Since the inception of the first Asian–Pacific Association for the study of liver (APASL) hepatocellular carcinoma (HCC) working party in 2007 and the publication of its first guidelines in 2010 ]1] (revised in 2017) [2], major advances in systemic therapy for HCC have been made [3,1,2,3,4,5,6]. To date, despite the availability of effective HCC surveillance and preventive measures, most of the HCC still present at advanced stage as reflected by the high mortality–incidence ratio across the Asia–Pacific region [7], [8]. Most of these patients diagnosed with HCC are therefore beyond curative measures such as surgical resection, local ablation or liver transplantation [9]. This is further compounded by the scarcity of living donors and organs in the Asia–Pacific region which precludes patients with HCC eligible for liver transplantation as a curative measure [10].

Even for those patients who received curative-intent surgery, liver transplantation or local ablation in accordance to various HCC treatment guidelines, recurrence is still a very common clinical problem [11, 12]. The major etiology of HCC in Asia–Pacific region is chronic hepatitis B (CHB) and C (CHC) infection [13,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15], compounded by the recent rise of metabolic dysfunction-associated fatty liver diseases (MAFLD) [16]. In countries like China which accounts for nearly half of the global annual cases of HCC, CHB is the major etiology of HCC [7, 8]. In Japan, Egypt, and Mongolia, CHC plays a major role in causing HCC [13,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. In the recent few years, new targeted therapy and immune-checkpoint inhibitors (ICIs) have been registered as first-line or second-line therapy for HCC that is unresectable or not eligible for locoregional therapy [17,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. There are also emerging data to support the use of ICIs-based therapy to prolong progression-free survival after locoregional therapy and recurrence-free survival after local ablation or curative-intent surgical therapy for patients with HCC [31, 32]. The gravity of CHB and CHC as etiology of HCC in the Asia–Pacific region is of great relevance, as the response to ICIs has been suggested to be much higher, as compared to targeted therapy [33]. The purpose of this clinical practice guideline is to provide an up-to-date recommendation based on clinical evidence and experience from expert Asia–Pacific key opinion leaders in HCC.

In 2023, the steering committee of the Asian Pacific Association for the Study of the Liver (APASL) initiated the working party on the use of systemic therapy for HCC. To this end, a panel of experts from different disciplines in the Asia–Pacific region with diverse and vast experiences in the management of HCC was assembled. Hepatologists, oncologists (medical and radiation), surgeons (hepatobiliary and transplant), radiologists (diagnostic and interventional), immunologists, pathologists, oncologists and palliative care nurses from different administrative regions/countries in the Asia–Pacific region were invited to form a working party which formulated this clinical practice guidance for the use of systemic therapy for HCC. All panel members were required to disclose their relationships with industry during the guideline formulation until accepted for publication by Hepatology International (official journal of APASL). The Chairs were responsible for writing up the guidelines with the support of all panel members. All recommendations were categorized as strong recommendation (Grade 1) or weak recommendation (Grade 2) according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system (Table 1) [34]. The guidelines were also presented at the 33rd APASL annual conference held at Kyoto, Japan (26th to 31st April, 2024). Further comments were incorporated into the guidelines according to open discussion (Fig. 1).

Workflow of APASL systemic therapy for the HCC working party

With the evolving complexity in the management of HCC due to rapidly renewed understanding of the complex pathophysiologic and biological nature of HCC, expanded use of surgical resection and liver transplantation, and the continuous emergence and evolution of locoregional and ICIs-based systemic treatment, it is increasingly recognized that the multidisciplinary team (MDT) plays a crucial role in the comprehensive management of HCC. MDT should comprise specialists in multiple fields including hepatology, radiology, surgery, transplant surgery, interventional radiology, medical oncology, radiation oncology and palliative care. MDT could enable comprehensive discussions with collective expertise of the team in interpreting imaging, pathology results, formulating diagnoses and devising management strategies [35,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. This is supported by the cumulating evidence that MDT can offer significant benefits in patient diagnosis, treatment planning and overall survival outcomes [39,1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,