Managing fibrolamellar hepatocellular carcinoma

Introduction: Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver malignancy historically designated as a variant of hepatocellular carcinoma (HCC), which comprises less than 1% of all HCC. FLC affects predominantly young people (< 40 years of age) in the absence of underlying liver disease. Diagnosis can be difficult with history and cross-sectional imaging alone, sometimes requiring a core biopsy for definitive diagnosis. Despite presenting with more advanced disease than patients with HCC, FLC has a high resectability rate and improved prognosis over HCC. Unfortunately, most FLC patients will recur and a subset of patients will die of the disease. Currently, FLC has no standardized regimen for systemic therapy. Areas covered: This review covers the diagnosis, management, and recent advancements of FLC. These advancements increase understanding of the genetic profile for FLC and provide potential molecular targets for anticancer therapy. This literature review includes publications from PubMed and clinical trials from ClinicalTrials.gov. Expert opinion: Despite a high resectability rate, many patients with FLC recur. Effective systemic therapy is needed to improve the prognosis of FLC. The recent discovery of chimeric transcript DNAJB1-PRKACA in FLC holds promise in further understanding the pathogenesis of FLC, becoming a diagnostic marker for FLC, and developing molecular targeted therapy for the treatment of FLC. However, given the rare nature of the disease, collaborative efforts on an international, multi-institutional level in clinical trials, tumor registries for tissue and blood banking, and the development of novel systemic therapies are essential for the future advancement of FLC.