Hepatic Function during Repeated TACE Procedures and Prognosis after Introducing Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: Multicenter Analysis

Background/Aim: We evaluated the relationship of hepatic function with repeated transarterial catheter chemoembolization (TACE) and prognosis after sorafenib treatment in various patient cohorts. Methods: Study 1 comprised of 212 Barcelona clinic liver cancer stage-B (BCLC-B) HCC patients classified as Child-Pugh A (CP-A) and who had received repeated TACE treatments (r-TACE) (naïve:recurrence = 66:146). Study 2 comprised of 435 patients with unresectable HCC classified as CP-A in who sorafenib was introduced (naïve:recurrence = 37:398; CP score 5:6 = 282:153; macro-vessel invasion [MVI]+: extrahepatic metastasis [EHM]+ both negative = 124:226:143). Changes in hepatic function along with CP and albumin-bilirubin (ALBI) score/grade during r-TACE in Study 1, and prognosis after introducing sorafenib in Study 2 were evaluated. Results: Hepatic function worsened to CP-B in 9-14% with each TACE procedure, while 18-21% had a change of classification from ALBI-1 to ALBI-2. When the prognosis of patients with the best CP score of 5 was analyzed, those with ALBI-1 (n = 154) had a better outcome than those with ALBI-2 (n = 128) (MST 17.5 vs. 9.9 months; p = 0.01), while ALBI-1 (n = 43) patients also showed a better outcome than ALBI-2 (n = 34) patients with a CP score of 5 without MVI/EHM (MST: 17.5 vs. 10.0 months; p = 0.029). The Akaike's Information criterion for ALBI-grade (MST: grade 1 vs. 2 = 16.9 vs. 10.4 months; p = 0.001) was also better than that for CP (MST: score 5 vs. 6 = 14.4 vs. 10.5 months; p = 0.003) (3195.6 vs. 3197.5) in all 435 patients. Conclusion: The rate of patients with downgraded hepatic function during r-TACE, especially with regard to ALBI-grade, was not low. ALBI-grade was shown to be a better hepatic function assessment tool than CP in patients receiving sorafenib treatment. Strict judgment of TACE-refractory status in patients with unresectable HCC is needed to improve prognosis before downgrading the hepatic function.

[1]  M. Kudo,et al.  Albumin-Bilirubin (ALBI) Grade as Part of the Evidence-Based Clinical Practice Guideline for HCC of the Japan Society of Hepatology: A Comparison with the Liver Damage and Child-Pugh Classifications , 2017, Liver Cancer.

[2]  M. Kudo Albumin-Bilirubin Grade and Hepatocellular Carcinoma Treatment Algorithm , 2017, Liver Cancer.

[3]  M. Zheng,et al.  Usefulness of albumin‐bilirubin grade for evaluation of long‐term prognosis for hepatitis B‐related cirrhosis , 2017, Journal of viral hepatitis.

[4]  M. Kudo,et al.  The albumin–bilirubin grade improves hepatic reserve estimation post‐sorafenib failure: implications for drug development , 2017, Alimentary pharmacology & therapeutics.

[5]  W. Yeo,et al.  Incorporating albumin–bilirubin grade into the cancer of the liver Italian program system for hepatocellular carcinoma , 2017, Journal of gastroenterology and hepatology.

[6]  M. Kurosaki,et al.  Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment , 2016, Liver Cancer.

[7]  M. Kudo,et al.  Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma , 2016, Liver Cancer.

[8]  M. Makuuchi,et al.  Survival Analysis over 28 Years of 173,378 Patients with Hepatocellular Carcinoma in Japan , 2016, Liver Cancer.

[9]  R. Finn,et al.  Personalized Clinical Trials in Hepatocellular Carcinoma Based on Biomarker Selection , 2016, Liver Cancer.

[10]  H. Toyoda,et al.  Usefulness of albumin–bilirubin grade for evaluation of prognosis of 2584 Japanese patients with hepatocellular carcinoma , 2016, Journal of gastroenterology and hepatology.

[11]  Lequn Li,et al.  Albumin–bilirubin versus Child–Pugh score as a predictor of outcome after liver resection for hepatocellular carcinoma , 2016, The British journal of surgery.

[12]  T. Murakami,et al.  Balloon-Occluded Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Single-Center Experience , 2015, Oncology.

[13]  M. Kudo,et al.  Effectiveness of Sorafenib in Patients with Transcatheter Arterial Chemoembolization (TACE) Refractory and Intermediate-Stage Hepatocellular Carcinoma , 2015, Liver Cancer.

[14]  M. Kudo Immune Checkpoint Blockade in Hepatocellular Carcinoma , 2015, Liver Cancer.

[15]  Chen-Chun Lin,et al.  Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment , 2015, Liver Cancer.

[16]  M. Kudo,et al.  Subclassification of BCLC B Stage Hepatocellular Carcinoma and Treatment Strategies: Proposal of Modified Bolondi's Subclassification (Kinki Criteria) , 2015, Digestive Diseases.

[17]  M. Kudo Molecular Targeted Therapy for Hepatocellular Carcinoma: Where Are We Now? , 2015, Liver Cancer.

[18]  Shin'pei Sato,et al.  Current Status of Hepatic Arterial Infusion Chemotherapy , 2015, Liver Cancer.

[19]  T. Murakami,et al.  Surgical and Locoregional Therapy of HCC: TACE , 2015, Liver Cancer.

[20]  M. Kudo Locoregional Therapy for Hepatocellular Carcinoma , 2015, Liver Cancer.

[21]  Y. Hiasa,et al.  Tumor Markers AFP, AFP-L3, and DCP in Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization , 2015, Oncology.

[22]  G. Gores,et al.  Liver cancer: Approaching a personalized care. , 2015, Journal of hepatology.

[23]  T. Murakami,et al.  Clinical Practice Guidelines for Hepatocellular Carcinoma Differ between Japan, United States, and Europe , 2015, Liver Cancer.

[24]  H. Toyoda,et al.  Tumor Markers for Hepatocellular Carcinoma: Simple and Significant Predictors of Outcome in Patients with HCC , 2015, Liver Cancer.

[25]  B. Sangro,et al.  Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M. Kudo Surveillance, Diagnosis, Treatment, and Outcome of Liver Cancer in Japan , 2015, Liver Cancer.

[27]  M. Kudo,et al.  Transarterial Chemoembolization Failure/Refractoriness: JSH-LCSGJ Criteria 2014 Update , 2014, Oncology.

[28]  M. Kudo,et al.  Characteristics of Long-Term Survivors following Sorafenib Treatment for Advanced Hepatocellular Carcinoma: Report of a Workshop at the 50th Annual Meeting of the Liver Cancer Study Group of Japan , 2014, Oncology.

[29]  Y. Imai,et al.  JSH Consensus-Based Clinical Practice Guidelines for the Management of Hepatocellular Carcinoma: 2014 Update by the Liver Cancer Study Group of Japan , 2014, Liver Cancer.

[30]  M. Yoshikawa,et al.  Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization , 2014, Oncology.

[31]  T. Ishikawa,et al.  Predictive Factor of Local Recurrence after Balloon-Occluded TACE with Miriplatin (MPT) in Hepatocellular Carcinoma , 2014, PloS one.

[32]  D. Palmer,et al.  The ART strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. , 2014, Journal of hepatology.

[33]  H. Heinzl,et al.  The ART-strategy: sequential assessment of the ART score predicts outcome of patients with hepatocellular carcinoma re-treated with TACE. , 2014, Journal of hepatology.

[34]  J. Dufour,et al.  Intermediate hepatocellular carcinoma: current treatments and future perspectives. , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[35]  Midterm follow-up after DC-BEAD™-TACE of hepatocellular carcinoma (HCC). , 2012, European journal of radiology.

[36]  S. Paggi,et al.  Sorafenib in Advanced Hepatocellular Carcinoma , 2008 .

[37]  Dieter Häussinger,et al.  Sorafenib in advanced hepatocellular carcinoma. , 2008, The New England journal of medicine.

[38]  G. Benea,et al.  Chemoembolization (TACE) of Unresectable Intrahepatic Cholangiocarcinoma with Slow-Release Doxorubicin-Eluting Beads: Preliminary Results , 2008, CardioVascular and Interventional Radiology.

[39]  M. Makuuchi,et al.  Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients. , 2006, Gastroenterology.

[40]  Masatoshi Kudo,et al.  Validation of a new prognostic staging system for hepatocellular carcinoma: The JIS score compared with the CLIP score , 2004, Hepatology.

[41]  Masatoshi Kudo,et al.  256 JIS scoring system combined with 3 tumor makers (modified JIS score) is an exellent prognostic staging system for hepatocellular carcinoma (HCC): Analysis of 4525 patients with HCC , 2004 .

[42]  M. Kudo,et al.  Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations, and a proposal for a new staging system, the Japan Integrated Staging Score (JIS score) , 2003, Journal of Gastroenterology.

[43]  Pietro Andreone,et al.  Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. , 2002, Radiology.

[44]  John Wong,et al.  Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma , 2002, Hepatology.