This study aimed to evaluate the impact of the revised deceased donor liver transplantation (DDLT) criteria on hepatocellular carcinoma (HCC) patients newly eligible under the Child-Pugh classification B (CP-B), by focusing on the prognosis and the risk of HCC recurrence beyond the Japan criteria while on the waiting list.

A retrospective analysis was carried out on 1155 patients diagnosed with HCC at Kanazawa University Hospital between 2006 and 2021. Prognosis and recurrence were analyzed for patients eligible for DDLT under the revised criteria.

Of the 1155 patients, 57 (4.9%) were eligible for DDLT according to the revised criteria. Five patients who underwent liver transplantation had a better prognosis compared to others who received treatments like radiofrequency ablation and transcatheter arterial chemoembolization. Patients with Child-Pugh score (CP) score of 7, a single tumor, and low des-γ-carboxy prothrombin (DCP) levels had favorable outcomes without transplantation, although long-term survival was superior with transplantation. However, 27.5% of eligible patients experienced recurrence or death within 30 months, which might disqualify them from DDLT. A scoring algorithm was developed based on CP score ≥8, multiple tumors, and DCP > 100 IU/dL. Patients with scores of 1 or 2 had 5-year survival rates of 40% and 30%, respectively, and most would meet the Japan criteria after 30 months. For patients with a score of 3, living donor liver transplantation should be prioritized.

The revised DDLT criteria improve access to transplantation for CP-B patients with HCC, but the risk of progression or recurrence during the waiting period remains. Careful evaluation, bridging therapies, and continuous assessment are crucial for optimal outcomes.

Background/Objectives: MVI is a relevant prognostic factor among patients with hepatocellular carcinoma (HCC) receiving liver transplantation (LT). The preoperative assessment of the risk for MVI is relevant to pre-LT patient management and selection. The objective of this study was to create and validate a model to predict microvascular invasion (MVI) based on preoperative variables in the LT setting. Methods: A total of 2170 patients from 11 collaborative centers in Europe, Asia, and the US, who received transplants between 1 January 2000 and 31 December 2017, were enrolled in the study. The entire cohort was split into a training and a validation set (70/30% of the initial cohort, respectively) using random selection. Results: MVI was reported in 586 (27.0%) explanted specimens. Using the training set data, multivariable logistic regression identified three preoperative parameters associated with MVI: α-fetoprotein (lnAFP; odds ratio [OR] = 1.19; 95% confidence interval [CI] = 1.13-1.27), imaging tumor burden score (lnTBS; OR = 1.66; 95%CI = 1.39-1.99), and a fast-track approach before LT due to the availability of a live donation (OR = 1.99; 95%CI = 1.56-2.53). In the validation set, the LT-MVI c-index was 0.74, versus 0.69 for the MVI score proposed by Endo et al. (Brier Skill Score +75%). The new score had a relevant net reclassification index (overall value = 0.61). Stratifying the validation set into three risk categories (0-50th, 51st-75th, and >75th score percentiles), a very good stratification was observed in terms of disease-free (5-year: 89.3, 75.5, and 50.7%, respectively) and overall survival (5-year: 79.5, 72.6, and 53.7%, respectively). Conclusions: The preoperative assessment of MVI using the proposed score demonstrated very good accuracy in predicting MVI after LT.

Hepatocellular carcinoma (HCC) remains the leading cause of cancer-related mortality worldwide and is characterized by high recurrence rates after curative resection. The tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis. However, their roles in the modern era of HCC epidemiology require reevaluation.

This multi-institutional retrospective study analyzed 1515 patients who underwent hepatectomy for primary HCC. Patients were classified into 4 clusters using k-means analysis based on preoperative DCP and AFP levels. Clinicopathologic characteristics, overall survival (OS), and recurrence rate (RR) were evaluated using Cox proportional hazards models and area under the receiver operating characteristic curve (AUROC) comparisons.

Cluster 3 (concurrent elevations of DCP and AFP) had the poorest 5-year OS (52.8%) and the highest RR (79.3%), whereas cluster 4 (low levels of both markers) had the most favorable outcomes, with a 5-year OS rate of 71.5% and an RR of 55.7%. Cluster 1 (elevated DCP alone) was associated with larger tumors (median of 45 mm) and more frequent vascular invasion (43%) than cluster 2 (elevated AFP alone, median tumor size of 24 mm, and vascular invasion of 36%). DCP was a stronger predictor of 5-year OS in patients with preserved liver function (AUROC, 0.63), whereas AFP was more effective in stratifying RR in patients with impaired liver function (AUROC, 0.57). Non-B, non-C hepatitis (NBNC)-related HCC exhibited a distinct biomarker profile, with an elevated DCP level correlating with a higher 5-year RR (67%) than other etiologies.

Our study introduces tumor marker clustering as a novel analytical approach, providing a nuanced understanding of AFP and DCP's combined utility in predicting prognosis and recurrence. Our findings highlight the independent and complementary roles of these biomarkers, particularly in NBNC-related HCC and in cases with impaired liver function. AFP and DCP remain crucial tools for recurrence risk assessment, guiding personalized management strategies, such as surveillance, neoadjuvant therapies, and tailored postoperative interventions.

Hepatocellular carcinoma arises in the setting of cirrhosis in most cases, requiring multidisciplinary input to define resectability. In this regard, more precise surgical management considers patient factors and anatomical states, including resection margins, tumour biology, and perioperative therapy. Together with advances in surgical techniques, this integrated approach has resulted in considerable improvements in patient morbidity and oncological outcomes. Despite this, recurrence rates in hepatocellular carcinoma remain high. As the systemic treatment landscape in hepatocellular carcinoma continues to evolve and locoregional options are increasingly used, we review current and future opportunities to individualise the surgical management of patients with hepatocellular carcinoma.

Transplant oncology integrates a wide variety of fields, such as surgery, oncology, and transplant medicine, intending to increase the range of studies and treatments for hepatobiliary cancers and other liver-related malignant lesions. Liver transplantation (LT) has proven to be an effective treatment for hepatocellular carcinoma. While the Milan criteria are still the gold standard, several new, more inclusive criteria have been proposed, and hepatocellular carcinoma has become a major indication for liver transplantation. The continuous evolution of diagnostic technologies supported this with higher image quality and more accurate staging. This review describes the current applications of transplant oncology in hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and liver metastatic disease from colorectal cancer and discusses the path that led to the development of transplant oncology as an organized approach to managing gastrointestinal malignancies through transplantation. More importantly, the significance of a multidisciplinary approach and criteria in the selection of suitable candidates are discussed. In addition, newer aspects of transplant oncology, such as immunotherapy, circulating tumor DNA (ctDNA), novel surgical techniques, and the utilization of artificial intelligence, are presented. Finally, the opportunities and challenges involved in the field's future, as well as the evolution of the criteria used over the years and insightful thoughts for the future of the criteria, are discussed.

In 2019, expanded criteria for hepatocellular carcinoma (HCC), known as 5-5-500 (size ≤5 cm, number ≤5, alpha-fetoprotein ≤500 ng/mL), as well as Model for End-stage Liver Disease (MELD) exception, were implemented in Japan. In the present study, we evaluated liver transplantation indications and the Japanese allocation policy for HCC.

Adults with HCC were evaluated between January 2013 and December 2017 in a multicenter study in Japan. The patients were aged ≤65 years, in line with the limits of Japanese transplant center limits.

HCC patients (n = 289) were classified as Child-Pugh A (74%), B (18%), or C (8%). Of these, 178 (62%) and 185 (64%) met the Milan and 5-5-500 criteria, respectively. The respective 1- and 5-year overall survival rates of patients who met the criteria were 100% and 88.1% in Child-Pugh A, 91.7% and 30.6% in B, and 72.9% and 0% in C without access to liver transplantation. For Child-Pugh A patients, we developed a risk score using the Child-Pugh score, des-gamma-carboxy prothrombin, tumor-node-metastasis stage grade, as well as albumin-bilirubin and albumin-bilirubin tumor-node-metastasis stage , which predicted worse prognosis. Additionally, we showed the characteristics of patients who achieved MELD exception points high enough to receive an organ: survival at least 2 years after waitlist registration, relatively good liver functional reserve, and sufficient tumor control with multiple treatments.

High-risk patients, identified by our scoring system and albumin-bilirubin tumor-node-metastasis stage ≥2 in Child-Pugh A, should be considered for liver transplantation eligibility. The allocation policy for HCC should be revised based on precise evaluations on a regular basis.

Hepatocellular carcinoma (HCC) remains a significant global health challenge, with over 800,000 new cases diagnosed annually. This comprehensive review examines current surgical approaches and emerging multidisciplinary strategies in HCC treatment. While traditional surgical criteria, such as the Barcelona Clinic Liver Cancer (BCLC) staging system, have been relatively conservative, recent evidence from high-volume Asian centers supports more aggressive surgical approaches in carefully selected patients. The review discusses the evolution of selection criteria, including the new "Borderline Resectable HCC" classification system, which provides more explicit guidance for surgical decision-making. Technical innovations have significantly enhanced surgical precision, including three-dimensional simulation, intraoperative navigation systems, and the advancement of minimally invasive approaches. The review evaluates the ongoing debate between anatomical versus non-anatomical resection and examines the emerging role of robotic surgery. In liver transplantation, expanded criteria beyond the Milan criteria show promising outcomes, while the integration of novel biomarkers and imaging techniques improves patient selection. The role of preoperative and adjuvant therapies is increasingly important, with recent trials demonstrating the potential of immune checkpoint inhibitors combined with anti-VEGF agents in both settings. Despite these advances, postoperative recurrence remains a significant challenge. The review concludes that successful HCC treatment requires a personalized approach, integrating surgical expertise with emerging technologies and systemic therapies while considering individual patient factors and regional variations in practice patterns.

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.

Liver transplantation (LT) provides significant survival benefits to patients with unresectable HCC. In the United States, organ allocation policies for HCCs within the United Network for Organ Sharing criteria do not prioritize patients based on their differences in oncological characteristics. This study assessed whether transplant-associated survival benefits (TASBs) vary among patients with different tumor burden scores (TBS) measured at the time of listing.

We analyzed data from adults applying for HCC MELD exception points between 2002 and 2019, with follow-up until December 2023, using the Scientific Registry of Transplant Recipients. TBS was determined based on the largest tumor diameter and number of HCCs. Patients were categorized into low (≤3), intermediate (3.1-5), and high (>5) TBS groups. TASB was measured as the difference in 5-year survival with and without LT.

This study included 36,634 LT candidates. High-TBS patients had higher waitlist dropout rates and marginally lower post-transplant survival, resulting in a significantly greater TASB. The 5-year TASB for the low, intermediate, and high TBS groups were 15.7, 22.1, and 25.0 months, respectively. The adjusted survival benefit expressed in 5-year survival differences was 21.9%, 34.5%, and 39.4% in the low, intermediate, and high TBS groups, respectively (p<0.001).

Higher TBS during listing correlates with greater LT benefits for patients with unresectable HCC within UNOS criteria. We conclude that organ allocation policies in the United States should prioritize patients with high TBS due to their increased risk of dropout and comparable post-transplant survival when compared to patients with less advanced tumors.

Background: Examinations of procalcitonin (PCT) and Ki-67 expression levels in hepatocellular carcinoma (HCC) patients who have undergone liver transplantation (LT) through immunohistochemical analyses of tumor tissue may reveal the biological characteristics of the tumor, thus informing the selection of HCC patients for LT. Methods: Hepatectomy specimens from 86 HCC patients who underwent LT were obtained and analyzed immunohistochemically for the expression of PCT and Ki-67. The percentage and intensity of PCT staining, as well as the percentage of Ki-67 expression, were assessed for each patient. The impacts of PCT and Ki-67 expression on disease-free survival, overall survival, and the recurrence rate were studied, as well as their correlations with other clinicopathological features. Results: The recurrent HCC group showed a higher Ki-67 level (p < 0.001), larger maximum dominant tumor diameter (p < 0.001), and higher rate of vascular invasion (p = 0.001). The pre-transplant AFP (p = 0.001), maximum dominant tumor diameter (p < 0.001), number of tumor nodules (p < 0.001), rate of vascular invasion (p = 0.001), and Ki-67 level (p = 0.044) were higher in patients beyond the Milan criteria. Similarly, the pre-transplant AFP (p < 0.001); maximum dominant tumor diameter (p < 0.001); number of tumor nodules (p < 0.001); rates of portal vein tumor thrombus (p = 0.002), poor differentiation (p = 0.021), and vascular invasion (p < 0.001); and Ki-67 level (p = 0.010) were higher in patients beyond the expanded Malatya criteria. The maximum dominant tumor diameter (p = 0.006); Ki-67 level (p = 0.003); rates of vascular invasion (p < 0.001), cases beyond the Milan criteria (p = 0.042) and the expanded Malatya criteria (p = 0.027), and portal vein tumor thrombus (p = 0.020); and presence of recurrence (p < 0.001) were higher in HCC patients with mortality. The Kaplan-Meier estimates indicated that Ki-67 levels exceeding 5% significantly affected DFS and OS. Although the Kaplan-Meier estimates indicated that a PCT staining percentage of ≥25% did not have a statistically significant effect on DFS or OS, the outcomes may be considered clinically significant. Conclusions: This study demonstrated that the Ki-67 proliferation index can be used as a predictive biomarker of the biological behavior of HCC. Furthermore, we claim that PCT expression over a particular threshold might impact recurrence and survival, and we believe that further multicenter prospective studies focused on standardized PCT antibody staining are crucial in order to determine its potential as a biomarker for HCC.

New guidelines propose a minimum 5-year survival of 60% for hepatocellular carcinoma (HCC) with living donor liver transplantation (LDLT). This study aimed to evaluate the 5- and 10-year survival rates after transplantation for the expanded criteria for HCC.

This single-center retrospective cohort study included 208 patients who underwent LDLT for the expanded criteria (the largest tumor diameter of ≤10 cm, any tumor number, and alpha-fetoprotein [AFP] level of <1000 ng/mL) and analyzed 5- and 10-year overall survival (OS) and recurrence risk (RR) rates.

With a median follow-up of 65.1 months (IQR, 19.1-80.2), the 5- and 10-year OS and RR rates were 67.0% and 61.0% and 20.5% and 22.5%, respectively. The largest tumor diameter of >6 cm (hazard ratio [HR], 3.7; 95% CI, 1.7-8.2; P = .001) and AFP level of >400 ng/mL (HR, 4.0; 95% CI, 1.8-9.0; P = .001) were predictors of recurrence. Patients outside the Milan criteria (MC) were grouped into low- and high-risk HCC based on tumor size and AFP level. For low-risk HCC (tumor size of <6 cm, any tumor number, and AFP level of <400 ng/mL), the 5-year RR was comparable to the MC and increased the transplant pool by 35.7% (P > .5). The median number of tumors and the rate of microvascular invasion in the high-risk group, low-risk group, and MC were 2.0 (1.0-3.2), 4.0 (2.0-5.0), and 1.0 (1.0-2.0) (P < .001) and 72.2% (13/18), 44.0% (22/50), and 22.8% (32/140) (P < .001), respectively.

The expanded criteria met the benchmark for 5-year survival. LDLT for the low-risk HCC in the expanded criteria was associated with an acceptable RR.

Recent advances in systemic therapy for hepatocellular carcinoma (HCC) have led to debates about the feasibility of combination therapies, such as systemic therapy combined with surgery or transarterial chemoembolization, for patients with advanced HCC. However, a lack of consensus on the oncological resectability criteria has hindered discussions of "conversion therapy" and the optimal management in patients with HCC. To address this issue, the Japan Liver Cancer Association (JLCA) and the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) established a working group and discussed the concept of borderline resectable HCC. Herein, we present a consensus statement from this expert panel on the resectability criteria for HCC from the oncological standpoint under the assumption of technically and liver-functionally resectable situations. The criteria for oncological resectability in HCC are classified into three grades: resectable, representing an oncological status for which surgery alone may be expected to offer clearly better survival outcomes as compared with other treatments; borderline resectable 1, representing an oncological status for which surgical intervention as a part of multidisciplinary treatment may be expected to offer survival benefit; and borderline resectable 2, representing an oncological status for which the efficacy of surgery is uncertain and the indication for surgery should be determined carefully under the standard multidisciplinary treatment. These criteria aim to provide a common language for discussing and analyzing the treatment strategies for advanced HCC. It is also expected that these criteria will be optimized, modified, and updated based on further advancements in systemic therapies and future validation studies.

This study compares selection criteria for liver transplant (LT) for hepatocellular carcinoma (HCC) for inclusivity and predictive ability to identify the most permissive criteria that maintain patient outcomes.

The Scientific Registry of Transplant Recipients (SRTR) database was queried for deceased donor LT's for HCC (2003-2020) with 3-y follow-up; these data were compared with a 2-center experience. Milan, University of California, San Francisco (UCSF), 5-5-500, Up-to-seven (U7), HALT-HCC, and Metroticket 2.0 scores were calculated.

Nationally, 26 409 patients were included, and 547 at the 2 institutions. Median SRTR-follow-up was 6.8 y (interquartile range 3.9-10.1). Three criteria allowed the expansion of candidacy versus Milan: UCSF (7.7%, n = 1898), Metroticket 2.0 (4.2%, n = 1037), and U7 (3.5%, n = 828). The absolute difference in 3-y overall survival (OS) between scores was 1.5%. HALT-HCC (area under the curve [AUC] = 0.559, 0.551-0.567) best predicted 3-y OS although AUC was notably similar between criteria (0.506 < AUC < 0.527, Mila n = 0.513, UCSF = 0.506, 5-5-500 = 0.522, U7 = 0.511, HALT-HCC = 0.559, and Metroticket 2.0 = 0.520), as was Harrall's c-statistic (0.507 < c-statistic < 0.532). All scores predicted survival to P  < 0.001 on competing risk analysis. Median follow-up in our enterprise was 9.8 y (interquartile range 7.1-13.3). U7 (13.0%, n = 58), UCSF (11.1%, n = 50), HALT-HCC (6.4%, n = 29), and Metroticket 2.0 (6.3%, n = 28) allowed candidate expansion. HALT-HCC (AUC = 0.768, 0.713-0.823) and Metroticket 2.0 (AUC = 0.739, 0.677-0.801) were the most predictive of recurrence. All scores predicted recurrence and survival to P  < 0.001 using competing risk analysis.

Less restrictive criteria such as Metroticket 2.0, UCSF, or U7 allow broader application of transplants for HCC without sacrificing outcomes. Thus, the criteria for Model for End-stage Liver Disease-exception points for HCC should be expanded to allow more patients to receive life-saving transplantation.

Liver transplantation (LT) is an effective method for curing hepatocellular carcinoma (HCC). However postoperative tumor recurrence can lead to higher mortality rates. To select suitable candidates for LT, the Milan Criteria (MC) were first proposed based on tumor morphological characteristics. For those patients who meet the MC, the MC can effectively reduce the postoperative tumor recurrence rate and improve the prognosis of patients undergoing LT. It has always been internationally recognized as the gold standard for selecting candidates for LT, marking a milestone in the history of LT for HCC. However, its strict conditions exclude some HCC patients who could benefit from LT. Therefore, comprehension consideration criteria, including serum biomarkers, tumor histology, and other factor, have been continuously proposed in addition to tumor morphology. This article summaries the prediction model for HCC recurrence after LT from five aspects: tumor morphology, serum markers, histopathology, cellular inflammatory factors and downstaging treatment before transplantation. The aim is to assist clinicians in accurately assessing HCC status, selecting appropriate liver transplant candidates, maximize graft and patients' survival, and optimizing the utilization of social health resources.

Standardized pathological evaluation based on immunohistochemical (IHC) analysis could improve hepatocellular carcinoma (HCC) diagnoses worldwide. We evaluated differences in clinicopathological subgroups in HCCs from two academic institutions in Tokyo-Japan, and Jakarta-Indonesia.

Clinicopathological parameters and molecular expression patterns were evaluated in 35 HCCs from Indonesia and 41 HCCs from Japan. IHC analysis of biliary/stem cell (B/S) markers (cytokeratin 19, sal-like protein 4, epithelial cell adhesion molecule) and Wnt/β-catenin (W/B) signaling-related molecules (β-catenin, glutamine synthetase) could determine the IHC-based subgroups. For immuno-subtypes categorization, CD3/CD79α double immunohistochemistry was done to evaluate the infiltration of T and B cells. CD34 staining allowed identification of vessels that encapsulated tumor clusters (VETC).

Indonesian HCC patients were mostly <60 years old (66%) with a hepatitis B virus (HBV) background (82%), in contrast to Japanese HCC patients (8% and 19%, respectively, both P < 0.001). In comparison with Japanese, Indonesian cases more frequently had >5 cm tumor size (74% vs 23%, P = 0.001), poor differentiation (40% vs 24%), portal vein invasion (80% vs 61%), and α-fetoprotein levels >500 ng/ml (45% vs 13%, P = 0.005). No significant differences were found in the proportions of B/S, W/B, and -/- subgroups from both countries. No immune-high tumors were observed among Indonesian cases, and immune-low tumors (66%) were more common than in Japanese cases (54%). VETC-positive tumors in Indonesia were significantly more common (29%), and most were in the HBV (90%) and -/- subgroups (90%), whereas Japanese VETC cases (10%, P = 0.030) were nonviral (100%) and W/B subgroups (75%).

IHC-based analysis more precisely reflected the clinicopathological differences of HCCs in Japan and Indonesia. These findings provide new insights into standardization attempts and HCC heterogeneity among countries.

In hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy.

Among 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis.

The early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis. The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group. When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001).

Patients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Reactivation of hepatitis B virus (HBV) after liver transplantation (LT) remains a problem; thus, development of more effective HBV reactivation prophylaxis is desirable. We evaluated the efficacy of a combination of a long-term nucleotide analog (NA), such as entecavir (ETV) or tenofovir alafenamide (TAF), and short-term hepatitis B immunoglobulin (HBIG) in preventing HBV reactivation and compared it with conventional HBV prophylaxis.

Between February 1999 and August 2023, 135 patients underwent living-donor liver transplantation for liver cirrhosis or acute liver failure caused by HBV infection or received an LT from a hepatitis B core antibody-positive donor. Recipients who had undergone LT were classified as being in the first or second era (namely until September 2017 and from October 2017), respectively, and outcomes of prophylaxis against HBV reactivation were compared between the two eras.

In the second era, recipients with HBV-related disease or who had received hepatitis B core antibody-positive liver received combination therapy with short-term HBIG and an NA such as TAF and ETV long-term. The duration of HBIG treatment was markedly shorter than in the first era in both categories of patients and HBIG could be discontinued in all cases. Surprisingly, we observed HBV reactivation in the first era, but not in the second era, in both groups.

We have established a protocol for prophylaxis against HBV reactivation using a combination of short-term HBIG and long-term NA. This protocol was found to be sufficient to prevent HBV reactivation after LT.

The superiority of anatomical liver resection (AR) for localized hepatocellular carcinoma (HCC) over nonanatomical liver resection (NR) remains controversial. This study aimed to investigate the impact of AR in preventing local and early HCC recurrence.

A total of 280 patients who underwent initial liver resection for solitary HCC ≤5 cm in diameter were categorized into the AR and NR groups and compared using propensity score matching analysis.

Between the matched pairs (n = 87 in each group), the incidence rates of local and early (recurrence within 2 years after surgery) recurrences in the AR group were significantly lower than those in the NR group (13.8% vs. 28.7%, p = .025; 20.7% vs. 35.6%, p = .028, respectively). The overall survival in the AR group was better than that in the NR group (median: 13.4 vs. 7.6 years, p = .003). NR was among independent risk factors for early recurrence (odds ratio: 1.98, 95% CI: 1.1-3.6, p = .023) and prognostic factors for local recurrence (hazard ratio: 2.44, 95% CI: 1.4-4.4, p = .003).

AR is superior in controlling local and early recurrence postoperatively for solitary HCC ≤5 cm in diameter compared with NR.

Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.

The Japanese indication criteria for liver transplantation (LT) for hepatocellular carcinoma (HCC) have been updated based on living donor LT data to include either the Milan criteria (MC) or the 5-5-500 rule, which requires a nodule size of ≤5 cm, ≤5 nodules, and an alpha-fetoprotein (AFP) level ≤500 ng/mL. We aimed to validate the 5-5-500 rule and the MC for deceased donor LT (DDLT).

Using national registry data from the United States from 2010 to 2014, we separated DDLT patients into four groups based on the MC and the 5-5-500 rule. The AFP values were stratified into categories: ≤100, 101-300, 301-500, and >500 ng/mL.

The 5-year survival rate was significantly lower for patients in the groups within MC/beyond 5-5-500 (56.3%) or beyond MC/5-5-500 (60.7%) than for patients in the groups within MC/5-5-500 (76.2%) and beyond MC/within 5-5-500 (72.3%) (p < 0.01). Hepatocellular carcinoma recurrence at 5 years was highest for the within MC/beyond 5-5-500 (25.4%) group, followed by the beyond MC/within 5-5-500 (13.1%), beyond MC/5-5-500 (9.6%), and within MC/5-5-500 (7.4%) groups. The stratified 5-year survival rates after DDLT were 76.5%, 72.4%, 58.4%, and 55.6% in the AFP ≤100, 101-300, 301-500, and >500 categories, respectively (p < 0.01).

The 5-5-500 rule guides the appropriate selection of patients with HCC for DDLT. Patients with AFP levels from 300 to 500 ng/mL had inferior outcomes even when they met the 5-5-500 rule, so further investigation is needed to guide their treatment.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death and the sixth most diagnosed malignancy worldwide. Serum alpha-fetoprotein (AFP) is the traditional, ubiquitous biomarker for HCC. However, there has been an increasing call for the use of multiple biomarkers to optimize care for these patients. AFP, AFP-L3, and prothrombin induced by vitamin K absence II (DCP) have described clinical utility for HCC, but unfortunately, they also have well established and significant limitations. Circulating tumor DNA (ctDNA), genomic glycosylation, and even totally non-invasive salivary metabolomics and/or micro-RNAS demonstrate great promise for early detection and long-term surveillance, but still require large-scale prospective validation to definitively validate their clinical validity. This review aims to provide an update on clinically available and emerging biomarkers for HCC, focusing on their respective clinical strengths and weaknesses.

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.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which was the third most common cause of cancer death worldwide in 2020. Transplantation remains the preferred treatment for cure in otherwise unresectable HCC. There are several areas of active research that have led to expansion of eligibility criteria for transplantation including local-regional therapy for downstaging patients presenting outside of the Milan criteria and identification of tumor biomarkers aiding in the early diagnosis, determining prognosis and likelihood of recurrence after transplantation for HCC. New neoadjuvant therapies and post-transplant immunosuppression regimens may also result in expansion of transplant eligibility criteria for HCC.

Liver transplantation (LT) was originally described by Starzl as a promising strategy to treat primary malignancies of the liver. Confronted with high recurrence rates, indications drifted towards non-oncologic liver diseases with LT finally evolving from a high-risk surgery to an almost routine surgical procedure. Continuously improving outcomes following LT and evolving oncological treatment strategies have driven renewed interest in transplant oncology. This is not only reflected by constant refinements to the criteria for LT in patients with HCC, but especially by efforts to expand indications to other primary and secondary liver malignancies. With new patient-centred oncological treatments on the rise and new technologies to expand the donor pool, the field has the chance to come full circle. In this review, we focus on the concept of transplant oncology, current indications, as well as technical and ethical aspects in the context of donor organs as precious resources.

Liver transplantation (LT) is a highly effective treatment for carefully selected patients with hepatocellular carcinoma (HCC). In this review, we explored the development of LT selection criteria and organ allocation policies, comparing original data to underscore their historical progression into the intricate task of quantitatively estimating pre- and post-LT survivals. We emphasized the role of biomarkers such as serum alpha-fetoprotein, Des-gamma-carboxy-prothrombin, circulating tumor cells, and circulating tumor DNA in predicting patient outcomes. Additionally, we examined the transplant-associated survival benefits and the difficulties in accurately calculating these benefits. We also reviewed recent advancements in targeted therapy and checkpoint inhibitors for advanced, inoperable HCC and projected their integration into LT for HCC. We further discussed the growing use of living donor liver transplants in the United States and compared its outcomes with those of deceased donor liver transplants. Furthermore, we examined the progress in machine perfusion techniques, which have shown potential in improving patient outcomes and enlarging the donor pool. These advancements present opportunities to enhance LT patient survivals, refine selection criteria, establish new priority metrics, develop innovative bridging and downstaging strategies, and formulate redesigned LT strategies for HCC treatments.

The recurrence rate after curative resection for hepatocellular carcinoma (HCC) reaches over 70% after 5 years and early recurrence (within 1 year) is now recognized as having a poor prognosis and has limited treatment options.

We retrospectively reviewed 184 consecutive patients who underwent curative hepatic resection for HCC. Severe early recurrence was defined as multiple (beyond up-to-7) liver recurrence or distant metastasis after hepatic resection within 1 year. We divided the participants into two groups according to severe early recurrence and analyzed clinicopathological and long-term outcomes.

Among the patients with multiple or distant metastasis (n = 59), 49 patients (83%) had recurrence within 1 year. Overall survival (OS) and recurrence-free survival (RFS) were significantly worse in the severe early recurrence group than in the others group. Logistic regression analysis revealed that severe early recurrence was significantly associated with macroscopic vascular invasion (MVI), tumor burden score (TBS) > 4.70, and ALBI grade 2. In patients with scores of 2 and 3 (the sum of the three factors), OS and RFS rates were significantly poorer than those of patients with scores of 0 or 1. Positive predictive value and negative predictive value for severe early recurrence was 68.4% and 84.2%, respectively. Furthermore, a validation study demonstrated that cases with these factors were at high risk of severe early recurrence and had poor prognosis.

In this retrospective analysis, MVI, TBS, and ALBI could predict severe early recurrence after hepatic resection for HCC, and patients with these risk factors had a poor prognosis.

Liver transplantation (LT) has emerged as a standard of care for patients with end-stage liver disease, providing a life-saving intervention for patients with severely compromised liver function in both the acute and chronic setting. While LT has also become a routine procedure for early-stage hepatocellular carcinoma (HCC), offering a potential cure by treating both the tumor and the underlying liver disease, its relevance in the context of other malignancies such as cholangiocellular carcinoma (CCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) or liver metastases is still the subject of intense debate and no definite recommendations have yet been established. This review summarizes the current therapeutic standards in the context of LT for gastrointestinal malignancies and provides a reflection and outlook on current scientific and clinical developments.

Research on liver transplantation (LT) for liver cancer has gained increasing attention. This paper has comprehensively described the current status, hotspots and trends in this field. A total of 2991 relevant articles from 1 January 1963 to 28 February 2023 were obtained from the Web of Science Core Collection. VOSviewer and CiteSpace software were utilized as bibliometric tools to analyze and visualize knowledge mapping. Between 1963 and 2023, the number of papers in the area of LT for liver cancer increased continuously. A total of 70 countries/regions, 2303 institutions and 14 840 researchers have published research articles, with the United States and China being the two most productive countries. Our bibliometric-based visual analysis revealed the expansion of LT indications for liver cancer and the prevention/treatment of cancer recurrence as ongoing research hotspots over the past decades. Meanwhile, emerging studies also focus on downstaging/bridging treatments before LT and the long-term survival of LT recipient, in particular the precise application of immunosuppressants.

To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score.

LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC).

Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method.

Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% ( P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% ( P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%.

Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer-related death in the United States. With advances in locoregional therapy for unresectable HCC during the last 2 decades and the recent expansion of transplant criteria for HCC, as well as ongoing organ shortages, patients are spending more time on the waitlist, which has resulted in an increased usage of locoregional therapies. The plethora of molecularly targeted therapies and immune checkpoint inhibitors under investigation represent the new horizon of treatment of HCC not only in advanced stages but also potentially at every stage of diagnosis and management.

To analyze 10,000 cases of living donor liver transplantation (LDLT) recipient data to elucidate outcomes with special reference to the graft-versus-recipient weight ratio (GRWR), based on the Japanese Liver Transplantation Society (JLTS) registry.

The JLTS registry has been accurate and complete in characterizing and following trends in patient characteristics and survival of all patients with LDLT.

Between November 1989 and August 2021, 10,000 patients underwent LDLT in Japan. The procedures performed during the study period included pediatric liver transplantation (age <18 years, n = 3572) and adult liver transplantation (age ≥18 years, n=6428). Factors related to patient survival (PS) and graft survival (GS) were also analyzed.

The GRWR was <0.7, 0.7 to <0.8, 0.8 to <3, 3 to <5, and ≥5 in 0.2%, 2.0%, 61.8%, 31.8%, and 2.6% of pediatric patients and <0.6, 0.6 to <0.7, 0.7 to <0.8, and ≥0.8 in 8.0%, 12.7%, 17.7%, and 61.5% of adult patients, respectively. Among pediatric recipients, the PS rate up to 5 years was significantly better in cases with a GRWR ≤5 than in those with a GRWR >5. When the GRWR and donor age were combined, among adult recipients 50 to 60 years old, the early PS and GS up to 5 years were significantly better in cases with a GRWR ≥0.7, than in those with a GRWR <0.7. (P = 0.02). In adults, a multivariate analysis showed that GRWR <0.6, transplant era (<2011), donor age (>60 years), recipient age (>60 years), model for end-stage liver disease score (≥20), and center volume (<10) were significant prognostic factors for long-term PS.

Although a satisfactory long-term PS and GS, especially in the recent era (2011-2021), was achieved in the JLTS series, a GRWR ≥5 in pediatric cases and relatively old donors with a GRWR <0.7 in adult cases should be managed with caution.

To clarify the Japan criteria (JC), as proposed in 2019, in order to identify the most appropriate treatment methods for hepatocellular carcinoma (HCC) recurrence and assess the feasibility of pre-living donor liver transplantation (LDLT) downstaging within these criteria.

The subjects of this study were 169 LDLT patients with HCC recurrence. We performed univariate and multivariate analyses of the factors contributing to HCC recurrence after LDLT and clarified the post-transplant outcomes of pre-LDLT downstaging.

Univariate and multivariate analysis identified beyond the JC (p = 0.0018) and a neutrophil-to-lymphocyte ratio > 2.01 (p = 0.029) as independent risk factors. Patients who met the JC had significantly higher recurrence-free and overall survival rates after LDLT (p < 0.0001) than those who did not (p = 0.0002). The post-transplant outcomes of patients within the JC after downstaging were significantly better than those of patients beyond the JC (p = 0.034) and equivalent to those within the JC without downstaging.

Even for HCC recurrence, the JC could play an important role in deciding on the best treatment strategy, and downstaging within the JC had good post-transplant outcomes.

An update on the management of Hepatocellular carcinoma (HCC) is provided in the present article for those interested in the UEMS/EBSQ exam in Surgical Oncology. The most recent publications in HCC, including surveillance, guidelines, and indications for liver resection, liver transplantation, and locoregional or systemic therapies, are summarised. The objective is to yield a set of main points regarding HCC that are required in the core curriculum of hepatobiliary oncological surgery.