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Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center

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Abstract

Background

Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC).

Methods

Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child–Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors.

Results

Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child–Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18–2.41) for cirrhotic stage B or C, 1.07 (1.04–1.10) for MELD scores, and 1.14 (1.04–1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14–0.33).

Conclusion

Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

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Data availability

No datasets were generated or analysed during the current study.

Abbreviations

ABI:

Albumin-Bilirubin index

ACLF:

Acute-on-chronic liver failure;

AFP:

Alpha fetoprotein

BMI:

Body mass index

CI:

Confidence interval

DDLT:

Deceased donor liver transplantation

DM:

Diabetes mellitus

EV:

Esophageal varices

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HCV:

Hepatitis C virus

HR:

Hazard ratio

IQR:

Interquartile ranges

LDLT:

Living donor liver transplantation

MELD:

Model for End-Stage Liver Disease

RFA:

Radiofrequency ablation

TACE:

Trans-arterial chemoembolization

USCF:

University of California San Francisco

References

  1. Llovet JM, Kelley RK, Villanueva A et al (2021) Hepatocellular carcinoma. Nat Rev Dis Primers 7(1):6

    Article  PubMed  Google Scholar 

  2. Craig AJ, von Felden J, Garcia-Lezana T, Sarcognato S, Villanueva A (2020) Tumour evolution in hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol 17(3):139–152

    Article  PubMed  Google Scholar 

  3. Granito A, Bolondi L (2017) Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis. Lancet Oncol 18(2):e101–e112

    Article  PubMed  Google Scholar 

  4. Hoshida Y, Villanueva A, Kobayashi M et al (2008) Gene expression in fixed tissues and outcome in hepatocellular carcinoma. N Engl J Med 359(19):1995–2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ho CM, Lee PH, Chen CL, Ho MC, Wu YM, Hu RH (2012) Long-term outcomes after resection versus transplantation for hepatocellular carcinoma within UCSF criteria. Ann Surg Oncol 19(3):826–833

    Article  PubMed  Google Scholar 

  6. Villanueva A (2019) Hepatocellular carcinoma. N Engl J Med 380(15):1450–1462

    Article  CAS  PubMed  Google Scholar 

  7. Reig M, Forner A, Rimola J et al (2022) BCLC strategy for prognosis prediction and treatment recommendation: the 2022 update. J Hepatol 76(3):681–693

    Article  PubMed  Google Scholar 

  8. Shao YY, Wang SY, Lin SM, Diagnosis Group,; Systemic Therapy Group (2021) Management consensus guideline for hepatocellular carcinoma: 2020 update on surveillance, diagnosis, and systemic treatment by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. J Formos Med Assoc. 120(4):1051–60

    Article  CAS  PubMed  Google Scholar 

  9. Ferrer-Fàbrega J, Sampson-Dávila J, Forner A et al (2021) Limited tumour progression beyond Milan criteria while on the waiting list does not result in unacceptable impairment of survival. J Hepatol 75(5):1154–1163

    Article  PubMed  Google Scholar 

  10. Ho CM, Lee PH, Shau WY, Ho MC, Wu YM, Hu RH (2012) Survival in patients with recurrent hepatocellular carcinoma after primary hepatectomy: comparative effectiveness of treatment modalities. Surgery 151(5):700–709

    Article  PubMed  Google Scholar 

  11. Ho CM, Lee CH, Lee MC et al (2021) Survival after treatable hepatocellular carcinoma recurrence in liver recipients: a nationwide cohort analysis. Front Oncol 10:616094

    Article  PubMed  PubMed Central  Google Scholar 

  12. Yao FY, Ferrell L, Bass NM et al (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33(6):1394–1403

    Article  CAS  PubMed  Google Scholar 

  13. Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC (2000) A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology 31(4):864–871

    Article  CAS  PubMed  Google Scholar 

  14. Child C, Turcotte J (1964) The liver and portal hypertension. In: Child CI (ed) Surgery and Portal Hypertension. W. B. Saunders, Philadelphia, pp 50–58

    Google Scholar 

  15. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646–649

    Article  CAS  PubMed  Google Scholar 

  16. Sarin SK, Choudhury A, Sharma MK et al (2019) Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL): an update. Hepatol Int 13(4):353–390

    Article  PubMed  Google Scholar 

  17. Lu CY, Chen CL, Ho CM et al (2020) Dynamic prognostication in transplant candidates with acute-on-chronic liver failure. J Pers Med 10(4):230

    Article  PubMed  PubMed Central  Google Scholar 

  18. Lin HY, Ho CM, Hsieh PY et al (2021) Circuitous path to live donor liver transplantation from the coordinator’s perspective. J Pers Med 11(11):1173

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kim SU, Jung KS, Lee S et al (2014) Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma. Liver Int 34(7):1008–1017

    Article  CAS  PubMed  Google Scholar 

  20. Huang ZY, Liang BY, Xiong M et al (2016) Severity of cirrhosis should determine the operative modality for patients with early hepatocellular carcinoma and compensated liver function. Surgery 159(2):621–631

    Article  PubMed  Google Scholar 

  21. Gu J, Liang BY, Zhang EL, Huang ZY (2022) Prognostic nomograms based on the cirrhotic severity scoring for preoperative prediction of long-term outcomes in patients with HBV-related hepatocellular carcinoma and Child-Pugh Grade A liver function. J Oncol 2022:7031674. https://doi.org/10.1155/2022/7031674

    Article  PubMed  PubMed Central  Google Scholar 

  22. Ho SY, Liu PH, Hsu CY et al (2017) Prognostic role of noninvasive liver reserve markers in patients with hepatocellular carcinoma undergoing transarterial chemoembolization. PLoS One 12(7):e0180408

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cucchetti A, Ercolani G, Vivarelli M et al (2006) Impact of model for end-stage liver disease (MELD) score on prognosis after hepatectomy for hepatocellular carcinoma on cirrhosis. Liver Transpl 12(6):966–971

    Article  PubMed  Google Scholar 

  24. Johnson PJ, Berhane S, Kagebayashi C et al (2015) Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol 33(6):550–558

    Article  PubMed  Google Scholar 

  25. Fagenson AM, Gleeson EM, Pitt HA et al (2020) Albumin-bilirubin score vs Model for End-Stage Liver Disease in predicting post-hepatectomy outcomes. J Am Coll Surg 230(4):637–645

    Article  PubMed  Google Scholar 

  26. Budhu A, Forgues M, Ye QH et al (2006) Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell 10(2):99–111

    Article  CAS  PubMed  Google Scholar 

  27. Tan DJH, Ng CH, Lin SY et al (2022) Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis. Lancet Oncol 23(4):521–530

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kelley RK, Greten TF (2021) Hepatocellular carcinoma - origins and outcomes. N Engl J Med 385(3):280–282

    Article  PubMed  Google Scholar 

  29. Pfister D, Núñez NG, Pinyol R et al (2021) NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature 592(7854):450–456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Halazun KJ, Tabrizian P, Najjar M et al (2018) Is it time to abandon the Milan criteria?: Results of a bicoastal US collaboration to redefine hepatocellular carcinoma liver transplantation selection policies. Ann Surg 268(4):690–699

    Article  PubMed  Google Scholar 

  31. Halazun KJ, Rosenblatt RE, Mehta N et al (2021) Dynamic α-fetoprotein response and outcomes after liver transplant for hepatocellular carcinoma. JAMA Surg 156(6):559–567

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank the coordinators (Hui-Ying Lin and Min-Heuy Lin) for their helpful efforts in data collection.

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Authors and Affiliations

  1. Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan

    Cheng-Maw Ho, Po-Huang Lee, Hou-Ying Cheng, Chih-Yang Hsaio, Yao-Ming Wu, Ming-Chih Ho & Rey-Heng Hu

  2. Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

    Po-Huang Lee

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Contributions

HCM, CHY, HCY, and HRH collected the data, HCM drafted the manuscript, and HCM, HRH, and LPH designed the study. HCM, WYM, and HMC conducted data processing, and HCM and LPH performed data analysis. HCM and HRH were the directors responsible for general organization and instruction. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Cheng-Maw Ho.

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Ethics approval and consent to participate

The Institutional Review Board of National Taiwan University Hospital approved this study (NTUH REC: 201701044RIND and 202004053RINB). Because this study retrospectively analyzed data through a chart review, the Institutional Review Board of National Taiwan University Hospital waived the need for informed consent. The research was conducted in accordance with both the Declarations of Helsinki and Istanbul.

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Not applicable.

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The authors declare no competing interests.

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Ho, CM., Lee, PH., Cheng, HY. et al. Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center. Langenbecks Arch Surg 409, 143 (2024). https://doi.org/10.1007/s00423-024-03336-6

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