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HEPATOLOGY Vol. 34, No . 4, Pt. 2, 2 0 0 1 A A S L D A B S T R A C T S 5 9 5 A

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CANDIDACY FOR HEPATITIS C ANTIVIRAL THERAPY: THE INFLU- ENCE OF REFERRAL SOURCE A N D S O C I O E C O N O M I C STATUS. Marius Laur inai t i s , M a m t h a Ba l a sub raman iam, A n n L Si lverman, Stuart C G or don , W i l l i a m B e a u m o n t Hospi ta l , Royal Oak , MI

Background : T h e p r o p o r t i o n of pa t ients w i t h ch ron ic hepa t i t i s C that is el igible for cu r r en t the rapy is no t k n o w n ; one repor t (Hepa to logy 2000;32:283A) s h o w e d that only 58% of all r e fe r red H C V pa t ien ts were cand ida tes for therapy, w i t h va r i a t ions based on referra l si te ( c o m m u n i t y vs. ter t iary medica l facility-). A ims : W e s o u g h t to d e t e r m i n e the p r o p o r t i o n of pa t ien ts r e fe r red for t r e a t m e n t of hepat i t i s C w h o w e r e cons ide red cand ida tes for Rebe t ron therapy, and w h e t h e r referraI sou rce or social s ta tus as ref lected by pa t ien t i n c o m e influ- enced eligibility" for t rea tment . Methods : W e r ev i ewed the char ts o f 280 con- secu t ive ly eva lua ted adul t pa t ien ts re fe r red to a ter t iary hepa to logy service for hepat i t i s C infec t ion ove r a two-year pe r iod e n d i n g 12-31-00. Each pa t ien t was H C V RNA posi t ive aud n o n e had p rev ious ly rece ived ant iv i ra l therapy. In add i t ion to s t anda rd d e m o g r a p h i c data, we also e x a m i n e d the role of referra l source (gas t roen te ro log i s t vs. other) and s o c i o e c o n o m i c s tatus. M e a n house- ho ld i n c o m e was assessed based on zip code of res idence and was p r o v i d e d b y Claritas (I thaca, NY). Results: Overal l , 57% of pa t ien ts were candida tes for therapy. The m o s t c o m m o n reasons for n o n - c a n d i d a c y w e r e m a j o r dep res s ion / o the r psychia t r ic cond i t ions (23% of all pa t ien ts no t of fered t rea tment ) , de- c o m p e n s a t e d c i r rhos is (14%), act ive a lcohol u se (10%), or a c o m b i n a t i o n of mul t ip l e med ica l and psych ia t r i c factors (25%). A m o n g pat ients refer red by gas t roentero logis t s , 17/29 (59%) were offered t rea tment , vs 141 /25 i (57%) of ind iv idua ls re fe r red by o the r sources ( p = l . 0 ) . Soc ioeconomic data s h o w e d a r ange of m e a n h o u s e h o l d i n c o m e of $12 ,600 to $153 ,500 (mean , $58,100) . 71/280 (25%) ref lected i n c o m e s less than $40 ,000 ( lower) , 171/280 (61%) f r o m $40-80 ,000 (mid) , a n d 38/280 (14%) grea te r than $80 ,000 (h ighes t ) . The overal l p reva lence of depress ive i l lness was 7 /7 i (9.9%), 18/171 (10.5%), and 2/38 (5.3%) in the lower, mid , a n d u p p e r i n c o m e levels, respect ively. 41/71 (57%), 94/171 (55%), and 24/38 (63%) of pa t ien ts in the lower , mid , and u p p e r i n c o m e levels, respect ively , were offered ant iv i ra l therapy. N o n e of these dif- fe rences was stat is t ical ly s ignif icant . No d e m o g r a p h i c or c l inical fea ture was re la ted to referra l source or s o c i o e c o n o m i c s tatus. Conc lus ion : T h e 57% of all re fe r red H C V pa t ien ts cons ide red to be t r ea tmen t cand ida tes is ve ry s imi la r to a p r ev ious repor t at a d i f ferent U.S. locat ion. Psychia t r ic i l lness was the most c o m m o n r eason for no t of fer ing therapy, b u t ne i the r the referral source no r social status as d e t e r m i n e d by m e a n h o u s e h o l d i n c o m e in f luenced t r e a t m e n t candidacy.

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HEALTH RELATED QUALITY OF LIFE IN HCV INFECTED PATIENTS RECEIVING INTERFERON A N D RIBAVIRIN. M onique Bohun, Brit ish Co- l umbia Ct r for Disease Contro l , Vancouve r , BC Canada; Lor i Lee Wals ton , V a n c o u v e r Hospi ta l and Heal th Sciences Centre , Vancouver , BC Canada; Mel Kra jden , Bri t ish C o l u m b i a Ctr for Disease Control , Vancouve r , BC Canada; F r a n k H Anderson , V a n c o u v e r Hospi ta l and Heal th Sciences Centre , Vancou- ver , BC Canada; W a r r e n D H i l l Bri t ish C o l u m b i a Ctr for Disease Contro l , Vancouver , BC Canada; Natal ie Rock, V a n c o u v e r Hospi ta l and Heal th Sciences Centre , Vancouver , BC Canada

Background: Hepatitis C virus (HCV) is a leading cause of liver disease. Combination therapy with inter feron-odribavirirx will produce a sustained virological response in approx. 30% of genotype 1 and 60% of non-genotype 1 patients. However little is known about the health-related quality of life (HRQL) of infected patients. This study measured the quality Of life of 49 community-based non-genotype 1 HCV infected patients prior to. during and post interferon-odribavirin therapy. Patients and Methods: A total of 49 patients undergoing inter feron~aYribavirin therapy undelwent HRQL testing using the SF-36®form, 31 of the patients reached the 48 wks post therapy assess- ment and were virological responders (AMPLICOR qualitative HCV PCR negative). The instru- ment was self-administered at baseline (pre-treatmem), 12 wks (mid-treatment), 24 wks (end of treatment), and 48 wks (post treatment). Mean 5F-36® scores from the HCV treatment cohort were compared to an age and gender-matched sample of healthy adults in Canada. Results: Patients prior to therapy demonstrated a statistically significant lower HRQL across most domains evalu- ated by the SF~36® (p<0.01). During therapy at wks 12 and 24 patients demonstrated a downward trend in their mean 6F-36® score which was statistically different from the general Canadian population (p<0.001). By wk 48 all sustained virological responders (n=31) had surpassed their pre-therapy baseline SF-36®seores and these scores were then not statistieany different from the mean scores of the general Canadian population. Conclusions: Prior to therapy the HRQL of HCV patients was statistically below the norms of age and gender matched Canadians measured by the SF-36® instrument. Therapy was associated with a HRQL deterioration trend. The SF-36® scores o f inter feron-odribavirin sustained virological responders rose above the baseline in all domains to a level not statistically different from an age and gender matched Canadian population score. An important limitation of these data was that patients were not blinded to their clinical status prior to, during and post therapy.

Week of S t y ' Comp~'ed to t~orma~

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COMBINATION THERAPY W I T H oL-2B INTERFERON A N D RIBAVIRIN IS SAFE A N D EFFECTIVE IN THE TREATMENT OF CHRONIC HEPATI- TIS C INFECTION IN PATIENTS W I T H T R A N S F U S I O N - D E P E N D E N T TtiALASSEMIA MAJOR. Averel l H Sherker , Made le ine Senosier , SMBD-Jew- ish Genera l Hospi ta l , McGil l Univers i ty , Montreal , Q C Canada; Del ia Kcr- mack , Mont rea l Chi ld ren ' s Hospi ta l , McGil l Univers i ty , Montreal , Q C Canada

Currently, the most effective licensed treatment for chronic hepatitis C virus (HCV) infec- tion is combination therapy with e-interferon (1FN) and rihavirin (RVN). Because of their lifelong requirements for blood transfusion, the vast majority of patients with thalassemia major born prior to the introduction of HCV screening of Mood donors have been infected with this virus. An almost universal effect of RVN is the occurence of hemolysis and according to the product monograph, this therapy should not be used in patients with hemoglobinopathies including thalassemia. We have treated 3 HCV-infected female thalas- semic patients with significant hepatic fibrosis on liver biopsy with standard dose combi- nation IFN(3MU tiw)/RVN(lgm/day) therapy. All tolerated treatment well with no dose modifications or premature withdrawals. Patients were transfused as required to maintain hemoglobin >9.0 gm/dl. The mean increase in transfusion requirements on treatment compared to the same time period immediately prior to treatment was 48%. Patients' transfusion requirements returned to their pretreatment baseline within 2 months of com- pleting antiviral therapy. All patients had undetectable HCV RNA 6 months after comple- tion of therapy and were thus sustained virological responders (SVR) despite significant iron overload at baseline. In summary, full dose combination therapy with IFN/RVN appears to be safe and effective in transfusion dependent-thalassemics. The increased transfusion requirements during treatment are acceptable if it is considered that these patients had already been transfused hundreds of blood units over their lifetimes. This is especially true in the context of significant hepatic fibrosis.

TRANSFUSION REQUIREMENTS AND ANTIVIRAL RESPONSE OF THALASSEMIC PATIENTS TREATED WITH IFN/RVN

PT

VIR TREA UNITS PRBC BASELI AL LIVER T- TRANSFUSE

D VIROLO AG NE GEN VIRAL BIOPSY MENT E FERRITI O- LOAD (GRADE; DURA (TREATMEN -GICAL

T/ RESP N TYP STAGE) -TION PRETREATM E (,wks) ENT)

gr 1-Z'4; SL 3! 2163 ND 6.2E6 st 3/4 48 46t36 (+28%) SVR

gr 2 4: s 48 44/29 (+52%) SVR Agl 25 1193 la &0E4 2/3/4

KS 30 2657 2a/c 3,2E2 gr 1-2/4; 24 18/tl (+64%) SVR st 2/4

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MIGRAINE HEADACHES DURING TREATMENT W I T H ORAL RIBAVI- RIN IN COMBINATION THERAPY FOR CHRONIC HEPATITIS C. Norbe r t Brau, Bronx VA Medica l Ctr, Bronx, NY; E d m u n d J Bini, VA N e w York Harbor HCS, N e w York, NY; Ayse Ay taman , VA N e w York Harbor HCS, Brooklyn, NY; Douglas A Finch, Bronx VA Medical Ctr, Bronx, NY; Saray Stancic, VA H u d s o n Valley HCS, Mont rose , NY

BACKGROUND: Headaches have been associated with oral ribavirin (RBV) in early trials of RBV mona- therapy for chronic hepatitis C. In treatment trials of RBV + interferon alfa-2b (IFN), headaches are described equally frequently in IFN monotherapy and in combination of IFN + RBV (63-68%). Specific links between migraine headaches and rihavirin therapy have not been reported to date. METHOD: During May 1998 and December 2000, 452 patients were treated with tEN + RBV for chronic hepatitis C in four centers. All pa dents who developed new migraine headaches ( confirmed by a neurologist) or had worsening of existing migraine during treatment were evaluated for a possible causal relationship with either IFN or RBV. RESULT: A total of 9 of 452 pauems (Z0 %, 95% CI 1.1% to 3.7%) developed migraines during treatment with IFN 3 MU TIW + RBV tO0O-1200 mg/d, 8 with a new diagnosis and 1 with worsening of existing migraine headaches. In 8 of 9 cases, a causal link with RBV treatment could be established, In 5 pa tlents, migraine symptoms improved significantly when RBV dose was reduced or stopped and symptoms resumed with full RBV dose. In 3 patierUs there were no headaches with prior IFN monotherapy. In one patient, a temporal relatiollship with RBV was made because headaches occurred daily, even on days off IFN doses. All nine patients had severe migraine headaches that required opioid analgesics. In all 6 patients where the RBV dose was reduced, migraine symptoms became less severe. In 7 of 8 patients with new onset migraine headaches, the headaches resolved completely upon discontinuation of RBV. One patient with prior diagnosis of migraine ceased having severe headaches after RBV was discontinued and only had rare migraine attacks in a similar way as before RBV treatment. The one patient with a new diagnosis of migraine headaches who continued to have symptoms had had chronic headaches since adolescence, which in retrospect were judged by the neurologist as undiagnosed migraine-style headaches. Table l describes the nine patients. CONCLUSION: Migraine headaches (usually new onset) may occur as a consequence of ribavirin therapy in about 2% of cases. They are typically severe and require opioid analgesics. Dose reduction of ribavirin therapy usually leads to improvement of migraine symptoms, and discontinuation leads to resolution in most cases.

Table___l: Characteristics of 9 patients with migrain e headaches on ribaviriu treatment outcome

HCV risk Daily RBV Migraine Onset of Link RBV of No, Age Sex factor dose [mg| new t migraine migraine migraine

worse on RBV Rx after RBV DIC

1 43 M IDU 1000 new 1 day' causal continued 2 44 M IDU 1200 worse 1 day causal mild, rare 3 37 M IDU 1200 new 1 day causal resolved 4 46 M IDU 1200 new 21 days causal resolved 5 51 M IDU 1000 new 4,5 mo causa~ resolved 0 52 M IDU 1200 new 4,0 mo causal resolved

Tattoo, 7 40 M cocaine, 1200 new 2,0 mo temporal resolved

sex 8 40 M IDU 1200 new 41 days causal resolved 9 45 M ID U 1200 new 30 days causal resolved