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"Nowadays studies have shown that liver fibrosis is a reversible process. Theraupetic target on Hepatic Stellate Cell (HSC) through inhibition of fibrotic signaling transduction is one of the way to treat liver fibrosis (e.g. pentoxifylline)..."

"Chronic hepatitis B is still a major health problem in Indonesia. Unfortunately, to date, treatment of chronic HBV (Hepatitis B virus) infection had not shown satisfactory result. Monotherapy with alpha interferon or lamivudine have been widely used as treatment of chronic HBV. However, treatment response to Alpha interferon in Asian people was not satisfactory (15% - 20%), while monotherapy with lamivudine was not sufficient to eradicate HBV in chronically infected patients and commonly induce drug resistance. The occurrence of chronic hepatitis B resistant to lamivudine had encouraged development of newer agents such as adefovir, entecavir, emtricitabine and nucleoside analog. New therapeutic strategy using combination therapy should be considered if there is no sufficient response to monotherapy"

"Background: Hepatitis B is endemic in Indonesia and treatment response need to be monitored during and after antiviral therapy. Liver stiffness measurement and alanine aminotransferase to platelet ratio index (APRI) are noninvasive method to detect liver fibrosis available in Indonesia. However, little is known about their ability to evaluate treatment response in chronic hepatitis B (CHB) patients in Indonesia. This study aimed to investigate liver stiffness changes by transient elastography (TE) and APRI before and after one year oral antiviral treatment in CHB patients and the correlation between TE and APRI.Methods: this study was retrospective cohort on CHB patients in CiptoMangunkusumo Hospital, Jakarta who uderwent treatment between January 2012 and December 2014. Patients received oral antiviral treatment with newer nucleoside analogues (entecavir or telbivudine) for at least one year. TE and APRI were obtained before and after treatment. TE and APRI reductions were analyzed statistically with Spearmans test.Results: a total of 41 patients were enrolled in this study. Median liver stiffness value was significantly reduced from 10.8 to 5.9 kPa after oral antiviral treatment (p<0.001, Wilcoxons test). Median APRI was also significantly reduced from 1.13 to 0.43 after treatment (p<0.001, Wilcoxons test). The correlation between liver stiffness and APRI before treatment was weak (r=0.40), but it was strong after treatment (r=0.73).Conclusion: the liver stiffness measured with transient elastography and APRI significantly decreased after one year of antiviral treatment in chronic HBV patients. There was a significant correlation between TE and APRI after one year of treatment."

"Amplifikasi DNA virus hepatitis B (VHB) dari sampel plasma sulit dilakukan apabila kadar DNA VHB <10.000 kopi/ml. Sehingga, langkah awal ekstraksi menjadi penting bagi keberhasilan amplifikasi dan sekuensing. Peningkatan konsentrasi DNA dalam jumlah yang cukup dan berkualitas baik memerlukan metode isolasi yang optimal. Tujuan penelitian ini adalah mendapatkan teknik isolasi DNA yang optimal untuk menghasilkan DNA VHB dalam jumlah yang cukup sehingga dapat digunakan untuk mendeteksi perubahan genetik gen polimerase VHB terkait resistensi obat antivirus pada kasus hepatitis B kronik. Optimasi prosedur penanganan sampel untuk mengekstraksi partikel DNA VHB dilakukan dengan mengisolasi sampel plasma dengan kadar virus 105 kopi/ml menggunakan delapan perlakuan yang berbeda yaitu 1 ml dan 200 µL plasma disentrifugasi 4000xg selama 20 menit pada suhu 25°C (P1 dan P2), 1 ml dan 200 µL plasma disentrifugasi 16000xg selama 1 jam pada suhu 4°C (P3 dan P4), 1 ml plasma disentrifugasi 21000xg selama 1 jam pada suhu 4°C (P5), 1 ml plasma dalam PEG6000 20% diinkubasi semalaman pada 2-8°C kemudian disentrifugasi 21000xg selama 1 jam pada suhu 4°C (P6), 1 ml plasma dalam PEG6000 20% dan NaCl 0.5M diinkubasi semalaman pada 2-8oC kemudian disentrifugasi 21000xg selama 1 jam pada suhu 4°C (P7), dan 200 µL sampel plasma tanpa penambahan perlakuan (P8). Kadar virus diukur menggunakan kuantitatif realtime PCR, dan hasil dari setiap perlakuan sampel dibandingkan dengan kontrol (P8). Uji simulasi dilakukan pada sampel plasma dengan kadar virus 105; 104; 103 dan 102 kopi/ml yang diberikan perlakuan 3 (P3) yang dipilih berdasarkan hasil sebelumnya, DNA kemudian disekuensing untuk dianalisis mutasi resistensinya terhadap obat antivirus dan hasilnya dibandingkan dengan sampel yang tanpa diberikan perlakuan. Hasil menunjukkan bahwa terjadi peningkatan konsentrasi DNA pada rerata sampel yang diisolasi menggunakan P3 jika dibandingkan dengan kontrol (P8). Sedangkan hasil sekuensing untuk analisis mutasi pada gen polimerase terkait resistensi terhadap obat antivirus dapat dilakukan pada sampel dengan kadar virus 105; 104; 103 kopi/ml baik yang diberikan perlakuan maupun tanpa perlakuan. Namun, sampel dengan kadar virus 102 kopi/ml hanya dapat dianalisis mutasi resistensinya pada sampel yang ditambahkan perlakuan 3 (P3). Kesimpulan: 1 ml plasma yang disentrifugasi 16000xg selama 1 jam pada suhu 4°C (perlakuan 3) merupakan metode isolasi DNA yang mampu meningkatkan perolehan DNA secara optimal dari sampel plasma penderita hepatitis B kronik, sehingga analisis resistensi terhadap obat antivirus menggunakan teknik in-house assay dapat di lakukan pada sampel dengan kadar virus <10.000 kopi DNA/ml.

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The amplification of hepatitis B virus DNA from plasma samples is difficult when HBV DNA levels <10.000 copies/ml. Thus, the initial step of extraction become crucial for the success of amplification and sequencing. Increasing concentrations of DNA in sufficient quantity and good quality need an optimal isolation method. The aim of this study is to obtain an optimal DNA isolation technique and generate HBV DNA in sufficient quantities, so that it can be used to detect genetic changes of HBV polymerase gene related to drugs resistance on chronic hepatitis B. The optimization of sample handling procedure for extracting HBV DNA particles were performed by isolating plasma samples with viral load 105 copies/ml using eight different kinds of treatment are 1 ml and 200 µL of plasma was centrifuged at 4000×g for 20 minutes at 25°C (P1 and P2); 1 ml and 200 µL of plasma centrifuged at 16000×g for 1 hour at 4°C (P3 and P4); 1 ml of plasma centrifuged at 21000×g for 1 hour at 4°C (P5); 1 ml of plasma in 20% PEG6000 were incubated overnight at 2-8°C then centrifuged at 21000xg for 1 hour at 4°C (P6), 1 ml of plasma in 20% PEG6000 and 0.5M NaCl were incubated overnight at 2-8oC then centrifuged at 21000xg for 1 hour at 4°C (P7), and 200 µL of plasma without treatment (P8). Hepatitis B virus level were measured using quantitative real-time PCR, and the results of each treatment compared to the control samples (P8). Simulation test performed on plasma samples with grading of virus level (i.e 105; 104; 103 and 102 copies/ml) were given treatment 3 (P3) were selected based on previous results, the DNA was sequenced and then analyzed for drugs resistance and the results were compared with samples without treatment.

Result showed that an increasing in average concentration of DNA samples was isolated using the P3 when compared with controls (P8). While the results of sequencing for analysis of mutations in polymerase gene associated with drugs resistance can be performed on samples with virus level 105; 104; 103 copies/ml were given either treatment or no treatment. However, samples with virus level 102 copies/ml can be analyzed only

on treatment samples.

Conclusion: 1 ml plasma were centrifuged at 16000xg for 1 h at 4°C (treatment 3) is a DNA isolation method that can improve the recovery of optimal DNA from plasma samples of patients with chronic hepatitis B, so that the analysis of drug resistance using in-house assay techniques can be done on samples with virus levels <10,000 copies/ml."

"Ruang lingkup dan Cara penelitian: Virus Hepatitis B (VHB) merupakan penyebab tersering hepatitis kronik, sirosis hepatis dan karsinoma hepatoselular di negara-negara Asia Tenggara.VHB merupakan virus DNA berukuran 3,2 kb, mempunyai untai ganda dengan susunan genom yang kompak dan sating tumpang tindih. Materi genetik VHB tersimpan daiam 4 Open Reading Frames pada untai negatif. Transmisi VHB terjadi melalui kontak dengan darah, komponen darah atau cairan tubuh lainnya. Diagnosis infeksi VHB didasarkan adanya HBsAg dalam serum. Hilangnya HBsAg dan terbentuknya anti-HBs merupakan petanda eliminasi virus. Namun demikian mutasi yang terjadi pada gen penyandi HBsAg mengakibatkan perubahan antigenisitas HBsAg sehingga virus lolos dart pemeriksaan yang menggunakan antibodi monoklonal terhadap HBsAg. Untuk mengetahui perubahan molekuler pada gen penyandi HBsAg maka dilakukan penelitian program magister ini dengan tujuan umum untuk mengetahui dasar molekuler kegagalan deteksi serologi HBsAg pada serum donor darah di Indonesia. Untuk itu dilakukan isolasi DNA VHB, ligasi ke vektor dan transformasi ke bakteri E.coli, dilanjutkan dengan reaksi sekuensing yang hasilnya dianalisis dengan perangkat bioinformatika.Hasil dan kesimpulan: Pada serum donor darah dengan HBsAg (-), anti-HBs (-) dan anti-HBc (+) berhasil didapat DNA VHB pada 20 (29,9%) dart 67 sampeI; pada donor darah dengan HBsAg (-), anti-HBs (+) dan anti-HBc (+) didapat DNA VHB pada 5 (7.5%) dart 67 sampel. Sehingga jumlah total DNA VHB (+) didapat pada 25 (8,I%) dari 309 sampel dengan HBsAg (-), Pada sekuensing determinan 'a' gen S DNA VHB didapat 7 (28%) dari 25 sampel menunjukkan mutasi asam amino. Terdapat 3 pola substitusi asam amino: pola pertama substitusi M I 33L sebanyak I (4%) dari 25 sampel, polar kedua T123A sebanyak I (4%) dari 25 sampel, dan pola ketigaTI43M sebanyak 5 (20%) dari 25 sampel. Semua virus; termasuk dalam subtipe adw.Pada studi bioinformatika, substitusi ini menyebabkan terjadinya penurunan nilai indeks antigenisitas asam amino yang bersangkutan dan asam amino yang berada di sekitarnya. Substitusi asam amino pada gen S mengakibatkan terjadinya perubahan sekuens gen P daerah reverse transcriplase yang tumpang tindih dengan gen S."

"Genotipe virus hepatitis B (VHB) mempunyai hubungan yang erat dengan prognosis dan terapinya serta diperlukan untuk studi epidemiologi. Pemeriksaan ini hanya bisa dikerjakan di kota-kota besar saja karena kesulitan pengiriman sampel akibat masalah geografis maupun fasilitas. Tujuan penelitian ini adalah untuk mengetahui apakah genotipe VHB dapat ditentukan dari serum kering pada kertas saring dan membandingkan hasil tersebut dengan serum yang diambil langsung dari pasien hepatitis B kronik (HBK) dan hepatoma. Dua puluh tiga sampel dapat diambil dari pasien HBK dan konsentrasi DNA VHB di tentukan dengan Cobas Amplicor HBM (Roche Diagnostics GmBH, Germany) kemudian diteteskan pada kertas saring (3 x 1 cm). Setelah dikeringkan dalam kantong plastik, diletakkan dalam amplop tertutup dan disimpan selama 1 minggu dalam suhu kamar (27 – 33 oC). Ekstraksi DNA dilakukan dari kertas saring tersebut setelah diinkubasi dan penentuan genotipe VHB dilakukan dengan PCR menggunakan primer-primer spesifik. Untuk perbandingan, telah didapatkan 20 sampel pasien HBK-HBe (+) dan 29 sampel pasien hepatoma yang tidak dikeringkan. Genotipe VHB dapat dideteksi pada 18/23 (78,2%) serum kering pada kertas saring sedangkan pada serum yang tidak dikeringkan, dari pasien HBK-HBe(+) 20/20 (100%) sampel terdeteksi dan dari pasien hepatoma 24/29 (82,7%) sampel. Proporsi genotipe yang terdeteksi sesuai dengan proporsi genotipe yang pernah dilaporkan di Indonesia. Kesimpulan penelitian ini adalah genotipe VHB dapat dideteksi dari serum kering pada kertas saring yang disimpan selama 1 minggu. (Med J Indones 2005; 14: 215-9)

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HBV genotype has a close association with prognosis and therapy as well as for epidemiology study. However, this examination can be done only in large cities that are not practical to send serum sample due to geographical burden and facilities. The aim of this study is to know whether HBV genotype can be determined from dried and stored serum on filter paper and compare the result with sera drawn directly from chronic hepatitis B (CHB) and hepatoma patients. Twenty-three serum samples were obtained from CHB patients. HBV DNA were quantitatively determined with Cobas Amplicor HBM (Roche Diagnostics GmBH, Germany) and dropped on to 3 x 1 cm filter papers. After allowed to dry in a plastic clip, it were put in a closed envelope then stored for 1 week in room condition (27 – 33 oC). DNA extraction were done from the filter papers after a short incubation period and HBV genotypes were determined with PCR and specific primers. For comparison, 20 CHB-Hbe(+) samples and 29 hepatoma samples were drawn directly and not dried. HBV genotype were detected in 18/23 (78.2%) from dried serum samples on filter paper while in sera that were not stored, from CHB-HBe(+) samples, 20/20 (100%) could be determined while from hepatoma patients, 24/29 (82.7%) samples. The proportion of genotype were in line with other reported HBV genotype examination for Indonesia. It is concluded that detection of HBV genotype can be done from dried serum in filter paper and stored for 1 week. (Med J Indones 2005; 14: 215-9)"

"Hepatitis B merupakan salah satu penyakit menular yang dapat menyebabkan kematian. Hepatitis B adalah penyakit hati yang disebabkan oleh virus hepatitis B. Penyakit ini dapat dicegah penularannya dengan melakukan vaksinasi. Pada skripsi ini dikonstruksi model matematika SVAKR yang membahas mengenai model matematika penyebaran penyakit hepatitis B dengan intervensi vaksinasi. Kajian analitik dan simulasi numerik telah dilakukan pada model tersebut untuk mempermudah dalam memahami dinamika populasi jangka panjang. Kajian analitik yang telah dilakukan meliputi konstruksi model matematika beserta interpretasi model tersebut, titik keseimbangan beserta kestabilannya, dan Basic Reproduction Number (R0). Pada kajian analitik, didapatkan hasil bahwa titik keseimbangan bebas penyakit ada dan stabil asimtotik lokal ketika R0 < 1. Berdasarkan simulasi numerik yang telah dilakukan, diperoleh informasi bahwa intervensi vaksinasi dapat mengendalikan penyebaran penyakit hepatitis B. Lebih lanjut apabila vaksinasi diiringi dengan peningkatan laju kesembuhan infeksi akut, maka penyebaran penyakit hepatitis B dapat dikendalikan dengan lebih optimal.

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Hepatitis B is an infectious disease that can cause death. Hepatitis B is a liver disease caused by the hepatitis B virus. This disease can be prevented from being transmitted by vaccination. In this undergraduate thesis, a mathematical model SV AKR is constructed which discusses the mathematical model of the spread of hepatitis B disease with vacci- nation intervention. Analytical studies and numerical simulations have been carried out on the model to make it easier to understand long-term population dynamics. Analytical studies that have been carried out includes the construction of a mathematical model and its interpretation, the equilibrium point and its stability, and Basic Reproduction Number (R0). In the analytical study, it was found that a disease-free equilibrium point exists and locally asymptotically stable when R0 < 1. Based on numerical simulations that have been carried out, it was found that vaccination intervention was able to control the spread of hepatitis B. Furthermore, if vaccination is accompanied by an increase in recovery rate of acute infection, the spread of hepatitis B can be controlled more optimally."

"ABSTRAKHepatitis virus B yang telah menjadi masalah kesehatan masyarakat, dapat ditularkan secara parenteral, oral, dan kemungkinan secara seksual. Infeksi virus hepatitis B (VHB) dapat diketahui dengan adanya antigen-antigen virus serta antibodinya yang dapat dideteksi di dalam serum penderita. Hepatitis B surface antigen (HBsAg) yang merupakan salah satu petanda serologi infeksi VHB, dilaporkan terdapat pada air susu ibu, sekret vagina, air liur, dan semen. Tetapi peranannya dalam penyebaran penyakit belum jelas. Dalam penelitian ini telah dilakukan pemeriksaan HBsAg secara kualitatif dan kuantitatif (titer) dengan teknik RPHA terhadap serum dan plasma semen 20 orang pria penderita hepatitis virus B. Plasma semen yang mengandung HBsAg terdapat pada 8 orang (40%) dari 20 orang yang diteliti. Dengan uji korelasi jenjang Spearman, diperoleh kesimpulan bahwa terdapat korelasi positif antara titer HBsAg serum dengan titer HBsAg plasma semen (db=0.001). Selain itu, juga dapat disimpulkan bahwa titer HBsAg di alam plasma semen rendah ("

"Latar Belakang: Pajanan nyeri menimbulkan efek merugikan baik pada neonatus kurang bulan maupun neonatus cukup bulan. Efek analgesik sukrosa pada penyuntikan intramuskular masih kontroversial. Efektivitas sukrosa untuk mengatasi nyeris saat vaksinasi hepatitis B pada neonatus cukup bulan belum pernah diteliti di Indonesia. Tujuan: untuk mengetahui efek analgesik pemberian sukrosa disertai empeng saat vaksinasi hepatitis B pada neonatus cukup bulan. Metode: penelitian ini menggunakan metode uji klinis acak tersamar ganda. Subjek secara random dibagi menjadi kelompok intervensi yang mendapatkan 2 mL sukrosa 24% disertai empeng, serta kelompok kontrol yang mendapatkan 2 mL aquabidestilata disertai empeng. Rasa nyeri yang dirasakan subjek dievaluasi dengan skor nyeri premature infant pain profile (PIPP). Hasil: median skor PIPP pada kelompok yang diberikan sukrosa lebih rendah dibandingkan kelompok kontrol (6 (2-15) vs 11 (2-15), p <0,0001). Lama tangis subjek pada kelompok yang mendapat sukrosa lebih singkat dibandingkan kelompok kontrol (11 (0-33) detik vs 19 (0-100) detik, p <0,0001). Pemberian empeng tidak memberikan efek sinergis dalam menurunkan skor nyeri maupun lama tangis subjek. Pada penelitian ini ditemukan satu subjek yang mengalami desaturasi hingga saturasi oksigen <88% saat pemberian sukrosa, namun efek samping ini tidak memerlukan terapi khusus. Simpulan: sukrosa secara statistik menurunkan skor nyeri PIPP dan lama tangis saat vaksinasi hepatitis B pada neonatus cukup bulan.

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Background: Pain causes adverse effect for preterm and also term newborn. Analgesic effect of sucrose during intramuscular injection is still a controversy. Sucrose effectivity in reducing pain in term newborn during hepatitis B vaccination has not been studied in Indonesia.

Objective: to examine analgesic effect of sucrose with pacifier during hepatitis B vaccination in term newborn.

Method: we used consecutive sampling to reach 70 subjects. Subject was randomised into intervension group receiving 2 mL of 24% sucrose solution with pacifier, and control group receiving 2 mL aquadest with pacifier. Pain was evaluated with the premature infant pain profile (PIPP) scoring system.

Result: median PIPP score in intervension group was significantly lower than control group (6 (2-15) vs 11 (2-15), p <0,0001). Cry duration in intervension group was significantly shorter than control group (11 (0-33) second vs 19 (0-100) second, p <0,0001). Pacifier had no synergistic effect in lowering PIPP score and cry duration. Decreased oxygen saturation below 88% was found in one subject receiving sucrose but additional therapy was not needed.

Conclusion: Sucrose was statistically significant in reducing pain score and cry duration during hepatitis B vaccination in term newborn."

"[Standard Operating of Procedur dalam melaksanakan tindakan medis, termasuk Pemasangan dan pencabutan implan sampai detik ini dipakai untuk meminimalir terjadinya sesuatu yang tidak diinginkan termasuk infeksi ataupun transmisi dari penyakit menular seperti Hepatitis B. Penelitian ini digunakan untuk melihat sejauh mana Pengetahuan, sikap dan perilaku bidan desa di Kabupaten Purworejo dalam mencegah transmisi Hepatitis B saat melaksanakan salah satu tugasnya yaitu memberikan pelayanan Implan. Desain dalam penelitian ini adalah cross sectional, dengan sampel bidan desa yang bertugas di Kabupaten Purworejo, berjumlah 80 orang, menggunakan kuesioner dan ceklis, Bidan desa yang berperilaku baik sebanyak 5,3%, ada hubungan antara Pengetahuan dengan perilaku pencegahan transmisi Hepatitis B dengan nilai p=0,028, Standard Operating of Procedure in carrying out of medical practice, including the installation and retraction until the second implant is used to reduce the occurrence of unwanted things including infection or transmission of infectious diseases such as Hepatitis B. This research is used to see the extent to which knowledge, attitudes and behavior in Purworejo midwife in preventing the transmission of Hepatitis B while executing one of his duties is to provide services Implants. Design in this study is cross-sectional, with a sample of midwives who served in Purworejo, with the number of 80 people, using questionnaires and checklists, the village midwife who behaved much as 5.3%, there is a relationship between knowledge of the behavior of the transmission prevention Hepatitis B, p value=0,028.;Standard Operating of Procedure in carrying out of medical practice, including the installation and retraction until the second implant is used to reduce the occurrence of unwanted things including infection or transmission of infectious diseases such as Hepatitis B. This research is used to see the extent to which knowledge, attitudes and behavior in Purworejo midwife in preventing the transmission of Hepatitis B while executing one of his duties is to provide services Implants. Design in this study is cross-sectional, with a sample of midwives who served in Purworejo, with the number of 80 people, using questionnaires and checklists, the village midwife who behaved much as 5.3%, there is a relationship between knowledge of the behavior of the transmission prevention Hepatitis B, p value=0,028.;Standard Operating of Procedure in carrying out of medical practice, including the installation and retraction until the second implant is used to reduce the occurrence of unwanted things including infection or transmission of infectious diseases such as Hepatitis B. This research is used to see the extent to which knowledge, attitudes and behavior in Purworejo midwife in preventing the transmission of Hepatitis B while executing one of his duties is to provide services Implants. Design in this study is cross-sectional, with a sample of midwives who served in Purworejo, with the number of 80 people, using questionnaires and checklists, the village midwife who behaved much as 5.3%, there is a relationship between knowledge of the behavior of the transmission prevention Hepatitis B, p value=0,028.;Standard Operating of Procedure in carrying out of medical practice, including the installation and retraction until the second implant is used to reduce the occurrence of unwanted things including infection or transmission of infectious diseases such as Hepatitis B. This research is used to see the extent to which knowledge, attitudes and behavior in Purworejo midwife in preventing the transmission of Hepatitis B while executing one of his duties is to provide services Implants. Design in this study is cross-sectional, with a sample of midwives who served in Purworejo, with the number of 80 people, using questionnaires and checklists, the village midwife who behaved much as 5.3%, there is a relationship between knowledge of the behavior of the transmission prevention Hepatitis B, p value=0,028. ]"