Hepatocellular Carcinoma Transplantation Research Articles

Recent Advances in Liver Transplantation for Hepatocellular Carcinoma.

Liver transplantation for hepatocellular carcinoma (HCC) remains an evolving field. Major challenges HCC transplant patients face today include liver organ donor shortages and the need for both better pre-transplant bridging/downstaging therapies and post-transplant HCC recurrence treatment options. The advent of immunotherapy and the demonstrated efficacy of immune checkpoint inhibitors in multiple solid tumors including advanced/unresectable HCC hold promise in expanding both the neoadjuvant and adjuvant HCC transplant treatment regimen, though caution is needed with these immune modulating agents leading up to and following transplant. New options for pre-transplant HCC management will expand access to this curative option as well as ensure patients have adequate control of their HCC prior to transplant to maximize the utility of a liver donor. Machine perfusion has been an active area of investigation in recent years and could expand the organ donor pool, helping address current liver donor shortages. Finally, additional HCC biomarkers such as AFP-L3 and DCP have shown promise in improving risk stratification of HCC patients. Together, these three recent advancements will likely alter HCC transplant guidelines in the coming years.

Expanding Selection Criteria in Deceased Donor Liver Transplantation for Hepatocellular Carcinoma: Long-term Follow-up of a National Registry and 2 Transplant Centers.

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.

Novel engineered regulatory macrophages combined with ICIs for post-transplant recurrence after liver transplantation for HCC.

e14582 Background: Liver transplantation is the most effective treatment for early-stage hepatocellular carcinoma (HCC), but post-transplant recurrence limits the efficacy of surgery and affects the patient prognosis. Most of the current attempts to apply immune checkpoint inhibitors (ICIs) to posttransplant recurrence have resulted in either acute allograft rejection or tumor progression, which may be related to the disruption of the immune balance that maintains immune tolerance and enhances immune activation. Methods: Therefore, we constructed an engineered regulatory macrophages (Mregs) with anti-tumor capacity in the transplant setting using reprogrammed liposomes to precisely regulate the immune microenvironment of post-transplant recurrence, in order to create suitable conditions for the safe use of ICIs. Results: Experimentally, Mregs were shown to prolonged allograft survival without promoting tumor development. Through fusing with the Mregs membrane, reprogrammed liposomes insert an anti-CD47 lipid shell onto the surface, enhancing phagocytosis against tumor. The drug-loaded inner core entered into the cytoplasm to reprogram Mregs. Tomivosertib downregulated the expression of PD-L1 and attenuated the immunosuppressive effect. Pexidartinib inhibited the polarization of the M2 pathway and upregulated the expression of CD80, CD86, and MHC II, enhancing the ability of antigen presentation. Combination with anti-PD-L1 antibodies can enhance anti-tumor effect without accelerating allograft rejection. Both in vivo and in vitro results demonstrate that engineered Mregs provide conditions for the safe use of anti-PD-L1 antibodies in the context of transplantation. Conclusions: Engineered Mregs combined with ICIs enhances immunotherapeutic efficacy and provides a viable therapeutic approach for posttransplant recurrence after liver transplantation for HCC.

Downstaging with Atezolizumab-Bevacizumab: A Case Series.

Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC (uHCC) for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezobev remains unknown. In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age: 58.5 years; women-17%; Barcelona Clinic Liver Cancer Stage System B/C:5/7) had received 3-12 cycles of atezo-bev, and 4 of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 (54-114) days following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 (4-30) months, none of the alive patients developed HCC recurrence or graft rejection. Surgical therapy, including LT, is possible after atezo-bev therapy in wellselected patients after downstaging.

Impact of a Liver Immune Status Index among Living Liver Transplant Recipients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a major global health challenge, being the fifth most prevalent neoplasm and the third leading cause of cancer-related deaths worldwide. Liver transplantation offers a potentially curative approach for HCC, yet the risk of recurrence posttransplantation remains a significant concern. This study investigates the influence of a liver immune status index (LISI) on the prognosis of patients undergoing living-donor liver transplantation for HCC. In a single-center study spanning from 2001 to 2020, 113 patients undergoing living-donor liver transplantation for HCC were analyzed. LISI was calculated for each donor liver using body mass index, serum albumin levels, and the fibrosis-4 index. This study assessed the impact of donor LISI on short-term recurrence rates and survival, with special attention to its correlation with the antitumor activity of natural killer (NK) cells in the liver. The patients were divided into two grades (high donor LISI, >-1.23 [n = 43]; and low donor LISI, ≤-1.23 [n = 70]). After propensity matching to adjust the background of recipient factors, the survival rates at 1 and 3 years were 92.6% and 88.9% and 81.5% and 70.4% in the low and high donor LISI groups, respectively (p = 0.11). The 1- and 3-year recurrence-free survival were 88.9% and 85.2% and 74.1% and 55.1% in the low and high donor LISI groups, respectively (p = 0.02). This study underscores the potential of an LISI as a noninvasive biomarker for assessing liver NK cell antitumor capacity, with implications for living-donor liver transplantation for HCC. Donor LISI emerges as a significant predictor of early recurrence risk following living-donor liver transplantation for HCC, highlighting the role of the liver antitumor activity of liver NK cells in managing liver malignancies.

48 Analyzing Changing Trends in Hepatocellular Carcinoma

OBJECTIVES/GOALS: To quantify changing trends in hepatocellular carcinoma (HCC) etiologies, mainly hepatitis C related HCC (HCV-HCC), nonalcoholic fatty liver disease related HCC (NAFLD-HCC), and alcoholic liver disease related HCC (ALD-HCC), at a single center as well as compared to large national databases. METHODS/STUDY POPULATION: This is a retrospective longitudinal study using a single-center database of patients presenting with HCC from January 1995 to September 2023. Etiologies were confirmed through patient history, clinical exam, and viral serologies. Trends in rate of etiology were analyzed using linear regression. Further investigation will include survival analysis. To improve generalizability, the single-center data were supplemented with national cross-sectional data from the NHANES database on liver disease prevalence from March 1999 to August 2023. Data were provided through questionnaire, clinical exam, and viral serologies. Trends in rates will be analyzed using linear regression. RESULTS/ANTICIPATED RESULTS: Among the single center cohort, NAFLD-HCC increased at an average rate of 1.3% per year (95% Confidence Interval (CI) = 1.1% to 1.4%) and HCV-HCC decreased at an average rate of -0.56% per year (95% CI = -0.83% to -0.29%). Projecting the linear models for the past ten years forward, HCV-HCC is predicted to take up a lower proportion than NASH-HCC by 2026 and lower proportion than ALD-HCC by 2028. Future results will include analysis of the changing proportions of etiologies for liver transplant and survival analysis for HCC by etiology from the single center cohort. Additionally, national trends in HCC etiologies will be provided from the NHANES database. The trends from liver transplant etiology and NHANES are expected to parallel the preliminary results. DISCUSSION/SIGNIFICANCE: As the prevalence of NAFLD increases in the general population, more cases of NAFLD-HCC will be seen in the future. Understanding the changing trends can guide surveillance recommendations, shape treatment algorithms, and frame research priorities.

Relationship between non-alcoholic fatty liver disease and hepatocarcinoma: An integrative review

This integrative review explores the connection between Non-Alcoholic Fatty Liver Disease (NAFLD) and Hepatocellular Carcinoma (HCC). NAFLD is characterized by the presence of steatosis in more than 5% of hepatocytes in the absence of excessive alcohol consumption (&gt; 20 g/day in men and &gt; 30 g/day in women) or other chronic liver diseases. On the rise globally, the vast majority is associated with risk factors, mainly obesity and type 2 diabetes mellitus. Advanced NAFLD, including non-alcoholic steatohepatitis, emerges as an important precursor to HCC, in some cases, even before the presence of cirrhosis, due in addition, recent studies highlight NAFLD as a main cause of liver transplantation for HCC. Non-invasive diagnostic methods, such as fibroscan liver elastography, exhibit promise for evaluating hepatic steatosis. Therapeutic interventions aim to slow the progression of NAFLD and mitigate the risks of HCC.

The impact of Karnofsky performance status on prognosis of patients with hepatocellular carcinoma in liver transplantation

BackgroundFunctional performance as measured by the Karnofsky Performance Status (KPS) scale has been linked to the outcomes of liver transplant patients; however, the effect of KPS on the outcomes of the hepatocellular carcinoma (HCC) liver transplant population has not been fully elucidated. We aimed to investigate the association between pre-transplant KPS score and long-term outcomes in HCC patients listed for liver transplantation.MethodsAdult HCC candidates listed on the Scientific Registry of Transplant Recipients (SRTR) database from January 1, 2011 to December 31, 2017 were grouped into group I (KPS 80–100%, n = 8,379), group II (KPS 50–70%, n = 8,091), and group III (KPS 10–40%, n = 1,256) based on percentage KPS score at listing. Survival was compared and multivariable analysis was performed to identify independent predictors.ResultsPatients with low KPS score had a higher risk of removal from the waiting list. The 5-year intent-to-treat survival was 57.7% in group I, 53.2% in group II and 46.7% in group III (P < 0.001). The corresponding overall survival was 77.6%, 73.7% and 66.3% in three groups, respectively (P < 0.001). Multivariable analysis demonstrated that KPS was an independent predictor of intent-to-treat survival (P < 0.001, reference group I; HR 1.19 [95%CI 1.07–1.31] for group II, P = 0.001; HR 1.63 [95%CI 1.34–1.99] for group III, P < 0.001) and overall survival(P < 0.001, reference group I; HR 1.16 [95%CI 1.05–1.28] for group II, P = 0.004; HR 1.53 [95%CI 1.26–1.87] for group III, P < 0.001). The cumulative 5-year recurrence rates was higher in group III patients (7.4%), compared with 5.2% in group I and 5.5% in group II (P = 0.037). However, this was not significant in the competing regression analysis.ConclusionsLow pre-transplant KPS score is associated with inferior long-term survival in liver transplant HCC patients, but is not significantly associated with post-transplant tumor recurrence.

Multiparametric assessment of microvascular invasion in hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Liver transplantation for treatment of nonresectable primary and secondary liver malignancies : Hepatocellular and cholangiocellular carcinomas and colorectal liver metastases

With the increasing efficacy of systemic therapy, liver transplantation plays an important role not only for hepatocellular carcinoma (HCC) but also for nonresectable intrahepatic cholangiocellular carcinoma (iCC), perihilar cholangiocellular carcinoma (phCC) and colorectal liver metastases (CRLM). To review the current state of knowledge regarding the indications, patient selection and expected outcomes of liver transplantation for HCC, iCC, phCC and CRLM. When combined with neoadjuvant locoregional therapy (LRT) and/or systemic therapy, patients with nonresectable HCC, iCC, pCC and CRLM confined to the liver can be successfully transplanted with 5‑year survival rates exceeding 65%. The key to success is strict patient selection, which includes oncogenetic (e.g., BRAFV600E mutation status) and clinical criteria indicative of individual tumor biology (tumor markers: alpha-fetoprotein, AFP/carbohydrate antigen 19‑9, CA19-9/carcinoembryonic antigen, CEA, stable response to neoadjuvant therapy) in addition to morphometric criteria. Liver transplantation offers the possibility of curative treatment even for nonresectable hepatic malignancies. Amajor limitation of this treatment is the lack of donor organs. Crucial for success is patient selection based on individual tumor biology.

Long-term outcomes of liver transplantation in hepatocellular carcinoma with bile duct tumor thrombus: a comparison with portal vein tumor thrombus

Long-term outcomes of liver transplantation in hepatocellular carcinoma with bile duct tumor thrombus: a comparison with portal vein tumor thrombus

Correlation Between NLR Combined with PLR Score and Prognosis of Hepatocellular Carcinoma After Liver Transplantation.

This investigation evaluated the prognostic significance of the neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), and introduced a combined NLR-PLR score to evaluate the correlation between NLR-PLR score and hepatocellular carcinoma (HCC) recurrence. We enrolled 110 patients who underwent orthotopic liver transplantation (LT) for HCC. The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were assessed, and appropriate cut-off values were established. The NLR-PLR score ranged from 0 to 2 as follows: score of 2, high NLR (≥3.37) and high PLR (≥105.96); score of 1, either high NLR or high PLR; score of 0, neither high NLR nor high PLR. The median overall survival (OS) of patients with NLR-PLR score of 0, 1 and 2 was 27, 26.5, and 6 months, respectively. The median OS of patients with NLR-PLR score of 2 was shorter than those with 0 (P < 0.001) and 1 (P < 0.001). The median disease-free survival (DFS) time of patients with NLR-PLR score of 0, 1 and 2 was 24.5, 24, and 6 months, The median DFS of patients with NLR-PLR score of 2 was shorter than those with 0 (P = 0.001) and 1 (P = 0.015). Multivariate analysis showed that NLR-PLR score was an independent risk factor for prognosis and survival. NLR, PLR and NLR-PLR score can predict the long-term survival of patients, and NLR-PLR score, having more predictive value than NLR and PLR alone is an independent risk factor for patient survival. more predictive value than NLR and PLR alone.

Liver transplantation for HCC in cirrhosis: Are Milan criteria outdated?

In Germany, organ allocation is based on the MELD-system and lab-MELD is usually low in patients with hepatocellular carcinoma (HCC) in cirrhosis. Higher medical urgency can be achieved by standard exception for HCC (SE-HCC), if Milan criteria (MC) are met. Noteworthy, UNOS T2 reflects MC, but excludes singular lesions < 2 cm. Thus, SE-HCC is awarded to patients with one lesion between 2 and 5 cm or 2 to 3 lesions between 1 and 3 cm. These criteria are static and do not reflect biological properties of HCC.We present a retrospective cohort of 111 patients, who underwent liver transplantation at UKSH, Campus Kiel between 2007 and 2017. No difference was found in overall survival for patient cohorts using Milan, UCSF, up-to-seven, and French-AFP criteria. However, there was a significantly reduced survival, if microvascular invasion was detected in the explanted organ and in patients with HCC-recurrence. The exclusive use of static selection criteria including MC appear to limit the access to liver transplantation.

Blood salvage and autotransfusion during orthotopic liver transplantation for hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is a significant cause of oncologic mortality worldwide. Liver transplantation represents a curative option for patients with significant liver dysfunction and absence of metastases. However, this therapeutic option is associated with significant blood loss and frequently requires various transfusions and intraoperative blood salvage for autotransfusion (IBS-AT) with or without a leukocyte reduction filter. This study aimed to analyze available evidence on long-term oncologic outcomes of patients undergoing liver transplantation for HCC with and without IBS-AT. Per PRISMA guidelines, a systematic review of keywords "Blood Salvage," "Auto-transfusion," "Hepatocellular carcinoma," and "Liver-transplant" was conducted in PubMed, EMBASE, and SCOPUS. Studies comparing operative and postoperative outcomes were screened and analyzed for review. Twelve studies totaling 1704 participants were included for analysis. Length of stay, recurrence rates, and overall survival were not different between IBS-AT group and non IBS-AT group. IBS-AT use is not associated with increased risk of recurrence in liver transplant for HCC even without leukocyte filtration. Both operative and postoperative outcomes are similar between groups. Comparison of analyzed studies suggest that IBS-AT is safe for use during liver transplant for HCC.

Overall Survival Prediction by Tumor Microenvironment Lymphocyte Distribution in Hepatocellular Carcinoma After Liver Transplantation

IntroductionOur previous research demonstrated that CD8+ cell density profiling using a hexagonal grid-based digital image analysis method provides predictors of patient outcomes after liver resection due to hepatocellular carcinoma (HCC). Continuing our study, we have further investigated the applicability of the methodology to patients receiving a liver transplant for HCC. MethodsThe retrospective study enrolled patients with HCC who underwent liver transplantation (LT) at the Vilnius University Hospital Santaros Clinics between 2007 and 2020. We determined the density profiles of CD8+ lymphocytes at the interface between HCC and stroma and the interface between the perineoplastic liver parenchyma and stroma. Both digital image analysis and the hexagonal grid-based immunogradient method were applied to CD8+ immunohistochemistry images. Survival statistics based on clinicopathological, peripheral blood analysis, and surgical data determined the prognostic value of these indicators. ResultsUnivariate clinicopathological predictors of worse OS after LT included: patient's age at the time of the transplantation, a higher number of HCC nodules, lower platelet count, longer activated thromboplastin time, lower serum albumin, higher serum total bilirubin, and lower serum creatinine levels. The two independent predictors of overall survival were mean CD8+ cell density at the epithelial edge of the explanted liver parenchyma-stroma interface and peripheral blood platelet count. ConclusionsOur model discloses that preoperative peripheral blood platelet count and mean CD8+ cell density at the epithelial edge of nonmalignant interface in the explanted liver parenchyma are independent predictors of OS for HCC after LT.

MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?

Alcohol-related Liver Disease (ALD) is the primary cause of chronic liver disorders and hepatocellular carcinoma (HCC) development in developed countries and thus represents a major public health concern. Unfortunately, few therapeutic options are available for ALD and HCC, except liver transplantation or tumor resection for HCC. Deciphering the molecular mechanisms underlying the development of these diseases is therefore of major importance to identify early biomarkers and to design efficient therapeutic options. Increasing evidence indicate that epigenetic alterations play a central role in the development of ALD and HCC. Among them, microRNA importantly contribute to the development of this disease by controlling the expression of several genes involved in hepatic metabolism, inflammation, fibrosis, and carcinogenesis at the post-transcriptional level. In this review, we discuss the current knowledge about miRNAs’ functions in the different stages of ALD and their role in the progression toward carcinogenesis. We highlight that each stage of ALD is associated with deregulated miRNAs involved in hepatic carcinogenesis, and thus represent HCC-priming miRNAs. By using in silico approaches, we have uncovered new miRNAs potentially involved in HCC. Finally, we discuss the therapeutic potential of targeting miRNAs for the treatment of these diseases.

Long-term outcomes of liver transplantation in hepatocellular carcinoma with bile duct tumor thrombus: a comparison with portal vein tumor thrombus

Long-term outcomes of liver transplantation in hepatocellular carcinoma with bile duct tumor thrombus: a comparison with portal vein tumor thrombus

Integrating single-cell and spatial transcriptomics to elucidate the crosstalk between cancer-associated fibroblasts and cancer cells in hepatocellular carcinoma with spleen-deficiency syndrome

Background and aimMost patients with hepatocellular carcinoma (HCC) in China have been diagnosed with spleen deficiency syndrome (SDS), which accelerates the progression of HCC by disrupting the tumor microenvironment homeostasis. This study aimed to investigate the intercellular crosstalk in HCC with SDS. Experimental procedureAn HCC-SDS mouse model was established using orthotopic HCC transplantation based on reserpine-induced SDS. Single-cell data analysis and cancer cell prediction were conducted using Seurat and CopyKAT package, respectively. Intercellular interactions were explored using CellPhoneDB and CellChat and subsequently validated using co-culture assays, ELISA and histological staining. We performed pathway activity analysis using gene set variation analysis and the Seurat package. The extracellular matrix (ECM) remodeling was assessed using a gel contraction assay, atomic force microscopy, and Sirius red staining. The deconvolution of the spatial transcriptomics data using the “CARD” package based on single-cell data. Results and conclusionWe successfully established the HCC-SDS mouse model. Twenty-nine clusters were identified. The interactions between cancer cells and cancer-associated fibroblasts (CAFs) were significantly enhanced via platelet-derived growth factor (PDGF) signaling in HCC-SDS. CAFs recruited in HCC-SDS lead to ECM remodeling and the activation of TGF-β signaling pathway. Deconvolution of the spatial transcriptome data revealed that CAFs physically surround cancer cells in HCC-SDS. This study reveals that the crosstalk of CAFs-cancer cells is crucial for the tumor-promoting effect of SDS. CAFs recruited by HCC via PDGFA may lead to ECM remodeling through activation of the TGF-β pathway, thereby forming a physical barrier to block immune cell infiltration under SDS.

Primary versus Salvage Liver Transplantation after Curative-Intent Resection or Radiofrequency Ablation for Hepatocellular Carcinoma: Long-Term Oncological Outcomes.

Liver transplantation for hepatocellular carcinoma (HCC) may be performed ab initio, primary liver transplantation (PLT), or for HCC recurrence after previous treatments such as liver resection (LR) or radiofrequency ablation (RFA), salvage liver transplantation (SLT). The aim of this study was to evaluate the oncological outcomes of SLT vs. PLT. For this, a retrospective study was carried out on patients undergoing liver transplantation for HCC. The outcomes of PLT were compared with those of SLT. The primary outcome was disease-free survival (DFS). The secondary outcomes included overall survival (OS), cancer-specific survival (CSS), and major postoperative complications. A sub-analysis of SLT-LR and SLT-RFA was also performed. In total, 141 patients were included: 96 underwent PLT and 45 SLT. Among the SLT group, 25 patients had undergone previous LR while 20 had had RFA. There were no differences in the major postoperative complications. Unadjusted DFS was significantly longer in the PLT group (p = 0.02), as were OS (p = 0.025) and CSS (p = 0.001). There was no difference in DFS between PLT and SLT-LR groups, while a significant difference was found between the PLT and SLT-RFA groups (p = 0.035). Nonetheless, DFS was no different between the SLT-LR and SLT-RFA groups. PLT appears to offer superior long-term oncological outcomes to SLT. Both SLT-LR and SLT-RFA offer acceptable OS and CSS. Further prospective studies are needed to confirm these results, but the re-direction of grafts and transplant philosophy towards PLT rather than SLT may need to be considered.

Real-World Epidemiology, Treatment Patterns, and Disease Burden of Chronic Hepatitis B and HDV Co-Infection in South Korea.

Long-term complications of chronic hepatitis B (CHB) viral infection, such as cirrhosis, hepatocellular carcinoma (HCC), and liver failure, cause a large disease burden. This study aimed to describe the epidemiology, clinical outcomes, and treatment patterns of CHB infection and co-infection with hepatitis Dvirus (HDV) in South Korea. The retrospective, observational study used existing data from the Health Insurance Review and Assessment Service (HIRA) database. Confirmed cases of (CHB) and HBV/HDV co-infection were identified between 2013 and 2019. Hepatitis C virus co-infections and acute HBV infections were excluded. Incident cases diagnosed between 2015 and 2018 with no prior disease history up to 2years were included. Patient characteristics, clinical outcomes, economic burden, and healthcare-resource utilization were described. The estimated 7-year prevalence of CHB and HBV/HDV co-infection were 0.9% and 0.0024%, respectively. The prevalence was higher among 45-54years old (CHB: 1.6%, HBV/HDV: 0.0049%) and males (1.1%, 0.0035%). The 5-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, HCC, and liver transplantation were 13.3%, 7.1%, 8.4%, and 0.7%, respectively. Hyperlipidemia (40.6%), hypertension (23.5%), and peptic ulcer (23.7%) were the more prevalent comorbidities. Among CHB patients, 48.1% received≥1 prescribed anti-HBV drug including interferon or nucleos(t)ide analogues and 64.4% had≥1 hospitalization compared to 80.4% and 79.4% HBV/HDV patients. Estimated total healthcare costs for CHB and HBV/HDV were US$786million and $62million, respectively. These findings provide insights to the epidemiology, clinical burden, treatment patterns, and healthcare costs of CHB and HBV/HDV co-infection in South Korea.