Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.

Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment modality for hepatocellular carcinoma (HCC). Evaluation of tumour responses following SABR are currently based on conventional radiological criteria used for locoregional therapies. Whether these criteria accurately reflect tumour responses following SABR remains unknown. In this study, we provide a direct comparison of post-SABR radiological evaluation and explant histology for patients with HCC who underwent bridging SABR prior to liver transplantation.

Patients with HCC who received SABR as bridging therapy prior to liver transplantation (January 2016-December 2022) in a large UK liver transplant centre were included. Post-SABR imaging was reported by two specialist hepato-pancreato-biliary radiologists, and histological examination of the explanted liver was performed by experienced liver histopathologists.

Six patients with residual active HCC received SABR as bridging therapy prior to undergoing liver transplantation in our cohort. Of five patients with viable HCC detected on explant histology, recent radiological evaluation using LI-RADS treatment response criteria had suggested no evidence of residual active HCC for three patients, difficulty delineating residual disease from post-radiotherapy changes for one patient, and accurately identified viable tumour in one patient.

In our case series conventional radiological criteria underestimated HCC tumour viability following SABR compared to explant histology. As the role for SABR expands in the management of HCC, caution is needed with radiological interpretation of HCC responses to radiotherapy using standard LI-RADS criteria. Prospective study in a larger cohort is required to identify radiological criteria capable of more conclusively evaluating HCC responses to SABR.

HCC is the fourth leading cause of cancer-related mortality with increasing incidence worldwide. Historically, treatment for early disease includes liver transplantation, surgical resection, and/or other local therapies, such as thermal ablation. As a result of technical advances and high-quality prospective data, the use of definitive external beam radiotherapy with ablative doses has emerged. Intermediate-stage disease has been generally addressed with arterially directed therapies (eg, chemoembolization or radioembolization) and external beam radiotherapy, while advanced stages have been addressed by systemic therapy or best supportive care. The role of each local/locoregional therapy has rapidly evolved in the context of novel pharmacotherapies, including immunotherapies and antiangiogenic agents. The combinations, indications, and timing of treatments vary widely among specialties and geographies. Here, we aim to synthesize the best quality evidence available regarding the efficacy and safety of different liver-directed modalities, with a focus on recent prospective clinical data of external beam radiotherapy within the context of other available liver-directed therapies across Barcelona Liver Classification (BCLC) stages.

Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies.

Radiation segmentectomy (RS) and ablative external beam radiation therapy (EBRT) are now accepted, definitive, local therapies for hepatocellular carcinoma (HCC). This report aimed to describe the clinical outcomes of RS and EBRT for treatment-naïve, solitary, HCC.

A multicenter retrospective review was performed of all patients treated with RS or EBRT from March 2016 through September 2023. Inclusion criteria were initial treatment for solitary HCC ≤8 cm and absence of macrovascular invasion or extrahepatic disease. Outcomes were censored for liver transplantation (LT).

Eighty-six patients (RS: 58; EBRT: 28) met inclusion criteria. The EBRT cohort had older patients (median 76 vs 66 years, p < 0.001), larger tumors (median 3.7 vs 2.4 cm, p < 0.001), and worse performance status (p = 0.02). The RS cohort had more patients with ≥ grade 3 liver fibrosis (p < 0.001). Radiologic complete response (rCR) was achieved in 97% of RS and 82% of EBRT patients (p = 0.02). Median time to rCR was 1 month (95% CI: 0.9-1.1) after RS and 7 months (95% CI: 6-7) after EBRT (p < 0.001). The 1-year local control was 97% vs 93% for RS and EBRT, respectively (p = 0.80). Subsequent LT was performed in 48% of RS and 11% of EBRT patients with tumor complete pathologic response rates of 76% (n=22/28) and 33% (n=1/3), respectively. Progression free survival at 1-year was 87% after RS vs 80% after EBRT (p = 0.26). 1- and 2-year overall survival was 88% and 85% after RS vs 84% and 59% after EBRT (p = 0.34).

RS and EBRT are effective therapies for solitary HCC. Treatment should be determined via multidisciplinary discussion based on individual patient characteristics.

Background/Objectives: Since their introduction in the 1990s, the Milan criteria have been the gold standard of indication for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Nevertheless, several institutions have reported wider indication criteria for LT with comparable survival outcomes. Methods: This paper summarizes the recent indications for LT for HCC through a literature review. Results: There are several criteria expanding the Milan criteria, which can be subdivided into the "based on tumor number and size only", "based on tumor number and size plus tumor markers", and "based on tumor differentiation" groups, with the outcomes being comparable to those of patients included within the Milan criteria. Besides the tumor size and number, which are included in the Milan criteria, recent criteria included biomarkers and tumor differentiation. Several retrospective studies have reported microvascular invasion (MVI) as a significant risk factor for postoperative recurrence, highlighting the importance of preoperatively predicting MVI. Several studies attempted to identify preoperative predictive factors for MVI using tumor markers or preoperative imaging findings. Patients with HCC who are LT candidates are often treated while on the waiting list to prevent the progression of HCC or to reduce the measurable disease burden of HCC. The expanding repertoire of chemotherapeutic regiments suitable for patients with HCC should be further investigated. Conclusions: There are several criteria expanding Milan criteria, with the outcomes being comparable to those of patients included within the Milan criteria.

Embolic and ablative locoregional therapies (LRTs) for hepatocellular carcinoma are widely used to cure, bridge, or downstage patients for more definitive therapies. Common ablative therapies include microwave ablation and radiofrequency ablation, while embolic options include transarterial chemoembolization and 90Y transarterial radioembolization. While these therapies can be highly effective for the appropriate stage of disease, LRTs can suffer from a high rate of posttreatment recurrences. Considerations for administration of specific therapies include disease burden and underlying liver function. Recent data on concomitant or adjuvant systemic therapy, with LRT, have the potential to improve disease control and improve outcomes in this high-risk patient population.

Radiotherapy can be used as a bridge therapy prior to liver transplantation. Radiotherapy generates immune reactions involving T cells, which are the main effectors of acute cellular rejection after transplantation. Here, we investigated the impact of radiotherapy on acute cellular rejection.

We retrospectively reviewed the data of oncological patients who benefited from liver transplantation. Patients who received radiotherapy prior to liver transplantation ("RT cohort", n=17) were compared to a matched cohort ("NoRTmatched cohort", n=17) obtained through propensity score-matching analysis of the total non-irradiated cohort ("NoRTall" cohort, n=136). The acute cellular rejection was evaluated using the Banff score for rejection (mild:<5, moderate: 5-6, and severe: 7-9) obtained on an early post-transplantation biopsy. Overall and disease-free survival were reported for patients with hepatocellular carcinoma.

Median Banff scores was significantly lower for the RT cohort compared to the NoRTall cohort (2.5 versus 5, respectively, P=0.043) but this statistical difference was eliminated after comparison with the NoRTmatched cohort (median: 4, P=0.62). The 5-year overall and disease-free survival rates were 62 % and 69 %, respectively, for hepatocellular carcinoma patients of the RT cohort (n=14) and did not differ from the 5-year overall (83 %, P=0.15) and disease-free survival rates (90 %, P=0.05) of those of the NoRTmatched cohort (n=16).

Radiotherapy given prior to liver transplantation did not impact the rate or severity of acute cellular rejection. Furthermore, overall and disease-free survival rates were not impacted by radiotherapy.

With the advances in transplant oncology in recent years, the role of liver transplantation has expanded to make curative treatment a possibility for a wider patient population. We highlight strategies in Hong Kong, China that have enabled preoperative prognostication for judicious patient selection, downstaging therapy to definitive treatment, and postoperative therapies that have provided a growing role for liver transplantation in patients with more advanced hepatocellular carcinoma.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape in advanced hepatocellular carcinoma and increasingly are being evaluated in earlier stage disease. Herein we explore the role of ICIs pre-liver transplant for liver cancers.

Given the high response rates with combination approaches including locoregional treatments, more patients with liver confined disease, without vascular invasion, who have received ICIs are now being rendered eligible for potential liver transplant. This opportunity to expand the population who may benefit from liver transplant has also come with challenges recognizing the global shortage of organs. Post-liver transplant immunosuppression potentially competes with the immune-stimulating effects of ICIs and graft rejection has been a concern. ICIs may provide an opportunity to maintain patients on the waiting list but an understanding of who is likely to benefit is needed, to circumvent possible toxicities. In addition, ICIs are now considered standard of care, in combination with chemotherapy, for advanced cholangiocarcinoma, where the role of liver transplant is evolving.

As the eligibility criteria globally for liver transplant in the setting of malignancy continues to expand, the integration of ICIs becomes increasingly important.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, with advanced stages posing significant treatment challenges. Although hepatic arterial infusion chemotherapy (HAIC) has emerged as a promising modality for treating advanced HCC, particularly in Asian clinical practice, its adoption in Western medicine remains limited due to a lack of large-scale randomized controlled trials. This editorial reviews and comments on the meta-analysis conducted by Zhou et al, which evaluates the efficacy and safety of HAIC and its combination strategies for advanced HCC. The authors performed a comprehensive meta-analysis of various clinical trials and cohort studies comparing HAIC and its combinations to other first-line treatments, such as sorafenib and transarterial chemoembolization (TACE). In this work, HAIC showed significantly better results regarding overall survival and progression-free survival compared to sorafenib or TACE alone and their combination. HAIC in combination with lenvatinib, ablation, programmed cell death 1 inhibitors, and radiotherapy further enhanced patient outcomes, indicating a synergistic effect. This editorial focuses on the critical role of multimodal treatment strategies in managing advanced HCC. It advocates for a paradigm shift towards integrated treatment approaches to enhance survival rates and improve the quality of life in patients with advanced HCC.

Stereotactic body radiation therapy (SBRT) is a therapeutic option in the guidelines for liver primaries after standard strategies like surgery or thermoablation have failed. To assess its efficacy and safety, we reviewed all patients treated by SBRT for a hepatocellular carcinoma (HCC) over a six-year period.

The study included all patients treated by SBRT for HCC between April 2015 and November 2021 in the University Cancer Institute at Toulouse-Oncopole. All patients were inoperable and not eligible for thermoablation, or after a failure. All tumor sizes were included and cirrhosis up to Child-Pugh B was accepted. Local control (LC), overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Treatment response was assessed using mRECIST criteria. Toxicity was graded using CTCAE (v4.0).

One hundred and nine patients with 118 lesions were treated. Half underwent prior standard treatment. Median dose was 50 Grays in five fractions for most patients. Chronic liver disease represented 90.8 % of cases with a median age of 69 years. Median tumor size was 4.0 cm. Median follow-up was 22.2 months [95 %CI: 15.1-30.4]. LC, OS and PFS at two years were 82.4 % [95 %CI: 71.3; 89.5], 73.2 % [95 %CI: 61.5; 81.8] and 35.8 % [95 %CI: 25.1; 46.7], respectively. Acute toxicities occurred in 20.2 % of patients, including 10.1 % grade 3-4 and 1.8 % grade 5. Late toxicities occurred in 5.5 % of patients including 4.6 % grade 3-4. Grade ≥ 3 toxicity was related to digestive perforation or liver failure.

SBRT provides good LC with an acceptable safety profile. It can be used in several settings such as salvage therapy or in combination with validated treatment. Prospective randomized trials are needed to validate SBRT as a standard alternative.

Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80-90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.

Stereotactic body radiation therapy (SBRT) is an emerging treatment for hepatocellular carcinoma (HCC), which provides excellent local control (LC) and prolongs overall survival (OS). However, in current guidelines, transcatheter arterial chemoembolization (TACE) has been proposed as a key treatment option for patients with early- and intermediate-stage HCC, whereas SBRT is not. Therefore, we performed a systematic review and meta-analysis of randomized controlled trials and retrospective studies using the propensity score (PS) to compare the outcomes of SBRT and TACE for HCC in a balanced manner. We systematically searched the PubMed, Cochrane, EMBASE, and Web of Science databases to identify randomized controlled trials and studies comparing SBRT and TACE using PS analysis. The hazard ratios (HRs) for OS and LC were pooled. The heterogeneity between the data collected from these studies was also assessed. SBRT led to a comparable OS (HR: 0.83; 95 % confidence interval (CI): 0.52-1.34; p = 0.44) to TACE, and significantly improved LC (HR: 0.25; 95 % CI: 0.09-0.67; p = 0.006). Considerable heterogeneity was observed in the HR of OS and LC. Although there was no significant difference in the rate of grade 3 or higher toxicities between TACE and SBRT, or between studies, liver toxicity was identified as a common adverse event associated with both SBRT and TACE. Compared to TACE, SBRT showed a comparable OS and improved LC without serious toxicity. Therefore, SBRT should be considered an effective treatment option for various stages of HCC, depending on the tumor factors and pretreatment liver function.

Immune checkpoint inhibitors are becoming a mainstay of cancer treatment. While first studied and approved for patients with unresectable disease, due to their efficacy, they are becoming increasingly used in the perioperative period across many cancer types. In patients with HCC, immune checkpoint inhibitors have now become the standard of care in the advanced setting and have shown promising results in the adjuvant setting after liver resection. While these drugs continue to show promise, their role in the peritransplant setting still remains a question. In this review, we explore the current use of this class of medications in patients with HCC, as well as the immunologic role of the pathways that they inhibit. We also identify potential for future research opportunities to better understand the role of these medications.

Hepatocellular carcinoma is the most common primary liver tumor. Orthotopic liver transplant is one of the best treatment options, but its waiting list has to be considered. Bridge therapies have been introduced in order to limit this issue. The aim of this study is to evaluate if bridge therapies in advanced hepatocellular carcinoma can improve overall survival and reduce de-listing. We selected 185 articles. The search was limited to English articles involving only adult patients. These were deduplicated and articles with incomplete text or irrelevant conclusions were excluded. Sorafenib is the standard of care for advanced hepatocellular carcinoma and increases overall survival without any significant drug toxicity. However, its survival benefit is limited. The combination of transarterial chemoembolization + sorafenib, instead, delays tumor progression, although its survival benefit is still uncertain. A few studies have shown that patients undergoing transarterial chemoembolization + radiation therapy have similar or even better outcomes than those undergoing transarterial chemoembolization or sorafenib alone for rates of histopathologic complete response (89% had no residual in the explant). Also, the combined therapy of transarterial chemoembolization + radiotherapy + sorafenib was compared to the association of transarterial chemoembolization + radiotherapy and was associated with a better survival rate (24 vs. 17 months). Moreover, immunotherapy revealed new encouraging perspectives. Combination therapies showed the most encouraging results and could become the gold standard as a bridge to transplant for patients with advanced hepatocellular carcinoma.

Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown.

To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC.

In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023.

Patients received SBRT followed by DDLT when matched deceased donor grafts were available.

Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety.

A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event.

This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

Inoperable hepatocellular carcinoma (HCC) can be treated by stereotactic body radiotherapy. However, carbon ion radiotherapy (CIRT) is more effective for sparing non-tumorous liver. High linear energy transfer could promote therapy efficacy. Japanese and Chinese studies on hypofractionated CIRT have yielded excellent results. Because of different radiobiological models and the different etiological spectrum of HCC, applicability of these results to European cohorts and centers remains questionable. The aim of this prospective study was to assess safety and efficacy and to determine the optimal dose of CIRT with active raster scanning based on the local effect model (LEM) I.

CIRT was performed every other day in four fractions with relative biological effectiveness (RBE)-weighted fraction doses of 8.1-10.5 Gy (total doses 32.4-42.0 Gy [RBE]). Dose escalation was performed in five dose levels with at least three patients each. The primary endpoint was acute toxicity after 4 weeks.

Twenty patients received CIRT (median age 74.7 years, n = 16 with liver cirrhosis, Child-Pugh scores [CP] A5 [n = 10], A6 [n = 4], B8 [n = 1], and B9 [n = 1]). Median follow up was 23 months. No dose-limiting toxicities and no toxicities exceeding grade II occurred, except one grade III gamma-glutamyltransferase elevation 12 months after CIRT, synchronous to out-of-field hepatic progression. During 12 months after CIRT, no CP elevation occurred. The highest dose level could be applied safely. No local recurrence developed during follow up. The objective response rate was 80%. Median overall survival was 30.8 months (1/2/3 years: 75%/64%/22%). Median progression-free survival was 20.9 months (1/2/3 years: 59%/43%/43%). Intrahepatic progression outside of the CIRT target volume was the most frequent pattern of progression.

CIRT of HCC yields excellent local control without dose-limiting toxicity.

To date, safety and efficacy of carbon ion radiotherapy for hepatocellular carcinoma have only been evaluated prospectively in Japanese and Chinese studies. The optimal dose and fractionation when using the local effect model for radiotherapy planning are unknown. The results are of particular interest for European and American particle therapy centers, but also of relevance for all specialists involved in the treatment and care of patients with hepatocellular carcinoma, as we present the first prospective data on carbon ion radiotherapy in hepatocellular carcinoma outside of Asia. The excellent local control should encourage further use of carbon ion radiotherapy for hepatocellular carcinoma and design of randomized controlled trials.

The study is registered at ClinicalTrials.gov (NCT01167374).

Hepatocellular carcinoma (HCC), the most prevalent liver tumor, is usually linked with chronic liver diseases, particularly cirrhosis. As per the 2020 statistics, this cancer ranks 6th in the list of most common cancers worldwide and is the third primary source of cancer-related deaths. Asia holds the record for the highest occurrence of HCC. HCC is found three times more frequently in men than in women. The primary risk factors for HCC include chronic viral infections, excessive alcohol intake, steatotic liver disease conditions, as well as genetic and family predispositions. Roughly 40-50% of patients are identified in the late stages of the disease. Recently, there have been significant advancements in the treatment methods for advanced HCC. The selection of treatment for HCC hinges on the stage of the disease and the patient's medical status. Factors such as pre-existing liver conditions, etiology, portal hypertension, and portal vein thrombosis need critical evaluation, monitoring, and appropriate treatment. Depending on the patient and the characteristics of the disease, liver resection, ablation, or transplantation may be deemed potentially curative. For inoperable lesions, arterially directed therapy might be an option, or systemic treatment might be deemed more suitable. In specific cases, the recommendation might extend to external beam radiation therapy. For all individuals, a comprehensive, multidisciplinary approach should be adopted when considering HCC treatment options. The main treatment strategies for advanced HCC patients are typically combination treatments such as immunotherapy and anti-VEGFR inhibitor, or a combination of immunotherapy and immunotherapy where appropriate, as a first-line treatment. Furthermore, some TKIs and immune checkpoint inhibitors may be used as single agents in cases where patients are not fit for the combination therapies. As second-line treatments, some treatment agents have been reported and can be considered.

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

To compare pathologic tumor necrosis rates after locoregional therapies (LRTs) for hepatocellular carcinoma (HCC) prior to liver transplantation and evaluate radiologic-pathologic correlation along with posttransplant HCC recurrence.

Consecutive patients with solitary HCC bridged or downstaged with LRT from 2010 to 2022 were included. LRTs were transarterial chemoembolization (TACE), radioembolization (yttrium-90 [90Y]), ablation, and stereotactic body radiotherapy (SBRT). Upfront combination therapy options were TACE/ablation and TACE/SBRT. Subsequent therapy crossover due to local recurrence was allowed. Posttreatment imaging closest to the time of transplant, explant histopathologic necrosis, and tumor recurrence after transplant were reviewed.

Seventy-three patients met inclusion criteria, of whom 5 (7%) required downstaging. 90Y alone (n = 36) and multimodal therapy (pooled upfront combination and crossover therapy, n = 23) resulted in significantly greater pathologic necrosis compared with TACE alone (n = 14; P = .01). High dose 90Y radiation segmentectomy (≥190 Gy; n = 27) and TACE/ablation (n = 7) showed highest rates of complete pathologic necrosis (CPN)-63% (n = 17) and 71% (n = 5), respectively. Patients with CPN had a mean lesion size of 2.5 cm, compared with 3.2 cm without CPN (P = .04), irrespective of LRT modality. HCC recurrence was more common in patients without CPN (16%, 6/37) than in those with CPN (3%, 1/36; P = .11). Using Liver Imaging Reporting and Data System (LI-RADS), a nonviable imaging response was 75% sensitive and 57% specific for CPN.

Radiation segmentectomy and multimodal therapy significantly improved CPN rates compared with TACE alone. A LI-RADS treatment response of nonviable did not confidently predict CPN.

Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial.

To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future.

We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted.

Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT.

The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.