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.

Management of liver disease and portal hypertension in common variable immunodeficiency (CVID).

Patients with common variable immunodeficiency (CVID) frequently develop liver disease and associated complications, which represent an increasingly prevalent unmet medical need. The main hepatic manifestation of CVID is nodular regenerative hyperplasia (NRH), resulting in non-cirrhotic portal hypertension (NCPH). Liver disease is often underdiagnosed, leading to poor outcomes and decreased survival. The increasing numbers of patients with CVID who are diagnosed late with progressive liver disease underscores the importance of appropriate clinical management and treatment of liver complications. At the same time, specific guidelines for the clinical management of CVID-related liver disease are still lacking. Here, we review the epidemiology of CVID-related liver disease, reveal new insights into NRH and NCPH biology and highlight recently uncovered opportunities for NCPH diagnostics in CVID. Finally, we focus on current management of liver disease, portal hypertension and its complications - the key challenge in patients with CVID. Specifically, we review recent data regarding the role of transjugular intrahepatic portosystemic shunt and liver transplantation in clinical management. The role for anticoagulants and immunosuppressants targeting the pathogenesis of NRH will also be discussed. We propose an updated algorithm for the diagnostic work-up and treatment of NCPH in CVID. Finally, we consider future needs and therapeutic opportunities for CVID-related liver disease.