Letter to the Editor: Hepatocellular carcinoma in patients without cirrhosis - urgent need to include Australasian populations

Abstract

We read with interest the recent review article by Sato-Espinoza et al published in World Journal of Gastroenterology. Non-cirrhotic hepatocellular carcinoma (HCC) is an increasingly recognised entity that constitutes over 20% of all HCC cases worldwide. However, contemporary reviews of non-cirrhotic HCC epidemiology have omitted data from Australasia, limiting representation of regions with distinct demographics and risk factor profiles. The diverse migrant and Indigenous populations of Australia and New Zealand include the Aboriginal and Torres Strait Islander peoples, Māori, and Pasifika. The high prevalence of chronic hepatitis B and rising burden of metabolic dysfunction-associated steatotic liver disease among this cohort highlight an urgent need for unbiased epidemiological overviews to inform equitable guideline development.

Key Words: Hepatocellular carcinoma; Non-cirrhotic; Metabolic dysfunction-associated steatotic liver disease; Hepatitis B; Hepatitis C; Australasia; Aboriginal and Torres Strait Islander people; Māori and Pasifika people

Core Tip: Global reviews of hepatocellular carcinoma (HCC) that exclude Australasian data risk overlooking important epidemiological patterns. In Australia and New Zealand, non-cirrhotic HCC accounts for a substantial proportion of cases, driven predominantly by chronic hepatitis B and an increasing burden of metabolic dysfunction-associated steatotic liver disease, particularly among Indigenous and migrant populations. Inclusion of Australasian data is essential for a truly comprehensive understanding of non-cirrhotic HCC risk and surveillance worldwide.

TO THE EDITOR

We read with interest the recent review article by Sato-Espinoza et al[1] entitled “Hepatocellular carcinoma in patients without cirrhosis” published in World Journal of Gastroenterology. While the authors state they provide a ‘comprehensive overview’ of global epidemiology, the complete omission of Australasian data represents a significant gap that undermines this claim. Although smaller in population than other continents, this region has a unique demographic composition, liver disease profile and evidence base that are essential to the global literature. These include a high prevalence of chronic hepatitis B (CHB) infection among indigenous communities (Aboriginal and Torres Strait Islander peoples, Māori and Pasifika) and significant disease burden among migrant communities and individuals of European, Asian, sub-Saharan African background in Australasia[2-4].

Non-cirrhotic hepatocellular carcinoma (HCC) is reported to account for 17%-43% of all HCC cases in Australia and New Zealand[5-7]. Data derived from a multicentre retrospective cohort study (2008-2021) revealed that in Australia, the major aetiology of non-cirrhotic HCC was CHB (36%), followed by metabolic-associated steatotic liver disease (MASLD; 28%) unknown (23%) hepatitis C virus (HCV; 12%), and alcohol-related liver disease (ARLD; 10%; Figure 1)[6].

Figure 1 Suggested addition to recommendations for hepatocellular carcinoma screening and surveillance by medical societies[1]. ALD: Alcohol-associated liver disease; ARLD: Alcohol-related liver disease; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MASLD: Metabolic dysfunction-associated steatotic liver disease. Citation: Sato-Espinoza K, Valdivia-Herrera M, Chotiprasidhi P, Diaz-Ferrer J. Hepatocellular carcinoma in patients without cirrhosis. World J Gastroenterol 2025; 31(23): 107100. Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc (Supplementary material).

In the CHB cohort, the annual incidence of HCC in those without cirrhosis is 0.4%-0.6% for Asian men older than 40 years and 0.3%-0.6% for Asian women older than 50 years[8]. Over 70% of people living with CHB in Australia were born overseas and 46% of this population were born in Asia[9]. People born in sub-Saharan Africa comprise 4.3% of all CHB infection cases in Australia[9], however there is no data on the incidence of HCC without cirrhosis in this population. The diverse migrant population results in a broad representation of HBV genotypes in Australia, with genotypes B and C predominating among Asian migrants and genotype D among European and Aboriginal populations[2,10]. These are precisely the genotypes the review identifies as having distinct oncogenic mechanisms even without cirrhosis. Inequalities in healthcare precipitate significant disparities in HCC incidence and mortality between the Aboriginal and Torres Strait Islander peoples and the non-indigenous population. For Indigenous and Torres Strait Islander people older than 50 years, the incidence of HCC in people living with CHB without cirrhosis is estimated to be 0.36%-0.9%[8], justifying their high-risk status that warrants HCC surveillance[8].

MASLD prevalence is growing rapidly in Australia, with an estimated 5.7 million Australians living with the disease in 2020 and MASLD-associated HCC is projected to increase by 75% by 2030[11]. Recent Australian data demonstrates that only 69% of MASLD-related HCC patients had overt cirrhosis, indicating that 31% developed HCC without cirrhosis—a proportion that aligns with or exceeds rates reported from North America and Europe in the review[12]. HCV and ARLD are the two major underlying liver diseases of HCC in Australia, constituting 41% and 39% of all HCC cases, respectively[8]. However, their representation in the non-cirrhotic HCC cohort remains unclear.

We would welcome the authors to include the current Gastroenterological Society of Australia guideline for HCC surveillance in their existing summary (Table 1), and suggest a revised figure that includes available Australian data (Figure 1), as well as reference a recently published clinical practice guidelines by George et al[13], which addresses gaps in HCC surveillance involving high-risk patients with non-cirrhotic liver disease and HCV-related advanced disease in the Australian population.

Table 1 Suggested addition to recommendations for hepatocellular carcinoma screening and surveillance by medical societies.

Medical societies	Cirrhotic individuals	Non-cirrhotic individuals	Both populations
	At-risk population	At-risk population additional notes	Surveillance tests	Frequency
GESA[14]	Individuals with Child-Pugh A or early B and Child-Pugh C if awaiting LT	Chronic HBV infection: (1) Asian men older than 40 years; (2) Asian women older than 50 years; and (3) People born in sub-Saharan Africa older than 20 years. Aboriginal and Torres Strait Islander people older than 50 years	Ultrasound + AFP	Every 6 months

GESA: Gastroenterological Society of Australia LT: Liver transplant; AFP: Alpha fetoprotein; HBV: Hepatitis B virus.

We wanted to ensure that the diverse populations, especially those in Australasian populations are not omitted in the medical literature. In conclusion, omitting an entire region from a review claiming to be ‘comprehensive’ undermines its utility as a global reference for clinicians and researchers and perpetuates the underrepresentation of diverse populations in medical literature. Australasia’s distinctive demographic diversity, including unique CHB prevalence and genotypic distribution, substantial Indigenous disease burden, and rapidly growing MASLD prevalence contribute valuable epidemiological perspectives that are essential for a truly global understanding of cirrhotic and non-cirrhotic HCC. We would encourage colleagues and journals to ensure there are safeguards to avoid geographic biases in future overviews, even if to say there is a lack of available data, to ensure that regional diversity is represented in the evolving understanding of the burden of gastrointestinal and liver diseases worldwide.