Elsevier

The Lancet

Volume 391, Issue 10127, 31 March–6 April 2018, Pages 1301-1314
The Lancet

Seminar
Hepatocellular carcinoma

https://doi.org/10.1016/S0140-6736(18)30010-2Get rights and content

Summary

Hepatocellular carcinoma appears frequently in patients with cirrhosis. Surveillance by biannual ultrasound is recommended for such patients because it allows diagnosis at an early stage, when effective therapies are feasible. The best candidates for resection are patients with a solitary tumour and preserved liver function. Liver transplantation benefits patients who are not good candidates for surgical resection, and the best candidates are those within Milan criteria (solitary tumour ≤5 cm or up to three nodules ≤3 cm). Image-guided ablation is the most frequently used therapeutic strategy, but its efficacy is limited by the size of the tumour and its localisation. Chemoembolisation has survival benefit in asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread. Finally, sorafenib, lenvatinib, which is non-inferior to sorafenib, and regorafenib increase survival and are the standard treatments in advanced hepatocellular carcinoma. This Seminar summarises the scientific evidence that supports the current recommendations for clinical practice, and discusses the areas in which more research is needed.

Introduction

Hepatocellular carcinoma is the most frequent primary liver cancer and is an important medical problem. With 782 000 cases diagnosed and 746 000 deaths in 2012, and an age-adjusted worldwide incidence of 10·1 cases per 100 000 person-years, hepatocellular carcinoma is ranked as the sixth most common neoplasm and the third leading cause of cancer death. Hepatocellular carcinoma has been recognised as a leading cause of death among patients with cirrhosis, and its incidence is expected to increase in the future.1 Together with the recognition of its clinical relevance, major progress has been made in prevention, detection, diagnosis, and treatment. In this Seminar, we summarise the knowledge that has emerged since our last update in 2012.2

Section snippets

Epidemiology

The development of hepatocellular carcinoma is closely related to the presence of chronic liver disease. The worldwide incidence is heterogeneous because of the variable prevalence of the risk factors. Most hepatocellular carcinoma cases (80%) occur in sub-Saharan Africa and eastern Asia, where the main risk factors are chronic hepatitis B and aflatoxin B1 exposure.3 In patients with hepatitis B, the incidence of hepatocellular carcinoma increases with viral load, duration of infection, and

Pathogenesis

Development of hepatocellular carcinoma is a complex multistep process that involves sustained inflammatory damage, including hepatocyte necrosis and regeneration, associated with fibrotic deposition. Risk of hepatocellular carcinoma emerges when cirrhosis is established, and it increases in parallel to progressive liver function impairment. Hepatocellular carcinoma is the result of the accumulation of somatic genomic alterations in passenger and driver genes in addition to epigenetic

Surveillance and diagnosis

Hepatocellular carcinoma surveillance aims to reduce disease-related mortality. Several non-randomised studies have shown that patients who were enrolled into a surveillance programme were diagnosed at an earlier stage, received potential curative therapies more frequently, and had better overall survival than did unenrolled peers.30 Regrettably, these uncontrolled studies are at risk of biases.31 A randomised controlled trial32 of surveillance done in China included 18 816 patients with

Staging and prognostic assessment

Prognostic assessment is a crucial step in the management of patients with hepatocellular carcinoma. Since most patients have an associated liver disease, the prognostic evaluation should incorporate not only tumour stage, but also the degree of liver function impairment. In addition, the presence of cancer-related symptoms has consistently shown a negative effect on survival. Finally, for any system to be clinically successful, prognostic prediction should be paired with treatment indication.63

Treatment

The aim of treatment is to increase survival while maintaining the highest quality of life. Very frequently, the treatment decision pivots around what can be done, rather than what is worth being done. For that reason, it is paramount to evaluate the strength of scientific evidence of any treatment approach for selecting the most appropriate option for each patient at each tumour stage. Furthermore, achievement of the best therapeutic effectiveness requires the careful selection of candidates

Future perspectives

In the past 10 years, treatment of hepatocellular carcinoma has evolved considerably. Nowadays, patients with hepatocellular carcinoma can benefit from effective options that improve their survival whatever the evolutionary stage of disease at diagnosis. However, improvement can still be made in several areas. Prevention of the acquisition of the risk factors for development of hepatocellular carcinoma is the best strategy for decreasing mortality. The high efficacy of direct acting antivirals

Search strategy and selection criteria

We searched in MEDLINE, Embase, and Cochrane Library (between Jan 1, 2005, and April 30, 2017), using hepatocellular carcinoma, liver cancer, and primary liver carcinoma as free text words. We also did a manual search and review of reference lists. We largely selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications. Only articles published in English were selected.

For the US National Cancer Institute see https://www.cancer.gov

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