The effect of treatment response to anticoagulant therapy on prognosis of patients with cirrhosis and portal vein thrombosis (PVT) remains unclear. Forty-one patients with cirrhosis and first PVT treated with intravenous anticoagulant therapy between January 2015 and April 2018 at 10 Japanese hospitals were included. Treatment response was defined based on change in size of PVT after anticoagulant therapy as the following: complete response (CR, 0%), partial response (PR, ≤ 50%), stable disease (SD, 51%-100%), and progressive disease (PD, ≥ 101%). CR and PR were combined as the effective group and SD and PD formed as the ineffective group. The median age was 69 years, and 56% of the patients had Child-Pugh class B. Overall, 5 (12%) achieved CR, 22 (54%) achieved PR, 12 (29%) had SD and 2 (5%) had PD. During a median follow-up of 31.8 months from the date of assessment of treatment response, 17 patients died. The overall survival rates at 1- and 3-year were 82.5% and 65.1%, respectively. In the multivariate analysis, the model for end-stage liver disease-Na score was significantly associated with overall survival, whereas treatment response was not significant. Twenty-five patients experienced liver-related events with hospitalization, and the 3-year cumulative rate of liver-related events was 63.9%. In the multivariate analysis, treatment response was significantly associated with liver-related events. The 3-year cumulative rates of liver-related events were 56.7% and 75.5% in the effective and ineffective groups, respectively (p = 0.008). Among patients with cirrhosis, treatment response to anticoagulant therapy for PVT correlated with the incidence of liver-related hospitalization events.
Systemic therapy is the standard care for patients with hepatocellular carcinoma (HCC) and extrahepatic metastases. However, the relative prognostic importance of the intrahepatic tumor burden versus the extent of extrahepatic disease in the era of immune checkpoint inhibitor-based therapy remains unclear. This study aimed to clarify the prognostic impact of intrahepatic tumor burden in patients with metastatic HCC treated with atezolizumab plus bevacizumab (Atez/Bev). We conducted a multicenter retrospective study of patients with HCC and extrahepatic metastases who received first-line Atez/Bev therapy. The intrahepatic tumor burden was assessed using established radiologic parameters, including tumor size, number, and vascular invasion, and the patients were stratified according to the intrahepatic disease severity. Overall survival (OS) was defined as the primary endpoint. Survival analyses were carried out using the Kaplan-Meier method and Cox proportional hazards models. Overall, 306 patients were included in the study. During a median follow-up of 13.5 months, the OS differed markedly according to the intrahepatic tumor burden and macrovascular invasion. The median OS was 17.8 months in the mild MVI group, 12.2 months in the severe MVI group, 29.8 months in the UT7 in group, and 15.2 months in the UT7 out group (p < 0.001). In multivariate analysis, the intrahepatic tumor burden remained an independent predictor of OS, whereas the extent and number of extrahepatic metastatic sites were not significantly associated with prognosis. In metastatic HCC treated with atezolizumab plus bevacizumab, intrahepatic tumor burden was associated with overall survival and may be useful for risk stratification and treatment optimization.
Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a leading global health burden, yet its diagnosis and staging rely heavily on invasive liver biopsies. Liquid biopsy, utilizing circulating cell-free DNA (cfDNA), offers a promising noninvasive alternative to capture hepatic genomic instability. This review consolidates current knowledge on cfDNA biomarkers in MASLD, moving from established quantitative metrics to emerging epigenetic insights. The role of mitochondrial DNA copy number (mtDNAcn) is examined as a dynamic marker of oxidative stress, highlighting its biphasic response: compensatory upregulation in early disease versus depletion in advanced fibrosis. Furthermore, key nuclear copy number variations (CNVs) specifically the XPO4 duplication (13q12.11), CES1 deletion (16q12.2), and ACOT1 deletion (14q24.3) are discussed regarding their mechanistic drivers of fibrogenesis and lipid metabolism dysregulation. Addressing the complexity of MASLD pathogenesis, the discussion extends to emerging multi-modal metrics, including DNA methylation and fragmentomics. These modalities offer superior specificity by tracing the "tissue of origin" and distinguishing apoptotic from necrotic fragmentation patterns, effectively addressing the diagnostic challenges posed by the "burnout" phenomenon in advanced cirrhosis. Finally, critical future directions are outlined, emphasizing the necessity for standardized pre-analytical protocols and the integration of multi-omics data with machine learning. This comprehensive approach will shed light on the transition cfDNA from a research tool to a precise clinical instrument for early risk stratification and therapeutic monitoring.
Chronic hepatitis B virus (HBV) infection remains a major cause of liver cirrhosis and hepatocellular carcinoma. NASVAC is a therapeutic vaccine containing hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg), which has shown clinical potential to induce loss of HBsAg and acquisition of anti-HBs antibodies. Indoleamine 2,3-dioxygenase (IDO), an enzyme that degrades tryptophan into kynurenine, plays a key role in viral persistence by suppressing effector T cell activity and promoting immunoregulatory pathways. This study aimed to elucidate the role of IDO in modulating immune responses to NASVAC. Wild-type and IDO knockout (KO) mice were immunized with NASVAC, and some wild-type mice received an IDO inhibitor. Serum amino acids and anti-HBc and anti-HBs titers, cellular immune responses, splenic CD4/CD8 T cell ratios, and IL-2 production from splenocytes were assessed. Additionally, pretreatment and posttreatment serum samples from NASVAC clinical trial were analyzed for tryptophan and kynurenine levels to assess their association with the efficacy of vaccination. Genetic deletion of IDO markedly enhanced NASVAC-induced humoral and cellular immune responses in mice, whereas pharmacological inhibition partially increased cellular responses. NASVAC treatment modulated the splenic CD4/CD8 ratio, with more pronounced effects in IDO-KO mice. In human participants, lower pretreatment serum kynurenine level was associated with successful acquisition of anti-HBs following NASVAC administration. These findings suggest that IDO activity negatively regulates both humoral and cellular immune responses to NASVAC. Modulation or suppression of IDO may potentially enhance the therapeutic efficacy of NASVAC, and serum kynurenine may represent a predictive biomarker for treatment outcomes in chronic HBV infection. REGISTRY AND THE REGISTRATION NO. The clinical trial was registered in the UMIN Clinical Trials Registry (no. UMIN000027442) and the Japan Registry of Clinical Trials (no. jRCTs061180100).
The prognostic value of serum C-X-C motif chemokine ligand 10 (CXCL10) levels for liver function was investigated in hepatitis C virus (HCV)-infected patients with compensated or decompensated cirrhosis (cLC and dLC, respectively) following treatment with direct-acting antivirals (DAAs). In this nationwide study involving multiple centers, 164 HCV-related liver cirrhosis patients (95 with cLC and 69 with dLC), who underwent treatment with DAAs, were analyzed. Serum levels of CXCL10 were assessed at the baseline (pre-CXCL10) and at 12 or 24 weeks after the end of therapy (post-CXCL10). Associations between CXCL10 levels and liver function after DAA therapy were evaluated. Of the 164 study patients, the albumin-bilirubin (ALBI) grade was reduced to Grade 1 in 85 patients at one year after end of therapy (EOT1Y). Serum CXCL10 ratios (post-CXCL10/pre-CXCL10 levels) were significantly lower in ALBI Grade 1 patients than the others (p = 0.014) at EOT1Y. Receiver operating curve analysis for distinguishing ALBI Grade 1 at EOT1Y demonstrated that the area under the curve was 0.611, with an optimal cutoff value of 0.504. Multivariate analysis revealed that body mass index (BMI; odds ratio [OR] 0.816; p < 0.001), absence of ascites (OR 3.340; p = 0.003), FIB-4 index (OR 0.872; p = 0.026), and serum CXCL10 ratios < 0.504 (OR 2.630; p = 0.010) were independently correlated to ALBI Grade 1 at EOT1Y. The post-to pretreatment serum CXCL10 ratio was independently associated with short-term liver function outcome following HCV eradication in cirrhotic patients. This study was registered to the University Hospital Medical Information Network (36,150).
Sofosbuvir/velpatasvir (SOF/VEL) treatment for hepatitis C virus (HCV)-related decompensated cirrhosis has been shown to achieve a high sustained virologic response (SVR) rate and to improve liver function. However, limited data are available regarding the association between improvements in liver function and long-term survival. This multicenter study aimed to evaluate longitudinal changes in liver function and factors associated with long-term prognosis in patients treated with SOF/VEL. Ninety-one patients who received SOF/VEL for HCV-related decompensated cirrhosis between March 2019 and December 2021 were enrolled. SVR rates, changes in Child-Pugh scores at 12, 24, 48, 72, and 120 weeks after treatment, changes in albumin-bilirubin (ALBI) scores, and overall survival (OS) were assessed. The impact of post-treatment ALBI improvement on prognosis was examined, and its predictive ability for 60-month OS was evaluated using receiver operating characteristic analysis. Survival was compared using the Kaplan-Meier method. The median age was 68.0 years; 36.3% of patients were male, and 24.2% had a history of hepatocellular carcinoma. SVR was achieved in 96.7% of patients. The median observation period was 57.0 months (IQR, 43.0-72.0), and 27 patients (29.7%) died during the observation period. Child-Pugh scores improved from the end of treatment and continued to improve; at 120 weeks, 55.9% of patients had scores of 5 or 6. The median OS was not reached, and the 5-year survival rate was 73.2%. ALBI improvement predicted 60-month OS with a sensitivity of 0.494, a specificity of 0.851, and an optimal cutoff value of a decrease in ALBI score of ≥ 0.103. Patients with ALBI improvement showed significantly better OS. SOF/VEL therapy achieved high SVR rates and demonstrated that post-treatment improvement in the ALBI score is strongly associated with a favorable long-term prognosis in patients with decompensated cirrhosis.
This study compared the efficacy and safety of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) located in the caudate lobe. This retrospective study included 57 patients with caudate lobe HCC who underwent either RFA (n = 39) or SBRT (n = 18) at seven institutions in Japan between January 2016 and August 2025. Local tumor progression (LTP), distant recurrence, overall survival (OS), and changes in albumin-bilirubin (ALBI) scores were analyzed. Propensity score matching (PSM) was performed to minimize baseline imbalances between the two groups. The median age was 74 years, and most patients were male. No significant difference was observed in LTP or distant recurrence between the two groups in the crude cohort (p = 0.856 and 0.622), the PSM cohort (p = 0.286 and 0.907), or the curative-intent subgroup (patients with no more than three lesions, each 3 cm or less) (p = 0.827 and 0.533). Although OS did not differ in the crude cohort (p = 0.090) or the curative-intent subgroup (p = 0.060), OS was better in the RFA group than in the SBRT group in the PSM cohort (p = 0.031). No grade ≥ 3 adverse events occurred in either group. However, ALBI scores worsened significantly in the SBRT group compared with the RFA group (p = 0.012). SBRT achieved favorable local control with an acceptable safety profile. It may represent a valuable alternative for patients in whom RFA is technically challenging.
eLearning has become an essential platform for continuing medical education in Japan, but engagement trends across regions and specialties remain poorly defined. Therefore, this study analyzed participation patterns in an eLearning program jointly organized by the Japanese Society of Alcohol-Related Problems and Addiction Medicine and the Japan Society of Hepatology in an effort to improve clinical skills in alcohol dependence management. Aggregate data from a nationwide eLearning platform as of June 2025 were analyzed, focusing on prefectural, specialty, and academic society distributions. In total, 3860 course completions were analyzed. Participation rose continuously from 2022 to 2025. Tokyo had the highest number of participants (n = 511), followed by Osaka (n = 269) and Kanagawa (n = 257). When adjusted for population, Nara Prefecture ranked first in participation (7.70 per 100,000), followed by Wakayama Prefecture (6.94) and Shimane Prefecture (6.24). Psychiatry accounted for 52.0% of participants (mean age, 44.7 years), whereas internal medicine accounted for 39.3% (mean age, 48.7 years). The Japanese Society of Psychiatry and Neurology contributed 44.3% of participants, whereas the Japan Society of Hepatology contributed 20.5%. More than half of the participants worked in hospitals (53.5%). Meanwhile, 60% of the participants completed courses during holidays or outside standard working hours. This large-scale eLearning initiative achieved nationwide adoption with distinctive regional and specialty disparities. The observed sustained participation in this initiative underscores the value of interdisciplinary collaboration and growing importance of digital education in alcohol-related medicine.
Nerve fibers in the liver help to regulate blood flow and metabolism. They spread from the porta hepatis along the Glissonean sheath (GS) to the hepatocytes and the surrounding areas. In liver transplants, these nerves are completely resected, but their regeneration is not well known. This study examined how and when these nerves regenerate following living donor liver transplantation (LDLT). The study included 7 patients who underwent LDLT, with follow-up periods ranging from 5 to 27 years. Six patients underwent follow-up biopsies, and 1 patient underwent whole-liver re-transplantation. A biopsy specimen obtained during transplantation was used as the control. Nerve regeneration was assessed using synaptophysin immunohistological staining to detect nerve fibers. In 6 cases, nerve fibers disappeared soon after the transplant and were not observed for months or years. In three cases with follow-up periods exceeding 15 years, nerve fibers were observed around the GS only after more than 15 years had elapsed. In the re-transplanted liver, thick nerve fibers grew around the large GS, but thin fibers did not appear around the smaller GS or within liver lobules. Nerve fibers from donor liver diminished immediately after LDLT. They grew mainly around the medium to large GS, with little or no growth within the lobules.
Mineralocorticoid receptor antagonists (MRAs) reduce proteinuria in chronic kidney disease, but their role in preventing bevacizumab-induced proteinuria remains uncertain. This study aimed to assess whether MRAs prevent proteinuria caused by atezolizumab plus bevacizumab in patients with hepatocellular carcinoma. The present retrospective study included patients with advanced hepatocellular carcinoma who received atezolizumab plus bevacizumab between September 2020 and December 2023 at five institutions in Japan. The primary outcome was the time to onset of grade ≥ 2 proteinuria during the first 6 months of bevacizumab treatment. Among 177 patients, 26 received MRAs and 151 did not. The onset of grade ≥ 2 proteinuria occurred significantly later in the MRA group than in the non-MRA group (p = 0.018). In multivariate Cox hazard analysis, diabetes (hazard ratio [HR] = 1.81, 95% confidence interval [CI]: 1.00-3.25, p = 0.049), higher average systolic blood pressure (HR = 2.08, 95% CI: 1.16-3.73, and p = 0.014), and MRA use (HR = 0.21, 95% CI: 0.047-0.90, and p = 0.035) were independently associated with time to grade ≥ 2 proteinuria. Bevacizumab interruption due to proteinuria within 6 months was lower in the MRA group than in the non-MRA group (0% vs. 13.2% and p = 0.049). MRA can suppress moderate or greater proteinuria induced by atezolizumab plus bevacizumab therapy and reduce the rate of bevacizumab interruption.
In hepatocellular carcinoma (HCC), molecularly targeted therapies have been the major focus of recent research. In this study, we evaluated the clinical and biological roles of tumor necrosis factor superfamily 4 (TNFSF4), an inflammatory cytokine, as a therapeutic target in HCC. Using a bioinformatics approach, we identified TNFSF4 as a candidate driver in HCC and assessed the prognostic significance of TNFSF4. Its biological role in HCC was clarified through in vitro experiments, such as cell cycle/colony formation assays, using TNFSF4-overexpressing HCC cells. Moreover, a candidate repositioned drug was identified from public drug sensitivity data, and its antitumor effects and mechanisms were examined both in vitro and in vivo. Analysis of The Cancer Genome Atlas datasets for HCC revealed that TNFSF4 was overexpressed in HCC cells owing to increased DNA copy numbers. Additionally, high TNFSF4 expression was significantly associated with poorer prognosis. Immunohistochemical staining showed that TNFSF4 was overexpressed in the cytoplasm of tumor cells. In vitro analysis showed that TNFSF4 overexpression promoted the G1/S transition in the cell cycle, stimulated proliferation, and increased phosphoinositol-3-kinase (PI3K) phosphorylation, resulting in p21 downregulation and enhanced Rb phosphorylation. In bioinformatics-based drug repositioning analysis, fluspirilene, a typical antipsychotic agent, was identified as a repositioned drug that inhibited HCC growth through cyclin D1 suppression, downstream of TNFSF4. TNFSF4 was a candidate driver and a prognostic biomarker, promoting HCC progression by activating the PI3K/Akt signaling pathway. Furthermore, fluspirilene may have applications as a repositioned drug for HCC with high TNFSF4 expression.
The incidence of non-B non-C hepatocellular carcinoma (NBNC-HCC), which is negative for Hepatitis B surface antigen and Hepatitis C virus antibodies, is on the rise. Relatively higher numbers of NBNC-HCC patients are Hepatitis B core antibody (HBcAb) positive, suggesting that previous HBV infection may play a role in NBNC-HCC development, though the exact mechanisms are unclear. This study aimed to investigate whether HBV genomes are integrated into the host genome of HBcAb-positive NBNC-HCC cases and how these integrations may contribute to cancer development and progression. HBV detection PCR using HBV-specific primers on DNA extracted from HBcAb-positive NBNC-HCC tissue samples was performed. Positive samples were further examined for HBV integration sites using Viral DNA-Capture sequencing Approach. Additionally, Hepatitis B core-related antigen (HBcrAg) serum levels were measured to assess whether they could be predictive for HBV detection PCR results. Among 90 HBcAb-positive NBNC-HCC samples, HBV genome amplification was detected in 19 samples, and differences in HBcrAg status were observed according to HBV detection PCR results. Eighteen of these samples showed HBV integration. The HBV genome was integrated near the TERT gene in 7 samples, resulting in significantly increased TERT mRNA levels, in the KMT2B gene (3 samples), and downstream of the LOC441666 gene (2 samples). The integration sites we identified in our samples have been previously reported in HBV-related HCC, suggesting that HBV integration may also contribute to hepatocarcinogenesis in HBcAb-positive NBNC-HCC. Furthermore, HBcrAg could serve as a potential, noninvasive marker for detecting the HBV genome in these cases.
To assess whether non-invasive test cutoffs recommended in Western guidelines appropriately identify treatment-eligible fibrosis (F2-3) in Japanese patients with MASLD. We analyzed Japanese patients with biopsy-proven MASLD who underwent FIB-4 screening, followed by VCTE or ELF testing. Patients with FIB-4 < 1.3 at age < 65 years or < 2.0 at age ≥ 65 years were excluded, leaving 838 patients in the VCTE cohort and 657 in the ELF cohort. Receiver operating characteristic (ROC) analyses were used to derive cohort-specific cutoffs. For predicting F2-4, a VCTE cutoff of 8 kPa yielded sensitivity/specificity/positive predictive value (PPV)/negative predictive value (NPV) of 83.7%/61.2%/80.2%/66.7%. For predicting F4, a VCTE cutoff of 15 kPa yielded 88.1%/76.8%/22.3%/98.8%. For ELF, a cutoff of 9.2 for predicting F2-4 yielded 94.7%/23.1%/66.5%/73.1%. For predicting F4, a ELF cutoff of 10.5 yielded 80.0%/58.4%/9.9%/98.1%. Using ROC-derived cutoffs (VCTE 9.5 and 15 kPa; ELF 10.3 and 10.8), the performance for predicting F2-4 was 74.0%/75.6%/85.1%/60.8% for VCTE and 66.2%/73.9%/80.6%/57.1% for ELF, whereas the performance for predicting F4 was 88.1%/76.8%/22.3%/98.8% for VCTE and 77.1%/69.8%/12.6%/98.2% for ELF. Among test-positive patients, the distribution of F0-1/F2-3/F4 was 28.7%/69.2%/2.1% for VCTE 8-15 kPa and 47.8%/49.8%/2.4% for ELF 9.2-10.5. Western guideline-recommended VCTE and ELF cutoffs showed high sensitivity in Japanese patients and can be used to exclude cirrhosis. Because the likelihood of cirrhosis increases with VCTE > 15 kPa or ELF > 10.5, treatment eligibility should be determined in conjunction with other clinical information, and confirmatory assessment should be considered when appropriate.
Malignant hepatocellular neoplasm, not otherwise specified (HCN, NOS), is a rare primary liver tumor showing overlapping features of hepatoblastoma and hepatocellular carcinoma. Because of its rarity and histopathologic heterogeneity, the optimal treatment strategy for HCN, NOS remains undefined. We report a case of a 20-year-old woman with initially unresectable HCN, NOS, who was treated with hepatic arterial infusion chemotherapy using a fine-powder formulation of cisplatin suspended in Lipiodol combined with continuous 5-fluorouracil administration (New FP). The therapeutic response was assessed radiologically and serologically after each treatment cycle, and the patient subsequently underwent surgical resection after adequate tumor regression. After eight cycles of New FP, marked tumor shrinkage and a significant decline in tumor markers were achieved, enabling subsequent systemic chemotherapy according to the SIOPEL-4 regimen. Thereafter, conversion hepatectomy was performed, and histological examination of the resected specimen demonstrated approximately 90% tumor necrosis. The patient has remained disease-free for 20 months after surgery. This case demonstrates the potential of New FP as an effective hepatic arterial infusion regimen capable of achieving conversion therapy in rare liver malignancies such as HCN, NOS.
With the increasing incidence of nonviral hepatocellular carcinoma (HCC), current surveillance markers such as alpha-fetoprotein (AFP) and des-gamma carboxyprothrombin (DCP) show limitations. We investigated the percentage of glycosylated ferritin relative to total ferritin (%GF) as a novel diagnostic biomarker for HCC. Samples from 660 patients (chronic liver disease [CLD], n = 278 and HCC, n = 382) were divided into training and validation cohorts (7:3). Glycosylated ferritin was measured using concanavalin A, and %GF was calculated as 100 × (glycosylated ferritin/total ferritin). A multivariate logistic regression analysis was carried out in the training cohort and validated in the validation cohort to improve diagnostic accuracy. In all HCC stages, %GF levels were significantly lower than CLD. The sensitivity and specificity of %GF were 73.7% and 70.8%, respectively, in the training cohort, and 74.1% and 69.8%, respectively, in the validation cohort. The area under the curve (AUC) values of 0.782 (training) and 0.800 (validation) were comparable to those of AFP and DCP. We developed the GFAD index, integrating age, sex, %GF, AFP, and DCP. The GFAD index showed superior diagnostic performance with AUCs of 0.939 (training) and 0.923 (validation). The sensitivity and specificity were 81.9% and 92.7%, respectively (training), and 78.6% and 87.2%, respectively (validation). For early stage HCC, the sensitivity was 67.0% (training) and 69.2% (validation), regardless of the etiology of HCC. The diagnostic performance of %GF for HCC was comparable to AFP and DCP. Moreover, the GFAD index showed excellent performance, even in early stage HCC, regardless of etiology.
Signal intensity on the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-magnetic resonance imaging (MRI) reflects Wnt/β-catenin signaling activity in hepatocellular carcinoma (HCC), and has been associated with poor response to immune monotherapy. However, whether such imaging findings predict resistance to combination immunotherapy has not been prospectively validated. This multicenter prospective study enrolled 152 patients with unresectable HCC treated with atezolizumab plus bevacizumab across 12 Japanese centers. All had Child-Pugh class A liver function and underwent Gd-EOB-DTPA-MRI prior to treatment. Hyperintensity was defined as a relative enhancement ratio ≥ 0.9. Treatment outcomes, including objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and time to partial response (TtPR), were compared between patients with and without hyperintense nodules. Of the 152 patients, 82 received immunotherapy as the first-line and 70 as a later-line therapy. Hyperintense nodules were identified in 57 (37.5%) patients. The hyperintense group showed a higher ORR (36.8% vs. 22.1%) and comparable PFS (8.9 vs. 7.9 months) and OS (16.7 vs. 23.9 months), though not statistically significant. The TtPR was significantly shorter in the hyperintense group (median 26.0 months vs. not reached, p = 0.033), although mainly influenced by prior systemic therapy. Overall, hyperintense lesions were not associated with reduced efficacy and tended to show more favorable responses. This prospective multicenter study demonstrates that hepatobiliary hyperintensity on Gd-EOB-DTPA-enhanced MRI-an imaging surrogate of Wnt/β-catenin activation-does not indicate resistance to atezolizumab plus bevacizumab. These findings support the use of combination immunotherapy in molecularly "immune-cold" HCC.
As of December 31, 2023, a total of 11,731 liver transplants were performed in 70 institutions in Japan. There were 922 deceased donor transplants (919 from heart-beating donors and 3 from non-heart-beating donors) and 10,809 living-donor transplants. The annual total of liver transplants in 2023 was 470. Deceased-donor transplants increased to 118 in 2023 from 86 in 2022. The most frequent indication was cholestatic disease, followed by hepatocellular disease and neoplastic disease. As for hepatocellular disease in 2023, alcoholic cirrhosis and non-alcoholic steatohepatitis were the most common. Five patients underwent so-called dual graft living-donor liver transplantation (1 in 2001, 1 in 2006, and 3 in 2023). Patient survival following transplantation from heart-beating donors (919 transplants: 1-year 89.1%, 3-year 86.8%, 5-year 84.0%, 10-year 76.6%, 15-year 68.9%, and 20-year 57.7%) was similar to that from living-donors (10,809 transplants: 1-year 86.1%, 3-year 82.4%, 5-year 80.0%, 10-year 75.0%, 15-year 70.1%, 20-year 65.3%, 25-year 61.9%, and 30-year 59.5%). Graft survival was very much the same as patient survival (heart-beating donor: 1-year 88.5%, 3-year 86.1%, 5-year 83.2%, 10-year 75.8%, 15-year 68.2%, and 20-year 53.8% and living-donor: 1-year 85.5%, 3-year 81.5%, 5-year 78.9%, 10-year 73.3%, 15-year 68.0%, 20-year 62.8%, 25-year 59.3%, and 30-year 56.7%). Survival data are reported according to age and sex of recipient, indication, graft type, age and sex of donor, ABO-compatibility, and other factors. Cause of death of living liver donors is also reported.
Conversion therapy, which seeks to achieve curative treatment following systemic therapy, is increasingly acknowledged in the management of unresectable hepatocellular carcinoma (HCC). However, validated criteria for predicting eligibility for conversion remain unclear. We investigated the utility of the recently proposed borderline resectable (BR) classification combined with the barcelona clinic liver cancer (BCLC) staging system to identify patients most likely to benefit from conversion following atezolizumab plus bevacizumab (ATZ/BEV) therapy. In this multicenter retrospective study, 532 patients with unresectable HCC treated with ATZ/BEV were categorized using the BR classification and stratified according to the BCLC stage. We evaluated objective response rate (ORR), conversion rate, and overall survival (OS) and carried out multivariate logistic regression analysis to identify predictors of conversion. Conversion therapy was performed in 5.9% of patients. Among those with BCLC-C HCC, the conversion rate was significantly higher in BR1 HCC than in BR2 HCC (15.2% vs. 2.0% and p < 0.01), and BR1 status was independently associated with conversion (odds ratio 7.0). Patients with BCLC-C/BR1 staging showed the highest ORR (45.0%) and favorable OS after conversion (p = 0.015). In contrast, the BR classification had limited predictive value in patients with BCLC-B HCC. Notably, downstaging from BR1 to resectable status was more common than from BR2, suggesting higher conversion feasibility. Integrating BR classification with BCLC staging identified BCLC-C/BR1 patients as optimal candidates for conversion therapy after ATZ/BEV treatment. These findings support incorporating anatomical and oncological criteria into systemic strategies to enable curative interventions in advanced HCC.
Atezolizumab plus bevacizumab (Atez/Bev) in unresectable hepatocellular carcinoma (uHCC) is a standard first-line therapy, but bleeding-related adverse events (BL-AEs) remain clinically concerning, particularly in real-world patients with advanced tumors, portal hypertension, or undergoing antithrombotic therapy (ATT). We aimed to evaluate whether ATT increases bleeding risk, identify pretreatment factors associated with BL-AEs, and assess the impact of bleeding on progression-free survival (PFS) and overall survival (OS) in patients with uHCC treated with Atez/Bev. This multicenter retrospective study included 981 patients with uHCC treated with Atez/Bev. BL-AEs were identified by clinical assessment, imaging, or endoscopy. Predictors of BL-AEs were analyzed using logistic regression. Survival outcomes were compared by Kaplan-Meier method, with inverse probability weighting (IPW) applied to adjust for baseline imbalances. BL-AEs occurred in 102 patients (10.4%) and led to treatment discontinuation in 2.7% patients. Independent predictors of BL-AEs included advanced tumor burden components, such as Vp ≥ 3 portal vein invasion and extrahepatic metastasis. Neither ATT nor portal hypertension-related factors were associated with bleeding risk. PFS did not differ between groups, whereas OS was significantly shorter in the BL group before IPW adjustment than after IPW adjustment. During Atez/Bev therapy, BL-AEs were primarily associated with advanced tumor burden rather than with ATT or baseline portal hypertension-related factors. Although BL-AEs were associated with poorer OS, this should be interpreted cautiously, as bleeding may reflect aggressive tumor biology rather than a direct mortality cause. Careful monitoring for bleeding complications may be required in patients with advanced tumor burden receiving Atez/Bev.
This study investigated the effects of the subcutaneous adipose tissue index (SATI) and visceral adipose tissue index (VATI) on the overall survival (OS) of patients with hepatocellular carcinoma (HCC). This study included 587 patients with HCC. The Cox proportional hazards model was used to identify independent prognostic factors. The optimal SATI cutoff value that yielded the most significant differences in OS was determined using the maximally selected statistics. Survival was estimated using the Kaplan-Meier method, and differences between survival curves were evaluated using the log-rank test. SATI (hazard ratio, 0.99; 95% confidence interval, 0.98-0.99; p < 0.001) was significantly associated with improved OS after adjustment for potential confounders. The high-SATI group (≥ 41.1 cm2/m2 for males and ≥ 48.9 cm2/m2 for females) demonstrated significantly longer survival than those in the low-SATI group (p < 0.001; median survival: 87.0 vs. 40.4 months). The results of the decision tree analysis showed that patients with SATI ≥ 41.0 cm2/m2 who received curative treatment demonstrated the best survival (median survival: 191.8 months). Subgroup analyses revealed that the survival advantage of the high-SATI group was consistent across most subgroups, except for patients with metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, body mass index > 25 kg/m2, VATI ≥ 85 cm2/m2, or hyperlipidemia. In the absence of findings indicative of ectopic lipid accumulation, SAT accumulation is associated with an improved prognosis in patients with HCC.