Albumin-bilirubin Grade Research Articles

A New Tumor Burden Score and Albumin-Bilirubin Grade-Based Prognostic Model for Hepatocellular Carcinoma.

Simple SummaryThe survival of patients with hepatocellular carcinoma (HCC) is highly variables, due to heterogeneous tumor burden and liver dysfunction. Tumor burden score (TBS) is a continuous variable to measure the extent of tumor involvement, and the albumin–bilirubin (ALBI) grade is an objective model to estimate hepatic functional reserve. Six prognostic predictors—including TBS, ALBI grade, ascites, serum α-fetoprotein level, vascular invasion or distant metastasis, and performance status—were linked with survival in a multivariate Cox model. We used these predictors to establish a new prognostic model—the TBS–ALBI system—to predict patient outcomes. Significant survival differences were found in different TBS–ALBI scores in the derivation and validation cohorts. This new system can also discriminate survival differences in patients with different viral etiologies, cancer stages, and treatment modalities. This study shows that the TBS–ALBI system is a feasible and user-friendly prognostic model for HCC.The prognosis of hepatocellular carcinoma (HCC) varies widely due to variable tumor extent and liver reserve. We aimed to develop and validate a new prognostic model based on tumor burden score (TBS) and albumin–bilirubin (ALBI) grade for HCC. We prospectively identified 3794 HCC patients who were randomized into derivation and validation groups. Survival predictors were evaluated by a multivariate Cox model. The TBS–ALBI system allocated two points for high TBS and ALBI grade 3, and one point each for the presence of ascites, serum α-fetoprotein ≥ 400 ng/mL, vascular invasion or distant metastasis, performance status 2–4, medium TBS, and ALBI grade 2, with a maximal score of 8 points. Significant survival differences were found across different TBS–ALBI score groups in the validation cohort (all p < 0.001). The TBS–ALBI system had the lowest corrected Akaike information criterion (AICc) and the highest homogeneity compared with other proposed staging models. The discriminative ability of the TBS–ALBI system was consistently stable across different viral etiologies, cancer stages, and treatment strategies. Conclusions: This new TBS–ALBI system is a feasible and robust prognostic system in comparison with other systems; it is a user-friendly tool for long-term outcome assessment independent of treatment modality and cancer stage in HCC.

Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma

Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p<0.001 and 2.04±1.35 vs. 1.40±1.16, p=0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.

Analysis of Survival and Response to Lenvatinib in Unresectable Hepatocellular Carcinoma.

Simple SummaryWith the recent increase in the number of drug therapy options for unresectable hepatocellular carcinoma (u-HCC), the key issue has become how to prolong overall survival (OS). The aim was to evaluate the association between radiological response and OS in patients treated with lenvatinib as a first-line systemic treatment for u-HCC. Radiological response using both Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST) is a predictor of OS and achieving an objective response at the first evaluation is an independent prognostic factor for OS. In addition, if an objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if stable disease is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.The association between radiological response and overall survival (OS) was retrospectively evaluated in patients treated with lenvatinib as a first-line systemic treatment for unresectable hepatocellular carcinoma. A total of 182 patients with Child–Pugh class A liver function and an Eastern Cooperative Oncology Group performance status of zero or one were enrolled. Radiological evaluation was performed using Response Evaluation Criteria in Solid Tumors (RECIST) and modified Response Evaluation Criteria in Solid Tumors (mRECIST). Initial radiological evaluation confirmed significant stratification of OS by efficacy judgment with both RECIST and mRECIST, and that initial radiological response was an independent prognostic factor for OS on multivariate analysis. Furthermore, in patients with stable disease (SD) at initial evaluation, macrovascular invasion at the initial evaluation on RECIST and modified albumin–bilirubin grade at initial evaluation on mRECIST were independent predictors of OS on multivariate analysis. In conclusion, if objective response is obtained at the initial evaluation, continuation of treatment appears desirable because prolonged OS can be expected; but, if SD is obtained at the initial evaluation, one should determine whether to continue or switch to the next treatment, with careful consideration of factors related to the tumor and hepatic reserve at the initial evaluation.

Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A Retrospective Multicenter Study

BackgroundLenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria.MethodsA retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed.ResultsPatients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC.ConclusionOverall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Albumin-Bilirubin (ALBI) Score is Superior to Platelet-Albumin-Bilirubin (PALBI) Score and Model for End-State Liver Disease (MELD-Na) for Predicting Post-Hepatectomy Liver Failure

Introduction: Scoring systems such as the Albumin-Bilirubin (ALBI) score and Model for End-Stage Liver Disease with Sodium (MELD-Na) are reliable predictors of post-hepatectomy outcomes. This study aims to compare the Platelet-Albumin-Bilirubin (PALBI) score with ALBI and MELD-Na for predicting 30-day post hepatectomy liver failure (PHLF) and mortality. Methods: The National Surgical Quality Improvement Program database was queried for patients who underwent elective hepatectomy from 2014-2018. Multivariable logistic regressions assessed associations of post-hepatectomy outcomes with patient and clinical characteristics. Predictive accuracy of the grading systems was evaluated by using receiver operator characteristic (ROC) curves and calculating area under the curve (AUC). Results: 30-day severe PHLF (Grade B/C) and mortality were present in 2.58% (N= 369) and 1.2% (N=171) of patients who underwent hepatectomy (N=13,925). The median scores for PALBI, ALBI, and MELD-Na were -2.64 (IQR -2.87,-2.41), -2.82 (IQR -3.07, -2.53), and 6.80 (IQR 6.40, 8.00), respectively. ALBI grade 2/3 had a stronger association with severe PHLF (OR=1.75, P<0.001) and mortality (OR= 1.97, P<0.001) than PALBI Grade 2/3 (OR=1.34, P<0.05 for PHLF and OR=1.57, P<0.01 for mortality) or MELD >10 (OR=1.38, P<0.05 for PHLF and OR=1.79, P<0.003). ALBI had a higher AUC (0.671) than PALBI (0.625) and MELD-Na (0.627) for predicting severe PHLF (both P<0.01). ALBI had a higher AUC (0.695) than PALBI (0.642) for predicting 30-day mortality (P<0.001). Conclusion: ALBI is a more accurate predictor of 30-day severe PHLF and mortality than MELD-Na and PALBI for patients who underwent hepatectomy. The role of PALBI for assessing post-hepatectomy outcomes warrants further investigation.

The Relationship of Albumin-Bilirubin Grade with Right and Left Colon in Patients with Colon Cancer Treated with Regorafenib

The Relationship of Albumin-Bilirubin Grade with Right and Left Colon in Patients with Colon Cancer Treated with Regorafenib

Assessment of the albumin-bilirubin grade as a prognostic factor in patients with non-small-cell lung cancer receiving anti-PD-1-based therapy

IntroductionThe albumin-bilirubin (ALBI) grade is a novel indicator of the liver function. Some studies showed that the ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. The association between the ALBI grade and outcomes in patients with non-small-cell lung cancer (NSCLC) treated with cancer immunotherapy, however, is poorly understood.MethodsWe retrospectively enrolled 452 patients with advanced or recurrent NSCLC who received anti-programmed cell death protein 1 (PD-1)-based therapy between 2016 and 2019 at three medical centers in Japan. The ALBI score was calculated from albumin and bilirubin measured at the time of treatment initiation and was stratified into three categories, ALBI grade 1-3, with reference to previous reports. We examined the clinical impact of the ALBI grade on the outcomes of NSCLC patients receiving anti-PD-1-based therapy using Kaplan–Meier survival curve analysis with log-rank test and Cox proportional hazards regression analysis.ResultsThe classifications of the 452 patients were as follows: grade 1, n = 158 (35.0%); grade 2, n = 271 (60.0%); and grade 3, n = 23 (5.0%). Kaplan–Meier survival curve analysis showed that the ALBI grade was significantly associated with progression-free survival and overall survival. Moreover, Cox regression analysis revealed that the ALBI grade was an independent prognostic factor for progression-free survival and overall survival.ConclusionThe ALBI grade was an independent prognostic factor for survival in patients with advanced or recurrent NSCLC who receive anti-PD-1-based therapy. These findings should be validated in a prospective study with a larger sample size.

Radiomics analysis of pretreatment MRI in predicting tumor response and outcome in hepatocellular carcinoma with transarterial chemoembolization: a two-center collaborative study.

To develop a machine-learning model by integrating clinical and imaging modalities for predicting tumor response and survival of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE). 140 HCC patients with TACE were retrospectively included from two centers. Tumor response were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Response-related radiomics scores (Rad-scores) were constructed on T2-weighted images (T2WI) and dynamic contrast-enhanced (DCE) imaging separately, and then integrated with conventional clinic-radiological variables into a logistic regression (LR) model for predicting tumor response. LR model was trained in 94 patients in center 1 and independently tested in 46 patients in center 2. Among 4 MRI sequences, T2WI achieved better performance than DCE (area under the curve [AUC] 0.754 vs 0.602 to 0.752). LR model by combining Rad-score on T2WI with Barcelona Clinic Liver Cancer (BCLC) stage and albumin-bilirubin (ALBI) grade resulted in an AUC of 0.813 in training and 0.781 in test for predicting tumor response. In survival analysis, progression-free survival (PFS) and overall survival (OS) presented significant difference between LR-predicted responders and non-responders. The ALBI grade and BCLC stage were independent predictors of PFS; and LR-predicted response, ALBI grade, satellite node, and BCLC stage were independent predictors of OS. The resulting Cox model produced concordance-indexes of 0.705 and 0.736 for predicting PFS and OS, respectively. The model combined MRI radiomics with clinical factors demonstrated favorable performance for predicting tumor response and clinical outcomes, thus may help personalized clinical management.

Infiltrative Hepatocellular Carcinoma: Transcatheter Arterial Chemoembolization Versus Hepatic Arterial Infusion Chemotherapy.

AimsTo compare the effectiveness, safety, and survival outcomes in patients with infiltrative hepatocellular carcinoma (HCC) who underwent hepatic arterial infusion chemotherapy (HAIC) and transarterial chemoembolization (TACE).MethodsA total of 160 patients with infiltrative HCCs who underwent initial TACE (n = 68) and HAIC (n = 92) treatment from January 2016 to March 2020. We applied the propensity score matching (PSM) to adjust for potential imbalances. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were compared between two groups. Multivariate analysis was evaluated through the forward stepwise Cox regression model and β coefficients was applied for the nomogram construction.ResultsThe median follow-up duration for the study population was 20.8 months. After PSM, the median OS and PFS in the HAIC group were significantly higher than those in the TACE group (OS, 13.3 vs 10.8 months; p = 0.043; PFS, 7.8 vs 4.0 months; p = 0.035) and the ORR and DCR in the HAIC group were significantly higher than those in the TACE group (ORR, 34.8% vs 11.8%; p = 0.001; DCR, 54.3% vs 36.8%; p = 0.028). A nomogram model comprising albumin-bilirubin grade, treatment responses, sessions, and treatment modalities, showed good predictive accuracy and discrimination (training set, concordance index [C-index] of 0.789; validation set, C-index of 0.757), which outperformed other staging systems and conventional indices.ConclusionHAIC improve significantly survival compared to TACE in patients with infiltrative HCC. A prospective randomized trial is ongoing to confirm this finding.

Prediction Efficacy of Prognostic Nutritional Index and Albumin-Bilirubin Grade in Patients With Intrahepatic Cholangiocarcinoma After Radical Resection: A Multi-Institutional Analysis of 535 Patients.

BackgroundThe preoperative nutritional status and the immunological status have been reported to be independent prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate whether prognostic nutritional index (PNI) + albumin–bilirubin (ALBI) could be a better predictor than PNI and ALBI alone in patients with ICC after radical resection.MethodsThe prognostic prediction evaluation of the PNI, ALBI, and the PNI+ALBI grade was performed in 373 patients with ICC who underwent radical resection between 2010 and 2018 at six Chinese tertiary hospitals, and external validation was conducted in 162 patients at four other Chinese tertiary hospitals. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan–Meier method. Multivariate analysis was conducted to identify independent prognostic factors. A time-dependent receiver operating characteristic (ROC) curve and a nomogram prediction model were further constructed to assess the predictive ability of PNI, ALBI, and the PNI+ALBI grade. The C-index and a calibration plot were used to assess the performance of the nomogram models.ResultsUnivariate analysis showed that PNI, ALBI, and the PNI+ALBI grade were prognostic factors for the OS and RFS of patients with ICC after radical resection in the training and testing sets (p < 0.001). Multivariate analysis showed that the PNI+ALBI grade was an independent risk factor for OS and RFS in the training and testing sets (p < 0.001). Analysis of the relationship between the PNI+ALBI grade and clinicopathological characteristics showed that the PNI+ALBI grade correlated with obstructive jaundice, alpha-fetoprotein (AFP), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), PNI, ALBI, Child–Pugh grade, type of resection, tumor size, major vascular invasion, microvascular invasion, T stage, and N stage (p < 0.05). The time-dependent ROC curves showed that the PNI+ALBI grade had better prognostic predictive ability than the PNI, ALBI, and the Child–Pugh grade in the training and testing sets.ConclusionPreoperative PNI+ALBI grade is an effective and practical predictor for the OS and RFS of patients with ICC after radical resection.

Levocarnitine Supplementation Suppresses Lenvatinib-Related Sarcopenia in Hepatocellular Carcinoma Patients: Results of a Propensity Score Analysis.

This study investigated the inhibitory effect of levocarnitine supplementation on sarcopenia progression in hepatocellular carcinoma (HCC) patients treated with lenvatinib. We evaluated the skeletal muscle index (SMI). After propensity score matching for age, sex, modified albumin-bilirubin grade, baseline presence of sarcopenia, and branched-chain amino acid administration, we selected 17 patients who received levocarnitine supplementation after starting lenvatinib therapy and 17 propensity-score-matched patients who did not receive levocarnitine. Sarcopenia was present in 76% of the patients at baseline. Changes in baseline SMI at 6 and 12 weeks of treatment were significantly suppressed in the group with levocarnitine supplementation compared with those without (p = 0.009 and p = 0.018, respectively). While there were no significant differences in serum free carnitine levels in cases without levocarnitine supplementation between baseline and after 6 weeks of treatment (p = 0.193), free carnitine levels were significantly higher after 6 weeks of treatment compared with baseline in cases with levocarnitine supplementation (p < 0.001). Baseline SMI and changes in baseline SMI after 6 weeks of treatment were significantly correlated with free carnitine levels (r = 0.359, p = 0.037; and r = 0.345, p = 0.045, respectively). Levocarnitine supplementation can suppress sarcopenia progression during lenvatinib therapy.

Simple Scoring System for Predicting TACE Unsuitable among Intermediate-Stage Hepatocellular Carcinoma Patients in the Multiple Systemic Treatment Era

Background/Aim: With the development of systemic treatment methods for unresectable hepatocellular carcinoma (uHCC), the concept of unsuitable for transcatheter arterial chemoembolization (TACE) has become important. This study aimed to establish a simple predictive scoring system for determining TACE unsuitable status. Materials/Methods: From 1998 to 2015, 196 patients with intermediate-stage uHCC with Child-Pugh A (score 5:6 = 108:88) and given TACE as the initial treatment were enrolled. At the baseline, tumor burden (Milan criteria-out, up-to-7 in/out, and up-to-11 in/out: 0–2 points) and modified albumin-bilirubin grade 1/2a or 2b (0–1 point) were added to determine the score for TACE unsuitable (CITRUS-MICAN score; low <2 and high ≥2). In addition, a previously reported tumor marker (TM) score, in which alpha-fetoprotein (AFP) was ≥100 ng/mL, fucosylated AFP ≥10%, and des-gamma-carboxy prothrombin ≥100 mAU/mL (each 1 point) (total 0, 1, or ≥2 points), was used for additionally evaluating tumor malignancy potential. Prognosis was retrospectively evaluated based on those scores. Results: Median survival time (MST) was better for low compared to high CITRUS-MICAN score (42.0 vs. 26.4 months) (p = 0.002). A 2-step evaluation using the combination of CITRUS-MICAN and TM scores showed an MST of 43.2 months for low CITRUS-MICAN/TM score 0/1 (rank-A) and 39.6 months for low CITRUS-MICAN/TM score ≥2 (rank-B2), while it was 46.8 months for high CITRUS-MICAN/TM score 0 (rank-B1), 28.8 months for high CITRUS-MICAN/TM score 1 (rank-B2), and 22.8 months for high CITRUS-MICAN/TM score ≥2 (rank-C). For rank-A cases (n = 51), MST was 43.2 months, while it was 46.8 months for rank-B1 (n = 12), 31.2 months for rank-B2 (n = 82), and 22.8 months for rank-C (n = 51) (p = 0.001). Conclusion: The results showed that rank-C indicates absolute TACE unsuitable status. For rank-A patients, good prognosis with TACE can be expected, while TACE refractoriness status during the clinical course should be carefully evaluated so as to anticipate the appropriate timing for switching to systemic treatment in rank-B1 and -B2 patients.

The Prognostic Value of the Albumin to Gamma-Glutamyltransferase Ratio in Patients with Hepatocellular Carcinoma Undergoing Radiofrequency Ablation.

Albumin to gamma-glutamyltransferase ratio (AGR) is a newly developed biomarker for the prediction of patients' prognosis in solid tumors. The purpose of the study was to establish a novel AGR-based nomogram to predict tumor prognosis in patients with early-stage HCC undergoing radiofrequency ablation (RFA). 394 hepatocellular carcinoma (HCC) patients who had received RFA as initial treatment were classified into the training cohort and validation cohort. Independent prognostic factors were identified by univariate and multivariate analyses. The value of AGR was evaluated by the concordance index (C-index), receiver operating characteristic (ROC) curves, and likelihood ratio tests (LAT). Logistic regression and nomogram were performed to establish the pretreatment scoring model based on the clinical variables. As a result, AGR = 0.63 was identified as the best cutoff value to predict overall survival (OS) in the training cohort. According to the results of multivariate analysis, AGR was an independent indicator for OS and recurrence-free survival (RFS). In both training cohort and validation cohort, the high-AGR group showed better RFS and OS than the low-AGR group. What is more, the C-index, area under the ROC curves, and LAT χ2 values suggested that AGR outperformed the Child-Pugh (CP) grade and albumin-bilirubin (ALBI) grade in terms of predicting OS. The AGR, AKP, and tumor size were used to establish the OS nomogram. Besides, the results of Hosmer-Lemeshow test and calibration curve analysis displayed that both nomograms in the training and validation cohorts performed well in terms of calibration. Therefore, the AGR-based nomogram can predict the postoperative prognosis of early HCC patients undergoing RFA.

Assessing the progression of segmental fibrosis in chronic liver disease using extracellular volume fractions

PurposeTo assess the segmental difference of liver fibrosis during the progression of chronic liver disease (CLD) using hepatic extracellular volume fractions (fECVs) obtained by dual-energy CT. MethodsA total of 218 patients (92 men and 126 women; mean age, 67.8 ± 11.7 years) with CLD and 85 patients (44 men and 41 women; mean age, 62.8 ± 13.7 years) without CLD as a control underwent dual-energy computed tomography (CT) of the liver (5-min equilibrium phase images). The iodine densities of the lateral, medial, anterior, and posterior segments and the aorta were measured, and fECVs were calculated. Comparisons of the fECV of each segment and for each albumin–bilirubin (ALBI) grade were then statistically analyzed. ResultsIn the control group and ALBI grades 1 and 3, no significant difference in fECV was found between each segment, whereas in ALBI grade 2, the fECVs were significantly larger in the medial and anterior than in the other segments (p < 0.001). The fECVs of the lateral and posterior segments significantly increased with higher ALBI grade (p < 0.001). The fECVs of the medial and anterior segments were significantly increased with higher ALBI grade, up to grade 2 (p < 0.001), but no significant difference was found between ALBI grades 2 and 3. ConclusionDuring the progression of CLD, fibrosis antecedently progressed in the medial and anterior segments, followed by the other liver segments.

Association between contrast enhancement on contrast-enhanced CT and lenvatinib effectiveness in hepatocellular carcinoma.

The aim of the present study was to investigate whether the degree of contrast enhancement on contrast-enhanced (CE)-CT can predict the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). A total of 67 consecutive patients with LEN-treated HCC were retrospectively analysed. In the pretreatment CE-CT, the CT values were measured using a region of interest within the main nodule and the liver parenchyma in the arterial phase, and the macroscopic degree of contrast enhancement of the tumour area was quantified by calculating the enhancement ratio (ER) of the liver parenchyma. The associations of pretreatment ER with progression-free survival (PFS) and overall survival (OS) were then investigated. There were 20, 27 and 20 patients in the ER ≥1.5, 1.0≤ ER <1.5 and ER <1.0 groups, respectively. There was no significant difference in the PFS and OS among the three ER groups (PFS, P=0.63; OS, P=0.455). The ER <1.0 group had significantly more patients with larger tumour diameters, Barcelona Clinic Liver Cancer (BCLC) stage C with extrahepatic metastases, and higher des-γ-carboxy prothrombin values compared with the ER ≥1.0 group, suggesting that ER <1.0 reflected more aggressive types of HCC. The multivariate analysis revealed tumour size and α-fetoprotein as independent predictors of shorter PFS. Albumin-bilirubin grade 2 and BCLC stage C were significant predictors of poor OS, whereas the ER was confirmed as a non-significant predictor of both PFS and OS. Only non-alternating LEN and transarterial therapy (AT) were identified as independent predictors of unfavourable OS in patients with BCLC stage B HCC. Therefore, LEN has a strong therapeutic effect on HCC, regardless of the degree of contrast enhancement. Furthermore, AT may prolong the OS of LEN-treated patients with BCLC stage B HCC, regardless of tumour vascularity.

Predictive Outcomes Using Child-Turcotte-Pugh and Albumin-Bilirubin Scores in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.

We assessed the ability of the Child-Turcotte-Pugh score and the albumin-bilirubin grade to predict the outcomes of hepatocellular carcinoma (HCC) in patients treated with transarterial chemoembolization. We retrospectively assessed 158 patients with HCC who underwent transarterial chemoembolization. The ability of the Child-Turcotte-Pugh score and the albumin-bilirubin grade to predict patient survival was assessed using the Kaplan-Meier method. The Cox proportional hazards model was used to evaluate survival-predictive variables and the relationship between the obtained score and overall survival. Child-Turcotte-Pugh A (n = 102 (64.6%)) patients showed better overall survival than Child-Turcotte-Pugh B (n = 56 (35.4%)) patients (log-rank P = 0.017), while no significant difference in the overall survival between albumin-bilirubin ≤ 1 (n = 37 (23.4%)) and albumin-bilirubin > 1 (n = 121 (76.6%)) was detected (log-rank P = 0.140). Multivariate analysis identified alcoholic liver disease (P = 0.029), tumor size > 5cm (P = 0.004), and serum alpha-fetoprotein > 200ng/mL (P < 0.001) as independent predictive factors of mortality risk. A higher Child-Turcotte-Pugh score was positively associated with decreased overall survival (P = 0.031); however, a higher albumin-bilirubin grade showed marginally significant association (P = 0.088). The Child-Turcotte-Pugh score precisely categorized the outcomes of HCC in patients undergoing transarterial chemoembolization, and cirrhotic patients with Child-Turcotte-Pugh A will have a better overall survival than those with Child-Turcotte-Pugh B, regardless of HCC status. These results suggest that the Child-Turcotte-Pugh classification system is a more powerful tool to predict patient outcomes than the albumin-bilirubin grading system.

Albumin-Bilirubin (ALBI) and Monocyte to Lymphocyte Ratio (MLR)-Based Nomogram Model to Predict Tumor Recurrence of AFP-Negative Hepatocellular Carcinoma.

PurposeIn this study, we aimed to develop a novel liver function and inflammatory markers-based nomogram to predict recurrence-free survival (RFS) for AFP-negative (<20 ng/mL) HCC patients after curative resection.Patients and MethodsA total of 166 pathologically confirmed AFP-negative HCC patients were included at the Ningbo Medical Center Lihuili Hospital. A LASSO regression analysis was used for data dimensionality reduction and element selection. Univariate and multivariate Cox regression analyses were performed to identify the independent risk factors relevant to RFS. Finally, clinical nomogram prediction model for RFS of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Receiver operating characteristic (ROC) and decision curve analysis (DCA) curve were used to validate the performance and clinical utility of the nomogram.ResultsMultivariate Cox regression analysis indicated that ALBI grade (hazard ratio, [HR] = 2.624, 95% confidence interval [CI]: 1.391–4.949, P = 0.003), INR (HR = 2.605, 95% CI: 1.061–6.396, P = 0.037), MLR (HR = 1.769, 95% CI: 1.073–2.915, P = 0.025) and MVI (HR = 4.726, 95% CI: 2.365–9.444, P < 0.001) were independent prognostic factors of RFS. Nomogram with independent factors was established and achieved a better concordance index of 0.753 (95% CI: 0.672–0.834) for predicting RFS. The ROC found that the area under curve (AUC) was consistent with the C-index and the sensitivity was 85.4%. The risk score calculated by nomogram could divide AFP-negative HCC patients into high-, moderate- and low-risk groups (P < 0.05). DCA analysis revealed that the nomogram could augment net benefits and exhibited a wider range of threshold probabilities by the risk stratification than the AJCC T and BCLC stage in the prediction of AFP-negative HCC recurrence.ConclusionThe ALBI grade- and MLR-based nomogram prognostic model for RFS showed high predictive accuracy in AFP-negative HCC patients after surgical resection.

Real-World Lenvatinib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

BackgroundLenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world.MethodsWe retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups.ResultsA total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3–0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively.ConclusionsIn clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

Long-term hepatic function of patients with compensated cirrhosis following successful direct-acting antiviral treatment for hepatitis C virus infection.

Direct-acting antivirals (DAAs) have contributed to the improvement of outcomes for all patients with chronic hepatitis C. The aim of this study was to evaluate the long-term hepatic benefits of hepatitis C virus (HCV) cure by DAAs in patients with compensated cirrhosis. This multicenter cohort study consisted of consecutive patients with compensated cirrhosis who initiated interferon-free DAA treatment before September 2016. The impact of treatment on long-term hepatic function was followed for at least 4years after the end of treatment, and the progression to decompensation was evaluated. The data of 394 patients were available for study. The median age was 70, and 41% had modified albumin-bilirubin (ALBI) grade 2b. During a short-term follow-up 1year after the end of treatment, FIB-4 index and ALBI score significantly improved. The achievement rates of FIB-4<3.25 (40%) and ALBI grade 1 (70%) reached their plateau in the first year; however, there were significant further improvements in platelet count and α-fetoprotein level after the first year. The annual incidence of decompensation was 1.30 (95% confidence interval 0.83-2.02) per 100 person-years. In multivariable analysis, male sex and modified ALBI grade 2b at baseline were associated with decompensation. In a large real-world cohort of patients with compensated cirrhosis treated with a DAA, remarkable improvement in hepatic function was seen after HCV cure, especially during the first year after the end of treatment. Treatment in the early stage of cirrhosis would be of great benefit for preventing liver deterioration to decompensation.

First-line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study.

Background and AimsSequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC.MethodsWe evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2).ResultsOverall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA.ConclusionsSequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.