Systemic Therapy For Hepatocellular Carcinoma Research Articles

History and Evolution of Yttrium-90 Radioembolization for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and affects millions worldwide. Due to the lack of effective systemic therapies for HCC, researchers have been investigating the use of locoregional tumor control with Yttrium-90 (Y90) radioembolization since the 1960s. Following the development of glass and resin Y90 microspheres in the early 1990s, Y90 radioembolization has been shown to be a safe and efficacious treatment for patients with HCC across Barcelona Clinic Liver Cancer (BCLC) stages. By demonstrating durable local control, good long term outcomes, and equivalent if not superior tumor responses and tolerability when compared to alternative therapies including transarterial chemoembolization (TACE) and sorafenib, Y90 radioembolization is being increasingly used in HCC treatment. More recently, investigations into variations in Y90 radioembolization technique including radiation segmentectomy and radiation lobectomy have further expanded its clinical utility. Here, we discuss the history and evolution of Y90 use in HCC. We outline key clinical trials that have established the safety and efficacy of Y90 radioembolization, and also summarize trials comparing its efficacy to existing HCC treatments. We conclude by reviewing the techniques of radiation segmentectomy and lobectomy, and by discussing dosimetry.

The future is now: beyond first line systemic therapy in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is becoming a worldwide concern due to its rising incidence. Although for the incipient stages there are curative therapies, the advanced disease represents a major provocation for the clinicians. 2008 marked as an important year for the hepatology community with the administration of sorafenib for late stages of HCC. Six years after this major discovery, the multikinase inhibitor still represents an important pillar, the first line treatment for the advanced liver cancer. Lenvatinib may represent a new promising first line strategy, but it is still unavailable in many countries. The last years represented an explosion in the research of HCC. Beyond the first line treatments there are a plethora of new emerging therapies. By far immunotherapy represents the major revolution in oncology. While adoptive immunotherapy is still at the beginning, immune check-point inhibitors bursted in many clinical trials with very encouraging results. This review summarises the major discoveries in the field of HCC with an emphasis on immunotherapy. It also briefly describes the important aspects of primary liver cancer immunology and the major ongoing clinical trials.

Staging systems of hepatocellular carcinoma: A review.

Staging of hepatocellular carcinoma (HCC) is necessary for guiding prognostication, management, and research purposes that further aid in the improvement of existing clinical and epidemiological health services. Though there are some new staging systems for HCC developed in different parts of the world, there is no globally accepted staging system that allows for comparison of current management protocols among heterogeneous populations. In this review, we discuss the evolution and applicability in clinical practice of different clinical staging systems of HCC-Okuda, CLIP (Cancer of the Liver Italian Program) score, MESIAH (Model to Estimate Survival In Ambulatory HCC patients) score, ITA.LI.CA (Italian Liver Cancer) score, BCLC (Barcelona Clinic Liver Cancer) staging, HKLC (Hong Kong Liver Cancer) staging, and the Alberta algorithm. This review aims to highlight the main criteria for assessing the prognosis of HCC that these different staging systems take into account, their strengths and limitations for use in modern clinical practice. Despite the limitations of the BCLC staging system, it remains the most validated and reliable system for prognostication. However, there is a need to update the BCLC staging system to include recent data on locoregional and systemic therapies for HCC, expanded criteria for transplantation, and systemic therapy for hepatitis C infection.

Systemic Therapy for Hepatocellular Carcinoma: Latest Advances.

Systemic therapy for hepatocellular carcinoma (HCC) has changed drastically since the introduction of the molecular targeted agent sorafenib in 2007. Although sorafenib expanded the treatment options for extrahepatic spread (EHS) and vascular invasion, making long-term survival of patients with advanced disease achievable to a certain extent, new molecular-targeted agents are being developed as alternatives to sorafenib due to shortcomings such as its low response rate and high toxicity. Every single one of the many drugs developed during the 10-year period from 2007 to 2016 was a failure. However, during the two-year period from 2017 through 2018, four drugs—regorafenib, lenvatinib, cabozantinib, and ramucirumab—emerged successfully from clinical trials in quick succession and became available for clinical use. The efficacy of combination therapy with transcatheter arterial chemoembolization (TACE) plus sorafenib was also first demonstrated in 2018. Recently, immune checkpoint inhibitors have been applied to HCC treatment and many phase III clinical trials are ongoing, not only on monotherapy with nivolumab, pembrolizumab, and tislelizumab, but also on combination therapy with checkpoint inhibitors, programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) antibody plus a molecular targeted agent (bevacizumab) or the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, tremelimumab. These combination therapies have shown higher response rates than PD-1/PD-L1 monotherapy alone, suggesting a synergistic effect by combination therapy in early phases; therefore, further results are eagerly awaited.

Recent Advances of Systemic Therapy for Hepatocellular carcinoma

Recent Advances of Systemic Therapy for Hepatocellular carcinoma

Systemic therapies for hepatocellular carcinoma: a recap of the current status

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Battle Royale: Systemic Versus Locoregional Therapy for Unresectable Hepatocellular Carcinoma.

This commentary discusses research examining comparisons of locoregional therapy with systemic therapy for unresectable hepatocellular carcinoma (HCC). Comparison of patient outcomes after locoregional or systemic therapy for HCC is confounded by selection bias, wherein patients chosen for locoregional therapy usually have better underlying liver function that may contribute to the observed longer survival.

Cabozantinib (C) versus placebo (P) in patients (pts) with advanced hepatocellular carcinoma (HCC) who have received prior sorafenib: Results from the randomized phase III CELESTIAL trial.

207 Background: C, an inhibitor of MET, VEGFR, and AXL, has previously shown clinical activity in pts with advanced HCC. This phase 3 trial (NCT01908426) evaluated C vs P in previously treated pts with advanced HCC. Methods: In this double-blind, global, phase 3 trial, pts were randomized 2:1 to receive C (60 mg qd) or matched P stratified by disease etiology (HBV, HCV, other), geographic region (Asia, other), and presence of extrahepatic spread and/or macrovascular invasion (EHS/MVI). Eligible pts had pathologic diagnosis of HCC, Child-Pugh score A, ECOG PS ≤1, and must have received prior sorafenib. Pts received up to two lines of prior systemic therapy for HCC and must have progressed following at least one. The primary endpoint was overall survival (OS). Secondary endpoints were investigator-assessed progression-free survival (PFS) and objective response rate (ORR) per RECIST 1.1. The study was designed to detect a hazard ratio (HR) for OS of 0.76 (90% power, 2-sided α = 0.05) at the final analysis with two prespecified interim analyses at 50% and 75% of the planned 621 events. Results: As of 1 Jun 2017, 707 pts were randomized, and 484 deaths had occurred (317 out of 470 for C; 167 out of 237 for P). Baseline characteristics were balanced between the two arms: median age was 64 years, 82% were male, 38% had HBV, 24% had HCV, 25% enrolled in Asia, 78% had EHS, 30% had MVI, 85% had EHS/MVI, and 27% had received two prior systemic therapy regimens for advanced HCC. The study met the primary endpoint at the second planned interim analysis with median OS 10.2 mo for C vs 8.0 mo for P (HR 0.76, 95% CI 0.63-0.92; p = 0.0049). Median PFS was 5.2 mo for C vs 1.9 mo for P (HR 0.44, 95% CI 0.36-0.52; p < 0.001), and ORR was 4% vs 0.4% (p = 0.0086). The most common grade 3/4 adverse events (predominantly grade 3) with higher incidence in the C vs P arm included hand-foot skin reaction (17% vs 0%), hypertension (16% vs 2%), increased aspartate aminotransferase (12% vs 7%), fatigue (10% vs 4%), and diarrhea (10% vs 2%). Conclusion: C significantly improved OS and PFS vs P in previously treated pts with advanced HCC. Adverse events were consistent with the known safety profile of C. Clinical trial information: NCT01908426.

Abstract IA25: Targeted therapies for hepatocellular carcinoma

Abstract In 2008, the multikinase inhibitor Sorafenib consistently proved to extend the survival of patients with Hepatocellular Carcinoma (HCC) that were treated in the advanced stage and had a good liver function, and it became the first agent to be specifically approved for this indication (ref). Although Sorafenib was a paradigm shift in the field, systemic therapy of HCC remains a major unmet need. The mechanism of action of Sorafenib is still poorly understood and the same is true for the mechanism of resistance after initial response, which usually reveals as disease stabilization for a few months. Molecular biomarkers predicting response and resistance to Sorafenib are also hardly defined. Furthermore, all subsequent novel targeted agents or regimens tested in large randomized controlled trials both in the first-line and second-line setting have been unable to reach or improve the magnitude of benefit obtained with Sorafenib. Strategies under study have included the blockade of other pro-angiogenic signals such as the FGFR pathway using Brivanib, proliferative signals such as the EGFR pathway using Erlotinib, or cell growth, proliferation, angiogenesis and apoptosis signals arising from the PI3K-Akt-mTOR pathway using Everolimus. The relevance of targeting these pathways is still not completely understood since biomarker data have not been reported, including EGFR and FGFR expression in tumor specimens. Besides, a number of trials have definitively shown the lack of efficacy of Doxorubicin, used for decades as a systemic therapy for HCC patients without formal scientific evidence. And no survival benefit was proven for combination chemotherapy based on 5-fluorouracil and oxaliplatin. The door was then opened to a more focused approach in which only patients with an altered targeted pathway are deemed candidates for a given agent. The anticancer activity of the c-met tyrosine kinase inhibitor Tivantinib was suggested in a randomized, placebo-controlled trial in the second-line setting where patients with high c-met expression survived significantly longer if they received Tivantinib. Patient enrichment based on molecular targets has been incorporated into the clinical development of other agents such as a monoclonal antibody that binds to glypican-3 or Refametinib a tyrosine kinase inhibitor that targets the MAPK (Ras-Raf-MEK-ERK) pathway. Agents targeting novel signaling pathways including TGF-β and FGF19, but also less explored pathways such as Wntβ-catenin, Hedgehog or Notch are being studied for the treatment of HCC. We will soon learn whether or not this more selective approach translates into positive results. Identification of driver molecular events in an individual patient using markers from tumor biopsies has proven successful in other tumors including breast or lung cancer. However, the reliability of this strategy has been challenged by studies showing intratumoural heterogeneity in various malignancies at advanced stages. HCC needs to be explored in this regard. Citation Format: Bruno Sangro. Targeted therapies for hepatocellular carcinoma [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr IA25.

Optimal therapy for patients with hepatocellular carcinoma and resistance or intolerance to sorafenib: challenges and solutions.

The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin). Multi-target kinase inhibitors such as lenvantinib and regorafenib have recently met their primary endpoints as first- and second-line therapy, respectively, with regorafenib now representing the only FDA-approved drug for second-line treatment of HCC. Other targeted therapies remain under investigation, but results so far have not significantly changed clinical practice. Immunotherapy is an interesting area of research in the treatment of HCC with preclinical and early clinical data demonstrating exciting results; thus numerous investigational studies are currently focusing on immunotherapy in the treatment of HCC. While systemic treatment options in HCC remain a challenge for providers, in this review, we summarize the current literature and highlight areas of progress with respect to the treatment of patients with HCC and resistance or intolerance to sorafenib.

Prognostic scores for sorafenib-treated hepatocellular carcinoma patients: A new application for the hepatoma arterial embolisation prognostic score

BackgroundNo prognostic classification is currently used for patients treated with systemic therapies for Hepatocellular Carcinoma (HCC). MethodsWe retrospectively analysed data from patients treated with sorafenib for HCC from five centres in France and in the United Kingdom (UK). The training set comprised data from two centres and the validation set from three. Variables independently associated with Overall Survival (OS) in the training set were used to build the SAP (Sorafenib Advanced HCC Prognosis) score. The score was tested in the validation set, then compared with other prognostication systems. ResultsThe training set and validation set included 370 and 468 patients respectively. In the training set, variables independently associated with OS in multivariable analysis were: performance status (PS) >0, alpha-fetoprotein (AFP) >400 ng/ml, tumour size >7 cm, bilirubin >17 μmol/l and albumin <36 g/l. The SAP score was built giving one point to each abnormal variable, and three classes were constructed. The SAP score was significantly associated with OS in the training set, with median OS of 14.9 months for SAP A, 7.2 months for SAP B and 2.5 months for SAP C (P < 0.001). In the validation set, the SAP score was significantly associated with OS, and showed greater discriminative abilities than Barcelona Clinic Liver Cancer (BCLC) and albumin-bilirubin (ALBI) scores. However, the hepatoma arterial embolisation prognostic (HAP) score showed greater discriminative abilities than the SAP score. ConclusionIn European patients treated with sorafenib, the HAP was the most discriminant prognostic score and may facilitate stratification in trials and inform clinical decision making.

Radiologic criteria of response to systemic treatments for hepatocellular carcinoma

Sorafenib has been the only approved systemic therapy for hepatocellular carcinoma until very recently. However, the radiologic assessment of its biological activity is a disputed matter as at least five different criteria have been proposed. In this review, we describe the characteristic of the Response Evaluation Criteria In Solid Tumors (RECIST), European Association for the Study of The Liver (EASL), modified RECIST (mRECIST), Response Evaluation Criteria In the Cancer of the Liver (RECICL) and Choi criteria. The existing comparative studies are reported together with recent pieces of evidence, analyzing the reasons behind the split between recommendations of the scientific societies and regulatory agencies. Future perspectives in the wake of the impending results of the immunotherapy trials are also discussed.

Functional Imaging and Assessment of Antitumor Activity in Systemic Therapy for Hepatocellular Carcinoma.

AbstractIncreasing use of novel systemic treatment options in the management of patients with advanced hepatocellular carcinoma (HCC) such as antiangiogenic and molecular-targeted therapies, poses unique challenges for effective treatment monitoring and efficacy assessment. The traditional morphological criteria such as response evaluation criteria in solid tumor (RECIST) rely on changes in tumor size to determine treatment efficacy. However, these criteria based on tumor morphology may not be suitable to monitor response to newer targeted therapies as early functional changes induced by these drugs precede changes in tumor size. Modifications of these morphological criteria that determine response based on tumor enhancement characteristics such as modified RECIST (mRECIST) will potentially allow improved determination of treatment response pending validation from prospective trials. Advanced functional imaging techniques such as perfusion imaging (computed tomography/magnetic resonance imaging [CT/MRI]), diffusion weighted MRI (DW-MRI) and positron emission tomography (PET/CT and PET/MRI) are being increasingly used as surrogate imaging biomarkers to provide superior assessment of changes in tumor physiology. Growing emphasis on precision oncological care tailored to specific tumor type and individual patients renders the use of these newer imaging modalities more pertinent and timely. In this review, the authors discuss the role of various imaging techniques and response assessment criteria in the evaluation of systemic therapy for advanced HCC with focus on functional imaging tools.

Postsorafenib systemic treatments for hepatocellular carcinoma: questions and opportunities after the regorafenib trial.

The search for systemic therapies for hepatocellular carcinoma has been characterized by difficulties and failures. Despite recent progresses, many issues are still to be settled. In particular, the development of drugs inhibiting different neoplastic pathways remains a priority for patients intolerant or resistant to antiangiogenic drugs. This task may be daunting, as previous failures extensively demonstrated. We aimed to identify the future perspective of postsorafenib trials analyzing the strengths and the critical points of past and currently undergoing studies, in the light of the most recent evidences in the field. We identified various points (including stratification, biomarkers, end points, radiologic criteria of response, treatment beyond radiologic progression) that should be considered by future trials to reduce the risks of failure.

A prospective biomarker study to assess IGF-1 score ability to sub-stratify Child-Turcotte-Pugh classes and predict response to systemic therapy in hepatocellular carcinoma.

e15662 Background: Our recent studies showed that lower insulin like growth factors-I (IGF-I) associated with shorter overall survival (OS) in HCC. Furthermore, integrating IGF-I into Child Pugh Score (CTP) (IGF-CTP) led to better prognostic stratification (Kaseb et al., JNCI 2014). Since CTP class A is the standard criterion for active therapy and trials entry, we aimed at assessing the ability of IGF-CTP to predict systemic therapy outcome. Methods: 78 patients were prospectively enrolled and treated with sorafenib. Pre-treatment blood sample were tested for IGF-I and IGF-CTP was calculated after study completion. Survival analysis was done to measure the estimated median OS and progression free survival (PFS), and log rank test was used to compare PFS and OS between subgroups of IGF-CTP score of patients. Results: For CTP A patients, the estimated median OS in months (95% confidence interval, CI) was 9.1m (5.3 – 19.7) and PFS was 5.6m (3.8 – 7.9). Patients who were reclassified as IGF-CTP (B) (OldA/newB = AB) had significantly shorter OS 5.2m (2.8 - NA) and PFS of 4.3m (2.1 – NA), as compared to patients’ who classified as class A by both scoring systems (AA), who had OS of 11.1m (5.7 – 21.3) and PFS of 7.2 m (3.9 – 15.1), P &lt; .001. Interestingly, patients who classified as CTP-B but IGF-CTP-A ( = BA) had significantly longer OS 10.2 (2.89 – NA) and PFS 8.1 (2.9 – NA), as compared to (BB) patients who had OS of 5.8 (3.2 –NA) and PFS of 5.1 (3.19 – NA), P &lt; .001 Conclusions: Our study concluded that IGF-CTP score was more accurate than original CTP score in predicting survival outcomes of systemic therapy in HCC. If validated, this approach may change the standard stratification criteria for active therapy in routine clinical practice and patient selection for clinical trial entry in HCC.

NatB-mediated protein N-α-terminal acetylation is a potential therapeutic target in hepatocellular carcinoma.

The identification of new targets for systemic therapy of hepatocellular carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB catalyzes the N-α-terminal acetylation of 15% of the human proteome and that this action is necessary for proper actin cytoskeleton structure and function. In tumors, cytoskeletal changes influence motility, invasion, survival, cell growth and tumor progression, making the cytoskeleton a very attractive antitumor target. Here, we show that hNatB subunits are upregulated in in over 59% HCC tumors compared to non-tumor tissue and that this upregulation is associated with microscopic vascular invasion. We found that hNatB silencing blocks proliferation and tumor formation in HCC cell lines in association with hampered DNA synthesis and impaired progression through the S and the G2/M phases. Growth inhibition is mediated by the degradation of two hNatB substrates, tropomyosin and CDK2, which occurs when these proteins lack N-α-terminal acetylation. In addition, hNatB inhibition disrupts the actin cytoskeleton, focal adhesions and tight/adherens junctions, abrogating two proliferative signaling pathways, Hippo/YAP and ERK1/2. Therefore, inhibition of NatB activity represents an interesting new approach to treating HCC by blocking cell proliferation and disrupting actin cytoskeleton function.

Locoregional and systemic therapy for hepatocellular carcinoma.

The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib. Given recent data, regorafenib is now an option following failure of sorafenib. Catheter directed intra-arterial therapy takes advantage of tumor hypervascularity and the unique dual blood supply of the liver, as hepatic tumors receive arterial perfusion via the hepatic artery while the rest of the liver is supplied by the portal vein. This allows selective embolization and delivery of chemotherapeutic agents to the tumor. Compared to best supportive care, intra-arterial therapy offers a survival benefit in intermediate stage HCC and is the recommended approach for treatment. None of the catheter based approaches; including bland embolization, conventional trans-arterial chemoembolization (cTACE), drug eluting bead trans-arterial chemoembolization (DEB-TACE) or trans-arterial radioembolization (TARE) offers a clear advantage over the other, although DEB-TACE may be characterized by less systemic toxicity. All of these approaches are contraindicated in patients with portal vein thrombosis (PVT). On the other hand, intra-arterial, radio embolization, with Yttrium-90 (Y90) can be offered to patients with PVT. The place of this modality in management of HCC is still being investigated. The role of sorafenib in advanced HCC is not in doubt, as until recently, it was the only systemic therapy approved for the management in this setting. This is despite multiple trials evaluating other agents. The addition of sorafenib to catheter-based therapy in intermediate stage disease has also failed to show any benefit. The modest survival benefit with sorafenib and the failure of other targeted agents suggest that it is important to look beyond inhibition of angiogenesis in advanced HCC. Identification of key drivers and mediators of HCC remains paramount for successful drug development. In line with this, it is refreshing that the excitement that has followed developments in cancer immunotherapy is finding its way to HCC with early trials of anti-PD1 monoclonal antibodies showing sufficient activity that phase III trials are now ongoing for Pembrolizumab and Nivolumab in advanced HCC. Future drug development efforts will focus on defining the feasibility of combining different treatment approaches targeting multiple important modulators of HCC.

Diagnosis and systemic therapy for hepatobiliary cancer

Cancer of the liver, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), is the second most common cause of cancer-related death, and its incidence rate is increasing. Clinical diagnosis is made by imaging methods based on contrast-enhanced techniques; some special types that include mixed differentiation may be picked up on biopsy. Advanced tumour stages are treated with systemic therapy. In HCC, therapy with the multikinase inhibitor sorafenib is established and new second-line therapies are expected. In CC, however, gemcitabine and cisplatin is standard in first-line therapy. This review highlights the diagnostic possibilities and current developments in the systemic therapy of HCC and CC.

PCN7 - A Systematic Review and Meta-Analysis To Access The Efficacy and Safety of Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

Although, sorafenib is considered as the standard systemic therapy for HCC, its efficacy & safety profile needs to be further explored. This research aims to further explore the efficacy and safety of sorafenib in recently published trials in patients with advanced HCC. This review is an update to meta-analysis conducted by Pang et al. (2014). For the current analysis, PubMed and Cochrane databases were searched for randomized controlled trials (RCTs) published from 2013 to 2016. Randomized controlled trials which compared Sorafenib with other active comparators were selected as per pre-defined inclusion criteria. The outcomes included overall survival (OS), time to progression (TTP) and adverse event profile. Two reviewers independently extracted data from the included studies. Data was analysed using RevMan (v5.3). Of the total 168 studies retrieved from database searches, three studies were included for data extraction and analysis with 1643 patients randomised to Sorafenib and 1621 patients randomised to comparator groups. Median overall survival with sorafenib ranged from 9.8 months to 10.2 months as compared to 7.9 months to 9.5 months with comparator groups. The median TTP was comparable with other groups and ranged from 3.8 months to 4.1 months with sorafenib. The overall adverse event profile of sorafenib was similar to comparator groups and grade 3/4 AE profile was significantly better than linifanib (p<0.001). The grade 3/4 AEs were more frequent with sunitinib and brivanib as compared to sorafenib. The results of meta-analysis will be presented in the poster as this is work-in-progress. In advanced HCC, sorafenib had similar OS as compared to linifanib and brivanib. Further, sorafenib had significantly superior or equivalent OS to sunitinib. Safety results favored sorafenib in all the three trials.

Treatments of Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection: Treat HBV-related HCC

There have been major advances recently on the therapeutic approaches of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Surgical treatments are the key curative treatments of HCC, whereas local ablative treatments may also achieve clinical remission in selected cases. Trans-arterial locoregional therapies are regarded as palliative but still lead to improved survival. There have been major breakthroughs in the systemic therapies for HCC. The first marketed targeted therapy, sorafenib, was shown to improve survival in patients with advanced HCC. Studies on other targeted therapies also showed promising results. Suppressing HBV with effective antiviral treatment would also benefit HCC patients by reducing recurrence and improving liver function.