ALBI and P-ALBI grade in Child-Pugh A patients treated with drug eluting embolic chemoembolization for hepatocellular carcinoma

Background Treatment outcome for hepatocellular carcinoma (HCC) is related to tumor burden and liver function. Grading systems assessing liver function need validation in different clinical settings. Purpose To evaluate drug-eluting embolic transarterial chemoembolization (DEE-TACE) in Child–Pugh A HCC with respect to albumin-bilirubin (ALBI) and platelet-albumin-bilirubin (P-ALBI) grade. Material and Methods Forty-nine patients with Child–Pugh class A, diagnosed with HCC and allocated to DEE-TACE treatment, were retrospectively analyzed regarding tumor and treatment characteristics, radiological response (mRECIST) one month post treatment, overall survival (OS), and adverse events (AEs; CTCAE, grades ≥3) with respect to ALBI and P-ALBI grade. Results There were 21 ALBI 1 patients, 29 P-ALBI 1 patients, and 19 patients were both ALBI and P-ALBI 1. Objective response rate was 74% with no statistically significant difference for ALBI (1 vs. 2; P = 0.08), or P-ALBI (1 vs. 2; P = 0.49). OS was 14.8 months (range = 1.7–62.0; ALBI 1 vs. 2: P = 0.08; P-ALBI 1 vs. 2: P = 0.003). OS in responders with ALBI 1 and 2 was 28.9 vs.10.2 months ( P = 0.02), and P-ALBI 1 and 2 was 26.7 vs. 8.6 months ( P < 0.001). In multivariate analyses, both ALBI 2 (HR = 2.4, P = 0.02) and P-ALBI 2 (HR = 3.3, P < 0.01) were negative prognostic factors for survival. There were 15 AEs in 13 patients, with hepatic failure only occurring in ALBI 2 and P-ALBI 2 patients. Conclusion P-ALBI grade 1 and 2 differentiated survival in Child–Pugh A patients treated with DEE-TACE. Both grading systems can differentiate survival in patients responding to treatment.

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Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.287 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 287-287

Author(s):

Thierry De Baere ◽

Filipe Veloso Gomes ◽

Gontran Verset ◽

Gerardo Tovar-Felice ◽

Katerina Malagari ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Transarterial Chemoembolization ◽

Tumor Response ◽

Objective Response ◽

Progression Free Survival ◽

Close Monitoring ◽

Bridge To Transplant ◽

Level Data ◽

Drug Eluting

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]

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Response to Lenvatinib Is Associated with Optimal RelativeDose Intensity in Hepatocellular Carcinoma: Experience in Clinical Settings

Cancers ◽

10.3390/cancers11111769 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1769 ◽

Cited By ~ 16

Author(s):

Sasaki ◽

Fukushima ◽

Haraguchi ◽

Miuma ◽

Miyaaki ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Evaluation Criteria ◽

Dose Intensity ◽

Hepatic Function ◽

University Hospital ◽

Clinical Settings ◽

Operating Characteristics ◽

Or Groups ◽

Significant Difference

Background: Lenvatinib is currently available as the first-line treatment for advanced unresectable hepatocellular carcinoma. We evaluated the relationship between its relative dose intensity (RDI) and response in clinical settings. Methods: From March 2018 to May 2019, 93 patients were administered lenvatinib at the Nagasaki University Hospital and its related facilities. Among these, 81 patients (66 men, 15 women, median age 72.0) who received lenvatinib were analyzed retrospectively. Results: Fourteen patients were Child–Pugh grade B, and 15 had received other systemic therapy. According to Response Evaluation Criteria in Solid Tumors (RECIST), the objective response (OR) rate was 17.3%. The overall survival (OS) was significantly better in the OR group (p = 0.011). There was a significant difference in RDI between the OR and non-OR groups (p < 0.05). The area under the receiver operating characteristics curve for OR prediction by the 4, 8, 12, and 16-week RDI were 0.666, 0.747, 0.731, and 0.704, respectively. In the 8-week RDI 67.0% group, OS was significantly better than in the 8-week RDI< 67.0% group (p = 0.003). Conclusions: Because a sufficient RDI is required to achieve an OR, it is strongly recommended that lenvatinib should be administered to patients with good hepatic function and status.

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CalliSpheres Drug-Eluting Bead Transcatheter Arterial Chemoembolization Presents With Better Efficacy and Equal Safety Compared to Conventional TACE in Treating Patients With Hepatocellular Carcinoma

Technology in Cancer Research & Treatment ◽

10.1177/1533033819830751 ◽

2019 ◽

Vol 18 ◽

pp. 153303381983075 ◽

Cited By ~ 9

Author(s):

Hua Xiang ◽

Lin Long ◽

Yuanhui Yao ◽

Zhiyong Fang ◽

Zhiming Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Function ◽

Transcatheter Arterial Chemoembolization ◽

Response Rate ◽

Objective Response ◽

Progression Free Survival ◽

Free Survival ◽

Drug Eluting ◽

Arterial Chemoembolization

The aim of this study was to compare the treatment response, survival, liver function, and adverse event incidence of drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres with conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Seventy-three patients with hepatocellular carcinoma who received drug-eluting bead transcatheter arterial chemoembolization (using CalliSpheres microspheres) or conventional transcatheter arterial chemoembolization treatment were consecutively enrolled. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors at month 1/month 3/month 6; posttreatment, liver function indexes, and adverse events were recorded. Progression-free survival and overall survival were also calculated. Objective response rate of patients at months 1, 3, and 6, disease control rate of patients and objective response rate of nodules at month 3 were increased in drug-eluting bead transcatheter arterial chemoembolization group compared with conventional transcatheter arterial chemoembolization group. In addition, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was an independent factor for predicting better objective response rate at month 1. Patients in drug-eluting bead transcatheter arterial chemoembolization group achieved longer progression-free survival and similar overall survival compared to those in conventional transcatheter arterial chemoembolization group; Cox proportional hazards regression model analyses revealed that drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was associated with better progression-free survival while it did not affect overall survival. Meanwhile, most of the occurrences of abnormal liver function indexes were similar between 2 groups, whereas drug-eluting bead transcatheter arterial chemoembolization group had a higher percentage of patients with total bile acid ≥2 upper limit of normal compared to conventional transcatheter arterial chemoembolization group at month 1. Moreover, the adverse event incidences between 2 groups were similar. In conclusion, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres achieves better treatment response and progression-free survival while equal safety compared to conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

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Lenvatinib for Hepatocellular Carcinoma: A Literature Review

Pharmaceuticals ◽

10.3390/ph14010036 ◽

2021 ◽

Vol 14 (1) ◽

pp. 36

Author(s):

Takeshi Hatanaka ◽

Atsushi Naganuma ◽

Satoru Kakizaki

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Cancer ◽

Liver Function ◽

Adverse Events ◽

Therapeutic Response ◽

Objective Response ◽

Intermediate Stage ◽

Tumor Burden ◽

Asia Pacific

Lenvatinib, which is an oral multikinase inhibitor, showed non-inferiority to the sorafenib in terms of overall survival (OS) and a higher objective response rate (ORR) and better progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). A good liver function and Barcelona Clinic Liver Cancer (BCLC) intermediate stage were the key factors in achieving therapeutic efficacy. The management of adverse events plays an important role in continuing lenvatinib treatment. While sequential therapies contributed to prolonging overall survival, effective molecular targeted agents for the administration after lenvatinib have not been established. Repeated transcatheter arterial chemoembolization (TACE) was associated with a decline in the liver function and poor therapeutic response in BCLC intermediate patients. Recently, the Asia-Pacific Primary Liver Cancer Expert (APPLE) Consensus Statement proposed the criteria for TACE unsuitability. Upfront systemic therapy may be better for the BCLC intermediate stage HCC patients with a high tumor burden, while selective TACE will be recommended for obtaining a curative response in patients with a low tumor burden. This article reviews the therapeutic response, management of adverse events, post-progression treatment after Lenvatinib, and treatment strategy for BCLC intermediate stage HCC.

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Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000507022 ◽

2020 ◽

Vol 9 (4) ◽

pp. 382-396 ◽

Cited By ~ 3

Author(s):

Susumu Maruta ◽

Sadahisa Ogasawara ◽

Yoshihiko Ooka ◽

Masamichi Obu ◽

Masanori Inoue ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Objective Response ◽

Dose Intensity ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

High Burden ◽

Advanced Hcc ◽

Class B ◽

Pugh Class

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial. Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan. Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7–6.9 for first line, 4.8 months; 95% CI 3.8–5.9 for second or later line, p = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin – bilirubin scores. Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.

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Transarterial Chemoembolization Combined with Iodine 125 Seeds Versus Transarterial Chemoembolization Combined with Radiofrequency Ablation in the Treatment of Early and Intermediate Hepatocellular Carcinoma

10.21203/rs.2.21964/v1 ◽

2020 ◽

Author(s):

chen lei ◽

Xuefeng Kan ◽

Tao Sun ◽

Yanqiao Ren ◽

Yanyan Cao ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Transarterial Chemoembolization ◽

Objective Response ◽

Progression Free Survival ◽

Free Survival ◽

Risk Of Death ◽

Significant Difference ◽

Pugh Class ◽

Iodine 125

Abstract Background To compare the efficacy of the combination of transarterial chemoembolization (TACE) and iodine 125 seeds implantation (TACE-Iodine 125) with the combination of TACE and radiofrequency ablation (RFA) in the treatment of patients with early and intermediate hepatocellular carcinoma (HCC). Methods The study included 134 patients diagnosed with early and intermediate HCC from January 1, 2014, to May 31, 2018. Among them, 47 patients were treated with TACE-Iodine 125, and 87 with TACE-RFA and the efficacy of both treatments was analyzed. To reduced selective bias, propensity score matching (PSM) was used to compare the outcomes of the treatments. Results In the absence of PSM, the median overall survival (OS) and progression-free survival (PFS) of the TACE-RFA group were slightly longer than those of the TACE-Iodine 125 group (OS: 42 months vs. 37 months; PFS: 18 months vs. 15 months). However, there was no significant difference in median OS, PFS, and the objective response rate (ORR) between the two groups (P>0.05). After adjusted for age, gender, liver resection, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage and Alpha-fetoprotein (AFP), TACE-Iodine 125 treatment was not associated with a significant increasing in risk of death (HR: 0.725; 95%CI: 0.423,1.241, P=0.241) and recurrence (HR: 1.008; 95%CI: 0.666,1.526, P=0.969). After PSM, 47 patient pairs were generated, and there was no significant difference in median OS and PFS between the two groups. Conclusions The combination of TACE and iodine 125 seeds implantation may represent an effective treatment for patients with early and intermediate HCC.

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Unresectable hepatocellular carcinoma: prospects for drug therapy with lenvatinib

Malignant tumours ◽

10.18027/2224-5057-2021-11-3-45-52 ◽

2022 ◽

Vol 11 (3) ◽

pp. 45-52

Author(s):

V. V. Breder ◽

D. T. Abdurakhmanov ◽

V. V. Petkau ◽

P. V. Balakhnin ◽

M. V. Volkonsky ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Therapy ◽

Liver Function ◽

Real World ◽

Systemic Therapy ◽

Efficacy And Safety ◽

Study Results ◽

Class B ◽

Pugh Class ◽

Positive Results

There is a number of unresolved issues regarding the systemic therapy administration for hepatocellular carcinoma (HCC). Their solution is facilitated by accumulating real‑world study results. Lenvatinib therapy is a recognized drug with a good efficacy and safety profile for the treatment of HCC. Subanalyses of the REFLECT study showed that the absence of stratification by baseline AFP and baseline liver function, as well as the lack of options for subsequent drug therapy after lenvatinib, also affects the outcomes. Once these factors are taken into account, the hypothesis of superiority of lenvatinib to sorafenib and other drugs can be tested. Real‑world clinical studies have demonstrated positive results of lenvatinib therapy in patients with Child‑Pugh class B liver function, provided recommendations on the sequence of systemic therapy after lenvatinib and on the use of lenvatinib in patients with BCLC stage B, along with considering the possibility of lenvatinib monotherapy and the prospects for its use in patients with nHCC. Further real‑world studies of lenvatinib for HCC in the Russian population are required.

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Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

Cancers ◽

10.3390/cancers12040897 ◽

2020 ◽

Vol 12 (4) ◽

pp. 897

Author(s):

Antonio Facciorusso ◽

Irene Bargellini ◽

Marina Cela ◽

Ivan Cincione ◽

Rodolfo Sacco

Keyword(s):

Hepatocellular Carcinoma ◽

Propensity Score ◽

Liver Toxicity ◽

Propensity Score Analysis ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Burden ◽

Y90 Radioembolization ◽

Group 2 ◽

Group 1

Background: Adjuvant sorafenib may enhance the efficacy of transarterial radioembolization with yttrium-90 in hepatocellular carcinoma patients. The aim of this study is to assess the efficacy and safety of radioembolization plus sorafenib in comparison to radioembolization alone. Methods: Out of 175 hepatocellular carcinoma (HCC) patients treated with radioembolization between 2011 and 2018, after propensity score matching, two groups were compared: a group of 45 patients that underwent radioembolization while being on sorafenib (Group 1) and a second group of 90 patients that underwent radioembolization alone (Group 2). Results: Baseline characteristics of the two groups were well balanced concerning liver function and tumor burden. No significant differences in survival outcomes were identified (median overall survival 10 vs. 10 months; p = 0.711), median progression-free survival 6 vs. 7 months (p = 0.992) in Group 1 and Group 2). The objective response rate in Group 1 vs. Group 2 was 45.5% vs. 42.8% (p = 1) according to mRECIST. No differences in toxicity nor in liver decompensation rates were registered. Conclusions: The association of sorafenib does not prolong survival nor delay progression in patients treated with radioembolization. Liver toxicity does not differ among the two therapeutic schemes.

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Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Oncology ◽

10.1159/000509387 ◽

2020 ◽

Vol 98 (11) ◽

pp. 787-797 ◽

Cited By ~ 2

Author(s):

Yuwa Ando ◽

Tomokazu Kawaoka ◽

Yosuke Suehiro ◽

Kenji Yamaoka ◽

Yumi Kosaka ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Multivariate Analysis ◽

Liver Function ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Class A ◽

Line Therapy ◽

Pugh Class ◽

Ecog Ps

Background: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. Methods: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. Results: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, p = 0.01) were significant prognostic factors. Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

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Baseline and Early Predictors of Good Patient Candidates for Second-Line after Sorafenib Treatment in Unresectable Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers11091256 ◽

2019 ◽

Vol 11 (9) ◽

pp. 1256 ◽

Cited By ~ 5

Author(s):

Hitomi Takada ◽

Masayuki Kurosaki ◽

Kaoru Tsuchiya ◽

Yasuyuki Komiyama ◽

Jun Itakura ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Disease Progression ◽

Kinase Inhibitors ◽

Tumor Burden ◽

Second Line ◽

Inclusion Criteria ◽

Sorafenib Treatment ◽

Unresectable Hepatocellular Carcinoma ◽

Early Predictors

Background: Recent advances in the development of tyrosine kinase inhibitors (TKIs) have enabled patients with unresectable hepatocellular carcinoma (HCC) to receive multiple TKIs in sequence. The aim of this study was to identify predictors of good candidates for second-line treatment after disease progression during sorafenib treatment. Methods: This is a retrospective cohort study of 190 consecutive HCC patients who were treated with sorafenib in our hospital. Three criteria of good candidates for second-line TKI at the time of disease progression during sorafenib treatment were defined as follows: criterion 1 was the same as the inclusion criteria of the regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE) study, criterion 2 was the inclusion criteria of the RESORCE study plus Child–Pugh score 5, and criterion 3 was the inclusion criteria of the RESORCE study plus albumin–bilirubin (ALBI) grade 1. Factors at baseline and at week 4 during sorafenib treatment were used to predict patients fulfilling each of these three criteria. Results: The distribution of patients was 29%, 13%, and 6% in criteria 1, 2, and 3, respectively. Significant factors for meeting criterion 1 was the combination of baseline albumin >3.7 g/dL (odds ratio (OR) 2.7) plus degree of decrease in albumin (Δalbumin) at week 4 <0.2 g/dL (OR 2.6), or the combination of baseline ALBI score <−2.33 (OR 2.5) and ΔALBI at week 4 <0.255 (OR 4.9). For criterion 2, the value of baseline albumin and ALBI score was identical to criterion 1; however, Δalbumin (<0.1 g/dL) and ΔALBI score (<0.19) became stricter. For criterion 3, the value of baseline albumin (>3.8 g/dL) and ALBI (<−2.55) became stricter, as did Δalbumin (<0.1 g/dL) and ΔALBI (<0.085). Furthermore, tumor burden (>11) was selected as an additional predictor (OR 5.4). Conclusion: Predictors to satisfy the RESORCE study inclusion criteria were as follows: preserved liver function at baseline, as reflected by albumin or ALBI score, and small deterioration of liver function early during sorafenib therapy, as reflected by Δalbumin or ΔALBI at week 4. Liver function at baseline and degree of change in liver function during sorafenib treatment need to be stricter for better outcomes of liver function with disease progression.

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