Metachronous hepatocellular carcinoma after partial response of advanced intrahepatic cholangiocarcinoma treated with radiotherapy combined with apatinib and camrelizumab: a case report.

We describe a case of metachronous double primary hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) in a 62-year-old male with occult hepatitis B virus (HBV) infection, an extremely rare entity easily misdiagnosed as iCCA recurrence, especially with an alpha-fetoprotein (AFP)-negative phenotype. The patient was initially diagnosed with stage IV iCCA (cT3N0M1) with bone metastases, receiving radiotherapy for primary and metastatic lesions, followed by 2-year sequential apatinib plus camrelizumab, achieving iCCA partial remission. At 56-month follow-up, abdominal CT detected new hepatic lesions, which pathological and immunohistochemical examinations confirmed as de novo HCC rather than iCCA recurrence, with the patient remaining AFP-negative throughout the course. We retrospectively analyzed this case and reviewed relevant literature to discuss its diagnostic clues, potential pathogenesis and therapeutic implications. This case highlights that occult HBV infection, chronic inflammation and liver radiotherapy may synergistically drive multi-pathway hepatocarcinogenesis. Radiotherapy combined with anti-angiogenic and immunotherapy is an effective option for advanced unresectable iCCA. It also emphasizes that active pathological biopsy is essential for new hepatic lesions after iCCA remission to clarify diagnosis and avoid misdiagnosis-induced inappropriate treatment.