Fatigue and depressive symptoms associated with chronic viral hepatitis patients health-related quality of life (HRQOL)

Transcription

1 Chronic virl heptitis nd HRQOL., 2010; 9 (4): ORIGINAL ARTICLE October-December, Vol. 9 No.4, 2010: Ftigue nd depressive symptoms ssocited with chronic virl heptitis ptients helth-relted qulity of life (HRQOL) Kterin Krivzoglou,* Gregoris Iconomou,* Christos Trintos,** Thoms Hyphntis,*** Konstntinos Thomopoulos,** Mri Lgdinou,**** Chrlmbos Gogos,**** Chryssoul Lbropoulou-Krtz,** Konstntinos Assimkopoulos* * Deprtment of Psychitry, University of Ptrs School of Medicine, Rion Ptrs, Greece. ** Deprtment of Internl Medicine (Heptology Unit), University of Ptrs School of Medicine, Rion Ptrs, Greece. *** Deprtment of Psychitry, Medicl School, University of Ionnin, Greece. **** Deprtment of Internl Medicine (Infectious Diseses Unit), University of Ptrs School of Medicine, Rion Ptrs, Greece. ABSTRACT Bckground nd rtionle. It is well estblished tht chronic virl heptitis (CVH) negtively ffects ptients helth-relted qulity of life (HRQOL). The im of the present study ws to ssess the extent to which ftigue nd depressive symptoms re ssocited with CVH ptients HRQOL. Methods. Eighty-four dult CVH outptients [45 with heptitis B virus (HBV) nd 39 with heptitis C virus (HCV) infection] prticipted in the study. The Short Form-36 Helth Survey (SF-36), the Beck Depression Inventory-II (BDI-II) nd the Ftigue subscle of the Functionl Assessment of Cncer Therpy-Anemi Scle (FACT-F) were used to ssess HRQOL, depression nd ftigue, respectively. Results. All spects of HRQOL perceived by CVH ptients were significntly impired compred to the generl popultion, s comprison with Greek popultion-bsed normtive dt reveled. HBV ptients presented similr HRQOL with HCV ptients. Clinicl prmeters including infection ctivity, fibrosis stge or inflmmtion grde, s well s depressive symptoms nd ftigue were found to be significntly ssocited with HRQOL. Multivrite nlyses showed tht older ge (p <0.001) nd higher ftigue scores (p <0.001) were the vribles most closely ssocited with the physicl HRQOL, wheres higher rtes on depressive symptoms (p <0.0005) nd ftigue (p <0.020) scles were the vribles most closely ssocited with the mentl HRQOL. Conclusions. In conclusion, CVH is ssocited with impired HRQOL. Ftigue nd impired psychologicl functioning is ssocited with diminished HRQOL in CHV, independent of the disese etiology. Consequently, mngement of ftigue nd depressive symptoms should be considered priority, in order to improve HRQOL in CVH ptients. Key words. CVH. HRQOL. Ftigue. Depression. INTRODUCTION Chronic virl heptitis (CVH) ffects sizeble proportion of ptients, who re referred to Heptology Deprtments seeking specilized cre. 1 The mngement of the disese requires multi-disciplinry pproch, considering both biologicl nd psychosocil spects. Although CVH usully runs n symptomtic course or is ccompnied by minor non specific symptoms, there re proportion of ptients with dvnced disese who present serious complictions. In Correspondence nd reprint request: Kterin Krivzoglou, MD Deprtment of Psychitry, University of Ptrs School of Medicine Rion Ptrs, Greece Tel.: E-mil: krivz@hotmil.com Mnuscript received: July 18, Mnuscript ccepted: August 30, ddition, the dignosis of CVH seems to exert lbelling effect on ptients, 2-4 modifying their wy of living, incresing their psychologicl burden 5-10 nd negtively ffecting their well-being. 1,7,9-13 Furthermore, ntivirl tretment hs been found to ugment psychitric co-morbidity nd dversely ffect severl domins of HRQOL, which could compromise ptients continuity of cre, dherence to medicl dvice, nd even their prognosis A resent comprehensive review by Foster 19 showed tht independently of liver disese, heptitis C (HCV) infection reduces the HRQOL of most chroniclly infected ptients. Surprisingly few studies, however, hve ssessed the HRQOL of chronic heptitis B ptients (HCB). 1,11,20 A recent study of Tillmnn, et l., 21 reported tht HCV-positive ptients scored worse in the mentl spects of HRQOL compred to other liver diseses, except for heptitis B infection

2 420 Krivzoglou K, et l., 2010; 9 (4): (HBC). In the ltter study, HRQOL ws lso significntly impired in ptients with virl clernce fter interferon therpy but not fter spontneous clernce, indicting the complex interply between severl disese nd tretment-relted prmeters with psychologicl distress nd other psychosocil fctors in the formtion of CVH ptients HRQOL. Given, however, tht HRQOL hs now been identified s n outcome of gret importnce in reserch nd clinicl prctice in severl diseses, the investigtion of its determinnts emerges s significnt necessity. 22 Severl studies hve ttempted to link HRQOL impirment of heptitis ptients to specific demogrphic, clinicl nd psychosocil prmeters of the disese. However, the existing evidence is suggestive rther thn conclusive, s there re still conflicting findings bout the extent to which ech prmeter independently contributes to HRQOL. Certin reserchers hve ssocited severity of liver disese nd presence of cirrhosis with greter impirment in HRQOL, 1,23,24 but others found tht no such reltionships exist. 9,11 Other clinicl indices of liver disese including ALT levels, virus type nd virl lod were lso found not relted to HRQOL impirment. 1,9,11-12,25 With respect to gender differences, recent investigtions hve indicted tht HCV-infected women present with decresed levels of physicl, emotionl nd socil well being compred to men. 18,26 The discrepncies between studies could be ttributed to the method nd timing of ssessment, nd heterogeneous CVH popultions. On the other hnd, ftigue, depression nd cognitive impirment re mong the most common complints of ptients nd occur independently of liver disese or tretment sttus; 11,19,27-30 ll these symptoms hve the potentil to impir ptients bility to function t work or in society. 5,19,31 Severl studies hve shown tht psychosocil distress symptoms, ftigue nd medicl co-morbidity re ssocited with CVH ptients HRQOL. 9,10,23,32-34 However, most of these studies focus on HCV-infected ptients nd scrce studies investigted the impct of these prmeters in HCB-infected ptients HR- QOL. 10,35 In ddition, lthough it is well known tht, prt from its physicl origins, ftigue could lso be mnifesttion of psychologicl disturbnces including depression, 34,36,37 very few studies investigted the concurrent impct of both depression nd ftigue on CVH ptients HRQOL. 34 Thus, further reserch is needed to ssess the complex reltionships between clinicl prmeters, ftigue nd psychologicl distress symptoms with HRQOL impirment nd its implictions, s hs been suggested. 38 Prompted by these fcts, the im of the present study ws to investigte the independent reltionships of demogrphic, clinicl nd psychologicl distress vribles with HRQOL in smple of Greek ptients infected with chronic virl heptitis, nd whether both ftigue nd depressive symptoms re independently ssocited with severl spects of HR- QOL in both HCV- nd HBC-infected ptients. It should be noted tht heptitis B remins mjor helth priority in Western Blkns. 39 In ddition, evidence suggests tht ethnicity nd socil prmeters my influence heptitis ptients HRQOL. 34,40 Since studies hve shown tht Greek ptients dopt illness behviour nd pssive ttitude towrds their well-being which is lrgely influenced by psychosocil prmeters compred to other Europen citizens, 41 we mintin tht ssessing psychosocil fctors ssocited with HRQOL in CVH ptients of different socil nd culturl bckground in which heptitis B is still mjor helth priority, my expnd the clinicl usefulness of the existing evidence nd could contribute to devising pproprite tretment strtegies tht would enhnce ptients totl functioning. METHOD Prticipnts nd procedure The current study ws conducted t the Heptology Unit nd t the Infectious Diseses Unit, Deprtment of Internl Medicine of the University of Ptrs Medicl School, Greece between My 2004 nd September The study protocol ws pproved by the Institutionl Review Bord of the University Hospitl of Ptrs, nd ll prticipnts gve written informed consent before study entry. Mle nd femle consecutive outptients ged 18 yers or older, infected with chronic heptitis B or C, were pproched during their scheduled visit to the Heptology Unit nd invited to tke prt in the study. Prticipnts were selected fter thorough screening of their medicl records to exclude co-morbid fctors tht could independently impir HRQOL. Exclusion criteri were: illicit drug use or lcohol buse during the lst 12 months, current tretment with psychotropic mediction, stroke, cncer, cerebrovsculr disese, mentl retrdtion, dementi, seizure disorder, HIV infection, other chronic liver disese, cirrhosis, child B/C, heptic encephlopthy, interferon tretment during the lst six months, nd lck of fluency in the Greek lnguge. Heptitis B nd heptitis C dignosis ws confirmed bsed on criteri published by the Americn Assocition for the Study of Liver Diseses. 42,43

3 Chronic virl heptitis nd HRQOL., 2010; 9 (4): Instruments HRQOL ws ssessed using the Short Form 36 Helth Survey (SF-36). It is self-report, generic HR- QOL instrument, which includes eight multi-item scles (36 items) tht evlute the extent to which n individul s helth limits his or her physicl, emotionl, nd socil well-being. The SF-36 covers eight domins of HRQOL, nmely physicl functioning, role limittions due to physicl problems, bodily pin, generl helth perception, vitlity, socil functioning, role limittions due to emotionl problems, nd mentl helth. Scores on ech subscle rnge from 0 to 100, with higher scores indicting better HRQOL results. 44 Summry scores for physicl helth (physicl component score-pcs) nd mentl helth (mentl component score-mcs) cn lso be derived. 45 SF-36 hs been widely used in liver disese nd hs exhibited stisfctory psychometric properties. 1,10,11,25,38 The Greek version of the SF-36 ws used, which lso provides popultion-bsed normtive dt. 46 Depressive symptoms were ssessed using the Greek version of the 21-item Beck Depression Inventory-BDI-II. 47,48 Higher scores indicte elevted depressive symptoms, while totl score of 0-13 is considered miniml rnge, is indictive of mild depression, is indictive of moderte, nd of severe depression. Ftigue ws ssessed by the Greek stndrdized version of the the Functionl Assessment of Chronic Illness Therpy Ftigue Scle (FACIT-F), 13-item self-dministered instrument rted on 5-point scle from 0 (Not t ll) to 4 (Very much). 49,50 Although the FACIT-F hs not previously been used in CVH ptients, it hs found wide ppliction cross diverse medicl fields nd popultions, including the generl popultion, 51 ptients with cncer, 51,52 rheumtoid rthritis, 53 psoritic rthritis, 54 nd chronic obstructive pulmonry disese. 55 FACIT-F scores rnge from 0 to 52, with higher vlues indicting less ftigue. Scores in the rnge of 30 nd below re in generl suggestive of significnt ftigue. 56 Sttisticl nlysis All the sttisticl nlyses were performed using the Sttisticl Pckge for the Socil Sciences (SPSS) 15.0 (SPSS Inc., Chicgo, IL, USA) for Windows. Summry sttistics for ll vribles were clculted. Normlity ws tested by the Kolmogorov-Smirnov test. 57 Univrite comprisons were first conducted to ssess differences in demogrphic, psychologicl nd HRQOL vribles between HBV nd HCV ptients. Student s t-tests nd chi-squre tests were clculted s pproprite. All the p-vlues were two-tiled. Univrite comprisons were lso conducted to ssess the reltionships between ll independent vribles nd the physicl s well s mentl HRQOL seprtely for HBV nd HCV ptients. Two-tiled t-tests were crried out nd Person s or Spermn s correltions were clculted, s pproprite. To ssess fctors ssocited with chronic virl heptitis ptients HRQOL, univrite comprisons were first conducted to ssess the reltionship of mjor demogrphic, clinicl nd psychologicl vribles with HRQOL in the entire smple. Two-tiled t-tests, Person s or Spermn s correltions were lso clculted, s pproprite. Subsequently, to ssess fctors most closely ssocited with HRQOL, two independently produced multiple regression nlyses were performed. The dependent vribles were the physicl (PCS) nd mentl (MCS) components of the SF-36. Independent vribles were the virus etiology (i.e., HBV or HCV), the mjor demogrphic vribles nd the sttisticlly significnt vribles of the previous univrite nlyses. Colinerity between independent vribles ws tested bsed on vrince infltion fctors (VIF) nd tolernces for individul vribles. 58 Ptient Chrcteristics A totl of 84 eligible ptients were enrolled into the study, 45 with HBV nd 39 with HCV infection. Demogrphic nd clinicl chrcteristics re provided in tble 1. The mjority were mles (65.5%); medin ge ws 46 yers nd medin eduction ws 8 yers. No sttisticlly significnt differences were observed between HBV nd HCV ptients regrding the mjor demogrphic vribles. Thirty ptients (35.7%) hd recently undergone liver biopsy (17 with HBV nd 13 with HCV). Ech biopsy specimen ws evluted ccording to the grding nd stging system described by Goodmn nd Ishk. 59 Medin fibrosis stge of those ptients who hd undergone liver biopsy ws 3, nd medin inflmmtion grde ws five. Twenty-seven ptients (32.1%) presented bnorml ALT/AST rtes t the time of the ssessment. There were no sttisticlly significnt differences between the two types of infection with respect to the severity or ctivity of the disese (Tble 1). Depressive symptoms, ftigue nd helth-relted qulity of life Twelve out of the 84 ptients (14.3%) presented with scores on BDI-II scle indictive of mild depression, while one ptient presented with score indic-

4 422 Krivzoglou K, et l., 2010; 9 (4): tive of moderte nd nother one of severe depression. Men depressive symptoms, ftigue nd HR- QOL scores re presented in tble 2. As shown in this Tble, HBV ptients presented similr to HCV ptients rtes in ftigue nd HRQOL components scores, while HCV ptients presented higher rtes in BDI-II scores, lthough the ltter difference filed to rech sttisticl significnce (p <0.083). SF-36 domin scores were lso compred with the respective scores obtined from the Greek dult smple from the generl popultion (N = 1007) of the Greek vlidtion study, 46 which provides popultion-bsed normtive dt. Although forml sttisticl test ws not performed becuse of the different smpling methods, certin differences relevnt to ll domins of the SF- 36 were observed between ptients nd the generl Tble 1. Clinicl nd demogrphic ptients chrcteristics. Chrcteristic Totl (N = 84) HBV (N = 45) HCV (N = 39) p-vlue Age, yers Rnge Men ± SD 46.0 ± ± ± * Eductionl level, yers Men ± SD 8.8 ± ± ± * Sex (N, %) Mle 55 (65.5%) 33 (73.3%) 22 (56.4%) 0.104** Femle 29 (34.5%) 12 (26.7%) 17 (43.6%) Fibrosis stge*** Medin Men ± SD 3.2 ± ± ± * Inflmmtion grde*** Medin Men ± SD 5.3 ± ± ± * Serum ALT levels Men ± SD 77.0 ± ± ± * Serum AST levels Men ± SD 55.8 ± ± ± * * Two-tiled t-tests. ** Chi-squre test. *** Fibrosis stge nd inflmmtion grde were clculted only in those ptients who hd recently undergone liver biopsy, i.e., N = 30. Tble 2. CVH ptients ftigue, depressive symptoms nd helth-relted qulity of life. Vrible Totl (N = 84) HBV (N = 45) HCV (N = 39) p-vlue* Ftigue FACT-F (Men ± SD) 8.3 ± ± ± Depressive symptoms BDI-II (Men ± SD ) 7.1 ± ± ± Helth-Relted QOL Physicl functioning 52.6 ± ± ± Role limittions due to physicl problems 50.4 ± ± ± Bodily pin 52.1 ± ± ± Generl helth 47.4 ± ± ± Vitlity 50.9 ± ± ± Socil functioning 50.6 ± ± ± Role limittions due to emotionl problems 48.0 ± ± ± Mentl helth 48.8 ± ± ± PCS 51.9 ± ± ± MCS 48.1 ± ± ± * Two-tiled t-tests. Functionl Assessment of Cncer Therpy-Anemi Ftigue Subscle. Beck Depression Inventory-II. Physicl component summry score of the SF-36. Mentl component summry score of the SF-36.

5 Chronic virl heptitis nd HRQOL., 2010; 9 (4): popultion (Figure 1). Tht is to sy, chronic virl heptitis ptients, either HBV or HCV, presented much more impired HRQOL in ll SF-36 components compred to the Greek generl popultion. The gretest degree of impirment ws observed in role emotionl, mentl helth nd generl helth perception subscles with 41.7%, 52.4% nd 67.9% of the ptients performing below verge, compred to the Greek generl popultion, respectively. Clinicl nd Psychologicl Prmeters Associted with HBV nd HCV ptients HRQOL Tble 3 presents the results of the nlyses performed to ssess fctors ssocited with summry scores for physicl helth (physicl component score-pcs) nd mentl helth (mentl component score-mcs) seprtely in HBV nd HCV ptients. As shown in this tble, mong HBV ptients, impired physicl HRQOL ws ssocited with older ge (p <0.001) nd higher fibrosis stge (p<0.028), while mong HCV ptients, impired physicl HR- QOL ws ssocited with fewer yers of eduction (p <0.003) nd higher ftigue rtes (p <0.0005). On the other hnd, impired mentl HRQOL mong HBV ptients ws ssocited with higher rtes on depressive symptoms (p <0.0005) nd ftigue (p <0.006) scles, nd in HCV ptients with mle gender (p <0.001), higher inflmmtion grde (p <0.025) nd higher rtes on depressive symptoms (p <0.0005) nd ftigue (p <0.001). In view of these differences mong the two infection types, disese ws included in the subsequent multivrite nlyses in the entire smple s independent vrible. % ptients PF RP BP GH VT SF RE MH CVH (N = 84) HBV (N = 45) HCV (N = 39) GR (N = 1,007) Figure 1. Helth relted qulity of life rtes ïn ech SF-36 component (i.e. physicl functioning [PF], Role limittions due to physicl problems [RP], bodily pin [BP], generl helth [GH], vitlity [VT], socil functioning [SF], role limittions due to emotionl problems [RE], mentl helth [MH]) for CVH, HBV nd HCV ptients, in comprison to the respective rtes of the Greek generl popultion (dt were derived from reference 31). Tble 3. Vribles ssocited with HBV nd HCV ptients HRQOL. Vrible HBV (N = 45) HCV (N = 39) PCS* MCS PCS* MCS r p-vlue r p-vlue r p-vlue r p-vlue Age Sex Yers of eduction Fibrosis stge, Inflmmtion grde, Serum ALT levels Serum AST levels BDI-II, ** FACT-Ftigue, *Physicl component summry score of the SF-36. Mentl component summry score of the SF-36. Person correltion. p-vlues derived from two-tiled t-tests. Fibrosis stge nd inflmmtion grde were clculted only in those ptients who hd recently undergone liver biopsy, i.e., N = 30 (HCV = 13, HBV = 17). Spermn correltion. **Beck Depression Inventory-II. Functionl Assessment of Cncer Therpy-Anemi Ftigue Subscle.

6 424 Krivzoglou K, et l., 2010; 9 (4): Tble 4. Vribles ssocited with CVH ptients Helth-Relted Qulity of Life (N=84). Vrible PCS* MCS Univrite Multiple Regression Univrite Multiple Regression Anlyses Anlysis Anlysis Anlysis p-vlue bet p-vlue p-vlue bet p-vlue Disese (HBV/HCV) Age Sex (Mle = 1, Femle = 2) Eduction Fibrosis stge, Inflmmtion grde, Serum ALT levels** Serum AST levels** BDI-II**, < FACT-Ftigue**, Regression R Squre Adjusted = R Squre Adjusted = Sttistics F, ** = 6.6, p <0.001 F, ** = 12.3, p < * Physicl component summry score of the SF-36. Mentl component summry score of the SF-36. Two independently produced multiple regression nlyses with dependent vribles the PCS HRQOL nd MCS HRQOL. Independent vribles were the importnt vribles bsed on the results of the univrite nlyses, long with the mjor demogrphic vribles. Two-tiled t-test. Person correltion. Fibrosis stge nd inflmmtion grde were clculted only in those ptients who hd recently undergone liver biopsy, i.e., N = 30; tking into considertion the smll smple size, these vribles were not included in the regression eqution. ** Spermn correltion. Beck Depression Inventory-II. Functionl Assessment of Cncer Therpy-Anemi Ftigue Subscle. Fctors Associted with Chronic Virl Heptitis Ptients HRQOL Tble 4 presents the results of the univrite nd multivrite nlyses performed in the entire smple to ssess fctors ssocited with chronic virl heptitis ptients physicl HRQOL nd mentl HRQOL. As shown in this tble, physicl component SF-36 score (PCS) ws ssocited with ge (p <0.001), eduction (p <0.004), serum ALT levels (p <0.050), fibrosis stge (p <0.034) nd ftigue (p <0.0005). Subsequent multiple regression nlysis with dependent vrible the PCS nd independent vribles the mjor demogrphic chrcteristics, the disese (HBV/HCV) nd the sttisticlly significnt vribles bsed on the previous multivrite nlyses (i.e., ALT levels nd ftigue) showed tht older ge (p <0.001) nd higher ftigue rtes (p <0.001) were the vribles most closely ssocited with physicl HRQOL. It should be noted tht, due to the smll smple size, fibrosis stge ws not included in the regression eqution. On the other hnd, summry mentl component SF-36 score (MCS) ws ssocited with both depressive symptoms (p <0.0005) nd ftigue (p <0.0005), nd these vribles were independently closely ssocited in the subsequent multiple regression nlysis (Tble 4). DISCUSSION The results of the present study showed tht ll spects of CVH ptients HRQOL were significntly impired, compred to the Greek popultion-bsed normtive dt. Clinicl prmeters such s infection ctivity, fibrosis stge or inflmmtion grde, s well s depressive symptoms nd ftigue were found to be significntly ssocited with HRQOL. Multivrite nlyses showed tht older ge nd higher ftigue scores were the vribles most closely ssocited with the physicl HRQOL, while both ftigue nd depressive symptoms were independent correltes of mentl HRQOL. As the results of the present study showed, heptitis B nd heptitis C ptients reported similr scores in ftigue nd HRQOL mesures, while HCV ptients ppered to be more depressed, lthough the difference ws not sttisticlly significnt. Despite the bsence of significnt differences in HRQOL scores between HBV nd HCV ptients, our nlysis reveled tht HRQOL correlted with different prmeters in these two sub-groups. However, in subsequent multivrite nlyses, the type of virus filed to significntly predict HRQOL. In ssessing the entire chronic virl heptitis smple, we found tht ftigue ws significntly relted to both physicl nd mentl HR- QOL. In similr vein, ge, eductionl level, fibrosis stge nd ALT levels were correlted with the physicl component of HRQOL, while depression ws relted to the mentl spect of HRQOL. However, in the multivrite nlysis, the effect of eduction nd disese severity indices on HRQOL vnished. Ftigue remined strong determinnt of both spects of

7 Chronic virl heptitis nd HRQOL., 2010; 9 (4): HRQOL independently of depressive symptomtology, while ge nd depression predicted the physicl nd mentl component, respectively. The reltively high scores on ll HRQOL subscles in our study, compred to previous reserch, 9,11 nd the impirment concerning psychologicl functioning nd generl perceptions of helth, while spring the physicl domins of SF-36, could be ttributed to the ppliction of strict criteri to exclude co-morbidities tht might ffect HRQOL. Medicl conditions co-existing with virl heptitis hve been shown to dversely influence ptients HRQOL. 32,38,60 We used those criteri to describe more ccurtely the impct of chronic virl heptitis on ptients physicl, emotionl nd socil well being. Erlier reserch hs shown ssocitions between HRQOL nd gender suggesting tht women re more likely to report poorer HRQOL thn men. 26,38,61 However, other reserchers 1,32,60 hve demonstrted tht gender plys no role in HRQOL. In the current study, no significnt differences were noted between men nd women in mentl nd physicl helth, lthough femles scored lower on both components of the SF-36. In the current investigtion, we hve focused eqully on HCV nd HBV ptients, considering the impct of both infections on ptients lives. To dte, reserch hs rther under-estimted the impct of chronic heptitis B on ptients HRQOL, since limited number of relevnt studies hve been conducted. 1,11,20 The lck of significnt differences in SF-36 scores between HCV nd HBV-infected ptients contrdicts the study by Foster, et l., 11 who reported tht heptitis C is ssocited with globl impirment, ffecting both physicl nd mentl domins of HR- QOL, while heptitis B ws relted only to mentl functioning decline. However, it is not cler whether the two heptitis groups in tht investigtion were well-blnced in bckground chrcteristics. Similr to our results, recent study found no significnt differences in HRQOL scores between HBV nd HCV ptients. 20 It seems tht HRQOL impirment does not necessrily depend on the virus itself, but lso on common fctors of the two liver infections. Disese severity nd ctivity, including fibrosis stge nd ALT levels, negtively correlted with the physicl component of SF-36. However, fibrosis stge ws not included in multivrite nlyses due to the gret number of missing vlues, wheres ALT levels proved not to be strong predictor of HRQOL. Significnt controversy remins regrding the ssocitions between liver disese progression nd HR- QOL 1,9,11,23,24,32,60 nd future investigtions re needed to clrify this issue. Psychologicl distress ffects significnt proportion of chronic disese ptients nd cts s mjor determinnt of their HRQOL. 22 In the cse of virl heptitis, psychitric co-morbidity constitutes n importnt clinicl prmeter, which plys mjor role to the disese burden imposed on ptients. 5,6,10 In relevnt study, Ozkn, et l., 10 found tht lmost hlf of virl heptitis ptients suffered from psychitric disorder, minly depression, suggesting tht mjor psychopthology my be the rule rther thn the exception in CVH ptients. In ddition, IFN tretment is often ccompnied by psychitric dverse-effects, which my result to tretment discontinution possibly compromising ptients prognosis The strong ssocitions observed in this nd erlier studies between depression nd the mentl component of HR- QOL, 9,10,32,60 underlines the importnce of stndrd psychitric evlution in the clinicl setting. Given tht the concept of helth entils both biomedicl nd psychosocil well-being, the mngement of virl heptitis should im not only t the normliztion of liver enzyme levels nd virl clernce, but lso t the remission of depressive symptoms nd HRQOL improvement. Clrifying the determinnts of HRQOL cross ll phses of virl heptitis, nd developing interventions to restore, mintin nd mximize HR- QOL re mong the tsks confronting reserch into modern heptology. Moreover, regulr psychitric ssessment during IFN-tretment is mndtory to ensure best dherence nd chieve mximum efficcy. Likewise, ftigue ws found to predict both physicl nd mentl summry scores of SF-36. According to the existing literture, ftigue is common complint of virl heptitis ptients, especilly in those infected by HCV, nd it is ttributble to both psychologicl nd physiologicl mechnisms. 62,63 However, being rther subjective symptom mkes its ccurte ssessment extremely difficult nd in stndrd clinicl prctice it is often discrded s n unspecific, minor complint. Our findings, in combintion with previous studies, 5,27,33 dd further evidence bout the significnt impct of ftigue on ll spects of HRQOL nd emphsize the need for further reserch to determine its pthogenesis nd, subsequently, to devise nd implement proper interventions. The results of the present study re suggestive rther thn conclusive. The smple size nd the limittion of using only self-reported mesures of ftigue nd psychologicl distress prevent us from generlizing the findings. Another mjor limittion of our study lies in the cross-sectionl design nd hence conclusions bout cuslity cnnot be ddressed. The findings need to be

8 426 Krivzoglou K, et l., 2010; 9 (4): replicted in prospective study. In ddition, due to the unvilbility of biopsy dt for significnt proportion of ptients, we filed to further explore the ssocitions between HRQOL nd disese progression, s mnifested by fibrosis stge nd the presence of cirrhosis. Future studies re needed to ddress these nd other issues in detil, using lrger numbers nd prospective longitudinl design. CONCLUSION The current investigtion met its purpose of delineting the min predictors of HRQOL in smple of Greek heptitis ptients. Our findings indicte tht heptitis ptients perceive themselves s unhelthy compred to the generl popultion nd report poor mentl helth nd impired function due to psychologicl distress. The decline in HRQOL scores eqully ffects HBV nd HCV ptients. In ddition, the current results confirm the importnce of ftigue nd depression s strong predictors of ptients HRQOL, emphsizing the necessity for stndrd psychitric evlution in clinicl prctice. 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