Advertisement

Performance of Liver and Spleen Stiffness Measurements in Predicting Postoperative Hepatic Decompensation After HCC Resection

  • Horia StefanescuEmail author
  • Oana Nicoara-Farcau
  • Andreea Ardelean
  • Bogdan Procopet
Chapter
  • 69 Downloads

Abstract

Portal hypertension (PH) is a major determinant of the outcome of patients with hepatocellular carcinoma (HCC) undergoing curative treatment, especially resection. Liver and spleen stiffness (LS and SS) are both validated noninvasive surrogates for PH estimation. This review summarizes the evidences regarding the use of liver and spleen stiffness as predictors of post-hepatectomy liver failure, late recurrence, and overall survival in patients with liver cirrhosis and HCC undergoing surgical resection, or other therapies (i.e., radiofrequency or microwave ablation or transarterial chemoembolization) and highlights the utility of integrating these simple investigations into clinical daily practice. Taken together, LS measurement is validated as a valuable clinical tool in decision-making in patients with cirrhosis and resectable HCC. It can predict the occurrence of post-hepatectomy liver failure as well as late (>2 years) recurrence and overall survival. If used together with the MELD score—as an accurate estimation of liver function, it can help to navigate between oncological benefit and risk of decompensation and death. Considering 10% as an acceptable postoperative risk of decompensation, only patients with LSM <10 kPa should undergo resection. Moreover, an increased baseline LS (>13 kPa) appears to be the sole independent non-cancer-related predictor of late recurrence after radiofrequency ablation therapy. SS measurement appears to be a valuable additional noninvasive predictor of post-hepatectomy liver failure (PHLF) and late recurrence, with doubtful benefit in predicting overall survival. In patients who undergo local therapies, early changes in tumor stiffness may predict response. However, prospective randomized controlled trials are still needed to elucidate controversial findings.

Keywords

Liver stiffness Spleen stiffness Hepatocellular carcinoma Prediction Post-hepatectomy liver failure Recurrence Survival 

References

  1. 1.
    Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul J-L, et al. EASL Clinical Practice Guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.CrossRefGoogle Scholar
  2. 2.
    Bruix J, Castells A, Bosch J, Feu F, Fuster J, Garcia-Pagan JC, et al. Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology. 1996;111(4):1018–22.PubMedCrossRefGoogle Scholar
  3. 3.
    Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology. 1999;30(6):1434–40.PubMedCrossRefGoogle Scholar
  4. 4.
    Procopet B, Bureau C, Métivier S, Selves J, Robic MA, Christol C, et al. Tolerance of liver biopsy in a tertiary care center. Eur J Gastroenterol Hepatol. 2012;24(10):1209–13.PubMedCrossRefGoogle Scholar
  5. 5.
    Thalheimer U, Bellis L, Puoti C, Burroughs AK. Should we routinely measure portal pressure in patients with cirrhosis, using hepatic venous pressure gradient (HVPG) as a guide for prophylaxis and therapy of bleeding and rebleeding? No. Eur J Intern Med. 2011;22(1):5–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Jung KS, Kim JH, Kim SU, Song K, Kim BK, Park JY, et al. Liver stiffness value-based risk estimation of late recurrence after curative resection of hepatocellular carcinoma: development and validation of a predictive model. PLoS One. 2014;9(6):e99167.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Bureau C, Metivier S, Peron JM, Selves J, Robic MA, Gourraud PA, et al. Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease. Aliment Pharmacol Ther. 2008;27(12):1261–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Salzl P, Reiberger T, Ferlitsch M, Payer BA, Schwengerer B, Trauner M, et al. Evaluation of portal hypertension and varices by acoustic radiation force impulse imaging of the liver compared to transient elastography and AST to platelet ratio index. Ultraschall Med. 2014;35(6):528–33.CrossRefPubMedGoogle Scholar
  9. 9.
    Vizzutti F, Arena U, Romanelli RG, Rega L, Foschi M, Colagrande S, et al. Liver stiffness measurement predicts severe portal hypertension in patients with HCV-related cirrhosis. Hepatology. 2007;45(5):1290–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Berzigotti A, Reig M, Abraldes JG, Bosch J, Bruix J. Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis. Hepatology. 2015;61(2):526–36.PubMedCrossRefGoogle Scholar
  11. 11.
    Castera L. Liver stiffness by ultrasound elastography. Diagnostic methods for cirrhosis and portal hypertension. Springer International Publishing; 2018. p. 95–111.Google Scholar
  12. 12.
    You MW, Kim KW, Pyo J, Huh J, Kim HJ, Lee SJ, et al. A meta-analysis for the diagnostic performance of transient elastography for clinically significant portal hypertension. Ultrasound Med Biol. 2017;43(1):59–68.PubMedCrossRefGoogle Scholar
  13. 13.
    Friedrich-Rust M, Ong MF, Martens S, Sarrazin C, Bojunga J, Zeuzem S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134(4):960–74.e8.CrossRefPubMedGoogle Scholar
  14. 14.
    Singh S, Fujii LL, Murad MH, Wang Z, Asrani SK, Ehman RL, et al. Liver stiffness is associated with risk of decompensation, liver cancer, and death in patients with chronic liver diseases: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11(12):1573–84.e2.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Tsochatzis EA, Gurusamy KS, Ntaoula S, Cholongitas E, Davidson BR, Burroughs AK. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol. 2011;54(4):650–9.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Dietrich CF, Bamber J, Berzigotti A, Bota S, Cantisani V, Castera L, et al. EFSUMB guidelines and recommendations on the clinical use of liver ultrasound elastography, update 2017 (long version). Ultraschall Med. 2017;38(4):e16–47.CrossRefPubMedGoogle Scholar
  17. 17.
    European Association for Study of Liver; Asociacion Latinoamericana para el Estudio del Higado. EASL-ALEH Clinical Practice Guidelines: non-invasive tests for evaluation of liver disease severity and prognosis. J Hepatol. 2015;63(1):237–64.CrossRefGoogle Scholar
  18. 18.
    Cucchetti A, Cescon M, Colecchia A, Neri F, Cappelli A, Ravaioli M, et al. Adding liver stiffness measurement to the routine evaluation of hepatocellular carcinoma resectability can optimize clinical outcome. Ultraschall Med. 2016;38(05):515–22.PubMedGoogle Scholar
  19. 19.
    Masuzaki R, Tateishi R, Yoshida H, Sato T, Ohki T, Goto T, et al. Assessing liver tumor stiffness by transient elastography. Hepatol Int. 2007;1(3):394–7.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Akima T, Tamano M, Hiraishi H. Liver stiffness measured by transient elastography is a predictor of hepatocellular carcinoma development in viral hepatitis. Hepatol Res. 2011;41(10):965–70.PubMedCrossRefGoogle Scholar
  21. 21.
    Kusaka K, Harihara Y, Torzilli G, Kubota K, Takayama T, Makuuchi M, et al. Objective evaluation of liver consistency to estimate hepatic fibrosis and functional reserve for hepatectomy. J Am Coll Surg. 2000;191(1):47–53.PubMedCrossRefGoogle Scholar
  22. 22.
    Ioannou GN, Splan MF, Weiss NS, McDonald GB, Beretta L, Lee SP. Incidence and predictors of hepatocellular carcinoma in patients with cirrhosis. Clin Gastroenterol Hepatol. 2007;5(8):938–45.e4.PubMedCrossRefGoogle Scholar
  23. 23.
    Llop E, Berzigotti A, Reig M, Erice E, Reverter E, Seijo S, et al. Assessment of portal hypertension by transient elastography in patients with compensated cirrhosis and potentially resectable liver tumors. J Hepatol. 2012;56(1):103–8.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Masuzaki R, Tateishi R, Yoshida H, Goto E, Sato T, Ohki T, et al. Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography. Hepatology. 2009;49(6):1954–61.CrossRefPubMedGoogle Scholar
  25. 25.
    de Franchis R. Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol. 2015;63(3):743–52.CrossRefPubMedGoogle Scholar
  26. 26.
    Boleslawski E, Petrovai G, Truant S, Dharancy S, Duhamel A, Salleron J, et al. Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis. Br J Surg. 2012;99(6):855–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Cescon M, Colecchia A, Cucchetti A, Peri E, Montrone L, Ercolani G, et al. Value of transient elastography measured with FibroScan in predicting the outcome of hepatic resection for hepatocellular carcinoma. Ann Surg. 2012;256(5):706–12; discussion 12–3.CrossRefPubMedGoogle Scholar
  28. 28.
    Chong CC-N, Wong GL-H, Chan AW-H, Wong VW-S, Fong AK-W, Cheung Y-S, et al. Liver stiffness measurement predicts high-grade post-hepatectomy liver failure: a prospective cohort study. J Gastroenterol Hepatol. 2017;32(2):506–14.CrossRefPubMedGoogle Scholar
  29. 29.
    Cucchetti A, Sposito C, Pinna AD, Citterio D, Cescon M, Bongini M, et al. Competing risk analysis on outcome after hepatic resection of hepatocellular carcinoma in cirrhotic patients. World J Gastroenterol. 2017;23(8):1469.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Fung J, Poon RTP, Yu W-C, Chan S-C, Chan ACY, Chok KSH, et al. Use of liver stiffness measurement for liver resection surgery: correlation with indocyanine green clearance testing and post-operative outcome. PLoS One. 2013;8(8):e72306.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kim SU, Ahn SH, Park JY, Kim DY, Chon CY, Choi JS, et al. Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan®) before curative resection of hepatocellular carcinoma: a pilot study. Hepatol Int. 2008;2(4):471–7.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Li C, Zhang J-Y, Zhang X-Y, Wen T-F, Yan L-N. FibroScan predicts ascites after liver resection for hepatitis B virus-related hepatocellular carcinoma: a prospective cohort study. Int J Surg. 2015;20:21–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Procopet B, Fischer P, Horhat A, Mois E, Stefanescu H, Comsa M, et al. Good performance of liver stiffness measurement in the prediction of postoperative hepatic decompensation in patients with cirrhosis complicated with hepatocellular carcinoma. Med Ultrason. 2018;20(3):272.CrossRefPubMedGoogle Scholar
  34. 34.
    Rajakannu M, Cherqui D, Ciacio O, Golse N, Pittau G, Allard MA, et al. Liver stiffness measurement by transient elastography predicts late posthepatectomy outcomes in patients undergoing resection for hepatocellular carcinoma. Surgery. 2017;162(4):766–74.PubMedCrossRefGoogle Scholar
  35. 35.
    Wong JS-W, Wong GL-H, Chan AW-H, Wong VW-S, Cheung Y-S, Chong C-N, et al. Liver stiffness measurement by transient elastography as a predictor on posthepatectomy outcomes. Ann Surg. 2013;257(5):922–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(10):698–711.PubMedCrossRefGoogle Scholar
  37. 37.
    Jung KS, Kim SU, Choi GH, Park JY, Park YN, Kim DY, et al. Prediction of recurrence after curative resection of hepatocellular carcinoma using liver stiffness measurement (FibroScan(R)). Ann Surg Oncol. 2012;19(13):4278–86.CrossRefPubMedGoogle Scholar
  38. 38.
    Qi M, Chen Y, Zhang GQ, Meng YJ, Zhao FL, Wang J, et al. Clinical significance of preoperative liver stiffness measurements in primary HBV-positive hepatocellular carcinoma. Future Oncol. 2017;13(30):2799–810.CrossRefPubMedGoogle Scholar
  39. 39.
    Marasco G, Colecchia A, Colli A, Ravaioli F, Casazza G, Bacchi Reggiani ML, et al. Role of liver and spleen stiffness in predicting the recurrence of hepatocellular carcinoma after resection. J Hepatol. 2019;70(3):440–8.CrossRefPubMedGoogle Scholar
  40. 40.
    Lee YR, Park SY, Kim SU, Jang SY, Tak WY, Kweon YO, et al. Using transient elastography to predict hepatocellular carcinoma recurrence after radiofrequency ablation. J Gastroenterol Hepatol. 2017;32(5):1079–86.CrossRefPubMedGoogle Scholar
  41. 41.
    Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, et al. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016;65(4):727–33.PubMedCrossRefGoogle Scholar
  42. 42.
    Reig M, Mariño Z, Perelló C, Iñarrairaegui M, Ribeiro A, Lens S, et al. Unexpected high rate of early tumor recurrence in patients with HCV-related HCC undergoing interferon-free therapy. J Hepatol. 2016;65(4):719–26.PubMedCrossRefGoogle Scholar
  43. 43.
    Degasperi E, D’Ambrosio R, Iavarone M, Sangiovanni A, Aghemo A, Soffredini R, et al. Factors associated with increased risk of de novo or recurrent hepatocellular carcinoma in patients with cirrhosis treated with direct-acting antivirals for HCV infection. Clin Gastroenterol Hepatol. 2019;17(6):1183–91.e7.CrossRefPubMedGoogle Scholar
  44. 44.
    Abdelaziz AO, Abdelhalim H, Elsharkawy A, Shousha HI, Abdelmaksoud AH, Soliman ZA, et al. Liver stiffness measurement changes following hepatocellular carcinoma treatment with percutaneous microwave ablation or transarterial chemoembolization: a cohort study. Eur J Gastroenterol Hepatol. 2019;31(6):685–91.CrossRefPubMedGoogle Scholar
  45. 45.
    Wu D, Chen E, Liang T, Wang M, Chen B, Lang B, et al. Predicting the risk of postoperative liver failure and overall survival using liver and spleen stiffness measurements in patients with hepatocellular carcinoma. Medicine. 2017;96(34):e7864.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Lee DH, Lee JM, Yoon J-H, Kim YJ, Lee J-H, Yu SJ, et al. Liver stiffness measured by two-dimensional shear-wave elastography: prognostic value after radiofrequency ablation for hepatocellular carcinoma. Liver Cancer. 2018;7(1):65–75.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Colecchia A, Montrone L, Scaioli E, Bacchi-Reggiani ML, Colli A, Casazza G, et al. Measurement of spleen stiffness to evaluate portal hypertension and the presence of esophageal varices in patients with HCV-related cirrhosis. Gastroenterology. 2012;143(3):646–54.CrossRefPubMedGoogle Scholar
  48. 48.
    Marasco G, Colecchia A, Dajti E, Ravaioli F, Cucchetti A, Cescon M, et al. Prediction of posthepatectomy liver failure: role of SSM and LSPS. J Surg Oncol. 2018;119(3):400–1.PubMedCrossRefGoogle Scholar
  49. 49.
    Peng W, Zhang XY, Li C, Wen TF, Yan LN, Yang JY. Spleen stiffness and volume help to predict posthepatectomy liver failure in patients with hepatocellular carcinoma. Medicine (Baltimore). 2019;98(18):e15458.CrossRefGoogle Scholar
  50. 50.
    Salvatore V, Baron Toaldo M, Marinelli S, Milazzo M, Palamà C, Venerandi L, et al. Early prediction of treatment response to sorafenib with elastosonography in a mice xenograft model of hepatocellular carcinoma: a proof-of-concept study. Ultraschall Med. 2013;34(06):541–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhang P, Zhou P, Tian S-M, Qian Y, Deng J, Zhang L. Application of acoustic radiation force impulse imaging for the evaluation of focal liver lesion elasticity. Hepatobiliary Pancreat Dis Int. 2013;12(2):165–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Grgurevic I, Bokun T, Salkic NN, Brkljacic B, Vukelić-Markovic M, Stoos-Veic T, et al. Liver elastography malignancy prediction score for noninvasive characterization of focal liver lesions. Liver Int. 2017;38(6):1055–63.PubMedCrossRefGoogle Scholar
  53. 53.
    Praktiknjo M, Krabbe V, Pohlmann A, Sampels M, Jansen C, Meyer C, et al. Evolution of nodule stiffness might predict response to local ablative therapy: a series of patients with hepatocellular carcinoma. PLoS One. 2018;13(2):e0192897.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Horia Stefanescu
    • 1
    • 2
    Email author
  • Oana Nicoara-Farcau
    • 2
    • 3
  • Andreea Ardelean
    • 2
    • 3
  • Bogdan Procopet
    • 1
    • 2
    • 3
  1. 1.Liver UnitRegional Institute of Gastroenterology and HepatologyCluj-NapocaRomania
  2. 2.Liver Research ClubCluj-NapocaRomania
  3. 3.3rd Medical Clinic, Department of Internal MedicineCluj-Napoca University of Medicine and PharmacyCluj-NapocaRomania

Personalised recommendations