Skip to main content
SpringerLink
Log in

Clinical manifestations and outcomes of patients with scirrhous hepatocellular carcinoma

  • Original Article
  • Published:
Hepatology International Aims and scope Submit manuscript

Abstract

Background

The scirrhous hepatocellular carcinoma (HCC) is a rare subtype characterized by prominent fibrous stroma separating nests of tumor cells histologically. The clinical characteristics of scirrhous HCC have not been clearly elucidated due to limited literatures. We aimed to investigate the clinical manifestations and outcomes of patients with scirrhous HCC.

Methods

A total of 4012 patients with histologically proven HCC from the Cancer Registry Database (2004–2016) of the National Taiwan University Hospital (NTUH) were enrolled; whereas, 30 patients with scirrhous HCC were identified from the pathology database of NTUH. We matched 120 patients with non-scirrhous HCC through propensity score according to sex, age, Barcelona Clinic Liver Cancer stage and initial treatment modality for comparison.

Results

No significant difference in baseline characteristics and presentations was observed between the patients with scirrhous and non-scirrhous HCC except baseline alpha-fetoprotein level. The overall survival was comparable in these two groups. For the patients undergoing curative therapy, the risk of recurrence in the patients with scirrhous HCC was significantly higher within 24 months after curative therapy (hazard ratio [HR], 2.88, 95% confidence interval [CI], 1.43–5.80, p value, 0.003) as compared with those with non-scirrhous HCC. The overall recurrence rate was comparable in these two groups.

Conclusions

Using propensity score matching, the risk of recurrence in the patients with scirrhous HCC was significantly higher in the first 2 years after curative therapy as compared to those with non-scirrhous HCC. An individualized post-curative treatment monitoring strategy should be considered for the patients with scirrhous HCC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

HCC:

Hepatocellular carcinoma

BCLC:

Barcelona Clinic Liver Cancer

AFP:

Alpha-fetoprotein

AJCC:

American Joint Committee on Cancer

FIB-4 score:

Fibrosis-4 score

ALBI score:

Albumin–bilirubin score

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HR:

Hazard ratio

CI:

Confidence interval

References

  1. Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, et al. The burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015. JAMA Oncol. 2017;3:1683–91.

    Article  Google Scholar 

  2. Liao SH, Su TH, Jeng YM, Liang PC, Chen DS, Chen CH, et al. Clinical manifestations and outcomes of patients with sarcomatoid hepatocellular carcinoma. Hepatology. 2019;69:209–21.

    Article  Google Scholar 

  3. Bosman FT, Carneiro F, Hruban RH, Theise ND. WHO classification of tumours of the digestive system. Geneva: World Health Organization; 2010.

    Google Scholar 

  4. Nagtegaal ID, Odze RD, Klimstra D, Paradis V, Rugge M, Schirmacher P, et al. The 2019 WHO classification of tumours of the digestive system. Histopathology. 2020;76:182–8.

    Article  Google Scholar 

  5. Shafizadeh N, Kakar S. Hepatocellular carcinoma: histologic subtypes. Surg Pathol Clin. 2013;6:367–84.

    Article  Google Scholar 

  6. Kurogi M, Nakashima O, Miyaaki H, Fujimoto M, Kojiro M. Clinicopathological study of scirrhous hepatocellular carcinoma. J Gastroenterol Hepatol. 2006;21:1470–7.

    PubMed  Google Scholar 

  7. Kim SH, Lim HK, Lee WJ, Choi D, Park CK. Scirrhous hepatocellular carcinoma: comparison with usual hepatocellular carcinoma based on CT-pathologic features and long-term results after curative resection. Eur J Radiol. 2009;69:123–30.

    Article  Google Scholar 

  8. Lee JH, Choi MS, Gwak GY, Lee JH, Koh KC, Paik SW, et al. Clinicopathologic characteristics and long-term prognosis of scirrhous hepatocellular carcinoma. Dig Dis Sci. 2012;57:1698–707.

    Article  Google Scholar 

  9. Farooq A, Merath K, Paredes AZ, Wu L, Tsilimigras DI, Hyer JM, et al. Outcomes of patients with scirrhous hepatocellular carcinoma: insights from the national cancer database. J Gastrointest Surg. 2019. https://doi.org/10.1007/s11605-019-04282-1.

    Article  PubMed  Google Scholar 

  10. Sugiki T, Yamamoto M, Taka K, Nakano M. Specific characteristics of scirrhous hepatocellular carcinoma. Hepatogastroenterology. 2009;56:1086–9.

    PubMed  Google Scholar 

  11. Bergstralh E, Kosanke J. Computerized matching of cases to controls. Technical Report 56. Rochester: Mayo Foundation; 1995.

    Google Scholar 

  12. Tseng TC, Liu CJ, Su TH, Yang WT, Chen CL, Yang HC, et al. Fibrosis-4 index helps identify HBV carriers with the lowest risk of hepatocellular carcinoma. Am J Gastroenterol. 2017;112:1564–74.

    Article  CAS  Google Scholar 

  13. Johnson PJ, Berhane S, Kagebayashi C, Satomura S, Teng M, Reeves HL, et al. Assessment of liver function in patients with hepatocellular carcinoma: a new evidence-based approach-the ALBI grade. J Clin Oncol. 2015;33:550–8.

    Article  Google Scholar 

  14. Management consensus guideline for hepatocellular carcinoma. 2016 updated by the Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan. J Formos Med Assoc. 2018;117:381–403.

    Article  Google Scholar 

  15. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia J, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317–70.

    Article  Google Scholar 

  16. Marrero JA, Kulik LM, Sirlin CB, Zhu AX, Finn RS, Abecassis MM, et al. Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases. Hepatology. 2018;68:723–50.

    Article  Google Scholar 

  17. EASL. EASL clinical practice guidelines: management of hepatocellular carcinoma. J Hepatol. 2018;69:182–236.

    Article  Google Scholar 

  18. Hatano M, Ojima H, Masugi Y, Tsujikawa H, Hiraoka N, Kanai Y, et al. Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features. Hum Pathol. 2019;86:222–32.

    Article  Google Scholar 

  19. Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S, et al. Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003;38:200–7.

    Article  Google Scholar 

  20. Wei T, Zhang XF, Bagante F, Ratti F, Marques HP, Silva S, et al. Early versus late recurrence of hepatocellular carcinoma after surgical resection based on post-recurrence survival: an international multi-institutional analysis. J Gastrointest Surg. 2020. https://doi.org/10.1007/s11605-020-04553-2.

    Article  PubMed  Google Scholar 

  21. Cheng Z, Yang P, Qu S, Zhou J, Yang J, Yang X, et al. Risk factors and management for early and late intrahepatic recurrence of solitary hepatocellular carcinoma after curative resection. HPB (Oxford). 2015;17:422–7.

    Article  Google Scholar 

  22. Xu XF, Xing H, Han J, Li ZL, Lau WY, Zhou YH, et al. Risk factors, patterns, and outcomes of late recurrence after liver resection for hepatocellular carcinoma: a multicenter study from China. JAMA Surg. 2019;154:209–17.

    Article  Google Scholar 

  23. Ding X, He M, Chan AWH, Song QX, Sze SC, Chen H, et al. Genomic and epigenomic features of primary and recurrent hepatocellular carcinomas. Gastroenterology. 2019;157(1630–1645):e1636.

    Google Scholar 

  24. Seok JY, Na DC, Woo HG, Roncalli M, Kwon SM, Yoo JE, et al. A fibrous stromal component in hepatocellular carcinoma reveals a cholangiocarcinoma-like gene expression trait and epithelial-mesenchymal transition. Hepatology. 2012;55:1776–86.

    Article  CAS  Google Scholar 

  25. Calderaro J, Couchy G, Imbeaud S, Amaddeo G, Letouzé E, Blanc JF, et al. Histological subtypes of hepatocellular carcinoma are related to gene mutations and molecular tumour classification. J Hepatol. 2017;67:727–38.

    Article  CAS  Google Scholar 

  26. Krings G, Ramachandran R, Jain D, Wu TT, Yeh MM, Torbenson M, et al. Immunohistochemical pitfalls and the importance of glypican 3 and arginase in the diagnosis of scirrhous hepatocellular carcinoma. Mod Pathol. 2013;26:782–91.

    Article  CAS  Google Scholar 

Download references

Funding

This paper was funded by National Taiwan University Hospital (grant number 108-S254) and the Ministry of Science and Technology, Executive Yuan, Taiwan (grant number 107-2314-B-002-036-MY3).

Author information

Author notes

  1. Shang-Chin Huang and Sih-Han Liao contributed equally to the work.

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

    Shang-Chin Huang, Sih-Han Liao, Tung-Hung Su & Jia-Horng Kao

  2. Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

    Sih-Han Liao

  3. Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

    Sih-Han Liao

  4. Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

    Tung-Hung Su & Jia-Horng Kao

  5. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    Yung-Ming Jeng

  6. Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

    Jia-Horng Kao

  7. Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, 1 Chang-Te St., Taipei, 10002, Taiwan

    Jia-Horng Kao

Authors
  1. Shang-Chin Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sih-Han Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tung-Hung Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yung-Ming Jeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia-Horng Kao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Study concept and design: SHL, JHK, SCH; Acquisition of data: SCH, SHL, THS; Statistical analysis: SHL, SCH; Analysis and interpretation of data: SCH, SHL; Drafting of the manuscript: SCH, SHL, JHK; Critical revision of the manuscript for important intellectual content: JHK, YMJ, THS; Obtained funding: JHK; Study supervision: JHK; Final approval of the version to be published: SCH, SHL, THS, YMJ, JHK.

Corresponding author

Correspondence to Jia-Horng Kao.

Ethics declarations

Conflict of interest

Shang-Chin Huang, Sih-Han Liao, Tung-Hung Su, Yung-Ming Jeng and Jia-Horng Kao declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board of National Taiwan University Hospital (201702028RIND) and conformed to the ethical guidelines of the 1975 Declaration of Helsinki. The informed consent was waived because this is a retrospective study conducted by a review of medical records only.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 240 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, SC., Liao, SH., Su, TH. et al. Clinical manifestations and outcomes of patients with scirrhous hepatocellular carcinoma. Hepatol Int 15, 472–481 (2021). https://doi.org/10.1007/s12072-021-10146-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12072-021-10146-1

Keywords

Search

Navigation