Epidemiological Profile of Hepatocellular Carcinoma in Brazil

Discussion

The progressive increase in the incidence and mortality of HCC in Brazil may reflect both a rising burden of chronic liver diseases–such as viral hepatitis, alcohol-related liver disease, and NASH− and improvements in diagnostic capability and reporting systems. However, persistent late diagnosis and limited access to effective treatments likely contribute to the observed rise in mortality, especially among men. This study found that only 38.7% of patients with HCC in Brazil received any form of treatment, despite treatment information being available for 98.6% of cases. This reveals a critical gap in access to oncological care in Brazil regardless of sex and may partly explain the high mortality rates observed in Brazilian patients with HCC. International data show similar trends. A population-based study in South Korea reported that 27.6% of newly diagnosed patients did not receive specific treatment and this percentage decreased from 33.4% in 2008 to 24.8% in 2013 (12).

In the United States, data from SEER-Medicare indicated that 70.3% of patients with HCC received either no active therapy or only palliative care (13). Among the patients with early-stage disease meeting the Milan criteria, 43% did not undergo curative surgery or ablation (14). In Ghana, nearly all patients received only supportive care, and up to 72% were eligible only for palliative management (15). These international findings confirm a global pattern of HCC undertreatment, largely driven by late-stage diagnosis, comorbidities, and substantial socioeconomic and structural barriers to specialized care (16, 17). Brazil’s untreated rate of 61.3% aligns with U.S. figures but is higher than that of countries such as South Korea, where centralized health systems and surveillance programs are well established. Nonetheless, it is not as extreme as in some low-income countries, such as Ghana. Brazil occupies an intermediate position, where universal health coverage has not yet ensured timely access to potentially curative therapies. This underscores the critical need to enhance oncology care networks by implementing active screening programs, optimizing early diagnostic pathways, and improving referral systems to specialized centers.

Another major finding was the high proportion of patients diagnosed at advanced or metastatic stages, particularly among women (52.8%). Overall, 46.9% of cases with staging data were classified as metastatic. This suggests that in Brazil, HCC is often diagnosed at a stage when curative treatments are no longer feasible. This scenario is partially consistent with the international literature. Clinical trials involving patients with advanced HCC, such as IMbrave150 and HIMALAYA, reported that 79-83% of the enrolled patients were classified as BCLC stage C (18). These data show that even in high-income settings, many patients receive a diagnosis only after the disease has advanced. However, in countries with a robust surveillance infrastructure, such as Taiwan, only 9.8% of patients with HCC are classified as BCLC stage C at diagnosis (19). This underscores the impact of structured follow-up systems for at-risk patients and the stronger integration between primary and specialized care. In African countries, such as Egypt, the situation is even more severe, with most HCC cases diagnosed at advanced stages. In this context, the Cancer of the Liver Italian Program system has been shown to be more predictive of prognosis than BCLC, although BCLC remains the globally accepted standard (20). These comparisons reinforce the fact that Brazil’s staging pattern resembles that of middle-income countries with limited access to early detection programs. Expanding surveillance protocols, promoting the use of tools such as Liver Imaging Reporting and Data System (LI-RADS), and improving access to diagnostic services–especially within the public healthcare system–are essential measures to reduce late-stage diagnoses.

A statistically significant sex disparity was observed in the surgical treatment for HCC in 2019, with 52.1% of women undergoing surgery compared to 35.3% of men (p<0.001). This finding is noteworthy, as surgery remains a primary curative treatment for HCC. International data on sex disparities in treatment are mixed. A recent JAMA Surgery study showed that women on liver transplant waitlists are less likely than men to receive a transplant, primarily due to body size differences affecting organ compatibility (21). In contrast, a U.S. SEER-based study found that women were more likely than men to undergo liver resection but less likely to receive a transplant (22). These patterns may reflect health system navigation biases, directing women toward certain procedures over others. In Germany, women were less likely to receive liver-directed therapies, such as transarterial or ablative treatments, which are associated with higher in-hospital mortality (23). In contrast, after adjusting for clinical and demographic factors, some studies suggest that women may have greater access to curative options, such as resection (24). Thus, the higher rate of surgical intervention among Brazilian women may mirror some international findings while diverging in key aspects. Although this trend could indicate better access or eligibility among women, the difference should be interpreted with caution, as greater access to surgery does not necessarily translate into improved survival-particularly in systems where delayed diagnosis and limited access to other treatment modalities remain challenges.

Patients in the SUS were more likely than those in the private healthcare sector to be of Black or Brown ethnicity, have lower educational levels, and be diagnosed at more advanced stages. Although early-stage diagnoses appeared to be slightly more frequent in the public system, this may reflect data incompleteness or reporting bias rather than true access advantages. Conversely, patients treated privately had greater access to early-stage diagnosis and curative treatment. These findings echo the global patterns. In South Africa, public-sector patients were more frequently diagnosed at advanced stages and had limited access to curative therapies, whereas private-sector patients had better outcomes (25). In USA, safety-net hospitals, which serve vulnerable populations, have reported lower rates of curative surgery and worse short-term outcomes (26). However, when surgery was performed, long-term outcomes were comparable, suggesting that disparities in access, rather than quality of care, are the main issue (27). Studies in China have also shown poorer survival among patients covered by basic health insurance than among those covered by employer-sponsored plans (28, 29). These global trends are mirrored in Brazil, where public system limitations in logistics, infrastructure, and access to specialized care contribute to worse outcomes. Expanding regional oncology reference centers, improving the integration between primary and specialist care, and implementing organized pathways for diagnosis and treatment are key to addressing these disparities and improving the outcomes of patients with HCC across the country.

Study limitations. It was based on a retrospective analysis of secondary data from national cancer registries (RCBP and RHC), which contain a high proportion of missing values, especially for variables such as staging, treatment type, and patient demographics. Inconsistencies in diagnostic and staging criteria across reporting institutions may have introduced classification biases. Additionally, the databases did not provide information on key clinical variables such as liver function [Child-Pugh and Model for End-Stage Liver Disease (MELD)], comorbidities, or treatment eligibility. It was also not possible to distinguish between patients who were clinically ineligible for treatment and those who did not receive care because of systemic access barriers. As hospital-based registries, these databases may not fully reflect the experiences of patients outside formal healthcare systems.

Given these findings, coordinated strategies are urgently required to improve early diagnosis and access to curative treatments for HCC in Brazil. Structured surveillance programs targeting at-risk populations particularly those integrated into primary care can promote earlier detection. Expanding the number of regional hepatobiliary oncology centers, standardizing clinical documentation practices, and training healthcare providers in proper cancer registry completion would enhance data quality and epidemiological monitoring. In addition, prospective multicenter studies incorporating detailed clinical data, such as liver function, performance status, and treatment eligibility, are essential to better understand the drivers of undertreatment and elevated mortality, enabling more effective and tailored interventions.