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12 pages, 616 KB  
Article
The Central Role of Liver Function at Treatment Initiation and Its Preservation at Progression for Post-Progression Survival After Atezolizumab Plus Bevacizumab in Advanced Hepatocellular Carcinoma
by Mizuki Ariga, Teiji Kuzuya, Hisanori Muto, Yoshihiko Tachi, Mariko Kobayashi, Hijiri Sugiyama, Sayaka Morisaki, Gakushi Komura, Takuji Nakano, Hiroyuki Tanaka, Kazunori Nakaoka, Eizaburo Ohno, Kohei Funasaka, Mitsuo Nagasaka, Ryoji Miyahara and Yoshiki Hirooka
Biomedicines 2026, 14(1), 232; https://doi.org/10.3390/biomedicines14010232 - 21 Jan 2026
Viewed by 104
Abstract
Background/Objectives: Atezolizumab plus bevacizumab (Atz+Bev) is widely used for advanced hepatocellular carcinoma (HCC), yet predictors of post-progression survival (PPS), a clinically meaningful endpoint reflecting the feasibility of treatment sequencing, remain unclear. We aimed to identify determinants of PPS and factors associated with [...] Read more.
Background/Objectives: Atezolizumab plus bevacizumab (Atz+Bev) is widely used for advanced hepatocellular carcinoma (HCC), yet predictors of post-progression survival (PPS), a clinically meaningful endpoint reflecting the feasibility of treatment sequencing, remain unclear. We aimed to identify determinants of PPS and factors associated with successful transition to subsequent therapy after progressive disease (PD) on Atz+Bev. Methods: We retrospectively analyzed 132 patients with HCC who initiated Atz+Bev with Child–Pugh A and Eastern Cooperative Oncology Group performance status (ECOG PS) 0/1. PPS was defined as survival from radiological PD to death; tumor response was assessed by RECIST v1.1. Results: Among 132 patients treated with Atz+Bev, median progression-free and overall survival were 9.2 and 21.2 months. PD occurred in 97 patients, with a median PPS of 9.2 months. At PD, 76 patients (78.4%) maintained both Child–Pugh A and ECOG PS 0/1; 93.4% of these patients transitioned to subsequent therapy, compared with 38.0% of patients who did not maintain Child–Pugh A and ECOG PS 0/1. The median PPS values were 14.7 and 2.0 months, respectively (p < 0.0001). In this PD cohort, disease control achieved with subsequent therapy after radiological PD was associated with longer PPS (16.1 vs. 5.0 mosnths; p = 0.0002). ECOG PS 0, Child–Pugh A, absence of portal vein invasion, and AFP < 400 ng/mL at PD independently predicted prolonged PPS. A baseline Child–Pugh score of 5 independently predicted preservation of Child–Pugh A and ECOG PS 0/1 at PD. Conclusions: Initiating Atz+Bev under optimal liver function (Child–Pugh 5) and preserving hepatic reserve and performance status through progression are critical for enabling subsequent therapy and achieving longer PPS. Full article
(This article belongs to the Special Issue Advanced Research in Anticancer Inhibitors and Targeted Therapy)
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14 pages, 2074 KB  
Article
Is There a Role for Hepatobiliary Scintigraphy in Thermal Ablation of Hepatocellular Carcinoma?
by Niek Wijnen, Joep de Bruijne, Rutger C. G. Bruijnen, Emma Ruijs, Hugo W. A. M. de Jong, Marnix G. E. H. Lam and Maarten L. J. Smits
Cancers 2026, 18(2), 322; https://doi.org/10.3390/cancers18020322 - 20 Jan 2026
Viewed by 84
Abstract
Purpose: Hepatobiliary scintigraphy (HBS) provides quantitative assessment of (future remnant) liver function, aiding clinical decision-making for surgical resection and radioembolization of hepatocellular carcinoma (HCC). However, its role for thermal ablation remains unexplored. This pilot study aimed to explore the potential role of [...] Read more.
Purpose: Hepatobiliary scintigraphy (HBS) provides quantitative assessment of (future remnant) liver function, aiding clinical decision-making for surgical resection and radioembolization of hepatocellular carcinoma (HCC). However, its role for thermal ablation remains unexplored. This pilot study aimed to explore the potential role of HBS in guiding patient selection and risk stratification for thermal ablation. Methods: All HCC patients who underwent thermal ablation between January 2021 and August 2025 and had HBS performed prior to ablation were retrospectively reviewed. Ablated non-tumor liver volumes (i.e., volume of ablated healthy parenchyma) were quantified using 3D segmentation. Absolute ablated liver function (i.e., the proportion of total HBS-derived liver function ablated) was also assessed. Clinical outcomes included changes in clinical scores (e.g., Child–Pugh) and the occurrence of hepatic decompensation after ablation. Results: Nine patients (13 tumors) were included. Median global HBS-derived liver function was 3.2%/min/m2 (range 1.6–6.8%/min/m2). Three patients developed hepatic decompensation > 3 months after ablation, unlikely related to thermal ablation itself. The patient with the lowest baseline function (1.6%/min/m2) tolerated ablation without hepatic decompensation. Median ablated non-tumor liver volume was 14.4 cm3 (range 3.1–46.7 cm3), corresponding to a median of 0.9% (range 0.2–3.6%) of total liver volume ablated per lesion. Median absolute ablated function was 0.05%/min/m2 (range 0.02–0.21%/min/m2). Conclusions: Thermal ablation was feasible and well tolerated even in patients with severely impaired liver function. Routine pre-ablation HBS does not appear necessary for thermal ablation of HCC, as only a small percentage of total functional liver volume is ablated. Full article
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15 pages, 531 KB  
Article
Disrupted Vitamin D Metabolism in Hepatocellular Carcinoma: Free and Bioavailable 25(OH)D as Novel Biomarkers of Hepatic Reserve and Clinical Risk
by Joško Osredkar, Matej Rakusa, Aleš Jerin, Borut Štabuc, Martin Zaplotnik, Saša Štupar and Darko Siuka
Molecules 2026, 31(2), 273; https://doi.org/10.3390/molecules31020273 - 13 Jan 2026
Viewed by 212
Abstract
Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. [...] Read more.
Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer. Full article
(This article belongs to the Special Issue Novel Metabolism-Related Biomarkers in Cancer)
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18 pages, 357 KB  
Review
Role of Liver Function in the Multiparametric Assessment of Hepatocellular Carcinoma
by Fabio Melandro, Leonardo Centonze, Ciro Celsa, Simone Famularo, Davide Ghinolfi, Silvia Nardelli, Maria Pallozzi, Ludovico Abenavoli, Fabrizio Romano, Francesca Romana Ponziani, Francesco Paolo Russo and Quirino Lai
Medicina 2026, 62(1), 138; https://doi.org/10.3390/medicina62010138 - 9 Jan 2026
Viewed by 296
Abstract
Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh [...] Read more.
Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh classification and the Model for End-Stage Liver Disease (MELD) score. This is supplemented by newer metrics, including the MELD-Na score, the albumin–bilirubin (ALBI) grade and liver stiffness measurements. These assessments are integral to tailoring treatments, ranging from curative approaches such as surgical resection and liver transplantation to locoregional options (percutaneous ablation, transarterial chemoembolisation and radioembolisation), and systemic therapies. This review explores strategies for balancing the aggressiveness of cancer therapy with the need to preserve hepatic function, particularly in patients with advanced liver dysfunction. A multidisciplinary approach, incorporating expertise from hepatology, oncology, radiology and surgery, is essential for optimising outcomes. Advanced imaging techniques and biochemical markers also improve decision-making and ensure individualised care. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
18 pages, 2033 KB  
Article
Unique Clinically Relevant Prognostic Indicators After TIPS Placement in Cirrhosis Patients with Pre-Existing Kidney Disease
by Rajesh Sasidharan, Cyriac Abby Philips, Akhil Baby, Tharun Tom Oommen, Arif Hussain Theruvath, Aryalakshmi Sreemohan, Ambily Baby, Rizwan Ahamed, Ajit Tharakan and Philip Augustine
J. Clin. Med. 2026, 15(2), 414; https://doi.org/10.3390/jcm15020414 - 6 Jan 2026
Viewed by 240
Abstract
Background: Transjugular intrahepatic portosystemic shunt (TIPSS) outcomes in patients with moderate-to-severe pre-existing kidney disease (PKD, stages G3a–G4) remain poorly characterized. This study aimed to identify potential predictors of mortality specifically in patients with an eGFR 15–59 mL/min/1.73 m2. Methods: [...] Read more.
Background: Transjugular intrahepatic portosystemic shunt (TIPSS) outcomes in patients with moderate-to-severe pre-existing kidney disease (PKD, stages G3a–G4) remain poorly characterized. This study aimed to identify potential predictors of mortality specifically in patients with an eGFR 15–59 mL/min/1.73 m2. Methods: We retrospectively analyzed 68 cirrhosis patients with PKD (eGFR < 60 mL/min/1.73 m2) undergoing a TIPSS between April 2021 and April 2024. Clinical outcomes, renal function changes, and 12-month survival were assessed. Statistical analyses included paired t-tests with false discovery rate adjustment and Kaplan–Meier survival analysis to identify potential predictors of mortality. Results: The cohort (mean age 61.0 ± 8.3 years, 83.8% male, 79.4% with PKD G3a–G3b) showed modest improvement in renal function (creatinine 1.93 to 1.75 mg/dL, p = 0.031), though this biochemical change did not predict survival. Overall mortality was 36.8% (95% CI: 25.4–49.5%) at mean follow-up of 6.7 months. Traditional severity scores (MELD, Child–Turcotte–Pugh) showed no significant association with survival (p > 0.05 for all comparisons). In exploratory analyses, mortality was significantly higher in patients with the following: (1) uncontrolled diabetes before a TIPSS (55.2% vs. 25.9%; RR 2.35, 95% CI: 1.08–5.15, p = 0.032); (2) post-TIPSS infection (70.0% vs. 31.0%; HR 5.44, 95% CI: 1.54–19.23, p = 0.009); and (3) post-procedural cardiac events (85.7% vs. 31.1%; p = 0.005). These associations persisted after false-discovery rate adjustment but require prospective validation given the modest sample size and wide confidence intervals. Conclusions: In this exploratory single-center study of patients with moderate PKD undergoing a TIPSS, we observed associations between mortality and pre-TIPSS poorly controlled diabetes, infections, and cardiac events. These hypothesis-generating findings suggest potential areas for future research. Prospective multi-center studies are needed to validate these associations and determine whether interventions targeting these factors improve outcomes. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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16 pages, 579 KB  
Article
Postoperative Survival Analysis of Elective Colorectal Cancer Surgery with Liver Cirrhosis: A Propensity-Matched Study
by Tsung-Jung Tsai, Kai-Jyun Syu, Xuan-Yuan Huang, Yu Shih Liu, Chang-Wei Chen, Yu-Yao Chang, Yen-Hang Wu and Tsung Chuang
Curr. Oncol. 2026, 33(1), 29; https://doi.org/10.3390/curroncol33010029 - 5 Jan 2026
Viewed by 225
Abstract
Background: Liver cirrhosis increases perioperative risk in colorectal cancer surgery, yet data on long-term outcomes remain limited. In this study, we evaluated postoperative morbidity, mortality, and survival in cirrhotic patients. Methods: In this single-center retrospective cohort, 53 cirrhotic patients undergoing elective colectomy or [...] Read more.
Background: Liver cirrhosis increases perioperative risk in colorectal cancer surgery, yet data on long-term outcomes remain limited. In this study, we evaluated postoperative morbidity, mortality, and survival in cirrhotic patients. Methods: In this single-center retrospective cohort, 53 cirrhotic patients undergoing elective colectomy or proctectomy (2011–2022) were propensity score-matched 1:1 with non-cirrhotic controls. Perioperative variables, complications, and survival were analyzed. Subgroup analyses were performed for right hemicolectomy and non-right hemicolectomy procedures. Kaplan–Meier and logistic regression analyses were implemented to assess outcomes and risk factors. Results: Cirrhotic patients had higher preoperative MELD-Na scores and lower albumin and hemoglobin levels. They experienced greater blood loss, longer operative times, more ICU admissions, and higher rates of major complications (18.9% vs. 3.8%, p = 0.01). Mortality was higher at in-hospital (7.5% vs. 0%), 3-month (9.4% vs. 0%), and 60-month (66% vs. 28.3%) intervals, and these patients’ overall survival was shorter (70.7 vs. 116.8 months, p < 0.001). The subgroup analysis showed that the adverse impact of cirrhosis persisted for both right hemicolectomy and non-right hemicolectomy procedures, with significantly worse long-term survival in cirrhotic patients. Postoperative complications after right hemicolectomy did not differ significantly between groups. Among cirrhotic patients, Child–Turcotte–Pugh class B predicted worse survival than class A (40.1 vs. 84.8 months, p = 0.006). Preoperative hypoalbuminemia (<3.5 g/dL) independently predicted long-term mortality (HR = 3.93). Conclusions: Elective colorectal surgery in patients with cirrhosis is associated with increased perioperative complications and significantly reduced long-term survival. However, postoperative outcomes after right hemicolectomy in cirrhotic patients were comparable to those of non-cirrhotic patients, despite their persistently poorer long-term survival. Optimization of nutritional status and careful preoperative assessment of hepatic reserve are essential to improving outcomes in this high-risk population. Full article
(This article belongs to the Special Issue Surgical Advances in the Management of Gastrointestinal Cancers)
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12 pages, 709 KB  
Article
Early-Stage Australian HCC Patients Treated at Tertiary Centres Show Comparable Survival Across Metropolitan and Non-Metropolitan Residency
by Jonathan Abdelmalak, Simone I. Strasser, Natalie L. Ngu, Claude Dennis, Marie Sinclair, Avik Majumdar, Kate Collins, Katherine Bateman, Anouk Dev, Joshua H. Abasszade, Zina Valaydon, Daniel Saitta, Kathryn Gazelakis, Susan Byers, Jacinta Holmes, Alexander J. Thompson, Jessica Howell, Dhivya Pandiaraja, Steven Bollipo, Suresh Sharma, Merlyn Joseph, Rohit Sawhney, Amanda Nicoll, Nicholas Batt, Myo J. Tang, Stephen Riordan, Nicholas Hannah, James Haridy, Siddharth Sood, Eileen Lam, Elysia Greenhill, Daniel Clayton-Chubb, John Lubel, William Kemp, Ammar Majeed, John Zalcberg and Stuart K. Robertsadd Show full author list remove Hide full author list
Livers 2026, 6(1), 2; https://doi.org/10.3390/livers6010002 - 4 Jan 2026
Viewed by 329
Abstract
Background: Hepatocellular carcinoma (HCC) poses a significant public health challenge in Australia, with poorer survival observed in non-metropolitan populations. This study investigated whether survival disparities persist between non-metropolitan and metropolitan patients if only those with early-stage HCC treated at metropolitan tertiary referral centres [...] Read more.
Background: Hepatocellular carcinoma (HCC) poses a significant public health challenge in Australia, with poorer survival observed in non-metropolitan populations. This study investigated whether survival disparities persist between non-metropolitan and metropolitan patients if only those with early-stage HCC treated at metropolitan tertiary referral centres are considered. Methods: We performed a retrospective cohort study across ten Australian tertiary centres involving patients with a new diagnosis of Barcelona Clinic Liver Cancer (BCLC) stage 0 or A, recorded from 1 January 2016 to 31 December 2020. Residential postcodes were entered using the Modified Monash (MM) model to define metropolitan versus non-metropolitan residence. The primary endpoint was adjusted for all-cause mortality. Results: Our study included 854 patients (metropolitan n = 612, and non-metropolitan n = 242) with a median follow-up of 42.6 months. We found no significant survival or mortality differences between the two groups with the unadjusted Kaplan–Meier survival analysis (log-rank test p = 0.612) and with the Cox proportional hazards regression analysis (adjusted HR 0.93, 95% CI 0.64–1.34, p = 0.690). As expected, tumour burden, Child–Pugh Score, and Charlson Comorbidity Index (CCI) were significant predictors of mortality. Conclusions: Our findings suggest that previously observed survival disparities may stem from delayed diagnosis and reduced access to tertiary care in non-metropolitan regions and highlight the need for improved HCC surveillance and referral pathways, particularly for rural and Indigenous communities, to mitigate geographic inequities. Full article
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14 pages, 1665 KB  
Article
Radiotherapy for Liver-Confined Hepatocellular Carcinoma in Elderly Patients with Comorbidity
by Sun Hyun Bae, Young Seok Kim, Sang Gyune Kim, Jeong-Ju Yoo, Jae Myeong Lee, Sanghyeok Lim, Jae Hong Jung and Chan Kyu Kim
Cancers 2026, 18(1), 91; https://doi.org/10.3390/cancers18010091 - 27 Dec 2025
Viewed by 369
Abstract
Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we [...] Read more.
Background: Globally, the incidence rate of hepatocellular carcinoma (HCC) has increased among elderly patients. Elderly patients often present with multiple comorbidities that affect treatment tolerance and outcomes, and the optimal management strategy for this population has not yet been established. Therefore, we assessed comorbidities in elderly patients and investigated the treatment outcomes of radiotherapy (RT) to liver-confined HCC. Methods: We retrospectively reviewed 40 elderly patients aged ≥70 years with liver-confined HCC, who were treated with RT between 2015 and 2023. Comorbidity was assessed by using the Charlson Comorbidity Index (CCI). Survival outcomes were analyzed using the Kaplan–Meier method. Results: The median age was 75 years (range, 70–87 years). The Barcelona Clinic Liver Cancer stage was 0 in 7 patients, A in 10 patients, B in 9 patients, and C in 14 patients. Most patients (85%) had Child–Pugh class A hepatic function before RT. The CCI scores ranged from 2 to 9 (median, 5). Various RT techniques were applied according to patients’ condition, tumor burden, and treatment aim: three-dimensional conformal radiotherapy in four patients, intensity-modulated radiotherapy in 20 patients; and stereotactic body radiotherapy in 16 patients. RT was delivered with radical intent in 30 patients and with palliative intent in 10 patients. The median biological effective dose calculated with an α/β ratio of 10 was 53.7 Gy10 (range, 39–134.4 Gy10). The median follow-up period after RT was 18 months. The 1-year local progression-free survival and overall survival (OS) rates were 74% and 81%, respectively, and the 3-year rates were 44% and 52%, respectively. Patients with CCI < 5 had more favorable OS than those with CCI ≥ 5, but the difference was not statistically significant. Conclusions: RT for liver-confined HCC appears to be a feasible treatment option for elderly patients with multiple comorbidities. Full article
(This article belongs to the Special Issue Combination Therapy in Geriatric Population with Cancer (2nd Edition))
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15 pages, 562 KB  
Article
Evaluation of Prognosis in Cirrhotic Patients with Esophageal Variceal Bleeding Using Non-Invasive Scores
by Murat Kırdar, Bünyamin Sarıtaş, Abdullah İlhan and Şehmus Ölmez
Medicina 2025, 61(12), 2194; https://doi.org/10.3390/medicina61122194 - 11 Dec 2025
Viewed by 595
Abstract
Background and Objectives: The aims of this study were to evaluate and compare the effectiveness of the Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, as well as the non-invasive fibrosis scores of the aspartate aminotransferase-to-platelet ratio index (APRI) and [...] Read more.
Background and Objectives: The aims of this study were to evaluate and compare the effectiveness of the Child–Turcotte–Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, as well as the non-invasive fibrosis scores of the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4), the Göteborg University Cirrhosis Index (GUCI), and the King’s score, in determining the 6-week and 6-month prognoses in cirrhotic patients with EVB. Materials and Methods: Cirrhotic patients presenting with EVB and admitted to Adana City Training and Research Hospital between September 2017, and October 2022 were included in this study. CTP, MELD, APRI, FIB-4, King’s, and GUCI scores were recorded. The CTP stage and CTP, MELD, APRI, FIB-4, King’s, and GUCI scores were compared according to the 6-week and 6-month prognoses of the patients, and a receiver operating characteristic (ROC) analysis was performed. Results: The mean age of the patients was 59.4 ± 13.9 years, and 55 (64.7%) were male. The 6-week and 6-month mortality rates were 21.2% and 28.2%, respectively. The CTP, MELD, APRI, FIB-4, King’s, and GUCI scores were compared according to the 6-week and 6-month prognoses of the patients. All scores were significantly different between survivors and non-survivors (p < 0.05). The MELD, CTP, and King’s scores were identified as the most effective scores for predicting 6-week mortality (area under the ROC curve (AUC) of 0.888, 0.857, and 0.770, respectively). The MELD, CTP, and King’s scores were identified as the most effective scores for predicting 6-month mortality (AUC of 0.835, 0.823, and 0.734, respectively). Conclusions: The prognosis of cirrhotic patients presenting with EVB is poor. CTP, MELD, APRI, FIB-4, King’s, and GUCI scores were statistically significantly higher in non-survivors than in survivors. CTP and MELD scores were found to be more effective than non-invasive scores in predicting 6-week and 6-month prognoses. The most effective non-invasive score was the King’s score. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
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11 pages, 410 KB  
Article
A Retrospective Cohort Study on Hassab’s Surgery as a Salvage Treatment for Patients with Secondary Prophylaxis Failure for Acute Variceal Bleeding
by Hongwei Zhang, Yuxue Xing, Danpu Wang, Rong He, Ke Zhang, Li Jiang and Zhe Jia
J. Clin. Med. 2025, 14(24), 8772; https://doi.org/10.3390/jcm14248772 - 11 Dec 2025
Viewed by 353
Abstract
Objective: To investigate the safety and efficacy of Hassab’s surgery as a salvage treatment for patients with secondary prophylaxis failure for acute variceal bleeding (AVB), and to determine the role of Hassab’s surgery in the recompensation of cirrhosis and nutritional improvement. Methods: This [...] Read more.
Objective: To investigate the safety and efficacy of Hassab’s surgery as a salvage treatment for patients with secondary prophylaxis failure for acute variceal bleeding (AVB), and to determine the role of Hassab’s surgery in the recompensation of cirrhosis and nutritional improvement. Methods: This study retrospectively analyzed data of 19 patients with AVB caused by cirrhosis and portal hypertension who underwent Hassab’s surgery as a salvage treatment after secondary prophylaxis failure in our center from March 2018 to June 2021. In addition, 47 patients with esophageal and gastric varices who underwent secondary prophylaxis during the same period were assigned to the control group to assess the safety and efficacy of the surgery. The objective laboratorial index and L3-SMA (the L3 skeletal muscle area, cm2, a radiological index for assessing whole-body skeletal muscle mass via CT measurement at the third lumbar vertebra level) of patients in the experimental group before and after surgery were compared to evaluate re-compensation of cirrhosis and nutritional improvement. Results: There was no significant difference in the incidence of perioperative complications and severe complications (Clavien–Dindo grade ≥ IIIb) between the experimental group and the control group. The 5-year re-bleeding-free survival rate and the 5-year overall survival rate in the experimental group were 73.7% and 94.7%, respectively, which were not significantly different from those in the control group. In addition, compared with before surgery, the white blood cell count, platelet count, hemoglobin level, model for end-stage liver disease (MELD) score, Child–Pugh grades, prothrombin time (PT), international normalized ratio (INR), and L3-SMA significantly increased in the experimental group after surgery. Conclusions: Hassab’s surgery proves to be a safe and effective salvage treatment for patients with AVB caused by liver cirrhosis and portal hypertension who failed to undergo secondary prophylaxis. Meanwhile, it was found that after surgery, not only were hypersplenism and coagulation abnormalities relieved, but also cirrhosis was compensated and nutritional status was improved significantly. Thus, this study revealed that Hassab’s surgery with safety and long-term survival effects can be used for patients with secondary prophylaxis failure for AVB in eligible patients Full article
(This article belongs to the Section General Surgery)
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21 pages, 1220 KB  
Article
Diagnostic and Prognostic Potential of CXCL9 and CXCL10 Chemokines in Alcohol-Associated Liver Disease
by Agnieszka Szczerbinska, Jacek Rolinski, Agata Surdacka and Halina Cichoz-Lach
Int. J. Mol. Sci. 2025, 26(23), 11717; https://doi.org/10.3390/ijms262311717 - 3 Dec 2025
Viewed by 556
Abstract
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of [...] Read more.
Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality. In ALD, excessive inflammatory response may induce a massive loss of hepatocytes and lead to irreversible liver damage with progressive fibrosis. Chemokines stimulate the migration of immune cells to the site of inflammation and contribute to the inflammatory cascade that may result in organ failure. We aimed to investigate blood concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 chemokines and their diagnostic and prognostic significance in patients with ALD. In a prospective observational study, 88 individuals were recruited, including 63 patients with ALD (44 men and 19 women, aged 48.49 ± 10.88) and 25 healthy control volunteers matched for age, sex, and ethnicity. In blood samples, concentrations of CXCL9/MIG, CXCL10/IP-10, and CXCL16 were measured using immunoenzymatic ELISAs. Correlations were examined between CXCL levels and (a) traditional inflammatory markers (C-reactive protein, white blood cell count, neutrophil count, lymphocyte count, and neutrophil-to-lymphocyte ratio-NLR) and (b) liver dysfunction severity scores: Child–Turcotte–Pugh (CTP), MELD-NA, MELD 3.0, and modified Maddrey’s discriminant function (mDF). Patients’ survival within 30 days of hospital admission was recorded for analysis. CXCL capabilities in predicting the severity of liver dysfunction and ALD outcome were validated. ALD patients showed significant systemic upregulation of all studied chemokines compared to the control group. Patients with advanced liver disease, classified as MELD-Na ≥ 20, MELD3.0 > 19, and CTP class C, as well as poor short-term outcomes, presented with significantly higher CXCL9 and CXCL10 levels compared to their counterparts. ALD non-survivors had significantly higher concentrations of all studied CXCLs in comparison to controls. Positive correlations between CXCL16 and CRP, leukocytosis, neutrophils, and NLR were confirmed (0.67; 0.46; 0.48; 0.54, respectively). Although none of the chemokines correlated with ALT activity, CXCL9, CXCL10, and CXCL16 showed positive correlations with bilirubin and alkaline phosphatase and inverse correlations with albumin levels. Our findings revealed the diagnostic and prognostic value of the studied CXCLs in ALD. In particular, CXCL9 and CXCL10 may have potential for discrimination of severe liver dysfunction and poor short-term prognosis. Further multicenter studies are required to confirm our results. Full article
(This article belongs to the Special Issue Immune-Liver Axis—from Disease Pathogenesis to Therapeutic Target)
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13 pages, 561 KB  
Article
Performance of GAAD and GALAD Biomarker Panels for HCC Detection in Patients with MASLD or ALD Cirrhosis
by Mohammad Jarrah, Sneha Deodhar, Lisa Quirk, Mohammed Al-Hasan, Ashish Sharma, Guruveer Bhamra, Julia Terrell, Fasiha Kanwal, Yujin Hoshida, Nicole E. Rich, Purva Gopal and Amit G. Singal
Cancers 2025, 17(23), 3835; https://doi.org/10.3390/cancers17233835 - 29 Nov 2025
Viewed by 863
Abstract
Background: Abdominal ultrasound is prone to hepatocellular carcinoma (HCC) surveillance failure, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD), prompting growing interest in blood-based biomarkers as an alternative strategy. Methods: We conducted a case–control study evaluating [...] Read more.
Background: Abdominal ultrasound is prone to hepatocellular carcinoma (HCC) surveillance failure, particularly in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or alcohol-associated liver disease (ALD), prompting growing interest in blood-based biomarkers as an alternative strategy. Methods: We conducted a case–control study evaluating two blood-based biomarker panels, GAAD and GALAD, for detection of early-stage HCC (Barcelona Clinic Liver Cancer (BCLC) stage 0 or A) in patients with MASLD or ALD cirrhosis. Blood specimens were collected within 6 months of HCC diagnosis (cases); controls were patients with cirrhosis but without HCC. GAAD and GALAD scores were measured using the Roche Elecsys platform, applying validated cutoffs of 2.57 and 2.47, respectively. Sensitivity and specificity were compared between the panels and versus ultrasound plus alpha fetoprotein (AFP) using McNemar’s chi square test. Results: Of 152 patients (56.6% men), 46.7% had HCC (54.9% BCLC 0/A) and 53.3% had cirrhosis without HCC. GAAD and GALAD each achieved a sensitivity of 87.2% for early-stage HCC, with specificities of 69.1% and 67.9%, respectively. In paired analyses (n = 90), GAAD had higher sensitivity for any-stage HCC (89.5% vs. 68.4%, p = 0.046) but lower specificity (71.8% vs. 93.0%, p = 0.006) than ultrasound plus AFP. GAAD and GALAD demonstrated consistently higher sensitivity than ultrasound plus AFP across subgroups by age, sex, cirrhosis etiology, and Child Pugh class. Conclusion: In this case–control study of patients with non-viral cirrhosis, GAAD and GALAD demonstrated high sensitivity for early-stage HCC. These findings highlight the potential of blood-based biomarkers to improve HCC surveillance in contemporary populations. Full article
(This article belongs to the Section Cancer Biomarkers)
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14 pages, 5669 KB  
Article
Integrating CTLA-4 Genetics and Soluble Isoforms for the Stratification of HCV-Related Hepatocellular Carcinoma Risk and Aggressiveness
by Marwa Hassan, Walaa H. El-Maadawy, Sally A. Fahim, Sherihan M. Youssef, Omaima Mostafa Badran and Mahmoud Balata
Int. J. Mol. Sci. 2025, 26(22), 11067; https://doi.org/10.3390/ijms262211067 - 15 Nov 2025
Cited by 1 | Viewed by 530
Abstract
Host genetic factors influencing immune regulation are believed to modulate susceptibility to hepatitis C virus (HCV) and related hepatocellular carcinoma (HCC). This study aimed to investigate the association of Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) genetic variants with HCV-related HCC risk, soluble CTLA-4 (sCTLA-4) levels, [...] Read more.
Host genetic factors influencing immune regulation are believed to modulate susceptibility to hepatitis C virus (HCV) and related hepatocellular carcinoma (HCC). This study aimed to investigate the association of Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) genetic variants with HCV-related HCC risk, soluble CTLA-4 (sCTLA-4) levels, and disease severity. 225 age- and sex-matched participants (75 controls, 75 HCV, and 75 HCV-HCC) were enrolled. TaqMan allelic discrimination assays were used for genotyping three CTLA-4 SNPs, and sCTLA-4 was quantified by ELISA. Our results demonstrated that the rs231726 TT genotype and T-allele were significantly associated with HCC. The rs11571317 CC genotype and C-allele, alongside the rs13384548 GG genotype and G-allele, conferred increased risk for both HCV and HCC. Clinically, these high-risk genotypes correlated with worse liver function (Child–Pugh C), higher MELD/Na scores, and larger tumors. Moreover, sCTLA-4 levels showed a stepwise elevation from controls to HCV to HCC patients, peaking in carriers of the rs231726 TT and rs13384548 GG genotypes. In conclusion, this study identifies rs231726, rs11571317, and rs13384548 as robust genetic markers for HCV-related HCC susceptibility and cancer aggressiveness. Our findings provide novel evidence of their role in immune evasion through sCTLA-4 upregulation, offering new perspectives into genotype-based risk stratification and tailored immunotherapeutic strategies. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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23 pages, 329 KB  
Article
Clinical Evaluation of Oxidative Stress Biomarkers in Cirrhosis: Associations with Child–Pugh Class and Hepatic Encephalopathy
by Vlad Pădureanu, Virginia Maria Rădulescu, Cristiana Gianina Moise, Marius Cristian Marinaș, Rodica Pădureanu, Denisa Marilena Săbiescu, Denisa Floriana Vasilica Pîrșcoveanu, Dragoș Forțofoiu and Lidia Boldeanu
Diagnostics 2025, 15(22), 2853; https://doi.org/10.3390/diagnostics15222853 - 11 Nov 2025
Viewed by 699
Abstract
Background/Objectives: Oxidative stress contributes to the pathogenesis of cirrhosis, but its value as a clinical biomarker remains uncertain. Methods: We retrospectively analysed 90 patients with decompensated cirrhosis. Serum malondialdehyde (MDA) and 8-epi-prostaglandin F2α (8-iso-PGF2α) were measured at admission. Biomarker levels were [...] Read more.
Background/Objectives: Oxidative stress contributes to the pathogenesis of cirrhosis, but its value as a clinical biomarker remains uncertain. Methods: We retrospectively analysed 90 patients with decompensated cirrhosis. Serum malondialdehyde (MDA) and 8-epi-prostaglandin F2α (8-iso-PGF2α) were measured at admission. Biomarker levels were compared between Child–Pugh classes B and C, across hepatic encephalopathy grades, and ascites severity, using Mann–Whitney, Kruskal–Wallis, and Spearman correlation tests. Results: Median MDA did not differ significantly between Child–Pugh classes B and C (2.67 [2.10–3.20] vs. 2.45 [1.98–3.05] μmol/L; p = 0.331), nor across ascites categories (p = 0.453). Similarly, 8-iso-PGF2α values did not vary between Child–Pugh classes (255.8 [220.0–310.0] vs. 250.1 [210.0–295.0] pg/mL; p = 0.784) or ascites groups (p = 0.828). Spearman analysis showed no significant correlations with albumin, INR, bilirubin, creatinine, or age, except for a non-significant trend with bilirubin (ρ = −0.18, p = 0.09). Importantly, MDA levels increased significantly across encephalopathy grades (p = 0.021), suggesting a link between systemic oxidative stress and neuropsychiatric impairment. Conclusions: In this clinical cohort, oxidative stress biomarkers did not provide discriminatory value for staging by Child–Pugh or ascites, but MDA was associated with encephalopathy severity. These findings highlight both the limitations and potential clinical relevance of oxidative stress markers in cirrhosis management. Full article
13 pages, 1838 KB  
Article
C-Reactive Protein Levels Predict Improvement in the Liver Functional Reserve by Long-Term Rifaximin Treatment
by Kensuke Kitsugi, Kazuhito Kawata, Go Murohisa, Yashiro Yoshizawa, Masaharu Kimata, Yosuke Kobayashi, Shuhei Unno, Hidenao Noritake, Takeshi Chida and Yoshisuke Hosoda
Diseases 2025, 13(10), 331; https://doi.org/10.3390/diseases13100331 - 8 Oct 2025
Viewed by 744
Abstract
Objectives: Rifaximin is a non-absorbable antibiotic that has an efficacy for hepatic encephalopathy (HE). We previously demonstrated that rifaximin improved liver functional reserve, but this was a single-center study with a limited number of cases, and there were few cases of long-term use. [...] Read more.
Objectives: Rifaximin is a non-absorbable antibiotic that has an efficacy for hepatic encephalopathy (HE). We previously demonstrated that rifaximin improved liver functional reserve, but this was a single-center study with a limited number of cases, and there were few cases of long-term use. Here, we conducted a multicenter study to evaluate the efficacy of long-term rifaximin administration on the liver functional reserve. Methods: A multicenter retrospective study was conducted on cirrhotic patients who received rifaximin for more than 12 months. We evaluated the efficacy of long-term rifaximin administration on the liver functional reserve. Results: A total of 65 cirrhotic patients were enrolled. Administration of rifaximin for 12 months significantly improved the Child–Pugh score (CPS) and albumin–bilirubin (ALBI) score. Regarding the parameters of the CPS, albumin scores significantly improved in addition to HE scores at 12 months. Univariate and multivariate analysis revealed that high C-reactive protein (CRP) levels (>0.69 mg/dL) at baseline were the predictive factor for improvement in the liver functional reserve. Conclusions: This study suggests that long-term rifaximin administration may improve the liver functional reserve in cirrhotic patients through improvement in albumin levels. CRP levels predict improvement in the liver functional reserve. Full article
(This article belongs to the Section Gastroenterology)
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