Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy

Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy

Reviewer: Marilyn Zelesco | ASA SIG: General

Authors: Singal A, Kanwal F & Llovet J

Why the study was performed

Liver cancer is the sixth most commonly diagnosed cancer and the third most common cause of cancer-related deaths globally. Hepatocellular carcinoma (HCC), which accounts for more than 80% of liver cancers, is among the top three causes of cancerrelated deaths in 46 countries and among the top five in 90 countries. Primary prevention strategies offer the best hope of reducing HCC-related mortality, although surveillance for HCC can also improve patient outcomes by ensuring that the disease is detected at an early stage amenable to curative therapies.

How the study was performed

In this review, the authors discussed trends in the epidemiology of HCC and their implications for screening, prevention and therapy. A comprehensive literature review was undertaken.

What the review found

The incidence of HCC varies across regions of the world, owing to differences in the distribution of aetiological risk factors and access to screening and treatments for underlying liver diseases. HCC incidence is highest in Asia and Africa, with lower incidence in the Americas, Europe and the Middle East. More than 70% of all HCC cases occur in Asia.

The epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. Hepatitis B vaccination and antiviral therapy for hepatitis B and C are effective for primary prevention of virus-related HCCs, but chemoprevention strategies for non-viral liver disease remain an unmet need. Emerging data suggest associations between aspirin, statins, metformin and coffee and reduced HCC incidence, although none has been proven to be causally related.

Secondary prevention of HCC via semiannual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early-stage HCC, particularly in patients with obesity and/or non-viral liver disease.

From an imaging perspective, cohort studies from South Korea have suggested that two-phase low-dose CT and contrastenhanced MRI can yield superior sensitivity for early-stage HCC detection versus ultrasonography (83% and 86% versus 28–29%, respectively). However, the broad use of CT or MRI surveillance is limited by concerns over costs, radiology service capacity and potential safety risks (for example, owing to contrast and/or radiation exposure).

Although resection almost always results in complete removal of the initial tumour, HCC recurrence is common, particularly in those with multinodular disease, microvascular invasion and/or poorly differentiated tumours. Antiviral therapies are safe and can improve overall survival (OS). Although resection almost always results in complete removal of the initial tumour (or tumours), HCC recurrence is common (with 5-year rates of 50–70%), particularly in those with multinodular disease, microvascular invasion and/or poorly differentiated tumours. Antiviral therapies are safe and can improve OS in patients who have previously undergone locoregional treatment for virus-related HCCs, including resection, although the effect on short-term HCC recurrence patterns is less clear. Other adjuvant therapies failed to show a benefit in improving RFS, with the exception of the aforementioned regimen consisting of atezolizumab plus bevacizumab for up to 1 year. The improvement in postoperative recurrence observed with this regimen might prompt some centres to consider the use of surgical resection in patients previously deemed to have an unacceptably high risk of recurrence.

Relevance to clinical practice

HCC is one of the few cancers with rising incidence and increasing mortality globally. Shifts in epidemiological patterns among at-risk patients, most notably an increasing proportion of HCCs with nonviral aetiology, have important implications for primary prevention, surveillance and treatment. Unmet needs include proven chemoprevention and effective surveillance strategies in patients with non-viral liver disease, although ongoing studies are investigating promising interventions in both areas. Surgical therapies, when applicable, still provide the best long-term survival outcomes for patients with HCC, although the introduction of ICI-based regimens has substantially improved OS for patients with advanced-stage, unresectable tumours. Sonographers should be cautious when scanning patients at risk of HCC to ensure small, early lesions are not missed.

… HCC is one of the few cancers with rising incidence and increasing mortality globally …