Journal of Pathology and Translational Medicine

Original Articles

Prognosis of Hepatocellular Carcinoma after Liver Transplantation: Comparative Analysis with Partial Hepatectomy: Kyuho Lee, Kyoung-Bun Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang; J Pathol Transl Med. 2017;51(1):79-86. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.13

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Background
Liver transplantation (LT) is the treatment of choice for hepatocellular carcinoma (HCC). The aim of this study was to investigate the recurrence rate of HCC after LT and prognostic factors for recurrence by comparing LT with non-transplanted resection. Methods: The participants were 338 patients who underwent LT between 1996 and 2012 at Seoul National University Hospital (LT group) and 520 HCC patients who underwent partial hepatectomy between 1995 and 2006 (control group, non-LT group). Results: In the LT group, 68 of 338 patients (19.8%) showed relapse, and the recurrence rate was lower than that in the non-LT group (64.9%, 357/520, p < .001). Stratification analysis by American Joint Committee on Cancer (AJCC) stage showed that the stage I-II LT group had a lower recurrence rate than the non-LT group. Univariate comparative analysis demonstrated that multiplicity of tumor, tumor size, gross type, Edmondson- Steiner (ES) nuclear grade, extent of tumor, angioinvasion, AJCC stage, Milan criteria, University of California at San Francisco criteria on explant pathology (all p < .001), positive expression of cytokeratin 19 (p = .002), and preoperative α-fetoprotein (AFP) (p < .001) were predictors of tumor recurrence. In multivariate analysis, LT, preoperative AFP, multiplicity of tumor, extent of tumor, size of tumor, and ES nuclear grade were independent prognostic factors. Conclusions: LT might have a protective effect against the late recurrence of stage I-II HCC compared to non-LT, and the prognostic factors for recurrence were similar to previously well-known prognostic factors for HCC.

Citations

Citations to this article as recorded by

Related Factors of Hepatocellular Carcinoma Recurrence Associated With Hyperglycemia After Liver Transplantation
Yujian Zheng, Qing Cai, Lishan Peng, Shibo Sun, Shaoping Wang, Jie Zhou
Transplantation Proceedings.2021; 53(1): 177. CrossRef
Oncological Outcomes of Hepatic Resection vs Transplantation for Localized Hepatocellular Carcinoma
A.T. Akcam, A.G. Saritas, A. Ulku, A. Rencuzogullari
Transplantation Proceedings.2019; 51(4): 1147. CrossRef
Clustering Asian Countries According to the Trend of liver cancer Mortality Rates: an Application of Growth Mixture Models
Maryam Salari, Anoshirvan Kazemnejad, Farid Zayeri
Iranian Red Crescent Medical Journal.2017;[Epub] CrossRef

Nuclear Expression of Hepatitis B Virus X Protein Is Associated with Recurrence of Early-Stage Hepatocellular Carcinomas: Role of Viral Protein in Tumor Recurrence: Jing Jin, Hae Yoen Jung, KyuHo Lee, Nam-Joon Yi, Kyung-Suk Suh, Ja-June Jang, Kyoung-Bun Lee; J Pathol Transl Med. 2016;50(3):181-189. Published online April 17, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.18

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Abstract PDF

Background
Hepatitis B virus (HBV) plays well-known roles in tumorigenesis of hepatocellular carcinoma (HCC) in infected patients. However, HBV-associated protein status in tumor tissues and the relevance to tumor behavior has not been reported. Our study aimed to examine the expression of HBV-associated proteins in HCC and adjacent nontumorous tissue and their clinicopathologic implication in HCC patients.
Methods
HBV surface antigen (HBsAg), HBV core antigen (HBcAg), and HBV X protein (HBx) were assessed in 328 HBV-associated HCCs and in 155 matched nontumorous tissues by immunohistochemistry staining.
Results
The positive rates of HBsAg and cytoplasmic HBx staining in tumor tissue were lower than those in nontumorous tissue (7.3% vs. 57.4%, p < .001; 43.4% vs. 81.3%, p < .001). Conversely, nuclear HBx was detected more frequently in tumors than in nontumorous tissue (52.1% vs. 30.3%, p < .001). HCCs expressing HBsAg, HBcAg, or cytoplasmic HBx had smaller size; lower Edmondson-Steiner (ES) nuclear grade, pT stage, and serum alpha-fetoprotein, and less angioinvasion than HCCs not expressing HBV-associated proteins. Exceptionally, nuclear HBx-positive HCCs showed higher ES nuclear grade and more frequent large-vessel invasion than did nuclear HBx-negative HCCs. In survival analysis, only nuclear HBx-positive HCCs had shorter disease-free survival than nuclear HBx-negative HCCs in pT1 and ES nuclear grade 1–2 HCC subgroup (median, 126 months vs. 35 months; p = .015).
Conclusions
Our data confirmed that expression of normal HBV-associated proteins generally decreases in tumor cells in comparison to nontumorous hepatocytes, with the exception of nuclear HBx, which suggests that nuclear HBx plays a role in recurrence of well-differentiated and early-stage HCCs.

Citations

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Relevance of HBx for Hepatitis B Virus-Associated Pathogenesis
Anja Schollmeier, Mirco Glitscher, Eberhard Hildt
International Journal of Molecular Sciences.2023; 24(5): 4964. CrossRef
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Lei Wang, Jin-Lin Peng, Ji-Zhou Wu
Medicine.2023; 102(13): e33319. CrossRef
Tertiary Prevention of HCC in Chronic Hepatitis B or C Infected Patients
Wei Teng, Yen-Chun Liu, Wen-Juei Jeng, Chien-Wei Su
Cancers.2021; 13(7): 1729. CrossRef
Suppression of hepatitis b virus by a combined activity of CRISPR/Cas9 and HBx proteins
S. A. Brezgin, A. P. Kostyusheva, V. N. Simirsky, E. V. Volchkova, D. S. Chistyakov, D. S. Kostyushev, V. P. Chulanov
Russian Journal of Infection and Immunity.2019; 9(3-4): 476. CrossRef
Hepatitis B virus surface gene pre‐S2 mutant as a high‐risk serum marker for hepatoma recurrence after curative hepatic resection
Chia‐Jui Yen, Yu‐Lin Ai, Hung‐Wen Tsai, Shih‐Huang Chan, Chia‐Sheng Yen, Kuang‐Hsiung Cheng, Yun‐Ping Lee, Chia‐Wei Kao, Yu‐Chun Wang, Yi‐Lin Chen, Cheng‐Han Lin, Tsunglin Liu, Huey‐Pin Tsai, Jen‐Ren Wang, Ih‐Jen Su, Wenya Huang
Hepatology.2018; 68(3): 815. CrossRef
Integrin α6 as an invasiveness marker for hepatitis B viral X-driven hepatocellular carcinoma
Yi Rang Kim, Mi Ran Byun, Jin Woo Choi
Cancer Biomarkers.2018; 23(1): 135. CrossRef
Clinical Implications of Hepatitis B Virus RNA and Covalently Closed Circular DNA in Monitoring Patients with Chronic Hepatitis B Today with a Gaze into the Future: The Field Is Unprepared for a Sterilizing Cure
Anastasiya Kostyusheva, Dmitry Kostyushev, Sergey Brezgin, Elena Volchkova, Vladimir Chulanov
Genes.2018; 9(10): 483. CrossRef

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