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ORIGINAL ARTICLE
Year : 2016  |  Volume : 12  |  Issue : 8  |  Page : 284-287

Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population


Department of Infection Disease, Lishui People's Hospital, Lishui, Zhejiang, P. R. China

Date of Web Publication22-Feb-2017

Correspondence Address:
Xiaolin Lan
Department of Infection Disease, Lishui People's Hospital, Lishui 323000, Zhejiang
P. R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.200763

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 > Abstract 

Objective: To assess the relationship between hepatitis B virus (HBV), hepatitis C virus (HCV), and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population.
Materials and Methods: The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case–control studies or cohort studies were included. The association between virus infection and hepatocellular carcinoma risk was demonstrated by odds ratio (OR) and 95% confidence interval (95% CI). The data were pooled by fixed or random effects model according to the statistical heterogeneity. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test.
Results: Finally, 13 publications were included in this meta-analysis. For significant statistical heterogeneity (I2 = 99.8%,P = 0.00), the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27–71.75); statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation of HCV infection and hepatocellular carcinoma risk across the included 13 studies I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20–3.47); significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%,P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58–18.20). No publication bias was found in the aspects of HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma.
Conclusion: For Chinese population, HBV, HCV or HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma.

Keywords: Hepatitis B virus, hepatitis C virus, hepatocellular carcinoma, meta-analysis


How to cite this article:
Li L, Lan X. Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population. J Can Res Ther 2016;12:284-7

How to cite this URL:
Li L, Lan X. Association between hepatitis B virus/hepatitis C virus infection and primary hepatocellular carcinoma risk: A meta-analysis based on Chinese population. J Can Res Ther [serial online] 2016 [cited 2017 May 30];12:284-7. Available from: http://www.cancerjournal.net/text.asp?2016/12/8/284/200763


 > Introduction Top


Hepatitis virus infection in China is common, especially for hepatic B virus infection. It was estimated about 1 in 10 people in China has been infected by hepatitis B virus (HBV).[1],[2] Epidemiology study has proven the significant association between HBV infection and hepatic risk.[3] However, for hepatitis C virus (HCV) infection or HBV and HCV double infection, the risk of developing hepatocellular carcinoma is not completely clear. In this meta-analysis, we assessed the HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population by pooling the open published data.


 > Materials and Methods Top


The databases of PubMed and CNKI were electronic searched by reviewers according to the searching words of HBV, HCV, and hepatocellular carcinoma. The related case–control studies or cohort studies were included. The publication inclusion criteria were as follows: (1) Chinese population; (2) case–control study or cohort study; (3) HBV infection was defined as one of the hepatitis B surface antigen, hepatitis B envelope antigen, anti-Hbe, anti-HBc or HBV DNA positive; HCV infection was defined as one of the anti-HCV or HCV DNA positive; (4) hepatocellular carcinoma was confirmed by pathology, cytology, or imaging diagnosis. The number of cases, controls, odds ratio (OR), 95% confidence interval (CI), first author, and year of publication of each included study were extracted by reviewers.

Statistical analysis

STATA/SE 11.0 (StataCorp LP, http://www.stata.com) was used to do statistical analysis. The association between virus infection and hepatocellular carcinoma risk was demonstrated by OR and 95% CI. The OR was pooled by fixed or random effects model according to statistical heterogeneity. If significant heterogeneity existed (P < 0.05), random effects model was used otherwise fixed effects model was applied. The publication bias was assessed by Begg's funnel plot and Egger's linear regression test.


 > Results Top


Information of the included papers

Five hundred and twenty-three publications were first identified. After reading the title and abstract, we excluded 445 studies for not suitable inclusion. Moreover, another 78 papers were excluded after reading the whole paper. Finally, 13 publications were included in this meta-analysis. The general information for the included 13 studies [4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16] is demonstrated in [Table 1].
Table 1: The general information for the included 13 studies

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Hepatitis B virus infection and hepatocellular carcinoma

Statistical heterogeneity was existed in evaluation HBV infection and hepatocellular carcinoma risk (I2 = 99.8%, P = 0.00). Hence, the OR was pooled by random effects model. The pooled results showed that HBV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 58.01, 95% CI: 44.27–71.75) [Figure 1].
Figure 1: The forest plot of association between hepatitis B virus infection and hepatocellular carcinoma

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Publication bias of evaluation hepatitis B virus infection and hepatocellular carcinoma

The Begg's funnel plot [Figure 2] and Egger's linear regression test (t = 0.16, P = 0.88) indicated no significant publication bias.
Figure 2: Begg's funnel plot for evaluation publication bias of hepatitis B virus and hepatocellular carcinoma

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Hepatitis C virus infection and hepatocellular carcinoma

Statistical heterogeneity analysis showed that significant heterogeneity existed in evaluation HCV infection and hepatocellular carcinoma risk across the included 13 studies (I2 = 77.78%, P = 0.00). The OR was pooled by random effects model. The pooled results showed that HCV infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 2.34, 95% CI: 1.20–3.47) [Figure 3].
Figure 3: The forest plot of association between hepatitis C virus infection and hepatocellular carcinoma

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Publication bias of evaluation hepatitis C virus infection and hepatocellular carcinoma

The Begg's funnel plot [Figure 4] and Egger's linear regression test (t = 0.46, P = 0.66) indicated no significant publication bias.
Figure 4: Begg's funnel plot for evaluation publication bias of hepatitis C virus and hepatocellular carcinoma

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Hepatitis B virus/hepatitis C virus double infection and hepatocellular carcinoma

Significant heterogeneity did not exist in evaluation HBV/HCV double infection and hepatocellular carcinoma risk for the included 13 studies (I2 = 0.00%, P = 0.80). The OR was pooled by fixed effects model. The pooled results showed that HBV/HCV double infection can significantly increase the risk of developing hepatocellular carcinoma (OR = 11.39, 95% CI: 4.58–18.20) [Figure 5].
Figure 5: The forest plot of association between hepatitis B virus and hepatitis C virus double infection and hepatic

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Publication bias of evaluation hepatitis B virus/hepatitis C virus infection and hepatocellular carcinoma

The Begg's funnel plot [Figure 6] and Egger's linear regression test (t = –0.20, P = 0.85) indicated no significant publication bias.
Figure 6: Begg's funnel plot for evaluation publication bias of hepatitis B virus/hepatitis C virus double infection and hepatocellular carcinoma

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 > Discussion Top


Primary hepatocellular carcinoma is common in China for the high prevalence of HBV infection for Chinese people. It was reported that about 50% primary hepatocellular carcinoma happened in China.[17],[18] Jiangsu province, Zhejiang, and Fujian province had the highest prevalence of hepatocellular carcinoma with the mortality of 30/100,000.[19] The known risk factors for hepatocellular carcinoma were hepatitis virus infection, food contaminated by aflatoxin, cirrhosis, diabetes, etc.

In our present meta-analysis, we assessed the relationship between HBV, HCV, and HBV/HCV double infection and hepatocellular carcinoma risk in Chinese population. We searched PubMed and CNKI databases and initially included after reading the title and abstract, we excluded 445 studies for not suitable inclusion. Moreover, another 78 papers were excluded after reading the whole paper. Finally, 13 publications were included in this meta-analysis. All of the included 13 studies were published in Chinese. For the effect size of association between HBV, HCV, HBV/HCV double infection and hepatocellular carcinoma risk, we found significant heterogeneity for HBV or HCV infection and hepatocellular carcinoma but without significant heterogeneity for HBV/HCV double infection. Hence, the data were pooled by random effects model in HBV, HCV infection, and hepatocellular carcinoma risk. Moreover, data were pooled by fixed effects model for HBV/HCV double infection. Meta-analysis showed that significant association between HBV, HCV or HBV/HCV double infection and hepatocellular carcinoma risk. In this study, we found that people with HBV infection had 58.01 times higher risk of hepatocellular carcinoma risk than people without HBV infection. People with HCV or HBV/HCV double infection had 2.34 and 11.39 times higher risk for than normal people.

The occurrence of hepatocellular carcinoma is the result of a variety of factors. In general, considering of different regions, different lifestyle, and different genetic background worldwide, the main cause of hepatic cancer may different.[20] However, in China, a country with a high rate of hepatitis virus infection had a very important role for hepatocellular carcinoma incidence. Hence, big effort should be made for controlling the hepatitis virus infection which would be the best way to deal with hepatocellular carcinoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Liu C, Chang L, Ji H, Guo F, Zhang K, Lin G, et al. Prevalence of HBV DNA among 20 million seronegative blood donations in China from 2010 to 2015. Sci Rep 2016;6:36464.  Back to cited text no. 1
    
2.
Wang Z, Zeng J, Li T, Zheng X, Xu X, Ye X, et al. Prevalence of hepatitis B surface antigen (HBsAg) in a blood donor population born prior to and after implementation of universal HBV vaccination in Shenzhen, China. BMC Infect Dis 2016;16:498.  Back to cited text no. 2
    
3.
Wu S, Yan P, Yang T, Wang Z, Yan Y. Epidemiological profile and risk factors of HIV and HBV/HCV co-infection in Fujian Province, Southeastern China. J Med Virol 2016;23:36-40.  Back to cited text no. 3
    
4.
Sji YJ. Amalysis of HBV amd HCV serum markers im 570 cases with primary liver cancer. Chin J Gerontol 2011;15:2820-1.  Back to cited text no. 4
    
5.
Kuang JX, Gang HW, Li RJ, Hu JM, Huang JS. HBV, HCV infection and primary liver cancer. China Med Herald 2010;33:42-3.  Back to cited text no. 5
    
6.
Li XY, Wamg JY, Li ZY, Zheng YR. Analysis of hepatitis virus infectiom in camcer cases. Chin J Nosocomiology 2012;11:2342-4.  Back to cited text no. 6
    
7.
Sun F. HBV and HCV infection in 100 cases in primary hepatic carcinoma. Med Innov China 2010;7:132.  Back to cited text no. 7
    
8.
Wang QM, Zhang ZM, Bian JC, Tang BM, Wang QJ, Zhuxin W, et al. Epidemiology study of hepatitis virus infection in cases with primary hepatic cancer in Luoyang city Henan province. Henan J Prev Med 2004;4:197-9.  Back to cited text no. 8
    
9.
Yu SZ, Mu LN, Cai L, Chen CW, Wei GR, Zhou XF, et al. Drinking water and environment factors for hepatic carcinoma in Taixing: A case-control study. Fudan Univ J Med Sci 2008;35:31-8.  Back to cited text no. 9
    
10.
Chen WQ, Wu JL, Chen MW. An investigation in the relationship betwen the superinfection of HBV, HCV and occurence of hepatocellular carcinoma. J Guangxi Med Univ 2003;4:530-2.  Back to cited text no. 10
    
11.
Xu QX, Guan D, Chen GY, Li HM. Investigation on HBV and HCV infection among people of HCC, other malignant tumor and health control. Chin J Clin Hepatol 2004;20:104-5.  Back to cited text no. 11
    
12.
Wang ZF. The study of the relationship between the primary carcinoma of liver and hepatitis B, C and TTV. Henan Med Res 2003;12:43-4.  Back to cited text no. 12
    
13.
Wu JZ, Su MH, Chen MW. A matching case-control study on the relationship between HBV, HCV infection and HCC in Guangxi China. J Guangxi Med Univ 2003;20:313-5.  Back to cited text no. 13
    
14.
Wang NC, Liu YP, Wu LP. Analysis on HBV, HCV infection situation in hepatocellular carcinoma patients. Dis Surveill 2002;5:165-7.  Back to cited text no. 14
    
15.
Su MH, Wu JZ, Luo GH, Huang LY, Chen MW. A case-control study on the relationship between HBV, HCV infection and HCC risk in Guangxi China. Clin Focus 2002;17:209-10.  Back to cited text no. 15
    
16.
Huang YW, Diao LQ. Study on the relationship between the primary hepatic carcinoma and HBV, HCV infection. Henan J Prev Med 2001;12:133-4.  Back to cited text no. 16
    
17.
Zhang Q, Liao Y, Chen J, Cai B, Su Z, Ying B, et al. Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China. Sci Rep 2015;5:17413.  Back to cited text no. 17
    
18.
Xu Y, Liu H, Wang Y, Hao R, Li Z, Song H. The next step in controlling HBV in China. BMJ 2013;347:f4503.  Back to cited text no. 18
    
19.
Song P. Standardizing management of hepatocellular carcinoma in China: Devising evidence-based clinical practice guidelines. Biosci Trends 2013;7:250-2.  Back to cited text no. 19
    
20.
Wang H, Fang M, Gu X, Ji Q, Li D, Cheng SQ, et al. The intracellular HBV DNAs as novel and sensitive biomarkers for the clinical diagnosis of occult HBV infection in HBeAg negative hepatocellular carcinoma in China. PLoS One 2014;9:e107162.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
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