Treatment Options For Hepatocellular Carcinoma Research Articles

Updates in the Systemic Treatment of Hepatocellular Carcinoma

Oncology drug development has recently introduced new systemic treatment options for hepatocellular carcinoma (HCC). Here we consider the general approaches to diagnostic workup, staging, and overall management of HCC with emphasis on systemic treatment options based on recent phase III clinical trials. Novel drug targets involving immunotherapy may change how we treat HCC in the near future.

Apatinib is effective for treatment of advanced hepatocellular carcinoma.

As treatment options for hepatocellular carcinoma (HCC) are currently limited, we evaluated the efficacy and safety of oral apatinib, a VEGFR-2 inhibitor, on patients with advanced HCC. Twenty-two patients from Tianjin Medical University Cancer Institute and Hospital were enrolled for evaluation. Apatinib was administered at 500 mg/day or 250 mg/day continuously. Clinical endpoints were time to disease progression (TTP), overall survival (OS), and safety. The median TTP of treated patients was 10.4 months (95% CI 3.4 -17.5). At the last follow-up, 50% patients had survived longer than 11.4 months from the first dose. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) rates were 0%, 40.9%, 40.9%, and 18.2%, respectively. The most common apatinib-related adverse events were hand-foot skin reaction (HFSR) (81.8%) and diarrhea (77.3%). Hypertension (27.3%) and HFSR (13.6%) were the most frequent grade 3/4 adverse events. In summary, results of this small study indicate that apatinib is well tolerated and extremely effective for the treatment of advanced HCC. It is therefore imperative to design and carry out well-controlled clinical trials to confirm its efficacy.

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.

Yes-associated protein: A novel molecular target for the diagnosis, treatment and prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common type of malignant tumor. The early-diagnosis and treatment options for HCC are limited, which is primarily due to an incomplete understanding of the underlying molecular mechanisms of the disease. Yes-associated protein (YAP) overexpression promotes proliferation and phenotypic transformation of HCC cells. Recently, elucidating the molecular mechanisms of the Hippo/YAP signaling pathway and investigating the interactions between the signaling molecules, as a potential strategy for the treatment of HCC, has become an area of interest. The present review will discuss the role of YAP in HCC pathogenesis, and the significance of YAP in diagnosis, treatment and determining the prognosis.

Individualized multidisciplinary treatment options for hepatocellular carcinoma in the department of liver surgery: experiences in Xiangya Hospital of Central South University

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease. Genomic and morphological heterogeneity has been well identified in HCC. The overall survival (OS) of HCC patients after hepatic resection (HR) is heterogeneous. The histology-based definition of the morphological heterogeneity of HCC has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. In this review article, we aim to give a summary of the recent the development of individualized multidisciplinary treatment for HCC.

Lidocaine Induces Apoptosis and Suppresses Tumor Growth in Human Hepatocellular Carcinoma Cells In Vitro and in a Xenograft Model In Vivo.

Recent epidemiologic studies have focused on the potential beneficial effects of regional anesthetics, and the differences in cancer prognosis may be the result of anesthetics on cancer biologic behavior. However, the function and underlying mechanisms of lidocaine in hepatocellular carcinoma both in vitro and in vivo have been poorly studied. Human HepG2 cells were treated with lidocaine. Cell viability, colony formation, cell cycle, and apoptosis were assessed. The effects of lidocaine on apoptosis-related and mitogen-activated protein kinase protein expression were evaluated by Western blot analysis. The antitumor activity of lidocaine in hepatocellular carcinoma with or without cisplatin was investigated with in vitro experiments and also with animal experiments. Lidocaine inhibited the growth of HepG2 cells in a dose- and time-dependent manner. The authors also found that lidocaine arrested cells in the G0/G1 phase of the cell cycle (63.7 ± 1.7% vs. 72.4 ± 3.2%; P = 0.0143) and induced apoptosis (1.7 ± 0.3% vs. 5.0 ± 0.7%; P = 0.0009). Lidocaine may exert these functions by causing an increase in Bax protein and activated caspase-3 and a corresponding decrease in Bcl-2 protein through the extracellular signal-regulated kinase 1/2 and p38 pathways. More importantly, for the first time, xenograft experiments (n = 8 per group) indicated that lidocaine suppressed tumor development (P < 0.0001; lidocaine vs. control) and enhanced the sensitivity of cisplatin (P = 0.0008; lidocaine plus cisplatin vs. cisplatin). The authors' findings suggest that lidocaine may exert potent antitumor activity in hepatocellular carcinoma. Furthermore, combining lidocaine with cisplatin may be a novel treatment option for hepatocellular carcinoma.

Factors Related to Hepatocellular Carcinoma Recurrence After Liver Transplantation—A Brazilian Multicenter Study

BackgroundLiver transplantation (LT) is a curative treatment option for hepatocellular carcinoma (HCC); recurrent HCC after liver transplantation (HCC-R) is diagnosed in 9%–16%. The objective of this study was to evaluate which factors are associated with R-HCC after liver transplantation. MethodsThis retrospective real-life study analyzed 278 LTs from 3 reference centers (2,093 LTs) in Brazil from 1988 to 2015. HCC-R with histologic confirmation was seen in 40 patients (14.4%). ResultsMost of them were male with cirrhosis secondary to viral hepatitis. Only 37.5% underwent chemoembolization, and 50% had cold ischemia time >8 hours. From the explant analysis, most of the patients were outside Milan criteria and 37.5% had microvascular invasion. The donors were mostly male, and the median intensive care unit time was >3 days. The Kaplan-Meier survival was lower according to alpha-fetoprotein (AFP) >200 ng/dL (P = .02), and older donors and more blood transfusions were risk factors for HCC-R death. ConclusionAFP >200 ng/mL was associated with lower survival, and older donors and more blood transfusions were risk factors for death after HCC-R. A trend to lower survival was observed in patients who did not have chemoembolization and had cold ischemia times >8 hours.

Safety and efficacy of HepaSphere 50–100 μm in the treatment of hepatocellular carcinoma

Aim: To evaluate the effects of HepaSphere 50–100 μm (Merit Medical) as a doxorubicin carrier and embolization agent for the treatment of hepatocellular carcinoma (HCC).Material and methods: A prospective analysis of 18 patients recruited from a national cancer center was conducted. This analysis evaluated the efficacy and safety of HepaSphere, as expressed by the treatment response rate (measured by the modified Response Evaluation Criteria in Solid Tumors, mRECIST) and by the prevalence of treatment-related adverse events, respectively.Results: The cohort was predominantly male, with a mean age of 69 years. The objective response rate (complete + partial response) was 53.3%. The variable most likely to be associated with objective response was Barcelona Clinic Liver Cancer (BCLC) staging. The most prevalent adverse events were nausea, vomiting and abdominal pain.Conclusion: HepaSphere chemoembolization yielded a substantial objective response rate with an acceptable toxicity profile and should be considered an option for HCC treatment.

Cytotoxic clerodane diterpenoids from Croton crassifolius

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and treatment options for HCC are limited. In addition, the discovery of new natural compounds with anti-hepatocarcinoma activity is attracting increasing attention. For this reason, phytochemical investigation of Croton crassifolius led to the isolation of 17 diterpenoids, including three new clerodane diterpenoids, named crassifolius A-C (1–3), along with 14 known ones (4–17). Their structures were established by 1D, 2D NMR, HR-ESI-MS, detailed calculated electronic circular dichroism (ECD) spectra and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. The cytotoxicities of all these compounds against human liver cancer lines (HepG2 and Hep3B) were determined. Among them, compound 1 exhibited good cytotoxicity with IC50 value of 17.91μM against human liver tumor cells Hep3B. Following further studies of the anti-tumor mechanism of compound 1-induced cell growth inhibition, we found that compound 1 caused apoptotic cell death in Hep3B cells by detecting morphologic changes and Western blotting analysis.

Outcome Results of Treatment with Selective Internal Radiation Therapy (SIRT) in Patients with Hepatocellular Carcinoma: A Single Center Experience

Background: Hepatocellular carcinoma (HCC) has a poor prognosis. Selective internal radiation therapy (SIRT) with microspheres is a treatment option for HCC. This study aimed to assess safety and survival (OS) in patients with HCC treated with SIRT, to stratify patients with tumor vascularization and analyze the impact of sequential sorafenib treatment. Methods: Thirty-nine patients who received SIRT for HCC between 2010 and 2013 at our center were included in this retrospective analysis. Tumor vascularization was assessed using a combination of MRI, MAA-scintigraphy and angiography. Tumor vascularization was correlated with survival. Subgroups are treated with two commercially available 90Y-labeled products SIR-Spheres (n = 16) and TheraSpheres (n = 23) and sequential therapy with sorafenib compared to SIRT only was analyzed. Results: Adverse events occurred in 49% of patients with only four grade 3 and no grade 4 event. Median survival for all patients was 12.5 months (95% CI: 8.7 - 16.3). No significant differences were detectable between Thera Spheres or SIR Spheres. Survival was shorter in patients with low tumor vascularization score (OS: 3.8 months (95% CI 0 - 15.0), p = 0.043). Survival was longer with sorafenib upon progression after SIRT (n=16) with an OS of 17.4 months (95% CI: 12.1 – 22.7) compared to no sorafenib (n = 13; 9.1 months; 95% CI: 3.0 - 15.1) or progression upon sorafenib before SIRT (n = 10; 8.6 months; 95% CI: 5.5 - 11.7). Conclusions: SIRT is safe in HCC patients. Tumor vascularization by radiography and scintigraphy may predict survival benefit. Sorafenib is active after SIRT and significantly prolongs survival.

Hepatocellular Carcinoma. Part 3: Surgical and Medical Treatment

Hepatocellular carcinoma (HCC) treatment is variable and depends on the size, location, and presence of extra hepatic metastasis and vascular invasion. HCC treatment options have advanced significantly over the past few decades and include surgical and non-surgical methods. In the past, systemic chemotherapy was the non-surgical treatment and there was no significant increase in overall survival rate. Nowadays sorafenib, a molecular targeted drug, is the treatment of choice and has shown proven benefits in increasing survival time; other systemic therapies did not show longer statistical superiority. However, surgical treatments, such as liver transplantation and surgical resection, are still the only methods offering a curative opportunity; however, these are not free of adverse effects and recurrence of the tumour. Non-surgical techniques including ablative treatment, radiotherapy, transarterial chemoembolisation, and percutaneous ethanol injection also show some benefit in the survival of patients with HCC. Future molecular targeted drugs are currently under investigation in different stages of clinical trials, and there are positive expectations regarding their benefit in treating HCC.

Promising new strategies for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide. It usually arises based on a background of chronic liver diseases, defined as the hypercarcinogenic state. The current treatment options for HCC ranging from locoregional treatments to chemotherapies, including sorafenib, effectively regulate the limited sizes and numbers of the nodules. However, these treatments remain unsatisfactory because they have insufficient antitumor effects on the large and numerous nodules associated with HCC and because of a high recurrence rate in the surrounding inflamed liver. To develop novel and promising therapies with higher antitumor effects, recent progress in identifying molecular targets and developing immunological procedures for HCC are reviewed. The molecular targets discussed include the intracellular signaling pathways of protein kinase B/mammalian target of rapamycin and RAS/RAF/mitogen-activated protein kinase, Wnt/β-catenin and glutamine synthetase, insulin-like growth factor, signal transducer and activator of transcription 3, nuclear factor-κB and telomerase reverse transcriptase, and c-MET. Immunological studies have focused mainly on target identification, T cells, natural killer cells, dendritic cells, natural killer T cells, and vaccine development.

Advances in How We Prioritize Liver Allocation for Hepatocellular Carcinoma in the USA

Treatment options for hepatocellular carcinoma (HCC) have changed significantly, beginning in 1994 with the establishment of successful long-term outcomes for HCC patients within Milan criteria who went on to receive liver transplantation (LT). Improved outcomes for patients with HCC undergoing LT led to challenges in determining the optimal liver allocation policy, which could provide relatively equal access for patients with and without HCC in the face of a long-standing critical shortage of available donor organs. United Network for Organ Sharing/Organ Procurement Transplantation Network (UNOS/OPTN) policy changes have aimed to optimize data collection for patients transplanted with HCC, improve the diagnostic criteria required for HCC, and reduce the disparity in access to transplantation for HCC and non-HCC patients observed between high- and low-model for end-stage liver disease (MELD) regions. Although current understanding of HCC tumor biology remains suboptimal, continued careful analysis of waitlist and post-transplant outcomes for both HCC and non-HCC patients combined with refinements to the allocation policy will hopefully result in improved survival both for waitlisted and post-transplant patients.

Validation of Kinki Criteria, a Modified Substaging System, in Patients with Intermediate Stage Hepatocellular Carcinoma

Background: The standard treatment option that is available for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is transarterial chemoembolization (TACE). However, the condition of the patients with BCLC stage B disease is heterogeneous showing different tumor statuses and Child-Pugh scores; treatment strategies other than TACE are frequently employed for the patients in this stage. Based on the subclassification system proposed by Bolondi et al. [Semin Liver Dis 2012;32:348-359], we developed the Kinki criteria focusing on a substaging for BCLC stage B disease, which is simpler and should be more suitable in actual clinical setting in Japan. In this study, we evaluated the performance of Kinki criteria. Summary: This study included 1,633 HCC patients who received first-line treatment at the Kindai University Hospital. Patients were classified into subgroups based on the Kinki criteria and the survival time was estimated for each group. There were 156 (33.3%) patients in subclass B1, 278 (59.3%) in B2, and 35 (7.4%) in B3. The median overall survival times and 95% CI for BCLC B subclasses B1, B2, and B3 were 4.3 years (3.7-4.9), 2.9 years (2.2-3.4), and 1.1 years (0.5-1.8), respectively (p < 0.001). Key Messages: Classification of HCC patients in BCLC stage B based on the Kinki criteria showed statistically significant differences in survival, indicating the performance of Kinki criteria, which takes Child-Pugh score and tumor status into account for determining treatment options for HCC in BCLC stage B.

Radio-frequency ablation-based studies on VX2rabbit models for HCC treatment.

Hepatocellular carcinoma (HCC) is the fifth most frequent cancer worldwide with high morbidity, mortality and increasing incidence. It is of note that the main curative therapies for HCC are hepatic resection and transplantation although the majority of patients at the time of presentation are not eligible for resection or orthotopic liver transplantation (OLT) due to the underlying cirrhosis. Currently, a variety of loco-regional therapies, including radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), microwave coagulation therapy (MCT), transarterial chemoembolization (TACE) and others, have been developed as alternative treatment options for HCC. Among these techniques, RFA is currently the most widely used treatment, due to its several advantages, such as safety and efficacy. To date, the effectiveness of RFA for HCC is reduced by the presence of residual tumor as a consequence of insufficient treatment. In order to ameliorate the effects of RFA on HCC, several in vivo studies, have been performed on its application as single or in combination treatment with drugs or others loco-regional therapies, by using rabbit VX2 liver model. This represents an ideal model of liver cancers and is widely used for imaging and other experimental studies due to the rapid growth of these tumors and their similarity to human hepatocellular carcinoma. In order to elucidate the therapeutic potential of RFA with adjuvant treatments for HCC, we reviewed the latest findings on the RFA-based studies in rabbit VX2 hepatocarcinoma models.

Transarterial chemoembolization of hepatocellular carcinoma with segmental portal vein tumour thrombus.

To evaluate the clinical outcome and safety of transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with segmental or subsegmental portal vein tumour thrombus (sPVTT) in patients with preserved hepatic function, and to address the efficacy of additional chemoinfusion after TACE (TACE+CI). From January 2003 to December 2012, TACE was conducted on 81 patients with Child-Pugh score ≤7 who had HCC with sPVTT. Thirty-one of them underwent TACE+CI. The overall survival (OS) and serious adverse events (SAEs) were evaluated. The efficacy of TACE+CI was appraised after adjustment with inverse probability of treatment weighting (IPTW). The OS after TACE (median, 15.5months) was significantly related with aspartate aminotransferase (hazard ratio [HR], 1.011), modified Barcelona Clinic Liver Cancer (BCLC) stage D (HR, 2.841), extrahepatic spread (HR, 4.862), and TACE+CI (HR, .367). The SAE incidence was significantly associated with modified BCLC stages (HR, 10.174 [proper-C] and 24.000 [D]). After IPTW adjustment, TACE+CI significantly improved OS (p = .028; HR, .511), but the SAE incidence was not significantly altered (p = .737; HR, .819). TACE can be an effective and safe treatment option for HCC with sPVTT in patients with preserved hepatic function. Furthermore, additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety. • TACE is effective and safe for treating HCC with sPVTT. • Modified BCLC stages can stratify the risk and benefit of TACE. • Additional chemoinfusion can enhance the therapeutic efficacy while maintaining the safety.

Abstract 3781: Combination therapy with a liver selective acetyl-CoA carboxylase inhibitor ND-654 and sorafenib improves efficacy in the treatment of cirrhotic rats with hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is increasing in incidence worldwide. Current treatment options for HCC are limited, and as such, prognosis is extremely poor with a 5-year survival less than 12%. Sorafenib is the only FDA-approved drug for the treatment of HCC but its effects are marginal as it only extends survival by a few months. Therefore, new treatment options are urgently needed. Metabolic attenuation is a promising approach to cancer therapy, and rate-limiting steps in key biosynthetic pathways are particularly attractive targets. We recently identified ND-654, a hepatoselective (∼3000:1 liver to muscle exposure), allosteric ACC inhibitor that binds to the ACC subunit dimerization site and inhibits the enzymatic activity of both ACC1 (IC50 = 3 nM) and ACC2 (IC50 = 8 nM). Daily oral administration of 10 mg/kg ND-654 reduced tumor incidence by 55% and significantly improved median survival time in a rat model of cirrhosis and HCC. Here, we examine the effects of ND-654 alone and in combination with sorafenib on HCC development in cirrhotic rats. Methods: Male Wistar rats were treated once weekly with 50 mg/kg diethylnitrosamine (DEN) for 18 weeks to induce sequential development of fibrosis, cirrhosis and HCC. After establishment of cirrhosis and when HCCs are first developing (13 weeks), rats were treated daily by oral gavage with either 1) vehicle control, 2) 10 mg/kg ND-654, 3) 10 mg/kg sorafenib, or 4) 10 mg/kg ND-654 and 10 mg/kg sorafenib. After 18 weeks, tumor nodules were counted and liver and tumor tissue was harvested for analysis. Results: Similar to our previous study, simultaneous inhibition of ACC1 and ACC2 significantly reduced HCC incidence by 41% (p &amp;lt; 0.05) which was comparable to results with sorafenib (57% reduction, p &amp;lt; 0.01). Remarkably, the combination of ND-654 and sorafenib significantly reduced HCC incidence by 81% (p &amp;lt; 0.001). We are currently examining the effects of combining ND-654 and sorafenib on markers of tumor proliferation and apoptosis. Conclusions: These results provide further evidence that de novo lipogenesis is an important mediator of hepatic carcinogenesis and that selective inhibition of hepatic ACC is a viable cancer metabolism therapeutic strategy for treating HCC that could be combined with sorafenib. Citation Format: Lan Wei, Geraldine Harriman, Sarani Ghoshal, Omeed Moaven, Jeremy Greenwood, Sathesh Bhat, William F. Westlin, H. James Harwood, Rosana Kapeller, Kenneth K. Tanabe, Bryan C. Fuchs. Combination therapy with a liver selective acetyl-CoA carboxylase inhibitor ND-654 and sorafenib improves efficacy in the treatment of cirrhotic rats with hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3781.

Circulating microRNAs for early detection of hepatitis B-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a major challenge for global health. Indeed, HCC represents the third leading and fastest rising cause of cancer death worldwide (1). About 90% of HCC cases can be associated with a well-characterized underlying risk factor including chronic hepatitis B, hepatitis C, ethanol consumption, aflatoxin exposure, non-alcoholic fatty liver disease, metabolic diseases like diabetes, and hereditary liver disease (1-3). Although the risk of developing HCC can be reduced in patients by treatment of the underlying cause, e.g., by viral clearance, strategies to prevent cancer development in patients with advanced fibrosis and established cirrhosis are still lacking (4). Furthermore, despite the recent improvements, treatment options for HCC remain largely unsatisfactory (5). Early diagnosis through surveillance of at-risk patients increases the chance of effective therapy. Clinical practice guidelines recommend periodic ultrasound-based surveillance of patients with cirrhosis (6). However, ultrasound detection of small liver tumors can be challenging and depends on the expertise of the operator. Therefore, several non-invasive biomarkers have been assessed for their utility in determining HCC risk and/or detecting HCC at early stages. Alpha-fetoprotein (AFP) is the most widely used diagnostic serum marker for HCC. However, since its diagnostic and predictive value is largely limited by the presence of AFP-negative HCC as well as the impact of the underlying liver disease (2,6), its use for HCC surveillance is currently not recommended by American and European guidelines. Thus there is an unmet need for novel serum biomarkers for HCC diagnosis capable of increasing the diagnostic and predictive power in surveillance programs.

Management of hepatocellular carcinoma: anoverview of major findings from meta-analyses.

This paper aims to systematically review the major findings from meta-analyses comparing different treatment options for hepatocellular carcinoma (HCC). A total of 153 relevant papers were searched via the PubMed, EMBASE, and Cochrane library databases. They were classified according to the mainstay treatment modalities (i.e., liver transplantation, surgical resection, radiofrequency ablation, transarterial embolization or chemoembolization, sorafenib, and others). The primary outcome data, such as overall survival, diseases-free survival or recurrence-free survival, progression-free survival, and safety, were summarized. The recommendations and uncertainties regarding the treatment of HCC were also proposed.

Expansion of the criteria for living donor liver transplantation for hepatocellular carcinoma.

Several expanded criteria for liver transplantation for hepatocellular carcinoma (HCC) have been suggested out of concern that the Milan criteria may be too strict, and thereby exclude patients who could benefit from this surgical procedure. However, most expanded criteria were designed for deceased donor liver transplantation. Living donor liver transplantation (LDLT) differs from that of deceased donor liver transplantation primarily because LDLT liver grafts are not public resources. In Asian countries, where HCC is endemic, LDLT is the main currently available treatment option for HCC. High-volume LDLT centers throughout Asia have adopted their own expanded selection criteria for LDLT for HCC with acceptable long-term results. Some centers utilize tumor markers as one of the criterion to help select suitable candidates. Indeed, such adjunctive biomarkers may have prognostic relevance for patients with HCC. The use of both biological and histomorphologic parameters may increase the number of transplantable patients. The overall chance of survival, and recipient/donor preferences as well as the risk of recurrence are considered in the LDLT setting. Therefore, the selection criteria for liver transplantation for HCC could benefit from expansion for LDLT.