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"Background: HIV infection in HCV-infected patients accelerates disease progression and reduces the success rate of Peg-IFN/RBV treatment. HCV mutation in NS5A-ISDR/PKR-BD region improved the outcome in HCV monoinfection treated with Peg-IFN/RBV. SNP-IL28B polymorphism is predicted to have an effect on HCV quasispecies evolution. However, the role of NS5A mutation and SNP IL-28B in HIV-HCV coinfection is still unclear. The aim of the study is to determine the role of HCV NS5A-ISDR/PKR-BD mutation and SNP IL-28 polymorphism on the successfulness of Peg-IFN/RBV therapy in HCV-HIV coinfection.Methods: prospective cohort was performed in this study. Plasma sample were obtained from 30 and 8 patients with HCV-HIV coinfection and HCV monoinfection, respectively. PCR nucleotide sequencing was performed after RNA virus extraction and cDNA synthesis. Protein secondary structure and prediction of mutation function were analyzed using PredictProtein (PP) program.Results: sixteen HCV-HIV coinfected patients and none from eight HCV patients achieved sustained virological response (SVR). ≥1 non-neutral mutation was found in 24/30 HCV-HIV coinfection and more frequent in SVR group (14 patients). ≥1 non-neutral mutation were found statistically significant for overall SVR achievement (p<0.05) in all patients regardless of coinfection or monoinfection status. Of the 27 HCV-HIV coinfected patients with CC-gene, 21 subjects had non-neutral mutation. The structure which was expected as NS5A binding site structure was different from consensus (wild type) in SVR group, while the structure was similar to consensus in non-SVR group.Conclusion: having ≥1 non-neutral mutation was associated with SVR achievement in Peg-IFN/RBV therapy, regardless of monoinfection and coinfection status."

"HIV coinfection in HCV-infected patients accelerates the course of disease and affects the outcome of Peg-IFN/RBV combination treatment. HCV-HIV coinfected patients are suspected to have HCV mutation in NS5A-ISDR/PKR-BD region that had a role to the successfulness of Peg-IFN/RBV therapy. SNP IL-28B polymorphism is predicted to have an effect on the HCV quasi-species evolution. However, until now the effect of HCV NS5A mutation and SNP IL-28B of the host to the response of treatment is still unclear.This study aimed to determine the presence and role of HCV NS5A-ISDR/PKR-BD region mutation and host SNP IL-28B on the succes of Peg-IFN/RBV combination treatment in HCV-HIV coinfected patients.Prospective cohort study design was conducted in this study. Plasma sample was collected from 22 monoinfected and 134 HCV-HIV coinfected patients prior to therapy. All of them were treated with Peg-IFN/RBV for 48 weeks. The examination of HCV RNA was performed 24 weeks after the end of therapy. PCR nucleotide sequencing was performed after the RNA virus extraction and cDNA synthesis had been performed. Analysis of secondary structure and prediction of mutation function were assessed by PredictProtein (PP) program.Sixteen from thirthy HCV-HIV co-infection patients and none from eight HCV patients achieved SVR. Nonneutral mutation ≥ 1 was found in 23/30 subjects with HCV-HIV co-infection. The presence of nonneutral mutation ≥ 1 was observed more frequent in SVR group than non-SVR group. Nonneutral mutation ≥ 1 was associated with SVR achievement, regardless the monoinfection or coinfection status (p = 0.04). Interaction of CC gene and nonneutral mutation was not associated with SVR. Secondary structure transformation of VHC NS5A was not associated with SVR in coinfected subjects. NS5A binding site structure was different from consensus in SVR group, while the structure was similar to consensus in non-SVR group.Nonneutral mutation ≥ 1 has the most important role on the SVR achievement in patients treated with Peg-IFN/RBV. The interaction of CC-gene and nonneutral mutation was not associated with SVR. The change of secondary structure was also not associated with SVR achievement, however, the changes of NS5A binding site structure were found in HCV-HIV coinfected patients who achieved SVR.

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Koinfeksi HIV pada pasien dengan infeksi VHC dapat memperberat perjalanan penyakit dan memengaruhi keberhasilan terapi kombinasi Peg-IFN/RBV. Pasien koinfeksi VHC-HIV diduga mengalami mutasi VHC pada regio NS5A-ISDR/PKR-BD yang mempunyai peran terhadap keberhasilan terapi Peg-IFN/RBV. Polimorfisme SNP IL-28B diprediksi berpengaruh terhadap evolusi quasi-spesies VHC, namun hingga saat ini keberadaan dan peran mutasi VHC NS5A serta SNP IL-28B pejamu pada koinfeksi VHC-HIV terhadap keberhasilan terapi masih belum diketahui secara jelas.Penelitian ini bertujuan untuk mengetahui keberadaan dan peran mutasi VHC NS5A-ISDR/PKR-BD serta SNP IL-28B pejamu terhadap keberhasilan terapi dengan kombinasi Peg-IFN/RBV pada pasien koinfeksi VHC-HIV.Penelitian ini menggunakan desain studi kohort prospektif. Sampel plasma dikumpulkan dari 22 subjek monoinfeksi dan 134 subjek koinfeksi sebelum menjalani terapi. Seluruh pasien mendapatkan terapi Peg-IFN/RBV selama 48 minggu. Pemeriksaan VHC RNA setelah 24 minggu dari akhir terapi dilakukan untuk menilai respons terapi (sustained virological response/SVR 24). Sekuensing nukleotida menggunakan PCR dilakukan setelah ekstraksi RNA virus dan sintesis cDNA dari sampel plasma. Analisis struktur sekunder dan prediksi fungsi mutasi menggunakan program PredictProtein (PP).Sebanyak 16 pasien dari 30 pasien koinfeksi VHC-HIV yang mengalami SVR serta tidak ada dari 8 pasien monoinfeksi VHC yang mengalami SVR. Mutasi nonnetral ≥ 1 ditemukan pada 23/30 pasien koinfeksi VHC-HIV. Keberadaan mutasi nonnetral ≥ 1 didapatkan lebih tinggi pada kelompok SVR (14 pasien) dibandingkan dengan non-SVR (9 pasien). Mutasi nonnetral ≥1 berhubungan dengan kejadian SVR, tanpa memandang status monoinfeksi dan koinfeksi (p = 0,04). Interaksi antara gen CC dan mutasi nonnetral tidak berhubungan dengan SVR. Perubahan struktur sekunder NS5A tidak berhubungan dengan SVR pada pasien koinfeksi. Struktur binding site NS5A pada kelompok SVR didapatkan berbeda dengan konsensus, sedangkan pada kelompok non-SVR mirip dengan konsensus.Mutasi nonnetral ≥ 1 berperan terhadap kejadian SVR pada pasien yang mendapat terapi Peg-IFN/RBV. Interaksi mutasi nonnetral dan gen CC tidak berhubungan dengan pencapaian SVR. Perubahan struktur sekunder juga tidak berhubungan dengan pencapaian SVR, akan tetapi perubahan struktur binding site NS5A-ISDR/PKR-BD ditemukan pada pasien koinfeksi VHC-HIV yang mencapai SVR dengan terapi Peg-IFN/RBV."

"Antiretroviral therapy (ART) given to HIV patients to improve their immune response that damaged by HIV infection. Some patients with ART experience Immune Restoration Disease (IRD) as worsening of clinical symptoms from certain pathogens infection. The incidence of IRD concided with an increased number of CD4+ T cells. Hepatitis C virus can also infect HIV patients and may also lead to HCV IRD. The immunopathogenecity of IRD has not known yet. This study aims to look at the function of dendritic cells producing IL-12 and IFNα, and IFNγ-producing T cell responses in incidence of HCV IRD. Research subjects were 50 patients with HIV/HCV who were initiating antiretroviral therapy (ART) for up to 6 months of therapy. There are 9 people with HCV IRD who compared with non HCV IRD patients. Blood specimens were collected from study subjects at months 0, 1, 3 and 6 after ART. Then PBMC isolation was done and used for flowsitometri and ELISpot analysis.The results showed that the percentage of myeloid (mDC) and plasmacytoid dendritic cells (pDC) did not differ between HCV IRD patients and non-HCV IRD patients. It appears that the percentage of IL-12-producing mDC did not correlate significantly with IFNγ- producing T cells both in HCV IRD and non-IRD HCV patients. The percentage of IL-12-producing mDC in HCV IRD patients were lower than in non-IRD patients (p=0.003). While percentage of IFNα-producing pDC and IFNγ- producing T cells did not differ significantly between the two groups of patients. Antibody response to HCV proteins (core, NS3, NS4, and NS5) did not differ between HCV IRD and non-HCV IRD patients. The role of dendritic cells and T cell responses in HCV IRD incidence have not clearly seen.

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Terapi antiretroviral (ART) diberikan kepada pasien HIV akan memperbaiki respon imun tubuh yang rusak karena infeksi HIV. Beberapa pasien dengan ART mengalami sindrom pulih imun atau Immune Restoration Disease (IRD) berupa perburukan gejala klinis dari infeksi patogen tertentu. Kejadian sindrom pulih imun ini terjadi bersamaan dengan peningkatan jumlah sel T CD4+. Virus Hepatitis C yang menjadi patogen penyerta pada pasien HIV juga menjadi penyebab sindrom pulih imun. Belum diketahui dengan jelas imunopatogenesitas dari sindrom pulih imun ini. Penelitian ini bertujuan untuk melihat fungsi sel dendritik penghasil IL-12 dan IFNα, serta respon sel T penghasil IFNγ pada kejadian sindrom pulih imun HCV. Subyek penelitian adalah 50 pasien HIV/HCV yang sedang memulai terapi antiretroviral (ART). Terdapat 9 orang pasien dengan sindrom pulih imun HCV yang dibandingkan dengan pasien tanpa sindrom pulih imun HCV. Spesimen darah lengkap dikumpulkan dari subyek penelitian pada bulan ke-0, 1, 3 dan 6 setelah ART. Kemudian dilakukan isolasi PBMC dan analisis flowsitometri dan ELISpot.Hasil penelitian menunjukkan bahwa persentase sel dendritik mieloid (mDC) dan plasmasitoid (pDC) tidak berbeda antara pasien dengan dan tanpa sindrom pulih imun HCV. Persentase sel mDC penghasil IL-12 tidak berkorelasi secara signifikan dengan jumlah sel T penghasil IFNγ baik pada pasien dengan maupun tanpa sindrom pulih imun HCV. Pasien dengan sindrom pulih imun HCV memiliki persentase sel mDC penghasil IL-12 yang lebih rendah dibandingkan pasien tanpa sindrom pulih imun HCV (p=0,003). Sedangkan persentase sel pDC penghasil IFNα dan jumlah sel T penghasil IFNγ tidak berbeda secara signifikan antara kedua kelompok pasien. Respon antibodi terhadap protein HCV (core, NS3, NS4 dan NS5) pun tidak berbeda antara kedua kelompok pasien. Disimpulkan bahwa belum terlihat adanya peran dari sel dendritik dan respon sel T terhadap kejadian sindrom pulih imun HCV."

"[LatarBelakang: Sekitar 3% populasi di dunia terinfeksi virus hepatitis C. Protein virus hepatitis C memodulasi apoptosis dan steatosis, cedera sel hati, mengaktifkan sel stelata hati dan fibrosis hati. Infeksi virus hepatitis C akan menimbulkan cedera pada hepatosit. Cedera pada hepatosit ini akan mengaktivasi sel stelata hati. Sel stelata berperan besar pada proses perkembangan fibrosis hati..Tujuan: Untuk mengetahui perbedaan jumlah sel stelata hati aktif CD38+ pada berbagai derajat fibrosis serta hubungnnya dengan AST, ALT, jumlah HCV RNA kuantitatif pada hepatitis C kronik.Metoda: Penelitian ini merupakan studi potong lintang yang dilakukan pada 32 pasien hepatitis C kronik yang sudah dilakukan USG hati dan tidak menderita hepatoma serta telah dilakukan biopsi hati. Paraffin block jaringan hati pasien selanjutnya diwarnai menggunakan teknik Hematoksilin Eosin untuk menilai derajat Metavir yang dikategorikan menjadi derajat ringan-sedang atau berat. Pewarnaan khusus dilakukan untuk menilai sel stelata hati yang dihitung rata-rata pada lima lapangan pandang.Hasil: Pada penelitian ini didapatkan perbedaan jumlah sel stelata hati CD38+ yang bermakna antara fibrosis derajat berat dan derajat ringan-sedang (p <0.001), tidak didapatkan hubungan antara sel stelata hati CD38+ dengan AST (p=0,2) maupun ALT (p =0,7), dan tidak didapatkan hubungan antara sel stelata hati CD38+ dengan HCV RNA kuantitatif (r = -0,372).Kesimpulan: Jumlah sel stelata hati CD38+ pada fibrosis berat lebih tinggi daripada jumlah sel stelata hati CD38+ pada fibrosis ringan-sedang. Tidak terdapat hubungan antara nilai AST, ALT dan HCV RNA kuantitatif dengan jumlah sel stelata hati CD38+.;Background: Approximately 3% of the population in the world are infected with hepatitis C. Hepatitis C virus proteins modulate apoptosis and steatosis, liver cell injury, activate liver stellate cells and liver fibrosis. Hepatitis C virus infection will injure to hepatocytes. Hepatocytes injury will activate the liver stellate cells. Stellate cells play a major role in the development of liver fibrosis.Aim: Knowing the CD38+ active hepatic stellate cells count difference at various fibrosis stage and correlation with AST, ALT, quantitative HCV RNA in chronic hepatitis C patientsMethod: Cross-sectional method. 32 paraffin block sample from liver tissue patient with chronic hepatitis C without hepatocellular carcinoma who have performed an abdomen ultrasound and liver biopsy, assess the Metavir score were categorized into mild or severe degree. Samples were stained for liver stellate cells by specific staining and the average of stellate cells were calculated in 10 flat field of view.Result: In this study, the liver stellate cells count CD38+ were significantly correlate with the degree of fibrosis (p <0.001), there were no relationship between liver stellate cells CD38+ with AST levels (p = 0,2) and ALT levels (p = 0,7), and there was no relationship between liver stellate cells CD38+ with quantitative HCV RNA levels (r = -0.372).Conclution: Stellate cells count CD38+ are increasing along with the fibrosis degree. There were no relationship between level of AST, ALT and quantitative HCV RNA with the stellate cells count CD38+., Background: Approximately 3% of the population in the world are infected with hepatitis C. Hepatitis C virus proteins modulate apoptosis and steatosis, liver cell injury, activate liver stellate cells and liver fibrosis. Hepatitis C virus infection will injure to hepatocytes. Hepatocytes injury will activate the liver stellate cells. Stellate cells play a major role in the development of liver fibrosis.Aim: Knowing the CD38+ active hepatic stellate cells count difference at various fibrosis stage and correlation with AST, ALT, quantitative HCV RNA in chronic hepatitis C patientsMethod: Cross-sectional method. 32 paraffin block sample from liver tissue patient with chronic hepatitis C without hepatocellular carcinoma who have performed an abdomen ultrasound and liver biopsy, assess the Metavir score were categorized into mild or severe degree. Samples were stained for liver stellate cells by specific staining and the average of stellate cells were calculated in 10 flat field of view.Result: In this study, the liver stellate cells count CD38+ were significantly correlate with the degree of fibrosis (p <0.001), there were no relationship between liver stellate cells CD38+ with AST levels (p = 0,2) and ALT levels (p = 0,7), and there was no relationship between liver stellate cells CD38+ with quantitative HCV RNA levels (r = -0.372).Conclution: Stellate cells count CD38+ are increasing along with the fibrosis degree. There were no relationship between level of AST, ALT and quantitative HCV RNA with the stellate cells count CD38+.]"

"The first observation of cold-induced precipitation of serum proteins dates back to 1933, when Wintrobe and Buell first described an unusual case of multiple myeloma in a woman whose serum reversibly precipitated at cold temperatures. In 1947 Lerner and Watson showed cold-precipitable proteins to be gammaglobulins and called them ‘cryoglobulins’ and the corresponding clinical condition ‘cryoglobulinemia’. Meltzer and Franklin in 1966 provided an accurate description of the typical clinical symptoms associated with cryoglobulinemia, showed that they consisted of two different globulin components and, because of the ignorance on its etiology, called this clinical condition ‘essential mixed cryoglobulinemia’. For almost 20 years progress has been rather slow in this field, but when at the end of the ‘80s it finally became possible to detect the occurrence in the serum of antibodies to the hepatitis C virus (HCV), many groups in Europe and the United States almost simultaneously reported that a high proportion of ‘essential’ cryoglobulinemias are in fact associated with HCV infection. This hallmark has resulted in a new impetus and great enthusiasm in carrying out new researches made possible by the awareness that cryoglobulinemia is to be considered an undisputable extrahepatic manifestation of HCV infection. In addition, the evidence that HCV has tropism for hepatocytes and lymphocytes has stimulated new approaches to the autoimmune phenomena and the potential transformation in non-Hodgkin’s lymphomas which not infrequently can be discovered in these patients. The same applies to the obvious therapeutic implications, once the association between HCV infection and mixed cryoglobulinemia has been firmly established. It was thus felt that times were ripe to produce a state-of-the-art survey of the multi-faceted picture of cryoglobulinemia. This book is indeed unique in the detail of its presentation, its completeness and its fundamental approach to the subject. The most qualified authors have been invited to contribute critical articles reviewing significant developments related to each of the eight sections in which the whole treatment has been divided: from basic mechanisms governing interactions between HCV and the immune system to the immunochemical characterization of cryoglobulins and the frequently concomitant serological abnormalities; from genetic features and the role of certain cytokines and chemokines to the cellular compartments of HCV infection and replication; from the clinical manifestations of cryoglobulinemic patients and their potential susceptibility to develop non-Hodgkin’s lymphoma to conventional treatment of the syndrome and the newer, promising therapeutic advances. The reader will appreciate the immediacy of style, the striking illustrations, and the color plates. In addition, the comprehensive review of a systemic disease such as cryoglobulinemia will interest basic scientists and specialists involved in several disciplines, including internal medicine, hepatology, hematology, oncology, infectious diseases, rheumatology, nephrology and dermatology. General practitioners, graduate and post-graduate students will also find in this book an irreplaceable source of update in this fascinating field."

"ABSTRAKDemam chikungunya adalah penyakit yang disebabkan oleh virus chikungunya (CHIKV) yang dapat menginfeksi manusia melalui gigitan nyamuk. CHIKV ditularkan melalui nyamuk Aedes aegypti dan Aedes albopictus. CHIKV juga merupakan penyakit arbovirus yang penting karena morbiditas yang tinggi. Kejadian Luar Biasa (KLB) infeksi CHIKV pertama kali dilaporkan pada tahun 1973 di Kalimantan Timur dan DKI Jakarta. Dengan besarnya frekuensi KLB dan tingginya prevalensi infeksi CHIKV di Indonesia maka diperlukan studi genotipe CHIKV. Faktor virus seperti variasi genotipe diyakini berperan dalam menentukan derajat keparahan penyakit. Pada penelitian ini menggunakan sampel yang tersimpan di Badan Litbangkes Jakarta sebagai Pusat Rujukan pemeriksaan infeksi CHIKV. Variasi genetik CHIKV dari 19 sampel dari 8 Propinsi di Indonesia tahun 2012?2014 dikerjakan dengan melakukan amplifikasi dan sekuensing gen E1 dan Capsid. Analisis filogenetik menunjukkan bahwa semua sampel pada penelitian adalah genotipe Asian. Homologi nukleotida dan asam amino gen E1 ditemukan berkisar 97,8%-100% dan 95,6%-100% untuk asam aminonya. Analisis epitop sel B dan sel T pada gen capsid memperlihatkan tidak adanya perbedaan antara CH12_069 dengan genotipe CHIKV di dunia. Epitop sel B di gen E1 ada beberapa perbedaan antara CH12_069 dengan genotipe Asian yaitu K196R dan L203I, sedangkan epitop sel T pada gen E1 tidak ditemukan perubahan asam amino.

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ABSTRACT

Chikungunya fever is a disease caused by the chikungunya virus (CHIKV) that can infect humans through mosquito bites. CHIKV is transmitted by Aedes aegypti and Aedes albopictus mosquitos. CHIKV is also an important arbovirus disease because of the high morbidity. The outbreaks of CHIKV infection was first reported in 1973 in East Kalimantan and Jakarta. With the magnitude of the frequency of outbreaks and the high prevalence of CHIKV infection in Indonesia, CHIKV genotype study is needed. Viral factor such as genotype variation is suggested play a role in determining the degree of severity of the disease. In this study, we used the stored samples in National Institute of Health Research and Development Jakarta as a Reference Laboratory Center of CHIKV infection. Genetic variation CHIKV of 19 samples from 8 provinces in Indonesia in 2012? 2014 done by performing amplification and sequencing of genes E1 and capsids. Phylogenetic analysis showed that all samples in this study were Asian genotype. E1 gene nucleotide homology was found ranging from 97.8%-100% and 95.6%- 100% for the amino acid. Analysis of B cell epitops and T cells epitop in the capsid gene showed no differences between CH12_069 with CHIKV genotype in the world. B cells epitops in E1 gene were showed no specific distinction between CH12_069 among CHIKV strains all over the world. B cell epitops in E1 gene there were some differences between CH12_069 with the Asian genotype such as K196R and L203I, whereas T cell epitops in E1 gene not found amino acid changes."