Hepatology International

, Volume 7, Issue 1, pp 188–198 | Cite as

Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy

  • Chia-Yang Hsu
  • Yun-Hsuan Lee
  • Yi-Hsiang Huang
  • Cheng-Yuan Hsia
  • Chien-Wei Su
  • Han-Chieh Lin
  • Rheun-Chuan Lee
  • Yi-You Chiou
  • Fa-Yauh Lee
  • Teh-Ia Huo
  • Shou-Dong Lee
Original Article

Abstract

Purpose

Ascites may develop in patients with hepatocellular carcinoma (HCC) with coexisting liver cirrhosis. Few studies had specifically evaluated the role of ascites in HCC. This study investigated its prevalence, associated factors, prognostic impact, and staging strategy in a large HCC patient cohort.

Patients and methods

A total of 2,203 HCC patients were analyzed. The grading of ascites was according to the European Association for the Study of Liver. The prognostic ability of the Cancer of the liver Italian Program (CLIP), Barcelona Clinic Liver Cancer, Japan Integrated Scoring system, and Taipei Integrated Scoring system in HCC patients with ascites was compared using the Akaike information criterion (AIC).

Results

Ascites was present in 498 (23%) patients at diagnosis. Grades 1, 2, and 3 ascites were found in 13, 5, and 5% of the patients, respectively. The severity of ascites significantly correlated with hyperbilirubinemia, hypoalbuminemia, hyponatremia, prothrombin time (PT) prolongation, and renal insufficiency (all p < 0.001). Large tumor burden and more frequent vascular invasion were often observed in patients with more severe ascites (both p < 0.001). In the Cox proportional hazard model, ascites was identified as an independent prognostic predictor with 80–94% increased risk of mortality (p < 0.001). Among HCC patients with ascites, the CLIP system had the lowest AIC value.

Conclusions

Ascites is often seen in HCC patients and is associated with both tumoral and cirrhosis factors and decreased long-term survival. The CLIP staging system is a more feasible prognostic model for HCC patients with ascites. The optimal treatment strategy for these patients remains to be investigated.

Keywords

Ascites Hepatocellular carcinoma Liver cirrhosis MELD 

Abbreviations

AFP

α-Fetoprotein

AIC

Akaike information criterion

BCLC

Barcelona Clinic Liver Cancer

CI

Confidence interval

CLIP

Cancer of the Liver Italian Program

CT

Computed tomography

CTP

Child–Turcotte–Pugh

HBV

Hepatitis B virus

HCV

Hepatitis C virus

HCC

Hepatocellular carcinoma

INR

International normalized ratio

JIS

Japan Integrated Scoring

MELD

Model for end-stage liver disease

PAI

Percutaneous acetic acid injection

PEI

Percutaneous ethanol injection

RFA

Radiofrequency ablation

SD

Standard deviation

TACE

Transarterial chemoembolization

References

  1. 1.
    Omata M, Lesmana LA, Tateishi R, et al. Asian Pacific association for the study of the liver consensus recommendations on hepatocellular carcinoma. Hepatol Int 2010;4:439–474PubMedCrossRefGoogle Scholar
  2. 2.
    El-Serag HB, Davila JA, Petersen NJ, et al. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139:817–823PubMedGoogle Scholar
  3. 3.
    Perz JF, Armstrong GL, Farrington LA, et al. The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 2006;45:529–538PubMedCrossRefGoogle Scholar
  4. 4.
    Moore KP, Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut 2006;55(Suppl 6):vi1–vi12PubMedCrossRefGoogle Scholar
  5. 5.
    Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med 2009;361:1279–1290PubMedCrossRefGoogle Scholar
  6. 6.
    Hsu CY, Huang YH, Su CW, et al. Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization. Liver Int 2010;30:77–84PubMedCrossRefGoogle Scholar
  7. 7.
    Huo TI, Lui WY, Wu JC, et al. Deterioration of hepatic functional reserve in patients with hepatocellular carcinoma after resection: incidence, risk factors, and association with intrahepatic tumor recurrence. World J Surg 2004;28:258–262PubMedCrossRefGoogle Scholar
  8. 8.
    The Cancer of the Liver Italian Program (CLIP) Investigators. Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. Hepatology 2000;31:840–845CrossRefGoogle Scholar
  9. 9.
    Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236PubMedCrossRefGoogle Scholar
  10. 10.
    Kudo M, Chung H, Haji S, et al. Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score. Hepatology 2004;40:1396–1405PubMedCrossRefGoogle Scholar
  11. 11.
    Hsu CY, Huang YH, Hsia CY, et al. A new prognostic model for hepatocellular carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol 2010;53:108–117PubMedCrossRefGoogle Scholar
  12. 12.
    Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol 2001;35:421–430PubMedCrossRefGoogle Scholar
  13. 13.
    Grant BF, Dufour MC, Harford TC. Epidemiology of alcoholic liver disease. Semin Liver Dis 1988;8:12–25PubMedCrossRefGoogle Scholar
  14. 14.
    European Association for the Study of the Liver. EASL clinical practice guidelines on the management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis. J Hepatol 2010;53:397–417CrossRefGoogle Scholar
  15. 15.
    Bosch J, García-Pagán JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000;32(Suppl 1):141–156PubMedCrossRefGoogle Scholar
  16. 16.
    Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology 2001;120:726–748PubMedCrossRefGoogle Scholar
  17. 17.
    Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–655PubMedCrossRefGoogle Scholar
  18. 18.
    Gonwa TA, Jennings L, Mai ML, et al. Estimation of glomerular filtration rates before and after orthotopic liver transplantation: evaluation of current equations. Liver Transpl 2004;10:301–319PubMedCrossRefGoogle Scholar
  19. 19.
    Lamb EJ, Tomson CR, Roderick PJ. Estimating kidney function in adults using formulae. Ann Clin Biochem 2005;42:321–345PubMedCrossRefGoogle Scholar
  20. 20.
    Mazzaferro V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996;334:693–699PubMedCrossRefGoogle Scholar
  21. 21.
    Huo TI, Lin HC, Huang YH, et al. The model for end-stage liver disease-based Japan Integrated Scoring system may have a better predictive ability for patients with hepatocellular carcinoma undergoing locoregional therapy. Cancer 2006;107:141–148PubMedCrossRefGoogle Scholar
  22. 22.
    Huo TI, Huang YH, Lin HC, et al. Proposal of a modified Cancer of the Liver Italian Program staging system based on the model for end-stage liver disease for patients with hepatocellular carcinoma undergoing loco-regional therapy. Am J Gastroenterol 2006;101:975–982PubMedCrossRefGoogle Scholar
  23. 23.
    Hsu CY, Hsia CY, Huang YH, et al. Selecting an optimal staging system for hepatocellular carcinoma: comparison of 5 currently used prognostic models. Cancer 2010;116:3006–3014PubMedCrossRefGoogle Scholar
  24. 24.
    Hosmer DW, Hosmer T, Le Cessie S, et al. A comparison of goodness-of-fit tests for the logistic regression model. Stat Med 1997;16:965–980PubMedCrossRefGoogle Scholar
  25. 25.
    Feinstein AR. Clinical biostatistics. XVI. The process of prognostic stratification. Clin Pharmacol Ther 1972;13:609–624PubMedGoogle Scholar
  26. 26.
    Yang JD, Kim WR, Coelho R, et al. Cirrhosis is present in most patients with hepatitis B and hepatocellular carcinoma. Clin Gastroenterol Hepatol 2011;9:64–70PubMedCrossRefGoogle Scholar
  27. 27.
    Casado M, Bosch J, García-Pagán JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 1998;114:1296–1303PubMedCrossRefGoogle Scholar
  28. 28.
    Huang HC, Lee FY, Huo TI. Major adverse events, pretransplant assessment and outcome prediction. J Gastroenterol Hepatol 2009;24:1716–1724PubMedCrossRefGoogle Scholar
  29. 29.
    Biggins SW, Kim WR, Terrault NA, et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology 2006;130:1652–1660PubMedCrossRefGoogle Scholar
  30. 30.
    Kim WR, Biggins SW, Kremers WK, et al. Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 2008;359:1018–1026PubMedCrossRefGoogle Scholar
  31. 31.
    Hsu CY, Huang YH, Su CW, et al. Transarterial chemoembolization in patients with hepatocellular carcinoma and renal insufficiency. J Clin Gastroenterol 2010;44:e171–e177PubMedGoogle Scholar
  32. 32.
    Tangkijvanich P, Anukulkarnkusol N, Suwangool P, et al. Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels. J Clin Gastroenterol 2000;31:302–308PubMedCrossRefGoogle Scholar
  33. 33.
    Huo TI, Hsu CY, Huang YH, et al. Prognostic prediction across a gradient of total tumor volume in patients with hepatocellular carcinoma undergoing locoregional therapy. BMC Gastroenterol 2010;10:146PubMedCrossRefGoogle Scholar
  34. 34.
    Huo TI, Hsu CY, Huang YH, et al. Diabetes mellitus as an independent prognostic predictor and its association with renal dysfunction in patients with hepatocellular carcinoma. Liver Int 2010;30:198–207PubMedCrossRefGoogle Scholar
  35. 35.
    Huo TI, Huang YH, Wu JC. Percutaneous ablation therapy for hepatocellular carcinoma: current practice and future perspectives. J Chin Med Assoc 2005;68:155–159PubMedCrossRefGoogle Scholar
  36. 36.
    Hsin IF, Hsu CY, Huang HC, et al. Incidence, risk factors and prognostic impact of liver failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization. J Clin Gastroenterol 2011;45:556–562PubMedCrossRefGoogle Scholar
  37. 37.
    Tsai YJ, Hsu CY, Huang YH, et al. Early identification of poor responders to transarterial chemoembolization for hepatocellular carcinoma. Hepatol Int 2011;5:975–984CrossRefGoogle Scholar
  38. 38.
    Cabibbo G, Enea M, Attanasio M, et al. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology 2010;51:1274–1283PubMedCrossRefGoogle Scholar
  39. 39.
    Yau T, Yao TJ, Chan P, et al. A new prognostic score system in patients with advanced hepatocellular carcinoma not amendable to locoregional therapy: implication for patient selection in systemic therapy trials. Cancer 2008;113:2742–2751PubMedCrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2012

Authors and Affiliations

  • Chia-Yang Hsu
    • 1
    • 4
    • 5
  • Yun-Hsuan Lee
    • 1
    • 5
  • Yi-Hsiang Huang
    • 1
    • 5
  • Cheng-Yuan Hsia
    • 1
    • 2
    • 5
  • Chien-Wei Su
    • 1
    • 5
  • Han-Chieh Lin
    • 1
    • 5
  • Rheun-Chuan Lee
    • 3
    • 5
  • Yi-You Chiou
    • 3
    • 5
  • Fa-Yauh Lee
    • 1
    • 5
  • Teh-Ia Huo
    • 1
    • 5
  • Shou-Dong Lee
    • 1
    • 5
  1. 1.Division of Gastroenterology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
  2. 2.Department of SurgeryTaipei Veterans General HospitalTaipeiTaiwan
  3. 3.Department of RadiologyTaipei Veterans General HospitalTaipeiTaiwan
  4. 4.Department of MedicineNational Yang-Ming University HospitalYilanTaiwan
  5. 5.National Yang-Ming University School of MedicineTaipeiTaiwan

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