Mode of transmission , rather than the hepatitis C virus , as a major determinant of poor interpersonal relationships in patients with chronic hepatitis C

Department of Medicine, McGill University, Montreal, Quebec Correspondence: Dr Marc Deschênes, McGill University Health Centre, Royal Victoria Hospital Site, Hepatology Division, Ross Pavilion Room R 2.11, 687 Pine Avenue West, Montreal, Quebec H3A 1A1. Telephone 514-843-1616, fax 514-843-1421, e-mail marc.deschenes@muhc.mcgill.ca Received for publication July 12, 2006. Accepted March 26, 2007 TP La, M Deschênes. Mode of transmission, rather than the hepatitis C virus, as a major determinant of poor interpersonal relationships in patients with chronic hepatitis C. Can J Gastroenterol 2007;21(12):815-819.

Mode of transmission, rather than the hepatitis C virus, as a major determinant of poor interpersonal relationships in patients with chronic hepatitis C Plutôt que le virus de l'hépatite C lui-même, son mode de transmission serait un facteur majeur de la piètre qualité des rapports interpersonnels chez les patients atteints d'hépatite C chronique H epatitis C infection affects over 170 million people world- wide, an overall prevalence of approximately 3% of the world's population (1).While it is well established that the hepatitis C virus (HCV) causes inflammation in the liver, leading to fibrosis, not all signs and symptoms expressed by infected patients can be related to the degree of fibrosis.A number of reports have indicated that symptoms such as fatigue, malaise and depression are common in patients with chronic HCV infection (2-10), but these symptoms cannot be correlated with hepatic histopathological findings or viral load (5,11,12).It has been postulated that this may be a further extrahepatic manifestation of HCV (13)(14)(15)(16)(17).However, little is known whether HCV infection, with this postulated extrahepatic manifestation, has an impact on patients' interpersonal relationships.
The aim of the present study was to assess whether chronic HCV infection, with its known neurocognitive impairment, is associated with impairment in the social functioning of patients.

PATIENTS AND METHODS
The charts of 428 anti-HCV-positive patients and 129 hepatitis B surface antigen-positive patients of one hepatologist at the McGill University Health Centre (Montreal, Quebec) were reviewed.Subjects with other chronic liver diseases were excluded from the study.For each patient, the data were collected from the original consultation document with the hepatologist.The possible predictor variables recorded were age, sex, ethnic background, mode of transmission, presence of decompensated liver disease (defined by Child-Pugh score class B or C) and etiology of liver disease (hepatitis B or hepatitis C).The outcome variables recorded were marital status, living arrangement and employment.Marital status was classified as married (or living in a common-law relationship), single or divorced.Living arrangement was classified as alone, with family or with friends.Employment was classified as employed, unemployed or retired.
The results of patients infected with the HCV were compared with those infected with the hepatitis B virus (HBV).Statistical analysis was performed using Sigma Stat 2.0 (Jandel Scientific, USA).Continuous variables were compared using Student's t test, and categorical variables were compared by χ 2 analysis.P<0.5 was used to define statistical significance.Using the variables of the present study's univariate analysis (Table 1) with a stepwise backward logistic regresion (P<0.10),multiple logistic regression was used to identify the best predictive model.

Patient characteristics
Table 2 shows the demographic characteristics of the patients evaluated.Both groups had similar age and sex distributions.Ethnic background was classified as Caucasian, African Canadian, East Asian and others.The subclass 'others' included Latin American (HCV, 2.1%; HBV, 4.0%), Native Canadian (HCV, 0.7%; HBV, 0%), Middle Eastern (HCV, 3.1%; HBV, 5.7%) and South Asian (HCV, 1.2%; HBV, 4.0%) patients.In the HCV group, Caucasian was the dominant ethnic background (79.8%), whereas in the HBV group the Caucasian background was noted for 44.4% of patients, followed by the East Asian background (36.3%).
Mode of transmission was categorized as intravenous (IV) drug use, blood products and/or solid organs before 1992, and  immigration from high-risk countries.High-risk countries of origin for HBV were countries from Southeast Asia.High-risk countries of origin for HCV were countries from the Middle East and Southern Europe (mostly Southern Italy).Exposure to blood products and past IV drug use were the most common modes of HCV transmission, and most subjects with HBV were from endemic areas.Among 129 IV drug users in the HCV group, 93.1% were Caucasian, 1.5% were African Canadian, 0% were East Asian and 5.3% were labelled as 'others'.All three IV drug use patients in the HBV group were Caucasian.Also, of the 402 HCV and 121 HBV patients with known alcohol status, 159 HCV patients were abstinent from alcohol (40%), compared with 75 of those with HBV (62%).Fortyfive patients with HCV (10%) and 17 with HBV (13%) were known to have decompensated liver disease.

Marital status
Overall, there was no difference observed in the marital status of patients infected with HBV (married [73%], single [21%] and divorced [6%]) versus HCV (married [66%], single [23%] and divorced [10%]) (P=0.20) as well as their frequency of having children (HCV, 63%; HBV, 65%; P=0.76).However, there were major differences among the subgroups, as shown in Table 1.Fewer men with HCV were involved in a meaningful relationship than men with HBV (63% versus 78%; P=0.03), whereas no significant difference was observed between the two groups of women.As well, fewer Caucasians with HCV were married or living in common-law relationships than patients with HCV of other ethnic backgrounds (62% versus 78%; P=0.02).Moreover, significantly fewer past IV drug users with HCV were involved in a meaningful relationship than patients who acquired HCV through other modes (46% versus 70%; P<0.001).
By multivariate analysis, mode of transmission was identified as the only predictor of the patients' marital status (OR 1.91; 95% CI 1.51 to 2.42).In other words, IV drug use was associated with a higher prevalence of not being married or living in a common-law relationship.

Living arrangement
Overall, more patients with HCV lived alone than those with HBV (13% versus 22%; P=0.02).As shown in Table 1, there was no significant difference among the subgroups based on sex.However, more HCV-infected Caucasians lived alone than HCV-infected patients of other ethnic groups (25% versus 10%; P=0.01).Also, many more past IV drug users with HCV lived alone than those who acquired the disease through other modes (40% versus 16%; P<0.001).
By multivariate analysis, mode of transmission and ethnic background were identified as predictors of the patients' living arrangements (mode of transmission -OR 1.58, 95% CI 1.20 to 2.09; ethnic background -OR 1.28, 95% CI 1.06 to 1.54).This means that being Caucasian and/or a past IV drug user with HCV was associated with a higher tendency to live alone.

Employment
In general, there was no difference in the unemployment rate between patients with HCV and those with HBV (19% versus 11%; P=0.09).As shown in Table 1, there was no difference between the subgroups based on ethnic background.However, in terms of sex distribution, more men with HCV were unemployed than men with HBV (21% versus 9%; P=0.04), whereas no significant difference was observed between the female groups.Moreover, regarding mode of transmission, more IV drug users with HCV were unemployed than patients with HCV who acquired it through other modes (36% versus 13%; P<0.001).
By multivariate analysis, mode of transmission was identified as the only predictor of the patients' employment status (OR 3.90; 95% CI 2.24 to 6.80).In other words, being a past IV drug user was associated with a higher probability of being unemployed.

DISCUSSION
As part of our expanding knowledge on HCV since its discovery in 1989, extrahepatic manifestations, such as glomerulonephritis and essential mixed cryoglobulinemia, have been uncovered (18).Compared with patients with other chronic liver diseases, patients living with chronic HCV frequently report a multiple of symptoms that they attribute to their infection.Besides complaints about physical unwellness such as fatigue, malaise, musculoskeletal and right upper abdominal discomfort, they have also reported memory impairment, depression, anxiety and mental clouding (2)(3)(4)(5)(6)(7)(8)(9)(10).
Clinicians have traditionally referred to the degree of inflammation to prioritize who should be treated.Given that quality of life is what drives consultation and that hepatic inflammation is a poor marker for detecting the patients whose quality of life has been significantly affected by HCV, the use of objective markers of inflammation alone is not sufficient.
The extrahepatic symtoms reported from patients have led many researchers to question whether patients with HCV infection have poorer quality of life and social functioning than those with HBV.Not surprisingly, most of the studies have reported a consistent and significant reduction in healthrelated quality of life in patients with chronic HCV compared with population norms (5,6,9,(19)(20)(21)(22).
For instance, Gallegos-Orozco et al ( 9) compared the quality of life of 157 HCV patients, without previous interferon therapy, to historical normal controls using the 36-item Short  Form Symptomatology Questionnaire (SF-36).They demonstrated that the chronic HCV patients in their study scored significantly lower in all eight domains of the SF-36.Similarly, Foster et al (5) used the SF-36 to compare the quality of life of patients with chronic HCV to those with chronic HBV.They showed that patients with HCV had significant reductions in their SF-36 scores for all modalities tested.For the social functioning domain in particular, Foster et al (5) reported that the subjects with chronic HCV perceived themselves to be more unwell than those with HBV.
In the present study, the patients' social functioning was assessed not through any standard questionnaire, but through direct questioning of their marital status, living arrangement and employment status at the time of their first encounter with the hepatologist.To assess patient social functioning, psychiatrists obtained a social history, which included marital status, living arrangement and employment status (23).In Bates' Guide to Physical Examination and History Taking (24), a classic reading for undergraduate medical training, 'significant others', 'home situation' and 'employment' were the first elements in the section on social history.So, for the practical purposes of the medical interview, marital status, living arrangement and employment were judged to be appropriate markers of the patient's social functioning.Language spoken was not assessed per se, but the questioning was simple and completed through an interpreter if needed.The assessed social functioning of the HCV patients was, overall, not significantly impaired.There were no statistical differences in marital status, frequency of having children and unemployment rate between the two groups, but more patients with HCV lived alone than those with HBV.The difference between our findings and previous studies on significantly reduced social functioning of HCV patients suggests that these patients perceive their ability to function more poorly than it is.
In the study by Zickmund et al (25), patients reported having experienced stigmatization, which they attributed to the infection; this was associated with higher anxiety, depression and worse quality of life.Zickmund et al showed concern that the emotionally burdensome experience of stigmatization can erode social support in patients infected with HCV.Our analysis did not support their concern.Indeed, no previous systematic evaluation has been done to study whether HCV infection, per se, has a significant impact on patients' social interactions.Overall, in our study, HCV did not appear to affect social functioning, but the IV drug use subgroup did not function as well, and social sigmatization could not be excluded.
HCV viremia per se, with its known neurocognitive impairment, did not seem to translate into significant problems in the social functioning of our patients.Mode of transmission, not HCV, is the only predictor of patients' marital and employment status.Mode of transmission and ethnic background, not HCV, were predictors of the patients' living arrangements.By multivariate analysis, the most important determinant identified was the mode of acquisition of the infection; past IV drug users performed at a lower level.Past IV drug use, more than HCV, was associated with a higher prevalence of being unmarried, living alone and being unemployed.
In our study, it was obvious that the contrast between social living and behaviours of HCV patients versus HBV patients was more socioeconomic and perhaps cultural than anything else.IV drug users had poor interpersonal relationships, independent of viremia.This finding was consistent with the finding of Foster et al (5), who showed that patients with chronic HCV who had used IV drugs in the past had the greatest impairment in the SF-36 scores.
Our study did have limitations.Viremia was not systematically measured in every patient included in the analysis.However, the presence of a significant risk factor, elevated aminotransferases and a positive anti-HCV test are associated with a high pretest probability, so that, for practical purposes, the patients included in the present analysis could be considered to have HCV viremia.It has been reported that healthrelated quality of life improves when sustained viral response is obtained (26,27).Our study was cross-sectional and did not assess the patients' social functioning longitudinally, or preversus post-treatment.Also, the level of questioning about social function was not elaborated; we did not assess a number of aspects of patients' social functioning, eg, education and hobbies.
Overall, HCV viremia did not seem to translate into significant problems in the social functioning of our patients.Despite the limitations of our study, a recent publication supports our finding that the patients' perceived reductions in functioning did not translate in measurable reduced social function.Schwarzinger et al (28) conducted a study in an Egyptian rural population whose serological status was unknown.They did not find a significant reduction in healthrelated quality of life in patients with chronic HCV compared with uninfected controls.Therefore, we recommend that more detailed qualitative assessments of the patient's quality of life in general, and their social interaction in particular, should be the focus of future studies.

TABLE 1
Comparison of the marital status, living arrangement and employment status among the subgroups of patients with hepatitis C virus (HCV) and hepatitis B virus (HBV)

TABLE 2
Information was not available for every patient, therefore some patients are not included in the presented data; † Included Latin American, Native Canadian, Middle Eastern and South Asian *