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"Sirosis dekompensata pada anak merupakan indikasi utama transplantasi hati. Mayoritas pasien yang menunggu transplantasi hati memiliki masalah malnutrisi dan infeksi yang berhubungan dengan prognosis buruk, sehingga dibutuhkan terapi antara untuk memperbaiki kondisi pasien sebelum transplantasi hati. Skor pediatric end-stage liver disease (PELD) adalah sistem penilaian yang digunakan untuk menentukan prioritas transplantasi hati. Semakin tinggi nilainya, semakin buruk kondisi pasien. Terapi granulocyte colony-stimulating factor (G-CSF) telah memberikan hasil yang menjanjikan pada pasien sirosis dewasa, namun penelitian pada sirosis dekompensata anak belum pernah dilakukan. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh G-CSF terhadap skor PELD dan status nutrisi. Juga dinilai pengaruh terapi G-CSF terhadap neutrofil, CD34+, sitokin pro-inflamasi dan anti-inflamasi, hepatocyte growth factor (HGF), biomarker fungsi hati, adverse event dan kesintasan.Penelitian ini dilaksanakan pada bulan September 2019–Februari 2022 di Rumah Sakit dr. Cipto Mangunkusumo (RSCM), bersifat uji acak terkontrol open-label. Subjek adalah pasien anak dengan usia antara 3 bulan hingga 12 tahun dengan diagnosis sirosis dekompensata yang dibagi dalam kelompok intervensi (n = 26) dan kelompok kontrol (n = 24). Subjek pada kelompok intervensi diberikan 12 kali injeksi subkutan G-CSF (5 µg/kg/hari) serta terapi standar sirosis, dan pada kelompok kontrol hanya diberikan terapi standar sirosis.Tidak terdapat penurunan skor PELD yang bermakna setelah pemberian G-CSF. Terdapat perubahan bermakna pada kadar neutrofil dan leukosit (uji ANOVA, p < 0,001, untuk kedua parameter). Terdapat tanda mobilisasi sel punca yang dilihat dari peningkatan kadar CD34+, namun hasilnya tidak bermakna. Pemberian G-CSF secara bermakna menurunkan kadar tumor necrosis factor (TNF)-α (uji ANOVA, p = 0,001), dan meningkatkan interleukin (IL)-10 dan HGF (uji ANOVA, p = 0,003 untuk kedua parameter) yang menunjukkan bahwa imunitas bawaan dan regenerasi hati subjek dapat diperbaiki. Tidak ada perbedaan bermakna antara lingkar lengan atas (LILA) dan triceps skinfold thickness (TST) berdasarkan z-score setelah pemberian G-CSF. Kadar alanine aminotransferase (ALT) menurun secara bermakna pada kelompok intervensi (uji ANOVA, p = 0,038). Subjek yang mengalami kejadian infeksi lebih rendah pada kelompok intervensi dibanding kelompok kontrol (uji eksak Fisher, p = 0.04).

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Decompensated cirrhosis in children is the main indication of liver transplantation. The majority of patients awaiting liver transplantation have malnutrition and infection problems that are associated with poor prognosis, thus requiring a bridging therapy to treat these conditions prior to liver transplantation. Pediatric end-stage liver disease (PELD) score is a scoring system used to determine liver transplantation priority, higher scores indicates a worse prognosis. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult liver cirrhosis. Our study aimed to investigate the effect of G-CSF on pediatric end-stage liver disease (PELD) scores and nutritional status in pediatric liver cirrhosis. The study also investigated the effects of G-CSF on neutrophils, CD34+ cells, pro-inflammatory and anti-inflammatory cytokines, hepatocyte growth factor (HGF), liver function markers, adverse events, and survival.

This study was conducted on September 2019–February 2022 at dr. Cipto Mangunkusumo Hospital (RSCM). This was an open-label, randomized controlled trial (RCT) including subjects between 3 months and 12 years of age with decompensated cirrhosis. The subjects were divided into intervention group (n = 26) and control (n = 24). Subjects from the intervention group received 12 courses of subcutaneous injection of G-CSF (5 μg/kg/day) plus standard medical treatment (SMT) for liver cirrhosis, while the control received SMT.

Our study did not identify a significant difference in PELD scores between the intervention and control groups after 3 months of G-CSF treatment. Leucocyte and neutrophil counts showed significant differences between the intervention and control groups (ANOVA test, p > 0.001, for both). There was evidence of stem cell mobilization based on increased CD34+ cells in the intervention group; however, the results were not significant. G-CSF administration significantly decreased TNF-α (ANOVA test, p = 0,001), and significantly increased IL-10 and HGF (ANOVA test, p = 0,0003, respectively) indicating improvement in subjects’ immunity. There was no significant difference in nutritional status according to mid-upper arm circumference (MUAC) and triceps skinfold thickness (TST) based on the z-scores. Alanine aminotransferase (ALT) levels significantly decreased in the intervention group (ANOVA test, p = 0,038). Subjects in the intervention group experienced fewer infection events, with a significant difference in the occurrence of sepsis in the intervention group compared to the control (Fisher’s exact test, p = 0.04)."

"Pendahuluan. Sel punca mesenkimal yang dilaporkan mengaugmentasi penyembuhan fraktur umumnya diperoleh dari sumsum tulang. Donor sel punca dari sumsum tulang terbatas pada volume aspirat dan menimbulkan morbiditas donor sehingga diperlukan sumber alternatif. Darah perifer menutupi kekurangan tersebut walaupun memiliki kandungan sel punca yang lebih sedikit. Pemberian Granulocyte Colony Stimulating Factor (GCSF) dapat meningkatkan mobilisasi sel mononuklear pada teknik afaresis untuk sel punca hematopoetik. Bila pemberian GCSF diikuti dengan teknik kultur kearah sel punca mesenkimal maka dapat meningkatkan jumlah sel punca darah perifer sehingga memungkinkan penggunaan darah perifer sebagai donor alternatif sel punca. Oleh karena itu, diperlukan penelitian untuk mengevaluasi penggunaan darah perifer sebagai donor sel punca pasca pemberian GCSF dengan menilai kemampuan mobilisasi, proliferasi dan diferensiasi. Metode Penelitian. Penelitian ini adalah penelitian eksperimental yang memakai hewan coba 14 ekor kelinci New Zealand White jantan, berat badan 2 kg di Pusat Studi Satwa Primata, Institut Pertanian Bogor. Sampel dibagi secara acak menjadi 4 kelompok yaitu kontrol dan perlakuan (injeksi GCSF dosis 10mcg/kg berat badan, subkutan, selama 7 hari) dimana pada masing-masing kelompok diambil aspirat darah perifer dan sumsum tulang (kelompok 1: kontrol sumsum tulang, kelompok 2: kontrol darah perifer, kelompok 3: perlakuan sumsum tulang, kelompok 4: perlakuan darah perifer). Pada tiap kelompok dilakukan isolasi, ekspansi dan diferensiasi menjadi osteoblas. Analisis statistik menggunakan uji one way Anova dan dilanjutkan uji posthoc untuk jumlah sel inisial, waktu konfluensi, jumlah sel konfluensi dan waktu diferensiasi. Temuan dan Diskusi Penelitian. Sel punca mesenkimal pada seluruh kelompok penelitian mampu diisolasi, berproliferasi dan berdiferensiasi menjadi osteoblas. Rerata jumlah sel inisial kelompok 1: 3.07 x 106/mL, kelompok 2: 2.11 x 106/mL, kelompok 3: 2.89 x 106/mL dan kelompok 4: 7.35 x 106/mL (p< 0.001). Rerata waktu konfluensi kelompok 1: 25.8 hari, kelompok 2: 35.7 hari, kelompok 3: 26 hari, kelompok 4: 19.7 hari (p< 0.001). Rerata jumlah sel konfluensi kelompok 1: 6.54 x 106/mL, kelompok 2: 4.61 x 106/mL, kelompok 3: 5.94 x 106/mL, kelompok 4: 11.14 x 106/mL (p< 0.001). Rerata waktu diferensiasi kelompok 1: 15.5 hari, kelompok 2: 25.4 hari, kelompok 3: 15.4 hari, kelompok 4: 11.2 hari (p< 0.001). Uji posthoc jumlah sel inisial ditemukan perbedaan pada kelompok 1 dan 4 (p= 0.000), 2 dan 4 (p< 0.001), serta 3 dan 4 (p< 0.001). Uji posthoc waktu konfluensi, jumlah sel konfluensi dan waktu diferensiasi didapatkan perbedaan diantara semua kelompok kecuali kelompok 1 dan 3 (p= 1.000, 0.670, 1.000). Simpulan. Sel punca mesenkimal darah perifer pasca induksi GCSF mampu diisolasi, berproliferasi dan berdiferensiasi. Pemberian GCSF meningkatkan jumlah sel punca mesenkimal dan mempersingkat durasi kultur. Darah perifer memberikan harapan baru sebagai donor alternatif sel punca mesenkimal.

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Introduction. Mesenchymal stem cells, which had been reported to augment fracture healing, were routinely harvested from bone marrow. Bone marrow had several drawbacks regarding its limited aspiration volume and donor site morbidity, therefore alternative donor is needed. Peripheral blood may cover those disadvantages despite the fewer stem cells number. Granulocyte colony stimulating factor (GCSF) administration in aphaeresis technique could mobilized mononuclear cells to hematopoietic stem cells. If it is followed by culture for mesenchymal stem cells expansion, thus will increase peripheral mesenchymal stem cells number therefore might facilitate peripheral blood as an alternative donor. For that reason, further research is needed to evaluate the effect of GCSF induction to peripheral blood as stem cells alternative donor by assessing its capability on mobilization, proliferation and differentiation.

Methods. This is an experimental study using 14 male New Zealand White rabbit, weighted 2-3 kg in Primate Research Centre, Bogor Agricultural Institute. Sample was randomized into 4 groups as follow, control and treatment group (GCSF administration, 10mcg/kg body weight, subcutaneous, 7 days) in which peripheral blood and bone marrow aspiration was collected (group 1: control bone marrow, group 2: control peripheral blood, group 3: treatment bone marrow, group 4: treatment peripheral blood). Isolation, expansion and osteoblast differentiation were followed subsequently. Statistical analysis used one-way Anova and posthoc for initial cell number, confluency time, confluency cell number, and differentiation time.

Result and Discussion. Mesenchymal stem cells in all groups were able to be isolated, proliferate and differentiate to osteoblast. Initial cell number (mean) group 1: 3.07 x 106/mL, group 2: 2.11 x 106/mL, group 3: 2.89 x 106/mL and group 4: 7.35 x 106/mL (p< 0.001). Confluency time (mean) group 1: 25.8 days, group 2: 35.7 days, group 3: 26 days, group 4: 19.7 days (p< 0.001). Confluency cell number (mean) group 1: 6.54 x 106/mL, group 2: 4.61 x 106/mL, group 3: 5.94 x 106/mL, group 4: 11.14 x 106/mL (p< 0.001). Differentiation time group 1: 15.5 days, group 2: 25.4 days, group 3: 15.4 days, group 4: 11.2 days (p< 0.001). Posthoc analysis for initial cell number was found significantly different for group 1 and 4 (p= 0.000), group 2 and 4 (p< 0.001) and group 3 and 4 (p< 0.001). Posthoc analysis for confluency time, confluency cell number and differentiation time was found significantly different for all groups except group 1 and 3 (p= 1.000, 0.670, 1.000).

Conclusion. Peripheral blood mesenchymal stem cells after GCSF induction are able to be isolated, proliferate and differentiate. GCSF administration increase mesenchymal stem cells number and shorten culture duration. Peripheral blood is a promising alternative donor for mesenchymal stem cells."

"Granulocyte Colony Stimulating Factor (G-CSF) merupakan faktor pertumbuhan hematopoetik yang berfungsi merangsang proliferasi dan diferensiasi neutrofil. Protein G-CSF rekombinan yang dikembangkan dan diproduksi menggunakan sel inang Escherichia coli dan Chinese Hamster Ovary (CHO) masih memiliki kelemahan, sehingga pada penelitian ini dikembangkan suatu produk biosimilar G-CSF rekombinan menggunakan sel inang Pichia pastoris. Fokus penelitian ini adalah memproduksi dan mempurifikasi protein G-CSF rekombinan. Produksi protein rekombinan dilakukan dengan menginduksi kultur menggunakan metanol konsentrasi 0,5% tiap 12 jam dan dilakukan sampling terhadap kultur pada jam ke-0, 12, 24, 36 dan 48. Hasil analisis western blot menunjukkan adanya peningkatan produksi protein rekombinan tiap 12 jam. Protein G-CSF rekombinan dipresipitasi menggunakan amonium sulfat konsentrasi 80%, kemudian didialisis. Konsentrasi protein total diukur dengan spektrofotometer menggunakan metoda Bicinchoninic Acid (BCA). Hasil pengukuran menunjukkan konsentrasi protein total tertinggi adalah sampel protein yang dipresipitasi dengan 80% amonium sulfat. Selanjutnya, purifikasi dilakukan menggunakan teknik kromatografi afinitas dengan resin Ni-NTA. Hasil analisis SDS PAGE menunjukkan protein GCSF rekombinan berukuran 18,5 kDa dan dengan analisis slot blot terdeteksi berwarna ungu.

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Granulocyte Colony Stimulating Factor (G-CSF) is a hematopoietic growth factor that acts to stimulate neutrophilic proliferation and differentiation. Recombinant protein G-CSF developed and produced using cellular host Escherichia coli and Chinese hamster ovary (CHO) still has a weakness, so that in this study we developed a bio similar product of recombinant G-CSF using cellular host Pichia pastoris. The aim of this research was to produce and purify recombinant protein G-CSF. Production of recombinant protein was done by inducing culture with methanol 0.5% every 12 hours and sampling was carried out at 0, 12, 24, 36 and 48 hours. The results of western blot analysis showed an increase the production of recombinant protein every 12 hours. Recombinant protein G-CSF was precipitated using ammonium sulfate 80% of concentration, and then dialyzed. Concentration of total protein was measured by a spectrophotometer using the Bicinchoninic Acid (BCA) method. The measurement results showed the highest concentrations of total protein was present in samples that precipitated with 80% ammonium sulfate. Furthermore, purification performed using affinity chromatography techniques with Ni-NTA resin. The results of SDS PAGE analysis showed the recombinant protein G-CSF sized 18.5 kDa and with a slot blot analysis detected a purple color."

"Pendahuluan: Delayed union merupakan permasalahan yang dapat terjadi pasca penyembuhan fraktur yang secara signifikan mengganggu kualitas hidup pasien. Telah banyak penelitian yang dilakukan berdasarkan pendekatan konsep diamond untuk memecahkan masalah delayed union. Granulocyte-colony stimulating factor (G-CSF) merupakan salah satu dari berbagai zat yang diketahui mempunyai peranan positif dalam penyembuhan jaringan skeletal atau regenerasi ajuvan. Penelitian ini dilakukan untuk melihat efek pemberian G-CSF dalam mempengaruhi penyembuhan fraktur delayed union. Material dan Metode: Penelitian eksperimental dilakukan dengan randomized post test only control group design pada 24 hewan coba tikus putih Sprague-Dawley yang telah mengalami model delayed union. Penelitian membandingkan antara kelompok perlakuan yg diinjeksi subkutan G-CSF dengan kelompok kontrol dan dibagi menjadi empat kelompok (n=6). Harvest dan follow up histomorfometri dan imunohistokimia dilakukan pada dua kelompok di minggu kedua (KM2 dan PM2) dan dua kelompok lagi pada minggu keempat (KM4 dan PM4). Analisis histomorfometri terdiri dari presentase area tulang imatur, tulang rawan dan area fibrosa dengan pulasan Hematoxylin-Eosin (HE). Sedangkan evaluasi semikuantitatif imunohistokimia dengan ekspresi BMP-2 melalui skor imunoreaktif (IRS).Hasil: Pada evaluasi parameter histomorfometri dan imunohistokimia didapatkan area fibrosis secara signifikan lebih sedikit (p<0,001) dan ekspresi BMP 2 lebih tinggi (p=0,008) pada kelompok perlakuan minggu kedua dibandingkan kontrol. Serta presentase area woven bone secara bermakna lebih besar (p=0,015), area fibrosis lebih sedikit (p=0,002) dan ekspresi BMP 2 lebih tinggi (p=0,004) pada perlakuan minggu keempat dibandingkan dengan kontrol. Kesimpulan: G-CSF terbukti meningkatkan kecepatan penyembuhan pada tikus putih Sprague-Dawley pada model delayed union dievaluasi dari aspek histomorfometri dan imunohistokimia.

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Introduction: Delayed union is a problem that can occur after fracture healing, which significantly impairs the patient's quality of life. Many studies were conducted based on the diamond concept approach to solve the problem of delayed union. Granulocyte-colony stimulating factor (G-CSF) is one of the various substances known to have a positive role in healing skeletal tissue or adjuvant regeneration. This study was conducted to see the effect of G-CSF in affecting delayed union fracture healing.

Methods: The experimental study was conducted by randomized posttest only control group design on 24 experimental animals Sprague-Dawley white rats that had experienced delayed union models. The study compared the treatment group injected with subcutaneous G-CSF with a control group and was divided into four groups (n=6). Harvest and follow-up histomorphometry and immunohistochemistry were performed in two groups in the second week (KM2 and PM2) and two more groups in the fourth week (KM4 and PM4). The histomorphometric analysis consisted of the percentage of immature bone area, cartilage, and fibrous area with Hematoxylin-Eosin (HE) streaks. Meanwhile, the semiquantitative evaluation of immunohistochemistry with the expression of BMP-2 through the immunoreactive score (IRS).

Results: In the evaluation of histomorphometric and immunohistochemical parameters, there were significantly differences less fibrosis area (p = 0,001) and higher BMP 2 expression (p = 0,008) in treatment week two compared to control. In addition, there were also significantly more woven bone area (p = 0,015), less fibrosis area (p = 0,002) and higher BMP 2 expression (p = 0,004) in treatment group week four compared to control.

Conclussion: G-CSF was shown to increase the speed of healing in Sprague- Dawley rats on delayed union models evaluated from histomorphometric and immunohistochemical aspects."

"Malnutrisi merupakan hal yang umum terjadi pada pasien sirosis hati Tata laksana nutrisi yang optimal bertujuan mempertahankan dan meningkatkan status gizi memperbaiki keadaan klinis dan meningkatkan kualitas hidup pasien Tatalaksana nutrisi pasien sirosis hati mencakup pemberian makronutrien mikronutrien dan nutrien spesifik serta cairan Pasien pada serial kasus ini terdiri atas tiga orang laki laki dan satu orang perempuan dengan rentang usia antara 30 sampai 57 tahun Tiga orang pasien menderita malnutrisi dan satu orang pasien berisiko malnutrisi Berdasarkan skrining seluruh pasien membutuhkan dukungan nutrisi Kebutuhan energi total KET pasien dihitung dengan menjumlahkan kebutuhan energi basal KEB yang didapat dengan menggunakan persamaan Harris Benedict dan faktor stres yang sesuai kondisi klinis pasien Pemberian nutrisi dimulai dengan 80 dari KEB sampai KEB kemudian ditingkatkan secara bertahap hingga mencapai KET Kebutuhan protein dan lemak disesuaikan dengan kondisi pasien Protein yang diberikan mempunyai kandungan asam amino rantai cabang AARC yang tinggi dan lemak jenis medium chain triglyceride MCT trigliserida rantai sedang Makanan diberikan dalam porsi kecil dengan jadwal pemberian sering dan malam hari diberikan late evening snack sebanyak 10 dari asupan harian total mengandung karbohidrat dan AARC Pada pasien dengan hiponatremia dilusional asupan cairan direstriksi Selama pemantauan dengan bertambah baiknya keadaan klinis maka asupan makan pasien dapat mencapai KET Serial kasus ini menunjukkan bahwa pada pasien sirosis hati dengan berbagai komplikasi tata laksana nutrisi yang baik dapat meningkatkan status gizi memperbaiki keadaan klinis dan meningkatkan kualitas hidup pasien

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Malnutrition is common in patients with liver cirrhosis Optimal nutrition support in patients with liver cirrhosis is required to maintain and improve clinical condition nutrition status and quality of life by providing macronutrient micronutrient specific nutrient and fluid according to the recommendation Patients in this case series were three males and one female with age ranged from 30 to 57 years old Three patients were malnourished while one was on risk of being malnourished Based on the screening conducted to these patients while their admission all four patients needed nutrition support therapy Total energy requirements were determined using Harris Benedict equation to calculate basal energy requirements and multiplied by stress factor Nutrition provision initiated from 80 basal energy requirement and increased gradually according to patient rsquo s tolerance until total energy requirements were achieved Protein and lipid were given in accordance with the patients clinical condition with protein contain high branched chain amino acid BCAA and fat which high in medium chain triglyceride MCT The diets delivered in small portion six times per day with late evening snack as much as 10 of total energy intake contained carbohydrate and BCAA Fluid restrictions were applied to patients with dilutional hyponatremia During hospitalization nutrition intake increased as general conditions improved Nutrition status clinical condition and quality of life of liver cirrhotic patients with various complications in this case series were improved by appopriate nutrition support ;Malnutrition is common in patients with liver cirrhosis Optimal nutrition support in patients with liver cirrhosis is required to maintain and improve clinical condition nutrition status and quality of life by providing macronutrient micronutrient specific nutrient and fluid according to the recommendation Patients in this case series were three males and one female with age ranged from 30 to 57 years old Three patients were malnourished while one was on risk of being malnourished Based on the screening conducted to these patients while their admission all four patients needed nutrition support therapy Total energy requirements were determined using Harris Benedict equation to calculate basal energy requirements and multiplied by stress factor Nutrition provision initiated from 80 basal energy requirement and increased gradually according to patient rsquo s tolerance until total energy requirements were achieved Protein and lipid were given in accordance with the patients clinical condition with protein contain high branched chain amino acid BCAA and fat which high in medium chain triglyceride MCT The diets delivered in small portion six times per day with late evening snack as much as 10 of total energy intake contained carbohydrate and BCAA Fluid restrictions were applied to patients with dilutional hyponatremia During hospitalization nutrition intake increased as general conditions improved Nutrition status clinical condition and quality of life of liver cirrhotic patients with various complications in this case series were improved by appopriate nutrition support "

"Pendahuluan: Sirosis hati merupakan penyebab mortalitas dan morbiditas global, terutama melalui komplikasi hipertensi porta yang menyebabkan perdarahan varises esofagus (VE). Pasien yang pernah mengalami perdarahan pertama memiliki tingkat kejadian perdarahan berulang yang tinggi dengan angka survival yang rendah. Meskipun endoskopi dapat memprediksi perdarahan berulang, pendekatan ini mahal dan bersifat invasif. Oleh karena itu, pemeriksaan non invasif lain dengan tingkat akurasi yang tinggi perlu dipelajari.Tujuan: Penelitian ini bertujuan untuk mengidentifikasi prediktor non-invasif perdarahan berulang VE (kekakuan hati, kekakuan limpa, skor Child Pugh, dan jumlah trombosit) pada pasien sirosis hati.Metode: Sebanyak 102 sampel pasien sirosis hati yang mengalami riwayat perdarahan VE. Variabel prediktor dalam memprediksi kejadian perdarahan berulang varises esofagus pada penelitian ini meliputi kekakuan hati, kekakuan limpa, skor Child Pugh, serta jumlah trombosit. Analisa multivariat dan uji skor dengan validasi internal untuk mendapatkan model performa terbaik sebagai prediktor perdarahan VE berulang.Hasil: Hasil menunjukkan bahwa kekakuan hati, kekakuan limpa, skor Child Pugh, dan trombositopenia signifikan sebagai prediktor perdarahan berulang VE. Dengan menggabungkan variabel ini, model prediksi dihasilkan dengan AUC 0,870. Diperoleh uji skor dengan validasi bahwa keempat variabel tersebut signifikan sebagai faktor yang berhubungan dengan perdarahan berulang varises esofagus. Kesimpulan: kombinasi kekakuan hati, kekakuan limpa, skor Child Pugh, dan jumlah trombosit memiliki performa baik dalam memprediksi risiko perdarahan varises esofagus berulang pada pasien sirosis hati.

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Background: Liver cirrhosis is a global cause of mortality and morbidity, especially through complications of portal hypertension which causes esophageal variceal (VE) bleeding. Patients who have experienced a first bleed have a high rate of recurrent bleeding with a low survival rate. Although endoscopy can predict recurrent bleeding, this approach is expensive and invasive. Therefore, other non- invasive examinations with a high accuracy need to be researched.

Objective: This study aims to identify non-invasive predictors of recurrent VE bleeding (liver stiffness, spleen stiffness, Child Pugh score, and platelet count) in liver cirrhosis patients.

Methods: A total of 102 samples of liver cirrhosis patients who had a history of VE bleeding were included in this study. Predictor variables in predicting the incidence of recurrent esophageal variceal bleeding in this study include liver stiffness, spleen stiffness, Child Pugh score, and platelet count. Multivariate analysis and internal validity test were used to obtain the best performance model as a predictor of recurrent VE bleeding.

Results: The results showed that liver stiffness, spleen stiffness, Child Pugh score, and thrombocytopenia were significant as predictors of recurrent VE bleeding. By combining these variables, a prediction model was generated with an AUC of 0.870. Validity test of these four variables were significant as factors associated with recurrent esophageal variceal bleeding.

Conclusion: The combination of liver stiffness, spleen stiffness, Child Pugh score, and platelet count has good performance in predicting the risk of recurrent esophageal variceal bleeding in patients with liver cirrhosis."

"Pendahuluan: Prevalensi sirosis tinggi di Indonesia yang mayoritas populasinya adalah muslim. Pada saat menjalani puasa Ramadhan yang merupakan kewajiban umat muslim terjadi berbagai proses metabolik yang dapat mempengaruhi keadaan klinis, nutrisi dan bokimiawi pasien sirosis hati . Penelitian tentang efek puasa Ramadhan pada pasien sirosis hati di Indonesia belum pernah dilakukan. Tujuan: Untuk mengetahui perubahan status nutrisi, status fungsi hati, pembentukan badan keton dan keseimbangan nitrogen pada pasien sirosis hati yang menjalankan puasa Ramadhan. Metode: Penelitian "pre dan post" dengan consecutive sampling dilakukan pada pasien sirosis hati yang berpuasa Ramadhan. Penilaian status fungsional hati dengan skor Child-Pugh (CP), antropometrik dengan mengukur indeks massa tubuh (IMT), ketebalan triceps skinfold (TSF) menggunakan kaliper Holtain, mid-arm muscle circumference, asupan makanan 24 jam, kadar 3-β-hidroksi butirat darah, serta pengukuran ekskresi nitrogen urin 24 jam, dilakukan pada minggu ke-4 Ramadhan dan 4 minggu pasca Ramadhan. Hasil: Didapatkan 24 pasien sirosis hati, 16 orang (66,7%) laki-laki dan 8 orang (33,3%) perempuan yang menjalankan puasa Ramadhan dengan rerata umur 60 tahun. Etiologinya virus hepatitis B 54,2%, hepatitis C 20,8%, dan penyebab yang tidak diketahui 25%. Status fungsi hati CP A 19 orang (79,2%), CP B 2 orang (8,3%), dan CP C 3 orang (12,5%). Tidak ada perubahan skor CP pasca Ramadhan. Rerata (SD) IMT, ketebalan TSF, MAMC saat puasa Ramadhan berturut-turut adalah 25,112 (4,05) kg/m2, 7,40 (3,61) mm, 25,77 (3,077) cm dan pasca Ramadhan berturut-turut 25,25 (4,01) kg/m2 (p = 0,438), 7,89 (4,33) mm (p=0,024), 25,96 (3,42) cm (p=0,228). Kadar 3-β-hidroksi butirat darah saat Ramadhan adalah 0,14 (0.07) mmol/L, pasca Ramadhan 0,11 (0.09) mmol/L (p=0,166). Rerata (SD) keseimbangan nitrogen saat puasa Ramadhan 2,44 (2,93) gram/24 jam, pasca Ramadhan 0,51 (3,16) gram/24 jam (p=0,037). Simpulan: Tidak ada pebedaan status fungsi hati dan kadar 3-β-hidroksi butirat darah pada saat dan pasca Ramadhan. Indeks massa tubuh dan ketebalan TSF membaik pasca Ramadhan. Keseimbangan nitrogen lebih positif saat Ramadhan. Puasa Ramadhan tampaknya tidak membahayakan pasien sirosis hati terutama pada kondisi fungsi hati yang terkompensasi.

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Introduction: The prevalence of cirrhosis is high in Indonesia which most of are predominantly moslems. There were various metabolic changes happened in Ramadhan fasting that obligated for moslems that could influence clinical, nutritional, and biochemistry condition of cirrhotic patients.The study of effects of Ramdhan fasting in cirrhotics patients (pts) in Indonesia has never been investigated.

Aim of Study: To evaluate changes of liver functional status, nutritional status, serum 3-β-hidroxy butyric and nitrogen balance in cirrhotic patients during Ramadhan fasting.

Methods: This was a ‘pre and post’ study with consecutive sampling conducted in cirrhotic patients during Ramdhan fasting. Assessment of liver functional status by Child-Pugh (CP) score, anthropometric by measuring body mass index (BMI), triceps skinfold (TSF) thickness measured by Holtain caliper, and mid-arm muscle circumference, 24-hours food intake, serum 3-β-hidroxi butyric, and 24-hours urine nitrogen excretion, were performed at fourth week and four weeks after the end of Ramadhan fasting.

Results: Of 24 cirrhotic patients, 16 male (66,7%) dan 8 female (33,3%) who performed Ramadhan fasting were 60 years old in this study. Etiologies were hepatitis B viral (54,2%), hepatitis C ( 20,8%), and unknown (25%). Liver functional status were CP A 19 pts (79,2%), CP B 2 pts (8,3%), and CP C 3 pts (12,5%). No changes of this status after Ramadhan. Mean (SD) of BMI, TSF thickness, MAMC at Ramadhan concecutively were 25,112 (4,05) kg/m2, 7,40 (3,61) mm, 25,77 (3,077) cm and after Ramadhan 25,25 (4,01) kg/m2 (p = 0,438), 7,89 (4,33) mm (p=0,024), 25,96 (3,42) cm (p=0,228). Mean (SD) of serum 3-β-hidroxy butyric at Ramadhan was 0,14 (0.07) mmol/L, after Ramadhan 0,11 (0.09) mmol/L (p=0,166). Mean (SD) of nitrogen balance at Ramadhan was 2,44 (2,93) gram/24 hour, after Ramadhan 0,51 (3,16) gram/24 hour (p=0,037).

Conclusion: No difference of liver functional status and serum 3-β-hidroxy butyric during and after Ramadhan. Body mass index and triceps skinfold were better after Ramadhan. Nitrogen balance was more positive during Ramadhan compared to after Ramadhan. Ramadhan fasting is likely harmless especially in compensated liver cirrhosis."

"ABSTRAK Latar Belakang : Malnutrisi merupakan faktor independen yang berhubungan dengan morbiditas, mortalitas dan tingginya biaya pengobatan sirosis hati. Kekuatan Genggam Tangan (KGT) merupakan suatu metode yang sering digunakan untuk mendeteksi malnutrisi dan menilai prognosis pasien. Hubungan KGT dengan Skor Child Pugh (CP) dan massa otot masih dalam kontroversi. Indonesia sampai saat ini belum memiliki data tersebutMetode : Studi potong lintang pada pasien sirosis hati di poliklinik hepatobilier RSCM dari Februari-Juni 2015. Status nutrisi dinilai berdasarkan KGT. Massa otot diukur menggunakan bioimpedans. Analisis statistik menggunakan uji korelasi spearmanHasil : Terdapat 115 pasien yang kontrol di poliklinik hepatobilier RSCM, 112 pasien memenuhi kriteria penelitian, terdiri dari 79 laki-laki dan 33 perempuan. Usia pasien rata-rata 54,15±10,55 tahun, median skor CP 6(5-13) dengan median KGT 26(11-50) kgF, rata-rata massa otot 44,43±8,12 kg. Median asupan energi 1334,82(604,75-3023,7) kkal, median protein 45,87(19-114,5) gram. Prevalensi malnutrisi berdasarkan KGT ditemukan sebanyak 33%. Kekuatan genggam tangan tidak berkorelasi dengan skor CP (p 0,046, r=-0,19) namun berkorelasi dengan massa otot (p <0,001, r= 0,70) Simpulan Terdapat 33% kasus malnutrisi berdasarkan KGT pada pasien sirosis rawat jalan. KGT tidak berkorelasi dengan skor Child Pugh namun berkorelasi dengan massa otot pasien sirosis hati.ABSTRACT Background : Malnutrition is independent factor related to morbidity, mortality and high cost of treatment in liver cirrhosis. Hand grip strength (HGS) is one of the method use for malnutrition detection and prognosis evaluation. The correlation of HGS with liver function (Child Pugh or CP score) and muscle mass is controversial. These important evaluation is not yet avalaible in Indonesia.Method : This is a cross-sectional study in liver cirrhosis patients at Hepatobiliary clinic of Cipto Mangunkusumo Hospital from February to June 2015. Nutritional status was assessed by HGS. Muscle mass was obtained from bioimpedance. Data were analyzed using Spearman correlation test. Results : There were 115 patients liver cirrhosis at Hepatobiliary clinic of Cipto Mangunkusumo Hospital, 112 patients who fit the inclusion criteria, consisted of 79 men and 33 women with mean age 54,15±10,55 years, median CP score 6(5-13) with median HGS 26 (11-50) kgF, mean muscle mass 44,43±8,12 kg. The median intake of energy 1334,82(604,75-3023,7) kkal, median protein 45,87(19-114,5) gram. Prevalence of malnutrition according HGS was 33%. Hand grip strength is not correlated with CP score (p 0,046, r=-0,19) however it is correlated with muscle mass (p<0,001, r= 0,70) Conclusion There are 33% malnutrition cases based on HGS in out patient liver cirrhosis. There is no correlation between hand grip strength with Child Pugh score however HGS is correlated with muscle mass in liver cirrhosis.;Background : Malnutrition is independent factor related to morbidity, mortality and high cost of treatment in liver cirrhosis. Hand grip strength (HGS) is one of the method use for malnutrition detection and prognosis evaluation. The correlation of HGS with liver function (Child Pugh or CP score) and muscle mass is controversial. These important evaluation is not yet avalaible in Indonesia.Method : This is a cross-sectional study in liver cirrhosis patients at Hepatobiliary clinic of Cipto Mangunkusumo Hospital from February to June 2015. Nutritional status was assessed by HGS. Muscle mass was obtained from bioimpedance. Data were analyzed using Spearman correlation test. Results : There were 115 patients liver cirrhosis at Hepatobiliary clinic of Cipto Mangunkusumo Hospital, 112 patients who fit the inclusion criteria, consisted of 79 men and 33 women with mean age 54,15±10,55 years, median CP score 6(5-13) with median HGS 26 (11-50) kgF, mean muscle mass 44,43±8,12 kg. The median intake of energy 1334,82(604,75-3023,7) kkal, median protein 45,87(19-114,5) gram. Prevalence of malnutrition according HGS was 33%. Hand grip strength is not correlated with CP score (p 0,046, r=-0,19) however it is correlated with muscle mass (p<0,001, r= 0,70) Conclusion There are 33% malnutrition cases based on HGS in out patient liver cirrhosis. There is no correlation between hand grip strength with Child Pugh score however HGS is correlated with muscle mass in liver cirrhosis.;Background : Malnutrition is independent factor related to morbidity, mortality and high cost of treatment in liver cirrhosis. Hand grip strength (HGS) is one of the method use for malnutrition detection and prognosis evaluation. The correlation of HGS with liver function (Child Pugh or CP score) and muscle mass is controversial. These important evaluation is not yet avalaible in Indonesia.Method : This is a cross-sectional study in liver cirrhosis patients at Hepatobiliary clinic of Cipto Mangunkusumo Hospital from February to June 2015. Nutritional status was assessed by HGS. Muscle mass was obtained from bioimpedance. Data were analyzed using Spearman correlation test. Results : There were 115 patients liver cirrhosis at Hepatobiliary clinic of Cipto Mangunkusumo Hospital, 112 patients who fit the inclusion criteria, consisted of 79 men and 33 women with mean age 54,15±10,55 years, median CP score 6(5-13) with median HGS 26 (11-50) kgF, mean muscle mass 44,43±8,12 kg. The median intake of energy 1334,82(604,75-3023,7) kkal, median protein 45,87(19-114,5) gram. Prevalence of malnutrition according HGS was 33%. Hand grip strength is not correlated with CP score (p 0,046, r=-0,19) however it is correlated with muscle mass (p<0,001, r= 0,70) Conclusion There are 33% malnutrition cases based on HGS in out patient liver cirrhosis. There is no correlation between hand grip strength with Child Pugh score however HGS is correlated with muscle mass in liver cirrhosis."

"ABSTRAKTujuan : Untuk menilai dan mengetahui pengaruh pemberian kombinasi asamamino rantai cabang (AARC) dengan L-ornitin L-aspartat (LOLA) larut malamterhadap status nutrisi dan ensefalopati hepatikum derajat rendah pada pasiensirosis hati.Metode : Populasi terjangkau penelitian adalah pasien poliklinik hati rumah sakitCipto Mangunkusumo periode Juni 2011 – Juni 2012 yang kemudian dilakukanevaluasi critical flicker frequency (CFF). Semua pasien yang masuk dalampopulasi penelitian adalah subjek penelitian yang memenuhi kriteria inklusipenelitian. Subjek penelitian kemudian diberikan edukasi diet sesuai dengankonsensus ESPEN. Subjek penelitian dibagi dalam 2 kelompok sesuai hasilrandomisasi, yaitu kelompok makanan selingan siang hari (MSSH) dan kelompokmakanan selingan malam hari (MSMH). Evaluasi terhadap anamnesis,pemeriksaan fisik, laboratorium dan CFF dilakukan 1 bulan setelah intervensi.Analisis statistik yang digunakan dalam penelitian uji acak tersamar tunggal iniadalah uji t independen.Hasil : Tiga puluh dua pasien yang sesuai dengan kriteria inklusi dibagi dalam 2kelompok intervensi. Kelompok A, MSSH (07.30 dan 12.30) dan kelompok B,MSMH (07.30 dan 22.30), masing-masing kelompok memiliki 16 subjekpenelitian. Setelah 1 bulan intervensi didapatkan hasil rerata lingkar lengan atas(LLA) kelompok MSMH (26.1±6.0 cm) (p = 0.001) dibandingkan kelompokMSSH (25.5±4.0 cm). Pada hasil CFF, didapatkan kelompok MSMH (39.5±3.9Hz) (p = 0.001) dibandingkan kelompok MSSH (38.4±4.2 Hz). Tidak didapatkanperbaikan kadar prealbumin dan derajat SGA setelah 1 bulan intervensi pada duakelompok. Hal ini dipikirkan karena perbedaan karakteristik dasar dan jumlahsampel yang relatif kecil.Simpulan : Proses randomisasi tidak berhasil menyamakan karakteristik dasarpada kedua kelompok. Terdapat peningkatan bermakna pada lingkar lengan atas,berat badan dan CFF setelah 1 bulan pemberian kombinasi AARC dan LOLAsebagai makanan selingan malam hari pada pasien sirosis hati.

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ABSTRACTAim : To determine the effect of L-ornithine L-aspartate (LOLA) and branchchain amino acids (BCAA) as a combination supplementation on nutritional statusand minimal hepatic encephalopathy improvement in liver cirrhosis patient.Methods : Liver cirrhosis patient in walk-in clinic of Cipto MangunkusumoHospital in June 2011 – June 2012 were evaluated by critical flicker frequency(CFF) test. Encephalopathy is defined when CFF < 38 Hz. All subjects whofulfilled the inclusion criteria received education for an adequate diet based on theESPEN Guidelines. They were divided into two groups based on randomization.One group was given the combination supplement as day snacks, while the othergroup as late evening snacks. The evaluation based on anamnesis, physicalfinding, laboratory result and CFF test after 1 month of interventions. Statisticalanalysis conducted for this single blind randomized clinical trial was independentt-test.Results : Thirty two patients who fit the inclusion criteria were divided into twogroups, group A : day snacks (7.30 am and 12.30 pm) and group B : late eveningsnacks groups (07.30 am and 10.30 pm), each groups has 16 subjects. Statisticalanalysis obtained the statistically significant (p = 0.001) of increasing of the meanmid arm circumference in group B (26.1±6.0 cm) compared to group A (25.5±4.0cm). Statistically significant (p = 0.001) were also revealed in mean CFF value ingroup B (39.5±3.9 Hz) compared to group A (38.4±4.2 Hz). However, the meanprealbumin level and SGA score after 1 month intervention in both groups wasnot met statistically significant, caused by the small subjects.Conclusion : The randomization process was not able to make a good comparisonin both groups. There is a significant increasing level of mid arm circumference,body weight and CFF after 1 month combination of LOLA and BCAA as lateevening snacks for liver cirrhosis patient."

"Latar Belakang: Pecahnya varises esofagus (EV) tetap menjadi salah satu komplikasi sirosis yang paling parah. Sebagai gold standard untuk memprediksi kecelakaan ini, Esophagogastroduodenoscopy (EGD) sendiri juga memiliki kelemahan. Tidak semua pasien nyaman dan mau menerima modalitas ini dalam praktik klinis terlepas dari risiko dan beban biaya. Oleh karena itu, pencarian modalitas noninvasif lain yang nyaman tetapi dengan akurasi tinggi masih perlu dipelajari. Diantaranya, Pengukuran Kekakuan Limpa (SSM), Pengukuran Kekakuan Hati (LSM), dan skor Aspartate Amino Transferase to Platelet Ratio Index (APRI) menjadi populer dan dipelajari secara intensif di banyak pusat dengan akurasi yang baik, tetapi hasilnya tetap bertentangan di beberapa penelitian.

Tujuan : Mengetahui kinerja skor SSM, LSM, APRI, dan kombinasinya untuk memprediksi EV pada pasien sirosis hati.

Metode : Sebanyak 141 pasien sirosis hati yang menjalani endoskopi, SSM, LSM, dan perhitungan skor APRI antara Januari 2023 dan Maret 2023. Analisa diagnostik dinilai menggunakan area di bawah kurva penerima-operator (AUC) untuk mengukur dan membandingkan kinerja setiap pengukuran dan kombinasi untuk memprediksi EV dan untuk mendapatkan nilai prediksi optimal yang sesuai. Pengukuran elastografi transien (TE) dilakukan menggunakan fibroscan khusus limpa dengan probe 100 hz.

 

Hasil : Dari 141 pasien, etiologi terbanyak adalah hepatitis B sebanyak 71 pasien (50,4%). Varises esofagus ditemukan pada 116 pasien (86,3%). Dengan menggunakan area under receiver, SSM pada titik potong 40,1 kPa memiliki kinerja terbaik untuk memprediksi EV pada sirosis dengan AUC 0,892 (sensitivitas 88,79%, spesifisitas 80%), diikuti oleh LSM pada titik potong  10,2 kPa dengan AUC 0,832 (sensitivitas 90,52%, spesifisitas 60%), dan skor APRI pada titik potong 0,72 memiliki AUC terendah antara lain 0,780 (sensitivitas 77,59%, spesifisitas 80%). Kombinasi ketiga pemerikssan tidak menunjukkan performa yang lebih baik dibandingkan SSM secara tunggal dengan AUC 0,892.

 

Kesimpulan : SSM memberikan kinerja yang lebih baik daripada skor LSM dan APRI untuk memprediksi EV.

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Background: Esophageal varices (EV) rupture remains one of the most severe complications of cirrhosis. As a gold standard to predict this accident, Esophagogastroduodenoscopy (EGD) itself also has a weakness. Not all patients are convenient and willing to accept this modality in clinical practice apart from the risk and cost burden. Hence, the search for other noninvasive modalities that are convenient but with high accuracy is still noteworthy to be studied. Among them, Spleen Stiffness Measurement (SSM), Liver Stiffness Measurement (LSM), and the Aspartate Amino Transferase to Platelet Ratio Index (APRI) score become popular and intensively studied in many centers with good accuracy, but the results remain conflicting in some studies.

 

Objective: To investigate the performance of SSM, LSM, APRI score, and their combination for predicting EV in liver cirrhosis patients.

 

Methods: A total of 141 patients with liver cirrhosis who had undergone endoscopy, SSM, LSM, and APRI score calculation between January 2023 and March 2023 were enrolled. Diagnostic applicability was assessed by the area under the receiver-operator curve (AUC) to measure and compare the performance of each measurement and combination for predicting EV and to obtain the corresponding optimal prediction value. Transient elastography (TE) measurement was done using spleen-dedicated fibroscan with a 100 Hz probe.

 

Results: Of the 141 patients, the most common etiology was hepatitis B 71 patients (50,4%). Esophageal varices were found in 116 patients (86,3%). Using area under receiver, SSM at cut-off 40,1 kPa had the best performance for predicting EV in cirrhosis with AUC 0,892 (sensitivity 88,79%, specificity 80%), followed by LSM at cut-off 10,2 kPa with AUC 0,832 (sensitivity 90,52%, specificity 60%), and APRI score at cut-off 0,72 had the lowest AUC among others 0,780 (sensitivity 77,59%, specificity 80%). The combination of all measurement tools did not show better performance than SSM alone with AUC 0,892.

 

Conclusion: SSM provides better performance than LSM and APRI score for predicting EV"