Albumin-bilirubin Grade Research Articles

Safety and Efficacy of Atezolizumab/Bevacizumab in Patients with Hepatocellular Carcinoma and Impaired Liver Function: A Systematic Review and Meta-Analysis

Background: Safety and outcome of atezolizumab/bevacizumab in Child-Pugh B patients with hepatocellular carcinoma (HCC) have not been completely characterized. Objectives: In this study, we aimed at addressing safety and efficacy of atezolizumab/bevacizumab in Child-Pugh B patients by reviewing the available data and analyzing them by meta-analysis. Methods: We compared the safety and efficacy of atezolizumab/becavizumab treatment in patients with unresectable HCC and various degrees of liver dysfunction. A total of 8 retrospective, non-randomized, cohort studies were included in this meta-analysis, for a total of 1,071 Child-Pugh A and 225 Child-Pugh B patients. The albumin-bilirubin (ALBI) grade was also used to assess liver function, when available. Results: Grade ≥3 adverse events were observed in 11.8% of Child-Pugh class A and 26.8% class B patients (p = 0.0001), with an odds ratio (OR) of 0.43 (confidence interval [CI] 0.21–0.90; p = 0.02). Progression-free survival (PFS) at both 6 months (4.90 ± 2.08 vs. 4.75 ± 2.08 months; p = 0.0004) and 12 months (8.83 ± 2.32 vs. 7.26 ± 2.33 months; p = 0.002) was lower in Child-Pugh class B patients. A trend toward a higher objective response rate (ORR) was observed in Child-Pugh class A patients (219/856, 25.6%) as compared to Child-Pugh class B patients (25/138, 18.1%; p = 0.070), while the probability of obtaining an ORR was significantly greater in Child-Pugh A patients (OR 1.79, CI 1.12–2.86; p = 0.02). Median overall survival (OS) was 16.8 ± 2.0 and 6.8 ± 3.2 months in Child-Pugh A and B patients, respectively (mean difference 9.06 months, CI 7.01–11.1, p < 0.0001). Lastly, OS was longer in patients with ALBI grades 1–2 than in those with grade 3 (8.3 ± 11.4 vs. 3.3 ± 5.0 months, p = 0.0008). Conclusions: Oncological efficacy of atezolizumab/bevacizumab is moderate in Child-Pugh class B patients, and the shorter PFS and OS associated with the greater likelihood of experiencing treatment-related adverse events observed in these patients suggest great caution and individualization of treatment, possibly with the support of the ALBI grade.

High albumin-bilirubin grade predicts worse short-term complications in gastric cancer patients with metabolic syndrome: a retrospective study.

Preoperative albumin-bilirubin (ALBI) grade has been proposed and applied in recent years to evaluate the prognosis of liver cancer, but its role in gastric cancer (GC) is still unclear. This research aimed to examine the prognostic value of ALBI grade after gastrectomy among patients with GC complicated with metabolic syndrome (MetS). There were 628 patients who received radical resection for GC. Laboratory data and short-term results were collected prospectively, and preoperative ALBI grades were calculated from the albumin and bilirubin levels. The appropriate ALBI cutoff value was calculated by receiver operating characteristic (ROC) curve analysis, which we used to put patients into high (>-2.54) and low (≤-2.54) ALBI grade groups. The differences between the short-term complication rates of the two groups were analyzed with the chi-square test. Of the included patients, 133 (21.2%) and 495 (78.8%) had high and low ALBI grades, respectively. A high ALBI grade (P=0.001), body mass index (BMI) ≥25 kg/m2 (P=0.001), and hypertension (P=0.018) were independent risk factors for postoperative complications. In GC patients with and without MetS, the high ALBI subgroup showed more overall complications than the low ALBI subgroup (P=0.028 and P=0.001). Among GC patients with MetS, those with a high ALBI grade showed a higher incidence of serious complications than those with a low ALBI grade (P=0.001); a similar, nonsignificant trend occurred in non-MetS patients (P=0.153). The preoperative ALBI grade is important in the prognosis of GC patients with MetS after gastrectomy. GC patients with MetS can lower their incidence of serious complications by adjusting their preoperative ALBI grade.

Evaluation of Liver Functionality after Liver Stereotactic Body Radiation Therapy (SBRT) Using Blood Tests and Imaging Examinations

Several studies have shown that liver function can be evaluated after hepatic stereotactic body radiation therapy (SBRT) using galactosyl human serum albumin (GSA) liver scintigraphy and Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). However, there are no reports investigating the relationship (including Chile-Pugh classification) between imaging and blood tests. Therefore, we investigated the changes that occur in the liver between before and after SBRT by combining imaging (GSA, computed tomography (CT), and MRI) with blood tests that assess total liver function (albumin-bilirubin (ALBI) grade, ICG-R15). We decided to find a method that could assess liver reserve capacity locally and globally MATERIALS/METHODS: Of the 23 patients who underwent hepatic SBRT, 12 patients underwent GSA, MRI, and ICG-R15 testing before treatment, 1 month after treatment, and 3 months after treatment. All patients underwent imaging studies and blood tests at the beginning of treatment, 1 month after treatment, and 3 months after treatment ended. The evaluation items were as follows: 1) changes over time in Child-Pugh classification, ICG-R15, and ALBI values before and after SBRT; 2) changes over time in GSA count and ICG; and 3) selection of the optimal sequence for recognizing radiation hepatitis on MRI. The ICG values were 14.4 before RT, 17.1 after 1 month, and 17.6 after 3 months. ICG worsened after 1 month of treatment, but was similar after 3 months. ALBI values were -2.61 before RT, -2.67 after 1 month, and -2.71 after 3 months. ALBl worsened slightly over time. Regarding the ICG-R15, there was an average worsening of 2.8 after 1 month of treatment compared with before SBRT, but only of 0.5 between 1 month and 3 months after SBRT. Therefore, evaluation using ICG-R15 after SBRT after 1 month alone may be sufficient.

Long-Term Clinical Outcome of Carbon Ion Radio Therapy for Hepatocellular Carcinoma in the Caudate Lobe

Surgical resection is the first-line treatment for hepatocellular carcinoma in the caudate lobe (caudate HCC), but it is often difficult due to the tumor's location. In addition, radiofrequency ablation and transcatheter arterial chemoembolization are also difficult for the same reason. This study aimed to evaluate the safety and efficacy of carbon-ion radiation therapy (C-ion RT) for caudate HCC. We performed a retrospective cohort study of patients with hepatocellular carcinoma treated by C-ion RT between April 2000 and March 2020 in our institution. The eligibility criteria for this study were: (1) located mainly in the caudate lobe (2) the treatment protocols of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions, which proved the safety and efficacy in the past clinical trials; (3) N0M0 status; (4) an Eastern Cooperative Oncology Group performance status (PS) of 0 to 2; (5) controllable ascites. The prescribed dose (Gy) used in this study is relative biological effectiveness (RBE) weighted dose. Overall survival (OS), progression-free survival (PFS), and local control rate (LC) were calculated by the Kaplan-Meier method. Adverse events were evaluated by NCI-CTCAE ver. 5.0. SPSS software version 27.0 (IBM Inc.) was used for all analyses. We defined p-value < 0.05 as statistically significant. A total of 25 patients met the criteria and were evaluated. The median patient age was 73 years (range 58-89), and 21 of 25 patients were male. The number of patients with PS 0 was 22, PS 1 was 1, and PS 2 was 2. The number of HBV-related HCC cases was in 8, HCV-related HCC cases was in 11, and non-B and non-C cases was in 6. The median maximum tumor diameter was 3.0 cm (1.1-4.8 cm). In 6 patients, identification of vascular invasion to the main trunk of the portal vein and/or major hepatic vein was confirmed. The Child-Pugh (CP) grade was A in 21 patients and B in 4. The modified albumin-bilirubin (mALBI) grade 1 is in 17 patients, 2a in 4, 2b in 4. Prescribed doses were 45 Gy / 2 fr in 3 cases, 48 Gy / 2 fr in 12 cases, 52.8 Gy / 4 fr in 7 cases, and 60 Gy / 4 fr in 3 cases. With a median follow-up period of 43.6 months (range 0.3-85.0), 3-year OS, PFS, and LC were 74% (95% confidence interval [CI], 54.8-93.8%), 32% (95% CI, 11.8-51.4%), and 93% (95% CI, 79.4-106%), respectively. All patients had no Grade 2 or higher adverse events during the observation period. The safety and efficacy of C-ion RT for caudate HCC were demonstrated. These results suggested that C-ion RT may be a promising treatment option for patients with caudate HCC.

Clinical Outcomes of Carbon-Ion Radiotherapy for Large-Sized (≥4cm) Hepatocellular Carcinoma

Radical treatment options for bulky unresectable locally advanced hepatocellular carcinoma (HCC) are limited. The purpose of this study is to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for bulky (≥4cm) locally advanced HCC. We performed a retrospective cohort study of patients with bulky (≥4cm) locally advanced HCC treated by C-ion RT between April 2000 and March 2020 in our institution. The eligibility criteria for this study were: (1) the treatment protocols of 45.0-48.0 Gy/2 fractions or 52.8-60.0 Gy/4 fractions, which proven the safety and efficacy in the past clinical trials; (2) Tumors within 3 intrahepatic lesions and with a maximum tumor diameter of 4 cm or greater; (3) N0M0 status; (4) an Eastern Cooperative Oncology Group performance status of 0 to 2; (5) controllable ascites; (6) Child-Pugh grade was A or B. Overall survival (OS), progression-free survival (PFS), and local control rate (LC) were calculated by the Kaplan-Meier method, and Cox regression analysis was used for multivariate analysis. Adverse events were evaluated by CTCAE ver. 5.0. JMP® 12 (SAS Institute Inc., Cary, NC, USA) was used for all analyses. We defined p < 0.05 as statistically significant. A total of 187 patients met the criteria and were evaluated. The median patient age was 73 years (range, 37-90), and 139 of 187 patients were male. Child-Pugh grade was A in 163 patients and B in 24. Modified albumin-bilirubin (mALBI) grade was 1 in 96 patients, 2a in 50, and 2b in 41. The number of HCV-related HCC cases was in 80, HBV in 32 and non-B and non-C in 75. In 51 patients, identification of vascular invasion to the first-order branch of the portal vein and/or major hepatic vein was confirmed. The median maximum tumor diameter was 5.1 cm (4.0-13.5 cm). In 76 patients, C-ion RT were treated for recurrence. With a median follow-up period of 25.9 months (range, 1.1-215.1), 2-year overall survival, progression-free survival and local control rates were 68.3% (95% confidence interval [CI], 64.7-72.0%), 39.0% (95% CI, 35.2 - 42.8%) and 86.7% (95% CI, 84.7 - 89.7%), respectively. Late adverse events were observed in 3 patients (1.6%) with Grade 3 liver dysfunction and in 3 patients (1.6%) with Grade 3 skin disorders, but there were no cases of Grade 4 or higher. Multivariate analysis of prognostic factors for overall survival revealed that mALBI grade in 2b(HR:3.13, 1.97-4.78, p<0.0001), tumor status in recurrent treatment (HR:1.50, 1.02-2.21, p = 0.039), the number of tumors in 2 or more (HR:2.16, 1.01-2.17, p = 0.045), and maximum tumor diameter in larger than 6 cm (HR:2.34, 1.50-3.61, p = 0.0001) were the predominant prognostic factors, while age, presence of vascular invasion, AFP and DCP were not. The safety and efficacy of C-ion RT for bulky (≥4cm) locally advanced HCC was demonstrated. These results suggested that C-ion RT may be a new treatment option for locally advanced bulky HCC with no curative treatment options.

Construction and validation of a novel prognostic model for intrahepatic cholangiocarcinoma based on a combined scoring system of systemic immune-inflammation index and albumin-bilirubin: a multicenter study.

The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.

Outcomes of Patients with Child-Pugh B and Unresectable Hepatocellular Carcinoma Undergoing First-Line Systemic Treatment with Sorafenib, Lenvatinib, or Atezolizumab Plus Bevacizumab

Introduction: Systemic therapy is recommended for patients with Child-Pugh A in hepatocellular carcinoma (HCC). We analyzed the outcomes of a cohort of patients with HCC who received either sorafenib (Sor), lenvatinib (Len) or atezolizumab plus bevacizumab (Atezo + Bev) as first-line systemic therapy for HCC, with the aim of identifying prognostic factors for survival. Methods: A total of 825 patients with advanced HCC and Child-Pugh A or B received either Sor, Len or Atezo + Bev as first-line systemic therapy. Liver function was assessed according to the Child-Pugh score and the modified albumin-bilirubin (mALBI) grade. Results: Prognosis was analyzed according to liver function such as Child-Pugh classifications, scores, and mALBI grades that worsened with a decline in liver function (p <0.001 for all). A Child-Pugh score of 7 was a factor significantly associated with OS. In patients with a Child-Pugh score of 7, an mALBI grade of 3 was an independent predictor of OS. In Child-Pugh B patients with HCC, receiving Atezo + Bev was identified as a factor associated with PFS. Conclusion: Determining the hepatic reserve of patients with unresectable HCC might be useful for identifying patents suitable for systemic treatment for HCC. Atezo + Bev might prolong the PFS of patients with a Child-Pugh score of 7.

Albumin‑bilirubin grade and INR for the prediction of esophagogastric variceal rebleeding after endoscopic treatment in cirrhosis.

Rebleeding following endoscopic treatment in patients with cirrhosis is a serious life-threatening complication. In the present study, a novel, reliable and non-invasive score for prediction of rebleeding following endoscopic therapy for esophagogastric variceal bleeding (EGVB) was developed. The present retrospective study recruited cirrhotic patients with EGVB (n=596) who underwent endoscopic therapy. Patients hospitalized from January 2015 to January 2020 were grouped into a training (n=437) cohort to develop the new score and those hospitalized from February 2020 to February 2022 were grouped into a validation (n=159) cohort to validate the score. The international normalized ratio (INR) and albumin-bilirubin (ALBI) grade were used to develop the INR-ALBI (IALBI) score to predict risk of rebleeding. In the training cohort, the prognostic performance of the IALBI score and other ALBI-associated scores (modified ALBI, platelet-ALBI and ALBI-fibrosis-4) at 1, 3 and 12 months was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. At each time point, most areas under the ROC curve of IALBI were higher than those of other ALBI-associated scores, particularly for prediction of early rebleeding. At 1 month, the rebleeding rates of patients with IALBI grade 2 and 3 were ~10.0- and 19.5-times higher than those of patients with grade 1, respectively. The negative predictive value (NPV) of IALBI for the training and validation cohort at 1 month was 100.0 and 97.8%, respectively. For viral and non-viral patients in the training cohort, IALBI showed good predictive ability and NPV for early rebleeding. The IALBI grading system successfully assessed rebleeding, particularly early rebleeding, in cirrhotic patients with EGVB following endoscopic therapy IALBI grade 1, predicted low risk of rebleeding and may not require endoscopic treatment again in the short-term.

Preoperative ALBI grade predicts mortality in patients undergoing curative surgery for pancreatic head cancer.

The clinical significance of the albumin-bilirubin (ALBI) grade in patients with pancreatic head cancer (PHC) undergoing surgery is unknown. Preoperative ALBI grade is believed to be influenced by tumor burden. This study aimed to develop and validate the ALBI grade as a preoperative prognostic model for predicting the survival of patients with PHC. This is a retrospective study of Whipple procedures performed on PHC patients between January 2013 and December 2022. ALBI grade was compared to age, gender, type of operation, presence of complications, type of complications, Clavien-Dindo classification, total bilirubin levels, and albumin levels. Of the series, 46 (41.1%) of the 112 patients were female, while 66 (58.9%) were male. The rate of complications following Whipple procedures was 36.6% (n = 41). The overall mortality hazard ratio increased significantly with increasing ALBI grades (HR: 1538, hazard ratio mean: -1602). Hospital mortality increased 2.84 times as the ALBI grade increased. The model's accuracy of 88.4% showed that the ALBI grade directly affected both the overall mortality rate and the hospital rate. But there was no statistically significant difference between the ALBI grade and other variables. Multivariate regression analysis identified the preoperative ALBI grade as an independent predictor of mortality (P = .006). To the best of our knowledge, this is the first study to identify preoperative ALBI grade as an independent predictor of survival in PHC. It was found that the ALBI grade of -1602 was a new grading system that would be more predictive of mortality in PHC.

Nomogram for predicting overall survival in patients with large (>5 cm) hepatocellular carcinoma based on real-world practice.

Patients with large (>5 cm) hepatocellular carcinoma (HCC) have limited treatment options, thus necessitating the identification of prognostic factors and the development of predictive tools. This study aimed to identify prognostic factors and to construct a nomogram to predict survival outcomes in patients with large HCC. A cohort of 438 patients, who were diagnosed with large HCC at a tertiary hospital between 2015 and 2018, was analyzed. Cox proportional hazards models were used to identify key prognosticators of overall survival (OS), and an independent set of prognostic factors was used to develop a nomogram. The discrimination and calibration abilities of the nomogram were assessed and internal validation was performed using cross-validation and bootstrapping methods. During a median follow-up of 9.3 months, the median OS was 9.9 months, and the 1-year OS rate was 43.9%. Multivariable Cox regression analysis revealed that performance status, modified albumin-bilirubin grade, tumor size, extent of portal vein tumor thrombosis, and initial treatment significantly affected OS. The newly developed nomogram incorporating these variables demonstrated favorable accuracy (Harrell's concordance index, 0.807). The newly developed nomogram facilitated the estimation of individual survival outcomes in patients with large HCC, providing an acceptable level of accuracy.

Report of the 23rd nationwide follow-up survey of primary liver cancer in Japan (2014-2015).

For the 23rd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 20889 newly registered patients and 42274 previously registered follow-up patients were compiled from 516 institutions over a 2-year period from January 1, 2014 to December 31, 2015. Basic statistics compiled for patients newly registered in the 23rd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathological diagnosis, recurrence status, and autopsy findings. Compared with the previous 22nd survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, had more patients with non-B non-C HCC, had smaller tumor diameter, and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2004 and 2015 whose final outcome was survival or death. The median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter, Child-Pugh grade, or albumin-bilirubin grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy, and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2015 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer in the world.

Efficacy of Lenvatinib Combined with Transcatheter Intra-Arterial Therapies for Patients with Advanced-Stage of Hepatocellular Carcinoma: A Propensity Score Matching.

This study aimed to evaluate the effect of lenvatinib (LEN) combined with transcatheter intra-arterial therapy (TIT) for advanced-stage hepatocellular carcinoma (HCC) after propensity score matching (PSM). This retrospective study enrolled 115 patients with advanced-stage HCC who received LEN treatment. The patients were categorized into the LEN combined with TIT group (n = 30) or the LEN monotherapy group (n = 85). After PSM, 38 patients (LEN + TIT group, n = 19; LEN monotherapy group, n = 19) were analyzed. The median overall survival (OS) in the LEN + TIT group was significantly higher than that in the LEN monotherapy group (median survival time (MST): 28.1 months vs. 11.6 months, p = 0.014). The OS in the LEN combined with transcatheter arterial chemoembolization and LEN combined with hepatic arterial infusion chemotherapy groups was significantly higher than that in the LEN monotherapy group (MST 20.0 vs. 11.6 months, 30.2 vs. 11.6 months, p = 0.048, and p = 0.029, respectively). Independent factors associated with OS were alpha-fetoprotein and LEN combined with TIT. The indications for LEN combined with TIT were age <75 years and modified albumin bilirubin (m-ALBI) grade 1. We concluded that LEN combined with TIT may improve prognosis compared with LEN monotherapy in patients with advanced-stage HCC.

Usefulness of Tumor Marker Score for Predicting the Prognosis of Hepatocellular Carcinoma Patients Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study.

This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin-bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6-21.3), 7.7 months (95% CI 5.3-8.9), and 5.8 months (95% CI 3.0-7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

Validation of the albumin-bilirubin score for identifying decompensation risk in patients with compensated cirrhosis.

The albumin-bilirubin (ALBI) score is an index of liver function recently developed to assess prognosis in patients with hepatocellular carcinoma (HCC). It can detect small changes in liver dysfunction and has been successfully applied to the prediction of survival in patients with non-malignant liver diseases of various etiologies. To investigate the ALBI score for identifying decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. One-hundred and twenty-three patients with compensated cirrhosis without HCC in King Chulalongkorn Memorial Hospital diagnosed by imaging were retrospectively enrolled from January 2016 to December 2020. A total of 113 patients (91.9%) had Child A cirrhosis with a median model for end-stage liver disease (MELD) score of less than 9. Baseline clinical and laboratory variables and decompensation events were collected. The ALBI score was calculated and validated to classify decompensation risk into low-, middle-, and high-risk groups using three ALBI grade ranges (ALBI grade 1: ≤ -2.60; grade 2: > -2.60 but ≤ -1.39; grade 3: > -1.39). Decompensation events were defined as ascites development, variceal bleeding, or grade 3 or 4 hepatic encephalopathy. Among 123 cirrhotic patients enrolled, 13.8% (n = 17) developed decompensating events at a median time of 25 [95% confidence interval (CI): 17-31] mo. Median baseline ALBI score in compensated cirrhosis was significantly lower than that of patients who developed decompensation events [-2.768 (-2.956 to -2.453) vs -2.007 (-2.533 to -1.537); P = 0.01]. Analysis of decompensation risk at 3 years showed that ALBI score had a time-dependent area under the curve (tAUC) of 0.86 (95%CI: 0.78-0.92), which was significantly better than that of ALBI-Fibrosis-4 (ALBI-FIB4) score (tAUC = 0.77), MELD score (tAUC = 0.66), Child-Pugh score (tAUC = 0.65), and FIB-4 score (tAUC = 0.48) (P < 0.05 for all). The 3-year cumulative incidence of decompensation was 3.1%, 22.6%, and 50% in the low-, middle-, and high-risk groups, respectively (P < 0.001). The odds ratio for decompensation in patients of the high-risk group was 23.33 (95%CI: 3.88-140.12, P = 0.001). The ALBI score accurately identifies decompensation risk at the 3-year follow-up in patients with compensated cirrhosis. Those cirrhotic patients with a high-risk grade of ALBI score showed a 23 times greater odds of decompensation.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.

The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10cm without vascular invasion and metastasis. From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.

Determination of prognostic predictors in patients with solitary hepatocellular carcinoma: histogram analysis of multiparametric MRI.

To evaluate the histogram parameters of preoperative multiparametric magnetic resonance imaging (MRI) and clinical-radiological (CR) characteristics as prognostic predictors in patients with solitary hepatocellular carcinoma ≤ 5 cm and to determine the optimal time window for histogram analysis. We retrospectively included 151 patients who underwent preoperative MRI between January 2012 and December 2017. All patients were randomly separated into training and validation cohorts (n = 105 and 46). Eight whole-lesion histogram parameters were extracted from T2-weighted images, apparent diffusion coefficient maps, and dynamic contrast-enhanced images. Univariate and multivariate logistic regression analyses were performed to evaluate these histogram parameters and CR variables related to early recurrence (ER) and recurrence-free survival. A nomogram was derived from the clinical-radiological-histogram (CRH) model that incorporated these risk factors. Kaplan-Meier survival analysis was performed to evaluate the prognostic performance of the CRH model. In total, 151 patients (male: female, 130: 21; median age, 54.46 ± 9.09 years) were evaluated. Multivariate logistic regression analysis revealed that the significant risk factors of ER were Mean Absolute Deviation and Minimum in the histogram analysis of the delayed phase images, as well as three important CR variables: albumin-bilirubin grade, microvascular invasion, and tumor size. The nomogram built by incorporating these risk factors showed satisfactory predictive ability in the training and validation cohorts with AUC values of 0.747 and 0.765, respectively. Furthermore, the prognostic nomogram can effectively classify patients into high- and low-risk groups (p < 0.05). Multiparametric MRI-derived histogram parameters provide additional value in predicting patient prognosis. The CRH model may be a useful and noninvasive method for achieving prognostic stratification and personalized disease management.

Performance of Albumin-Bilirubin (ALBI) score in comparison to other non-invasive markers in the staging of liver fibrosis in chronic HCV patients

BackgroundThe prognostic ability of albumin-bilirubin score (ALBI) to assess the hepatic dysfunction in patients with hepatocellular carcinoma (HCC) was previously studied. Its role in the staging of liver fibrosis post chronic hepatitis C Virus (HCV) infection needs to be investigated.Aimto assess the diagnostic value of the ALBI score compared to other non-invasive fibrosis scores in chronic HCV patients.MethodsThis cross-sectional study included consecutive chronic HCV patients from January 2015 till December 2018. Liver stiffness measurement (LSM) by transient elastography (TE) is currently one of the most validated noninvasive methods for liver fibrosis staging and is used in daily practice as a reference for fibrosis assessment. ALBI grade as well as Fibrosis-4 (FIB-4), Aspartate aminotransferase to platelet ratio index (APRI), LOK index and Göteborg University Cirrhosis (GUCI) scores were calculated for all of the patients.ResultsA total of 781 chronic HCV patients were included. Around 54% of them had compensated cirrhosis. GUCI score was the most sensitive one to difference between early fibrosis stages, F0 vs. F1. LOK index and ALBI score did not differ significantly between F1 and F2 stages unlike the other study markers. ROC curves revealed good diagnostic capability of FIB-4 (AUROC: 0.85, 0.84), APRI (AUROC: 0.83, 0.83) and GUCI score (AUROC: 0.83, 0.83) for detecting advanced fibrosis and cirrhosis, respectively. ALBI score had a moderate diagnostic role for diagnosing advanced fibrosis and cirrhosis, AUROC of 0.73 and 0.74 respectively. At a cutoff value of -2.95, the sensitivity of ALBI score approached 79%, the specificity was 53% for advanced fibrosis.ConclusionALBI score has a moderate diagnostic power score in the diagnosis of HCV-associated advanced liver fibrosis and cirrhosis; however, FIB-4, APRI and GUCI scores outperformed the ALBI score.

The outcomes and prognostic factors of patients with hepatocellular carcinoma and Child-Turcotte-Pugh class B.

The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients. We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0. Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score. Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B.

Modified integrated tumor burden, liver function, systemic inflammation, and tumor biology score to predict long-term outcomes after resection for hepatocellular carcinoma

BackgroundA preoperative predictive score for hepatocellular carcinoma (HCC) can help stratify patients who undergo resection relative to long-term outcomes and tailor treatment strategies. MethodsPatients who underwent curative-intent hepatectomy for HCC between 2000 and 2020 were identified from an international multi-institutional database. A risk score (mFIBA) was developed using an Eastern cohort and then validated using a Western cohort. ResultsAmong 957 patients, 443 and 514 patients were included from the Eastern and Western cohorts, respectively. On multivariable analysis, alpha-feto protein (HR1.97, 95%CI 1.42–2.72), neutrophil-to-lymphocyte ratio (HR1.74, 95%CI 1.28–2.38), albumin-bilirubin grade (HR1.66, 95%CI 1.21–2.28), and imaging tumor burden score (HR1.25, 95%CI 1.12–1.40) were associated with OS. The c-index in the Eastern test and Western validation cohorts were 0.69 and 0.67, respectively. Notably, mFIBA score outperformed previous HCC staging systems. 5-year OS incrementally decreased with an increase in mFIBA. On multivariable Cox regression analysis, the mFIBA score was associated with worse OS (HR1.18, 95%CI 1.13–1.23) and higher risk of recurrence (HR1.16, 95%CI 1.11–1.20). An easy-to-use calculator of the mFIBA score was made available online (https://yutaka-endo.shinyapps.io/mFIBA_score/). DiscussionThe online mFIBA calculator may help surgeons with clinical decision-making to individualize perioperative treatment strategies for patients undergoing resection of HCC.

Residual risk of hepatocellular carcinoma development for chronic hepatitis C patients treated by all oral direct-acting antivirals with sustained virological response.

The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan. Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models. The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047). Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies.