A global view of hepatocellular carcinoma: trends, risk, prevention and management

Abstract

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease (particularly nonalcoholic fatty liver disease) and exposure to dietary toxins such as aflatoxins and aristolochic acid. All these risk factors are potentially preventable, highlighting the considerable potential of risk prevention for decreasing the global burden of HCC. HCC surveillance and early detection increase the chance of potentially curative treatment; however, HCC surveillance is substantially underutilized, even in countries with sufficient medical resources. Early-stage HCC can be treated curatively by local ablation, surgical resection or liver transplantation. Treatment selection depends on tumour characteristics, the severity of underlying liver dysfunction, age, other medical comorbidities, and available medical resources and local expertise. Catheter-based locoregional treatment is used in patients with intermediate-stage cancer. Kinase and immune checkpoint inhibitors have been shown to be effective treatment options in patients with advanced-stage HCC. Together, rational deployment of prevention, attainment of global goals for viral hepatitis eradication, and improvements in HCC surveillance and therapy hold promise for achieving a substantial reduction in the worldwide HCC burden within the next few decades.

Fig. 1 |. Global disease burden of primary liver cancer.

Global variation exists in the incidence (part a) and mortality (part b) of primary liver cancer, with the highest burden seen in East Asia and sub-Saharan Africa where medical resources are often limited. Hepatocellular carcinoma accounts for 80–90% of primary liver cancer. Numbers are per 100,000 person-years. Data from Globocan 2018 (https://gco.iarc.fr/today/home).

Fig. 2 |. Global variation in the overall survival of patients with HCC.

Taiwan and Japan have the best clinical outcomes for patients with hepatocellular carcinoma (HCC), probably owing to the high proportion of HCCs that are detected at an early stage as a result of nationwide intensive surveillance programmes in both countries. By contrast, outcomes in other East Asian countries are not as good as in Japan or Taiwan, as more patients present at an advanced stage. Overall survival of patients with HCC in Egypt was longer than in the other African countries, probably because more patients with HCC are diagnosed whilst under surveillance for HCC, so that a lower proportion of patients present with advanced- or terminal-stage disease and a higher proportion of patients receive HCC treatment. Data from Park et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int. 35, 2155–2166 (2015) and Yang et al. Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium. Lancet Gastroenterol. Hepatol. 2, 103–111 (2017).

Fig. 3 |. Strategy for HCC treatment in countries with different resource levels.

The optimal-treatment for hepatocellular carcinoma (HCC) should be considered even in intermediate-resource or low-resource countries if the treatment option is available; however, not all forms of treatment are equally cost-effective and years-of-life-saving in every setting, regardless of their cost. For early-stage HCC, potentially curative treatment should be considered whereas locoregional treatment would be the first-line treatment for intermediate-stage HCC. However, these therapeutic modalities are resource-intensive and sorafenib could be considered as an alternative option in countries with limited resources. For advanced-stage HCC, targeted or immunotherapy should be considered regardless of resource level. Best supportive care should be provided in patients with terminal-stage HCC. TACE, transarterial chemoembolization; TAE, transarterial embolization; TARE, transarterial radioembolization.