European Radiology

, Volume 27, Issue 6, pp 2600–2609 | Cite as

The impact of clinically significant portal hypertension on the prognosis of patients with hepatocellular carcinoma after radiofrequency ablation: a propensity score matching analysis

  • Kuan-Chieh Fang
  • Chien-Wei Su
  • Yi-You Chiou
  • Pei-Chang Lee
  • Nai-Chi Chiu
  • Chien-An Liu
  • Ping-Hsien Chen
  • Wei-Yu Kao
  • Yi-Hsiang Huang
  • Teh-Ia Huo
  • Ming-Chih Hou
  • Han-Chieh Lin
  • Jaw-Ching Wu
Hepatobiliary-Pancreas

Abstract

Objectives

To assess the impact of clinically significant portal hypertension (CSPH) on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA).

Methods

We retrospectively enrolled 280 treatment-naïve early-stage HCC patients who had Child–Pugh grade A or B and received upper gastrointestinal endoscopy at the time of HCC diagnosis. CSPH was defined as (1) a platelet count < 100,000/mm3 associated with splenomegaly and/or (2) the presence of oesophageal/gastric varices by endoscopy. Factors determining poor overall survival and recurrence after RFA were analysed by Cox proportional hazards model and propensity score matching analysis.

Results

A total of 192 (68.6 %) patients had CSPH. The cumulative 5-year survival rates were 50.6 % and 76.7 % in patients with and without CSPH, respectively (p = 0.015). Based on multivariate analysis, age > 65 years (hazard ratio (HR) 1.740, p = 0.025), serum albumin levels ≤ 3.5 g/dL (HR 3.268, p < 0.001) and multiple tumours (HR 1.693, p = 0.046), but not CSPH, were independent risk factors associated with poor overall survival after RFA. Moreover, the overall survival rates were comparable between patients with and without CSPH after adjusting for confounding factors via propensity score matching analysis.

Conclusions

CSPH was not associated with poor outcomes after RFA.

Key points

CSPH was common in HCC patients who underwent RFA therapy.

CSPH was not an independent risk factor in determining poor prognosis.

Serum albumin level was more important to determine the outcomes.

Keywords

Oesophageal varices Hepatocellular carcinoma Portal hypertension Prognosis Radiofrequency ablation 

Abbreviations

AASLD

American Association for the Study of Liver Disease

AFP

alpha-fetoprotein

Alk-P

alkaline phosphatase

ALT

alanine aminotransferase

AST

aspartate aminotransferase

BCLC

Barcelona Clinic Liver Cancer

CI

confidence interval

CSPH

clinically significant portal hypertension

CT

computed tomography

EASL

European Association for the Study of the Liver

EGV

oesophageal-gastric varix

EV

oesophageal varix

GV

gastric varix

HBsAg

hepatitis B surface antigen

HBV

hepatitis B virus

HCC

hepatocellular carcinoma

HCV

hepatitis C virus

HR

hazard ratio

HVPG

hepatic venous pressure gradient

IRB

Institutional review board

MRI

magnetic resonance imaging

OS

overall survival

PH

portal hypertension

PT/INR

prothrombin time/international ratio

RFA

radiofrequency ablation therapy

RFS

recurrence-free survival

TACE

transarterial chemoembolization

Notes

Acknowledgments

The authors thank American Manuscript Editors for English editing and writing assistance. This work was supported by grants from the National Science Council of Taiwan (NSC 101-2314-B-075-013-MY2), Ministry of Science and Technology of Taiwan (MOST 103-2314-B-075-077, and 104-2314-B-075-076), grants from Taipei Veterans General Hospital (V102C-117 and V104-111), a grant from the Ministry of Education Aim for the Top University Plan (103 AC-T402) and a grant from the Center of Excellence for Cancer Research at TVGH (MOHW104-TDU-B-211-124-001) in Taipei, Taiwan. We also thank for the Clinical Research Core Laboratory of Taipei Veterans General Hospital for providing experimental space and facilities. We thank Pui-Ching Lee for kindly providing statistical advice for this manuscript. Yi-You Chiou is the guarantor for the entire study. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Institutional review board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in an oral presentation at the 23rd United European Gastroenterology Week in 2015. Methodology: retrospective, observational, performed at one institution.

Supplementary material

330_2016_4604_MOESM1_ESM.docx (29 kb)
ESM 1 (DOCX 28 kb)
330_2016_4604_Fig4_ESM.gif (50 kb)
Fig. S1

Cumulative curves of OS rates in HCC patients after RFA stratified by CSPH status and serum albumin levels. Patients with serum albumin levels > 3.5 g/dL had a higher OS rate than their counterparts among both patients with CSPH (S1A, p = 0.003) and patients without CSPH (S1B, p = 0.006). (GIF 49 kb)

330_2016_4604_Fig5_ESM.gif (47 kb)
Fig. S1

Cumulative curves of OS rates in HCC patients after RFA stratified by CSPH status and serum albumin levels. Patients with serum albumin levels > 3.5 g/dL had a higher OS rate than their counterparts among both patients with CSPH (S1A, p = 0.003) and patients without CSPH (S1B, p = 0.006). (GIF 49 kb)

330_2016_4604_MOESM2_ESM.tif (52 kb)
High resolution image (TIF 51 kb)
330_2016_4604_MOESM3_ESM.tif (50 kb)
(TIF 50 kb)
330_2016_4604_Fig6_ESM.gif (47 kb)
Fig. S2

Cumulative curves of OS rates after RFA in patients with BCCL stage 0 HCC stratified by CSPH status and serum albumin levels. Patients with serum albumin levels > 3.5 g/dL had a higher OS rate than their counterparts among all patients (S1A, p < 0.001), among patients with CSPH (S1B, p < 0.001) and among patients without CSPH (S1C, p = 0.010). (GIF 46 kb)

330_2016_4604_Fig7_ESM.gif (43 kb)
Fig. S2

Cumulative curves of OS rates after RFA in patients with BCCL stage 0 HCC stratified by CSPH status and serum albumin levels. Patients with serum albumin levels > 3.5 g/dL had a higher OS rate than their counterparts among all patients (S1A, p < 0.001), among patients with CSPH (S1B, p < 0.001) and among patients without CSPH (S1C, p = 0.010). (GIF 46 kb)

330_2016_4604_Fig8_ESM.gif (40 kb)
Fig. S2

Cumulative curves of OS rates after RFA in patients with BCCL stage 0 HCC stratified by CSPH status and serum albumin levels. Patients with serum albumin levels > 3.5 g/dL had a higher OS rate than their counterparts among all patients (S1A, p < 0.001), among patients with CSPH (S1B, p < 0.001) and among patients without CSPH (S1C, p = 0.010). (GIF 46 kb)

330_2016_4604_MOESM4_ESM.tif (48 kb)
High resolution image (TIF 48 kb)
330_2016_4604_MOESM5_ESM.tif (49 kb)
(TIF 48 kb)
330_2016_4604_MOESM6_ESM.tif (50 kb)
(TIF 49 kb)
330_2016_4604_Fig9_ESM.gif (353 kb)
Fig. S3

Cumulative RFS curves after RFA for patients with HCC stratified by CSPH. A. The cumulative RFS rates were similar between patients with and without CSPH both before (S3A, p = 0.575) and after propensity score matching analysis (S3B, p = 0.856). In addition, for patients with BCLC stage 0 HCC, the RFS rates were also comparable between the two groups of patients (S3C, p = 0.719). (GIF 352 kb)

330_2016_4604_Fig10_ESM.gif (66 kb)
Fig. S3

Cumulative RFS curves after RFA for patients with HCC stratified by CSPH. A. The cumulative RFS rates were similar between patients with and without CSPH both before (S3A, p = 0.575) and after propensity score matching analysis (S3B, p = 0.856). In addition, for patients with BCLC stage 0 HCC, the RFS rates were also comparable between the two groups of patients (S3C, p = 0.719). (GIF 352 kb)

330_2016_4604_Fig11_ESM.gif (82 kb)
Fig. S3

Cumulative RFS curves after RFA for patients with HCC stratified by CSPH. A. The cumulative RFS rates were similar between patients with and without CSPH both before (S3A, p = 0.575) and after propensity score matching analysis (S3B, p = 0.856). In addition, for patients with BCLC stage 0 HCC, the RFS rates were also comparable between the two groups of patients (S3C, p = 0.719). (GIF 352 kb)

330_2016_4604_MOESM7_ESM.tif (176 kb)
High resolution image (TIF 175 kb)
330_2016_4604_MOESM8_ESM.tif (103 kb)
(TIF 103 kb)
330_2016_4604_MOESM9_ESM.tif (102 kb)
(TIF 102 kb)

References

  1. 1.
    Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53:1020–1022CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    de Lope CR, Tremosini S, Forner A, Reig M, Bruix J (2012) Management of HCC. J Hepatol 56(Suppl):S75–S87CrossRefPubMedGoogle Scholar
  3. 3.
    Lin SM, Lin CJ, Lin CC, Hsu CW, Chen YC (2005) Randomised controlled trial comparing percutaneous radiofrequency thermal ablation, percutaneous ethanol injection, and percutaneous acetic acid injection to treat hepatocellular carcinoma of 3 cm or less. Gut 54:1151–1156CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lencioni R (2010) Loco-regional treatment of hepatocellular carcinoma. Hepatology 52:762–773CrossRefPubMedGoogle Scholar
  5. 5.
    Livraghi T, Meloni F, Di Stasi M et al (2008) Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: is resection still the treatment of choice? Hepatology 47:82–89CrossRefPubMedGoogle Scholar
  6. 6.
    Hung HH, Chiou YY, Hsia CY et al (2011) Survival rates are comparable after radiofrequency ablation or surgery in patients with small hepatocellular carcinomas. Clin Gastroenterol Hepatol 9:79–86CrossRefPubMedGoogle Scholar
  7. 7.
    Shiina S, Tateishi R, Arano T et al (2012) Radiofrequency ablation for hepatocellular carcinoma: 10-year outcome and prognostic factors. Am J Gastroenterol 107:569–577, quiz 578 CrossRefPubMedGoogle Scholar
  8. 8.
    Kao WY, Chiou YY, Hung HH et al (2012) Younger hepatocellular carcinoma patients have better prognosis after percutaneous radiofrequency ablation therapy. J Clin Gastroenterol 46:62–70CrossRefPubMedGoogle Scholar
  9. 9.
    Kim YS, Lim HK, Rhim H et al (2013) Ten-year outcomes of percutaneous radiofrequency ablation as first-line therapy of early hepatocellular carcinoma: analysis of prognostic factors. J Hepatol 58:89–97CrossRefPubMedGoogle Scholar
  10. 10.
    Seror O, N'Kontchou G, Nault JC et al (2016) Hepatocellular carcinoma within Milan criteria: no-touch multibipolar radiofrequency ablation for treatment-long-term results. Radiology. doi: 10.1148/radiol.2016150743:150743 Google Scholar
  11. 11.
    Fernandez M (2015) Molecular pathophysiology of portal hypertension. Hepatology 61:1406–1415CrossRefPubMedGoogle Scholar
  12. 12.
    de Franchis R, Baveno VIF (2015) Expanding consensus in portal hypertension: report of the Baveno VI Consensus Workshop: stratifying risk and individualizing care for portal hypertension. J Hepatol 63:743–752CrossRefPubMedGoogle Scholar
  13. 13.
    D'Amico G, Pasta L, Morabito A et al (2014) Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther 39:1180–1193CrossRefPubMedGoogle Scholar
  14. 14.
    King LY, Canasto-Chibuque C, Johnson KB et al (2015) A genomic and clinical prognostic index for hepatitis C-related early-stage cirrhosis that predicts clinical deterioration. Gut 64:1296–1302CrossRefPubMedGoogle Scholar
  15. 15.
    Fischer MA, Kartalis N, Grigoriadis A et al (2015) Perfusion computed tomography for detection of hepatocellular carcinoma in patients with liver cirrhosis. Eur Radiol 25:3123–3132CrossRefPubMedGoogle Scholar
  16. 16.
    Bucci L, Garuti F, Camelli V et al (2016) Comparison between alcohol- and hepatitis C virus-related hepatocellular carcinoma: clinical presentation, treatment and outcome. Aliment Pharmacol Ther 43:385–399CrossRefPubMedGoogle Scholar
  17. 17.
    Llovet JM, Fuster J, Bruix J (1999) Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: resection versus transplantation. Hepatology 30:1434–1440CrossRefPubMedGoogle Scholar
  18. 18.
    Bruix J, Castells A, Bosch J et al (1996) Surgical resection of hepatocellular carcinoma in cirrhotic patients: prognostic value of preoperative portal pressure. Gastroenterology 111:1018–1022CrossRefPubMedGoogle Scholar
  19. 19.
    Boleslawski E, Petrovai G, Truant S et al (2012) Hepatic venous pressure gradient in the assessment of portal hypertension before liver resection in patients with cirrhosis. Br J Surg 99:855–863CrossRefPubMedGoogle Scholar
  20. 20.
    Cucchetti A, Cescon M, Golfieri R et al (2016) Hepatic venous pressure gradient in the preoperative assessment of patients with resectable hepatocellular carcinoma. J Hepatol 64:79–86CrossRefPubMedGoogle Scholar
  21. 21.
    European Association For The Study Of The L, European Organisation for Research and Treatment of Cancer (2012) EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol 56:908–943CrossRefGoogle Scholar
  22. 22.
    Bruix J, Reig M, Sherman M (2016) Evidence-based diagnosis, staging, and treatment of patients with hepatocellular carcinoma. Gastroenterology 150:835–853CrossRefPubMedGoogle Scholar
  23. 23.
    Bruix J, Sherman M, Llovet JM et al (2001) Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL Conference. J Hepatol 35:421–430CrossRefPubMedGoogle Scholar
  24. 24.
    Su CW, Chau GY, Hung HH et al (2015) Impact of steatosis on prognosis of patients with early-stage hepatocellular carcinoma after hepatic resection. Ann Surg Oncol 22:2253–2261CrossRefPubMedGoogle Scholar
  25. 25.
    D'Agostino RB Jr (1998) Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med 17:2265–2281CrossRefPubMedGoogle Scholar
  26. 26.
    Ishizawa T, Hasegawa K, Aoki T et al (2008) Neither multiple tumors nor portal hypertension are surgical contraindications for hepatocellular carcinoma. Gastroenterology 134:1908–1916CrossRefPubMedGoogle Scholar
  27. 27.
    Roayaie S, Jibara G, Tabrizian P et al (2015) The role of hepatic resection in the treatment of hepatocellular cancer. Hepatology 62:440–451CrossRefPubMedGoogle Scholar
  28. 28.
    Santambrogio R, Kluger MD, Costa M et al (2013) Hepatic resection for hepatocellular carcinoma in patients with Child–Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB (Oxford) 15:78–84CrossRefGoogle Scholar
  29. 29.
    Berzigotti A, Reig M, Abraldes JG, Bosch J, Bruix J (2015) Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: a systematic review and meta-analysis. Hepatology 61:526–536CrossRefPubMedGoogle Scholar
  30. 30.
    Nault JC, De Reynies A, Villanueva A et al (2013) A hepatocellular carcinoma 5-gene score associated with survival of patients after liver resection. Gastroenterology 145:176–187CrossRefPubMedGoogle Scholar
  31. 31.
    Wu WC, Chiou YY, Hung HH et al (2012) Prognostic significance of computed tomography scan-derived splenic volume in hepatocellular carcinoma treated with radiofrequency ablation. J Clin Gastroenterol 46:789–795CrossRefPubMedGoogle Scholar
  32. 32.
    Ding Y, Rao SX, Chen C, Li R, Zeng MS (2015) Assessing liver function in patients with HBV-related HCC: a comparison of T(1) mapping on Gd-EOB-DTPA-enhanced MR imaging with DWI. Eur Radiol 25:1392–1398CrossRefPubMedGoogle Scholar
  33. 33.
    Lee DH, Lee JM, Lee JY et al (2014) Radiofrequency ablation of hepatocellular carcinoma as first-line treatment: long-term results and prognostic factors in 162 patients with cirrhosis. Radiology 270:900–909CrossRefPubMedGoogle Scholar
  34. 34.
    Garcia-Tsao G, Bosch J (2015) Varices and variceal hemorrhage in cirrhosis: a new view of an old problem. Clin Gastroenterol Hepatol 13:2109–2117CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Lee TY, Lin JT, Zeng YS, Chen YJ, Wu MS, Wu CY (2015) Association between nucleos(t)ide analogue and tumor recurrence in HBV-related hepatocellular carcinoma after radiofrequency ablation. Hepatology. doi: 10.1002/hep.28266 Google Scholar
  36. 36.
    Reig M, Marino Z, Perello C et al (2016) Unexpected early tumor recurrence in patients with hepatitis C virus -related hepatocellular carcinoma undergoing interferon-free therapy: a note of caution. J Hepatol. doi: 10.1016/j.jhep.2016.04.008 Google Scholar
  37. 37.
    Marcellin P, Gane E, Buti M et al (2013) Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 381:468–475CrossRefPubMedGoogle Scholar
  38. 38.
    Hosaka T, Suzuki F, Kobayashi M et al (2013) Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection. Hepatology 58:98–107CrossRefPubMedGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • Kuan-Chieh Fang
    • 1
  • Chien-Wei Su
    • 1
    • 2
  • Yi-You Chiou
    • 2
    • 3
  • Pei-Chang Lee
    • 2
    • 4
    • 5
  • Nai-Chi Chiu
    • 2
    • 3
  • Chien-An Liu
    • 2
    • 3
  • Ping-Hsien Chen
    • 2
    • 6
    • 7
  • Wei-Yu Kao
    • 2
    • 8
    • 9
    • 10
  • Yi-Hsiang Huang
    • 1
    • 11
  • Teh-Ia Huo
    • 1
    • 5
  • Ming-Chih Hou
    • 1
    • 2
    • 6
  • Han-Chieh Lin
    • 1
    • 2
  • Jaw-Ching Wu
    • 11
    • 12
  1. 1.Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Faculty of Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  3. 3.Division of Gastrointestinal Radiology, Department of RadiologyTaipei Veterans General HospitalTaipeiTaiwan
  4. 4.Division of Gastroenterology, Department of Internal Medicine, Yuanshan BranchTaipei Veterans General HospitalYilanTaiwan
  5. 5.Department and Institute of Pharmacology, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Endoscopy Center for Diagnosis and TreatmentTaipei Veterans General HospitalTaipeiTaiwan
  7. 7.Institute of BiophotonicsNational Yang-Ming UniversityTaipeiTaiwan
  8. 8.Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University HospitalTaipeiTaiwan
  9. 9.Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  10. 10.Graduate Institute of Clinical Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  11. 11.Institute of Clinical Medicine, School of MedicineNational Yang-Ming UniversityTaipeiTaiwan
  12. 12.Division of Translational Research, Department of Medical ResearchTaipei Veterans General HospitalTaipeiTaiwan

Personalised recommendations