Narrative review of hepatocellular carcinoma: from molecular bases to therapeutic approach

Abstract

: Hepatocellular carcinoma (HCC) is considered a serious health problem worldwide as it is one of the most prevalent malignancies in the world and with devastating outcomes. According to the 2020 estimation of global burden cancer by the International Agency for Research on Cancer (IARC), HCC ranks third in mortality among cancer deaths despite the incidence rate ranks sixth. In most cases, a history of preexisting chronic liver disease (CLD) is mandatory, usually established in the stage of cirrhosis. Globally, hepatitis B virus (HBV) continues to be the main cause of cirrhosis and HCC, especially in countries of East Asia and Sub-Saharan Africa where there are no universal vaccination programs against this virus. Other CLD include alcoholic liver disease (ALD), hepatitis C virus, nonalcoholic fatty liver disease, and in more infrequent cases, chronic aflatoxins exposure. Due to this large clinical spectrum that encompasses HCC, it is necessary to systematically review each CLD associated with the development of this cancer by studying its prevalence, molecular pathogenesis, risk factors associated with the progression of HCC, and specially prevention strategies. Finally, regarding the treatment of HCC, great advances have been made in the last decade. Surgical resection, transplantation, and in some cases ablation, are the only curative treatment for HCC, although tumor recurrence is commonly seeing in the follow-up process. Locoregional therapies are still controversial, whether they really provide an overall survival benefit or not, as well as in what type of patients would benefit most from this therapy. Regarding systemic therapies, a recently published phase 3 clinical trial demonstrated greater superiority in the overall survival of atezolizumab plus bevacizumab compared to Sorafenib as a first-line treatment in unresectable HCC patients. This finding will definitely bring a new perspective in the management of these kind of patients.