Implementation of Universal Hepatitis C Virus Screening in a Tertiary Cancer Center.

BACKGROUND: The prevalence of chronic hepatitis C virus (HCV) infection in the United States is ≤1%. Universal HCV screening is recommended nationwide. Here we describe our experience implementing universal HCV screening at a cancer center. METHODS: In October 2016, universal HCV screening with HCV antibody (anti-HCV) was initiated for all new outpatients. Universal screening was promoted through widespread provider education, orders in the Epic electronic health records (EHRs), SmartSets, and automated EHR reminders. The effort focused on patients with solid tumors, because universal screening in patients with hematologic malignancies was already standard practice. Primary outcomes were the proportion of patients screened and the proportion of patients with reactive anti-HCV test results linked to HCV care. The secondary outcome was the incidence of HCV-associated hepatocellular carcinoma as a second primary malignancy (HCC-SPM) in patients with a history of other cancers before HCC diagnosis. Epic's Reporting Workbench Business Intelligence tools were used. Statistical significance was defined as P<.05 on chi-square analysis. RESULTS: From April 2016 through April 2023, 56,075 patients with solid tumors were screened for HCV, of whom 1,300 (2.3%) had reactive anti-HCV test results. The proportion of patients screened was 10.1% in the 6 months before study implementation and 34.4% in the last 6 months of the study (P<.001). HCV screening was ordered using SmartSets in 39,332 (45.8%) patients and in response to automated EHR reminders in 10,972 (12.8%) patients. Most patients with reactive anti-HCV test results were linked to care (765/1,300; 59%), most with proven HCV infection were treated (425/562; 76%), and most treated patients achieved sustained virologic response (414/425; 97%). The incidence of HCC-SPMs was 15% in historical controls treated from 2011 to 2017 and 5.7% following implementation of universal screening (P=.0002). CONCLUSIONS: Universal HCV screening can be successfully implemented in cancer hospitals using an EHR-based multipronged approach to eliminate HCV and prevent HCV-associated HCC-SPMs.

Hepatitis B Virus Reactivation in Patients Receiving Bruton Tyrosine Kinase Inhibitors.

BACKGROUND: Bruton tyrosine kinase (BTK) inhibitors are used to treat B-cell hematologic malignancies. Ibrutinib has been associated with hepatitis B virus (HBV) reactivation. We sought to identify patients with hematologic malignancies who developed HBV reactivation after receiving first-generation (ibrutinib) or second-generation (acalabrutinib and zanubrutinib) BTK inhibitors. METHODS: We retrospectively studied all consecutive patients with hematologic malignancies with past HBV infection (HBV surface antigen [HBsAg] negative and hepatitis B core antibody [anti-HBc] positive) or chronic HBV infection (HBsAg positive and anti-HBc positive) treated with BTK inhibitors at our institution from November 1, 2015, through November 1, 2022. RESULTS: Of 82 patients initially identified, 53 were excluded (11 because of false-positive anti-HBc results, and 42 because they were receiving anti-HBV prophylaxis owing to recent receipt of anti-CD20 monoclonal antibodies). The 29 remaining patients were further analyzed and 3 (10%; 2/28 with past and 1/1 with chronic HBV infection) were found to have HBV reactivation. One patient received ibrutinib, and 2 received acalabrutinib. All developed HBV-associated hepatitis requiring anti-HBV therapy and survived. One patient continued receiving acalarutinib. Among the patients with past HBV infection, 13 received ibrutinib and 1 (8%) had HBV reactivation; 14 received acalabrutinib and 1 (7%) had HBV reactivation (P = 1.0). CONCLUSIONS: HBV reactivation risk is intermediate in patients with past HBV infection who receive BTK inhibitors. For patients with past HBV infection who received BTK inhibitors, data are insufficient to recommend universal anti-HBV prophylaxis, but monitoring for HBV reactivation is warranted.

Safety and Efficacy of Immune Checkpoint Inhibitors in Patients with Cancer and Viral Hepatitis: The MD Anderson Cancer Center Experience.

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.

Hepatobiliary and Pancreatic Adverse Events.

The expanded approval of immune checkpoint inhibitors (ICIs) for the treatment of multiple cancer types has offered patients more opportunities in treatment selection and survival.Hepatotoxicity is a well-recognized immune-related adverse event (irAE) associated with treatment with ICI. It is considered a type of drug-induced liver injury (DILI). Depending on the specific ICI and whether the patient receives single- or dual-drug therapy, the incidence of hepatotoxicity in general could be as high as 30%. As more patients receive treatment with ICI, more cases of hepatotoxicity are expected to occur. Clinicians must exercise close pharmacovigilance to recognize liver-related irAEs early.ICI-mediated hepatobiliary toxicity (or "IMH") generally presents as asymptomatic elevations of alanine transaminase and aspartate transaminase, with or without alkaline phosphatase elevation. Some patients may present with jaundice, fever, or malaise. Rarely, it may cause liver failure and death. The diagnosis of IMH is made after careful exclusion of other causes of acute hepatitis based on medical history, laboratory evaluation, imaging, and liver histological findings. In clinically significant cases of IMH, the management involves discontinuation of ICI followed by close monitoring and the initiation of immunosuppression. Current society guidelines, which are not based on robust evidence, specify treatment recommendations depending on the grade of liver injury, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. However, our clinical experience suggests possible alternatives, including lower corticosteroid dosing with adjunct therapies. Whereas current guidelines endorse permanent cessation of future ICI treatment in patients diagnosed with grades 3-4 IMH, published clinical experience suggests potential for flexibility when assessing for candidacy of resuming ICI.Because histologic bile duct injury has been observed in cases ascribed to IMH, ICI-mediated cholangiopathic disease probably exists on a spectrum within IMH. Even extrahepatic bile duct involvement has been observed. This phenotype warrants special considerations in treatment and surveillance.ICI-related cholecystitis has been rarely reported in the literature. Management follows current standards of care for typical cases of cholecystitis. No relationship with ICI-mediated cholangiopathic disease has been observed.Assessing for and managing ICI-associated pancreatic injury remain challenging to the clinician. Many cases of asymptomatic serum lipase elevation are detected on routine labs without clinical signs or symptoms of typical acute pancreatitis. However, symptomatic patients should be initially managed like traditional cases of acute pancreatitis requiring hospitalization for evaluation and inpatient management.

Patients with Non-Hodgkin's Lymphoma Are at Risk of Adenomatous Colon Polyps.

BACKGROUND: Patients with non-Hodgkin's lymphoma (NHL) are frequently referred for colonoscopy to evaluate gastrointestinal symptoms during their treatment course. Here, we described the rate of colonic adenomas in patients with NHL. METHODS: This was a retrospective study of patients with NHL who underwent colonoscopy after being diagnosed with NHL between January 2000 and December 2017. RESULTS: Of the 17,938 patients who had been diagnosed with NHL in the study period, 2176 met the inclusion criteria. The mean age at the time of colonoscopy was 61 years. Most patients were male (61%). Overall, 1273 polyps were detected in 811 patients (37%). Sessile serrated adenomas were detected in 102 (5%) patients. The overall ADR was 12% in patients younger than 40 years of age (n = 103), 26% in patients aged 40-50 (n = 251), 34% in patients aged 51-60 (n = 630), and 43% in patients older than 60 (n = 1212). Most polyps were located in the right colon (63%), and 101 (8%) were larger than 1 cm. Villous adenomatous features were present in 1% of polyps, while high-grade dysplasia was detected in 22%. Invasive adenocarcinoma was identified in 4%. The median interval from lymphoma diagnosis to adenoma detection was 1.4 years (interquartile range 0.5-3.8 years). A repeat colonoscopy was performed in 343 patients. The overall ADR on repeat colonoscopy was 30%. Cox regression analysis revealed that age (hazards ratio 1.04; 95% confidence interval 1.03-1.05; P < 0.001) and male sex (hazards ratio 1.35; 95% confidence interval 1.13-1.60; P = 0.001) were independent factors associated with worse overall survival. By contrast, screening colonoscopy was associated with longer survival duration (hazards ratio 0.48; 95% confidence interval 0.36-0.63; P < 0.001). CONCLUSION: The ADR in NHL patients aged 40-50 years was equivalent to that reported in the literature in non-cancer patients aged 50-70 years. Early screening colonoscopy may be warranted in NHL patients younger than 50 years. Screening colonoscopy significantly improved the overall survival of patients with NHL.