Skip to main content
Erschienen in: Current Treatment Options in Gastroenterology 2/2017

19.04.2017 | Liver (J Bajaj, Section Editor)

Hepatocellular Carcinoma and Liver Transplantation: Changing Patterns and Practices

verfasst von: Nicole E. Rich, MD, Neehar D. Parikh, MD, Amit G. Singal, MD MS

Erschienen in: Current Treatment Options in Gastroenterology | Ausgabe 2/2017

Einloggen, um Zugang zu erhalten

Opinion Statement

Benefits of liver transplantation (LT) for patients with hepatocellular carcinoma (HCC) are well established. However, there is debate regarding optimal and equitable selection of patients best served by LT, particularly in the face of limited organ availability. Herein, we discuss topics regarding LT selection criteria for patients with HCC. Recent change in UNOS policy currently mandates a 6-month observation period prior to priority listing and institutes a cap of 34 MELD exception points for patients with HCC. Additionally, two further proposed changes to UNOS policy include (1) requiring locoregional therapy for those with small (2–3 cm) unifocal HCC prior to applying for exception points and (2) allowing downstaging in select patients with UNOS T3 lesions. These policies move beyond simply using tumor burden to using markers of tumor biology for selecting patients who have the lowest risk of post-transplant recurrence and best chance at long-term post-transplant survival. Given increasing time on transplant waiting lists and shortage of donor grafts, LT should be reserved for patients who may achieve significant benefit compared to non-transplant therapies. Potential benefit to HCC patients must be weighed against the harm from delaying or precluding LT for non-HCC patients on the waiting list, particularly in regions with limited donor availability. The relative benefit of LT in patients with small (<3 cm) HCC is likely limited; surgical resection (in absence of portal hypertension) and local ablative therapy (if portal hypertension present) are both efficacious and more cost-effective and should likely be regarded as first line therapies for these patients. Salvage LT can be considered as a rescue option for those with recurrent disease. Downstaging for selected patients with UNOS T3 lesions may identify those with good tumor biology and acceptable post-transplant outcomes; however, current studies have had a wide variation in reported outcomes. While awaiting more data, a standardized downstaging protocol including a priori inclusion criteria and a mandatory waiting time prior to LT to observe tumor biology likely yields the best outcomes.
Literatur
2.
Zurück zum Zitat Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRefPubMed Mazzaferro V, Bhoori S, Sposito C, et al. Milan criteria in liver transplantation for hepatocellular carcinoma: an evidence-based analysis of 15 years of experience. Liver Transpl. 2011;17(Suppl 2):S44–57.CrossRefPubMed
3.
Zurück zum Zitat •• Heimbach JK, Hirose R, Stock PG, et al. Delayed hepatocellular carcinoma model for end-stage liver disease exception score improves disparity in access to liver transplant in the United States. Hepatology. 2015;61(5):1643–50. Authors demonstrated a 6–9-month delay in receipt of MELD exception points reduces disparity in transplant rates between HCC and non-HCC candidates. •• Heimbach JK, Hirose R, Stock PG, et al. Delayed hepatocellular carcinoma model for end-stage liver disease exception score improves disparity in access to liver transplant in the United States. Hepatology. 2015;61(5):1643–50. Authors demonstrated a 6–9-month delay in receipt of MELD exception points reduces disparity in transplant rates between HCC and non-HCC candidates.
4.
Zurück zum Zitat Sotiropoulos GC, Molmenti EP, Losch C, et al. Meta-analysis of tumor recurrence after liver transplantation for hepatocellular carcinoma based on 1,198 cases. Eur J Med Res. 2007;12(10):527–34.PubMed Sotiropoulos GC, Molmenti EP, Losch C, et al. Meta-analysis of tumor recurrence after liver transplantation for hepatocellular carcinoma based on 1,198 cases. Eur J Med Res. 2007;12(10):527–34.PubMed
5.
Zurück zum Zitat Halazun KJ, Patzer RE, Rana AA, et al. Standing the test of time: outcomes of a decade of prioritizing patients with hepatocellular carcinoma, results of the UNOS natural geographic experiment. Hepatology. 2014;60(6):1957–62.CrossRefPubMed Halazun KJ, Patzer RE, Rana AA, et al. Standing the test of time: outcomes of a decade of prioritizing patients with hepatocellular carcinoma, results of the UNOS natural geographic experiment. Hepatology. 2014;60(6):1957–62.CrossRefPubMed
6.
Zurück zum Zitat • Mehta N, Heimbach J, Harnois DM, et al. Short waiting time predicts early recurrence of hepatocellular carcinoma after liver transplantation: a multicenter study supporting the “ablate and wait” principle. Paper presented at: The Liver Meeting 2014; Boston, MA. Multi-center study demonstrated liver transplant waiting times less than 6 months is predictive of post-transplant recurrence of hepatocellular carcinoma. • Mehta N, Heimbach J, Harnois DM, et al. Short waiting time predicts early recurrence of hepatocellular carcinoma after liver transplantation: a multicenter study supporting the “ablate and wait” principle. Paper presented at: The Liver Meeting 2014; Boston, MA. Multi-center study demonstrated liver transplant waiting times less than 6 months is predictive of post-transplant recurrence of hepatocellular carcinoma.
7.
Zurück zum Zitat Wang JH, Wang CC, Hung CH, et al. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56(2):412–8.CrossRefPubMed Wang JH, Wang CC, Hung CH, et al. Survival comparison between surgical resection and radiofrequency ablation for patients in BCLC very early/early stage hepatocellular carcinoma. J Hepatol. 2012;56(2):412–8.CrossRefPubMed
8.
Zurück zum Zitat Hung HH, Chiou YY, Hsia CY, et al. Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas. Clin Gastroenterol Hepatol. 2011;9(1):79–86.CrossRefPubMed Hung HH, Chiou YY, Hsia CY, et al. Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas. Clin Gastroenterol Hepatol. 2011;9(1):79–86.CrossRefPubMed
9.
Zurück zum Zitat Naugler WE, Sonnenberg A. Survival and cost-effectiveness analysis of competing strategies in the management of small hepatocellular carcinoma. Liver Transpl. 2010;16(10):1186–94.CrossRefPubMed Naugler WE, Sonnenberg A. Survival and cost-effectiveness analysis of competing strategies in the management of small hepatocellular carcinoma. Liver Transpl. 2010;16(10):1186–94.CrossRefPubMed
10.
Zurück zum Zitat • Mehta N, Sarkar M, Dodge JL, Fidelman N, Roberts JP, Yao FY. Intention-to-treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl. 2016;22(2):178–87. The risk of tumor progression from T1 directly to beyond T2 is low (< 5%) within 6 months, although the ideal strategy in these patients (immediate ablation vs. watchful waiting) remains unknown. • Mehta N, Sarkar M, Dodge JL, Fidelman N, Roberts JP, Yao FY. Intention-to-treat outcome of T1 hepatocellular carcinoma with the “wait and not ablate” approach until meeting T2 criteria for liver transplant listing. Liver Transpl. 2016;22(2):178–87. The risk of tumor progression from T1 directly to beyond T2 is low (< 5%) within 6 months, although the ideal strategy in these patients (immediate ablation vs. watchful waiting) remains unknown.
11.
Zurück zum Zitat Nathan H, Segev DL, Mayo SC, et al. National trends in surgical procedures for hepatocellular carcinoma: 1998-2008. Cancer. 2012;118(7):1838–44.CrossRefPubMed Nathan H, Segev DL, Mayo SC, et al. National trends in surgical procedures for hepatocellular carcinoma: 1998-2008. Cancer. 2012;118(7):1838–44.CrossRefPubMed
12.
Zurück zum Zitat Zheng Z, Liang W, Milgrom DP, et al. Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies. Transplantation. 2014;97(2):227–34.CrossRefPubMed Zheng Z, Liang W, Milgrom DP, et al. Liver transplantation versus liver resection in the treatment of hepatocellular carcinoma: a meta-analysis of observational studies. Transplantation. 2014;97(2):227–34.CrossRefPubMed
13.
Zurück zum Zitat • Vitale A, Huo TL, Cucchetti A, et al. Survival benefit of liver transplantation versus resection for hepatocellular carcinoma: impact of MELD score. Ann Surg Oncol. 2015;22(6):1901–7. Surgical resection is the cost effective approach to HCC patients with compensated cirrhosis if MELD score is below 10 and there is no evidence of microvascular invasion. • Vitale A, Huo TL, Cucchetti A, et al. Survival benefit of liver transplantation versus resection for hepatocellular carcinoma: impact of MELD score. Ann Surg Oncol. 2015;22(6):1901–7. Surgical resection is the cost effective approach to HCC patients with compensated cirrhosis if MELD score is below 10 and there is no evidence of microvascular invasion.
14.
Zurück zum Zitat Cho YK, Kim JK, Kim MY, et al. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology (Baltimore, Md). 2009;49(2):453–9.CrossRef Cho YK, Kim JK, Kim MY, et al. Systematic review of randomized trials for hepatocellular carcinoma treated with percutaneous ablation therapies. Hepatology (Baltimore, Md). 2009;49(2):453–9.CrossRef
15.
Zurück zum Zitat Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRefPubMed Zheng SS, Xu X, Wu J, et al. Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation. 2008;85(12):1726–32.CrossRefPubMed
16.
Zurück zum Zitat Guiteau JJ, Cotton RT, Washburn WK, et al. An early regional experience with expansion of Milan criteria for liver transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2010;10(9):2092–8.CrossRef Guiteau JJ, Cotton RT, Washburn WK, et al. An early regional experience with expansion of Milan criteria for liver transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. 2010;10(9):2092–8.CrossRef
17.
Zurück zum Zitat Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRefPubMed Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology. 2001;33(6):1394–403.CrossRefPubMed
18.
Zurück zum Zitat Freeman RB, Mithoefer A, Ruthazer R, et al. Optimizing staging for hepatocellular carcinoma before liver transplantation: a retrospective analysis of the UNOS/OPTN database. Liver Transpl. 2006;12(10):1504–11.CrossRefPubMed Freeman RB, Mithoefer A, Ruthazer R, et al. Optimizing staging for hepatocellular carcinoma before liver transplantation: a retrospective analysis of the UNOS/OPTN database. Liver Transpl. 2006;12(10):1504–11.CrossRefPubMed
19.
Zurück zum Zitat Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9. discussion 509-511 Duffy JP, Vardanian A, Benjamin E, et al. Liver transplantation criteria for hepatocellular carcinoma should be expanded: a 22-year experience with 467 patients at UCLA. Ann Surg. 2007;246(3):502–9. discussion 509-511
20.
Zurück zum Zitat Xu X, Lu D, Ling Q, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016;65(6):1035–41.CrossRefPubMed Xu X, Lu D, Ling Q, et al. Liver transplantation for hepatocellular carcinoma beyond the Milan criteria. Gut. 2016;65(6):1035–41.CrossRefPubMed
21.
Zurück zum Zitat Kim PT, Onaca N, Chinnakotla S, et al. Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation. Clin Transpl. 2013;27(2):311–8.CrossRef Kim PT, Onaca N, Chinnakotla S, et al. Tumor biology and pre-transplant locoregional treatments determine outcomes in patients with T3 hepatocellular carcinoma undergoing liver transplantation. Clin Transpl. 2013;27(2):311–8.CrossRef
22.
Zurück zum Zitat Sapisochin G, Goldaracena N, Laurence JM, et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64(6):2077–88.CrossRefPubMed Sapisochin G, Goldaracena N, Laurence JM, et al. The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. 2016;64(6):2077–88.CrossRefPubMed
23.
Zurück zum Zitat Yao FY, Mehta N, Flemming J, et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015;61(6):1968–77.CrossRefPubMedPubMedCentral Yao FY, Mehta N, Flemming J, et al. Downstaging of hepatocellular cancer before liver transplant: long-term outcome compared to tumors within Milan criteria. Hepatology. 2015;61(6):1968–77.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Mehta N, Guy J, Frenette CT, et al. Multicenter Study of Down-staging of hepatocellular carcinoma (HCC) to within Milan criteria before liver transplantation (LT). Paper presented at: The Liver Meeting Boston, MA; 2014 Mehta N, Guy J, Frenette CT, et al. Multicenter Study of Down-staging of hepatocellular carcinoma (HCC) to within Milan criteria before liver transplantation (LT). Paper presented at: The Liver Meeting Boston, MA; 2014
25.
Zurück zum Zitat • Parikh ND, Waljee AK, Singal AG. Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transpl. 2015;21(9):1142–52. There is variation in post-transplant recurrence rates and post-transplant survival with downstaging, although a priori inclusion criteria, mandatory waiting time prior to transplantation, and a standardized downstaging protocol are the approaches that likely yield the best outcomes. • Parikh ND, Waljee AK, Singal AG. Downstaging hepatocellular carcinoma: a systematic review and pooled analysis. Liver Transpl. 2015;21(9):1142–52. There is variation in post-transplant recurrence rates and post-transplant survival with downstaging, although a priori inclusion criteria, mandatory waiting time prior to transplantation, and a standardized downstaging protocol are the approaches that likely yield the best outcomes.
26.
Zurück zum Zitat Volk ML, Vijan S, Marrero JA. A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant. 2008;8(4):839–46.CrossRefPubMed Volk ML, Vijan S, Marrero JA. A novel model measuring the harm of transplanting hepatocellular carcinoma exceeding Milan criteria. Am J Transplant. 2008;8(4):839–46.CrossRefPubMed
27.
Zurück zum Zitat Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.CrossRefPubMed Mazzaferro V, Llovet JM, Miceli R, et al. Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol. 2009;10(1):35–43.CrossRefPubMed
Metadaten
Titel
Hepatocellular Carcinoma and Liver Transplantation: Changing Patterns and Practices
verfasst von
Nicole E. Rich, MD
Neehar D. Parikh, MD
Amit G. Singal, MD MS
Publikationsdatum
19.04.2017
Verlag
Springer US
Erschienen in
Current Treatment Options in Gastroenterology / Ausgabe 2/2017
Print ISSN: 1092-8472
Elektronische ISSN: 1534-309X
DOI
https://doi.org/10.1007/s11938-017-0133-3

Weitere Artikel der Ausgabe 2/2017

Current Treatment Options in Gastroenterology 2/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.