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"Because of the increasing burden of hepatitis C and fatty liver disease, there is an explosion in the prevalence of chronic liver failure and hence its complications. The onset of Hepatic Encephalopathy (HE) in these patients has a significant impact on the quality of life, morbidity and mortality. Unfortunately, the approach observed by most clinicians to this complex disorder is minimalistic.This book provides a comprehensive review on pathophysiology and clinically important aspects in HE. Topics in basic physiology, nitrogen metabolism, new insights into pathogenesis and brain edema are covered in great detail. The authors have made a special effort by simplifying the complex aspects of pathogenesis and diagnosis so that it can be easily understood and applied clinically. This volume also focuses on recent developments regarding diagnoses of subtle forms of HE, also known as minimal or covert HE as well as on new treatments. Hepatic Encephalopathy will be of great value to gastroenterologists, hepatologists, pathologists, medical residents, fellows, internists and general practitioners who treat patients with hepatic encephalopathy."

"Latar Belakang: Asam lemak rantai pendek (SCFA) merupakan metabolit utama yang diproduksi di kolon, hasil dari fermentasi bakteri terhadap serat dan resistant starch. SCFA diperkirakan memiliki peran pada patogenesis ensefalopati hepatik (EH), meskipun mekanisme yang mendasarinya belum sepenuhnya dimengerti. Disbiosis mikrobiota yang terjadi pada sirosis mengubah komposisi SCFA pada feses dan berperan dalam patogenesis EH.Tujuan: Penelitian ini bertujuan untuk membandingkan proporsi SCFA feses pasien sirosis yang mengalami EH dan non EH.Metode: Penelitian ini merupakan studi potong lintang yang dilaksanakan di Klinik Hepatobilier dan Ruang Prosedur Terpadu, IPINB Hepatobilier RSUP Dr. Cipto Mangunkusumo Jakarta periode 2023. Pasien sirosis akan dilakukan tes flicker atau stroop, pemeriksaan SCFA feses (asetat, butirat, dan propionat), dan kuesioner dengan teknik food recall untuk menilai pola diet. Analisis bivariat dan multivariat dilakukan dengan aplikasi SPSS Statistics (IBM, 2024).Hasil: 86 pasien sirosis dengan rerata usia 53 tahun ± 8,10 dan jenis kelamin mayoritas (68,6%) laki-laki mengikuti penelitian ini. 20 pasien sirosis (23,25%) mengalami EH. Analisa bivariat tidak ditemukan perbedaan bermakna (p>0,05) antara jumlah SCFA feses, komponen SCFA, ataupun proporsi komponen SCFA. Analisa multivariat terhadap proporsi SCFA absolut [OR 2,47; IK95% (0,64 – 9,56); p=0,191], proporsi asetat absolut [OR 4,72; IK 95%(0,25 – 64,01); p=0,243], dan proporsi butirat [OR 1,91; IK 95% (0,450 – 8,09); p=0,381] bersifat sebagai prediktor kejadian EH, sekalipun tidak bermakna.Simpulan: Prevalensi EH pada pasien sirosis rawat jalan di Poliklinik Hepatobilier RSCM adalah 23,3% dengan EH covert sebesar 19,8% dan EH overt sebesar 3,5%. Proporsi SCFA feses tidak berhubungan dengan kejadian EH pada pasien sirosis.

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Background: Short chain fatty acids (SCFA) are the main metabolites of the intestinal microbiota which play a role as colonocyte trophic factors and maintain the integrity of the gastrointestinal tract and blood-brain barrier. Microbiota dysbiosis that occurs in cirrhosis changes SCFA composition in feses and plays a role in the pathogenesis of hepatic encephalopathy (HE).

Objective: This study aims to compare the amount and composition of fecal SCFA in cirrhotic patients with HE and non-HE.

Methods: This research is a cross-sectional study carried out at the Hepatobiliary Clinic and Integrated Procedure Room, IPINB Hepatobiliary Hospital Dr. Cipto Mangunkusumo Jakarta period 2023. Cirrhosis patients will undergo a flicker or Stroop test, fecal SCFA examination (acetate, butyrate and propionate), and a questionnaire with a food recall technique to assess dietary patterns. Bivariate and multivariate analyzes were carried out with the SPSS Statistics application (IBM, 2024).

Results: 86 cirrhosis patients with a mean age of 53 years ± 8.10 and the majority gender (68.6%) male took part in this study. 20 cirrhosis patients (23.25%) experienced EH. Bivariate analysis found no significant differences (p>0.05) between the amount of fecal SCFA, SCFA components, or proportion of SCFA components. Multivariate analysis of absolute SCFA proportions [OR 2.47; IK95% (0.64–9.56); p=0.191], absolute proportion of acetate [OR 4.72; IK95% (0.25- 64.01); p=0.243], and the proportion of butyrate [OR 1.91; CI 95% (0.450 – 8.09); p=0.381] is a predictor of EH events, even though it is not significant. Conclusions: The prevalence of HE in outpatients with cirrhosis at the Hepatobiliary Polyclinic of RSCM was 23.3% with covert HE of 19.8% and overt HE of 3.5%. The proportion of fecal SCFA was not associated with the incidence of HE in cirrhosis patients."

"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."

"Sirosis hati merupakan salah satu masalah kesehatan yang terjadi pada masyarakat perkotaan. Keadaan malnutrisi ditemukan pada 65-90% pasien sirosis hepatis. Kondisi malnutrisi ini berhubungan dengan terjadinya komplikasi serius pada pasien sirosis hepatis, yaitu asites, ensefalopati hepatikum, dan kematian. Penelitian sebelumnya menunjukkan bahwa pemberian diet tinggi protein, khususnya yang kaya akan asam amino rantai cabang (AARC) dapat memperbaiki kondisi klinis pasien sirosis dan mengurangi komplikasi serius tersebut. Tujuan penulisan ini adalah untuk melakukan analisis evidence based mengenai pemberian AARC dalam memperbaiki kondisi klinis (nutrisi, nilai albumin, dan mengurangi terjadinya ensefalopati hepatikum). Hasilnya pada pasien ini adalah terbukti status nutrisi dapat ditingkatkan, tidak terjadi penurunan yang signifikan pada nilai albumin, dan tidak terjadi ensefalopati hepatikum. Rekomendasi penulisan ini adalah agar perawat memberikan pendidikan kesehatan tentang pentingnya diet tinggi protein yang kaya akan AARC.

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Cirrhosis hepatic is one of problem in urban health. Malnutrition is commonly found in 65-90% cirrhosis hepatic patients. This condition correlated with serious complications such as ascites, hepatic encephalopathy, and mortality. Previous researches recommend that high protein intake enriched in branched chain amino acids (BCAA) can improve clinical outcome of cirrhosis hepatic patients and reduce complications. This final clinical nursing report aimed to analyze evidence based about BCAA administered to improve clinical outcome (nutritional status, albumin, and reduce hepatic encephalopathy). The results showed that nutritional status improved, no decreased of albumin concentration, and hepatic encephalopathy not reported. It is recommended to deliver health education to patients about the important of high protein intake enriched in BCAA."

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Latar Belakang: Perkembangan saraf adalah perkembangan utama pada anak, setiap hal yang mengganggu proses perkembangan akan menimbulkan kelainan neurologis, termasuk Ensefalopati Hipoksik Iskemik (EHI). Faktor risiko gawat janin merupakan faktor terbesar terjadinya EHI, diikuti perdarahan antepartum dan preeklamsia/eklamsia. Kelainan neurologis jangka pendek dapat dinilai di usia 7 sampai 10 hari, berupa penurunan kesadaran, kejang, refleks primitif yang menurun atau menghilang, kesulitan dalam proses menelan, atau kesulitan dalam pernapasan.

Tujuan: Mengetahui luaran neurologis jangka pendek pada bayi dengan EHI. 

Metode: Studi kohort retrospektif dan prospektif melalui rekam medis dan pengamatan langsung, pada bayi baru lahir dengan EHI yang menjalani rawat inap dan rawat jalan di beberapa rumah sakit, rentang waktu 1 Januari 2014 sampai 31 Maret 2020.

Hasil: Sebanyak 73 subyek memenuhi kriteria inklusi dan eksklusi. Kelainan neurologis terbanyak pada subyek saat rawat inap adalah masalah pernapasan, sedangkan pada subyek yang kontrol saat rawat jalan adalah hipertonus. Sembilan belas subyek meninggal saat perawatan. Hasil USG kepala pada 20 dari 51 subyek terbanyak didapatkan leukomalasia periventrikular. Tiga dari 9 subyek menunjukkan hasil EEG yang abnormal.

Kesimpulan: Bayi dengan EHI memiliki luaran klinis jangka pendek berupa kelainan neurologis. Tidak terdapat pengaruh antara gawat janin, preeklamsia/eklamsia, dan perdarahan antepartum terhadap gangguan neurologis jangka pendek pada bayi dengan EHI.

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Background: Neurodevelopmental, suppose to be the main developmental in children. Any interferences with the development process will cause neurological abnormalities in the child, including hypoxic-ischemic encephalopathy (EHI). Risk factors of HIE are fetal distress which is the most frequent cause, followed by antepartum hemorrhage, and preeclampsia/eclampsia. Short-term neurological disorder can be assessed on the age of 7 to 10 days, such as seizure, decreasing consciousness, declining or disappearing primitive reflexes, and difficulty of swallowing or breathing. 

Objective: To determine short-term neurological outcomes in infants with HIE.

Methods: A retrospective and prospective cohort study from medical records and direct observations of inpatient and outpatient infants with HIE from January 1^st, 2014 to March 31^st, 2020 in several hospitals. 

Results: Seventy-three subjects fulfilled inclusion and exclusion criteria. Neurological disorder which mostly found in inpatient subjects were respiratory problems, while in outpatient subjects were hypertonus. Nineteen subjects deceased during treatment. Head ultrasounds examination in 20 of 51 subjects mostly showed periventricular leukomalacia. Three of 9 subjects with EEG examination showed abnormality.

Conclusion: Infants with HIE experienced short-term clinical outcomes as neurological disorders. There was no influence between fetal distress, preeclampsia/eclampsia, and antepartum hemorrhage on short-term neurological disorders in infants with HIE.

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"ABSTRACTBackground: there are currently three iron chelator readily available for patients Indonesia; deferiprone/DFP (branded as Ferriprox), deferasirox/DFX (branded as Exjade) and deferoxamine/DFO (branded as Desferal). This study aims to determine which iron chelator is the most efficient in reducing cardiac and hepatic iron overload (measured by means of T2 MRI). Methods: journal search with determined MeSH term was done in PubMed and Scopus. Studies that looked upon thalassemia major patient in all ages with usage of monotherapy iron chelation and its effect on myocardial T2 MRI and/or liver T2 MRI was included. Appraisal of studies was done using Oxford CEBM appraisal tools and Joanna Brigs Institute critical appraisal tools. Results: total of 11 studies with grand total of 611 samples were included. Mean T2 MRI value or (when available) mean changes in T2 MRI value after usage of specific iron chelator was gained from all the studies included. Comparison study and individual studies shows better control and increase of myocardial T2 MRI in those with DFP, and of liver T2 in those with good adherence to DFO chelation. Conclusion: DFP is superior in controlling or reducing myocardial iron load (as proven by mT2 MRI) and DFO had better capabilities in controlling or reducing hepatic iron load (as proven by liver T2* MRI). Studies with longer observation and larger samples is needed to see a significant changes of T2 MRI in DFX."

"ABSTRAKLatar Belakang: Transplantasi sel sumsum tulang dilaporkan memperbaiki fibrosis hati. Beberapa studi in vitro menunjukkan bukti mekanisme perbaikan dengan melakukan ko-kultur 2D sel sumsum tulang dan sel stelata hepatik. Pada studi tersebut, sel sumsum tulang menghambat aktivasi sel stelata hepatik dan mengurangi deposisi matriks ekstra sel. Pada penelitian ini, mekanisme perbaikan tersebut diteliti dengan melakukan ko-kultur sel sumsum tulang dan sel stelata hepatik pada model kultur 3D dan meneliti efeknya terhadap ekspresi tenascin-C, suatu glikoprotein matriks yang memiliki kontribusi dalam fibrogenesis hati.Metode: Sel stelata hepatik dan sel sumsum tulang yang diisolasi dari tikus dikultur sendiri (monokultur) dan diko-kultur direk dengan metode hanging drop. Karakterisasi sel sumsum tulang dilakukan dengan analisis flowcytometry CD90CD34. Sampel dari kedua kelompok kultur dipanen pada hari ke-7 untuk analisis imunositokimia tenascin-C.Hasil: Persentase sel CD90+CD34- dari sel sumsum tulang yang diisolasi adalah 35,2%. Hasil yang diperoleh pada penelitian ini menunjukkan bahwa sel sumsum tulang memilki efek antifibrotik yang dibuktikan dengan penurunan signifikan ekspresi tenascin-C pada kelompok ko-kultur (p < 0,05) dibandingkan dengan kelompok monokultur pada hari kultur ke-7.Kesimpulan: Temuan tersebut menunjukkan bahwa sel sumsum tulang memiliki efek terapeutik potensial terhadap proses fibrosis hati melalui efeknya dalam meminimalkan ekspresi matriks ekstra sel tenascin-C.

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ABSTRACT

Background: Transplantation of bone marrow derived cells (BMCs) has been reported to improve liver fibrosis. Several in vitro studies have shown evidence for the mechanism of improvement by co-culturing BMCs and hepatic stellate cells (HSCs) in 2D models. In those studies, BMCs were reported to inhibit HSCs activation and reduce extracellular matrix deposition. In this study, we investigated the mechanism by co-culturing BMCs and HSCs in 3D model and its effect on tenascin-C expression, an extracellular matrix glycoprotein that has a contribution in liver fibrogenesis.

Methods: Primary isolated rat HSCs and BMCs were cultured alone (monoculture) and directly co-cultured with hanging drop method. Characterization of BMSCs was performed by flowcytometry CD90CD34 analysis. The monoculture and co-culture samples were harvested on day 7 for tenascin-C immunocytochemistry.

Results: The percentage of CD90+CD34- cells from the isolated BMCs was 35.2%. Result of the present study showed that BMCs have a significant antifibrotic effect as evidenced by the significant decrease in in tenascin-C expression in the co-culture group (p < 0.05) compared to the monoculture group on day 7.

Conclusions: This finding demonstrates that BMSCs have a potential therapeutic effect against liver fibrotic process through their effect in minimizing extracellular matrix tenascin-C expression."

"Pendahuluan: Cedera iskemia reperfusi CI/R merupakan masalah serius yang dihadapi pascahipoksia menyebabkan kerusakan sel yang letaknya berjauhan remote organ injury. Strategi yang digunakan untuk mengurangi kerusakan hepar pascaiskemia adalah melalui penerapan ischemic pre conditioning PI/R dan hiportemia. PI/R telah terbukti mengurangi kerusakan jaringan melalui mekanisme resistensi terhadap iskemia dan kebutuhan energi lebih rendah. Sedangkan hipotermia menghambat laju kematian sel sehingga dapat diterapkan sebagai terapi awal pada tatalaksana trauma dengan tujuan mencegah kerusakan bertambah berat. Penelitian ini bertujuan untuk diketahuinya efek protektif PI/R dan hipotermia terhadap perubahan morfologi jaringan hepar dan peningkatan kadar malondialdehyde MDA sebagai respon stress oksidatif. Metode: Studi eksperimental pada 24 ekor Oryctolagus cuniculus. Kelompok iskemia dilakukan ligasi arteri femoralis komunis dalam pembiusan selama empat jam untuk menginduksi iskemia, kemudian ligasi dibuka dan kelinci dibiarkan beraktivitas selama delapan jam. Pada kelompok PI/R dilakukan ligasi berulang arteri femoralis komunis kanan selama dua menit, dilepaskan tiga menit sebanyak dua siklus, kemudian diligasi selama empat jam. Kelompok hipotermia, dilakukan iskemia disertai membungkus ekstremitas bawah kanan dengan es, suhu antara 31-33oC Kemudian dilakukan laparotomi, dan diambil organ hepar. Pemeriksaan histopatologi hepar dilihat dari 3 zona, sentral, midzonal, perifer. Untuk menilai stress oksidatif jaringan dilakukan pemeriksaan biokimia dengan malondialdehyde MDA. Dilakukan uji statistik terhadap variabel tersebut dengan kemaknaan. Hasil: Pada pemeriksaan histomorfologi terdapat perbedaan perubahan histomorfologi pada sampel kontrol PI/R, dan Hipotermia terhadap iskemia (p<0,05). Derajat kerusakan histomorfologi pada kelompok PI/R lebih rendah dibandingkan kelompok iskemia reperfusi pada semua zona (p sentral = 0,015, p medial = 0,019, p perifer = 0,026). Analisis kadar MDA memperlihatkan terjadi peningkatan pada kelompok iskemia reperfusi menujukkan adanya stress oksidatif. Kadar MDA pada kelompok PI/R dan hipotermia lebih rendah dibandingkan kelompok iskemia.(p = 0,002). Konklusi: Keadaan iskemia reperfusi menyebabkan perubahan histomorfologi dan stres oksidatif sel–sel hepar. PI/R dan hipotermia mempunyai efek protektif pada cedera iskemia reperfusi. Efek protektif PI/R lebih baik dari hipotermia.

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Introduction: Ischemia-reperfusion injury IRI is a serious problem occuring after hypoxia it causes injuries to cells located remotely from one another remote organ injury. Strategies used to decrease hepatic injuries post ischemic condition are composed as ischemic pre-conditioning IPC and hypothermia management procedures. IPC has been proven to decrease tissue injuries through resistance mechanisms towards ischemia and lower energy requirements. Meanwhile, hypothermia detained the rate of cell deaths, therefore, it can be used as initial therapy on trauma management in order to prevent worsening of the injuries. This research aims to evaluate the protective effects of IPC and hypothermia towards morphological changes of hepatic tissues and the increase of malondialdehyde MDA level as a response to oxidative stress.Methods.

Methods: This research is an experimental, descriptive-analytical study on 24 Oryctolagus cuniculus. The specimens were divided into four groups, with one group as control. The ischemia group underwent femoral artery ligations under anesthesia for four hours to induce ischemia. Afterwards, the ligations were released and the rabbits were free to roam for eight hours. The IPC group underwent repeated ligations of right communal femoral artery for two minutes and three minutes of release in two cycles. Afterwards, the arteries were ligated for four hours. The hypothermia group underwent ischemia and wrapping of right lower extremities using ice, with temperature around 31-33oC. Afterwards, laparotomies were conducted on all groups to obtain and evaluate the liver. Hepatic histopathology assessment were conducted from 3 zones, the central, midzone, and peripheral zone. To evaluate the effects of oxidative stress on the tissue, a biochemical assessment with malondialdehyde MDA was conducted. Statistical tests were then conducted to assess the relationship between the variables with significance level p < 0.05.

Results: On histomorphological assessment, there were histomorphologic changes on control samples for IPC and hypothermia compared to ischemia p < 0.05. On MDA level analysis, there were increases in all four groups p < 0.05. However, there were no significant differences for the histomorphological changes when compared between central, medial, and peripheral zones.

Conclusion: Ischemic reperfusion condition causes histomorphological changes and oxidative stress on hepatic cells. IPC and hypothermia have protective effects from ischemia-reperfusion injuries. The protective effects of IPC was better than hypothermia."