Adjuvant Therapy for Hepatocellular Carcinoma After Curative Treatment: Several Unanswered Questions.

Most patients with hepatocellular carcinoma (HCC) have a poor prognosis. Hepatectomy and local ablation are the main curative treatments for HCC. Nevertheless, the recurrence rate after hepatectomy or ablation is up to 70%, which seriously affects patient prognosis. Several adjuvant therapies have been explored to reduce postoperative recurrence. However, although a variety of adjuvant therapies have been shown to reduce the recurrence rate and improve overall survival, a standard consensus of national HCC guidelines for adjuvant treatment is lacking. Therefore, there are significant differences in the recommendations for adjuvant therapy for HCC between the Eastern and Western guidelines. A variety of adjuvant treatment methods, such as antiviral therapy, transarterial chemoembolization or traditional Chinese medicine, are recommended by the Chinese HCC guidelines. However, Western guidelines make few recommendations other than antiviral therapy. Adjuvant immune checkpoint inhibitors are recommended only in the recently updated American Association for the Study of Liver Diseases guidelines. This review summarized the existing adjuvant therapy options after curative hepatectomy or ablation and discusses several important dilemmas of adjuvant treatments.

Prevalence of metabolic syndrome among patients with hepatocellular carcinoma of different etiologies: a retrospective study.

AIMS: This study compared the prevalences of metabolic syndrome and of cardiac or kidney comorbidities among patients with hepatocellular carcinoma (HCC) associated with metabolic dysfunction-related fatty liver disease (MAFLD), chronic infection with hepatitis B or C virus (HBV or HCV), or the combination of MAFLD and chronic HBV infection. METHODS: Medical records were retrospectively analyzed for patients with HCC who underwent hepatectomy between March 2013 and March 2023. Patients with HCC of different etiologies were compared in terms of their clinicodemographic characteristics and laboratory data before surgery. RESULTS: Of the 2422 patients, 1,822 (75.2%) were chronically infected with HBV without MAFLD and HCV, 415 (17.2%) had concurrent MAFLD and chronic HBV infection but no HCV infection, 121 (5.0%) had MAFLD without hepatitis virus infection, and 64 (2.6%) were chronically infected with HCV in the presence or absence of MAFLD and HBV infection. Compared to patients chronically infected with HBV without MAFLD and HCV, those with MAFLD but no hepatitis virus infection showed significantly lower prevalence of cirrhosis, ascites, portal hypertension, alpha-fetoprotein concentration ≥ 400 ng/mL, tumor size > 5 cm, multinodular tumors and microvascular invasion. Conversely, they showed significantly higher prevalence of metabolic syndrome, hypertension, type 2 diabetes, abdominal obesity, history of cardiovascular disease, T-wave alterations, hypertriglyceridemia and hyperuricemia, as well as higher risk of arteriosclerotic cardiovascular disease. Compared to patients with MAFLD but no hepatitis virus infection, those with concurrent MAFLD and chronic infection with HBV showed significantly higher prevalence of cirrhosis, ascites and portal hypertension, but significantly lower prevalence of hypertension and history of cardiovascular disease. Compared to patients with other etiologies, those chronically infected with HCV in the presence or absence of MAFLD and HBV infection, showed significantly higher prevalence of cirrhosis, portal hypertension, ascites, and esophagogastric varices. CONCLUSION: Patients with HCC associated with MAFLD tend to have a background of less severe liver disease than those with HCC of other etiologies, but they may be more likely to suffer metabolic syndrome or comorbidities affecting the heart or kidneys.

Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: a multicenter retrospective study.

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Global prevalence of metabolic dysfunction-associated fatty liver disease-related hepatocellular carcinoma: A systematic review and meta-analysis.

BACKGROUND/AIMS: The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). METHODS: This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity-specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD, and non-MAFLD HCC. RESULTS: 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% confidence interval [CI] 34.5-63.0%) and 12.4% (95% CI 8.3-17.3%), respectively. In HCC due to chronic hepatitis B, C, and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI 30.2-50.3%), 54.1% (95% CI 40.4-67.6%) and 64.3% (95% CI 52.7-75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. CONCLUSION: MAFLD is common as a sole aetiology, but more so as a co-factor in mixed-aetiology HCC, supporting the use of positive diagnostic criteria.

Deep learning of pretreatment multiphase CT images for predicting response to lenvatinib and immune checkpoint inhibitors in unresectable hepatocellular carcinoma.

Objectives: Combination therapy of lenvatinib and immune checkpoint inhibitors (CLICI) has emerged as a promising approach for managing unresectable hepatocellular carcinoma (HCC). However, the response to such treatment is observed in only a subset of patients, underscoring the pressing need for reliable methods to identify potential responders. Materials & methods: This was a retrospective analysis involving 120 patients with unresectable HCC. They were divided into training (n = 72) and validation (n = 48) cohorts. We developed an interpretable deep learning model using multiphase computed tomography (CT) images to predict whether patients will respond or not to CLICI treatment, based on the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1). We evaluated the models' performance and analyzed the impact of each CT phase. Critical regions influencing predictions were identified and visualized through heatmaps. Results: The multiphase model outperformed the best biphase and uniphase models, achieving an area under the curve (AUC) of 0.802 (95% CI = 0.780-0.824). The portal phase images were found to significantly enhance the model's predictive accuracy. Heatmaps identified six critical features influencing treatment response, offering valuable insights to clinicians. Additionally, we have made this model accessible via a web server at http://uhccnet.com/ for ease of use. Conclusions: The integration of multiphase CT images with deep learning-generated heatmaps for predicting treatment response provides a robust and practical tool for guiding CLICI therapy in patients with unresectable HCC.

Adjuvant therapy for hepatocellular carcinoma: Dilemmas at the start of a new era.

Approximately 50%-70% of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation. As a result, many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival. The therapy recommended by national guidelines can differ, and guidelines do not specify when to initiate adjuvant therapy or how long to continue it. These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient. These questions need to be addressed by clinicians and researchers.

Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial.

BACKGROUND: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection. METHODS: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery. DISCUSSION: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Prognostic value of aspartate aminotransferase/alanine aminotransferase ratio in hepatocellular carcinoma after hepatectomy.

BACKGROUND: The prognostic significance of the aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio in hepatocellular carcinoma remains uncertain. The aim of the current study was to evaluate the association between the AST/ALT ratio and prognosis in patients with hepatocellular carcinoma after hepatectomy, and to explore the role of underlying liver diseases as mediators. METHODS: This retrospective study included patients with hepatocellular carcinoma who underwent hepatectomy between January 2014 and January 2018 at two Chinese hospitals. The maximally selected rank statistic and g-computation approach were used to quantify and visualize the association between the AST/ALT ratio and overall survival or recurrence-free survival. The role of mediators (chronic hepatitis B, hepatic steatosis and liver cirrhosis) was analysed. RESULTS: Among the 1519 patients (mean(s.d.) age at baseline, 50.5(11.3) years), 1309 (86.2%) were male. During a median follow-up of 46.0 months, 514 (33.8%) patients died and 358 (23.6%) patients experienced recurrence. The optimal cut-off value for the AST/ALT ratio was 1.4, and the AST/ALT ratio greater than or equal to 1.4 was independently associated with a 39.0% increased risk of death and a 30.0% increased risk of recurrence (overall survival: hazard ratio (HR), 1.39; 95% c.i. 1.15 to 1.68; recurrence-free survival: HR, 1.30; 95% c.i. 1.12 to 1.52) after adjusting for confounders. Chronic hepatitis B significantly mediated the association of the ratio of AST/ALT with both overall survival and recurrence-free survival (20.3% for overall survival; 20.1% for recurrence-free survival). CONCLUSION: The AST/ALT ratio greater than or equal to 1.4 was associated with shorter overall survival and recurrence-free survival in patients with hepatocellular carcinoma after hepatectomy, and chronic hepatitis B may play a role in their association.

Prognoses of Patients Treated With Surgical Therapy Versus Continuation of Local-Plus-Systemic Therapy Following Successful Down-Staging of Intermediate-Advanced Hepatocellular Carcinoma: A Multicenter Real-World Study.

BACKGROUND: The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS: Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS: Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS: Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

Importance of optimizing duration of adjuvant immune checkpoint inhibitor therapy to treat postoperative hepatocellular carcinoma after conversion therapy: a case report.

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events.

Hepatectomy combined with apatinib and camrelizumab for CNLC stage IIIb hepatocellular carcinoma: a phase II trial protocol.

INTRODUCTION: Current clinical guidelines recommend systematic antitumour therapy as the primary treatment option for patients with stage IIIb hepatocellular carcinoma (HCC) based on the China liver cancer (CNLC) staging criteria. Several different targeted therapeutics have been applied in combination with immunotherapeutic regimens to date in patients with advanced HCC. The present study was developed to evaluate the relative safety and efficacy of hepatectomy of HCC in combination with targeted apatinib treatment and immunotherapeutic camrelizumab treatment CNLC-IIIb stage HCC patients with the goal of providing evidence regarding the potential value of this therapeutic regimen in individuals diagnosed with advanced HCC. METHODS AND ANALYSIS: This is a multicentre phase II trial with single-arm in which patients undergo hepatectomy in combination with targeted treatment (apatinib) and immunotherapy (camrelizumab). Patients will undergo follow-up every 2-3 months following treatment initiation to record any evidence of disease progression and adverse event incidence for a minimum of 24 months following the discontinuation of treatment until reaching study endpoint events or trial termination. The primary endpoint for this study is patient mortality. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of the Guangxi Medical University Cancer Hospital (KS2022[124]). The results of this study will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05062837.

Adjuvant immune checkpoint inhibitors associated with higher recurrence-free survival in postoperative hepatocellular carcinoma (PREVENT): a prospective, multicentric cohort study.

BACKGROUND: Adjuvant therapy may improve survival of patients with hepatocellular carcinoma (HCC) after curative resection. This study compared safety and efficacy outcomes between patients at high risk of recurrence who received different types of adjuvant therapy or no such therapy after hepatic resection for HCC. METHODS: Recurrence-free survival (RFS), overall survival, and adverse events were compared among patients who received adjuvant immune checkpoint inhibitors (ICIs) alone, ICIs with tyrosine kinase inhibitors (TKIs), or no adjuvant therapy between 13 March 2019 and 19 March 2022. This study was registered on ClinicalTrials.gov (NCT05221398). RESULTS: Of the 517 patients in final analysis, 432 (83.6%) received no adjuvant therapy, 53 (10.2%) received ICIs alone, and 32 (6.2%) received adjuvant ICIs and TKIs. During median follow-up of 34.0 months (IQR 27.8 to 41.6 months), RFS was significantly longer among patients who received either type of adjuvant therapy (25.2 months, 95%CI 16.4-34.0) than among those who received none (16.1 months, 95%CI 12.9-19.4), and this difference remained significant after propensity score matching (HR 0.52, 95%CI 0.35-0.76, P = 0.004). Overall survival was unaffected by either type of adjuvant therapy, while significant difference was observed between patients who received adjuvant therapy or not after propensity score matching (HR 0.31, 95%CI 0.17-0.59, P = 0.005). The rate of grade 3 or 4 adverse events was similar between the two types of adjuvant therapy. CONCLUSIONS: ICIs alone or with TKIs may improve RFS of patients at high risk of HCC recurrence after curative resection.

Predictors and long-term prognosis of early and late recurrence for patients undergoing hepatic resection of hepatocellular carcinoma: a large-scale multicenter study.

Background: Recurrence is common among patients undergoing hepatic resection for hepatocellular carcinoma (HCC), which greatly limits long-term survival. We aimed to identify predictors and long-term prognosis of early and late recurrence after HCC resection. Methods: Multicenter data of patients who underwent HCC resection between 2002 and 2016 were analyzed. Recurrence was divided into early (≤2 years) and late recurrence (>2 years after surgery). Predictors of early and late recurrence, and prognostic factors of post-recurrence survival (PRS) were identified by univariate and multivariate analyses. Results: Among 1,426 patients, 554 (38.8%) and 348 (24.4%) developed early and late recurrence, respectively. Independent predictors associated with early recurrence included preoperative alpha-fetoprotein level >400 µg/L, resection margin <1 cm, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor at the first diagnosis of HCC; independent predictors associated with late recurrence included male, cirrhosis, and tumor size >5.0 cm, multiplicity, macrovascular and microvascular invasion, and satellites of the initial tumor. Patients with early recurrence had a lower likelihood of undergoing potentially curative treatments for recurrence (37.2% vs. 48.0%, P<0.001) and a worse median PRS (13.5 vs. 36.6 months, P<0.001) vs. patients who had late recurrence. Multivariate analysis revealed that early recurrence and irregular postoperative surveillance were independently associated with worse PRS [hazard ratio (HR) =1.250, 95% CI: 1.016-1.538, P=0.035; and HR =1.983, 95% CI: 1.677-2.345, P<0.001]. Conclusions: Predictors associated with early and late recurrence after curative resection for patients with HCC were generally same, although several did differ. Patients with late recurrence had better long-term survival than patients with early recurrence.

Systemic therapy with or without transcatheter intra-arterial therapies for unresectable hepatocellular carcinoma: a real-world, multi-center study.

Background: Systemic therapy is the standard care of unresectable hepatocellular carcinoma (uHCC), while transcatheter intra-arterial therapies (TRITs) were also widely applied to uHCC patients in Chinese practice. However, the benefit of additional TRIT in these patients is unclear. This study investigated the survival benefit of concurrent TRIT and systemic therapy used as first-line treatment for patients with uHCC. Methods: This real-world, multi-center retrospective study included consecutive patients treated at 11 centers accross China between September 2018 and April 2022. Eligible patients had uHCC of China liver cancer stages IIb to IIIb (Barcelona clinic liver cancer B or C stage), and received first-line systemic therapy with or without concurrent TRIT. Of 289 patients included, 146 received combination therapy and 143 received systemic therapy alone. The overall survival (OS), as primary outcomes, was compared between patients who received systemic therapy plus TRIT (combination group) or systemic therapy alone (systemic-only group) using survival analysis and Cox regression. Imbalances in baseline clinical features between the two groups were adjusted through propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Moreover, subgroup analysis was conducted based on the different tumor characteristics of enrolled uHCC patients. Results: The median OS was significantly longer in the combination group than the systemic-only group before adjustment [not reached vs. 23.9 months; hazard ratio (HR), 0.561; 95% confidence interval (CI), 0.366 to 0.861; P = 0.008], after PSM (HR, 0.612; 95% CI, 0.390 to 0.958; P = 0.031) and after IPTW (HR, 0.539; 95% CI, 0.116 to 0.961; P = 0.008). Subgroup analyses suggested the benefit of combining TRIT with systemic therapy was greatest in patients with liver tumors exceeding the up-to-seven criteria, with an absence of extrahepatic metastasis, or with alfa-fetoprotein ≥ 400 ng/ml. Conclusion: Concurrent TRIT with systemic therapy was associated with improved survival compared with systemic therapy alone as first-line treatment for uHCC, especially for patients with high-intrahepatic tumor load and no extrahepatic metastasis.

miR-17-5p slows progression of hepatocellular carcinoma by downregulating TGFßR2.

OBJECTIVE: Downregulation of miR-17-5p has been reported in several cancers, but whether and how miR-17-5p is downregulated in hepatocellular carcinoma (HCC) is unknown. Here, we examined whether miR-17-5p is downregulated in HCC and whether that affects expression of its target gene encoding transforming growth factor ß receptor 2 (TGFßR). METHODS: We screened for potential microRNAs (miRNAs) involved in HCC by analyzing published transcriptomes from HCC patients. Expression of miR-17-5p was measured in HCC cell lines and in tissues from HCC patients using quantitative real-time PCR. The in vitro effects of miR-17-5p on HCC cells were assessed by EdU proliferation assay, CCK-8 cell proliferation assay, colony-formation assay, transwell migration/invasion assay, wound healing assay, and flow cytometry. Effects of miR-17-5p were evaluated in vivo using mice with subcutaneous tumors. Effects of the miRNA on the epithelial-mesenchymal transition (EMT) were assessed, while its effects on TGFßR2 expression were analyzed using bioinformatics and a dual luciferase reporter assay. RESULTS: Patients with low miR-17-5p expression showed lower rates of overall and recurrence-free survival than patients with high miR-17-5p expression, and multivariate Cox regression identified low miR-17-5p expression as an independent predictor of poor overall survival in HCC patients. In vitro, miR-17-5p significantly inhibited HCC cell proliferation, migration, invasion, and the EMT, while promoting apoptosis. In vivo, it slowed the development of tumors. These protective effects of miR-17-5p were associated with downregulation of TGFßR2. CONCLUSION: The miRNA miR-17-5p can negatively regulate the expression of TGFßR2 and inhibit the EMT, thereby slowing tumor growth in HCC, suggesting a potential therapeutic approach against HCC.

Comparison of survival rates as predicted by total tumor volume or tumor burden score in patients with hepatocellular carcinoma concurrent with fatty liver disease and hepatitis B virus.

OBJECTIVES: To analyze prognostic value of total tumor volume (TTV) and tumor burden score (TBS) in surgically treated patients with hepatocellular carcinoma and concurrent fatty liver disease and hepatitis B virus (FLD-HCC). METHODS: FLD-HCC patients who treated with hepatectomy from 2010 to 2018 were analyzed. Prognostic performance of TTV and TBS was determined by ROC analysis. Patients were stratified into low and high tumor burden by optimal cutoff value of 113.4 cm3 for TTV or 6.3 points for TBS. Survival rates were compared between subgroups and independent risk factors were identified by Cox regression. Correlation between TTV and TBS was evaluated. RESULTS: This study enrolled 342 FLD-HCC patients. Survival was significantly higher among patients with low tumor burden than among those with high tumor burden (p < 0.001). High TTV and TBS were independent risk factors for poor survival of FLD-HCC (HR: 3.27 (2.17-4.93) and 3.48 (2.31-5.26), respectively, all p < 0.001). ROC analyses revealed that TTV and TBS had comparable discriminative ability in stratifying overall and recurrence-free survival of FLD-HCC. Correlation analysis revealed a strong correlation between TTV and TBS. CONCLUSIONS: Both TTV and TBS have comparable prognostic value and high TTV/TBS predicts poor survival of patients with FLD-HCC.

Non-classic radiation-induced liver disease after intensity-modulated radiotherapy for Child-Pugh grade B patients with locally advanced hepatocellular carcinoma.

BACKGROUND: The incidence of classic radiation-induced liver disease (cRILD) has been significantly reduced. However, non-classic radiation-induced liver disease (ncRILD) remains a major concern following radiotherapy in patients with hepatocellular carcinoma (HCC). This study evaluated the incidence of ncRILD following intensity-modulated radiotherapy (IMRT) for Child-Pugh grade B (CP-B) patients with locally advanced HCC and established a nomogram for predicting ncRILD probability. METHODS: Seventy-five CP-B patients with locally advanced HCC treated with IMRT between September 2014 and July 2021 were included. The max tumor size was 8.39 cm ± 5.06, and the median prescribed dose was 53.24 Gy ± 7.26. Treatment-related hepatotoxicity was evaluated within three months of completing IMRT. A nomogram model was formulated to predict the probability of ncRILD, using univariate and multivariate analysis. RESULTS: Among CP-B patients with locally advanced HCC, ncRILD occurred in 17 (22.7%) patients. Two patients (2.7%) exhibited a transaminase elevation of ≥ G3, fourteen (18.7%) exhibited a Child-Pugh score increase of ≥ 2, and one (1.3%) demonstrated both a transaminase elevation of ≥ G3 and a Child-Pugh score increase of ≥ 2. No cRILD cases were observed. A mean dose to the normal liver of ≥ 15.1 Gy was used as the cutoff for ncRILD. Multivariate analysis revealed that the prothrombin time before IMRT, tumour number, and mean dose to the normal liver were independent risk factors for ncRILD. The nomogram established on the basis of these risk factors displayed exceptional predictive performance (AUC = 0.800, 95% CI 0.674-0.926). CONCLUSIONS: The incidence of ncRILD following IMRT for CP-B patients with locally advanced HCC was acceptable. A nomogram based on prothrombin time before IMRT, tumour number, and mean dose to the normal liver accurately predicted the probability of ncRILD in these patients.