Occult hepatitis B in patients with cancer during immunotherapy with or without chemotherapy: A real-life retrospective single-center cohort study

Abstract

IntroductionFew data about the safety of immune checkpoint inhibitors (ICIs) in the patients with solid tumor with Occult Hepatitis B Virus (OBI) are available. According to the Taormina Workshop on Occult HBV Infection Faculty Members we defined as potential-OBI (pOBI) the HBV DNA negativity with anti-hepatitis B core antibody (anti-HBc) positivity (pOBI seropositive), and the patients with HBsAg–negative and anti-HBc–negative and Hepatitis B surface antibody (anti-HBs)–negative are defined pOBI seronegative. The aim of this study is to investigate the prevalence of OBI in patients with solid tumors undergoing ICIs with or without chemotherapy and the incidence of reactivation (HBVr).MethodsWe retrospectively enrolled all HBsAg negative subjects who had received ICIs for at least three months. HBsAg and HBV DNA levels were repeated every 3 months until the end of the study and/or in case of ALT alterations. A univariate analysis was conducted in order to study for each variable available its ability to distinguish a potential OBI seropositive patient from a seronegative one.Results150 patients in our Oncology Unit were eligible. One hundred and seventeen patients (78%) received ICI as monotherapy, whereas 33 patients (22%) were treated with chemo-immunotherapy. The mainly used drugs for the ICI monotherapy were Pembrolizumab (47%), Nivolumab (33%) and Atezolizumab (11%). The prevalence of pOBI seropositive patients was 25.3%. We did not observe alterations of liver biochemistry nor HBVr.DiscussionThis study highlights that about a quarter of our population had a potential occult hepatitis B. Immunotherapy might be considered as low risk of reactivation, regardless of the potential presence of episomal covalently closed circular DNA (cccDNA) in the liver, but the correct management still represents a challenge for oncologists and hepatologists.

Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen

“…In the treatment of malignant lymphoma also, the higher the value on pretreatment HBc antibody testing, the higher the risk of reactivation in HBs antigen-negative anti-HBc antibodypositive patients [66]. Although immune checkpoint inhibitors (ICIs) have been used for the treatment of many cancers in recent years, as of now, no OBI reactivation due to ICIs has been reported [67,68]. Clarke et al used anti-TNF preparations in 120 HBs antigennegative anti-HBc antibody-positive cases and found that positive conversion of HBs antigen occurred in only one case (0.8%), indicating a low frequency of reactivation [69].…”

The ABC of Immune-Mediated Hepatitis during Immunotherapy in Patients with Cancer: From Pathogenesis to Multidisciplinary Management

“…In our retrospective cohort study, we evaluated 150 potential-OBI (pOBI) patients (HbsAg negative) without HBV prophylaxis during immunotherapy. Only one pOBI patient (anti-Hbc+, anti-Hbs+ and anti-Hbe−) showed an increase in ALT (>3× ULN) with concomitant transient detectability of HBV-DNA [74]. Lin and colleagues demonstrated that seropositive HBsAg (OR = 6.30, p = 0.020), the existence of liver involvement (OR = 2.10; p = 0.030), and detectable baseline HBV DNA levels (OR = 2.39, p = 0.012) were risk factors for any-grade hepatotoxicity during ICIs, while the prophylactic antiviral therapy decreased hazard for the incidence of grade 3-4 hepatotoxicity (OR = 0.10, p = 0.016) [75].…”

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies in the targeted therapy era

“…Table 3 summarizes the data on HBV reactivation in patients receiving ICIs[ 126 - 129 ]. The rate of HBV reactivation among HBsAg-positive cancer patients is 0.5% to 5.3% during ICI therapy.…”