S5719 Spontaneous Remission of Hepatocellular Carcinoma in Chronic Hepatitis B: A Case Series

Introduction: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the prognosis of advanced HCC is low. The spontaneous regression of HCC, which refers to tumor regression in the absence of treatment, is extremely rare and occurs in fewer than 1% of HCC cases. Insight into the mechanisms responsible for these regressions may provide insight in the biology of tumor and in future therapeutic strategies. We report 3 cases of spontaneous regression of HCC in patients with chronic hepatitis B virus (HBV) infection. Case Description/Methods: Case 1: A 35-year-old Liberian born man with chronic HBV, Hepatitis D (HDV) co-infection, and compensated cirrhosis was diagnosed with a 5 cm HCC on imaging and alpha-fetoprotein (AFP) of 3959 ng/mL. On follow-up imaging few months later, there were subcapsular hemorrhagic in the mass without typical HCC features. Without intervention, AFP normalized, and imaging demonstrated complete tumor regression 26 months. Case 2: A 69-year-old Vietnamese born man, with serology suggesting prior HBV infection and clearance with subsequent low-level viremia, diagnosed with chronic HBV with imaging showing have a 6.5 cm HCC. Interval imaging over 37 months showed signs of regression and AFP decreased from 478.5 ng/mL to <5 ng/mL. Case 3: A 27-year-old Liberian man with chronic HBV and hepatitis D virus co-infection, presented with a 9 cm infiltrative hepatic mass (HCC), portal vein thrombus, and AFP of 1429 ng/mL. The patient declined systemic therapy and opted for lifestyle changes. Subsequent imaging 13 months later showed complete tumor regression, with AFP normalizing and no detectable tumor 6 years post-diagnosis. Discussion: These cases highlight the rare occurrence of spontaneous HCC regression in patients with chronic HBV infection. Common features include male gender, foreign birth, HBeAg-negative status, low viral loads, right lobe tumor location, significantly elevated AFP levels at diagnosis and placement on antiviral treatment. The regressions occurred over 1–3 years without recurrence. Potential mechanisms may involve tumor hypoxia and host immune responses, such as CD8+ T-cell activity, macrophage infiltration, and cytokine release (e.g., TNF-α, IL-18). Understanding these mechanisms may inform novel immunotherapeutic strategies for HCC.