Case Control Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 28, 2015; 21(12): 3554-3563
Published online Mar 28, 2015. doi: 10.3748/wjg.v21.i12.3554
Primary biliary cirrhosis-associated hepatocellular carcinoma in Chinese patients: Incidence and risk factors
Xue-Xiu Zhang, Li-Feng Wang, Lei Jin, Yuan-Yuan Li, Shu-Li Hao, Yan-Chao Shi, Qing-Lei Zeng, Zhi-Wei Li, Zheng Zhang, George KK Lau, Fu-Sheng Wang
Xue-Xiu Zhang, Qing-Lei Zeng, Fu-Sheng Wang, The Institute of Translational Hepatology, 302 Military Hospital of China-Peking University Teaching Hospital, Beijing 100039, China
Li-Feng Wang, Lei Jin, Yuan-Yuan Li, Zheng Zhang, Fu-Sheng Wang, George KK Lau, Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China
Shu-Li Hao, Non-Infectious Liver Disease Diagnosis and Treatment Center, 302 Military Hospital of China-Peking University Teaching Hospital, Beijing 100039, China
Yan-Chao Shi, Research Center for Liver Transplantation, 302 Military Hospital of China-Peking University Teaching Hospital, Beijing 100039, China
Zhi-Wei Li, Department for Hepatobiliary Surgery, Beijing 302 Hospital, Beijing 100039, China
Author contributions: Zhang XX designed and performed the study and wrote the manuscript; Wang LF performed the study and was involved in editing the manuscript; Jin L, Li YY, Hao SL, Shi YC, Zeng QL, Li ZW and Zhang Z performed the study, statistical analysis, and interpretation of the data; Lau GKK revised the manuscript; and Wang FS designed the study, acquired the clinical data, revised and edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81470837, No. 81101589 and No. 81302593.
Ethics approval: The study was reviewed and approved by the Beijing 302 Hospital Research Ethics Committee.
Informed consent: The Beijing 302 Hospital Research Ethics Committee waived the need for written informed consent from the participants due to the de-identified secondary data analyzed in this study.
Conflict-of-interest: All authors declare no conflict of any interest.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Fu-Sheng Wang, MD, PhD, The Institute of Translational Hepatology, 302 Military Hospital of China-Peking University Teaching Hospital, No. 100 Western 4th Middle Ring Road, Beijing 100039, China.
Telephone: +86-10-66933332 Fax: +86-10-66933332
Received: October 20, 2014
Peer-review started: October 21, 2014
First decision: November 14, 2014
Revised: December 1, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: March 28, 2015

AIM: To investigate the incidence, characteristics, and risk factors for hepatocellular carcinoma (HCC) in Chinese patients with primary biliary cirrhosis (PBC).

METHODS: We reviewed the data of 52 PBC-associated HCC patients treated at Beijing 302 Hospital from January 2002 to December 2013 and analyzed its incidence and characteristics between the two genders. The risk factors for PBC-associated HCC were analyzed via a case-control study comprising 20 PBC patients with HCC and 77 matched controls without HCC. The matched factors included gender, age, follow-up period and Child-Pugh scores. Conditional logistic regression was used to evaluate the odds ratios of potential risk factors for HCC development. A P < 0.05 was considered statistically significant.

RESULTS: The incidence of HCC in Chinese PBC patients was 4.13% (52/1255) and was significantly higher in the males (9.52%) than in the females (3.31%). Among the 52 PBC patients with HCC, 55.76% (29/52) were diagnosed with HCC and PBC simultaneously, and 5.76% (3/52) were diagnosed with HCC before PBC. The males with PBC-associated HCC were more likely than the females to have undergone blood transfusion (18.75% vs 8.33%, P = 0.043), consumed alcohol (31.25% vs 8.33%, P = 0.010), smoked (31.25% vs 8.33%, P = 0.010), had a family history of malignancy (25% vs 5.56%, P = 0.012), and had serious liver inflammation, as indicated by the elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase (P < 0.05). Conditional logistic regression analysis revealed that body mass index (BMI) ≥ 25 [adjusted odds ratio (AOR) = 1.116, 95%CI: 1.002-1.244, P = 0.045] and history of alcohol intake (AOR = 10.294, 95%CI: 1.108-95.680, P = 0.040) were significantly associated with increased odds of HCC development in PBC patients.

CONCLUSION: HCC is not rare in Chinese PBC patients. Risk factors for PBC-associated HCC include BMI ≥ 25 and a history of alcohol intake. In addition to regular monitoring, PBC patients may benefit from abstinence from alcohol and body weight control.

Keywords: Primary biliary cirrhosis, Hepatocellular carcinoma, Body mass index, History of alcohol intake, Case-control study

Core tip: Previous studies have suggested that many factors are associated with hepatocellular carcinoma (HCC) development in primary biliary cirrhosis (PBC) patients. However, the evaluation of risk factors using a case-control study has not been reported. This case-control study analyzed the characteristics of PBC-associated HCC and investigated the relevant risk factors. The incidence of HCC was 4.13% in Chinese PBC patients, and it was more frequent in the male patients. Our results show for the first time that body mass index ≥ 25 and a history of alcohol intake are independent risk factors for HCC in PBC patients.