Experimental and Clinical Transplantation -
Hepatocellular carcinoma is typically diagnosed late in its course, and the median survival following diagnosis is short. The recommended therapy for localized hepatocellular carcinoma is surgical resection, but most patients are not eligible because of extensive tumor or underlying liver dysfunction. New treatments and indications for various treatments are evolving rapidly. For patients who are ineligible for liverdirected therapy or for patients showing progression on locoregional therapy, systemic therapy is an option if performance status and underlying liver function are within eligible requirements. Until 2008, no effective therapy existed for patients with advanced-stage hepatocellular carcinoma or for those who did not respond to local therapies. The molecularly targeted agents sorafenib and regorafenib have been shown to improve survival compared with best supportive care alone; a survival benefit has also been shown in the second-line setting for ramucirumab and immune checkpoint inhibitors. Lenvatinib has demonstrated noninferiority to first-line sorafenib. Most recently, the combination of atezolizumab plus bevacizumab was superior to front-line sorafenib. These results have radically changed the treatment landscape for patients with advanced hepatocellular carcinoma.