Publication: Kronik B Hepatitli Hastaların Geriye Dönük Olarak Değerlendirilmesi
Abstract
Bu çalışma Ondokuz Mayıs Üniversitesi Tıp Fakültesi Çocuk Gastroenteroloji Bölümünde 1997-2007 yılları arasında kronik hepatit B tanısı ile izlenen hastalarda ki; demografik verileri incelemek, başvuru sırasındaki klinik ve laboratuvar bulguları belirlemek, tedavi verilen kronik aktif hepatitli hastalarda interferon ve lamivudin tedavi etkinliğini değerlendirmek, tedavi sırasında görülen yan etkileri incelemek amacıyla planlandıVerileri düzenli olarak kaydedilmiş ve en az 6 ay takip edilmiş olan toplam 194 hasta (110 erkek/84 kız, ortalama yaşları 9,4±3,9 yıl) çalışmaya alındı. Çalışmada ki 194 olgunun 145'inde (%74,7) ailede hasta dışında en az bir kişide HBsAg pozitifliği vardı. Aile öyküsü pozitif olan 145 hastadan 90 hastanın (%62) annesinde HBsAg'i pozitifti. Olguların büyük bir kısmı (%73) başka nedenlerle yapılan incelemeler sırasında tesadüfen kronik hepatit B tanısı almışlardıKronik hepatit B enfeksiyonlu hastaların 34'ü (%18) inaktif taşıyıcı, 47'si (%24) immüntoleran, 113'ü (%58) ise kronik aktif hepatitli idi. Kronik aktif hepatitli 8 hastaya interferon, 13 hastaya lamivudin ve 92 hastaya kombine tedavi verilmişti. Hastaların tedaviye verdikleri yanıt, tedavi başlangıcından 18 ay sonra değerlendirildi. İnterferon monoterapisi uygulanan hastaların %50'sinin, lamivudin monoterapisi uygulanan hastaların %50'sinin ve kombinasyon tedavisi uygulanan hastaların %56'sının tedaviye tam yanıt verdiği belirlendiKombinasyon tedavisi verdiğimiz hastalar standart ve yüksek doz interferon uygulaması ile gelişen yan etki ve tedaviye verilen yanıt açısından değerlendirildi. Standart doz (5-7 MÜ/m2) uygulanan hastaların %52,7'si, yüksek doz (8-10 MÜ/m2) uygulanan hastaların %58,6'sı tedaviye tam yanıt verdi. İnterferon yan etkileri ve tedaviye verilen yanıt açısından iki grup arasında anlamlı fark bulunmadı (p>0,05Tedavi cevabını etkileyebilecek bazı prognostik faktörler (hasta yaşı, cinsiyeti, HAİ skoru, HBV DNA düzeyi) kombinasyon tedavisine cevap alınan ve alınamayan hastalarda karşılaştırıldı, anlamlı fark olmadığı görüldü (p>0.05). Diğer gruplar, hasta sayısı az olduğu için değerlendirme dışı bırakıldı. Başlangıç ALT değeri normalin üst sınırının 2 katından yüksek olan hastaların %67,7'si, düşük olan hastaların %49,1'i tedaviye tam yanıt verdi (p<0,05Lamivudin alan hastalarda yan etki gözlenmedi. İnterferon alan hastaların ise tümünde grip benzeri bulgular gözlendi. Grip benzeri bulgulara ek olarak hastalarımızın %7,6'sında iştahsızlık ve kilo kaybı, %2,1'inde saç dökülmesi %1'inde anksiyete-depresyon gibi yan etkiler görüldü. Anksiyete-depresyon görülen sadece bir hastamızda, bu yan etkiler nedeniyle interferon dozu azaltıldı. Hastalarımızın %13,3'ünde nötropeni, %5,5'inde trombositopeni, %5,5`inde anemi geliştiği görüldü. Ancak görülen bu hematolojik yan etkilerden hiçbiri tedavinin kesilmesini ya da interferon dozunun azaltılmasını gerektirecek düzeyde olmadı.Sonuçta kronik hepatit B enfeksiyonunun çocukluk çağında çoğunlukla belirti vermeden seyrettiği, hastaların büyük bir kısmının başka nedenlerle yapılan incelemeler sırasında tesadüfen tanı aldıkları görülmüştür. Tanı anında aile bireylerinde hepatit B oranının yüksek olması da enfeksiyonun daha çok aile içinde vertikal yada horizontal yolla bulaştığını düşündürmektedir. ALT düzeyi iki katından yüksek olan hastalarda tedaviye yanıtın daha iyi olduğu, diğer faktörlerin yanıtı etkilemediği görüldü. Lamivudine bağlı yan etki görülmemiş olup interferon tedavisi sırasındaki yan etkiler nedeniyle hastaların dikkatle izlenmeleri gereklidir.Anahtar Kelimeler: Kronik hepatit B, çocukluk çağı, kombinasyon tedavisi.
The study aimed to identify the demographic data of the patients who were diagnosed with chronic hepatitis B in Pediatric Gastroenterology Department of Ondokuz Mayıs University between the years 1997 and 2007. The study was designed to identify the clinical and laboratory findings of the patients on admission and evaluate the efficiency of interferon and lamivudine therapy and the side effects that may occur during interferon and lamivudine therapy.A total of 194 patients (110 male/84 female and mean age 9,4+3,9 years) the data of whom were regularly recorded and who were observed for at least 6 months were included in the study. At least one person in the family except the patient had positive test for HBsAg in 145 (74,7%) of 194 cases in the study. HBsAg was positive in the mothers of 90 (62%) patients out of 145 whose family history was positive. Most of the cases (73%) were diagnosed with hepatitis B incidentally during the other examinations.Thirty-four (18%), 47(24%) and 113 (58%) of the patients with chronic hepatitis B were inactive carriers, immunotolerant and chronic active hepatitis patients respectively. Eight patients with chronic active hepatitis received interferon,13 patients received lamivudine and 92 patients received o combined therapy. Patients responses to the treatment were evaluated the beginning of treatment eighteen months after. Fifty percent of the interferon administrated patients, 50% of the lamivudine administrated patients and 56% of the interferon-lamivudine combination administrated patients showed a complete response to the therapy.Interferon-lamivudine combination administrated patients were evaluated in terms of side effects of the standard and high-dose and the response to the therapy. 52,7% of the patients who received standard dose (5-7 MÜ/m2) and 58,6% of patients who received high-dose (8-10 MÜ/m2) showed complete response to the therapy. No significant difference was observed between the two groups in terms of the response to the therapy and side effects of the interferon therapy (p>0,05).Some prognostic factors that might affect the response to the combination therapy (the age, gender of the patient, HAI score, and the level of HBV DNA) were compared in the patients who responded to the therapy and those who did not respond to the therapy and no significant difference was observed (p>0,05). The other groups were excluded from the study as the numberof the patients was low. 67,7% of the patients with initial alt level greater than 2 times the upper limit of normal and 49,1% of the patients with alt level less than 2 times the upper limit of normal reported complete response to the therapy (p<0,05).No side effect was observed in patients receiving lamivudine. Flu-like syndrome findings were observed in patients receiving interferon. In addition to the flu-like syndrome findings, anorexia and weight loss, hair loss, anxiety-depression were observed in the patients by 7,6%, 2,1% and 1% respectively. Interferon dose was reduced in only one patient in whom side effects such as anxiety-nervousness-depression were observed. 13,3% of the patients developed neutropenia, 5,5% of the patients developed thrombocytopenia and 5,5% of the patients developed anemia. On the other hand, none of these hematological findings required the reduction of the dose or cessation of the therapyIn conclusion, it is revealed that hepatitis B infection progresses without displaying any symptoms in childhood and that the most of the patients were diagnosed with hepatitis B incidentally during the other examinations. That the family members have a high rate of hepatitis B at diagnosis demonstrates that infection spreads especially among family members in a vertical and horizontal fashion. The study revealed that the response rate was higher in patients with ALT level greater than 2 times the upper limit of normal. Other factors were not significant. No side effect due to lamivudine was observed but the patients should be carefully observed in terms of side effects during the interferon therapy.Key Words: Chronic hepatitis B, childhood, combination therapy.
The study aimed to identify the demographic data of the patients who were diagnosed with chronic hepatitis B in Pediatric Gastroenterology Department of Ondokuz Mayıs University between the years 1997 and 2007. The study was designed to identify the clinical and laboratory findings of the patients on admission and evaluate the efficiency of interferon and lamivudine therapy and the side effects that may occur during interferon and lamivudine therapy.A total of 194 patients (110 male/84 female and mean age 9,4+3,9 years) the data of whom were regularly recorded and who were observed for at least 6 months were included in the study. At least one person in the family except the patient had positive test for HBsAg in 145 (74,7%) of 194 cases in the study. HBsAg was positive in the mothers of 90 (62%) patients out of 145 whose family history was positive. Most of the cases (73%) were diagnosed with hepatitis B incidentally during the other examinations.Thirty-four (18%), 47(24%) and 113 (58%) of the patients with chronic hepatitis B were inactive carriers, immunotolerant and chronic active hepatitis patients respectively. Eight patients with chronic active hepatitis received interferon,13 patients received lamivudine and 92 patients received o combined therapy. Patients responses to the treatment were evaluated the beginning of treatment eighteen months after. Fifty percent of the interferon administrated patients, 50% of the lamivudine administrated patients and 56% of the interferon-lamivudine combination administrated patients showed a complete response to the therapy.Interferon-lamivudine combination administrated patients were evaluated in terms of side effects of the standard and high-dose and the response to the therapy. 52,7% of the patients who received standard dose (5-7 MÜ/m2) and 58,6% of patients who received high-dose (8-10 MÜ/m2) showed complete response to the therapy. No significant difference was observed between the two groups in terms of the response to the therapy and side effects of the interferon therapy (p>0,05).Some prognostic factors that might affect the response to the combination therapy (the age, gender of the patient, HAI score, and the level of HBV DNA) were compared in the patients who responded to the therapy and those who did not respond to the therapy and no significant difference was observed (p>0,05). The other groups were excluded from the study as the numberof the patients was low. 67,7% of the patients with initial alt level greater than 2 times the upper limit of normal and 49,1% of the patients with alt level less than 2 times the upper limit of normal reported complete response to the therapy (p<0,05).No side effect was observed in patients receiving lamivudine. Flu-like syndrome findings were observed in patients receiving interferon. In addition to the flu-like syndrome findings, anorexia and weight loss, hair loss, anxiety-depression were observed in the patients by 7,6%, 2,1% and 1% respectively. Interferon dose was reduced in only one patient in whom side effects such as anxiety-nervousness-depression were observed. 13,3% of the patients developed neutropenia, 5,5% of the patients developed thrombocytopenia and 5,5% of the patients developed anemia. On the other hand, none of these hematological findings required the reduction of the dose or cessation of the therapyIn conclusion, it is revealed that hepatitis B infection progresses without displaying any symptoms in childhood and that the most of the patients were diagnosed with hepatitis B incidentally during the other examinations. That the family members have a high rate of hepatitis B at diagnosis demonstrates that infection spreads especially among family members in a vertical and horizontal fashion. The study revealed that the response rate was higher in patients with ALT level greater than 2 times the upper limit of normal. Other factors were not significant. No side effect due to lamivudine was observed but the patients should be carefully observed in terms of side effects during the interferon therapy.Key Words: Chronic hepatitis B, childhood, combination therapy.
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