of cancer, but physicians may at least consider screening patients who belong to groups at heightened risk of HCV infection, including those born during 1945 through 1965 and those at high risk for infection. Patients with evidence of HCV infection should be assessed by an expert to evaluate liver disease severity, comorbidities associated with HCV infection, and treatment opportunities. DAA therapy should be tailored on the basis of patient prognosis, type of cancer, cancer treatment plan, and hepatic and virologic parameters. HCV-infected patients with cancer who have cirrhosis (or even advanced fibrosis) and those at risk for liver disease progression, especially patients with HCV-associated comorbidities, should have ongoing follow-up, regardless of whether there is a sustained virologic response, to ensure timely detection and treatment of hepatocellular carcinoma. HCV infection and its treatment should not be considered contraindications to cancer treatment and should not delay the initiation of an urgent cancer therapy. CA Cancer J Clin 2017. © 2017 American Cancer Society. CA Cancer J Clin 2017;67:411-431. © 2017 American Cancer Society.

Background and aimChronic HCV infection is associated with several extrahepatic manifestations (EHMs). Data on the effect of sustained virological response (SVR) on the risk of EHMs are limited.MethodsWe conducted a retrospective cohort study using data of patients from the US Veterans Affairs HCV Clinical Case Registry who had a positive HCV RNA test (10/1999-08/2009). Patients receiving interferon-based antiviral therapy (AVT) were identified. SVR was defined as negative HCV RNA at least 12 weeks after end of AVT. Risks of eight incident EHMs were evaluated in Cox regression models.ResultsOf the 160 875 HCV-infected veterans, 31 143 (19.4%) received AVT, of whom 10 575 (33.9%) experienced SVR. EHM risk was reduced in the SVR group compared with untreated patients for mixed cryoglobulinaemia (adjusted HR (aHR)=0.61; 95% CI 0.39 to 0.94), glomerulonephritis (aHR=0.62; 95% CI 0.48 to 0.79), porphyria cutanea tarda (PCT) (aHR=0.41; 95% CI 0.20 to 0.83), non-Hodgkin’s lymphoma (NHL) (aHR=0.64; 95% CI 0.43 to 0.95), diabetes (aHR=0.82; 95% CI 0.76 to 0.88) and stroke (aHR=0.84; 95% CI 0.74 to 0.94), but not for lichen planus (aHR=1.11; 95% CI 0.78 to 1.56) or coronary heart disease (aHR=1.12; 95% CI 0.81 to 1.56). Risk reductions were also observed when patients with SVR were compared with treated patients without SVR for mixed cryoglobulinaemia, glomerulonephritis, PCT and diabetes. Significant reductions in the magnitude of aHRs towards the null with increasing time to initiation of AVT after HCV diagnosis were observed for glomerulonephritis, NHL and stroke.ConclusionsRisks of several EHMs of HCV infection are reduced after AVT with SVR. However, early initiation of AVT may be required to reduce the risk of glomerulonephritis, NHL and stroke.

BACKGROUND Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. METHODS This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. RESULTS HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. CONCLUSIONS HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202–1211. © 2016 American Cancer Society.

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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.

This study will be presented in part at the 52nd Annual Meeting of American Society of Clinical Oncology (ASCO), 3–7 June 2016, Chicago, IL.Chronic hepatitis C virus (HCV) infection affects more th...

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.

Purpose of review To provide an update on recent studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in cancer patients with an emphasis on viral reactivation after cancer treatment, new antiviral therapies, and safety concerns. Recent findings The diagnostic criteria for HBV reactivation in patients receiving cancer therapy were revised in 2018. HBV reactivation in these patients is preventable, even with the use of new cancer therapies. HCV reactivation also has been reported in cancer patients, particularly those with hematologic malignancies, and is not a virologic condition usually associated with poor outcome. Prophylaxis to prevent HCV reactivation is not recommended because therapy with direct-acting antivirals eradicates the infection in the majority of cancer patients. Summary Cancer patients with HBV or HCV infection are at risk for viral reactivation, with many similarities between these two infections. Patients at high risk for reactivation will benefit significantly from taking oral antivirals, which will reduce the risk of HBV reactivation or prevent development of HCV reactivation following its virologic cure.

Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) in the world, mostly with genotype 4 that is highly associated with severe fibrosis. As a consequence, hepatocellular carcinoma has become the leading cause of cancer in this country. Mauritania is a highly endemic area for hepatitis B virus (HBV). HBV and HCV could both be iatrogenically transmitted through infected blood products, infected needles, and medical equipment improperly sterilized. Adequate and efficient healthcare and public health measures with good surveillance programs, access for screening, prevention strategies, and successful treatment are needed to halt the spread of these diseases. Herein, we have reviewed the epidemiology, modes of transmission, predisposing factors, and novel treatment modalities of these viruses. We have proposed practices and interventions to decrease the risk of transmission of HCV and HBV in the affected countries, including strict adherence to standard precautions in the healthcare setting, rigorous education and training of patients and healthcare providers, universal screening of blood donors, use of safety-engineered devices, proper sterilization of medical equipment, hepatitis B vaccination, as well as effective direct-acting antiviral agents for the treatment of HCV.

Purpose Most patients with cancer are not screened for hepatitis B virus (HBV) infection before undergoing anticancer therapy, and optimal screening strategies are unknown. We sought to develop selective HBV screening strategies for patients who require systemic anticancer therapy. Methods This prospective cohort study included adults age ≥ 18 years with solid or hematologic malignancies who received systemic anticancer therapy at a comprehensive cancer center during 2013 and 2014. Patients underwent hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody testing, and completed a 19-question modified Centers for Disease Control and Prevention (CDC) HBV survey. Multivariable models that predict chronic or past HBV infection were developed and validated using bootstrapping. Results A total of 2,124 patients (mean age, 58 ± 13 years) completed the risk survey and HBV testing. Of these, 54% were women; 77% were non-Hispanic white, 11% Hispanic, 8% black, and 4% Asian; and 20% had a hematologic malignancy and 80% a solid tumor. Almost 12% were born outside the United States. The prevalence was 0.3% for chronic HBV infection and 6% for past HBV infection. Significant predictors of positive hepatitis B surface antigen or hepatitis B core antibody tests were as follows: men who had sex with men, black or Asian race, birthplace outside the United States, parent’s birthplace outside the United States, household exposure to HBV, age ≥ 50 years, and history of injection drug use. The area under the receiver operating characteristic curve of the model on the basis of these seven predictors was 0.79 (95% CI, 0.73 to 0.82). The modified CDC survey and brief tools with fewer than seven questions yielded similar false-negative rates (0% and 0% to 0.7%, respectively). Conclusion An internally validated risk tool performed as well as the modified CDC survey; however, more than 90% of patients who completed the tool would still require HBV testing. Universal HBV testing is more efficient than risk-based screening.

Background Several cases of severe bacterial, fungal, and viral infections have been reported following ibrutinib therapy. Here, we report a case of a patient with non-Hodgkin lymphoma who developed hepatitis B virus (HBV)–associated liver failure after anti-cancer treatment most recently with ibrutinib. We also review reported cases of HBV reactivation (HBVr) after ibrutinib. Methods We searched the Medline and Embase databases and identified 5 patients with HBVr related to ibrutinib for a total of 6 study patients, including our case (figure). HBV-related outcomes were defined according to the 2018 AASLD HBV guidance document. Results All 6 patients were men and most (5 or 83%) had chronic lymphocytic leukemia and past HBV infection (table). Three patients (50%) developed HBV-related hepatitis and 2 of them progressed to liver failure. Four patients (67%) had a remote history (≥24 months) of other potential risk factors besides ibrutinib that could contribute to HBVr, including the use of direct-acting antivirals for hepatitis C co-infection (1 pt), hematopoietic cell transplant (HCT) (1 pt) and rituximab use (4 patients). HBVr occurred at least 6 months after initiation of ibrutinib in most patients (4 or 67%), with a median of 9.7 months (range, 1.5–42). In all 4 patients pretreated with rituximab, that treatment was completed at least 24 months before HBVr. Two of these patients received anti-HBV prophylaxis that was stopped 12 months after the completion of rituximab; the other 2 patients were only monitored without antivirals. The HCT recipient received anti-HBV prophylaxis per guidelines. None of the 6 patients treated with ibrutinib were receiving anti-HBV prophylaxis at the time of HBVr, but 5 patients were started on anti-HBV drugs at the first sign of HBVr. Four received entecavir and 1, tenofovir. All treated patients recovered from HBVr. No pt died of HBVr. Conclusion Life-threatening HBVr can occur following ibrutinib therapy in patients with past or chronic HBV infection. The temporal association between ibrutinib therapy and reactivation indicates that ibrutinib is the likely cause of the HBVr, and clinicians should be aware of the risk of HBVr in these patients. A provisional approach could be HBV monitoring at regular intervals with initiation of antiviral therapy at the earliest sign of HBV reactivation. Disclosures All authors: No reported disclosures.

Background & Aims Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to determine body mass index (BMI) accurately, and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC. Methods We interviewed 622 patients newly diagnosed with HCC from January 2004 through December 2013, along with 660 healthy controls (frequency-matched by age and sex) to determine weights, heights, and body sizes (self-reported) at various ages before HCC development or enrollment as controls. Multivariable logistic and Cox regression analyses were performed to determine the independent effects of early obesity on risk for HCC and patient outcomes, respectively. BMI was calculated, and patients with a BMI of 30 kg/m 2 or greater were considered obese. Results Obesity in early adulthood (age, mid-20s to mid-40s) is a significant risk factor for HCC. The estimated odds ratios were 2.6 (95% confidence interval [CI], 1.4–4.4), 2.3 (95% CI, 1.2−4.4), and 3.6 (95% CI, 1.5–8.9) for the entire population, for men, and for women, respectively. Each unit increase in BMI at early adulthood was associated with a 3.89-month decrease in age at HCC diagnosis ( P Conclusions Early adulthood obesity is associated with an increased risk of developing HCC at a young age in the absence of major HCC risk factors, with no effect on outcomes of patients with HCC.

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 Eightynine 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.

AIM 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. METHODS As part of a prospective study of HCV-infected cancer patients conducted at our center, we investigate the characteristics associated with progression of their liver disease. RESULTS Of the 115 patients tested, 13 (11%) were positive for HEV immunoglobulin G. HEV seropositivity was associated with advanced age (P = 0.004), race (P = 0.02), place of birth outside the USA (P = 0.021), cirrhosis (P = 0.027), history of reused needles/syringes during massive vaccination campaigns (P = 0.015) and coronary artery disease (P = 0.039). Overall, 47 (41%) of the patients had cirrhosis. Factors independently associated with cirrhosis were male sex (odds ratio [OR], 2.8; P = 0.028) and HEV seropositivity (OR, 4.1; P = 0.032). CONCLUSION HEV seropositivity is present in 11% of HCV-infected cancer patients and seems to be associated with cirrhosis. Our results suggest that HEV screening should be implemented in HCV-infected patients with cancer.