No association between schizophrenia and female hepatocellular carcinoma: a case-control study in Taiwan

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Date 2013/June/17

 Type of manuscript：Research article

 Manuscript title: No association between schizophrenia and female hepatocellular carcinoma: a case-control study in Taiwan

 Running head：schizophrenia and hepatocellular carcinoma  Authors' full names:

 Shih-Wei Lai1,2_{, Cheng-Li Lin}3,4_{, Kuan-Fu Liao}5,6,7

 1_{School of Medicine,}_{China Medical University and}2_{Department of} Family Medicine, China Medical University Hospital, Taichung, Taiwan  3_{Department of Public Health, China Medical University and}

4_{Management Office for Health Data, China Medical University} Hospital, Taichung, Taiwan

 5_{Graduate Institute of Integrated Medicine, China Medical University,} Taichung, Taiwan

 6_{Department of Internal Medicine, Taichung Tzu Chi General Hospital,} Taichung, Taiwan

 7_{Department of Health Care Administration, Central Taiwan University} of Science and Technology, Taichung, Taiwan

 Corresponding author: Kuan-Fu Liao, Department of Internal Medicine, Taichung Tzu Chi General Hospital, No.66, Sec. 1, Fongsing Road, Tanzi District, Taichung City, 427, Taiwan

Phone: 886-4-2205-2121 Fax: 886-4-2203-3986

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ABSTRACT

Objective: This study was to investigate the relationship between schizophrenia and hepatocellular carcinoma in women in Taiwan.

Design: We designed a case-control study by analyzing the database from the Taiwan National Health Insurance program.

Subjects: There were 922 female subjects aged 40 years or older with newly diagnosed hepatocellular carcinoma as the case group and 3688 female subjects aged 40 years or older without hepatocellular carcinoma as the control group.

Main outcome measure: The risk of hepatocellular carcinoma was compared between cases and controls.

Results: After controlling for confounding factors, multivariable logistic regression analysis showed that the odds ratio of hepatocellular carcinoma was 1.82 (95% CI =0.64, 5.18) in subjects with schizophrenia, when compared with non-schizophrenia subjects.

Conclusions: No association is detected between schizophrenia and hepatocellular carcinoma in women in Taiwan.

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INTRODUCTION

In order to investigate the relationship between schizophrenia and

hepatocellular carcinoma in women in Taiwan, we designed a case-control study by controlling for the confounding factors of hepatocellular carcinoma. The database from the Taiwan National Health Insurance program was analyzed. The previous studies have documented the details of this insurance program.

MATERIALS AND METHODS

There were 922 female subjects aged 40 years or older with newly diagnosed hepatocellular carcinoma as the case group (mean age 70.98 years and standard deviation 8.43 years) from 2000 to 2010 (based on International Classification of Diseases 9th_{Revision-Clinical Modification, ICD-9 155, 155.0} and 155.2) and 3688 female subjects without hepatocellular carcinoma as the control group (mean age 70.41 years and standard deviation 8.84 years). Both groups were matched with age (every 5 years) and index year. We defined the index date as the date of diagnosing hepatocellular carcinoma. Schizophrenia(ICD-9 295 and V11.0) and other co-morbidities were

diagnosed before the index date. We excluded all subjects with any cancer diagnosed before the index date (ICD-9 140-208).

RESULTS

There were 10 subjects with schizophrenia among hepatocellular carcinoma cases (1.08%) and 30 subjects with schizophrenia among control subjects

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hepatitis C infection (41.54% vs. 1.95%) than those in the control group, with statistical significance (Chi-square test for P <0.0001). After controlling for cofounding factors, multivariable logistic regression analysis showed that the odds ratio of hepatocellular carcinoma was 1.82 (95% CI =0.64, 5.18) in subjects with schizophrenia, when compared with non-schizophrenia subjects (Table 1).

DISCUSSION

To date, no consistent results exist about the relationship between schizophrenia and risk of hepatocellular carcinoma. Lichtermann et al in Finlandreported that no significant association is detected between

schizophrenia and hepatocellular carcinoma (standardized incidence ratio = 1.55, 95%CI= 0.67, 3.04). In contrast, Chou et al in Taiwan reported that female schizophrenia patients have lower risk of hepatocellular carcinoma (hazard ratio= 0.5, 95%CI= 0.35, 0.73). In this present study, after adjusted for the key confounding factors of hepatocellular carcinoma, no association is found between schizophrenia and hepatocellular carcinoma in women. This means that both diseases have their unique pathogenesis beyond existing knowledge. Moreover, only 40 female schizophrenia subjects were included. That is, the number is too small to achieve statistical significance.

Because of presence of conflicting results, further studies with more cases are needed to clearly determine the relationship between schizophrenia and hepatocellular carcinoma in women.

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ACKNOWLEDGEMENTS

The authors thank the National Health Research Institute in Taiwan for providing the insurance claims data.

Conflict of Interest Statement: The authors disclose no conflicts of interest

Funding:

This study was supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW103-TDU-B-212-113002). The funding agency did not influence the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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REFERENCES

[1] Lai SW, Liao KF, Liao CC, Muo CH, Liu CS, Sung FC. Polypharmacy correlates with increased risk for hip fracture in the elderly: a population-based study. Medicine (Baltimore). 2010;89:295-9.

[2] Lai SW, Chen PC, Liao KF, Muo CH, Lin CC, Sung FC. Risk of

hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study. Am J

Gastroenterol. 2012;107:46-52.

[3] Lichtermann D, Ekelund J, Pukkala E, Tanskanen A, Lonnqvist J. Incidence of cancer among persons with schizophrenia and their relatives. Arch Gen Psychiatry. 2001;58:573-8.

[4] Chou FH, Tsai KY, Su CY, Lee CC. The incidence and relative risk factors for developing cancer among patients with schizophrenia: a nine-year follow-up study. Schizophr Res. 2011;129:97-103.

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Table 1. Odds ratio and 95% confidence interval of hepatocellular carcinoma associated with Schizophrenia and other co-morbidities

Crude Adjusted †

Variable OR (95%CI) OR (95%CI)

Age (per one year) 1.01 (0.999, 1.02)

Co-morbidities before index date (yes vs. no) * Schizophrenia 1.34 (0.65, 2.75) 1.82 (0.64, 5.18) Diabetes mellitus 1.69 (1.45, 1.96) 1.09 (0.86, 1.38) Cirrhosis 120.78 (89.06, 163.81) 49.32 (35.67, 68.20) Alcoholic liver damage 4.31 (2.17, 8.57) 1.00 (0.32, 3.14) Other chronic hepatitis 8.61 (7.34, 10.10) 2.09 (1.62, 2.70) Hepatitis B infection 19.25 (13.70, 27.04) 5.63 (3.50, 9.06) Hepatitis C infection 35.69 (27.31, 46.63) 8.41 (5.84, 12.11) † _{Adjusted for diabetes mellitus, cirrhosis, alcoholic liver damage, other chronic}

hepatitis, hepatitis B infection and hepatitis C infection

*_{The co-morbidities included before index date were as follows: Schizophrenia} _(ICD-9 295 and V11.0), diabetes mellitus (ICD-9 250), cirrhosis (ICD-9 571.2, 571.5 and 571.6), alcoholic liver damage (ICD-9 571.0, 571.1 and 571.3), other chronic hepatitis (ICD-9 571.40, 571.41, 571.49, 571.8 and 571.9), hepatitis B infection (ICD-9 V02.61, 070.20, 070.22, 070.30 and 070.32) and hepatitis C infection (ICD-9 V02.62, 070.41, 070.44, 070.51 and 070.54)