Liver Cancer最新文献

{"title":"Deep Response as a Novel Efficacy Endpoint in Hepatocellular Carcinoma.","authors":"Masatoshi Kudo","doi":"10.1159/000553391","DOIUrl":"10.1159/000553391","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":"497-505"},"PeriodicalIF":10.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to Poly- and Perfluoroalkyl Substances and Risk of Hepatocellular Carcinoma in Male Patients with Cirrhosis Related to Hepatitis C Virus Infection.","authors":"Aaron P Thrift, Noura Abdulrahman, Priya B Shetty, Hyeyeun Lim, Yanyan Chen, Hashem B El-Serag","doi":"10.1159/000551746","DOIUrl":"https://doi.org/10.1159/000551746","url":null,"abstract":"<p><strong>Introduction: </strong>Prior studies suggest that per- and polyfluoroalkyl substances (PFAS) may increase risk of liver disease including hepatocellular carcinoma (HCC) via changes in hepatic lipid, amino acid, and glucose metabolism. However, whether PFAS promotes HCC among individuals with cirrhosis has not been examined. We examined associations of PFAS exposure and risk of HCC among patients with cirrhosis.</p><p><strong>Methods: </strong>In this nested case-control study, pre-diagnostic serum PFAS concentrations were measured using liquid chromatography-tandem mass spectrometry in 47 male patients with cirrhosis who developed incident HCC (cases) and 47 sex- and race/ethnicity-matched male cirrhosis patients who did not progress to HCC (controls). We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using conditional logistic regression.</p><p><strong>Results: </strong>All cases and controls were male, and there were no differences in the distributions of age and race/ethnicity between matched cases and controls. Most cases and controls (81%) had hepatitis C virus, and 85% were overweight/obese. Higher levels of perfluorooctanoic acid-type compounds, including L-perfluorooctanoic acid (OR, 1.63; 95% CI: 1.00-2.74), perfluorodecanoic acid (OR, 2.16; 95% CI: 1.00-5.12), perfluorononanoic acid (OR, 4.26; 95% CI: 1.84-11.9), and perfluoroundecanoic acid (OR, 3.18; 95% CI: 1.27-8.77), were associated with increased risk of HCC. Similarly, higher levels of perfluorooctane sulfonate (PFOS) were associated with higher HCC risk but only in patients with HCV (total PFOS, OR, 1.81; 95% CI: 1.08-4.00). Conversely, higher perfluorobutanesulfonic acid levels were associated with lower risk of HCC, and there was no significant association between perfluoroethylcyclohexane sulfonate level and HCC risk.</p><p><strong>Conclusions: </strong>Exposure to higher PFAS levels was associated with an increased risk of HCC among patients with cirrhosis. These preliminary findings need to be confirmed in large studies and may provide a new insight into the mechanisms of environmental-associated HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148764782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective Conventional Transarterial Chemoembolization Using a Glass Membrane Emulsification Device in Hepatocellular Carcinoma: Multicenter Clinical Trial in Japan.","authors":"Toshihiro Tanaka,Hiroshi Anai,Tetsuya Masada,Satoru Sueyoshi,Takeshi Sato,Shohei Toyoda,Takeshi Matsumoto,Yuto Chanoki,Keisuke Oshima,Sho Shimizu,Mariko Irizato,Ryosuke Taiji,Kiyoyuki Minamiguchi,Hideki Kunichika,Hiroyuki Kurakami,Shigeo Ichihashi,Hideyuki Nishiofuku","doi":"10.1159/000552424","DOIUrl":"https://doi.org/10.1159/000552424","url":null,"abstract":"ObjectiveThe aim of the study was to evaluate the complete response (CR) rate achieved with selective conventional transarterial chemoembolization (cTACE) using a porous glass membrane emulsification device in hepatocellular carcinoma (HCC).MethodsIn a multicenter phase II trial (jRCTs052200095) conducted between January 2021 and June 2023, 50 patients with unresectable HCC (tumor diameter ≤5 cm; Child-Pugh A or B) were enrolled. An emulsion of epirubicin and ethiodized oil (Lipiodol) prepared using the emulsification device was injected into the tumor-feeding arteries, followed by embolization with gelatin sponge particles. The primary endpoint was the CR rate at 3 months post-treatment. Secondary endpoints included the CR rate at 1 month and the incidence of adverse events. Outcomes were compared with a historical control cohort from the JIVROSG-1302 study in exploratory analyses.ResultsTwo patients were excluded after enrollment, leaving 48 patients who received cTACE (safety set). An additional 3 patients were excluded post-treatment, yielding 45 patients for efficacy analysis. The CR rate at both 1 month and 3 months was 97.8% (95% confidence interval: 88.2-99.9%). Serious adverse events (grade ≥3) included elevated AST in 50.0% of patients, elevated ALT in 29.2%, thrombocytopenia in 2.1%, and elevated ALP in 2.1%. The proportion of patients with deterioration in ALBI grade (≥1 grade increase) at 3 months was 17.8%. In exploratory analyses, CR rates were numerically higher than those observed in the historical control.ConclusionSelective cTACE using a W/O emulsion prepared with a glass membrane pumping emulsification device was associated with high short-term CR rates in patients with HCC, with an acceptable safety profile. These findings support further clinical investigation.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"33 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148416156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lenvatinib Versus Sorafenib in First-Line Treatment of Older Patients With Unresectable Hepatocellular Carcinoma: A Subgroup Analysis of the REFLECT Trial","authors":"Masatoshi Kudo, Arndt Vogel, Thomas R. Jeffry Evans, Yuk Ting Ma, Bruno Daniele, Ari David Baron, Amit Mahipal, Shukui Qin, Jean Frederic Blanc, Carlos Lopez Lopez, Ann-Lii Cheng, Su Pin Choo, Fabio Piscaglia, Kalgi Mody, Min Ren, Stephen Lam Chan","doi":"10.1159/000553375","DOIUrl":"https://doi.org/10.1159/000553375","url":null,"abstract":"Background: In the open-label, phase 3 REFLECT trial, lenvatinib had noninferior overall survival (OS) to sorafenib, as well as improved progression-free survival (PFS) and objective response rate (ORR) in patients with unresectable hepatocellular carcinoma (uHCC). We report post hoc safety and efficacy in older patients. Methods: In REFLECT (NCT01761266), patients with histologically/cytologically confirmed uHCC were randomized 1:1 to lenvatinib (12 mg/day [bodyweight ≥60 kg] or 8 mg/day [bodyweight &lt;60 kg]) or sorafenib 400 mg twice daily in 28-day cycles. In this analysis, OS, PFS, ORR, and safety were evaluated in patients aged ≥65 and ≥75 years. Efficacy was evaluated per modified Response Evaluation Criteria in Solid Tumors by masked independent imaging review. Results: By data cutoff (November 13, 2016), 401 patients (208 receiving lenvatinib, 193 receiving sorafenib) were aged ≥65 years; of them, 125 (58 receiving lenvatinib, 67 receiving sorafenib) were aged ≥75 years. In the age ≥65 group, median OS was 14.6 months (95%CI: 13.0−18.7) in the lenvatinib arm and 13.4 months (95%CI: 11.6−16.3) in the sorafenib arm (hazard ratio [HR]: 0.844; 95%CI: 0.664−1.074); the OS HR was 0.807 (95%CI: 0.634−1.028) after adjusting for baseline alpha-fetoprotein. Median PFS was 7.4 months (95%CI: 5.6−9.1) with lenvatinib and 5.4 months (95%CI: 3.6−5.5) with sorafenib (HR: 0.571; 95%CI: 0.432−0.755). ORRs were 42.8% (95%CI: 36.1−49.5) with lenvatinib and 14.5% (95%CI: 9.5−19.5) with sorafenib. The most frequent treatment-emergent adverse events (TEAEs) were hypertension (47.3%) in the lenvatinib arm and palmar-plantar erythrodysesthesia syndrome (50.8%) in the sorafenib arm. The incidence of grade ≥3 TEAEs was 82.1% and 72.5% in the lenvatinib and sorafenib arm, respectively. Similar results were observed in patients aged ≥75 years. Conclusions: Consistent with the overall REFLECT population, older patients in the lenvatinib arm generally showed improved efficacy versus the sorafenib arm, supporting lenvatinib as an option for older patients with uHCC.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"24 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An updated systematic review and meta-analysis of modern radiotherapy techniques for hepatocellular carcinoma","authors":"Sun Hyun Bae, Won Il Jang, Jeong Il Yu, Ji Eun Moon, Hee Chul Park, Mi Sook Kim","doi":"10.1159/000552470","DOIUrl":"https://doi.org/10.1159/000552470","url":null,"abstract":"Introduction: The practice of radiotherapy (RT) is worldwide transitioning from 3-dimensional conformal RT to modern RT techniques for hepatocellular carcinoma (HCC); however, evidence remains insufficient to determine whether these advanced RT techniques improve treatment outcomes. Therefore, we updated the treatment outcomes of modern RT techniques, including intensity-modulated radiotherapy (IMRT), stereotactic body radiotherapy (SBRT), and proton beam therapy (PBT), for patients with liver-confined HCC. Methods: A systematic review of IMRT, SBRT, and PBT was conducted individually following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to April 2025. Results: We included 23 IMRT studies comprising 1,479 patients, 22 PBT studies comprising 1,968 patients, and 35 SBRT studies comprising 3,208 patients. When the total doses were converted to the biologically equivalent doses (BED, Gy10), the median BED (mBED) values ranged 48–180 Gy10 (median, 86) for SBRT, 69–110 GyE10 (median, 101) for PBT, and 55–75 Gy10 (median, 67) for IMRT. The pooled 3-year local progression-free survival rates were 64% (95% confidence interval [CI], 45–81%) for IMRT, 89% (95% CI, 86–91%) for PBT, and 86% (95% CI, 82–90%) for SBRT, respectively (p = 0.0076). The pooled 3-year overall survival rates were 19% (95% CI, 11–29%) for IMRT, 55% (95% CI, 48–62%) for PBT, and 65% (95% CI, 57–72%) for SBRT, respectively (p &lt;0.0001). In addition, the pooled survival rates differed significantly according to the mBED using three cutoff points of 65 Gy10, 80 Gy10, and 100 Gy10. Meta-regression analysis showed that liver function, median tumor size, and portal vein tumor thrombosis were association with survivals in varying degrees. The incidence of severe toxicities after modern RT techniques was low. Conclusions: Modern RT techniques provide remarkable treatment outcomes in patients with HCC. The efficacies of SBRT and PBT were similar and superior to those of IMRT. This difference should be interpreted with caution as controlling for clinical parameters affecting efficacy is not feasible. And a minimal ablative dose between 65 and 100 Gy10 is required to achieve optimal efficacy for HCC.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"45 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alcohol plays a detrimental role in the prognosis of hepatocellular carcinoma related to steatotic liver disease","authors":"Stefano Gitto, Alessandro Vitale, Gianluca Svegliati-Baroni, Giulio Marchesini, Francesco Paolo Russo, Luca Miele, Claudia Campani, Valentina Adotti, Martina Rosi, Francesco Vizzutti, Mariarosaria Marseglia, Andrea Martini, Angelo Sangiovanni, Giuseppe Cabibbo, Giacomo Zaccherini, Giorgia Ghittoni, Maria Di Marco, Francesco Giuseppe Foschi, Filomena Morisco, Sara Grasselli, Carlo Saitta, Francesca Romana Ponziani, Maurizia Rossana Brunetto, Donatella Magalotti, Francesco Azzaroli, Andrea Mega, Rodolfo Sacco, Gerardo Nardone, David Sacerdoti, Sara Boninsegna, Gianpaolo Vidili, Franco Trevisani, Edoardo G. Giannini, Fabio Marra","doi":"10.1159/000553063","DOIUrl":"https://doi.org/10.1159/000553063","url":null,"abstract":"Introduction: The recently adopted nomenclature of steatotic liver disease (SLD) introduces new diagnostic categories, including metabolic dysfunction-associated steatotic liver disease (MASLD), the intermediate metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD). However, their specific impact on the outcomes of hepatocellular carcinoma (HCC) remains unclear. This study aims to evaluate how alcohol consumption influences prognosis in patients with SLD-related HCC. Methods: We analyzed data from 2,864 HCC patients enrolled in the nationwide ITA.LI.CA database (2008–2022), stratifying those with SLD based on alcohol intake into MASLD, MetALD, and ALD. A comparator group with hepatitis B virus (HBV)-related HCC was also included. Multivariable Cox regression and competing risk analyses were employed to assess survival and cause-specific mortality. Results: Among SLD-related HCC, MASLD accounted for 47.1%, ALD 18.7%, and MetALD 7.2%. Patients with ALD showed the poorest liver function, more advanced tumor stage, and the highest mortality risk. Alcohol use progressively worsened prognosis from MASLD to ALD. MetALD and ALD were both associated with increased liver failure- and extrahepatic-related deaths compared to MASLD. In multivariable models, tumor burden, liver decompensation, and alcohol intake were significant predictors of mortality. Notably, metabolic comorbidities impacted prognosis predominantly in MetALD and ALD, suggesting an interaction between alcohol and systemic metabolic dysfunction. Conclusion: Alcohol consumption exerts a dose-dependent detrimental effect on clinical outcomes in SLD-related HCC. These findings support a distinct prognostic stratification for HCC patients with MetALD and ALD, reinforcing the need for alcohol abstinence in individuals with metabolic liver disease.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"17 1","pages":""},"PeriodicalIF":13.8,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carvedilol versus Propranolol in Patients with Hepatocellular Carcinoma: A Nationwide Cohort Study.","authors":"Byeong Geun Song, Myeongcheol Lee, Juhee Cho, Geum-Youn Gwak, Danbee Kang, Dong Hyun Sinn","doi":"10.1159/000553325","DOIUrl":"10.1159/000553325","url":null,"abstract":"<p><strong>Introduction: </strong>Beta-blockers reduce portal hypertension; however, evidence comparing carvedilol and propranolol in patients with hepatocellular carcinoma (HCC) is lacking. We aimed to compare the clinical outcomes of carvedilol versus propranolol in patients with HCC.</p><p><strong>Methods: </strong>Using the Korean National Health Insurance Service database (2009-2023), we identified 11,124 patients with newly diagnosed HCC who were prescribed either carvedilol (<i>n</i> = 2,457) or propranolol (<i>n</i> = 8,667) within 180 days of diagnosis. The primary outcome was all-cause mortality, and the secondary outcome was hepatic decompensation. Multivariable Cox regression and 1:2 PS matching were used as primary analytical approaches, with sensitivity analyses restricted to 6-month survivors and a new-user design.</p><p><strong>Results: </strong>During a median follow-up of 1.5 years, carvedilol use was associated with a significantly lower risk of hepatic decompensation (adjusted hazard ratio [aHR] 0.67; 95% confidence interval [CI] 0.62-0.72) and all-cause mortality (aHR 0.84; 95% CI 0.79-0.90) compared to propranolol. In the 1:2 PS-matched cohort (<i>n</i> = 5,922), these associations remained consistent for both decompensation (HR 0.68; 95% CI 0.63-0.74) and mortality (HR 0.84; 95% CI 0.78-0.90). These benefits were consistent across various subgroups, and in sensitivity analysis excluding early death within 6 months from diagnosis and using a new-user design.</p><p><strong>Conclusion: </strong>In patients with HCC, carvedilol was associated with better survival and lower risk of hepatic decompensation than propranolol. Carvedilol may be the preferred beta-blocker over propranolol in the setting of HCC.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456687/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Regeneration Paradox in Liver Cancer: How Chronic Injury Transforms Healing into Carcinogenesis.","authors":"Chun-Nan Yeh, Miin-Fu Chen","doi":"10.1159/000550897","DOIUrl":"10.1159/000550897","url":null,"abstract":"<p><strong>Background: </strong>The liver presents a fundamental paradox: it possesses unparalleled regenerative capacity yet demonstrates exquisite cancer susceptibility under chronic injury, with 85-90% of hepatocellular carcinoma (HCC) arising from chronic liver disease. Despite decades of research, the field lacks a unifying framework explaining this contradiction.</p><p><strong>Summary: </strong>We propose that HCC arises not from regeneration failing but from regeneration succeeding too long. The identical molecular pathways that safely restore hepatic mass after acute injury become carcinogenic when activated for decades rather than weeks - duration determines destiny. Living donor hepatectomy (60% resection) demonstrates zero cancer risk despite maximal proliferation because activation lasts only 2-4 weeks. Conversely, chronic HCV infection triggers identical responses monthly for 25-30 years, yielding 40-60% cumulative HCC incidence. When regeneration persists chronically, seven corruptions progressively accumulate: division trap (mutational accumulation), selection engine (clonal expansion), memory lock (epigenetic cementing), physical prison (mechanical oncogenesis), immune betrayal (tolerance induction), termination failure (brake inactivation), and senescence trap (SASP-mediated promotion). These develop in parallel and interact synergistically. Clinical evidence validates stage-dependent reversibility: HCV cure at F0-F1 achieves >95% cancer prevention, while cure at F4 cirrhosis provides 70% risk reduction despite irreversible corruptions. Taiwan's HBV vaccination program demonstrates >80% cancer reduction sustained over 40 years when chronic injury is prevented entirely.</p><p><strong>Key messages: </strong>Duration of pathway activation - not pathway identity - determines whether regeneration remains safe or becomes carcinogenic. Understanding HCC pathways as regenerative pathways stuck \"ON\" enables rational therapeutic strategies through corruption-specific targeting. Early intervention prevents >95% of cancers; even late intervention at cirrhosis achieves 70% benefit. The regeneration paradox transforms HCC from mysterious misfortune into predictable consequence, enabling precision prevention and treatment.</p>","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":" ","pages":""},"PeriodicalIF":10.5,"publicationDate":"2026-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Genetic Variants, not Tumor Mutation Burden, Drive Resistance to Immunotherapy in Hepatocellular Carcinoma","authors":"Jinho Lee, Hye Won Lee, Mi Ri Park, Saeam Shin, Jong Rak Choi, Hye Jung Park, Kyung Joo Cho, Seung-Tae Lee, Jun Yong Park","doi":"10.1159/000553049","DOIUrl":"https://doi.org/10.1159/000553049","url":null,"abstract":"Introduction: While immunotherapy has emerged as a promising treatment option, no reliable predictive biomarker has been established for immunotherapy in hepatocellular carcinoma (HCC). In this study, we used genetic analyses to verify the prognostic significance of tumor mutation burden (TMB) in HCC and to search for other cancer characteristics related to prognosis. Methods: Patients with HCC who received a combined therapy of atezolizumab and bevacizumab were prospectively enrolled between July 2020 and April 2023. Circulating tumor DNA analysis was performed using next-generation sequencing before immunotherapy (baseline) and 3 weeks after initiation of immunotherapy (follow-up), from which we retrieved non-synonymous baseline, follow-up, vanished (detected only at baseline), and acquired (detected only at follow-up) variants. Gene sets related to cancer hallmarks and representative oncogenic pathways were curated. Results: Forty-two patients were enrolled in this study. Higher TMB was not correlated with better prognosis. Instead, it showed an inverse relationship, with higher baseline TMB significantly associated with shorter progression-free survival (PFS) (median 2.73 vs 9.17 months, P=0.04). Among other cancer characteristics, acquired variants in the Wnt/β-catenin (PFS: P=1.14×10-4; overall survival (OS): P=0.004) and ATP-dependent chromatin remodeling (PFS: P=0.002; OS: P=0.006) pathways were significantly correlated with worse prognosis. Conclusion: In HCC, TMB is not a reliable predictive biomarker for immunotherapy. Instead, the emergence of acquired genetic variants in the Wnt/β-catenin and chromatin remodeling pathways act as a key driver of resistance.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"101 1","pages":"1-21"},"PeriodicalIF":13.8,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to “Comment on the Article ‘Prognostic Usefulness of Clinical Complete Response after PD-1 Inhibitor Based Combination Therapy for Unresectable Hepatocellular Carcinoma’ ”","authors":"Zhi-Hao Huang, Jian-Li Huang, Lei-Po Lin, Da-Long Yang, Liang Ma, Jian-Hong Zhong","doi":"10.1159/000553004","DOIUrl":"https://doi.org/10.1159/000553004","url":null,"abstract":"","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"27 1","pages":"1-4"},"PeriodicalIF":13.8,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148285685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}