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Treatment with interferon alfa-2b of chronic HDV hepatitis in children
s175
Treatment with I~tmferon Alfa-2b of Chmnit HDV Hepatitis in Children A Crax3,V Di Mard, R VoQeG, S Mamax,M RfzzcHo$ F Rosina%C Barbera$ F BmtolMtP, C CrivelI~&, C Iurnupi$ R calzks, R GiKch*, A TiiiiiW, P Vajmi A FontanelW, C Pit@ Cattedra di GaWwMemlq$a, University of Palemu, Qwkione di Gastroentemlogia, Osp. Molinette, Turin, *Muto di CIinica Medica II and Divisiom MaIattte Infet~iw, Unive&y of Padua, ‘11CKca Malattk Infettive, University of Genoa, %titub WeWifi#, Medicha Interna, Genoa, 6clinica hUbHi@ Infettive, UniversiQ of Genoa, Tlinica PediatricaII, University of Naples, aDirezione Sdentifica, ESSPXk& Italy.
Introduction Incountries with a high
Results incidence of khe hepatikis delta
virus MDV), chronic HDV hepatitis is common in the &Wren ofHiWMti MkAgcarrigrs. This cunditim tends to have a severp outcome later in adult life, often leading to &ho& and liver-relatti deaths. HDV-Stied children are mostly asymptomatic and often display complete hepatitis I3virus (HBV) replication, at variance with HDV infect& adults, who are usually low-Ieve HBV replicators. Treatment with recombinant alpha-interferon is known toMtHEw Ii&ion both in adults and children, reducing n ecroE/x anunation. It mn also, ternp-rily stop HDV replication in adult patients-
*
Patients I Tenchild~ncarryingHEkAgati
chmnically if&&d with HDV (5 mak, 5 female; mean age II, rar;;.~_~ S-14 years); seven had a history of acute hepatitis. W Akl patients had been HBsAg and anti-HI3 positive with serum ALT >2 x nod for rl year, M All had serum HDV-RNA and HDAg in the liver at first biopsy. l AllwmMsympbmaticandgrowjngnmtalIy.
children
0~ pilot study of with chronic HDV hepatitis. n R~mhiit interferon alfa-2b WTRON A) given at5MU#m*TM: for3montkandthereaftmat 3 Mu/ml for 9 mo#Iths. n Liver biopsy prior to inclusion anti at the end of treatmer.t l Monthly follow up, for up to 6 months after the end of &atment.
Methods l Serum HkAg, HBeAg, and total anti-HDV test&l bycomnw&lEIA. l Serum HBV-WA tested by dot-blot DNA-DNA hybridization using a XP-&beIed HBV-DNA robe. M Serum HDV-RNA tested by slot-blot rib0 pmge hyMd&tion. H Gver H30%g and HDAg staked oxi Zen tivet ~oIEbyindiwt~wloflu~using human pdyclmal antibtxk.
’ L++ 0
l
:
Study Design I
0
w
a n n
3
6
9
12
18
No patients tithdreworq 1 major complicationsNormal growth maintained inall cases. 416 patients tith active HBV replications converted to low-grade HW infection after 12 months of interkron alfa-2b. Two children HDAg negative on second biopy, but no significant mlrr:?lon of HDAg was ~WII in the other eight. SrumHDV-RNAwasstiUprewntinthreecases __ in liiva histchgy. months after inkrfertm ak2b, ALT to 105 {mnge 44kZ5@IUD,, and HDV-RNA reappeared in 517 patients. Reactivation of HBV replication did not occur once it had SubsidEd.
_ mpovement
aH&Ag and/or liver HkAg
and/or H8V DNA.
m Reduction of ALT ti the loss of HBV repkative markers confixms the effectiveness of interferon aMa-2b against HBV. W HDV isoy temporatily and partially i&Sited by this 5cheduk and often zeapjxars after treatmentn No clinical or hktolq#c improvement after 1 year, tkefore nwoinfknmation and liver disease are probably sustained by HDV. m ThereductioninHBV~licationinduaedby interferon alfaG& does not affect the t&&or d HDV tition, and may notbeclinkally meimingful.
Treatment with I~tmferon Alfa-2b of Chmnit HDV Hepatitis in Children A Crax3,V Di Mard, R VoQeG, S Mamax,M RfzzcHo$ F Rosina%C Barbera$ F BmtolMtP, C CrivelI~&, C Iurnupi$ R calzks, R GiKch*, A TiiiiiW, P Vajmi A FontanelW, C Pit@ Cattedra di GaWwMemlq$a, University of Palemu, Qwkione di Gastroentemlogia, Osp. Molinette, Turin, *Muto di CIinica Medica II and Divisiom MaIattte Infet~iw, Unive&y of Padua, ‘11CKca Malattk Infettive, University of Genoa, %titub WeWifi#, Medicha Interna, Genoa, 6clinica hUbHi@ Infettive, UniversiQ of Genoa, Tlinica PediatricaII, University of Naples, aDirezione Sdentifica, ESSPXk& Italy.
Introduction Incountries with a high
Results incidence of khe hepatikis delta
virus MDV), chronic HDV hepatitis is common in the &Wren ofHiWMti MkAgcarrigrs. This cunditim tends to have a severp outcome later in adult life, often leading to &ho& and liver-relatti deaths. HDV-Stied children are mostly asymptomatic and often display complete hepatitis I3virus (HBV) replication, at variance with HDV infect& adults, who are usually low-Ieve HBV replicators. Treatment with recombinant alpha-interferon is known toMtHEw Ii&ion both in adults and children, reducing n ecroE/x anunation. It mn also, ternp-rily stop HDV replication in adult patients-
*
Patients I Tenchild~ncarryingHEkAgati
chmnically if&&d with HDV (5 mak, 5 female; mean age II, rar;;.~_~ S-14 years); seven had a history of acute hepatitis. W Akl patients had been HBsAg and anti-HI3 positive with serum ALT >2 x nod for rl year, M All had serum HDV-RNA and HDAg in the liver at first biopsy. l AllwmMsympbmaticandgrowjngnmtalIy.
children
0~ pilot study of with chronic HDV hepatitis. n R~mhiit interferon alfa-2b WTRON A) given at5MU#m*TM: for3montkandthereaftmat 3 Mu/ml for 9 mo#Iths. n Liver biopsy prior to inclusion anti at the end of treatmer.t l Monthly follow up, for up to 6 months after the end of &atment.
Methods l Serum HkAg, HBeAg, and total anti-HDV test&l bycomnw&lEIA. l Serum HBV-WA tested by dot-blot DNA-DNA hybridization using a XP-&beIed HBV-DNA robe. M Serum HDV-RNA tested by slot-blot rib0 pmge hyMd&tion. H Gver H30%g and HDAg staked oxi Zen tivet ~oIEbyindiwt~wloflu~using human pdyclmal antibtxk.
’ L++ 0
l
:
Study Design I
0
w
a n n
3
6
9
12
18
No patients tithdreworq 1 major complicationsNormal growth maintained inall cases. 416 patients tith active HBV replications converted to low-grade HW infection after 12 months of interkron alfa-2b. Two children HDAg negative on second biopy, but no significant mlrr:?lon of HDAg was ~WII in the other eight. SrumHDV-RNAwasstiUprewntinthreecases __ in liiva histchgy. months after inkrfertm ak2b, ALT to 105 {mnge 44kZ5@IUD,, and HDV-RNA reappeared in 517 patients. Reactivation of HBV replication did not occur once it had SubsidEd.
_ mpovement
aH&Ag and/or liver HkAg
and/or H8V DNA.
m Reduction of ALT ti the loss of HBV repkative markers confixms the effectiveness of interferon aMa-2b against HBV. W HDV isoy temporatily and partially i&Sited by this 5cheduk and often zeapjxars after treatmentn No clinical or hktolq#c improvement after 1 year, tkefore nwoinfknmation and liver disease are probably sustained by HDV. m ThereductioninHBV~licationinduaedby interferon alfaG& does not affect the t&&or d HDV tition, and may notbeclinkally meimingful.