MD967Z - Method for treating chronic viral hepatitis B with cholestatic syndrome in children - Google Patents
Method for treating chronic viral hepatitis B with cholestatic syndrome in children Download PDFInfo
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- MD967Z MD967Z MDS20150032A MDS20150032A MD967Z MD 967 Z MD967 Z MD 967Z MD S20150032 A MDS20150032 A MD S20150032A MD S20150032 A MDS20150032 A MD S20150032A MD 967 Z MD967 Z MD 967Z
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Abstract
Description
Invenţia se referă la medicină, în special la hepatologia pediatrică şi boli infecţioase şi poate fi utilizată pentru tratamentul hepatitei virale B cronice cu sindrom colestatic la copii. The invention relates to medicine, in particular to pediatric hepatology and infectious diseases and can be used for the treatment of chronic viral hepatitis B with cholestatic syndrome in children.
Este cunoscută metodă de tratament al hepatitei virale cronice B (HVCB) la copii, care include, în caz de acutizare, spitalizarea pacientului cu respectarea regimului igieno-dietetic (regim de salon, dieta nr.5 după Pevzner), tratamentul hepatoprotector (silimarină, fosfolipide esenţiale, legalon, acidul ursodezoxiholic), terapia de dezintoxicare la indicaţii clinice (administrarea i/v a soluţiilor fiziologice, de glucoză, hepasolului etc.) şi de corecţie a proceselor metabolice (vitaminele grupelor C, B1, B6, B12) [1]. There is a known method of treating chronic viral hepatitis B (CHBV) in children, which includes, in case of exacerbation, hospitalization of the patient with compliance with the hygienic-dietary regimen (parlor regimen, diet no. 5 according to Pevzner), hepatoprotective treatment (silymarin, essential phospholipids, legalon, ursodeoxycholic acid), detoxification therapy according to clinical indications (i/v administration of physiological solutions, glucose, hepasol, etc.) and correction of metabolic processes (vitamins of groups C, B1, B6, B12) [1].
În faza de replicare a hepatitei virale B (HVB) se recomandă tratamentul antiviral cu administrarea interferoanelor ca: Interferon 2α şi β standard sau pegilate cu acţiune imunomodulatoare şi antivirală în monoterapie pe o durată de 24 de săptamâni [2]. In the replication phase of viral hepatitis B (HVB), antiviral treatment is recommended with the administration of interferons such as: Interferon 2α and β standard or pegylated with immunomodulatory and antiviral action in monotherapy for a period of 24 weeks [2].
Dezavantajele constau în aceea că o parte din aceste remedii sunt foarte costisitoare şi provoacă dezvoltarea reacţiilor adverse, ceea ce limitează aplicarea lor în practică pentru majoritatea pacienţilor, mai ales a celor de vârstă mică. The disadvantages are that some of these remedies are very expensive and cause the development of adverse reactions, which limits their application in practice for most patients, especially young ones.
O altă metodă de tratament constă în utilizarea în tratamentul hepatitei virale cronice B a terapiei simptomatice şi a unui remediu imunomodulator şi antiviral aşa ca 5α-furostan-3β,22,26-triol-3-[O-β-D-glucopiranozil(1→2)-β-D-glucopiranozil(1→4)-β-D-galactopiranozil]-26-O-β-D-glucopiranozidă (Pacovirină), aplicat timp de 6 luni, începând cu prima zi de manifestări clinice, în doză de 50 mg o dată pe zi, per os [3]. Another treatment method consists in the use of symptomatic therapy and an immunomodulatory and antiviral remedy such as 5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl(1→2)-β-D-glucopyranosyl(1→4)-β-D-galactopyranosyl]-26-O-β-D-glucopyranoside (Pacovirine) in the treatment of chronic viral hepatitis B, applied for 6 months, starting with the first day of clinical manifestations, in a dose of 50 mg once a day, orally [3].
Dezavantajele acestor metode constau în eficacitatea joasă a preparatelor antivirale, care nu permit de a obţine rezultatele scontate, şi în faptul că sunt contraindicate în cazul nivelului înalt de citoliză, totodată aceste metode de tratament rezolvă parţial problemele terapeutice ce stau în faţa medicului, şi anume stoparea sau diminuarea activităţii procesului hepatic şi prevenirea evoluţiei hepatitei spre ciroză. Pe de altă parte, copiii cu (HVCB), care au contraindicaţii sau nu s-au soldat cu aviremie (VHB) la administrarea terapiei antivirale cu remedii din clasa interferoanelor, recomandate de protocoalele internaţionale, sunt lipsiţi de posibilitatea efectuării unui alt tratament etiopatogenetic antiviral. Nu întotdeauna este obţinută normalizarea indicilor biochimici şi regresarea viremiei (HVB). The disadvantages of these methods are the low effectiveness of antiviral drugs, which do not allow to obtain the expected results, and the fact that they are contraindicated in the case of high levels of cytolysis, at the same time these treatment methods partially solve the therapeutic problems facing the doctor, namely stopping or reducing the activity of the liver process and preventing the evolution of hepatitis to cirrhosis. On the other hand, children with (HCV), who have contraindications or have not resulted in aviremia (HBV) when administering antiviral therapy with interferon class drugs, recommended by international protocols, are deprived of the possibility of performing another etiopathogenetic antiviral treatment. Normalization of biochemical indices and regression of viremia (HCV) is not always achieved.
Problema pe care o rezolvă invenţia dată este sporirea eficacităţii tratamentului (HVCB) la copii prin diminuarea nivelului de colestază, precum şi a nivelului de viremie înaltă a (HVB), care pot conduce la dezvoltarea fibrozei hepatice cu instalarea cirozei hepatice. The problem solved by this invention is to increase the effectiveness of (HVCB) treatment in children by reducing the level of cholestasis, as well as the level of high viremia of (HVB), which can lead to the development of liver fibrosis with the onset of liver cirrhosis.
Esenţa invenţiei constă în aceea că se efectuează tratamentul de bază, iar concomitent se administrează per os 5α-furostan-3β,22,26-triol-3-[O-β-D-glucopiranozil(1→2)- β-D-glucopiranozil(1→4)- β-D-galactopiranozil]-26-O-β-D-glucopiranozidă 100 mg, de 2 ori pe zi, 3-Ο-[β-D-glucopiranozil(1→2)]-[ β-D-glucopiranozil(1→3)]-[ β-D-glucopiranozil(1→4)]- β-D-galactopiranozil[(25R)-5α-furostan-2α, 3β, 22α, 26-tetraol]-26-Ο-β-D-glucopiranozidă 50 mg (Capsicozidă) şi acid ursodezoxicolic 15 mg/kg masă corp, o dată pe zi, timp de 24 de săptămâni. The essence of the invention consists in that the basic treatment is performed, and at the same time 5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl(1→2)- β-D-glucopyranosyl(1→4)- β-D-galactopyranosyl]-26-O-β-D-glucopyranosyl]-26-O-β-D-glucopyranoside 100 mg, 2 times a day, 3-Ο-[β-D-glucopyranosyl(1→2)]-[ β-D-glucopyranosyl(1→3)]-[ β-D-glucopyranosyl(1→4)]- β-D-galactopyranosyl[(25R)-5α-furostane-2α, 3β, 22α, 26-tetraol]-26-Ο-β-D-glucopyranoside 50 mg (Capsicoside) and ursodeoxycholic acid 15 mg/kg body weight, once a day are administered orally. day, for 24 weeks.
Rezultatul obţinut constă în obţinerea unei metode de tratament al hepatitei virale cronice B cu sindrom de colestază bazată pe sinergismul a trei preparate: Pacovirină, acid ursodezoxicolic şi Capsicozidă cu ameliorarea indicilor biochimici şi micşorarea duratei de spitalizare a acestora. Această metodă de tratament poate fi aplicată copiilor cu (HVCB) cu viremie (HVB) şi colestază chiar şi în cazul unei citolize, viremii înalte şi prezenţa markerilor (VHB), inclusiv la copiii, care au contraindicaţii la administrarea terapiei antivirale clasice. The result obtained consists in obtaining a method of treatment of chronic viral hepatitis B with cholestasis syndrome based on the synergism of three preparations: Pacovirin, ursodeoxycholic acid and Capsicoside with improvement of biochemical indices and reduction of their hospitalization duration. This treatment method can be applied to children with (HCV) with viremia (HBV) and cholestasis even in the case of cytolysis, high viremia and the presence of markers (HBV), including children who have contraindications to the administration of classical antiviral therapy.
Pentru aprobarea metodei propuse de tratament a (HCVB) la copii cu sindrom de colestază în baza secţiei de Hepatologie pediatrică a IMSP Institutul Mamei şi Copilului Clinica „Em. Coţaga” au fost efectuate investigaţii clinice, paraclinice, imunologice, virusologice cu confirmarea diagnosticului, determinarea ADN (HVB) cantitativ prin PCR, gradului de fibroză prin metoda de elastografie (Fibroscan) la copiii cu (HVCB) şi lotul-martor pentru aprecierea eficacităţii variantei noi propuse de tratament. Studiul a fost realizat randomizat prin metoda dublu-orb. For the approval of the proposed method of treatment of (HCVB) in children with cholestasis syndrome based on the Pediatric Hepatology Department of IMSP Institute of Mother and Child Clinic "Em. Coţaga" clinical, paraclinical, immunological, virological investigations were performed with confirmation of the diagnosis, quantitative determination of (HVB) DNA by PCR, the degree of fibrosis by elastography (Fibroscan) in children with (HVCB) and the control group to assess the efficacy of the new proposed treatment variant. The study was conducted in a randomized double-blind manner.
Astfel, au fost selectaţi în lotul experimental 7 bolnavi cu (HVCB) în fază de viremie (HVB) şi sindrom de colestază exprimat prin majorare de gama glutamiltranspeptidază (γGT), grad mediu şi înalt de activitate, cu vârstele cuprinse între 9…16 ani, care s-au soldat cu recădere după anularea tratamentului standard antiviral cu interferoane pegilate. Acestui grup de bolnavi li s-a iniţiat tratamentul tradiţional, care a inclus respectarea regimului igieno-dietetic (regim de salon, dieta nr. 5 după Pevzner), tratamentul hepatoprotector (silimarină sau fosfolipide esenţiale, legalon), terapia de dezintoxicare la indicaţii clinice (administrarea i/v a soluţiilor fiziologice, de glucoză, a hepasolului etc.) şi de corecţie a proceselor metabolice (vitaminele grupelor C, B1, B6, B12). Concomitent a fost administrat per os acidul ursodezoxicolic în doză de 15 mg/kg masă corp în 24 de ore per os, suplimentat cu Pacovirină (forma medicamentoasă în capsule), care a fost administrată timp de 6 luni în doze de 100 mg de 2 ori/zi per os şi Capsicozidă administrată în doze de 50 mg o dată pe zi. Thus, 7 patients with (HVCB) in the viremia phase (HVB) and cholestasis syndrome expressed by increased gamma glutamyltranspeptidase (γGT), medium and high degree of activity, aged between 9…16 years, who relapsed after the cancellation of standard antiviral treatment with pegylated interferons, were selected in the experimental group. This group of patients was initiated on traditional treatment, which included compliance with the hygienic-dietary regimen (salon regimen, diet no. 5 according to Pevzner), hepatoprotective treatment (silymarin or essential phospholipids, legalon), detoxification therapy according to clinical indications (i/v administration of physiological solutions, glucose, hepasol, etc.) and correction of metabolic processes (vitamins of groups C, B1, B6, B12). Concomitantly, ursodeoxycholic acid was administered orally at a dose of 15 mg/kg body weight in 24 hours orally, supplemented with Pacovirine (capsule dosage form), which was administered for 6 months at a dose of 100 mg 2 times/day orally, and Capsicoside administered at a dose of 50 mg once a day.
În lotul martor (n=7) bolnavii au fost selectaţi conform aceloraşi criterii, astfel ca grupurile să fie comparabile. În cadrul acestui grup, Pacovirina, Capsicozida şi acidul ursodezoxicolic au fost substituite. În rest, tratamentul a fost identic celui aplicat pacienţilor din lotul experimental. In the control group (n=7) patients were selected according to the same criteria, so that the groups were comparable. Within this group, Pacovirin, Capsicoside and ursodeoxycholic acid were substituted. Otherwise, the treatment was identical to that applied to the patients in the experimental group.
Rezultatele comparării metodei de tratament a (HVCB) la copii, conform invenţiei, cu cea mai apropiată soluţie (metoda tradiţională) au fost analizate la finele tratamentului, după 6 luni. The results of comparing the treatment method of (HVCB) in children, according to the invention, with the closest solution (the traditional method) were analyzed at the end of the treatment, after 6 months.
Rezultatele: Results:
Evaluarea comparativă a semnelor clinice de bază la copiii bolnavi cu hepatită virală cronică B cu sindrom de colestază trataţi cu Pacovirină, Capsicozidă şi acid ursodezoxicolic este prezentată în tabelul 1. Comparative evaluation of basic clinical signs in children with chronic viral hepatitis B with cholestasis syndrome treated with Pacovirin, Capsicoside and ursodeoxycholic acid is presented in Table 1.
Tabelul 1 Table 1
Evoluţia comparativă a principalelor sindroame clinice la bolnavii cu (HVCB) (lotul experimental) trataţi şi netrataţi (lotul martor II) cu Pacovirină, Capsicozidă şi acid ursodezoxicolic Comparative evolution of the main clinical syndromes in patients with (HCV) (experimental group) treated and untreated (control group II) with Pacovirin, Capsicoside and ursodeoxycholic acid
Nr Parametrii clinici / numărul de pacienţi Lotul I (experimental) (n=7) Lotul II (martor) (n=7) Până la tratament După tratament Până la tratament După tratament Abs. % Abs. %) Abs. % Ab.s % 1 Slăbiciune generală 7 100 1 14,3 7 100 7 100 2 Sindromul dolor în hipocondrul drept 5 71 0 0 6 86 6 86 3 Inapetenţă 7 100 0 0 7 100 7 100No. Clinical parameters / number of patients Group I (experimental) (n=7) Group II (control) (n=7) Before treatment After treatment Before treatment After treatment Abs. % Abs. %) Abs. % Abs.s % 1 General weakness 7 100 1 14.3 7 100 7 100 2 Pain syndrome in the right hypochondrium 5 71 0 0 6 86 6 86 3 Loss of appetite 7 100 0 0 7 100 7 100
Analiza şi evaluarea prezumtivă a datelor prezentate în tabelul 1 demonstrează că administrarea concomitentă a preparatelor Pacovirină, Capsicozidă şi a acidului ursodezoxicolic a avut acţiune benefică asupra evoluţiei principalelor semne clinice după tratament. În special merită atenţie evoluţia sindromului dolor în hipocondrul drept, care a dispărut la cei 5 copii din 7, şi inapetenţa, care a dispărut după tratament la toţi cei 7 bolnavi ai lotului experimental. Evoluţie favorabilă au înregistrat şi astfel de semne clinice ca senzaţia de greaţă, cefaleea, concomitent s-au micşorat şi dimensiunile ficatului. În lotul martor nu a fost constatată dispariţia semnelor clinice sau ameliorarea lor la un număr anumit de bolnavi. Evoluţia comparativă a indicilor de laborator (biochimici) la copiii bolnavi cu hepatită virală cronică B cu sindrom de colestază, trataţi cu Pacovirină, Capsicozidă şi acid ursodezoxicolic, până la şi după tratament este prezentată în tabelul 2. The analysis and presumptive evaluation of the data presented in Table 1 demonstrate that the concomitant administration of Pacovirin, Capsicoside and ursodeoxycholic acid preparations had a beneficial effect on the evolution of the main clinical signs after treatment. Particularly noteworthy is the evolution of the pain syndrome in the right hypochondrium, which disappeared in 5 out of 7 children, and inappetence, which disappeared after treatment in all 7 patients of the experimental group. Favorable evolution was also recorded in such clinical signs as nausea, headache, and at the same time the size of the liver decreased. In the control group, the disappearance of clinical signs or their improvement was not observed in a certain number of patients. The comparative evolution of laboratory (biochemical) indices in children with chronic viral hepatitis B with cholestasis syndrome, treated with Pacovirin, Capsicoside and ursodeoxycholic acid, before and after treatment is presented in Table 2.
Tabelul 2 Table 2
Caracteristica indicatorilor biochimici la pacienţii cu (HVCB) până la şi după tratament Characteristics of biochemical indicators in patients with (HVCB) before and after treatment
Indicatorii biochimici Lotul I experimental (n=7) Lotul II martor (n=7) Valorile normale > norma Valorile normale > norma Abs. M±m (%) Abs. M±m(%) Abs. M±m (%) Abs. M±m (%) ALAT (norma <41 U/l) Până la tratament 3 36,7±1,6 4 90,2±43,2 2 23±4 5 61,2±11,8 După tratament 7 100 0 1 27±0 6 73,2±11,75 ASAT (norma 0-37 U/l) Până la tratament 3 32,6±1,5 4 74±40 2 31,5±0,5 5 54,8±6,6 După tratament 7 100 0 2 30,5±0,5 5 44,4±6,0 γGTP (norma < 35 mmol/l) Până la tratament 0 0 7 59,1±22,5 1 32±0 6 72,3±21,1 După tratament 5 29,2±1,8 2 40±1 1 32±0 6 67,3±15,5Biochemical indicators Experimental group I (n=7) Control group II (n=7) Normal values > norm Normal values > norm Abs. M±m (%) Abs. M±m(%) Abs. M±m (%) Abs. M±m (%) ALAT (norm <41 U/l) Before treatment 3 36.7±1.6 4 90.2±43.2 2 23±4 5 61.2±11.8 After treatment 7 100 0 1 27±0 6 73.2±11.75 AST (norm 0-37 U/l) Before treatment 3 32.6±1.5 4 74±40 2 31.5±0.5 5 54.8±6.6 After treatment 7 100 0 2 30.5±0.5 5 44.4±6.0 γGTP (norm <35 mmol/l) Before treatment 0 0 7 59.1±22.5 1 32±0 6 72.3±21.1 After treatment 5 29.2±1.8 2 40±1 1 32±0 6 67.3±15.5
Conform rezultatelor înregistrate, în lotul experimental s-a depistat o evoluţie pozitivă a indicilor biochimici ALAT, ASAT, γGTP, care după tratament a fost în limitele normei la toţi pacienţii din lotul experimental incluşi în studiu. ALAT şi ASAT s-au normalizat la 4 din cei 4 pacienţi cu indicatori majoraţi până la tratament, γGTP la 5 din 7 cu indicatorii majoraţi anterior. În lotul martor, evoluţia favorabilă a indicatorilor biochimici s-a înregistrat la un număr mai mic de pacienţi. Deşi diferenţă între valorile medii ale parametrilor la sfârşitul tratamentului cu Pacovirină, Capsicozidă şi acid ursodezoxicolic faţă de aceiaşi indicatori din lotul martor este, se observă clar normalizarea indicatorilor biochimici de bază ALAT, ASAT şi tendinţa de normalizare a γGTP, caracteristici pentru contingentul de bolnavi cu hepatită virală cronică B cu sindrom de colestază. According to the recorded results, in the experimental group a positive evolution of the biochemical indices ALAT, ASAT, γGTP was detected, which after treatment was within the normal limits in all patients in the experimental group included in the study. ALAT and ASAT normalized in 4 of the 4 patients with increased indicators before treatment, γGTP in 5 of 7 with previously increased indicators. In the control group, the favorable evolution of the biochemical indices was recorded in a smaller number of patients. Although the difference between the average values of the parameters at the end of treatment with Pacovirin, Capsicoside and ursodeoxycholic acid compared to the same indicators in the control group is, the normalization of the basic biochemical indices ALAT, ASAT and the tendency to normalize γGTP are clearly observed, characteristics for the contingent of patients with chronic viral hepatitis B with cholestasis syndrome.
În tabelul 3 sunt prezentate nivelurile comparative de viremie ADN (HVB) exprimată în UI/ml în cele două loturi. Astfel copiii cu hepatita virală cronică B trataţi cu Pacovirină în doze de 100 mg, de 2 ori pe zi combinată cu Capsicozidă în doză de 50 mg, o dată pe zi şi acid ursodezoxicolic în doză de 15 mg/kg masă corp în 24 de ore pentru o perioadă de 24 de săptămâni au prezentat tendinţă spre diminuarea nivelului ADN (HVB). În total toţi cei 6 copii din lotul martor au prezentat semne de diminuare a nivelului de viremie ADN (HVB) (tabelul 3). Table 3 presents the comparative levels of DNA viremia (HVB) expressed in IU/ml in the two groups. Thus, children with chronic viral hepatitis B treated with Pacovirin at doses of 100 mg, 2 times a day combined with Capsicoside at a dose of 50 mg, once a day and ursodeoxycholic acid at a dose of 15 mg/kg body weight in 24 hours for a period of 24 weeks showed a tendency towards a decrease in the DNA level (HVB). In total, all 6 children in the control group showed signs of a decrease in the DNA viremia level (HVB) (table 3).
Tabelul 3 Table 3
Evoluţia comparativă a nivelului de ADN (HVB) în rândul copiilor din loturile experimental şi martor Comparative evolution of DNA (HVB) levels among children in the experimental and control groups
Lotul experimental Lotul martor Nr. d/o ADN (HVB) UI/ml până la tratament ADN (HVB) UI/ml după tratament Nr. d/o ADN (HVB) UI/ml până la tratament ADN (HVB) UI/ml după tratament 1 647902,6 153200 1 2000 25605 2 25605,8 697,6 2 275 275 3 2237499,6 1433664,6 3 1363 1363 4 155299020 65726814 4 15115 15115 5 167400264 56774217,6 5 3411 913 6 63008378,4 3813689,6 6 3492299 3492299 7 409 409 Media 388618670,4 127902283,4 Media 3514872 3535979Experimental group Control group No. d/o DNA (HVB) IU/ml before treatment DNA (HVB) IU/ml after treatment No. d/o DNA (HVB) IU/ml before treatment DNA (HVB) IU/ml after treatment 1 647902.6 153200 1 2000 25605 2 25605.8 697.6 2 275 275 3 2237499.6 1433664.6 3 1363 1363 4 155299020 65726814 4 15115 15115 5 167400264 56774217.6 5 3411 913 6 63008378.4 3813689.6 6 3492299 3492299 7 409 409 Average 388618670.4 127902283.4 Average 3514872 3535979
Remarcă: UI/ml - unităţi internaţionale de evaluare a încărcăturii virale Note: IU/ml - international units for viral load assessment
Pentru a da o apreciere statistică rezultatelor obţinute au fost comparate nivelurile medii şi dinamica evoluţiei ADN (HVB) din cele două loturi. S-a constatat că la copiii din lotul experimental a avut loc o diminuare semnificativă, cu 67,1±19,1% a nivelului ADN (HVB) (P<0,05). În acelaşi timp printre pacienţii din lotul martor s-a atestat o uşoară creştere a nivelului de viremie ADN (HVB) cu 0,6±2,9% (tabelul 4). In order to give a statistical assessment of the results obtained, the average levels and dynamics of DNA (HVB) evolution in the two groups were compared. It was found that in the children in the experimental group there was a significant decrease, by 67.1±19.1%, of the DNA (HVB) level (P<0.05). At the same time, among the patients in the control group, a slight increase in the level of DNA (HVB) viremia was observed by 0.6±2.9% (table 4).
Tabelul 4 Table 4
Dinamica reducerii încărcăturii virale la pacienţii cu hepatită cronică virală B ca rezultat tratamentului cu Pacovirină, Capsicozidă şi acid ursodezoxicolic (ADN (HVB) exprimat în UI/ml) Dynamics of viral load reduction in patients with chronic viral hepatitis B as a result of treatment with Pacovirin, Capsicoside and ursodeoxycholic acid (DNA (HVB) expressed in IU/ml)
Nivelul mediu de viremie ADN (HVB) înainte de tratament Nivelul mediu de viremie ADN (HVB) după tratament Dinamica evoluţiei nivelului de viremie ADN (HVB) P Lotul experimental 388618670,4 127902283,4 -67,1±19,1% P<0,05 Lotul martor 3514872 3535979 +0,6±2,9 -Average level of DNA viremia (HVB) before treatment Average level of DNA viremia (HVB) after treatment Dynamics of evolution of DNA viremia level (HVB) P Experimental group 388618670.4 127902283.4 -67.1±19.1% P<0.05 Control group 3514872 3535979 +0.6±2.9 -
Rezultatele prezentate denotă o acţiune benefică a remediilor Pacovirină, Capsicozidă şi acid ursodezoxicolic asupra evoluţiei principalelor semne clinice, biochimice şi imunologice la copiii cu hepatită virală cronică B colestatică, confirmată prin rezultatele investigaţiilor de laborator. The presented results denote a beneficial action of the remedies Pacovirin, Capsicoside and ursodeoxycholic acid on the evolution of the main clinical, biochemical and immunological signs in children with chronic cholestatic viral hepatitis B, confirmed by the results of laboratory investigations.
Toţi bolnavii incluşi în studiu au suportat bine Pacovirina, Capsicozida şi acidul ursodezoxicolic, nesemnalându-se reacţii adverse. Nici într-un caz nu a fost necesară sistarea tratamentului indicat pe parcursul perioadei de tratament, astfel demonstrându-se că Pacovirina, Capsicozida şi acidul ursodezoxicolic în combinaţie pot fi administrate copiilor cu hepatită virală cronică B. All patients included in the study tolerated Pacovirin, Capsicoside and ursodeoxycholic acid well, with no adverse reactions reported. In no case was it necessary to discontinue the indicated treatment during the treatment period, thus demonstrating that Pacovirin, Capsicoside and ursodeoxycholic acid in combination can be administered to children with chronic viral hepatitis B.
Exemplul 1 Example 1
Pacienta R.M., în varstă de 10 ani, este supravegheată în secţia de hepatologie pediatrică de la vârsta de 4 ani (din 2003) cu diagnosticul de “Hepatită virală cronică B colestatică, activitate biochimică medie, fază replicativă a (HVB). Colecistită cronică în remisie. Gastroduodenită cronică în remisie”. Patient R.M., aged 10, has been monitored in the pediatric hepatology department since the age of 4 (since 2003) with the diagnosis of “Chronic cholestatic viral hepatitis B, medium biochemical activity, replicative phase (HVB). Chronic cholecystitis in remission. Chronic gastroduodenitis in remission”.
Conform anamnesticului, este născută în familie cu risc sporit de infecţie cu (HVB). Ambii părinţi sunt “purtători” de AgHBs, fiind depistaţi concomitent cu maladia pacientei. La varsta de 4 ani pacienta a fost ocazional depistată cu hepatită virală acută B, forma anicterică, gravitate medie, fiind tratată şi supravegheată de medicul infecţionist. Conform datelor fişei medicale de ambulator, în perioada anilor 2004-2008 s-a menţinut starea generală alterată, persistenţa sindromului astenic cu apetitul scăzut şi activitate biochimică moderată. În 2008 în timpul examenului de monitorizare în dinamică la copil a fost constatată hepatomegalie moderată cu proeminarea ficatului sub rebordul costal drept cu 3 cm, ALAT- 55 U/l, ASAT- 43 U/l, sindromul de colestază exprimat prin gama glutamiltranspeptidază majorată 95 mmol/l şi nivel înalt de viremie (HVB) - 3 239 513 UI/ml. Ecografia abdominală a constatat hepatomegalie moderată cu diametrul venei porte în limita normei 10 mm, modificări difuze în parenchimul ficatului cu hiperecogenitate difuză, semne de colecistită cronică acalculoasă, sindrom de sludj al vezicii biliare. According to the anamnesis, she was born into a family with an increased risk of infection with (HVB). Both parents are “carriers” of AgHBs, being detected simultaneously with the patient’s illness. At the age of 4, the patient was occasionally detected with acute viral hepatitis B, anicteric form, moderate severity, being treated and supervised by the infectious disease physician. According to the outpatient medical record data, during the period 2004-2008, the general condition was maintained altered, the persistence of asthenic syndrome with low appetite and moderate biochemical activity. In 2008, during the dynamic monitoring examination in the child, moderate hepatomegaly was found with liver protrusion below the right costal margin by 3 cm, ALAT- 55 U/l, ASAT- 43 U/l, cholestasis syndrome expressed by increased gamma glutamyltranspeptidase 95 mmol/l and high level of viremia (HVB) - 3,239,513 IU/ml. Abdominal ultrasound found moderate hepatomegaly with portal vein diameter within the normal range of 10 mm, diffuse changes in the liver parenchyma with diffuse hyperechogenicity, signs of chronic acalculous cholecystitis, gallbladder sludge syndrome.
Pacientei i-a fost administrată dieta nr. 5 după Pevzner, Pacovirină, per os, în doză de 200 mg/zi în combinaţie cu Capsicozidă, 50 mg/zi şi acid ursodezoxicolic 500 mg/zi pentru o perioadă de 24 de săptămâni. Examenul repetat după finalizarea seriei de tratament a atestat normalizarea ALAT până la 41 U/l, ASAT 37 U/l, o diminuare a nivelului ADN (HVB) de 2 ori până la 1 614 931 UI/ml, o ameliorare a stării generale. Drept concluzie poate fi constatat efectul benefic al tratamentului de alternativă prin administrarea combinată a Pacovirinei în doze de 200 mg/zi, Capsicozidei în doze de 50 mg/zi şi a acidului ursodezoxicolic în doze de 15 mg/kg/masă corp în 24 de ore pentru 24 de săptămâni, cu ameliorarea stării generale, a transaminazelor hepatice şi diminuarea nivelului viremiei ADN (HVB) cu 51%. The patient was administered diet No. 5 according to Pevzner, Pacovirin, per os, in a dose of 200 mg/day in combination with Capsicoside, 50 mg/day and ursodeoxycholic acid 500 mg/day for a period of 24 weeks. The repeated examination after completing the treatment series attested to the normalization of ALAT up to 41 U/l, ASAT 37 U/l, a decrease in the DNA level (HVB) by 2 times up to 1 614 931 IU/ml, an improvement in the general condition. In conclusion, the beneficial effect of alternative treatment can be observed through the combined administration of Pacovirine in doses of 200 mg/day, Capsicoside in doses of 50 mg/day and ursodeoxycholic acid in doses of 15 mg/kg/body weight in 24 hours for 24 weeks, with improvement in general condition, liver transaminases and a decrease in the level of DNA viremia (HVB) by 51%.
Exemplul 2 Example 2
Pacienta B.A., în varstă de 9 ani, este supravegheată de la vârsta de 7 ani în sectia de hepatologie pediatrică cu diagnosticul de “Hepatită virală cronică B colestatică. Activitate biochimică înaltă, fază de replicare înaltă a (HVB). Epilepsie“. Patient B.A., aged 9, has been under observation since the age of 7 in the pediatric hepatology department with the diagnosis of “Chronic cholestatic viral hepatitis B. High biochemical activity, high replication phase of (HVB). Epilepsy“.
Conform anamnesticului, este născută din prima sarcină, care a evoluat cu eminenţă de avort pe parcursul întregii perioade, în familie cu risc sporit de infecţie cu (HVB). Mama fetiţei până la naştere a fost diagnosticată cu (HVCB), grad înalt de activitate, viremie înaltă (HVB). Fratele mai mic al pacientei în vârstă de 3 ani, de asemenea la naştere a fost depistat cu HBsAg pozitiv, fiind probabil infectat cu (HVB) intranatal şi actualmente se află în supraveghere şi tratament cu (HVCB) grad III de activitate, fază de viremie înaltă (HVB). According to the anamnesis, she was born from the first pregnancy, which progressed with eminence of abortion throughout the entire period, in a family with an increased risk of infection with (HVB). The mother of the girl was diagnosed with (HVCB), high degree of activity, high viremia (HVB) before birth. The patient's younger brother, aged 3, was also detected with HBsAg positive at birth, being probably infected with (HVB) intranatally and is currently under surveillance and treatment with (HVCB) degree III activity, high viremia phase (HVB).
Pacienta la vârsta de 7 ani, fiind în supravegherea neuropediatrului de la naştere pentru convulsii epileptiforme, a fost ocazional examinată şi depistată cu HBsAg. După examenul complex a fost confirmată hepatita virală cronică B, manifestată prin inapetenţă, slăbiciuni generale, dureri abdominale în hipocondrul drept. La examenul clinic şi paraclinic al pacientei în dinamică în 2009 a fost determinată starea generală de gravitate medie, care se manifesta prin sindrom astenic, inapetenţă, dureri abdominale şi hepatomegalie cu proeminarea cu 3 cm a ficatului sub rebordul costal drept, sensibil la palpare. Paraclinic a fost determinată hiperfermentemia cu ALAT 55 U/l, ASAT 43 U/l, sindromul de colestază exprimat prin gama glutamiltranspeptidază majorată 57 mmol/l şi nivel înalt de viremie (HVB) 207 000 000 UI/ml. Ecografia abdominală a constatat hepatomegalie moderată cu diametrul venei porte în limita normei 8 mm, modificări difuze în parenchimul ficatului cu hiperecogenitate difuză în ficat. The patient at the age of 7, being under the supervision of the neuropediatrician since birth for epileptiform convulsions, was occasionally examined and detected with HBsAg. After the complex examination, chronic viral hepatitis B was confirmed, manifested by loss of appetite, general weakness, abdominal pain in the right hypochondrium. During the clinical and laboratory examination of the patient in dynamics in 2009, the general condition of medium severity was determined, which was manifested by asthenic syndrome, loss of appetite, abdominal pain and hepatomegaly with a 3 cm protrusion of the liver under the right costal margin, sensitive to palpation. Laboratory tests determined hyperfermentemia with ALAT 55 U/l, ASAT 43 U/l, cholestasis syndrome expressed by increased gamma glutamyltranspeptidase 57 mmol/l and high viremia level (HVB) 207 000 000 IU/ml. Abdominal ultrasound revealed moderate hepatomegaly with a portal vein diameter within the normal range of 8 mm, diffuse changes in the liver parenchyma with diffuse hyperechogenicity in the liver.
Din motivele prezenţei afecţiunii organice a sistemului nervos central, care este o contraindicaţie la tratamentul clasic antiviral cu interferoane, pacientei i-a fost administrată dieta nr. 5 după Pevzner, Pacovirină, per os, în doză de 200 mg/zi în combinaţie cu Capsicozidă, câte 50 mg/zi şi acid ursodezoxicolic 500 mg/zi pentru o perioadă de 24 de săptămâni. Tratamentul a fost suportat sătisfăcător, fără reacţii adverse. Monitorizarea în dinamică a parametrilor clinici şi paraclinici după finalizarea seriei de tratament a constatat normalizarea ALAT până la 23 U/l, ASAT 19 U/l, o diminuare a nivelului ADN (HVB) de 2,5 ori de la 207 000 000 UI/ml până la 77 085 860 UI/ml, o ameliorare a stării generale şi în plan neurologic cu remisia timp de 6 luni. Drept concluzie poate fi constatat că administrarea combinată a Pacovirinei în doze de 200 mg/zi, a Capsicozidei 50 mg/zi şi a acidului ursodezoxicolic în doze de 15 mg/kg masă corp pentru 24 de săptămâni a contribuit la ameliorarea stării generale a pacientei, normalizarea ALAT şi ASAT şi la diminuarea nivelului viremiei ADN (HVB) de 2,5 ori. Due to the presence of organic disease of the central nervous system, which is a contraindication to classical antiviral treatment with interferons, the patient was administered diet No. 5 according to Pevzner, Pacovirin, per os, in a dose of 200 mg/day in combination with Capsicoside, 50 mg/day each and ursodeoxycholic acid 500 mg/day for a period of 24 weeks. The treatment was tolerated satisfactorily, without adverse reactions. Dynamic monitoring of clinical and paraclinical parameters after the completion of the treatment series found normalization of ALAT to 23 U/l, ASAT 19 U/l, a decrease in DNA level (HVB) by 2.5 times from 207 000 000 IU/ml to 77 085 860 IU/ml, an improvement in the general condition and neurologically with remission for 6 months. In conclusion, it can be stated that the combined administration of Pacovirine in doses of 200 mg/day, Capsicoside 50 mg/day and ursodeoxycholic acid in doses of 15 mg/kg body weight for 24 weeks contributed to the improvement of the patient's general condition, the normalization of ALAT and ASAT and the reduction of the level of DNA viremia (HVB) by 2.5 times.
Este necesar de menţionat că tratament cu Pacovirină, Capsicozidă şi acid ursodezoxicolic în aceleaşi doze a fost efectuat şi fratelui mai mic, în vârstă de 3,5 ani cu (HVCB), gr.III de activitate, şi după finalizarea seriei de tratament s-a diminuat nivelul ADN (HVB) de la 5 821 448 UI/ml (pretratament) până la 2 353 UI/ml (posttratament). It is necessary to mention that treatment with Pacovirin, Capsicoside and ursodeoxycholic acid in the same doses was also performed on the younger brother, aged 3.5 years with (HVCB), activity grade III, and after completing the treatment series, the DNA level (HVB) decreased from 5,821,448 IU/ml (pretreatment) to 2,353 IU/ml (posttreatment).
1. American Association for Study of Liver Deseases (AASLD). Guidelines for children, 2001 1. American Association for the Study of Liver Diseases (AASLD). Guidelines for children, 2001
2. Lous-Jacques O., Olson A.D. Cost-Benefit Analysis of Interferon Therapyin Children with Chronic Active Hepatitis B. J. Ped. Gastr. Nutr. 1997, Nr. 24, p. 25-32 2. Lous-Jacques O., Olson A.D. Cost-Benefit Analysis of Interferon Therapy in Children with Chronic Active Hepatitis B. J. Ped. Gastr. Nutrition 1997, No. 24, pp. 25-32
3. MD 1875 G2 2002.03.31 3. MD 1875 G2 2002.03.31
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