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"ABSTRAK<

Karsinoma hepatoseluler (KHS) merupakan karsinoma primer tersering pada sel hati. Sebagian besar KHS disebabkan oleh virus hepatitis B (VHB) dan virus hepatitis C (VHC) yang memiliki patogenesis yang berbeda dalam menyebabkan KHS. Alfa-fetoprotein (AFP) sebagai penanda tumor pada KHS dan dipengaruhi oleh berbagai faktor, salah satunya status infeksi. Berbagai penelitian sudah dilakukan untuk mengetahui pengaruh pengaruh jenis virus penyebab KHS dengan kadar AFP namun hasilnya sangat beragam. Berdasarkan hal tersebut dan ditambah dengan belum adanya penelitian serupa yang menggunakan data pasien di Indonesia maka penelitian ini bertujuan untuk membandingkan kadar AFP pada pasien KHS terkait infeksi VHB terhadap VHC. Penelitian ini dilakukan dengan desain studi potong lintang menggunakan 199 data AFP pasien KHS yang terdiri dari 129 kasus KHS terkait VHB dan 70 kasus KHS terkait VHC. Dari penelitian ini didapatkan sebanyak 97% dan 87.3% pasien KHS terkait VHC dan VHB mengalami peningkatan kadar AFP secara berurutan. Nilai median kadar AFP pada pasien KHS terkait VHB adalah 419 IU/mL sedangkan pada pasien KHS terkait VHC sebesar 400 IU/mL. Perbedaan nilai tersebut memiliki nilai p = 0.97 dalam uji Mann-Whitney U sehingga disimpulan tidak ada perbedaan bermakna pada rerata kadar AFP antara pasien KHS terkait VHB dibanding dengan VHC.

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ABSTRACT

Hepatocellular carcinoma (HCC) is the most primary common carcinoma in liver cells. Most HCC are caused by the hepatitis B virus and hepatitis C that have different pathogenesis in causing carcinoma. Alpha-fetoprotein as tumor marker in HCC is influenced by various factors, one of which is infection status. Various studies have been carried out to determine the influence of the types of viruses causing HCC with AFP levels but the results are very diverse. Based on this and coupled with the absence of similar studies using patient data in Indonesia, this study aims to compare AFP levels in HCC patients related to HBV and HCV. Using cross-sectional design, this study included 199 data of AFP in patient with HCC comprises of 129 cases of HCC related to HBV and 70 cases of HCC related to HCV. From this study, it was found that 97% and 87.3% of HCC patients related to HCV and HBV experienced an increase in AFP levels consecutively. The median value of AFP levels in HBV-related HCC patients was 419 IU / mL while in HCV-related HCC patients was 400 IU / mL. The difference in value has a p value = 0.97 in the Mann-Whitney U test thus it is concluded that there is no significant difference in AFP levels between HBV-related HCC patients compared with HCV-related HCC.

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"Karsinoma hepatoseluler (KHS) adalah salah satu kanker dengan laju mortalitas tertinggi di dunia. Kadar serum alfa-fetoprotein (AFP) dapat digunakan sebagai biomarker untuk menegakkan diagnosis dini. Tetapi, perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus belum diketahui. Mengetahui perbandingan antara kadar serum AFP dan KHS dengan etiologi infeksi virus dan etiologi non infeksi virus. Penelitian potong lintang dilakukan di RSUPN Cipto Mangunkusumo, Jakarta pada Januari-Oktober 2018 dengan melihat data rekam medis dari 287 pasien yang terdiagnosis KHS dalam periode 2013-2017. Nilai median (minimum-maksimum) dari kadar AFP pada pasien KHS dengan etiologi infeksi VHB atau VHC adalah 419 (0.8-400.000). Nilai median (minimum-maksimum) kadar AFP pada pasien KHS dengan etiologi non infeksi VHB-VHC adalah 7.18 (0.6-90.944). Terdapat perbedaan bermakna antara kadar AFP dengan KHS dengan etiologi infeksi VHB atau VHC dan etiologi non infeksi VHB-VHC.

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Hepatocellular carcinoma (HCC) is one of the highest rates of mortality in the world. Serum alpha-fetoprotein (AFP) levels can be used as a biomarker for early diagnosis. However, the comparison between serum AFP and HCC with viral infections etiology and non-viral etiology is unknown. This research aims to determine the comparison between serum AFP and HCC with viral infections etiology and non-viral aetiology. A cross-sectional study conducted in Cipto Mangunkusumo Hospital, Jakarta in January to October 2018 by reviewing 287 medical records of patients diagnosed with HCC from 2013-2017 period of time. The median (minimum-maximum) value of AFP levels in HCC patients with the etiology of HBV or HCV infection is 419 (0.8-400,000). The median value (minimum-maximum) of AFP levels in HCC patients with the etiology of non HBV-HCV infection was 7.18 (0.6-90,944). There were significant differences between AFP levels and KHS with the etiology of HBV or HCV infections and the etiology of non HBV-HCV infections."

"Latar Belakang: Mutasi Al762T/GI764A basal core promoter (BCP) dan Gl896A precore pada genom virus hepatitis B (VHB) berhubungan dengan tingkat keparahan penyakit hati, namun demikian peran mutasi-mutasi tersebut pada perjalanan infeksi hepatitis B kronis masih belum jelas. Olch karena itu, penelitian ini bertujuan untuk mengetahui prevalensi mutasi Al762T/Gl764A dan Gl896A serta hubungannya dengan fase-fase pada perjalanan infeksi hepatitis B kronis. Metodologi: Seratus empat puluh pasien hepatitis B kronis yang dilibatkan dalam pcnelitian ini, belum mendapatkan pengobatan, dan dikelompokkan ke dalam fase immunotolerant (IT), immunoclearance (IC), non/Iow replicative (LR) dan hepatitis "c" negatif (ENH). DNA VHB diperiksa dan diul-cur kadarnya dengan teknik polymerase chain reaction, kemudian disekuensing untuk dianalisis. Hasil: Usia subjek lebih tua pada kelompok ENH dan LR dibandingkan dengan fase lain (p<0.05). Kadar DNA paling tinggi pada fase IC dan paling rendah pada fase LR (p<0.00l), sementara pria mempunyai risiko lebih besar terjadi reaktivasi dengan HBeAg negatif (p<0.05). Mutasi Al 762T/GI764A tidak berbeda bermakna pada semua fase (p=0.56) dan lebih tinggi pada genotipe C dan subtipe adr (p<0.05). Mutasi Gl896A paling tinggi pada Pass LR (p<0.05), dan tidak berbeda bcrmakna pada genotipe dan subtipe VHB. Tidak ada hubungan antara kadar DNA V1-IB dengan mutasi di prccore dan BCP. Kesimpulan: Prevalensi mutasi Gl896A berbeda pada fase hepatitis B kronis di Indonesia, ditemukan lebih sering pada usia lebih tua dan fase lanjut. Mutasi A1762T/Gl764A berkorelasi dengan genotipe dan subtipe VHB, sebaliknya tidak berhubungan dengan fase infeksi. Studi ini mengindikasikan bahwa mutasi BCP tidak berhubungan dcngan serokonversi HBeAg pada perjalanan infeksi hepatitis B kronis.

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Background: Precore Gl896A and basal core promoter (BCP) A1762T/G1764A mutations of hepatitis B virus (HBV) genome have been correlated with severe liver diseases; however, their role in the pathogenesis of chronic hepatitis B (CHB) remains unclear. We assessed the prevalence and association of these mutations in different phases of CHB in Indonesian patients.

Methods: One-hundred and forty CHB patients, not undergoing antiviral therapy, were classified into immune-tolerance (IT), immune-clearance (IC), nonllow- replicative (LR), and hepatitis B e antigen (HBeAg)-negative hepatitis (ENH) phases. HBV DNA was detected and quantified by polymerase chain reaction then analyzed by sequencing.

Results: ENH and LR patients were older than IC or IT patients (p <0.05). HBV DNA levels were highest in IC patients and lowest in LR (p<0.0001). The A1896 pre-core mutants were most prevalent in LR (p<0.00l) and higher in ENH (p<0.00I) than in IT and IC patients, while the Al762T/Gl764A BCP mutants were comparable between all phases. The Al762T/Gl764A BCP mutants were more frequently identified in genotype C than in genotype B (p <0.05), and in subtype adr than in subtypes adw and ayw (p <0.05). The Tl858 mutants were detected in almost all HBV isolates regardless the genotypes (B and C). N0 associations were observed between HBV DNA levels and precore as well as BCP mutations.

Conclusions: The prevalence of precore A1896 mutation differed in phases of CHB in Indonesian patients with preponderance in older ages and later stages. BCP AI762T/Gl764A mutations were associated with HBV genotypes and subtypes, itrespective of infection phases. These findings indicate that BCP mutations could be independent of HBeAg seroconversion in the natural history of chronic HBV infection."

"ABSTRAKHepatitis B adalah suatu penyakit yang disebabkan oleh virus hepatitis B. Salah satu faktor yang berpengaruh dalam pembentukan virus hepatitis B adalah core protein Cp . Sehingga Cp dapat digunakan sebagai salah satu target pengobatan hepatitis B. Pada penelitian ini dilakukan penapisan virtual senyawa dari basis data tanaman herbal Indonesia sebagai core protein allosteric modulator CpAM menggunakan peranti lunak AutoDock dan AutoDock Vina. Metode divalidasi dengan menggunakan parameter Enrichment Factor EF , Receiver Operating Characteristics ROC , dan Area Under Curve AUC . Pada penapisan menggunakan AutoDock digunakan grid box ukuran 55x55x55 dengan nilai EF10 0.7652 dan AUC 0.6709 sementara grid box ukuran 20.625x20.625x20.625 untuk penapisan menggunakan AutoDock Vina dengan nilai EF5 0.5075 dan AUC 0.7832. Sepuluh senyawa terbaik hasil penapisan virtual menggunakan AutoDock memiliki rentang DG: -11.74 -10.31 kkal/mol adalah yuehchukene, lansionic acid, stigmast-4-en-3-one, myrtillin, sanggenol O, lanosterol, erycristagallin, alpha-spinasterol, cyanidin 3-arabinoside, dan cathasterone. Sepuluh senyawa terbaik hasil penapisan virtual menggunakan AutoDock Vina memiliki rentang DG: -12.1 -10.7 kkal/mol adalah sanggenol O, cucumerin A, yuehchukene, palmarumycin CP1, dehydrocycloguanandin, myrtilin, liriodenine, myricetin 3-alpha-L-Arabinopyranoside, myricetin 3-galactoside, dan cassameridine.

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ABSTRACTHepatitis B is a disease caused by hepatitis B virus. One of the main factor in virus assembly is core protein Cp . Therefore Cp is suitable to use as one of therapeutic target for hepatitis B. In this study virtual screening of Indonesia herbal database as CpAM of hepatitis B virus was performed using AutoDock and AutoDock Vina software. The methode was validated by Enrichment Factor EF , Receiver Operating Characteristics ROC , and Area Under Curve AUC parameters. The grid box size used in virtual screening with AutoDock is 55x55x55 with EF10 0.7652 and AUC 0.6709 meanwhile grid box size that will be use in virtual screening using AutoDock Vina is 20.625x20.625x20.625 with EF5 0.5075 and AUC 0.7832. The best top ten compounds from virtual screening with AutoDock has DG levels 11.74 10.31 kkal mol theare yuehchukene, lansionic acid, stigmast 4 en 3 one, myrtillin, sanggenol O, lanosterol, erycristagallin, alpha spinasterol, cyanidin 3 arabinoside, dan cathasterone. The best top ten compounds from virtual screening with AutoDock Vina has DG levels 12.1 10.7 kkal mol adalah sanggenol O, cucumerin A, yuehchukene, palmarumycin CP1, dehydrocycloguanandin, myrtilin, liriodenine, myricetin 3 alpha L Arabinopyranoside, myricetin 3 galactoside, dan cassameridine"

"Latar Belakang : Karsinoma Sel Hati (KSH) merupakan kanker dengan prognosis yang buruk dan Indonesia termasuk negara dengan prevalensi hepatitis B yang tinggi. Performa alfa fetoprotein (AFP) sebagai penanda tumor pada surveilans KSH terutama dipengaruhi oleh etiologi penyakit hati yang mendasari. Titik potong AFP untuk surveilans KSH di Indonesia tidak berdasarkan etiologi penyakit hati yang mendasari.Tujuan : Mengetahui titik potong terbaik pemeriksaan biomarker AFP untuk surveilans KSH dengan etiologi hepatitis B kronik.Metode : Penelitian mengambil data rekam medis Divisi Hepatobilier RSUPN Dr. Cipto Mangunkusumo periode tahun 2017-2023. Sebanyak 506 subjek hepatitis B kronik semua spekturm (hepatitis B tanpa sirosis, sirosis hati, dan KSH stadium awal BCLC 0 dan A) diambil secara total sampling dalam kurun waktu 26 Juli 2023 hingga 31 Agustus 2023. Penentuan nilai titik potong AFP dilakukan dengan metode receiver operating characteristics (ROC).Hasil : Untuk surveilans KSH dengan etiologi hepatitis B, analisis kurva ROC memberikan area under the curve (AUC) didapatkan 0.792 (IK 95%, 0.719-0.866), dan titik potong dengan index Youden tertinggi adalah 8.7 ng/ml, dengan nilai sensitivitas 58%, spesifisitas 94%, nilai duga positif (NDP) 56.14%, nilai duga negatif (NDN) 94.43%. Analisis kurva ROC dilanjutkan berdasarkan status sirosis pasien. Untuk menentukan titik potong yang membedakan KSH dengan sirosis hati dari sirosis hati saja, menghasilkan AUC 0.803 (IK 95%, 0.722-0.884) dengan titik potong yang didapatkan adalah 8.6 ng/ml, dengan sensitivitas, spesifisitas, NDP, NDN, dan RK + adalah 60.5%, 92.4%, 45,10%, 95,24%, dan 7,09 masing-masing. Untuk menentukan titik potong yang membedakan KSH tanpa sirosis hati dari hepatitis B kronik tanpa sirosis hati, menghasilkan AUC 0.777 (IK 95%, 0.631-0.923) dengan titik potong yang didapatkan adalah 6.6 ng/ml yang memberikan hasil sensitivitas, spesifisitas, NDP, NDN, dan RK positif adalah 63.16%, 98.35%, 85.71%, 94.44%, dan 38.21 masing-masing.Kesimpulan : Titik potong surveilans KSH dengan etiologi spesifik hepatitis B lebih rendah dibandingkan dengan nilai titik potong AFP surveilans KSH sebelumnya yang tidak spesifik etiologi. Nilai titik potong 8.7 ng/ml menghasilkan sensitivitas dan spesifisitas terbaik untuk titik potong surveilans KSH dengan etiologi hepatitis B. Pada pasien KSH non sirosis, titik potong surveilans AFP lebih rendah yakni 6.6 ng/ml. Hal ini perlu menjadi perhatian klinisi dalam surveilans kelompok pasien hepatitis B kronik tanpa sirosis.

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Background: Hepatocellular carcinoma (HCC) is a cancer with a poor prognosis. Indonesia is a country with a high prevalence of chronic hepatitis B infection. The performance of alpha fetoprotein (AFP) as a tumor marker in HCC surveillance is primarily influenced by the etiology of the underlying liver disease. The AFP cutoff value for HCC surveillance in Indonesia is not based on the etiology of the underlying liver disease.

Objective: To determine the best cut-off value of AFP biomarker examination for HCC surveillance in chronic hepatitis B patients.

Methods: The study took medical record data from the Hepatobiliary Division of RSUPN Dr. Cipto Mangunkusumo for the 2017-2023 period. A total of 506 chronic hepatitis B subjects of all spectrums (hepatitis B without cirrhosis, liver cirrhosis, and early stage HCC, BCLC 0 and A) were taken by total sampling in the period 26 July 2023 to 31 August 2023. Determination of the AFP cut-off value was carried out using the receiver operating characteristics (ROC) method.

Results: For HCC surveillance caused by hepatitis B virus, ROC curve analysis gave an area under the curve (AUC) of 0.792 (95% CI, 0.719-0.866), and the cut-off value with the highest Youden index was 8.7 ng/ml, with a sensitivity value of 58%, specificity 94%, positive predictive value (PPV) 56.14%, negative predictive value (NPV) 94.43%. ROC curve analysis was then performed based on the patient's cirrhosis status. ROC curve analysis to determine the cut-off point that distinguishes HCC with liver cirrhosis from liver cirrhosis alone, resulted in an AUC of 0.803 (95% IK, 0.722-0.884) with a cut-off point 8.6 ng/ml, with sensitivity, specificity, PPV, NPV, and LR+ of 60.5%, 92.4%, 45.10%, 95.24%, and 7.09 respectively. ROC curve analysis to determine the cut-off point that distinguishes HCC without liver cirrhosis from chronic hepatitis B without liver cirrhosis resulted in an AUC of 0.777 (95% CI, 0.631-0.923) with a cut-off point 6.6 ng/ml which gave sensitivity, specificity, PPV, NPV, and LR positive results of 63.16%, 98.35%, 85.71%, 94.44%, and 38.21 respectively.

Conclusion: The cut-off value of AFP in HCC surveillance on hepatitis B specific etiology is lower than the cut-off value of AFP in previous HCC surveillance which was not etiology specific. The cut-off value of 8.7 ng/ml produces the best sensitivity and specificity for the cut-off value for HCC surveillance with hepatitis B etiology. In non- cirrhotic HCC patients, the AFP surveillance cut-off point is lower than cirrhotic HCC patients (6.6 ng/ml). This needs to be of concern to clinicians in surveillance of groups of chronic hepatitis B patients without cirrhosis."

"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)"

"[ABSTRAKStudi cross sectional pada pasien hepatitis B di Indonesia menunjukkan korelasi mutasi kodon start pre-S2 dengan keparahan penyakit hati. Peran protein-protein HBs pada aktivasi NF-ĸB sebagai salah satu faktor dalam induksi keparahan penyakit hati. Studi ini dilakukan untuk melihat efek varian mutan HBs virus hepatitis B subgenotipe B3 sebagai strain endemik di Indonesia pada keparahan penyakit hati dilihat dari ekspresi dan aktivasi NF-ĸB. Gen HBs dari tiga pasien yang membawa tiga varian HBs berbeda diamplifikasi dan diklon dengan plasmid pcDNA3.1, ditransfeksikan dengan metode lipofektamin ke dalam sel Huh7. Nilai ekspresi mRNA dianalisis dengan real-time PCR terhadap mRNA HBs, IĸB-α, dan NF-ĸB (p50). Ekspresi IĸB-α yang diregulasi oleh NF-ĸB digunakan sebagai parameter untuk aktivasi NF-ĸB. Diperoleh plasmid ekspresi HBs dengan mutasi kodon start pre-S2, delesi pre-S2 dan wild type VHB subgenotipe B3. Plasmid rekombinan pcDNA HBs dapat mengekspresikan mRNA HBs dan menurun pada 48 hingga 72 jam. Kecuali pada mutan delesi pre-S2 yang stabil hingga 72 jam. Ekspresi protein HBs berdasar ELISA menunjukkan nilai relatif konstan pada HBs wild type, sedangkan pada HBs mutan kodon start dan delesi meningkat pada 72 jam. Aktivasi NF-ĸB relatif lebih tinggi oleh tipe wild type dibanding mutan kodon start pre-S2 dan delesi pre-S2, sehingga variasi mutasi tidak memberikan pengaruh pada aktivasi NF-ĸB, meski varian mutan delesi pre-S2 menunjukkan peningkatan aktivasi NF-ĸB setelah waktu kultur yang lebih lama dibanding HBs wild type dan mutan kodon start pre-S2. Ekspresi NF-ĸB (p50) dipengaruhi oleh variasi mutasi, ekspresi p50 lebih tinggi pada mutan kodon start pre-S2 dibanding varian HBs lainnya. Keparahan penyakit hati oleh mutasi kodon start pre-S2 dapat terkait dengan peningkatan ekspresi p50.

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ABSTRACTCross sectional study on hepatitis B patients in Indonesia showed association of pre-S2 start codon mutation with severity liver disease. Role of HBs proteins on the activation of NF-ĸB as one of the factor in liver disease progression. This study was to see the effects of different HBs mutant variants of Hepatitis B Virus (HBV) subgenotype B3 as the endemic strain in Indonesia on the expression and activation of NF-ĸB. HBs genes of three hepatitis B patients were amplified and cloned to pcDNA3.1, and were transfected using lipofectamine into Huh7 cell line. Expressions on mRNA level for HBs, IĸB-α and NF-ĸB (p50) were evaluated using real-time PCR. IĸB-α expression which is regulated by NF-ĸB was used as parameter to measure NF-ĸB activation. Recombinant plasmid for HBs expression with pre-S2 start codon mutation, pre-S2 deletion and wild type of HBV subgenotipe B3 were obtained. All three clones showed high level of mRNA expression which decreased after 48 to 72 hours, except for pre-S2 deletion which was relatively stabil up to72 hours. HBs protein expression detected using ELISA was constant for HBs wild type whilst increased at 72 hours for pre-S2 start codon mutation and pre-S2 deletion. NF-ĸB activation was higher for HBs wild type compared to the two mutant variants, suggesting no effect of mutation to increment of NF-ĸB activation, however pre-S2 deletion mutant showed higher NF-ĸB activation after longer period of incubation. NF-ĸB (p50) expression was higher for pre-S2 start codon mutation, suggesting liver disease progression by pre-S2 start codon mutation might associated to increased expression of p50.;Cross sectional study on hepatitis B patients in Indonesia showed association of pre-S2 start codon mutation with severity liver disease. Role of HBs proteins on the activation of NF-ĸB as one of the factor in liver disease progression. This study was to see the effects of different HBs mutant variants of Hepatitis B Virus (HBV) subgenotype B3 as the endemic strain in Indonesia on the expression and activation of NF-ĸB. HBs genes of three hepatitis B patients were amplified and cloned to pcDNA3.1, and were transfected using lipofectamine into Huh7 cell line. Expressions on mRNA level for HBs, IĸB-α and NF-ĸB (p50) were evaluated using real-time PCR. IĸB-α expression which is regulated by NF-ĸB was used as parameter to measure NF-ĸB activation. Recombinant plasmid for HBs expression with pre-S2 start codon mutation, pre-S2 deletion and wild type of HBV subgenotipe B3 were obtained. All three clones showed high level of mRNA expression which decreased after 48 to 72 hours, except for pre-S2 deletion which was relatively stabil up to72 hours. HBs protein expression detected using ELISA was constant for HBs wild type whilst increased at 72 hours for pre-S2 start codon mutation and pre-S2 deletion. NF-ĸB activation was higher for HBs wild type compared to the two mutant variants, suggesting no effect of mutation to increment of NF-ĸB activation, however pre-S2 deletion mutant showed higher NF-ĸB activation after longer period of incubation. NF-ĸB (p50) expression was higher for pre-S2 start codon mutation, suggesting liver disease progression by pre-S2 start codon mutation might associated to increased expression of p50.;Cross sectional study on hepatitis B patients in Indonesia showed association of pre-S2 start codon mutation with severity liver disease. Role of HBs proteins on the activation of NF-ĸB as one of the factor in liver disease progression. This study was to see the effects of different HBs mutant variants of Hepatitis B Virus (HBV) subgenotype B3 as the endemic strain in Indonesia on the expression and activation of NF-ĸB. HBs genes of three hepatitis B patients were amplified and cloned to pcDNA3.1, and were transfected using lipofectamine into Huh7 cell line. Expressions on mRNA level for HBs, IĸB-α and NF-ĸB (p50) were evaluated using real-time PCR. IĸB-α expression which is regulated by NF-ĸB was used as parameter to measure NF-ĸB activation. Recombinant plasmid for HBs expression with pre-S2 start codon mutation, pre-S2 deletion and wild type of HBV subgenotipe B3 were obtained. All three clones showed high level of mRNA expression which decreased after 48 to 72 hours, except for pre-S2 deletion which was relatively stabil up to72 hours. HBs protein expression detected using ELISA was constant for HBs wild type whilst increased at 72 hours for pre-S2 start codon mutation and pre-S2 deletion. NF-ĸB activation was higher for HBs wild type compared to the two mutant variants, suggesting no effect of mutation to increment of NF-ĸB activation, however pre-S2 deletion mutant showed higher NF-ĸB activation after longer period of incubation. NF-ĸB (p50) expression was higher for pre-S2 start codon mutation, suggesting liver disease progression by pre-S2 start codon mutation might associated to increased expression of p50., Cross sectional study on hepatitis B patients in Indonesia showed association of pre-S2 start codon mutation with severity liver disease. Role of HBs proteins on the activation of NF-ĸB as one of the factor in liver disease progression. This study was to see the effects of different HBs mutant variants of Hepatitis B Virus (HBV) subgenotype B3 as the endemic strain in Indonesia on the expression and activation of NF-ĸB. HBs genes of three hepatitis B patients were amplified and cloned to pcDNA3.1, and were transfected using lipofectamine into Huh7 cell line. Expressions on mRNA level for HBs, IĸB-α and NF-ĸB (p50) were evaluated using real-time PCR. IĸB-α expression which is regulated by NF-ĸB was used as parameter to measure NF-ĸB activation. Recombinant plasmid for HBs expression with pre-S2 start codon mutation, pre-S2 deletion and wild type of HBV subgenotipe B3 were obtained. All three clones showed high level of mRNA expression which decreased after 48 to 72 hours, except for pre-S2 deletion which was relatively stabil up to72 hours. HBs protein expression detected using ELISA was constant for HBs wild type whilst increased at 72 hours for pre-S2 start codon mutation and pre-S2 deletion. NF-ĸB activation was higher for HBs wild type compared to the two mutant variants, suggesting no effect of mutation to increment of NF-ĸB activation, however pre-S2 deletion mutant showed higher NF-ĸB activation after longer period of incubation. NF-ĸB (p50) expression was higher for pre-S2 start codon mutation, suggesting liver disease progression by pre-S2 start codon mutation might associated to increased expression of p50.]"

"Latar belakang: Insidensi dan faktor risiko karsinoma hepatoseluler (KSH) pada pasien hepatitis C virus (HCV) yang sudah mencapai sustained virological response (SVR) pasca terapi direct acting antiviral (DAA) belum banyak diketahui. Mengingat terdapat perbedaan jenis DAA, genotype virus, dan profil pasien di Indonesia, dilakukan studi untuk menilai insidensi dan faktor-faktor yang memengaruhi KSH pada pasien HCV pasca SVR post terapi DAA.Tujuan: Mengetahui insidensi dan faktor-faktor yang memengaruhi kejadian KSH pada pasien HCV yang mencapai SVR pasca pengobatan DAA.Metode: Desain penelitian kohort retrospektif di RSUPN Cipto Mangunkusumo, sampel pasien HCV yang SVR pasca DAA tahun 2017 – 2019, diikuti hingga 2024. Pasien dilakukan skrining USG abdomen, alpha-fetoprotein (AFP) dan CT Scan abdomen 3 fase apabila terdapat indikasi. Dilakukan analisis deskriptif, bivariat dengan Fisher’s exact, dan multivariat dengan regresi logistik bila terdapat faktor risiko di analisis bivariat (p <0,25).Hasil: Dari 180 subjek penelitian, insidensi dan rasio insidensi KSH pada seluruh populasi mencapai 4,4% (rasio insidens 0,91/100PY). Terdapat hubungan signifikan dari analisis bivariat variabel sirosis hepatis (RR 10,5; IK 95% (1,32 – 83,5); p =0,0073) dan DM tipe 2 (RR 8,47; IK 95% (2,3 – 31,1) p = 0,0048). Terdapat hubungan signifikan dari analisis multivariat variabel DM tipe 2 (aRR 3,1; IK 95% (0,86 – 3,83); p=0,002).Kesimpulan: Insidensi KSH mencapai 4,4% dari total populasi. DM tipe 2 memiliki hubungan yang signifikan terhadap kejadian KSH pada pasien HCV yang mencapai SVR pasca pengobatan DAA.

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Background: The incidence and risk factors for hepatocellular carcinoma (HCC) in hepatitis C (HCV) patients who have achieved sustained virological response (SVR) after direct-acting antiviral (DAA) therapy are not well established. Considering there are differences in DAA types, virus genotypes, and patient profiles in Indonesia, this study was conducted to assess the incidence and factors influencing HCC in HCV patients after SVR post DAA therapy.

Objective: To determine the incidence and factors influencing HCC in HCV patients achieving SVR after DAA treatment.

Method: Retrospective cohort study conducted at Cipto Mangunkusumo National General Hospital, sample of HCV patients had SVR after DAA therapy in 2017 – 2019, followed until 2024. Patients were screened for abdominal ultrasound, alpha-fetoprotein (AFP) and 3-phase abdominal CT scan, if indicated. Descriptive, bivariate analysis with Fisher's exact, and multivariate analysis with logistic regression were conducted.

Results: Among 180 subjects, the incidence and incidence ratio of HCC is 4.4% (0.91/100PY). Significant correlation in bivariate analysis from the variables liver cirrhosis (RR 10.5; CI 95% (1. 32 – 83.5); p = 0.0073) and type 2 DM (RR 8.47; CI 95% (2, 3 – 31.1) p = 0.0048). In multivariate analysis, there was significant correlation from type 2 DM variable (aRR 3.1; CI 95% (0.86 – 3.83); p=0.002).

Conclusion: The incidence of HCC reaches 4.4% of the total population. Type 2 DM has significant correlation with the incidence of HCC in HCV patients who achieve SVR after DAA treatment."