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Abstrak :

Introduksi: Relaparotomi dini pascatransplantasi hati donor hidup pada anak kerap dihadapkan pada luaran yang lebih buruk dibandingkan dengan pasien pascatransplantasi hati yang tidak memerlukan relaparotomy dini. Penelitian ini dilakukan untuk mengetahui faktor yang berhubungan dengan relaparotomi dini pascatransplantasi donor hidup pada anak

Metode: Penelitian potong lintang ini melibatkan seluruh resipien anak pascatransplantasi donor hidup di RSCM. Berdasarkan data rekam medis, setiap pasien dinilai skor PELD, lama operasi, jumlah perdarahan intraoperasi, warm ischemic time, dan cold ischemic time. Keempat faktor tersebut kemudian dianalisis hubungannya dengan kejadian relaparotomi dini.

Hasil: Terdapat 50 resipien anak pascatransplantasi donor hidup di RSCM dengan median usia subjek 17 bulan (5-61 bulan). Dari 50 subjek, 14 diantaranya memerlukan relaparotomi pascatransplantasi. Setelah dilakukan analisis, dari keempat faktor yang dinilai, hanya jumlah perdarahan intraoperasi yang bermakna secara statistik berhubungan dengan kejadian relaparotomi (p= 0.014).

Konklusi: Perdarahan intraoperasi merupakan salah satu faktor yang memengaruhi kejadian relaparotomi dini pada pasien anak dengan transplantasi hati donor hidup. Akan tetapi perlu diperhatikan faktor lain seperti power penelitian yang dapat memengaruhi hasil dan masih perlu ditingkatkan pada studi ini.

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Introduction: Early relaparotomy post living donor liver transplant in children usually faced with poor outcome compare to liver transplant patient without early relaparotomy. This study aims to identify factors associated with early relaparotomy in children undergone living donor liver transplant.

Methods: This is a cross sectional study including all of the children recipient of living donor liver transplant in Cipto Mangunkusumo Hospital (RSCM). Using the medical records, the PELD score, duration of the operation, total intraoperation blood loss, warm ischemic time, and cold ischemic time were measured. All of these factors were analyzed with the incidence of relaparotomy.

Results: Fifty children recipient of living donor liver transplant in RSCM were included in this study. The median age of the subject was 17 months old (5-61 months old). From 50 subjects, 14 of them were undergone relaparotomy post liver transplant. The total intraoperation blood loss has statistically significant associated with the incidence of relaparotomy (p= 0.014)

Conclusion: Intraoperation blood loss is one of the factors associated with the incidence of relaporotomy in children recipient of living donor liver transplant. Other factors associated with early relaparotomy still need to be explored to improve the power of this study.

 

Abstrak :
Latar Belakang: Fibrosis hati disebabkan cedera hati kronis akan menjadi sirosis. Vesikel ekstraseluler (VE) dan Hepatocyte Growth Factor (HGF) banyak dipelajari sebagai terapi fibrosis dan regenerasi hati. Penelitian ini memanfaatkan kombinasi VE dan recombinant human-HGF ( rh-HGF) sebagai terapi alternatif fibrosis hati pada model tikus ligasi duktus bilier (LDB). Metode: Sebelas tikus Sprague Dawley (SD) menjalani LDB, 5 tikus kontrol dan 6 tikus mendapat perlakuan injeksi VE 150 uL dan rh-HGF 0,1 mg intravena sejak 3 minggu pasca LDB, selama 7 hari. Satu tikus kontrol diterminasi 3 minggu pasca LDB sebagai data dasar. Tikus-tikus kelompok kontrol dan perlakuan diterminasi pada 1 hari dan 2 minggu setelah injeksi terakhir. Dilakukan penilaian skor Laennec hati serta kadar HGF, alanine aminotransferase (ALT) dan aspartate aminotransferase (AST). Hasil: Histopatologi 3 minggu pasca LDB menunjukkan skor Laennec 2. Skor fibrosis kelompok kontrol (KK) dan kelompok perlakuan (KP) 1 minggu dan 2 minggu pasca injeksi VE dan rh-HGF seluruhnya dengan skor 2. Kadar HGF pada KP lebih rendah secara signifikan dibandingkan dengan KK 1 hari pasca injeksi terakhir (1,35+0,06 vs 1,53+0,06; p<0,001), semakin menurun setelah 2 minggu pasca injeksi terakhir namun tidak bermakna secara statistik 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). Kadar AST 1 hari pasca injeksi terakhir; KK 1,66+0,05 KP 0,91+0,12 debgan p = 0,001. Setelah 2 minggu pasca injeksi; kadar AST pada kedua kelompok menurun 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021). Kadar ALT pada kelompok perlakuan lebih rendah secara signifikan pada 1 hari pasca injeksi dan 2 minggu pasca injeksi dengan nilai p<0,001 dan 0,033a ......Background: Fibrosis of the liver due to a chronic liver injury will become cirrhosis at the end-stage. The Extracellular Vesicles (EV) and hepatocyte growth factor (HGF) are recently learned as much as fibrosis and liver regeneration therapy. This study aims to know the result of using a combination of EV and recombinant human HGF (rh-HGF) as an alternative therapy due to liver fibrosis on the rat bile duct ligation (BDL) model. Methods: Eleven BDL Sprague Dawley (SD) were divided into two groups, five mice as the untreated control group and six mice as the treatment group was getting an EV 150 ul and rh-hgf 0.1 mg intravenous injection three weeks after BDL, for seven days. One control rat is expanded three weeks after BDL as baseline data. The control and treatment group mice were projected at day one and two weeks after the final injection. This study was assessed from liver fibrosis by using Laennec score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Hepatocyte Growth Factor (HGF) level. Results: Scoring of histopathology by using the Laennec score at 3 weeks after BDL was 2. Meanwhile scoring of fibrosis of the control group and treatment group at 1 week and 2 weeks after ve and rh-hgf injection were 2. HGF level of the treatment group was lower significantly than control group at day 1 after last injection (1,35+0,06 vs 1,53+0,06; p<0,001), and within 2 weeks, the number of HGF levels decreased but statistically insignificant; 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). AST level at day 1 after last injection; control group vs treatment group ;1,66+0,05 vs 0,91+0,12, p value = 0,001. 2 weeks after injection; AST level for both group were become lower 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021), and ALT level on treatment group was significantly lower at day 1 and 2 weeks after injection with p value <0,001 and 0, 033a

Abstrak :
Latar Belakang: Fibrosis hati disebabkan cedera hati kronis akan menjadi sirosis. Vesikel ekstraseluler (VE) dan Hepatocyte Growth Factor (HGF) banyak dipelajari sebagai terapi fibrosis dan regenerasi hati. Penelitian ini memanfaatkan kombinasi VE dan recombinant human-HGF ( rh-HGF) sebagai terapi alternatif fibrosis hati pada model tikus ligasi duktus bilier (LDB). Metode: Sebelas tikus Sprague Dawley (SD) menjalani LDB, 5 tikus kontrol dan 6 tikus mendapat perlakuan injeksi VE 150 uL dan rh-HGF 0,1 mg intravena sejak 3 minggu pasca LDB, selama 7 hari. Satu tikus kontrol diterminasi 3 minggu pasca LDB sebagai data dasar. Tikus-tikus kelompok kontrol dan perlakuan diterminasi pada 1 hari dan 2 minggu setelah injeksi terakhir. Dilakukan penilaian skor Laennec hati serta kadar HGF, alanine aminotransferase (ALT) dan aspartate aminotransferase (AST). Hasil: Histopatologi 3 minggu pasca LDB menunjukkan skor Laennec 2. Skor fibrosis kelompok kontrol (KK) dan kelompok perlakuan (KP) 1 minggu dan 2 minggu pasca injeksi VE dan rh-HGF seluruhnya dengan skor 2. Kadar HGF pada KP lebih rendah secara signifikan dibandingkan dengan KK 1 hari pasca injeksi terakhir (1,35+0,06 vs 1,53+0,06; p<0,001), semakin menurun setelah 2 minggu pasca injeksi terakhir namun tidak bermakna secara statistik 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). Kadar AST 1 hari pasca injeksi terakhir; KK 1,66+0,05 KP 0,91+0,12 debgan p = 0,001. Setelah 2 minggu pasca injeksi; kadar AST pada kedua kelompok menurun 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021). Kadar ALT pada kelompok perlakuan lebih rendah secara signifikan pada 1 hari pasca injeksi dan 2 minggu pasca injeksi dengan nilai p<0,001 dan 0,033a ......Background: Fibrosis of the liver due to a chronic liver injury will become cirrhosis at the end-stage. The Extracellular Vesicles (EV) and hepatocyte growth factor (HGF) are recently learned as much as fibrosis and liver regeneration therapy. This study aims to know the result of using a combination of EV and recombinant human HGF (rh-HGF) as an alternative therapy due to liver fibrosis on the rat bile duct ligation (BDL) model. Methods: Eleven BDL Sprague Dawley (SD) were divided into two groups, five mice as the untreated control group and six mice as the treatment group was getting an EV 150 ul and rh-hgf 0.1 mg intravenous injection three weeks after BDL, for seven days. One control rat is expanded three weeks after BDL as baseline data. The control and treatment group mice were projected at day one and two weeks after the final injection. This study was assessed from liver fibrosis by using Laennec score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Hepatocyte Growth Factor (HGF) level. Results: Scoring of histopathology by using the Laennec score at 3 weeks after BDL was 2.Meanwhile scoring of fibrosis of the control group and treatment group at 1 week and 2weeks after ve and rh-hgf injection were 2. HGF level of the treatment group was lower significantly than control group at day 1 after last injection (1,35+0,06 vs 1,53+0,06; p<0,001), and within 2 weeks, the number of HGF levels decreased but statistically insignificant; 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). AST level at day 1 after last injection; control group vs treatment group ;1,66+0,05 vs 0,91+0,12, p value = 0,001. 2 weeks after injection; AST level for both group were become lower 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021), and ALT level on treatment group was significantly lower at day 1 and 2 weeks after injection with p value <0,001 and 0, 033a

Abstrak :
Pendahuluan: Kembar siam adalah gangguan kongenital yang langka dengan insiden 1/50.000 hingga 1/500.000 kelahiran di seluruh dunia.1 Operasi pemisahan adalah pengobatan utama yang memiliki tingkat kematian tinggi hingga 60%. Penelitian sebelumnya menunjukkan bahwa kembar siam memiliki tingkat kejadian penyakit jantung kongenital hingga 66%, dengan kejadian tertinggi terlihat pada kembar siam thorakopagus.2 Penelitian ini bertujuan untuk mengevaluasi hubungan antara penyakit jantung kongenital (PJK) dan mortalitas kembar siam setelah operasi pemisahan. Metode: Kami melakukan studi retrospektif, pada semua pasien kembar siam yang menjalani operasi pemisahan di Rumah Sakit Dr. Cipto Mangunkusumo (RSCM) dari tahun 2009 hingga 2022. Dua puluh enam subjek ditemukan telah memenuhi kriteria inklusi dan eksklusi kami. Kompleksitas penyakit jantung kongenital didefinisikan oleh klasifikasi kompleksitas penyakit Bethesda. Hubungan antara kompleksitas PJK dan mortalitas dalam satu tahun pada pasien kembar siam yang menjalani operasi pemisahan dianalisis menggunakan uji Fisher. Hasil: Penyakit jantung kongenital terjadi pada kembar omfalopagus di RSCM. Tingkat kematian kembar siam dengan PJK yang menjalani operasi pemisahan di pusat kami adalah 40%, menunjukkan tidak adanya korelasi signifikan antara PJK dan mortalitas setelah operasi pemisahan, (p= 0,369). Kesimpulan: Kembar siam dengan PJK tidak menunjukkan korelasi dengan tingkat mortalitas setelah operasi pemisahan dalam studi awal ini. Penelitian lebih lanjut diperlukan dengan lebih banyak subjek untuk mendapatkan hasil yang lebih konklusif. ......Introduction: Conjoined twins are a rare congenital disorder with an incidence of 1/50.000 up to 1/500.000 births around the world.1 Separation surgery is the mainstay treatment which yields a high mortality rate of up to 60%. Previous studies show conjoined twins have a high incidence of congenital heart disease up to 66%, with the highest incidence evident in thoracopagus conjoined twins.2 This study aimed to evaluate the relationship between congenital heart disease (CHD) and conjoined twins mortality after separation surgery. Methods: We performed a retrospective study, on all conjoined twin patients who underwent separation surgery in Dr. Cipto Mangunkusumo Hospital (CMH) from 2009 until 2022. Twenty-six subjects were found to have fulfilled our inclusion and exclusion criteria. Congenital heart disease complexity was defined by Bethesda disease complexity classification. The relationship between CHD complexity within one-year mortality in conjoined twins patients who underwent separation surgery was analysed using Fischer’s exact test. Results: Congenital heart disease occurs in omphalopagus twins in CMH. The mortality rate of conjoined twins with CHD who underwent separation surgery in our centre was 40%, showing no significant correlation between CHD and mortality after separation surgery, (p= 0,369). Conclusion: Conjoined twins with CHD showed no correlation to mortality rates following separation surgery in this preliminary study. Further research is needed with more subjects to make more conclusive results.

Abstrak :
Latar Belakang: Di negara maju, angka mortalitas gastroskisis adalah 5-10%, berbeda dengan di negara berkembang. Angka mortalitas gastroskisis mencapai 52% di Brazil, 43% di Afrika Selatan, 35% di Iran, dan 79% di Jamaika. Di RSUPN Cipto Mangunkusumo (RSCM), sampai saat ini belum ada data mengenai angka mortalitas gastrosksis. Angka mortalitas gastroskisis di RSCM perlu diketahui karena karakteristik pasien yang diperkirakan berbeda dengan di negara maju. Tujuan dari penelitian ini adalah untuk mengetahui angka mortalitas gastroskisis di RSCM serta mengidentifikasi faktor risiko yang berpengaruh terhadap mortalitas gastroskisis, antara lain: usia kehamilan, berat badan lahir, jumlah operasi, usia saat operasi pertama kali, serta gastroskisis komplikata. Metode: Metode penelitian ini adalah studi kohort retrospektif dengan total sampling seluruh neonatus yang menjalani operasi penutupan defek di RSCM dari Januari 2015 – September 2020. Analisis bivariat dilakukan menggunakan uji Chi Square atau uji Fisher. Didapatkan 49 subjek neonatus dengan 7 data masuk kategori drop out sehingga 42 subjek diambil untuk dianalisis. Hasil: Angka mortalitas neonatus dengan gastroskisis di RSCM tahun 2015-2020 adalah 69% (29 dari 42 subjek). Pada penelitian ini didapatkan usia saat operasi (<1 hari) berpengaruh menurunkan angka mortalitas gastrosksis (p = 0,005). Usia kehamilan, berat badan lahir, jumlah operasi, dan gastroskisis komplikata didapatkan tidak berpengaruh terhadap angka mortalitas gastroskisis. Kesimpulan: Angka mortalitas gastrokisis di RSCM adalah 69% dan dipengaruhi oleh usia saat operasi. ......Background: Unlike developing countries, the mortality rate of gastroschizis in developed countries is much lower, accounting at 5-10%. In developing countries, for example, Brazil, the mortality rate can reach up to 52%, 43% in South Africa, 35% in Iran, and 79% in Jamaica. Until recently, there are no data regarding gastrochizis-related mortality rate in Cipto Mangkunkusumo National Referral Hospital, Indonesia. This is important as it reflects patient characteristics that is different with developed countries. The objective of this research is to find out the mortality rate of gastroschizis in Indonesia along with other possible influencing risk factors such as; gestational age, birth weight, number of operations, age at closure, and the presence of complicated gastroschizis. Methods: A cohort retrospective study with total sampling is used to document all neonates who undergo defect closure surgery from January 2015 to September 2020. Bivariate analysis is done using Chi Square test or Fisher test. A total of 49 neonates were documented, however 7 neonates were excluded due to drop out criteria, resulting in 42 neonates who were included in the analysis. Results: The mortality rate of gastroschizis in Cipto Mangkunkusumo National Referral Hospital is 69% (29 out of 42 subjects). The age at closure is related to lower mortality rate (p = 0.005), while other factors such as gestational age, birth weight, number of operations, and the presence of complicated gastroschizis has no impact on mortality. Conclusions: The mortality rate of gastroschizis in Cipto Mangkunkusumo National Referral Hospital is 69% and is influenced by age at closure.

Abstrak :
Latar Belakang: Vesikel ekstrasel (VE) dari sel punca mesenkimal (MSCs) telah banyak dipelajari dan memberikan hasil yang baik terhadap fibrosis dan regenerasi hati. Prekondisi MSCs dengan sitokin spesifik dapat meningkatkan aktivitas terapeutik dari VE. TNF-a dan TGF-b telah terbukti menghambat respon inflamasi dan memicu perbaikan jaringan bila digunakan untuk prekondisi MSCs pada penelitian bidang urologi dan ortopedi. Penelitian ini menggunakan VE dari sel punca mesenkimal tali pusat manusia (hUC-MSC) yang diprekondisikan dengan serum pasien atresia bilier yang mengandung TNF-a dan TGF-b sebagai terapi atresia bilier pada model tikus. Metode: Vesikel ekstrasel dari hUC-MSCs dikultur dalam medium komplit dan diprekondisikan dengan serum pasien atresia bilier. Dilakukan ekstraksi VE dengan sentrifugasi serial pada conditioned medium (CM) hUC-MSC tersebut. Sebelas tikus Sprague Dawley menjalani ligasi duktus koledokus (CBD), lima tikus sebagai kontrol dan enam tikus sebagai penerima perlakuan. Kelompok perlakuan mendapatkan injeksi EV intravena ekor yang dimulai 3 minggu pascaligasi CBD, sebanyak tujuh dosis 150 uL selama tujuh hari berturut-turut. Satu ekor tikus kontrol diterminasi 3 minggu pascaligasi CBD untuk melihat skor fibrosis sebelum diberikan perlakuan. Tikus-tikus kelompok kontrol dan perlakuan diterminasi pada 1 hari dan 2 minggu setelah injeksi VE terakhir. Dilakukan penilaian skor Laennec jaringan hati serta kadar hepatocyte growth factor (HGF), aspartate transaminase (AST), dan alanine transaminase (ALT) darah. Hasil: Pemeriksaan histopatologi jaringan hati 3 minggu pascaligasi CBD menunjukkan skor fibrosis 2. Skor fibrosis kelompok kontrol dan perlakuan 1 hari dan 2 minggu pascainjeksi VE seluruhnya mendapatkan nilai 2. Kadar HGF pada kelompok perlakuan lebih rendah secara signifikan dibandingkan dengan kelompok kontrol 1 hari pascainjeksi VE (1,04+0,11 vs 1,53+0,06; p<0,001), namun lebih tinggi pada 2 minggu pascainjeksi VE meskipun tidak bermakna secara statistik (1,18 (1,18-1,18) vs 0,83 (0,73-0,84); p=0,064). Kadar AST 1 hari pascainjeksi VE kelompok kontrol 1,66+0,05 dan kelompok perlakuan 1,29+0,15 dengan nilai p 0,001. Dua minggu pascainjeksi VE, perbedaan kadar AST pada kedua kelompok menurun (1,12(1,11-1,22) vs 0,74(0,70-0,78); p=0,064). Kadar ALT pada kelompok perlakuan lebih rendah secara signifikan pada 1 hari dan 2 minggu pascainjeksi VE dengan nilai p <0,001 dan 0,025. Kesimpulan: Vesikel ekstrasel dari hUC-MSC yang diprekondisikan dengan serum pasien atresia bilier tidak menurunkan skor fibrosis, namun dapat meningkatkan kadar HGF dan menurunkan penanda cedera hati. ......Introduction: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have long been studied and yield a satisfactory result in liver fibrosis and regeneration. Preconditioning of MSCs by specific cytokines can enhance the therapeutic activities of EVs. TNF-a and TGF-b were cytokines that has the potency to inhibit inflammatory responses and promote tissue repair when used as pre-conditioning agent of MSCs in nonliver studies. This study used serum of biliary atresia patients that contain TNF-a and TGF-b as pre-conditioning agent of human umbilical cord mesenchymal stem cells (hUCMSCs)- derived EVs for the treatment of biliary atresia rat model. Methods: hUC-MSCs were cultured in complete medium and pre-conditioned with serum of human biliary atresia patient. The conditioned medium (CM) from preconditioned hUC-MSCs underwent serial centrifugation to extract EVs. Eleven 5 weeks old Sprague Dawley rats underwent bile duct ligation (BDL). Five rats among the BDL group act as control while six rats were given EVs injection 3 weeks after BDL procedure, seven doses in seven consecutive days, 150 uL each dose. One rat were sacrificed 3 weeks post BDL for fibrosis staging prior to treatment. Rats from control and EVs group were sacrificed at 1 day and 2 weeks after the last EVs injection. Liver tissue were assessed for fibrosis score and blood were analysed for hepatocyte growth factor (HGF), aspartate transaminase (AST), and alanine transaminase (ALT). Results: Liver histopathology 3 weeks post BDL showed Laennec score 2. Fibrosis score of control and EVs group 1 day and 2 weeks after the last EVs injection were all 2. Hepatocyte growth factor level on EVs group were significantly lower than control group on 1 day post EVs injection (1,04+0,11 vs 1,53+0,06; p<0,001), but higher on EVs group on 2 weeks post EVs injection although not statistically significant (1,18 (1,18-1,18) vs 0,83 (0,73-0,84); p=0,064). The level of AST were 1,66+0,05 in control group and 1,29+0,15 in EVs group 1 day after EVs injection, with p value 0,001. Two weeks post EVs injection, the AST levels decreased furthermore (1,12(1,11-1,22) vs 0,74(0,70-0,78); p=0,064). Alanine transaminase level were significantly lower on EVs group both 1 day and 2 weeks post EVs injection, with p value <0,001 and 0,025. Conclusion: Extracellular vesicles from hUC-MSCs pre-conditioned with serum of biliary atresia patients could not lessen fibrosis score, but can increase HGF level and decrease markers of liver injury.

Abstrak :
Latar belakang: Sel punca mesenkim (SPM) telah menjadi salah satu alternatif untuk menghambat proses fibrosis dan memperbaiki fungsi hati. Berbagai jalur dapat digunakan untuk pemberian SPM, namun belum banyak studi yang membandingkan jalur pemberian. Pada studi ini dibandingkan pemberian SPM intrahepatika dan intrasplenika terhadap fungsi hati dan derajat fibrosis hati Oryctolagus cuniculus ligasi duktus bilier. Metode penelitian: Penelitian ekperimental dengan menggunakan model hewan kelinci (Oryctolagus cuniculus) yang dilakukan ligasi duktus bilier (LDB). Kelinci dibagi ke dalam 4 kelompok, yaitu kelompok sham surgery, LDB, injeksi SPM intrahepatika(LDB + SPM IH) dan injeksi SPM intrasplenika (LDB + SPM IS). Injeksi SPM tali pusat dilakukan pada hari kelima LBD, kemudian kelinci diobservasi sebelum diterminasi seluruhnya pada hari ke-14. Dinilai fungsi hati yang dinilai dengan kadar serum AST, ALT, bilirubin total dan direk, serta derajat fibrosis hati yang dinilai dengan skor Laennec.   Hasil penelitian: Dari total 23 kelinci, dibagi menjadi 4 kelompok, yaitu kelompok sham 2 ekor dan masing-masing 7 ekor untuk kelompok LDB, LDB + SPM IH, dan IS. Didapatkan mortalitas sebesar 57,1% pada kelompok LDB, mortalitas 14,3% pada kelompok LDB + SPM IH dan mortalitas 28,6 pada kelompok LDB + SPM IS sebelum penelitian selesai. Tidak didapatkan perbedaan yang bermakna untuk fungsi hati seperti AST, ALT, bilirubin total, dan direk antarkelompok, namun terkesan median fungsi hati pada kelompok LDB lebih tinggi dibanding sham surgery, serta median kelompok LDB + SPM IH dan IS lebih menyerupai normal. Fungsi hati tampak lebih baik pada kelompok LDB + SPM IS dibanding LDB + SPM IH, meskipun secara statistik tidak bermakna. Pemeriksaan histopatologi kelinci yang dilakukan ligasi duktus bilier menunjukkan derajat fibrosis Laennec 4B, yang tidak berbeda antar ketiga kelompok. Area fraction fibrosis, jumlah hepatosit yang viabel dan nekrosis, serta jumlah sel progenitor dianalisis, tidak terdapat perbedaan yang ditemukan antara kelompok LDB + SPM IH dan LDB + SPM IS, namun kelompok yang diberikan SPM memiliki jumlah hepatosit viabel yang lebih banyak dibandingkan kelompok LDB. Kesimpulan: Pemberian SPM intrahepatika dan intrasplenika tidak berpengaruh pada fungsi hati dan derajat fibrosis hati Oryctolagus cuniculus pascaligasi duktus bilier. Pemberian SPM akan meningkatkan jumlah hepatosit yang viabel pada model cuniculus pascaligasi duktus bilier. ......Background: Mesenchymal stem cell (MSC) becomes an alternative to attenuate liver fibrosis and to improve liver function. A couple of administration route had been studied, but few compared one to another. This study aims to compare intrahepatic and intrasplenic route of administration of MSC in regards of liver function and degree of liver fibrosis in Oryctolagus cuniculus bile duct ligation model. Method: This is an experimental study using rabbit (Oryctolagus cuniculus) bile duct ligation model. The subjects were randomized into 4 groups: sham surgery, bile duct ligation (BDL), intrahepatic route of MSC (BDL + MSC IH), and intrasplenic route of MSC (BDL + MSC IS). Umbilical cord MSC was administered in the fifth day of bile duct ligation, and the subject was observed until terminated on 14th day post BDL. The liver function, such as AST, ALT, total and direct bilirubin were evaluated, and the degree of fibrosis was evaluated with Laennec score.  Result: The subjects were grouped into 4 group: 2 sham surgery, and each had 7 in BDL, BDL + MSC IH and BDL + MSC IH groups. Mortality rate in control group was 57,1%, mortality in BDL + MSC IH group was 14,3% and in BDL + MSC IS group was 28,6%. No significant difference was found regarding liver function in each group such as AST, ALT, total and direct bilirubin, but the median of liver function in BDL group seemed worse than in sham sugery group, and the median of liver function in BDL + MSC IH and BDL + MSC IS groups were closed to sham operated (normal). Liver function seemed to be better in BDL + MSC IS group compared to BDL + MSC IH group, but showed no statistical difference. Histopathology examination in subjects undergone bile duct ligation (regardless of MSC) show the degree of fibrosis of Laennec 4B. Fibrosis area fraction, the number of viable and necrosis hepatocyte, and progenitor cell are analysed; no significant difference was found between BDL + MSC IH and BDL + MSC IS group, but the group administered with MSC shows larger number of viable hepatocyte compared to BDL group. Conclusion: Administration of intrahepatic or intrasplenic MSC did not show significant improvement the liver function and liver fibrosis in Oryctolagus cuniculus bile duct ligation model. Administration of MSC would increase the number of viabel hepatocyte in Oryctolagus cuniculus bile duct ligation model.

Abstrak :
Latar belakang: Atresia bilier merupakan penyebab paling umum fibrosis hati pada anak, dan menjadi indikasi terbanyak transplantasi hati. Fibrosis hati dapat dinilai dengan pemeriksaan histopatologis dan kuantifikasi skor Laennec. Pemeriksaan biomarker dari darah dan metode pencitraan radiologis merupakan upaya lain untuk menilai derajat fibrosis hati. Penelitian ini dimaksudkan untuk meneliti perbandingan biomarker penanda fibrosis transforming growth factor (TFG-β), matrix metalloproteinase (MMP)-7, dan ultrasonografi (USG) Acoustic Radiation Force Impulse (ARFI) dengan derajat fibrosis berdasarkan pemeriksaan histopatologi. Metode penelitian: Penelitian ini merupakan penelitian desain cross sectional pada pasien anak dengan kolestasis yang dicurigai akibat atresia bilier di ruang rawat anak RSUPN Cipto Mangunkusumo. Data penelitian ini adalah data primer dari anamnesis, pemeriksaan fisik, serta data sekunder dari rekam medis untuk melihat riwayat penyakit pasien. Dilakukan pemeriksan serum biomarker TGF-β dan MMP-7, dan USG ARFI oleh operator yang telah ditentukan. Dibandingkan hasil pemeriksaan TGF-β, MMP-7, USG ARFI dengan hasil skoring fibrosis biopsi hati. Hasil penelitian: Dari total 15 pasien dengan AB, terdapat 6 pasien F2-F3, dan 9 pasien F4 berdasarkan derajat fibrosis biopsi hati. Terdapat peningkatan kadar TGF-β dengan adanya peningkatan derajat fibrosis biopsi hati, namun tidak terdapat hubungan bermakna antara derajat fibrosis hati dengan kadar TGF-β (uji Mann-Whitney, p=0.768). Pada penelitian ini, rerata kadar MMP-7 pada kelompok F2-3 dan F4 menunjukan peningkatan, namun tidak terdapat hubungan yang bermakna (Uji Mann-Whitney, p=0.409). Terdapat hubungan bermakna antara derajat fibrosis hati F2-F3 dengan derajat F4 yang diperoleh berdasarkan hasil USG ARFI dan hasil biopsi hati (p<0,01). Kesimpulan: TGF-β dan MMP-7 merupakan biomarker yang cukup efektif namun memiliki keterbatasan tidak spesifik untuk AB. USG ARFI merupakan pemeriksaan minimal invasive yang efektif untuk menentukan derajat fibrosis. ......Background: Biliary atresia is the most common cause of liver fibrosis and the highest indication for liver transplantation in pediatrics. Liver fibrosis is quantified through Laennec score based on histopathology of liver biopsy. Blood serum biomarkers and radiological examinations are alternative methods that could determine liver fibrosis. This study aimed to compare the significance of serum biomarkers transforming growth factor (TFG-β), matrix metalloproteinase (MMP)-7, and Acoustic Radiation Force Impulse (ARFI) ultrasonography (USG) in determining the degree of liver fibrosis compared to histopathology score from liver biopsy. Method: This was a cross-sectional study, on patients in the pediatric ward at dr. Cipto Mangunkusumo National Hospital, that were admitted with cholestasis with biliary atresia as the suspected etiology. Primary data was obtained through anamnesis, and physical examination, and secondary data was obtained through patients’ medical records. Serum biomarkers TGF-β and MMP-7, and USG ARFI were examined by related experts and results were obtained through medical records. Results of TGF-β, MMP-7, and USG ARFI were compared with fibrosis scores based on liver biopsy. Result: From a total of 15 patients with AB, there were 6 F2-F3 patients, and 9 F4 patients according to the biopsy results. TGF-β levels showed and increasing trend alongside increase in liver biopsy fibrosis score, however it was not statistically significant (Mann- Whitney test, p=0.768). In this study, there was an increase in MMP-7 levels in F2-3 group compared to f4 group, however there was no statically significant difference (Mann-Whitney test, p=0.409). The ARFI USG results showed significant difference between F2-F3 group and F4 group based on ARFI USG compared to liver biopsy (p<0.01). Conclusion: TGF-β and MMP-7 are effective serum biomarkers, however, lacked specificity to determine fibrosis levels in biliary atresia. A minimally invasive test that is effective in determining the degree of fibrosis can be done through ARFI USG.