East Asian Arch Psychiatry 2012;22:160-8

ORIGINAL ARTICLE

一间本地传染病诊所内华籍慢性乙型肝炎患者的精神病患研究

陈鸿、余枝胜、李常友

Dr Hung Chan, MBBS, MRCPsych, FHKAM (Psychiatry), FHKCPsych, Kwai Chung Hospital, Hong Kong SAR, China.
Dr Chi-Sing Yu, FHKAM (Psychiatry), FHKCPsych, Kwai Chung Hospital, Hong Kong SAR, China.
Dr Sheung-Yau Li, FRCPsych, FHKCPsych, Kwai Chung Hospital, Hong Kong SAR, China.

Address for correspondence: Dr Hung Chan, Kwai Chung Hospital, 3-15< Kwai Chung Hospital Road, Hong Kong SAR, China.
Tel: (852) 9130 8263; email: chanhung@graduate.hku.hk

Submitted: 23 March 2012; Accepted: 4 June 2012

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Introduction

Hepatitis B virus (HBV) infection is a major global health problem, and is one of the commonest infections in the world. The virus can cause both acute and chronic infections in humans. Chronic hepatitis B (CHB) infection is defined as chronic necroinflammatory disease of the liver caused by persistent HBV infection for more than 6 months. Approximately 120 million people living in China have CHB.¹ The prevalence of CHB is more than 10% in South China, including Hong Kong.² Most patients with CHB in this region acquired the infection in the perinatal period or during childhood.³ As newborns are considered to be ‘immune tolerant’, 90% of infected newborns will develop CHB, whereas less than 5% of infected adults will develop CHB.^4-7

Patients with CHB have been found to have significant reductions in both physical and mental health– related functioning.⁸ If CHB is not well treated, 15 to 40% of patients will develop serious sequelae.⁹ Antiviral drugs are prescribed for suppression of HBV replication and remission of liver disease, with the ultimate goal of prevention of cirrhosis, liver failure, and hepatocellular carcinoma (HCC).¹⁰

There have been many studies of psychiatric morbidity in patients with hepatitis C infection in western countries, where it is far more prevalent than hepatitis B infection, while studies for CHB are relatively few. The prevalence rate for psychiatric morbidity is as high as 44.7% for patients with CHB.⁸ Major depressive disorder is the commonest diagnosis among CHB patients, of which the point prevalence is up to 14%.¹¹ Psychiatric morbidity in CHB patients might encourage other behaviours hazardous to health such as smoking, which may further affect health functioning for these patients.¹² Moreover, it has been found that the anxiety state of patients with CHB is negatively correlated with CD4+ and CD4+ / CD8+, which would affect the immune function of patients.¹³

Chronic hepatitis B is prevalent in Chinese societies, but the prevalence of associated psychiatric morbidity has not been adequately investigated. The study aimed to explore the prevalence of psychiatric morbidity in Chinese HBV-infected patients attending a local specialist infectious disease (ID) clinic. The correlates of current psychiatric disorders, current depressive disorders, and current anxiety disorders were also examined. This is also the first local study to examine the psychiatric morbidity of Chinese patients with CHB infection in Hong Kong.

Methods

Study Design

This was a cross-sectional study conducted in a public specialist outpatient ID clinic at the Princess Margaret Hospital (PMH) of the Hospital Authority in Hong Kong from October 2008 to June 2009. The clinic acts as a major local centre for the management and isolation of patients with ID. Providing treatment for patients with viral hepatitis is one of its major roles. Patients with complications of cirrhosis or HCC are referred to other hepatology clinics. Approval for conducting the present study was obtained from the hospital’s Clinical Research Ethics Committee.

Patients

Patients who attended the ID clinic from September 2007 to September 2008 with a confirmed diagnosis of HBV infection, and without other viral hepatitis virus or human immunodeficiency virus co-infection were included in the randomised sampling. According to the prevalence rate for major depressive disorders found in a previous study,¹¹ 160 patients were needed for the study. Each patient was assigned a number, and a computerised random number generator was used to generate 160 samples out of 1144 patients. They were recruited on the day when they attended the ID clinic for routine clinical follow-up. Patients were excluded if they were not Chinese, unable to understand Cantonese, or illiterate. Patients with dementia, mental retardation, or communication difficulties who were unable to give informed consent were also excluded.

Procedure

The selected potential patients were approached by one of the authors on the day of their scheduled follow-up visit. All patients aged ≥ 60 years or suspected of having cognitive impairment affecting their capacity to give valid consent were screened for dementia with the Mini-Mental State Examination (MMSE). Patients with MMSE scores of < 22 were excluded.¹⁴ A 12-item General Health Questionnaire was completed by the patients. Demographic and clinical data were collected by the author from the patients and from their medical records.

The Chinese-Bilingual Structured Clinical Interview for the DSM-IV (Axis I, Patient version) [SCID]¹⁵ was administered by the author who has completed the required training in using the instrument.

Data Analyses

All statistical analyses were performed using the Statistical Package for the Social Sciences, Windows version 15.0 (SPSS Inc., Chicago [IL], US). Descriptive statistics were performed using the socio-demographic and clinical data. Student t test was used to compare the means of continuous variables in 2 independent samples when the data were normally distributed or the assumptions for the t test were met. Pearson Chi-square test for independence was used to analyse the association between nominal variables and dichotomous independent variables in contingency tables. Fisher’s exact test was employed if the assumptions for the Chi-square test were not fulfilled. The variables employed included sex, age, marital status, dependent children, living arrangements, education level, employment status, job satisfaction, family income, receipt of government allowance, duration of known HBV infection, clinical stage of HBV infection, religion, antiviral treatment and herbal medicine used, knowledge of mode of infection, co-morbidities, forensic record, suicidal attempt, history of psychiatric illness, family history of psychiatric illness, confidant support, and contact hours with the confidant.

The diagnoses of major depressive disorder, depressive disorder (not otherwise specified), dysthymic disorder, and adjustment disorder with depressed mood were grouped under the category of depressive disorders. Similarly, the diagnoses of panic disorder, agoraphobia, social phobia, generalised anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, specific phobia, adjustment disorder with anxiety symptoms, and anxiety disorder (not otherwise specified) were grouped under the category of anxiety disorders. The variables were compared between: (1) CHB patients with current psychiatric disorders of any type and those without any current psychiatric disorders diagnosed by SCID; (2) CHB patients with current depressive disorders and those without any current psychiatric disorders diagnosed by SCID; and (3) CHB patients with current anxiety disorders and those without any current psychiatric disorders diagnosed by SCID.

Two-tailed analyses were used in all tests. Variables with significant association with psychiatric illnesses (i.e. p < 0.2) were entered into binary logistic regression to examine the impact of different variables on current psychiatric disorders, depressive disorders, and anxiety disorders. Multicollinearity among entered variables was considered if the variance inflation factor was above 2.5. Adjusted odds ratio (OR) and 95% confidence interval were calculated. The OR represented the relative odds of having current psychiatric disorders, depressive disorders, and anxiety disorders when the value of the associated factor increased by 1 unit. All tests for statistical significance were set at 0.05.

Results

Recruitment of Patients

Among the 160 selected patients, 6 did not attend for follow-up, 3 were excluded because of low MMSE scores and dialect problems, and 2 refused to participate in the study. Thus, 149 patients were recruited with a response rate of 93.1%. No statistically significant differences were found for age (t = 1.209; p = 0.23) and sex (χ² = 2.803; p = 0.10) between randomly selected patients and those who did not attend for follow-up. There were also no statistically significant differences for age (t = 1.509; p = 0.13) and sex (Fisher’s exact test, p = 0.51) between patients who participated and those who did not though they had been selected. The socio-demographic variables of the patients are shown in Table 1.

Clinical Characteristics and Co-morbid Chronic Illness of the Patients

Of these 149 patients, most (n = 124; 83%) had known that they were infected with HBV for more than 5 years. In all, 90 (60%) of the patients had uncomplicated CHB, 44 (30%) had impaired liver function, and 15 (10%) had cirrhosis of the liver or a history of HCC.

A total of 90 patients (60%) were being treated with antiviral medications; among these, 32 (36%) were treated with lamivudine and 16 (11%) were treated with combination therapy, of which lamivudine and adefovir was the most common type. Besides, 20 patients (13%) had used herbal medicine specifically for the health of their liver in the previous month. None of the patients were taking propranolol or spironolactone.

All of the patients understood that HBV was infectious, however, 81% did not know how they were infected. Besides, about one-third (n = 50) could not correctly give any of the modes of HBV transmission. For those who knew the mode of viral transmission, blood (n = 32) was the most well-known transmission medium.

In all, 55 patients (37%) had 1 or more co-morbid diseases, of which the most common was diabetes mellitus (n = 20; 13%). The functional status of the patients was satisfactory. There was only 1 who walked with aids and all 149 patients were independent in activities of daily living.

A psychiatric history was found in 12 patients (8%). Among these, 7 (5%) had depressive disorders, 4 (3%) had anxiety disorders, and 1 (0.7%) had psychotic disorders. Only 5 (3%) were actively receiving treatments for mental illness. Besides, 21 patients (14%) had first-degree relatives with a history of psychiatric illness. The most common diagnosis was depressive disorder which contributed to more than half of the cases.

About three-quarters of the patients (n = 112) had confidant(s) who could share their distress with them. The contact time varied considerably from 1 to 28 hours per week, with a mean (standard deviation) of 6.80 (4.02) hours per week.

Prevalence of Psychiatric Morbidity

The point and lifetime prevalences of psychiatric morbidity are summarised in Table 2. The point prevalence of psychiatric disorders was 32% (29% in male and 40% in female). Six patients (4%) were diagnosed to have 2 concurrent psychiatric disorders.

Current depressive disorders were the commonest diagnostic category. Its point prevalence was 16% (11% in male and 27% in female). Major depressive disorder was the commonest diagnosis (n = 15), among whom 5 had recurrent episodes.

The point prevalence of anxiety disorders was 14% (15% in male and 13% in female). Generalised anxiety disorder was the commonest type with a point prevalence of 5% (6% in male and 4% in female).

Three patients (2%) had a current diagnosis of alcohol abuse and 1 (0.7%) had a current diagnosis of schizophrenia.

Correlates of Psychiatric Morbidity

Univariate Analysis

Comparisons between the patients with current psychiatric disorders, current depressive disorders, and current anxiety disorders and those without these 3 types diagnosed by SCID are summarised in Table 3. Patients with current psychiatric, depressive, or anxiety disorders were found to have a higher prevalence of family history of psychiatric illness and absence of knowledge of HBV transmission.

Patients whose total family income was less than HKD10,000, with absence of a confidant, and currently not working were more likely to have psychiatric and depressive disorders, but not anxiety disorders. A higher rate of herbal medicine use in the previous month was found among patients with psychiatric disorders and anxiety disorders, but this was not associated with depressive disorders.

Female sex and receipt of social security allowance were associated with depressive disorders, but these associations were not observed for anxiety or psychiatric disorders.

There were no statistically significant differences between the 3 groups of patients with and without current psychiatric disorders in the following aspects: clinical stage of HBV infection, different antiviral medications used, duration of knowledge of known CHB, medical history, history of psychiatric illness, and contact hour(s) with a confidant.

Regression Analysis

In the second stage of statistical analysis, factors associated with psychiatric disorders, depressive disorders or anxiety disorders with p values of < 0.2 in the t test, Chi-square test or Fisher’s exact test were entered into logistic regressions. No multicollinearity among factors was found. The results are summarised in Table 4.

Two independent factors, a family history of psychiatric disorder and absence of knowledge of HBV transmission mode, were identified as being associated with current psychiatric disorders, current depressive disorders, and current anxiety disorders. Absence of a confidant was an independent factor for current depressive disorders, and use of herbal medicine for the liver in the previous month was an independent factor for anxiety disorders.

Discussion

Prevalence of Psychiatric Morbidity

Overall Psychiatric Disorders

The point prevalence of psychiatric disorder was 32% in this study, consistent with previous studies^8,11 using the standardised research interview method.

Among the CHB patients with psychiatric morbidities, depressive disorders and anxiety disorders were the major diagnoses, which are also consistent with previous studies.^8,11 The point prevalence of depressive disorders (16%) was slightly higher than that of anxiety disorders (14%). For individual psychiatric disorders, major depressive disorder (10%) was the predominant diagnosis in this study, which is the same as in previous studies,^11,16 but in contrast to those reported in studies on the side-effects of pegylated interferon (peginterferon) in CHB patients,^17,18 in which psychiatric morbidity was reported to be uncommon among patients with CHB.

Due to a significant proportion of CHB patients having psychiatric morbidities, the psychiatric health of CHB patients should not be overlooked. However, among the 48 patients who were diagnosed with current psychiatric disorders, only 10% of them were receiving psychiatric treatment. Under-recognition of psychiatric morbidity is not an uncommon phenomenon, and has been found in similar local studies of psychiatric morbidity in other medical illnesses.^19,20 Thus, more attention should be paid to recognising psychiatric morbidities in this group of patients.

Depressive Disorders

The point prevalence of major depressive disorder was 10%, which is consistent with the estimated prevalence of 6.4 to 14.0% in other similar studies.^8,11 This prevalence is higher than that reported in the peginterferon studies.^17,18 This discrepancy can be explained by the different instruments employed for defining depression. When comparing the findings with the local epidemiological data from the Shatin Community Mental Health Survey,²¹ CHB-infected Chinese patients had a higher rate of depression than the general population.

The point prevalence of depressive disorders (16%) is similar to that in studies of Chinese patients with other medical illnesses, such as rheumatoid arthritis by using SCID interviews.²² This finding suggests that the prevalence of depression in CHB patients is not lower than those with other medical illness.

There are hypotheses as to why depression is common in patients with chronic hepatitis. It has been postulated that the stress from having this potentially life- threatening illness made patients vulnerable to depression⁸; the infectious characteristic and social isolation might be reasons for the higher rate of psychiatric disorders among this group of patients.¹¹ Changes in immune function in CHB patients may lead to depression, but further research should be conducted to investigate this hypothesis.

Anxiety Disorders

In our study, the point prevalence of anxiety disorder was 14%, slightly higher than that in 2 Turkish studies, of which the respective point prevalence was 10.6% and 9.3%.^8,11 Patients in the Turkish studies had better educational backgrounds, and those in the latter study¹¹ were informed about the transmission modes and preventive measures on hepatitis B prior to the study. Having sufficient information about transmission of the virus may lead to a reduction of anxiety about its transmissibility, which is a major concern of patients.²³ This may explain a lower prevalence of anxiety disorder in the above Turkish study.¹¹

Concerning the different types of current anxiety disorder in CHB patients, the commonest was generalised anxiety disorder (5%), the figure of which was higher than the 6-month prevalence of 4.1% in the general population in a local study.²⁴ However, the diagnostic criteria of generalised anxiety disorder were modified, with the requirement of ‘excessive worries’ being removed in the latter study,²⁴ as the authors believed that excessiveness is unduly restrictive. If the original DSM-IV criteria were employed, the prevalence of generalised anxiety disorder in the general population could have been lower by as much as 40%.²⁴ Thus, the difference in the prevalence rate of generalised anxiety disorder between patients with CHB and the general population would have been greater if both studies employed the same criteria.

Factors Associated with Psychiatric Morbidity

Given the high prevalence of psychiatric morbidity, it is useful to look into the associated factors, so that high-risk patients can be identified for early referral and treatment. In this study, several independent factors were identified.

Knowledge of Hepatitis B Virus Transmission Mode

In this study, 81% of patients did not report knowledge of how they were infected, and 34% could not accurately name any mode of HBV transmission. This result reflected inadequate knowledge of HBV among the patients. This is common worldwide. Many misconceptions about the modes of HBV transmission exist among patients.²⁵ In a study of Chinese patients who had emigrated to America in 2005, less than one-quarter knew that HBV could be spread by eating food that was prepared by an infected person and by sharing eating utensils with an infected person.²⁶ A similar conclusion was drawn in a study of Canadian Chinese patients with HBV.²⁷ This finding is not limited to Chinese people living in western countries. In a study from Singapore in 2007, many Singaporeans held misconceptions about HBV, especially with regard to the mode of transmission,²⁸ which might lead to excessive or unnecessary worry during daily activities. This factor was significantly associated with overall psychiatric disorders, depressive disorders and anxiety disorders, with adjusted odd ratios of 3.828, 3.294, and 3.325, respectively. As demonstrated in the study by Kunkel et al,²⁹ the continuation of worry about transmission to others has also been shown to have an association with depression.

Use of Herbal Medicine

Among Chinese societies in Hong Kong, people like to use Chinese medicine as a complementary medicine to maintain health. According to a local study on the habit of taking Chinese herbal medicine, more than 90% of patients used Chinese herbal remedies on a regular basis before an operation.³⁰ It is believed that most herbal medicines, being of ‘natural’ origin, are harmless and have no side-effects.³¹ Additionally, many products claim that they can boost or maintain the health of the liver. In this study, 13% of patients had taken herbal medicine in the previous month specifically for the health of their liver. This finding is similar to another local study of CHB patients in an outpatient setting³² that around 16% of the patients were actively using Chinese herbal medicine for liver disease, and more than 40% of those patients considered it effective or very effective. In the present study, this habit was significantly associated with the presence of current anxiety disorder, consistent with the results of a local study of patients with systemic lupus erythematosus.²⁰ The association of current anxiety disorder is seldom discussed in previous studies of HBV infection, and the reason for this association should be further evaluated. It seems that herbal medicine causing psychiatric disorders is unlikely as many different kinds of herbs have been taken by patients. However, it could be postulated that patients with this habit may be reflecting their higher level of worry about their illness progression. Patients were willing to pay extra money in the hope that the alternative medicine would help to treat the liver disease.

Taking complementary medicine without directions from a physician should not be encouraged as certain herbs or health food could aggravate hepatitis.³³ Local physicians actively advise CHB patients not to take herbal medicine. Some evidence suggested that psychosomatic symptoms were predictive of complementary medicine use.³⁴ This provides an indication that treating psychiatric illness in CHB patients may reduce the use of complementary medicine.

Perceived Absence of Confidants

The perceived absence of confidants, but not the mean contact time with confidants, was found to be significantly associated with current depressive disorders. This suggests that having the feeling of ‘not being alone’ or ‘not being socially isolated’ may be important in relieving psychological distress. This factor has not been directly discussed in previous studies of HBV infection, but this finding is consistent with another local study of breast cancer patients.¹⁹

The infectious characteristics of HBV, inadequate knowledge about the transmission modes, and undue anxiety about the transmissibility of the virus may lead to isolation of patients.²³ In a study of Korean immigrants, 34% of patients avoided social relationships.²⁹ This finding is supported by the results of this study in that perceived absence of a confidant was found to be significantly associated with current depressive disorders. In other studies, social isolation was found to be a risk factor for developing depression,^35,36 particularly in later life.

Clinical Factors not Associated with Psychiatric Morbidity

There was no association between different antiviral treatments used and psychiatric morbidity in this study. This finding contrasts with other studies showing that peginterferon causes depression as a side-effect.^17,18 This can be explained in 2 ways. First, the definition of depression was different between the studies. Second, the number of patients receiving peginterferon as antiviral treatment was low (n = 4) in this study, because of the unsatisfactory response in patients infected with HBV³⁷ and it is an expensive self-financed item. The small number of patients in this sub-group may have affected the statistical significance of this association.

Although higher prevalences of psychiatric disorders were expected in association with more severe clinical stages, e.g. cirrhosis or HCC, this is not particularly well shown. Some studies only employed virus carriers or pre-cirrhotic patients,^8,11 and only 1 study employed a heterogeneous group of patients at different stages of illness to detect psychiatric morbidity.²⁹ The association between clinical stage and psychiatric morbidity was not established in this study, consistent with the study by Kunkel et al.²⁹ However, this result should be interpreted with caution as the sample sizes of the sub-groups were imbalanced in both studies.

Clinical Implications

This study showed that psychiatric morbidities were common among CHB patients of a local specialist ID clinic. However, only 10% of patients with psychiatric disorders were receiving active psychiatric treatment. Chronic hepatitis B, as the name implies, is a chronic medical illness. Depression can impair functioning.¹¹ Chronic hepatitis B patients with depression have a significant reduction in quality of life when compared with those without.⁸ Early detection of psychiatric disorders is important as clinical interventions are effective for both depression and anxiety.

This study recognises factors associated with psychiatric disorders in CHB patients. More attention should be paid to patients with a family history of psychiatric illness, absence of knowledge of mode of HBV transmission, absence of a confidant, and use of herbal medicine to treat the liver in the previous month as these factors are associated with psychiatric morbidities. Intervention of educating CHB patients to improve their knowledge of transmission modes and the risk of transmitting the virus through different modes may help reduce the feeling of unnecessary worry about this illness.

Limitations

There are several limitations to this study. First, the cross- sectional design did not allow the establishment of a causal relationship. The patients of this study were recruited from single specialist ID clinic. Thus, the findings might not be generalisable to CHB patients treated in other settings. Further studies can be carried out by recruiting Chinese patients in different settings. Regarding the prevalence of psychiatric disorders, there was no control group for comparing CHB patients with those without this disease.

The relatively small sample size of the respective groups with depressive disorders and anxiety disorders may have affected the statistical power of this study to detect any differences between groups regarding the independent factors. Due to the small number of patients with concurrent psychiatric diagnoses, they were not analysed as a separate group.

A number of variables such as personality and detailed social support assessment were not measured in this study. These factors may be important in predicting psychiatric disorders. However, it was not possible to employ too many questionnaires in a single study, as this may have affected the response rate and the dropout rate of patients could be high if too many questionnaires were required to be completed.

Conclusion

This study is the first to offer data on psychiatric morbidity among the local Chinese CHB patients using a structured diagnostic interview. The results suggest that psychiatric disorders are common in CHB patients in an ID clinic in Hong Kong. Depressive disorders and anxiety disorders are the commonest psychiatric disorders, while major depressive disorder is the commonest specific psychiatric disorder. Several factors were identified and shown to have a significant association with current psychiatric, depressive, and anxiety disorders. Identification of these factors can help physicians to recognise and manage psychiatric disorders among CHB patients. Further research with a prospective design is suggested to examine the causal relationship between the associated factors and psychiatric disorders among CHB patients.

Acknowledgements

We are most grateful to Dr Sik-To Lai, Team Head of the Infectious Disease Team of Princess Margaret Hospital and Dr Man-Kit So, Senior Medical Officer of the Infectious Disease team. It would have been impossible to have accomplished this study without collaborating with their clinical team. I would like to convey my appreciation to Prof Helen Chiu for granting permission to use the Chinese- Bilingual SCID Axis I Disorders in this study.

Declaration

The authors declare that they have no source of financial support for the study.

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