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"ABSTRACTThe effects of dietary food fortified with orotic acid (1.0%)on liver function were studied in rats. The rats fed with orotic acid promoted liver triglyceride content markedly, that was 5-fold higher than that of the control. The liver malondialdehyde (MDA) content increased by 10%, but the gluthation peroxidase (GSH-Px) activity decreased by 50%. The serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities increased by 25% and 30%,respectively. Therefore, the decreased GSH-Px activity was associated with the promotions of AST, ALT, and the liver MDA levels. In conclusion: dietary orotic acid promotes lipid peroxidation but reduces the rate of the antioxidant enzyme. Therefore, dietary food fortified with orotic acid attenuates the liver function. "

"kegagalan hati. Organoid hati dapat digunakan sebagai bahan untuk BAL. Organoid hati merupakan rekonstruksi hati kultur 3D dari sel punca dan sel-sel lainnya yang menyerupai mikrostruktur hati in vivo dan memiliki fungsi hati. Organoid hati juga dapat digunakan untuk uji obat dan sebagai model unutk mempelajari penyakit hati.Metode : Organoid hati pada penelitian ini direkonstruksi dari hepatosit, sel stelata hepatika (LX2), sel punca mesenkimal asal tali pusat (UC-MSCs), dan sel punca hematopoiesis asal darah tali pusat (UCB-CD34+). Hepatosit primer tikus, LX2, UC-MSCs dan UCB-CD34+ diko-kultur dalam 11 formulasi rasio selama 2 hari. Formulasi rasio yang membentuk sferoid dikultur dalam 4 medium kultur selama 5 hari, dipanen dan dilakukan analisa viabilitas. Rasio dengan viabilitas tertinggi merupakan rasio optimal dalam medium kultur optimal untuk rekonstruksi organoid hati. Rasio hepatosit : LX2 : UC-MSCs : UCB-CD34+ optimal 5 : 1 : 2 : 2 diko-kultur dalam medium kultur optimal Williams E yang disuplementasi dengan PRP, ITS dan dexamethasone selama 14 hari dan dilakukan analisa morfologi, fungsi hati dan potensi angiogenesis.Hasil : Viabilitas organoid bertahan hingga hari ke-14 dan ekspresi protein albumin, ekspresi protein GOT dan ekspresi protein CD31 cukup stabil hingga hari ke-14. Ekspresi gen Albumin meningkat hingga hari ke-14 sedangkan ekspresi gen GOT menurun hingga hari ke-14. Sekresi urea menurun hingga hari ke-5 dan sekresi albumin menurun hingga hari ke-7.Kesimpulan : Organoid hati ini direkonstruksi dari hepatosit primer, LX2, UC-MSCs, UCB-CD34+ dengan rasio optimal 5 : 1 : 2 : 2 dalam medium kultur optimal sederhana dan ekonomis Williams E yang disuplementasi PRP, ITS dan dexamethasone. Organoid hati ini dapat mempertahankan viabilitas dan fungsi hingga hari ke-14. Organoid hati penelitian ini dapat digunakan sebagai model untuk uji obat dan dapat dikembangkan untuk menjadi bahan BAL.

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Introduction : Bioartificial Liver (BAL) is being developed to be an alternative therapy for liver failure. Liver organoids can be used as prototype material for BAL. Liver organoids are 3D cultured liver reconstructions of stem cells and other cells that resemble the liver microstructure in vivo and perform liver function. Liver organoids also can be used for drug testing and as a model for liver disease pathogenesis.

Methods : Liver organoids in this study were reconstructed from hepatocytes, hepatic stellate cells (LX2), human umbilical cord-mesenchymal stem cells (UC-MSCs), and human umbilical cord blood (UCB) hematopoiesis stem cells CD34+. Rat primary hepatocytes, LX2, UC-MSCs and UCB-CD34+ were co-cultured in 11 ratio formulations for two days. The ratio formed spheroid were cultured in four culture medium for five days, harvested and analyzed for viability. The ratio with the highest viability was the optimal ratio in the optimal culture medium for hepatic organoid reconstruction. The optimal ratio 5 : 1: 2 : 2 of Hepatocytes : LX2 : UC-MSCs : UCB-CD34+ was co-cultured in optimal culture medium Williams E supplemented with PRP, ITS and dexamethasone for 14 days and analyzed for morphology, liver function and angiogenesis potential.

Results : Liver organoids viability maintained until day 14 and albumin protein expression, GOT protein expression and CD31 protein expression were quite stable until day 14. Albumin gene expression increased until day 14, while GOT gene expression decreased until day 14. Urea secretion decreased until day 5 and albumin secretion decreased until day 7. Conclusion : These liver organoids were reconstructed from optimal ratio 5 : 1 : 2 : 2 of primary hepatocytes, LX2, UC-MSCs, UCB-CD34+ in simple and economical optimal culture medium Williams E supplemented by PRP, ITS and dexamethasone. These liver organoids maintained viability and liver function until day 14. These liver organoids can be used as a model for drug testing and can be developed to become a BAL material for future application."

"Latar Belakang. COVID-19 merupakan penyakit infeksi dengan manifestasi klinis utama di saluran pernapasan. Selain mempunyai manifestasi klinis pada saluran pernapasan, manifestasi COVID-19 juga ditemukan di saluran gastrointestinal, terutama pada organ hati. Gangguan fungsi hati pada pasien COVID-19 ditandai dengan peningkatan enzim alanine aminotransferase (ALT), peningkatan aspartate aminotransferase (AST), dan peningkatan serum bilirubin. Penelitian ini bertujuan mengetahui perbandingan kesintasan pasien konfirmasi positif COVID-19 yang mengalami gangguan fungsi hati dan mengetahui hubungan gangguan fungsi hati terhadap kesintasan pasien konfirmasi positif COVID-19 di RS Cipto Mangunkusumo.Metode. Penelitian ini menggunakan desain kohort retrospektif. Populasi dalam penelitian ini adalah pasien rawat inap dewasa dengan konfirmasi positif COVID-19 pada periode Oktober 2020 hingga Januari 2021. Analisis untuk mengetahui perbandingan kesintasan pasien konfirmasi positif COVID-19 yang mengalami gangguan fungsi hati. Analisis Cox Regresi Extended digunakan untuk mengetahui hubungan kausal gangguan fungsi hati terhadap kesintasan pasien COVID-19. Hasil dilaporkan dalam bentuk Hazard Rasio dengan Interval Kepercayaan 95%.Hasil. Sebanyak 354 pasien konfirmasi positif COVID-19 masuk dalam penelitian ini. Hasil penelitian menunjukan probabilitas kesintasan kumulatif 30 hari pada pasien COVID-19 lebih rendah pada kelompok pasien dengan adanya gangguan fungsi hati dibandingkan dengan kelompok pasien tanpa adanya gangguan fungsi hati, yaitu sebesar 31,1% vs. 69,4%, nilai p <0,001. Pada 14 hari masa awal pengamatan, terdapat hubungan gangguan fungsi hati yang signifikan terhadap kesintasan pasien konfirmasi positif COVID-19 setelah dikontrol dengan variabel confounder berupa ARDS, D-dimer, dan ventilator. HR adjusted 2,81 (IK 95%: 1,43-5,53, nilai p 0,003). Sementara pada > 14 hari pengamatan, tidak ditemukan adanya perbedaan risiko kematian pada kelompok pasien yang mengalami gangguan fungsi hati dan tidak mengalami gangguan hati. HR adjusted 0,33 (IK 95%: 0,06-1,75), nilai p 0,195.Kesimpulan. Kesintasan pasien COVID-19 lebih rendah pada pasien yang mengalami gangguan fungsi hati. Adanya gangguan fungsi hati yang ditemukan di 14 hari masa awal pengamatan merupakan faktor risiko yang berkontribusi terhadap kesintasan pasien COVID-19.

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Background. COVID-19 is an infectious disease with the main clinical manifestations in the respiratory tract. In addition, manifestations of COVID-19 are also found in the gastrointestinal tract, especially in the liver. Abnormal liver function in COVID-19 patients is characterized by an increasing enzyme alanine aminotransferase (ALT), an increase in aspartate aminotransferase (AST), and an increase in serum bilirubin. This study aims to compare the survival rates of COVID-19 patients with abnormal liver function and to evaluate the association between abnormal liver function with the survival of COVID-19 confirmation positive in Cipto Mangunkusumo Hospital.

Method. This study was a retrospective cohort. The population in this study were inpatients adult with positive confirmation of COVID-19 in the period October 2020 to January 2021. Survival analysis with Kaplan Meier was used to compare the survival of patients with positive confirmation of COVID-19 whose had abnormal liver function. Extended Regression Cox analysis was used to determine the causal relationship of abnormal liver function with the survival of COVID-19 patients. Results were reported in Hazard Ratio with 95% Confidence Interval.

Result. A total of 354 confirmed positive COVID-19 patients were included in this study. The results showed that the cumulative 30-day survival rate in COVID-19 patients was lower in the group of patients with abnormal liver function compared to the group of patients without abnormal liver function (31.1% vs. 69.4%, p value < 0.001). In the early 14 days of observation, there was a significant association of abnormal liver function with the survival of confirmed positive COVID-19 patients after controlling for confounder variables ARDS, D-dimer, and ventilator. HR adjusted 2.81 (95% CI: 1.43-5.53, p value 0.003). While at > 14 days observations, there was no difference in the risk of death in the group of patients with abnormal liver function and without abnormal liver function. HR adjusted 0.33 (95% CI: 0.06-1.75), p value 0.195.

Conclusion. The survival rate of COVID-19 patients was lower in patients with abnormal liver function. The presence of abnormal liver function in the initial 14 days of observation was a risk factor that contributed to the survival of COVID-19 patients."

"Latar belakang: Prevalensi adverse drug reaction (ADR) pada pasien tuberkulosis (TB) sensitif obat yang mendapat pengobatan antituberkulosis fase intensif cukup tinggi. ADR dapat mempengaruhi pengobatan pasien TB dan jika tidak ditangani dengan tepat, dapat menyebabkan komplikasi serius yang mengancam jiwa. Komplikasi gastrointestinal (GI) dan peningkatan fungsi liver merupakan ADR yang paling umum dijumpai pada pasien TB. Penelitian ini bertujuan untuk mengetahui proporsi dan faktor risiko komplikasi GI serta peningkatan fungsi liver berupa peningkatan enzm GGT, AST, ALT pada pasien TB sensitif obat yang menerima pengobatan antituberkulosis fase intensif.Metode: Penelitian ini merupakan penelitian cross-sectional terhadap 110 subjek yang menjalani pengobatan TB fase intensif. Subjek akan dilakukan evaluasi gejala mual, muntah, penilaian status gizi serta pemeriksaan laboratorium serial yaitu darah perifer lengkap, elektrolit, gula darah, albumin, fungsi hati dan ginjal sebelum memulai pengobatan, serta hari ke-7 dan ke-14 pengobatan.Hasil: Komplikasi GI terjadi pada 40,9% pasien TB dengan pengobatan TB fase intensif, dengan gejala terbanyak merupakan mual dan muntah. Peningkatan enzim gamma glutamyl transferase (GGT) terjadi pada 60% populasi sedangkan peningkatan alanine aminotransferase (ALT) dan aspartate aminotransferase (AST) terjadi pada 17,3% populasi. Di antara pasien TB yang menjalani pengobatan fase intensif, 57,3% mengalami underweight. Namun, penelitian ini menemukan adanya hubungan antara kejadian komplikasi gastro intestinal (GI) dengan overweight (p=0.021; OR= 11.428). Selain itu, peningkatan fungsi liver juga ditemukan berhubungan dengan usia yang lebih tua (p= 0,041).Kesimpulan: Proporsi peningkatan fungsi liver dan komplikasi GI pada pasien yang menerima pengobatan antituberkulosis fase intensif cukup tinggi, dengan mual dan muntah menjadi gejala yang paling umum. Overweight berhubungan dengan terjadinya komplikasi GI, sedangkan usia lebih tua berhubungan dengan peningkatan fungsi liver. Diperlukan studi prospektif dengan durasi yang lebih lama untuk menilai efek GI dan peningkatan fungsi liver mulai dari munculnya gejala hingga perbaikan fungsi liver..

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Background: The prevalence of adverse drug reaction (ADR) in tuberculosis (TB) patient receiving intensive phase antituberculosis treatment is high. ADR can affect the treatment of TB patients and if not treated appropriately, can cause serious, life-threatening complications. Gastrointestinal (GI) and increasing of liver function are two of the most common ADR in TB patients. This research aims to provide the proportion and risk factors of GI and increasing of liver function marked by increase level of GGT, AST, ALT in drug sensitive TB patients receiving intensive phase antituberculosis treatment.

Method: This study is a cross sectional study of 110 subjects who underwent intensive phase TB treatment. Subjects will be evaluated regarding the nausea, vomiting, nutritional status assessment and undergo serial laboratory test evaluation i.e. complete peripheral blood, electrolytes, blood sugar, albumin, liver and renal function before treatment, and also 7th and 14th day of treatment.

Results: GI complications occurred in 40.9% TB patients in intensive phase TB treatment, the most common symptoms were nausea and vomiting. Increasing of GGT enzyme occur in 60% of the population, while increase in ALT and AST occured in 17,3% of the population. Among the TB patients in intensive phase TB treatment, 57,3% were underweight. However, this study found an association between GI complication occurrence with overweight (p=0.021; OR= 11.428). In addition, increasing of liver enzymes was also found to be associated with older age (p= 0.041).

Conclusion: The proportion of improved liver function and GI complications in patients receiving intensive phase antituberculosis treatment is high, with nausea and vomiting being the most common symptoms. Being overweight is associated with GI complication occurrence, where as older age is associated with increased liver function. The prospective studies with a longer duration is needed to assess GI effect and improvement in liver function from the first appearence of symptoms until the improvement of the liver function."

"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"