Albumin-bilirubin Grade Research Articles

Comparison of Liver Fibrosis and Function Indices with Extracellular Volume Using Dual-energy CT: A Retrospective Study.

Dual-Energy Computed Tomography (DECT) enables the direct measurement of iodine accumulation in the extracellular space. To compare measures of liver fibrosis and function with Extracellular Volume (ECV) from iodine/water images using DECT. Data was obtained from 119 consecutive patients who underwent abdominal DECT. A region of interest was set in the right lobe of the liver, pancreas, spleen, and aorta on iodine density images. ECV was calculated using the following formula: ECV = (1 - hematocrit) × [iodine concentration in the liver (or pancreas, spleen) / iodine concentration in the aorta]. The severity of liver fibrosis was estimated using the aminotransferase/platelet ratio index (APRI) and the Fibrosis-4 (FIB-4) index. Liver function was assessed by the Child-Pugh classification and albumin-bilirubin (ALBI) grade. Data were analyzed by the Spearman rank correlation coefficient, one-way analysis of variance, and post hoc analysis. The correlation between ECV and fibrosis indices (APRI and FIB-4) was only significant, with a weak magnitude for liver ECV quantification at the equilibrium phase (r=0.25 and r=0.20, respectively). The correlations between liver function index and ECV quantification were more robust than with fibrosis index. The highest correlations (r=0.50) were found between ALBI grade and liver ECV at the equilibrium phase. Liver ECV values at the equilibrium phase had a significant difference between ALBI grade 1 vs. 2 and grade 1 vs. 3. Liver ECV quantification by DECT is more suitable for evaluating liver function than liver fibrosis severity.

ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma

AbstractBackground & AimsPreserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.MethodsDemographic, tumour and therapy‐related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary endpoint was percentage of patients with Child‐Pugh class A (CP‐A) liver disease and PS 0–1 after sorafenib discontinuation.ResultsSorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP‐A and 60 patients (33%) were PS 0–1; 43 patients (24%) were both CP‐A and PS 0–1. On multivariable analysis, patients with Albumin‐Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post‐sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72–8.25, P = .0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (P = .008).ConclusionsMost patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.

Modified Albumin-Bilirubin Grade and Alpha-Fetoprotein Score (mALF Score) for Predicting the Prognosis of Hepatocellular Carcinoma after Hepatectomy.

We developed and evaluated a modified albumin-bilirubin grade and α-fetoprotein (mALF) score, a nutritional and oncological assessment tool for patients with hepatocellular carcinoma (HCC) after surgical resection. Patients (n = 480) who underwent R0 resection between 2010 and 2020 were analyzed retrospectively. The mALF score assigned one point for a modified albumin-bilirubin (mALBI) grade 2b or 3 and one point for an α-fetoprotein (AFP) level ≥ 100 ng/mL. Patients were classified by mALF scores of 0 (mALBI grade 1/2a, AFP < 100 ng/mL), 1 (mALBI grade 2b/3 or AFP ≥ 100 ng/mL), or 2 (mALBI grade 2b/3, AFP ≥ 100 ng/mL) points. Liver reserve deteriorated and cancer progressed with increasing score. Postoperative complications (Clavien−Dindo classification ≥ 3) differed significantly among groups. The 5-year recurrence-free survival (RFS) rates were 34.8%, 11.2%, and 0.0% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The 5-year overall survival (OS) rates were 66.0%, 29.7%, and 17.8% for 0, 1, and 2 points, respectively (1 or 2 versus 0 points, p < 0.001). The mALF score was an independent prognostic predictor of RFS and OS. In HCC, the mALF score was effective for predicting postoperative complications and long-term survival.

Evaluation of Pretreatment Albumin-Bilirubin Grade as a Better Prognostic Factor than Child-Pugh Classification in Hepatocellular Carcinoma Patients Administered Transarterial Chemoembolization Combined with Radiotherapy

<h3>Purpose/Objective(s)</h3> This study evaluated the use of pretreatment albumin-bilirubin (ALBI) grade as a prognostic factor in hepatocellular carcinoma (HCC) patients receiving combined transarterial chemoembolization (TACE) and radiotherapy (RT). <h3>Materials/Methods</h3> Patients receiving RT following TACE between January 2011 and December 2020 were analyzed. The exclusion criteria were other biopsy-proven cancers than HCC, distant metastasis, double primary cancer requiring active treatment, history of abdominal RT, and an interval between TACE and RT of >24 weeks. A total of 73 patients were included. ALBI grade was defined as grade 1 (ALBI score ≤-2.60), grade 2 (ALBI score >-2.60 and ≤-1.39), or grade 3 (ALBI score >-1.39). The survival outcomes of patients according to ALBI grade and Child-Pugh (C-P) classification were measured by Kaplan–Meier analysis using log-rank tests. The potential prognostic factors were evaluated using Cox regression analysis. <h3>Results</h3> The median follow-up was 16.3 months (range, 3.6–107.5). Thirty-three (45.2%) and 40 patients (54.8%) were ALBI grades 1 and 2–3, while 64 (87.7%) and 9 (12.3%) were C-P classes A and B, respectively. The difference in the distribution of patients according to each grading system was statistically significant (<i>p=</i>0.003). The ALBI scores ranged from -3.29 to -0.89 (median -2.44). The median progression-free survival (PFS) and overall survival (OS) for ALBI grade 1 <i>vs.</i> 2–3 were 8.6 months <i>vs.</i> 5.0 months (<i>p</i>=0.016), and 27.0 months <i>vs.</i> 15.9 months (<i>p</i>=0.006), respectively. The median PFS and OS for C-P class A <i>vs.</i> B were 6.3 months <i>vs.</i> 6.1 months (<i>p</i>=0.265) and 24.8 months <i>vs.</i> 19.0 months (<i>p</i>=0.630), respectively. In multivariate Cox regression analysis, along with other clinically relevant variables such as age, performance status, tumor marker, C-P classification, and modified Union for International Cancer Control (mUICC) stage, ALBI grade 2–3 was statistically significantly associated with worse PFS and OS compared to ALBI grade 1 (<i>p</i>=0.035, hazard ratio [HR] 1.728, 95% confidence interval [CI] 1.038–2.875 for PFS; <i>p</i>=0.021, HR 2.161, 95% CI 1.124–4.156 for OS). Other than ALBI grade, only mUICC stage 4A was significantly associated with worse OS in multivariate analysis (<i>p</i>=0.009, HR 2.472, 95% CI 1.251–4.885). <h3>Conclusion</h3> These results suggested that ALBI grade could be a better survival probability indicator than C-P classification in patients treated by TACE combined with RT. As many clinical situations, such as vessel-invading HCC, require TACE and RT collectively, further validation of ALBI grade as a prognosticator under these circumstances is warranted.

Prediction of Hepatic Toxicity after Radiotherapy Using a Neural Network Including Blood Biomarkers and Liver Dose Distributions

<h3>Purpose/Objective(s)</h3> ASTRO recently published practical guidelines for treating unresectable hepatocellular carcinoma with radiotherapy, recommending hypofractionated dose escalated regimens when tolerated by the liver. This highlights the need for patient-specific prediction models of radiation-induced hepatic toxicities, which necessitates inclusion not only of radiation dose, but also baseline liver function biomarkers. <h3>Materials/Methods</h3> We developed a shallow neural network to predict declines in Child-Pugh score (CP) of 2 or more, with a focus on robustness, interpretability and ability to include both proton and photon radiation dose distributions. The network uses 1 convolution layer to extract 8 dosimetric features that are representative of the differential DVH (dDVH) and interactions of different dose levels within, which are then combined in a fully connected layer with baseline platelet counts and liver function biomarkers—CP and albumin-bilirubin grade. After registering a study analysis plan, we trained the model on 117 patients from a single institution and independently validated it on 88 patients from another institution, where 47%/36% of the training/validation cohorts received proton radiotherapy. We compared the model to logistic regression to evaluate the importance of feature interactions on predictive power, measured by the area under the receiver operating characteristics (AUC). <h3>Results</h3> The model prediction of CP decline had a cross-validation AUC = 0.86; 95%CI: 0.69-0.97 and independent validation AUC = 0.74 with 89% accuracy in 10% high-risk group. In contrast, logistic regression showed cross-validation AUC 0.73; 95%CI: 0.56-0.88 and validation AUC 0.56, demonstrating a significant importance of feature interactions. Sensitivity analysis of the neural network revealed that patients with low baseline platelet counts were most sensitive to high doses to the normal liver compared to other patient groups, indicating a potential benefit of liver-sparing therapies in these patients. <h3>Conclusion</h3> We developed a patient-specific hepatic toxicity model that can take into account both proton and photon dose distributions and the interaction of radiation dose to normal liver with baseline liver function. Robust model performance across institutions and particularly in high-risk patients could allow stratification of patients to standard, hypofractionated regimens, or proton therapy based on a patient's risk score.

Disease Control and Hepatotoxicity Following Stereotactic Body Radiotherapy for Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> Stereotactic body radiotherapy (SBRT) is increasingly utilized in the definitive management of patients with hepatocellular carcinoma (HCC), but long-term data regarding treatment efficacy and hepatotoxicity are lacking. We present our experience with SBRT and analyze patient and tumor characteristics associated with local control (LC), overall survival (OS), worsening of Child-Pugh (CP) score, and albumin-bilirubin grade (ALBI). <h3>Materials/Methods</h3> Patients with HCC treated with SBRT at a large referral center were included in this IRB-approved retrospective institutional database. Baseline patient characteristics, SBRT dose and fractionation, and laboratory data were collected by chart review. LC and OS were calculated using the Kaplan-Meier method starting from the date of the cross-sectional imaging study diagnosing the HCC lesion treated with SBRT. LC (at lesion level) was computed with a cumulative incidence function censoring for death. Local progression was defined by the interpreting radiologist, interdisciplinary review, or any decision to intervene with salvage therapy. A mixed-effects multivariable analysis (MVA) using a Cox proportional hazards model was performed using patient age, performance status, gender, HCC diameter (maximum length per-lesion), biological effective dose (alpha/beta = 10), number of prior treatments to the target lesion, and pre-treatment CP score as regression variables. CP score and ALBI were used to quantify hepatotoxicity following SBRT. <h3>Results</h3> A total of 130 HCC lesions in 104 patients (69% male) were included and median follow up was 1.6 years (range 0.3 – 6.8). Hepatitis C was the most common etiology for underlying liver disease (n = 44, 42%). The medians for MVA variables were age = 65 years, ECOG performance status = 1, maximum lesion diameter = 2.4 cm, BED10 = 112.5 Gy, CP = A6, and ALBI = grade 1. LC and OS for the entire cohort were 92% and 80% at 1-year, and 89% and 46% at 3-years, respectively. On MVA, no variables were significantly associated with either LC or OS (all p-values > 0.05). At 3-months post-SBRT, the number of patients with a worsening in CP score of 2 and 3+ points were 7 (7%) and 4 (4%), respectively, while the number of patients with a decline in ALBI score of 1 and 2 grades was 27 (26%) and 2 (2%), respectively. Of 12 lesions with local progression following radiation, salvage therapy was delivered in 11 with the most common technique being thermal ablation (n = 7, 64%). There was one documented local failure after salvage treatment. <h3>Conclusion</h3> SBRT with an ablative dose is associated with excellent LC with little hepatotoxicity in well-selected patients. High rates of LC after SBRT appear maintained with longer follow up, but overall survival remains limited.

Outcomes for Salvage Abdominal Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma after Liver Transplantation

<h3>Purpose/Objective(s)</h3> While orthotopic liver transplantation (OLT) is considered curative for most hepatocellular carcinoma (HCC) patients, recurrence can occur in 10-20% of these patients. Data has shown stereotactic body radiation therapy (SBRT) to be safe and effective as treatment for primary HCC, however few studies have investigated the safety and efficacy of SBRT as treatment for HCC after OLT. The aim of this study is to evaluate the safety and efficacy of intra-abdominal salvage SBRT for HCC in patients who previously underwent OLT. <h3>Materials/Methods</h3> A retrospective chart review of a single, large institution was conducted to identify patients who received intra-abdominal SBRT as treatment for recurrent HCC after OLT from 1/1/2013 to 12/1/2021. Clinical safety was measured by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0 for grading adverse events, Child-Turcott-Pugh (CTP) score, and Albumin-Bilirubin (ALBI) grade for HCC. Dosimetric analysis was performed. Efficacy was measured by local control (LC) and objective response using modified Response Evaluation Criteria in Solid Tumors (mRECIST). The Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS). <h3>Results</h3> 18 lesions, treated among 15 patients were identified that received intra-abdominal SBRT for HCC recurrence after OLT. Nine patients were male, median age was 62 (interquartile range 52 to 80). The American Joint Committee on Cancer stage at diagnosis was most often T1N0M0 (n=8, 53%) or T2N0M0 (n=5, 33%). The most common etiology for HCC diagnosis was hepatitis C virus (n=9, 56%). Median CTP and ALBI scores at baseline were 5 (range 5 to 11) and -3.02 (range -3.36 to -1.35), respectively. Median change in CTP score from baseline to CTP at 3, 6, and 12 months was 0.00, 1.00, and 1.00. Median change in ALBI score from baseline to at 3, 6, and 12 months was 0.14, 0.40, and 0.42. The median treatment dose was 4750 cGy (interquartile range 500 cGy), all patients received 5 fractions. There was no grade 3 or above CTCAE toxicities. During 6 (33%) SBRT treatments, patient experienced grade 1 or 2 CTCAE toxicity with nausea, emesis, or fatigue. Local control was achieved in 94% of lesions (n=17). Local treatment response was: 11 (61.2%) complete response, 5 (27.8%) partial response, 1 (5.5%) stable disease, and 1 (5.5%) progressive disease. After median follow up of 19.2 months, 8 patients (53%) were deceased and 7 (47%) had no evidence of disease progression. OS was 100% at 6 months and 60.8% at 12 months. PFS was 92.9% at 6 months and 60.9% at 12 months. No dosimetric factor was found to predict for increased toxicity. <h3>Conclusion</h3> For patients with HCC after OLT, SBRT appears to be a safe and effective treatment modality, as no patients experienced significant toxicities and the majority had complete treatment response.

Clinical Outcomes of Image-Guided Proton Therapy for Recurrent Hepatocellular Carcinoma after TACE and/or RFA Treatment

<h3>Purpose/Objective(s)</h3> Additional treatment options for recurrent hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) and/or radiofrequency ablation (RFA) treatment are limited. Although proton therapy provides a more focused dose distribution on the tumor compared with X-ray therapy, the efficacy and safety of proton therapy for recurrent HCC remains unclear. The aim of this study was to evaluate the efficacy and safety of image-guided proton therapy (IGPT) for recurrent HCC after TACE and/or RFA. <h3>Materials/Methods</h3> Eligibility criteria were as follows: (1) histologically-confirmed or image-diagnosed recurrent HCC after TACE and/or RFA treatment; (2) intrahepatic recurrence cases other than treatment site recurrence are not included (3) no previous radiotherapy around the lesion and other HCC; (4) age > 20 and ≤ 80 years; (5) ECOG-PS ≤ 2; (6) Child-Pugh classification A5-B9; (7) dose constraints of the organs at risk achievable; (8) no portal vein or inferior vena cava tumor thrombus; and (9) written informed consent. Overall survival (OS), local control (LC), and progression-free survival rates were estimated using the Kaplan-Meier method. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 5.0. Quality of life (QOL) scores were evaluated with EORTC QLQ-C30 version 3.0, QLQ-HCC18, and SF-36. Prior to treatment planning, the fiducial marker was placed just adjacent to a recurrent tumor. IGPT was performed under respiratory gating. <h3>Results</h3> From June 2013 to December 2020, 80 patients were enrolled. Major underlying liver diseases were hepatitis B (n=19), hepatitis C (n=35), alcoholic hepatitis (n=9), and nonalcoholic fatty liver disease (n=17). The Child-Pugh score was A5 in 49 patients, A6 in 16, and B7-9 in 15. The number of Albumin-Bilirubin Grade 1, 2, and 3 were 40, 40, and 0, respectively. Nineteen patients had a history of hepatic resection for other HCC. Fifty-four patients with a peripherally-located tumor were given 66 GyE in 10 fractions and 26 with a central tumor received 72.6 GyE in 22 fractions. Maximum tumor diameter ranged from 10 to 174 mm (median, 31). The median follow-up period of surviving patients was 38.0 months (range: 12.0-96.0). The 3-year OS, LC and PFS were 81% (95% confidence interval: 71-90%), 92% (86-100%), and 38% (26-49%) respectively. In univariate analysis, Child classification, operability, and tumor diameter were associated with better survival, while only Child classification was associated in multivariate analysis. Clinical remission or sustained viral response were significant factors for OS in patients with HCC recurrence derived from hepatitis virus. Non-classic radiation-induced liver disease was observed in only 1 patient with decrease of Child-Pugh score (≥ 2 points). The QOL score did not change after 1 year. <h3>Conclusion</h3> IGPT is safe and effective for recurrent HCC after TACE and/or RFA treatment. IGPT may become one of standard treatments as a curative treatment for recurrent HCC.

Modified Albumin-Bilirubin Model for Stratifying Survival in Patients with Hepatocellular Carcinoma Receiving Anticancer Therapy.

Simple SummaryAlbumin–bilirubin (ALBI) grade is an objective and reproducible model for evaluating overall survival (OS) in patients with hepatocellular carcinoma (HCC). The original ALBI grade was established for patients with Child–Pugh classes A–C. HCC patients with Child–Pugh class C or poor performance status usually receive hospice care. Thus, optimized cutoffs for the ALBI grade for stratifying OS in HCC patients receiving anticancer therapy are critical. The modified ALBI (mALBI) grade was as follows: an ALBI score ≤−3.02 for mALBI grade 1, an ALBI score >−3.02 to ≤−2.08 for mALBI grade 2, and an ALBI score > −2.08 for mALBI grade 3. The mALBI model can differentiate between patients with early, intermediate, or advanced HCC who received anticancer therapy.Albumin–bilirubin (ALBI) grade is an objective and reproducible model for evaluating overall survival (OS) in patients with hepatocellular carcinoma (HCC). However, the original ALBI grade was established for patients with Child–Pugh classes A–C. HCC patients with Child–Pugh class C or poor performance status (Barcelona Clinic Liver Cancer (BCLC) stage D) usually receive hospice care. Thus, optimized cutoffs for the ALBI grade for stratifying OS in HCC patients receiving anticancer therapy are pertinent for accurate prognostication. This study retrospectively enrolled 2116 patients with BCLC stages A–C HCC after the exclusion of those ineligible for receiving anticancer therapy. The modified ALBI (mALBI) grades were: an ALBI score ≤−3.02 for mALBI grade 1, an ALBI score >−3.02 to ≤−2.08 for mALBI grade 2, and an ALBI score >−2.08 for mALBI grade 3. The original ALBI and mALBI grades were independent predictors of OS in all the enrolled patients and those receiving transarterial chemoembolization. In patients receiving curative therapy (radiofrequency ablation and surgical resection), the mALBI grade (grade 2 vs. 1 and grade 3 vs. 2) was an independent predictor of OS. Original ALBI grade 2 vs. 1 was an independent predictor of OS but not ALBI grade 3 vs. 2. The mALBI model can differentiate between patients with early, intermediate, or advanced HCC who received anticancer therapy into three prognostic groups. External validation of the proposed mALBI grade is warranted.

Determinants of Treatment Benefit and Post-Treatment Survival for Patients with Hepatocellular Carcinoma Enrolled in Second-Line Trials after the Failure of Sorafenib Treatment.

Second-line treatments are standard care for advanced hepatocellular carcinoma (HCC) patients with preserved liver function who are intolerant of or progress on first-line therapy. However, determinants of treatment benefit and post-treatment survival (PTS) remain unknown. HCC patients previously treated with sorafenib and enrolled in second-line clinical trials were pooled according to the investigational treatment received and the subsequent regulatory approval: approved targeted agents and immune checkpoint inhibitors (AT) or other agents (OT) not subsequently approved. Univariate and multivariate analyses using Cox proportional hazards models established relationships among treatments received, clinical variables, and overall survival (OS) or PTS. For 174 patients (80 AT; 94 OT) analyzed, baseline factors for longer OS in multivariate analysis were second-line AT, absence of both portal vein thrombosis and extrahepatic spread (EHS). Treatment with AT (versus OT) was associated with significantly longer OS among patients with EHS (pinteraction = 0.005) and patients with low neutrophil-to-lymphocyte ratio (NLR; pinteraction = 0.032). Median PTS was 4.0 months (95% CI 2.8–5.3). At second-line treatment discontinuation, alpha-fetoprotein (AFP) levels <400 ng/dl, albumin-bilirubin (ALBI) grade 1, and enrolment onto subsequent trials independently predicted longer PTS. Treatment with AT, PVT, and EHS were prognostic factors for OS, while AFP, ALBI grade and enrolment onto a third-line trial were prognostic for PTS. Presence of EHS and low NLR were predictors of greater OS benefit from AT.

Prognostic Factors for Overall Survival in Patients with HCV-Related HCC Undergoing Molecular Targeted Therapies: Beyond a Sustained Virological Response.

Simple SummaryThe eradication of the hepatitis C virus (HCV) has had a significant impact on the management of patients with HCV-related hepatocellular carcinoma (HCC). However, its eradication has not completely resolved survival issues in patients with HCV-related HCC. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC undergoing molecular targeted therapies. In total, 359 HCC patients treated with first-line chemotherapy were enrolled. The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.7 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin-bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP level ≥ 90 (p = 0.038), baseline DCP level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as independent prognostic factors for overall survival.Background: The treatment of the hepatitis C virus (HCV) has reduced the risk of hepatocellular carcinoma (HCC)-related mortality. Many patients with advanced HCC have achieved longer survival through systemic chemotherapy. However, survivors of HCC may develop liver cancer during and after treatment. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC in the new era of molecular targeted therapy. Methods: A total of 359 patients with HCV-related HCC treated with first-line chemotherapy were reviewed. A Cox proportional hazards model and Kaplan–Meier curve were used to identify prognostic factors associated with survival outcomes. Results: The median follow-up duration was 16.0 months (range, 1.0–115.7) and the median duration of first-line systemic therapy was 3.73 months (range, 0.7–86.9). The achievement of a sustained virological response (SVR) (p < 0.001), albumin–bilirubin (ALBI) grade II/III (p < 0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p = 0.005), extrahepatic spread (p < 0.001), baseline AFP (alpha-fetoprotein) level ≥ 90 (p = 0.038), baseline DCP (des-γ-carboxy prothrombin) level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p = 0.003) were identified as prognostic factors for overall survival. Conclusions: The achievement of SVR was most strongly associated with overall survival. Other factors, such as the BCLC stage, extrahepatic spread, baseline tumor marker (AFP/DCP) levels, ALBI grade, and FIB-4 index need to be considered in the management of patients with HCV-related HCC.

Long-term Outcomes and Prognostic Factors of Stereotactic Body Radiotherapy for Hepatocellular Carcinoma.

This study was conducted to determine the prognosis and risk factors for survival in patients treated with stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC). This retrospective study analyzed 73 patients who underwent SBRT for HCC at Nagasaki University Hospital from December 2012 to July 2019 and examined the relationship between baseline information and prognosis. The Kaplan-Meier analysis and log-rank test were used to estimate the survival rate. Cox regression analysis was performed to determine the factors associated with overall survival (OS) after SBRT. The 1- and 2-year local control rates were 98.6% and 89.9%, respectively. Survival rates at 1, 3, and 5 years were 94.5%, 63.9%, and 45.5%, respectively. In the univariate analysis, baseline modified albumin-bilirubin grade (mALBI grade) [2b/3, hazard ratio (HR)=2.762, p=0.001], tumor size (≥2 cm, HR=2.479, p=0.003), and Barcelona Clinic Liver Cancer stage (BCLC) (B/C, HR=3.284, p<0.001) were significantly associated with poor prognosis. In multivariate analysis, baseline mALBI grade (2b/3, HR=2.283, p=0.009) and BCLC stage (B/C, HR=2.330, p=0.013) were significantly associated with poor prognosis. Only three patients (4.1%) developed grade 3 adverse events related to SBRT. SBRT is effective and safe in patients with HCC. The baseline mALBI grade is useful for predicting patient prognosis after SBRT. Patients with an mALBI grade of 1/2a are expected to have a better prognosis than patients with an mALBI grade of 2b/3.

The prognostic role of albumin-bilirubin grade in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors.

Our aim was to explore the prognostic role of baseline albumin-bilirubin levels (ALBI) on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). This retrospective study enrolled 58 cases of advanced NSCLC patients who received immune checkpoint inhibitor therapy from January 2019 to February 2022 in People's Hospital of Macheng. Patients were grouped according to the levels of baseline ALBI. The corresponding cut-off values ​​were determined by receiver operating characteristic (ROC) curves. We also assessed potential predictive models for predicting efficacy of immunotherapy in advanced NSCLC. The median overall survival (OS) was not reached. The median OS of patients with PS ≤ 1 after immunotherapy was significantly longer than that of PS ≥ 2, which was NR vs. 6.67 months (HR=0.14, 95% CI: 0.05-0.46; p<0.01). The risk of death for patients with low ALBI (<-2.52) was significantly lower than that of patients with high ALBI (HR=0.28, 95% CI: 0.08-0.94; p=0.03). Univariate analysis showed that baseline ALBI and PS were factors significantly affecting OS in patients with advanced NSCLC after immunotherapy (p<0.05 for all). The combination of ALBI and PS showed a good predictive value in prognosis of these patients after immunotherapy (p<0.01). The baseline ALBI and PS may serve as prognostic factors for advanced NSCLC patients treated with immunotherapy.

Leaky Gut and Severe Adverse Events in Advanced Hepatocellular Carcinoma Treated With Lenvatinib.

To identify predictors of severe adverse events (≥grade 3) in patients with advanced hepatocellular carcinoma treated with lenvatinib. Of 41 patients, 25 and 16 were stratified into the severe and non-severe adverse events groups, respectively. Of these, 19 formed a lactulose-mannitol test subgroup, which was divided into severe adverse events (n=11) and non-severe adverse events (n=8) groups. Severe adverse events were assessed by liver disease etiology and modified albumin-bilirubin grade. Intestinal permeability by lactulose-mannitol test and serum soluble CD163, soluble mannose receptor, and zonulin levels. Severe adverse event incidence rates were higher in patients with advanced hepatocellular carcinoma related to alcoholic liver disease and nonalcoholic fatty-liver disease than in those with advanced hepatocellular carcinoma of other etiologies (p=0.014). The rates were higher for modified albumin-bilirubin grades 2a and 2b compared to modified albumin-bilirubin grade 1 (p=0.0104). Zonulin levels were higher in the severe adverse event group (p=0.0331) and were independently associated with severe adverse events (odds ratio=140, 95% confidence interval=1.66-11800; p=0.029). Patients with high zonulin levels (≥0.518 ng/ml) experienced more severe adverse events than those with low levels (<0.518 ng/ml) (p=0.0137). In the lactulose-mannitol test subgroup, the urine lactulose:mannitol ratio was higher in the severe vs. non-severe adverse event group (p=0.0164). Moreover, it was higher in patients with alcoholic liver disease and nonalcoholic fatty-liver disease-related advanced hepatocellular carcinoma compared to those with other advanced hepatocellular carcinoma etiologies (p=0.0108). Serum zonulin levels predict severe adverse events in patients with advanced hepatocellular carcinoma treated with lenvatinib.

VariScreen secures the screening of high-risk varices in patients with hepatitis B virus-related cirrhosis beyond Baveno VI criteria.

We aimed to validate the performance of the ratio of the platelet count (PLT) to liver stiffness measurement (LSM) in excluding high-risk varices (HRVs) in patients with hepatitis B virus (HBV)-related compensated cirrhosis beyond Baveno VI criteria. A total of 310 patients were assessed. The performances of the PLT:LSM ratio (PLER), PLER adjusted for the international normalized ratio, etiology, age, and sex (PLEASE), and the sequential algorithm for HRV screening (VariScreen) in excluding HRVs were evaluated and compared with those of expanded Baveno VI criteria (LSM <25 kPa and PLT >110×109/L, EB6C); PLT >150×109/L and model for end-stage liver disease score = 6 (P150M6 criterion); PLT >120×109/L and albumin >36 g/L (P120A36 criterion); and albumin-bilirubin (ALBI) grade and PLT score (ALBI-PLT score). Among the enrolled patients, 43 (13.9%) had HRVs. The area under the receiver operating characteristic curve of PLER for predicting HRVs (0.771, 95% confidence interval, 0.720–0.817) was significantly higher than that for PLT and LSM (p < 0.01). PLER was an independent risk factor for HRVs. VariScreen, PLEASE, and PLER could spare 20 (6.5%), 91 (29.4%), and 60 (19.4%) endoscopies, with 0, 3 (3.3%), and 1 (1.7%) HRVs missed, respectively. The EB6C and P120A36 criteria could spare 45 (14.5%) and 36 (11.6%) endoscopies, with 1 (2.2%) and 1 (2.8%) HRVs missed, respectively. The P150M6 criterion and ALBI-PLT score missed 6.8% and 10.3% of HRVs, respectively. We found that PLER performed better than other non-invasive tests. VariScreen secured the screening of HRVs in patients with HBV-related cirrhosis beyond Baveno VI criteria.

Reproducible safety and efficacy of atezolizumab plus bevacizumab for HCC in clinical practice: Results of the AB-real study

BackgroundIMbrave150 has established the superiority of atezolizumab plus bevacizumab over sorafenib in patients with unresectable hepatocellular carcinoma (HCC). MethodsWe generated a prospectively maintained database including patients treated with atezolizumab plus bevacizumab for unresectable HCC across Europe, Asia and USA. Clinico-pathologic characteristics were assessed for their prognostic influence on overall survival (OS) and progression-free survival (PFS) in univariable and multivariate analyses. Overall response rate by RECIST v1.1 and treatment-related adverse events (TRAEs) per CTCAE v.5.0 were reported. ResultsOut of 433 patients, 296 Child-Pugh A and ECOG performance status01 patients received atezolizumab plus bevacizumab in first line and were included. Patients were mostly male (82.7%), cirrhotic (75%) with history of viral hepatitis (65.9%). Overall, 68.9% had Barcelona Clinic Liver Cancer C-stage HCC with portal vein tumour thrombosis (PVTT, 35%) and extrahepatic spread (EHS, 51.7%). After a median follow-up of 10.0 months (95% confidence interval (CI): 9.4–10.4), median OS and PFS were 15.7 (95% CI: 14.5-NE) and 6.9 months (95% CI: 6.1–8.3), respectively. In the response-evaluable patients (n = 273), overall response rate was 30.8%. Overall, 221 patients (74.6%) developed TRAEs, with 70 (23.6%) reporting grade 3 or higher TRAEs; 25 (8.4%) patients had bleeding events. OS was independently associated with baseline Albumin-bilirubin (ALBI) grade and PVTT. Shorter PFS was associated with AFP≥ 400 ng/ml, worse ALBI and presence of EHS. ConclusionThis global observational study confirms the reproducible safety and efficacy of atezolizumab plus bevacizumab in routine clinical practice. Within Child-Pugh-A criteria, the presence of PVTT and higher ALBI grade identify patients with poorer survival.

Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT

BackgroundTransarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. MethodsWe analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. ResultsThe median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. ConclusionIncluding easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Proton Beam Therapy for Treatment-Naïve Hepatocellular Carcinoma and Prognostic Significance of Albumin-Bilirubin (ALBI) Grade.

Simple SummaryProton beam therapy (PBT) has not been generally recommended as an initial treatment for hepatocellular carcinoma (HCC) due to the insufficiency of data on PBT for treatment-naïve HCC until now, and albumin-bilirubin (ALBI) grade has been shown to be an effective assessment of liver dysfunction and more discriminatory for survival than the Child–Pugh classification. This study evaluated the efficacy of PBT as first-line treatment in treatment-naïve HCC and assessed the prognostic significance of ALBI grade in these patients. Our findings showed that PBT could result in comparable local tumor control and survival outcomes in treatment-naïve HCC patients to those of other recommended first-line treatments, with a safe toxicity profile compared to our institutional cohort data and previous other studies, and ALBI grade and tumor stage were independent predicting factors for overall survival.To evaluate the efficacy of proton beam therapy (PBT) as an initial treatment in treatment-naïve hepatocellular carcinoma (HCC) patients and to assess the prognostic significance of albumin-bilirubin (ALBI) grade, 46 treatment-naïve HCC patients treated with PBT were analyzed. The ALBI grade distribution was grade 1 in 11 (23.9%) patients, grade 2 in 34 (73.9%) patients, and grade 3 in 1 (2.2%) patient. The median duration of follow-up was 56.5 months (95% confidence interval [CI], 48.2–64.7). Among the 46 patients, disease progression was observed in 23 (50%) patients: local progression in 3 (6.5%) patients; intrahepatic progression in 22 (47.8%); and extrahepatic progression in 5 (10.9%). The 5-year freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were 92.7% (95% CI, 84.7–100.7), 43.3% (95% CI, 28.2–58.4), and 69.2% (95% CI, 54.9–83.5), respectively. In multivariate analysis, there were no independent factors for FFLP (p > 0.05 each), but tumor stage and ALBI grade were independent factors for PFS and OS (p < 0.05 each). PBT could result in comparable OS in treatment-naïve HCC patients to other recommended first-line treatments, and ALBI grade, in addition to tumor stage, could be useful for predicting OS.

Hepatic decompensation after transarterial radioembolization: A retrospective analysis of risk factors and outcome in patients with hepatocellular carcinoma.

Transarterial radioembolization (TARE) is a well‐established therapy for intermediate and advanced tumor stages of hepatocellular carcinoma (HCC). Treatment‐associated toxicities are rare. Previous studies have outlined that the prognosis after TARE is determined primarily by tumor stage and liver function. The subset of patients benefiting from TARE remains to be defined. Sixty‐one patients with HCC treated with TARE between 2015 and 2020 were retrospectively included in the study. Hepatic decompensation was defined as an increase of bilirubin or newly developed ascites that was not explained by tumor progression within 3 months after TARE. Predictive factors of hepatic decompensation and prognostic factors were assessed. Hepatic decompensation was observed in 27.9% (n = 17) of TARE‐treated patients during follow‐up. Albumin‐bilirubin (ALBI) score at baseline and radiation dose on nontumor liver proved to be independent risk factors for the development of hepatic decompensation in multivariable regression models (ALBI score: odds ratio [OR] 6.425 [1.735;23.797], p < 0.005; radiation dose: OR 1.072 [1.016;1.131], p < 0.011). The occurrence of hepatic decompensation markedly impaired the prognosis of the patients. Survival was significantly worsened. Hepatic decompensation has shown to be an independent negative prognostic factor for death, adjusted for Barcelona Clinic Liver Cancer stage, age and ALBI grade (hazard ratio 5.694 [2.713;11.952], p < 0.001). Conclusion: Hepatic decompensation after TARE for HCC treatment is a highly relevant complication with major effects on the prognosis of patients. Main risk factors are the pretreatment ALBI score and radiation dose. There is an urgent need to define safe cutoff values and exclusion criteria for TARE to limit complications and improve patient outcomes.

Tumor burden score as a new prognostic surrogate in patients with hepatocellular carcinoma undergoing radiofrequency ablation: role of albumin-bilirubin (ALBI) grade vs easy ALBI grade

ABSTRACT Introduction Tumor burden score (TBS) was proposed to represent tumor burden in solid tumors, including hepatocellular carcinoma (HCC). The prognostic role of TBS in HCC patients in relation to recently introduced liver reserve markers, albumin-bilirubin (ALBI) grade, and easy (EZ)-ALBI grade, is unclear. We aimed to investigate the feasibility of TBS in HCC patients undergoing radiofrequency ablation (RFA). Research design and methods A total of 576 treatment-naïve patients with HCC undergoing RFA were analyzed. The multivariate Cox analysis was used to identify independent predictors associated with tumor recurrence and long-term survival. Results Patients with high TBS had increased risk of tumor recurrence and mortality compared with those with low TBS. The Cox analysis showed that serum ɑ-fetoprotein (AFP) level >20 ng/mL, medium and high TBS, ALBI grade 2 and grade 3, EZ-ALBI grade 2 and grade 3 were associated with tumor recurrence and decreased patient survival (all p <0.05). In addition, TBS can reliably stratify tumor recurrence and overall survival in different ALBI and EZ-ALBI grade groups. Conclusions TBS is a simple and feasible prognostic surrogate to predict tumor recurrence and survival in HCC patients undergoing RFA. Its prognostic ability remains stable in patients with variable liver functional reserve.