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"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.

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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. "

"Latar Belakang dan tujuan: Penyakit hati kronik pada pasien pediatrik merupakan salah satu masalah utama kesehatan pada populasi anak-anak dengan angka morbiditas dan mortalitas yang cukup tinggi. Penilaian derajat fibrosis hati diperlukan untuk menentukan tatalaksana yang sesuai, menentukan prognosis, dan tindak lanjut pasca pengobatan. Pemeriksaan USG elastografi acoustic radiation force impulse ARFI merupakan metode penilaian derajat fibrosis hati yang bersifat tidak invasif, mudah dan cepat dikerjakan. Penelitian ini bertujuan untuk mendapatkan nilai titik potong derajat fibrosis USG elastografi ARFI pada pasien pediatrik dengan penyakit hati kronik. Metode: Pasien pediatrik dengan penyakit hati kronik menjalani pemeriksaan USG elastografi ARFI. Didapatkan nilai shear wave velocity SWV dari pemeriksaan ARFI yang menunjukkan elastisitas jaringan hati pada 18 subjek dan dihubungkan dengan hasil biopsi hati METAVIR . Kurva receiver-operating characteristic ROC dilakukan untuk menentukan titik potong derajat fibrosis hati. Hasil: Rerata nilai median ARFI pada pasien pediatrik dengan penyakit hati kronik tanpa fibrosis hati 1,21 m/s; fibrosis ringan F1 1,13 m/s; fibrosis signifikan F2 ; fibrosis berat F3 2,76 m/s; dan sirosis F4 3,84 m/s. Kurva ROC menunjukkan titik potong ARFI pada 1,98 m/s memiliki sensitivitas 100 untuk mendeteksi derajat fibrosis ge;F3. Kesimpulan: USG elastografi ARFI merupakan metode yang dapat diandalkan, cepat, dan non invasif untuk menentukan derajat fibrosis berat dan sirosis pada pasien pediatrik. Hasil pemeriksaan ARFI dapat membantu klinisi dalam tindak lanjut pengobatan dan alternatif biopsi hati pada kondisi tertentu.

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Background and objectives: Chronic liver disease in pediatric patients is one of the major health problems with high rates of morbidity and mortality. Assessment of the degree of liver fibrosis is needed to determine appropriate management, determine prognosis, and post treatment follow up. Ultrasound acoustic radiation force impulse ARFI elastography examination is a non invasive, easily and rapidly performed liver fibrosis assessment method. The objective of this study was to obtain the cut off value of fibrosis degree with ARFI examination in pediatric patients with chronic liver disease.

Methods: Pediatric patients with chronic liver disease underwent ARFI ultrasound measurements. Shear wave velocity SWV value obtained from ARFI examination showing elasticity of liver tissue in 18 subjects and associated with liver biopsy results METAVIR . The receiver operating characteristic ROC curve is performed to determine cut off value of degree of liver fibrosis.

Results Mean of SWV value in pediatric patients with chronic liver disease without liver fibrosis 1.21 m s mild fibrosis F1 1.13 m s significant fibrosis F2 severe fibrosis F3 2.76 m s and cirrhosis F4 3.84 m s. The ROC curve shows the cut off at 1.98 m s yielded a 100 sensitivity to detect the degree of fibrosis ge F3.

Conclusions USG elastographic ARFI is a reliable, rapid, and non invasive method for determining the degree of severe fibrosis and cirrhosis in pediatric patients. The results of the ARFI examination may assist the clinician in the follow up of treatment and alternatives of liver biopsy in certain condition."

"Background: acoustic radiation force impulse (ARFI) is a new proposed noninvasive method for liver fibrosis staging. Integrated with B mode ultrasonography, ARFI can be used to assess liver tissue condition. However its diagnostic accuracy is still being continuously evaluated. Also, there is lack of data regarding the utilization of ARFI in our population. This study aimed to evaluate the diagnostic value of ARFI as an alternative noninvasive modality for fibrosis staging in chronic hepatitis B and hepatitis C patients in our population.Methods: we conducted cross sectional comparison of ARFI imaging and transient elastography on patients who underwent liver biopsy at Cipto Mangunkusumo Hospital. Fibrosis staging using METAVIR scoring system presented as standard reference. A total of 43 patients underwent liver biopsy was evaluated by ARFI imaging and transient elastography. Cut off values were determined using receiver operating characteristic (ROC).Results: both liver stiffness determined by ARFI and transient elastography (TE) were moderately correlated with METAVIR score with value of 0.581 and 0.613, respectively (both P<0.01). Diagnostic accuracy of ARFI predicted significant fibrosis (F>2) with area under receiver operating characteristic curve (AUROC) of 0.773 (95% CI 0.616-0.930) and even better for cirrhosis (F4 fibrosis), expressed as AUROC of 0.856 (95% CI 0.736-0.975). Transient elastography was better for significant fibrosis with AUROC of 0.761 (95% CI 0.601-0.920) and was best for prediction of cirrhosis, expressed as AUROC of 0.845 (95% CI 0.722-0.968).Conclusion: ARFI is provided with more convenient evaluation of liver tissue condition, and its diagnostic accuracy is not significantly different from TE for staging liver fibrosis."

"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.

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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."

"ABSTRAKLatar Belakang: Mangiferin merupakan senyawa bioaktif yang diketahui dapat menghambat fibrosis, yaitu proses reversibel akibat jejas pada hati. Penelitian ini bertujuan untuk membuktikan efek mangiferin dalam menghambat fibrogenesis melalui hambatan terhadap ekspresi mRNA TGF-?, yaitu sitokin profibrogenik utama. Metode: Penelitian eksperimental ini menggunakan RNA yang diisolasi untuk mendapatkan cDNA, di mana kelompok perlakuan diberikan tioasetamid 200 mg/kg BB sebanyak 3 kali/minggu selama 5 minggu oleh Arozal W, dkk. Perlakuan dibagi menjadi kelompok kontrol, tioasetamid 200 mg/kg BB, tioasetamid 200 mg/kg BB mangiferin 50 mg/kg BB/hari, dan tioasetamid 200 mg/kg BB mangiferin 100 mg/kg BB/hari. Tingkat ekspresi mRNA TGF-? diukur dengan RT-PCR dan dihitung dengan metode Livak. Hasil: Terdapat peningkatan ekspresi mRNA TGF-? pada kelompok yang hanya diberikan tioasetamid terhadap kelompok kontrol. Pada kelompok yang diberikan mangiferin, terdapat penurunan ekspresi mRNA TGF-? terhadap kelompok yang hanya diberikan mangiferin, dengan penurunan ekspresi mRNA pada kelompok yang diberikan mangiferin 50 mg/kg BB/hari lebih besar. Kesimpulan: Mangiferin dapat menurunkan tingkat ekspresi mRNA TGF-? pada hati tikus yang diinduksi oleh tioasetamid, namun efeknya tidak linear antara dosis mangiferin dengan respon yang diberikan.

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ABSTRACT

Background Mangiferin is a bioactive compound that is known to inhibit fibrosis, a reversible process that occurs as a result of liver injury. This study aims to prove the antifibrotic effect of mangiferin through inhibition of mRNA expression of TGF , which is the main profibrogenic cytokine. Method This experimental design uses isolated RNA to get cDNA, which treatment groups are given thioacetamid with dose of 200 mg kg BW, three times a week for five weeks consecutively, in study from Arozal W, et al. The treatment groups are control group, thioacetamid 200 mg kg BW, thioacetamid 200 mg kg BW mangiferin 50 mg kg BW day, and thioacetamid 200 mg kg BW mangiferin 100 mg kg BW day. The expression of TGF mRNA is measured with RT PCR and quantified with Livak method. Result There is an increase mRNA expression of TGF in group that was given thioacetamide only compare to the control group. In the groups that were on treatment of mangiferin, the mRNA expressions of TGF are lower than the thioacetamid only group. The mRNA expression of TGF of the group that was given mangiferin of dose 50 mg kg BW day is also lower compare to the group that was given higher dose of mangiferin. Conclusion Mangiferin can lower the expression of TGF in rats liver induced by thioacetamide. However, mangiferin does not give linear effect between dose and response."

"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

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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"

"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

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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"

"mengalami kerusakan dan sirosis hati. Walaupun tidak ada data terbaru mengenai insiden kerusakan hati di Indonesia, Riskesdas 2013 menyampaikan adanya prevalensi yang tinggi dari persentase HBsAg, anti-HBs, dan anti-HBc. Selain itu, dalam kurun waktu 30 tahun (1980—2010), terdapat peningkatan tingkat kematian sirosis hati sebanyak 25,1%. Model hewan yang sesuai sangatlah penting dalam meneliti kerusakan hati. Karbon tetraklorida (CCl4) sudah lama digunakan untuk menginduksi fibrosis hati pada model tikus. Walaupun dapat menginduksi pengendapan jaringan ikat, regenerasi hepatoseluler, proliferase sel stelata, dan infiltrasi sel-sel inflamasi, kerusakan pada model tikus yang diinduksi CCl4 hanya merepresentasikan kerusakan hati sampai batas tertentu, mirip dengan kerusakan hati akibat obat. Dengan tujuan meniru kerusakan hati yang lebih parah, penelitian ini mengkombinasikan penggunaan CCl4 dengan asetilaminofluorena-2 (2AAF) karena 2AAF terbukti dapat menekan proliferasi hepatosit sehingga terjadi proliferasi sel oval yang berakibat pada proliferasi duktular. Metode: Desain penelitian ini adalah penelitian observasional terhadap penelitian analitik eksperimental dengan bahan biologis tersimpan yang diambil dari Departemen Patologi Anatomi Fakultas Kedokteran Universitas Indonesia. Penelitian ini menggunakan data primer eksperimental dengan 15 sampel yang dikategorikan dalam 3 kelompok: kontrol sehat, diinduksi CCl4, dan diinduksi 2AAF/CCl4, dan dianalis di bawah mikroskop dalam hal tingkat fibrosis, daerah cakupan fibrosis, dan jumlah proliferasi duktus. Analisis statistik yang digunakan meliputi uji Fisher, Shapiro-Wilk, Kruskal Wallis, dan Mann Whitney menggunakan program SPSS. Hasil: Kelompok 2AAF/CCl4 dan CCl4 memiliki perbedaan derajat fibrosis yang signifikan dengan kontrol sehat (p=0,024 dan p=0,048 secara berurutan), tanpa perbedaan signifikan di antara kedua kelompok tersebut (p=0,286). Perbedaan cakupan area fibrosis antara kedua kelompok juga tidak signifikan (p=0,055), walau kelompok 2AAF/CCl4 dan CCl4 berbeda signifikan dengan kontrol sehat (p=0,007 dan p=0,008 secara berurutan). Dalam hal proliferasi duktular, kelompok CCl4 tidak menunjukkan perbedaan signifikan dengan kontrol sehat (p=0,101), namun berbeda signifikan dengan kelompok 2AAF/CCl4 (p=0,000). Kesimpulan: Tidak terdapat perbedaan derajat dan cakupan area fibrosis yang signifikan antara kelompok 2AAF/CCl4 dan CCl4. Namun demikian, terjadi proliferasi duktular yang secara signifikan lebih tinggi pada kelompok 2AAF/CCl4 dibandingkan kelompok CCl4 saja.

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Background: In 2017, approximately 1.8% of adult in United States suffer from chronic liver disease and cirrhosis. Although there is not any recent data, Riskesdas 2013 showed a high percentage of HBsAg, anti-HBs, and anti-HBc prevalence in Indonesia. On top of that, in Indonesia, in the course of 30 years (1980—2010), liver cirrhosis mortality rate increased by 25,1%. In order to study liver disease, having an appropriate animal model is crucial. Carbon tetrachloride (CCl4) has been used to induce liver fibrosis in mouse model. Although able to induce connective tissue deposition, hepatocellular regeneration, stellate cells proliferation, and inflammatory infiltration, CCl4-induced rat models only represent liver injury to some extent, similar to drug-induced liver injury. In order to mimic a more severe liver injury, this study combined the use of CCl4 with 2- acetylaminofluorene (2AAF), as 2AAF has proven to be able to suppress hepatocyte proliferation and allow oval cells proliferation that leads to ductular proliferation. Method: This research design is an observational research on an analytic experimental study with stored biological material taken from the Department of Anatomy Faculty of Medicine University of Indonesia. This research uses experimental primary data, with 15 samples categorized into three groups: healthy control, CCl4-induced, and 2AAF/CCl4- induced, and analysed for the degree of fibrosis, fibrosis-affected area, and number of proliferating ductules under the microscope. A statistical analysis is then conducted using Shapiro-Wilk, Kruskal Wallis, and Mann Whitney by using SPSS programme. Result: There is a significant difference in the degree of fibrosis between both 2AAF/CCl4 and CCl4 groups with the healthy control (p=0,024 dan p=0,048 respectively), without any significant difference in between the two groups (p=0,286). The affected fibrosis area difference between the two groups is also insignificant (p=0,055), though the 2AAF/ CCl4 and CCl4 groups are significantly different to the healthy control (p=0,007 and p=0,008 respectively). For ductular proliferation, CCl4 group did not show any significant difference compared to the healthy group (p=0,101), but was significantly different to the 2AAF/CCl4 group (p=0,000). Conclusion: There is not any significant difference regarding the degree of fibrosis and its affected area between the 2AAF/CCl4 and CCl4 groups. However, there is a significant difference between the two groups in terms of ductular proliferation, in which the 2AAF/CCl4 group’s ductular proliferation was higher."

"Latar Belakang: Penyakit thalassemia tinggi prevalensinya di Indonesia. Modalitas MRI digunakan pasien transfusion-dependent thalassemia (TDT) yang menjalani transfusi darah berkesinambungan untuk menilai tingkat zat besi di organ hati. Pemeriksan ini memerlukan biaya tinggi dan hanya tersedia di dua kota besar di Indonesia. Kandungan zat besi yang tinggi dalam waktu yang lama di hati dapat berakibat pada kerusakan hati. Modalitas yang lebih terjangkau dari segi lokasi dan biaya diperlukan dalam menilai tingkat zat besi di organ hati pada kelompok pasien ini.Tujuan : Mengetahui kekuatan korelasi antara nilai shear wave velocity (SWV) acoustic radiation force impulse (ARFI) dengan nilai T2* MRI dalam menilai zat besi organ hati.Metode : Data primer SWV ARFI dan nilai T2* MRI dari 29 pasien TDT dikumpulkan lalu dianalisis dengan SPSS untuk mengukur korelasi.Hasil : Penelitian ini menunjukkan korelasi negatif dengan kekuatan yang moderat antara nilai SWV ARFI dan nilai T2* MRI hati (R = -0,383) yang bermakna secara statistik (Spearman P = 0,040).Kesimpulan : ARFI merupakan pemeriksaan yang memiliki korelasi dengan pemeriksaan MRI dalam menilai kandungan zat besi organ hati pasien TDT. Namun demikian, penelitian ini tidak menunjukkan hubungan yang kuat, dan oleh sebab itu mungkin dibutuhkan penelitian lebih lanjut.

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Background : Thalassemia has a high prevalence in Indonesia. MRI modalities used by patients with transfusion-dependent thalassemia (TDT) who undergo continuous blood transfusions to assess iron levels in the liver. This examination require high cost and is only available in two major cities in Indonesia. High iron content over a long time in the liver can result in liver damage. More affordable modalities in terms of location and cost are needed to assess iron levels in the liver in this group of patients.

Objective: Determine the correlation strength between acoustic radiation force impulse (ARFI) shear wave velocity and T2* MRI values in assessing liver iron.

Methods: ARFI SWV primary data and T2* MRI values of 29 TDT patients were collected and then analyzed with SPSS to measure correlation.

Results: This study showed negative correlation with moderate strength between ARFI SWV values and liver T2* MRI values (R = -0,383) which was statistically significant (Spearman P = 0.040).

Conclusion: ARFI has a correlation with MRI examination in assessing the iron content of TDT patients liver organs. However, the correlation is not strong and further studies might be needed."

"Latar Belakang: Penyakit thalassemia tinggi prevalensinya di Indonesia. Modalitas MRI digunakan pasien transfusion-dependent thalassemia (TDT) yang menjalani transfusi darah berkesinambungan untuk menilai tingkat zat besi di organ hati. Pemeriksan ini memerlukan biaya tinggi dan hanya tersedia di dua kota besar di Indonesia. Kandungan zat besi yang tinggi dalam waktu yang lama di hati dapat berakibat pada kerusakan hati. Modalitas yang lebih terjangkau dari segi lokasi dan biaya diperlukan dalam menilai tingkat zat besi di organ hati pada kelompok pasien ini.Tujuan: Mengetahui kekuatan korelasi antara nilai shear wave velocity (SWV) acoustic radiation force impulse (ARFI) dengan nilai T2* MRI dalam menilai zat besi organ hati.Metode: Data primer SWV ARFI dan nilai T2* MRI dari 29 pasien TDT dikumpulkan lalu dianalisis dengan SPSS untuk mengukur korelasi.Hasil: Penelitian ini menunjukkan korelasi negatif dengan kekuatan yang moderat antara nilai SWV ARFI dan nilai T2* MRI hati (R = -0,383) yang bermakna secara statistik (Spearman P = 0,040).Kesimpulan: ARFI merupakan pemeriksaan yang memiliki korelasi dengan pemeriksaan MRI dalam menilai kandungan zat besi organ hati pasien TDT. Namun demikian, penelitian ini tidak menunjukkan hubungan yang kuat, dan oleh sebab itu mungkin dibutuhkan penelitian lebih lanjut.

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Background: Thalassemia has a high prevalence in Indonesia. MRI modalities used by patients with transfusion-dependent thalassemia (TDT) who undergo continuous blood transfusions to assess iron levels in the liver. This examination require high cost and is only available in two major cities in Indonesia. High iron content over a long time in the liver can result in liver damage. More affordable modalities in terms of location and cost are needed to assess iron levels in the liver in this group of patients.

Objective: Determine the correlation strength between acoustic radiation force impulse (ARFI) shear wave velocity and T2* MRI values in assessing liver iron.

Methods: ARFI SWV primary data and T2* MRI values of 29 TDT patients were collected and then analyzed with SPSS to measure correlation.

Results: This study showed negative correlation with moderate strength between ARFI SWV values and liver T2* MRI values (R = -0,383) which was statistically significant (Spearman P = 0.040).

Conclusion: ARFI has a correlation with MRI examination in assessing the iron content of TDT patients liver organs. However, the correlation is not strong and further studies might be needed."