P-277 Factors predictive of response to interferon therapy in patients with hepatitis C virus infection and analyses of nucleotide and amino acid sequences obtained from treated patients

S106

Posters / International Hepatoiogy Communications 3 SuppL (1995) $37-$169

P-277

FACTORSPREDICTIVEOFRESPONSETO INTERFERONTHERAPY IN PATIENTS WITH HEPATITIS C VIRUS INFECTION AND ANALYSES OF NUCLEOTIDEAND AMINO ACID SEQUENCESOBTAINED FROMTREATED PATIENTS K. Chayama, M. Kobayashi, A. Tsubota, Y. Suzuki, Y. Arase, I. Koida, S. Saitoh, N. Murashima, K. Ikeda, H. Kumada, M. Kobayashi, H. Koike, M. Hashimoto Dept. of Gastroenterology, Toranomon Hospital

P-278

AS

THERAPY

P-279 CHANGES OF HEPATITIS C VIRUS (HCV) RNA TITERS AND HCV QUASISPECIES POPULATION IN THE EARLY PHASE OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C H. Matsumoto 1, T. Yamaguchi 2, Y. Chuganji 3, M. Momoi3. 1.Dept. of Gastroenterology, Mito Kyodo General Hospital, 2. Dept. of Gastroenterology, National Mito Hospital, Ibaraki, Japan 3. Dept. of Gastroenterology, Tokyo Metropolitan Bokutou Hospital, Tokyo, Japan We studied the relationship between the responsiveness to interferon(IFN) and serum HCV RNA titers 1 to 2 weeks after IFN cxtherapy in 40 patients with c h r o n i c hepatitis C Furthermore, the changes of HCV quasispecies of h y p e r v a r i a b l e region 1 in the early phase of IFN t h e r a p y were analyzed by fluorescence-based polymerase chain reaction-single s t r a n d conformation polymorphism(F-SSCP). Eight of n i n e patients (88.9%), who were HCV RNA negative 1 week after IFN started, had sustained responses to IFN, whereas among 19patients who were HCVRNA negative 2 weeks after, thirteen(B8.4%) had sustained responses. Serum HCV RNA titers 1 week after the start of IFN were useful predictive factor for IFN efficacy. F-SSCP revealed that in patients exhibiting rapid HCV RNA titer decrease at 1 to 2 weeks of IFN therapy, HCV quasispecies pattern c h a n g e d significantly at these weeks. In contrast, HCV quasispecies pattern continued to be almost similar in patients showing slow HCV RNA decrease at 1 to 2 weeks of IFN therapy.

A

PREDICTOR

OF

RESPONSE

TO

IFN

IN CHILDREN W I T H CHRONIC HEPATITIS

A.Inui,

T.Fujisawa, T.Ohkawa,

H.Komatsu,

M.Ishikawa,

Department

of

Y.Kuroki,

Pediatrics,

C

H.Miyagawa,

M.Onoue

National

Defense

Medical College, Saitama, Japan We

HCV genotype 1 b and high pretreatment virus titer have been shown to be predictive of poor response to IFN therapy. To further investigate such predictive factors we retrospectively analyzed 215 patients treated with lymphoblastoid IFN-alpha. A slow decrease in virus titer observed in patients with genotype 1 b suggested low IFN susceptibility by this genotype. Six of seven patients with genotype 3b also showed a poor response to IFN. We also analyzed the entire nucleotide and amino acid sequences obtained from four type 1 b patients treated by IFN. One patient was a complete responder despite having a high initial virus titer. The other three patients were non- responders. Multiple mutations were seen when comparing sequences obtained before and after IFN especially in the El, E2/NS1 and NSSA regions. Although it was impossible to identify specific nucleotide or amino acid mutations related to resistance to IFN in this study, further study might identify key factor(s) related to IFN resistance by genotype l b and 3b.

DNA (bDNA) ANPLIFICATION

THE B ~ C . E D

ASSAY

evaluated

investigated the

outcome

CAH:I4) RT-PCR.

chronic

were

daily

week

for

for

an

followed

weeks

for 18 months

22

C.

serum

0.1 and

additional

IFN

(M/F=16/4,

for

received 2

of

that may

hepatitis

positive

Children

alfa

effect assay

in 20 children

with

children

the

the bDNA

MIU/Kq then

weeks.

or longer.

therapy

in

10

no

difference

in

histoloqic

activity.

liver

children

They

a

were

levels

(complete

for at least 12 months after the

There 13

times

ALT

of

between

20 by

of IFN-

3

cessation was

CPN:6, All

HCV-RNA

were normal and HCV-RNA disappeared response;CR)

and

predict

(62%)

whose

children the

serum

bDNA

(50%). titers

8 of

bDNA

the

titers

were
(29%)

had CR.

whose

bDNA

titers

were

a ]

Pretreatment serum bDNA assay

were usuful to predict IFN response.

P-280

CORRELATION BETWEEN HCV QUASISPECIES POPULATION ANDTHE EFFECTOFINTERFERON THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C T. To mid a, S .N akano, I.Taked a, T. K u mad a,T. O sad a, S. K i riy ama M.Takahashi, S.Shimada, T.Samori, Y.Numaguchi, H.Toyoda* Dept. of Gastroenterology, Ogaki Municipal Hospital * 2nd Dept. of Medicine, Nagoya Univ.of Medicine Nagoya, Japan Objective: We investigated the influence of HCV quasispecies population on effectiveness of interferon therapy in chronic hepatitis C patients. Materials and Methods:Fiftytwo patients with chronic hepatitis Cwere treated with 480 MU of ,~ -interferon. We determined the genotype and the viral concentration(competitive PCRand branched-DNA probe assay) in all patients. The mutation of E2/NS1 region was measured by the PCR-FSA method. Continuous nor realization of serumtransaminaseand negative HCVRNA was judged as CR(complete response), and the remains as NR(no response). Results: Thirteen patients(25%) showed CRs. In patientswith low viralconcentration, or geno type 2a and 2b, CR rate was significantly high. In cases having below 1 Meq/ml of viral concentration by bDNA probe assay, quasispecies population in CRs were lower than in NRs significantly (p=0.O086),however significant difference amomg genotypes was not observed. Conclusion:On the basis of the findings in our study we consider the quasispecies population may be more useful factors predicting responsiveness to interferon therapy than genotype in patients with Iowviral concentration.