Advances in Pharmacotherapy of Hepatocellular Carcinoma: A State-of-the-Art Review

Dig Dis. 2022;40(5):565-580. doi: 10.1159/000520095. Epub 2021 Oct 13.


Background: Due to the number of emerging new treatment options, the systemic treatment of hepatocellular carcinoma (HCC) is rapidly changing. We provide here an overview of the current landscape of systemic treatment of HCC and discuss its potential future development.

Summary: HCC is a leading cause of tumor-related death worldwide. Despite the efforts aimed at reducing the prevalence of HCC through vaccination and antiviral treatment, and the implementation of screening programs for early tumor detection, most patients are diagnosed with or progress to advanced HCC. For approximately 10 years, sorafenib has been the only effective systemic treatment available for these patients. Recently, however, a number of new systemic compounds, comprising several multi-kinase inhibitors and immune-checkpoint inhibitors, have been approved for treatment of HCC. These new agents are opening a plethora of therapeutic options for the future therapy of HCC.

Key messages: The rapid progress in the treatment of HCC raises the question of the optimal combination and sequence of these agents in the treatment of patients with advanced disease. The substantial improvements in terms of objective response and survival indicate that the use of immune-checkpoint inhibitors-based treatment combinations may be extended to patients with intermediate-stage HCC.

Keywords: Hepatocellular carcinoma; Immunotherapy; Pharmacotherapy.

Publication types

  • Review

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Immune Checkpoint Inhibitors
  • Immunotherapy
  • Liver Neoplasms* / pathology
  • Sorafenib / therapeutic use


  • Immune Checkpoint Inhibitors
  • Sorafenib