HBV reactivation and clinical resolution in an isolated anti-HBc-positive patient during immune checkpoint inhibition.

BACKGROUND: Immune checkpoint inhibitor (ICI)-related liver injury is a growing concern as ICIs are increasingly used in cancer treatment regimens. Interestingly, ICIs have exhibited antiviral effects among patients with chronic hepatitis B virus (HBV). However, the underlying mechanisms remain unclear, and clinical data on patients with previous HBV infection/exposure and isolated anti-HBV core antibodies (IAHBcs) are lacking. METHODS: We report a case illustrating the dual effects of ICIs in a patient experiencing panlobular hepatitis and concurrent HBV reactivation. FINDINGS: A 68-year-old male patient positive for IAHBcs was admitted with panlobular hepatitis and HBV reactivation after receiving systemic chemotherapy (several months before admission) and ICI treatment (4 weeks before admission) subsequent to metastatic primary lung cancer (NSCLC stage IV). This was followed by a rapid and significant decrease of HBV DNA viral load before and during antiviral treatment. CONCLUSIONS: This unique case sheds light on the dynamics of ICI therapy in IAHBc-positive patients experiencing HBV reactivation during chemotherapy and underscores the dual impact of ICIs. Moreover, it emphasizes the need for assessment of HBV serology and prophylaxis in IAHBc-positive patients undergoing chemotherapy and ICI treatment. FUNDING: R.T.C. was supported by the MGH Research Scholars Program.

Immune checkpoint inhibitor use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.

BACKGROUND: The safety of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). The authors analyzed the incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients in a real-world setting. METHODS: A total of 1277 NSCLC patients treated with ICIs were analyzed. Among them, 52 patients were hepatitis B surface antigen (HBsAg) (+) (group A, CHB), 759 patients were HBsAg (-)/hepatitis B core antibody immunoglobulin G (anti-HBc IgG) (+) (group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (group C). Among the 52 patients with CHB, 38 (73.1%) were receiving antiviral therapy. The primary end point was HBV reactivation, immune-related hepatitis, and jaundice. The secondary end points included other immune-related adverse events and efficacy. RESULTS: HBV reactivation was observed in two patients (0.2%) who were both in group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed in 14.3% (2 of 14 patients). The incidences of immune-related hepatitis and jaundice were comparable among the three groups. The incidence of ≥grade 3 other immune-related adverse events and efficacy were all comparable among the three groups (p > .05 for all comparisons). CONCLUSIONS: In this large, real-world cohort study, the safety and efficacy of ICIs were comparable in patients with CHB and OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis should be required for them. For patients with OBI, the risk of HBV reactivation was minimal.

Expression of Th1 and Th2 type cytokines responding to HBsAg and HBxAg in chronic hepatitis B patients

The cytokine pattern on viral antigen recognition is believed to exert a profound influence on the resolution of viral infections and viral clearance. This study was initiated to investigate whether a cytokine imbalance oriented toward Th2 type response plays a role in chronic hepatitis B. Cytokine profiles of peripheral blood mononuclear cells associated with chronic hepatitis B were analysed by RT-PCR. Upon HBsAg stimulation, expression of IFN-gamma, IL-2, IL-4, and IL-10 was detected in 41%, 8%, 41%, and 50% of the patients, respectively. Among these cytokines, the expression of IFN-gamma was associated with high levels of serum AST/ALT. However, we could not prove that Th2 type cytokines had a protective effect on hepatocytes. Upon HBxAg stimulation, there was no recognizable association of cytokine patterns with AST/ALT levels. In conclusion, production of a Th1 cytokine, IFN-gamma, by HBsAg-reactive cells was associated with hepatocyte damage in chronic hepatitis B, while no counteracting effect of Th2 cytokines produced by those cells was observed.