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

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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.

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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. 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;4:439–474

    Article  PubMed  Google Scholar 

  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;139:817–823

    PubMed  Google Scholar 

  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;45:529–538

    Article  PubMed  Google Scholar 

  4. Moore KP, Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut 2006;55(Suppl 6):vi1–vi12

    Article  PubMed  Google Scholar 

  5. Ginès P, Schrier RW. Renal failure in cirrhosis. N Engl J Med 2009;361:1279–1290

    Article  PubMed  Google Scholar 

  6. Hsu CY, Huang YH, Su CW, et al. Renal failure in patients with hepatocellular carcinoma and ascites undergoing transarterial chemoembolization. Liver Int 2010;30:77–84

    Article  PubMed  CAS  Google Scholar 

  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;28:258–262

    Article  PubMed  Google Scholar 

  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;31:840–845

    Article  Google Scholar 

  9. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005;42:1208–1236

    Article  PubMed  Google Scholar 

  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;40:1396–1405

    Article  PubMed  Google Scholar 

  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;53:108–117

    Article  PubMed  Google Scholar 

  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;35:421–430

    Article  PubMed  CAS  Google Scholar 

  13. Grant BF, Dufour MC, Harford TC. Epidemiology of alcoholic liver disease. Semin Liver Dis 1988;8:12–25

    Article  PubMed  CAS  Google Scholar 

  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;53:397–417

    Article  Google Scholar 

  15. Bosch J, García-Pagán JC. Complications of cirrhosis. I. Portal hypertension. J Hepatol 2000;32(Suppl 1):141–156

    Article  PubMed  CAS  Google Scholar 

  16. Garcia-Tsao G. Current management of the complications of cirrhosis and portal hypertension: variceal hemorrhage, ascites, and spontaneous bacterial peritonitis. Gastroenterology 2001;120:726–748

    Article  PubMed  CAS  Google Scholar 

  17. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–655

    Article  PubMed  CAS  Google Scholar 

  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;10:301–319

    Article  PubMed  Google Scholar 

  19. Lamb EJ, Tomson CR, Roderick PJ. Estimating kidney function in adults using formulae. Ann Clin Biochem 2005;42:321–345

    Article  PubMed  Google Scholar 

  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;334:693–699

    Article  PubMed  CAS  Google Scholar 

  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;107:141–148

    Article  PubMed  Google Scholar 

  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;101:975–982

    Article  PubMed  Google Scholar 

  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;116:3006–3014

    Article  PubMed  Google Scholar 

  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;16:965–980

    Article  PubMed  CAS  Google Scholar 

  25. Feinstein AR. Clinical biostatistics. XVI. The process of prognostic stratification. Clin Pharmacol Ther 1972;13:609–624

    PubMed  CAS  Google Scholar 

  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;9:64–70

    Article  PubMed  Google Scholar 

  27. Casado M, Bosch J, García-Pagán JC, et al. Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. Gastroenterology 1998;114:1296–1303

    Article  PubMed  CAS  Google Scholar 

  28. Huang HC, Lee FY, Huo TI. Major adverse events, pretransplant assessment and outcome prediction. J Gastroenterol Hepatol 2009;24:1716–1724

    Article  PubMed  Google Scholar 

  29. Biggins SW, Kim WR, Terrault NA, et al. Evidence-based incorporation of serum sodium concentration into MELD. Gastroenterology 2006;130:1652–1660

    Article  PubMed  Google Scholar 

  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;359:1018–1026

    Article  PubMed  CAS  Google Scholar 

  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–e177

    PubMed  Google Scholar 

  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;31:302–308

    Article  PubMed  CAS  Google Scholar 

  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;10:146

    Article  PubMed  Google Scholar 

  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;30:198–207

    Article  PubMed  CAS  Google Scholar 

  35. Huo TI, Huang YH, Wu JC. Percutaneous ablation therapy for hepatocellular carcinoma: current practice and future perspectives. J Chin Med Assoc 2005;68:155–159

    Article  PubMed  Google Scholar 

  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;45:556–562

    Article  PubMed  CAS  Google Scholar 

  37. Tsai YJ, Hsu CY, Huang YH, et al. Early identification of poor responders to transarterial chemoembolization for hepatocellular carcinoma. Hepatol Int 2011;5:975–984

    Article  Google Scholar 

  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;51:1274–1283

    Article  PubMed  Google Scholar 

  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;113:2742–2751

    Article  PubMed  Google Scholar 

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Acknowledgements

We thank Ms Ya-Ju Tsai for her help on data collection and manuscript preparation. This study was supported by grants from the Center of Excellence for Cancer Research at Taipei Veterans General Hospital, Taiwan (DOH100-TD-C-111-007), Taipei Veterans General Hospital, Taipei, Taiwan (V100C1-155), National Yang-Ming University Hospital, Yilan, Taiwan (RD-2011-017), and the Ministry of Education, Aim for the Top University Plan, Taiwan (100AC-D103).

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan

    Chia-Yang Hsu, Yun-Hsuan Lee, Yi-Hsiang Huang, Cheng-Yuan Hsia, Chien-Wei Su, Han-Chieh Lin, Fa-Yauh Lee, Teh-Ia Huo & Shou-Dong Lee

  2. Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

    Cheng-Yuan Hsia

  3. Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

    Rheun-Chuan Lee & Yi-You Chiou

  4. Department of Medicine, National Yang-Ming University Hospital, Yilan, Taiwan

    Chia-Yang Hsu

  5. National Yang-Ming University School of Medicine, Taipei, Taiwan

    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

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  1. Chia-Yang Hsu
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Correspondence to Teh-Ia Huo.

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Hsu, CY., Lee, YH., Huang, YH. et al. Ascites in patients with hepatocellular carcinoma: prevalence, associated factors, prognostic impact, and staging strategy. Hepatol Int 7, 188–198 (2013). https://doi.org/10.1007/s12072-011-9338-z

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  • DOI: https://doi.org/10.1007/s12072-011-9338-z

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