Hepatitis Flare During Immunotherapy in Patients With Current or Past Hepatitis B Virus Infection

Abstract

INTRODUCTION: Immunotherapy has dramatically improved the survival of patients with advanced or metastatic malignancies. Recent studies suggest that immunotherapy may increase the risk of hepatitis, whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy. METHODS: This was a territory-wide observational cohort study in Hong Kong. We identified patients through electronic medical records based on the prescriptions of immune checkpoint inhibitors from July 1, 2014, to December 31, 2019. Patients who were HBsAg positive or HBsAg negative with results for antibody to hepatitis B surface or core antigen (anti-HBs or anti-HBc) were included. RESULTS: A total of 990 patients (397 HBsAg-positive, 593 HBsAg-negative with 482 anti-HBc and/or anti-HBs positive, and 111 both anti-HBc and anti-HBs negative) were identified. All of HBsAg-positive and 15.9% HBsAg-negative patients were put on oral antiviral treatment. Hepatitis flare (alanine aminotransferase >2 times of the upper limit of normal) occurred in 39.3% HBsAg-positive and 30.4% HBsAg-negative patients. High baseline alanine aminotransferase and combination of immunotherapy increased the risk of hepatitis. HBV reactivation (≥2 log increase in HBV DNA from baseline) occurred in 2 HBsAg-positive patients; HBsAg seroclearance and seroreversion was observed in 1 HBsAg-positive and 1 HBsAg-negative patient, respectively (<1%). DISCUSSION: Hepatitis flare occurs in approximately 40% of HBsAg-positive patients and 30% of HBsAg-negative patients during immunotherapy. HBV reactivation, HBsAg seroclearance, and HBsAg seroreversion are rare. Current or past HBV infection has no impact on the emergence of hepatic flare associated with immunotherapy.

Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients

“…In a study of 60 CHB-HCC patients, no patients on antiviral therapy (regardless of HBV viral load at baseline) developed HBV reactivation, and one out of six not receiving Nucs had HBV reactivation [159]. In another large cohort of 397 patients, HBV reactivation only occurred in 2 HBsAg-positive patients (<1%) [160]. HCV reactivation is less studied in HCC patients but appears to be safe in patients with melanoma [161] and non-small cell lung cancer [162].…”

Immune checkpoint inhibitor-related hepatotoxicity: A review

“…Patients receiving certain systemic chemotherapies are at increased risk of reactivation of chronic hepatitis B. Although hepatitis B reactivation is very rare (< 1%) with ICI therapy[ 44 ], it can also occur with other co-administered chemotherapies or during treatment of ICH with corticosteroids. Therefore, patients should have their hepatitis B status checked routinely prior to commencing treatment with ICIs[ 45 ] and be considered for prophylactic antiviral therapy.…”

Novel strategies for the early diagnosis of hepatitis B virus reactivation

“…These findings can be adopted by the oncology community as well. Recently, a report from China described the incidence of hepatitis flares, HBV reactivation, and HBsAg seroclearance or seroreversion in patients with current or past HBV infection who had received ICIs 45 . In the HBsAg‐positive cohort, 388 patients (97.7%) had received antiviral treatment at baseline.…”

“…In the HBsAg‐positive cohort, 388 patients (97.7%) had received antiviral treatment at baseline. HBV reactivation was rare, because all patients with HBsAg received antiviral treatment 45 . Therefore, the prophylactic administration of NAs before administering ICIs is recommended for HBsAg‐positive patients to control immune reaction against HBV during ICIs administration (Figure 1b).…”