NASKAH LENGKAP Liver Update and The Scientific Meeting of …staff.ui.ac.id/system/files/users/rino.gani/publication/... · FKUI/RSCM Dr. Cipto Mangunkusumo Jakarta David Handojo

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TIM EDITOR :Rino Alvani Gani

Irsan HasanC. Rinaldi A. Lesmana

PERHIMPUNAN PENELITI HATI INDONESIA

NASKAH LENGKAP The 11th Liver Update and

The Scientific Meeting of INA ASL/PPHIIn Conjunction with

The 7th China-Indonesia Joint Symposium onHepatobiliary Medicine and Surgery (CISHMS)

2018

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cover bk Liver Update.indd 2 11/7/2018 10:16:10 AM

NASKAH LENGKAP

The 11th Liver Update and

The Scientific Meeting of INA ASL/PPHI

In Conjunction with

The 7th China-Indonesia Joint Symposium on

Hepatobiliary Medicine and Surgery (CISHMS)

2018

Theme:

Future Treatment in Hepatopancreatobiliary Diseases

EDITORRino Alvani Gani

Irsan HasanC. Rinaldi A. Lesmana

Perhimpunan Peneliti Hati Indonesia

Hotel Raffles Jakarta, July 5th-7th 2018

Proceeding Book

The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI

In Conjunction with

The 7th China-Indonesia Joint Symposium on Hepatobiliary Medicine and Surgery

(CISHMS) 2018

Theme: Future Treatment in Hepatopancreatobiliary Diseases

Susunan Panitia:Ketua Liver Update & CISHMS: Rino Alvani GaniBendahara: Andri SanityosoPublikasi: Indra Marki

Reviewer: Rino Alvani Gani

Tim Editor:Rino Alvani GaniIrsan HasanC. Rinaldi A. Lesmana

150 x 230 mm

ISBN 978-602-18991-9-9

Hak Cipta Dilindungi Undang-undang:Dilarang memperbanyak, mencetak dan menerbitkan sebagian atau seluruh isi buku ini dengan cara dan bentuk apapun tanpa seizin penulis dan penerbit

Diterbitkan oleh:Perhimpunan Peneliti Hati IndonesiaGedung Wisma Bhakti Mulya Lt. 6 Ruang 602Jl. Kramat Raya No. 160Jakarta 10430

Prohepa

Highlight

vThe 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Aida LydiaDivisi Ginjal Hipertensi Departemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

David Handojo MuljonoLembaga Biologi Molekuler EijkmanJakarta

Alex ThompsonDirector, Department of GastroenterologySt Vincent’s HospitalThe University of MelbourneSVHM, Victoria, Australia

Fauzi YusufDivisi Gastroentero-hepatologi Bag/SMF Ilmu Penyakit DalamFK UNSYIAH/RSU Dr. Zainoel AbidinAceh

Anthony TeohDeputy Director of EndoscopyDepartment of Surgery The Chinese University of Hong KongHong Kong

Henry LY ChanThe Chinese University of Hong Kong, Hong Kong

Andri SanityosoDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Hery Djagat PurnomoSubbag. Gastroentero-hepatologiBagian Ilmu Penyakit DalamFK UNDIP / RSUP Dr. KariadiSemarang

Chyntia Olivia Maurine JasirwanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Hui Ying RaoPeking University Hepatology InstitutePeking University People’s HospitalBeijing, China

Cleopas Martin RumendeDivisi Respirologi & Penyakit KritisDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Irsan HasanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

C. Rinaldi A. LesmanaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

I Dewa Nyoman WibawaDivisi Gastroentero-Hepatologi Bag/SMF Ilmu Penyakit DalamFK UNUD/RSUP SanglahDenpasar, Bali

KONTRIBUTOR

vi The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Ji Dong JiaDirector, Liver Research CenterBeijing Friendship HospitalCapital Medical UniversityBeijing, China

Li Ying SunVice Director, Department of Critical Care MedicineBeijing Friendship HospitalCapital Medical University, Beijing, China

Juferdy KurniawanDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Lim Seng GeeDivision of Gastroenterology and HepatologyUniversity Medicine ClusterNational University HospitalSingapore

Jun Qi NiuDirector, Department of HepatologyThe First Hospital of Jilin UniversityChangcun, China

Manoj Kumar SharmaInstitute of Liver and Biliary ScienceNew Delhi, India

Kemal Fariz KalistaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

Masashi MizokamiDirector, Genome Medical Sciences ProjectNational Center for Global Health and MedicineJapan

Lai WeiDirector of Peking University Hepatology InstituteChief Department of HepatologyPeking University People’s HospitalBeijing, China

Meta Dewi ThedjaLembaga Biologi Molekuler EijkmanJakarta

Laurentius A. LesmanaDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

M. Begawan BestariDivisi Gastroentero-hepatologi Departemen Ilmu Penyakit DalamFKU UNPAD/RSUP Dr. Hasan SadikinBandung

Lawrence Ho Khek YuDivision of Gastroenterology and HepatologyNational University Hospital Singapore

Poernomo Boedi SetiawanSubbag. Gastroentero-hepatologiBagian Ilmu Penyakit DalamFK UNAIR / RSUP Dr. SoetomoSurabaya

Lianda SiregarSMF Gastroentero-HepatologiRS Kanker DharmaisJakarta

Rino Alvani GaniDivisi HepatobilierDepartemen Ilmu Penyakit DalamFKUI/RSCM Dr. Cipto MangunkusumoJakarta

viiThe 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Sang Hoon AhnInstitute of GastroenterologyDepartment of Internal MedicineYonsei University College of MedicineSeoul, Korea

Stephen KY ChangMedical Director, GLAD ClinicMount Elizabeth HospitalSingapore

Shuichiro ShiinaDepartment of Gastroenterological Imaging and Interventional OncologyJuntendo UniversityJapan

Toar JM LalisangDepartemen Bedah Digestif FKUI/RSCM Dr. Cipto MangunkusumoJakarta

x The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Symposium 1

Non-Surgical Approach in Gallbladder Empyema with Biliary SepsisM. Begawan Bestari.......................................................................................................................... 38

Symposium 2

Evaluation of HCV RNA Viral Load with Using GenXpertChyntia Olivia Maurine Jasirwan, Andri Sanityoso Sulaiman, Irsan Hasan, Rino Alvani Gani, Cosmas Rinaldi A. Lesmana, Juferdy Kurniawan, Kemal Fariz Kalista, Saut Horas Nababan, Wahyu Purnama ......................................... 42

Performance Evaluation of Point-Of-Care Test X-Pert® HCV Viral Load: a Simple Step for Starting and Monitoring Hepatitis C Virus (HCV) Infection TreatmentMeta Dewi Thedja, Dhita Prabasari Wibowo, Turyadi, Susan Irawati Ie, Ignatia Sinta Murti, David Handojo Muljono......................................................................... 52

Symposium 3

High Mobility Group Box 1 (HMGB1) in Liver DiseaseDavid Handojo Muljono ................................................................................................................. 55

Hepatic Fibrosis: Concept to TreatmentC. Rinaldi A. Lesmana ...................................................................................................................... 57

Symposium 4

What is Needed to Fight Hepatitis C Virus in Indonesia?Irsan Hasan, Putra Nur Hidayat .................................................................................................. 61

The New Story in Curing Hepatitis C Virus: Focused on Clinical Power of Sofosbuvir + VelpatasvirAlex Thompson .................................................................................................................................. 66

Short Lecture 4

Update Management in Hepatobiliary Infection: Overcome Anti-Microbial ResistanceAndri Sanityoso Sulaiman, M. Yusuf Hanif ............................................................................. 67

Lunch Symposium 1

Indonesia Experience of Liver TransplantToar JM Lalisang ................................................................................................................................ 74

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42 The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

Evaluation of HCV RNA Viral Load

with Using GeneXpert

Chyntia Olivia Maurine Jasirwan1,

Andri Sanityoso Sulaiman1, Irsan Hasan1,

Rino Alvani Gani1, Cosmas Rinaldi A. Lesmana1,

Juferdy Kurniawan1, Kemal Fariz Kalista1,

Saut Horas Nababan1, Wahyu Purnama2

1 Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/ Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia2 Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

SYMPOSIUM 02

Abstract

Background: HCV infection is a leading burden on human health worldwide and associated with significant liver-related morbidity and mortality globally. Detection of HCV RNA is necessary to diagnose infection. Therefore, we need for a fast, accurate assay to enhance the access to viral load monitoring. This study aimed to evaluate the quantification of HCV RNA in serum and plasma by the GeneXpert viral load assay in comparison to the Cobas TaqMan 96 system as tool standard.

Methods: This study consisted of 54 samples of HCV RNA viral load analysed and nine samples were negative controls. The present study used a diagnostic test to compare HCV RNA viral load testing with GeneXpert and with an integrated laboratory standard.

Results: Based on the univariate analysis, we found that Genexpert's highest viral load was lower than the Cobas Taqman viral load 96 whereas in the Bland-Altman plot analysis showed that the HCV RNA tolerance difference that was tolerable in both devices was determined by <1 log IU / mL. Bland-Altman plot showed that there was one GeneXpert sample which had 1 log difference with Cobas Taqman 96 tool. In this sample, the lowest viral load value <10 IU / mL could be detected by GeneXpert while in Cobas Taqman the viral load value was undetectable. Whereas based on the results of qualitative HCV RNA showed nine negative samples in the GeneXpert tool were also negative by Cobas TaqMan 96, on the other hand, in 45 positive samples in

Evaluation of HCV RNA Viral Load with Using GeneXpert

43The 11th Liver Update and The Scientific Meeting of INA ASL/PPHI in Conjunction with The 7th CISHMS 2018

GeneXpert there was 1 sample that was not detected in Cobas Taqman. There was viral load correlation analysis suggesting (R = 0.99) between the two devices.

Conclusion: There were highly correlation between HCV RNA viral load testing using GeneXpert compared to the Cobas Taqman 96 tool as a standard diagnostic tool.

Keywords: HCV infection; GeneXpert; HCV Viral load

Introduction

Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease in the world. The long-term effects of hepatitis C infection vary greatly from minimal changes in liver histology to fibrosis leading to cirrhosis with or without hepatocellular carcinoma. The number of individuals infected with hepatitis C in the world reaches 180 million, this infection is generally asymptomatic. HCV is a blood-borne virus that infects the liver; chronic infection cause liver disease and extrahepatic manifestations, cirrhosis, hepatocellular carcinoma, and death. 1,2

Detection of HCV RNA is necessary to diagnose infection. The frequent investigations used for the diagnosis of acute and chronic hepatitis C are immunological testing (immunoassay enzymes) with hepatitis C virus (HCV) antibodies, but the disadvantages of this examination are the acute phase of hepatitis C disease resulting in negative immunoassay enzyme test results, due to seroconversion anti HCV generally ranges from 5-10 weeks after exposure. In addition, in patients with immunosuppressed like HIV patients, patients with hemodialysis, and immunosuppressant drug use) may produce false-negative results. Therefore, HCV RNA examination is very useful for diagnosis and monitoring of therapy. 3,4

Viral load testing is one tool that can be used to monitor the success of therapy. The Xpert HCV Viral Load assay is a recently marked test for HCV viral load determination in plasma and serum. There are currently several commercially available HCV viral load assays. GeneXpert HCV Viral Load was once compared to Abbott m 2000 and the result is GeneXpert can provide better results in detection and quality control of samples as well as excel in rapid turn around. This assay combines the steps of sample preparation,

Chyntia Olivia Maurine Jasirwan, Andri Sanityoso Sulaiman, Irsan Hasan, Rino Alvani Gani, Cosmas Rinaldi A. Lesmana, Juferdy Kurniawan, Kemal Fariz Kalista, Saut Horas Nababan, Wahyu Purnama


nucleic acid extraction, amplification and detection of target sequences in one cartridge.5Time needed for the development of platforms which are fully automated. These processes are less prone to contamination, have a high throughput and low turnaround time, and can serve to decentralize molecular testing facilities especially in low-income countries, so it is expected to be generally used in Indonesia. Therefore, the authors intend to conduct a study to evaluate and compare HCV viral load testing with GeneXpert and with existing standard tools.

Method

This study used a diagnostic test to compare viral load HCV RNA with using GeneXpert and with an integrated laboratory standard. This study had already started for 8 months from March 2017 through November 2017 at Cipto Mangunkusumo Hospital, a university hospital of Universitas Indonesia, Jakarta.

The inclusion criteria of this study were patients who tested positive for hepatitis C as evidenced by anti-HCV positive and willing to follow the research while the exclusion criteria are patients who are not in place for long periods of time. The samples in the study were selected using convenience sampling, it means that patients who had found for ambulatory and outpatient and they have included in the inclusion criteria. Patients with hepatitis C would take their blood samples for HCV RNA viral load. A blood sample would be examined with two different diagnostic tools were Roche Cobas Taqman 96 as a standard tool and GeneXpert, then an analysis of the two devices will be performed.

Statistical Analysis

Categorical data were compared using Chi-square test as appropriate because both of variables using the categorical scale. Significance was defined as P less than 0.05. All statistical analyses were carried out using SPSS software version 19.0.

Results

There were 54 samples of HCV RNA viral load analyzed and 9 samples were negative controls. Based on the results of interassay testing (table 1)



below, it was found that the highest GeneXpert viral load was lower than the Cobas Taqman 96 viral load.

Based on the median values of GeneXpert and Cobas Taqman 96 viral loads (table 2) below, there was no differentiation of the HCV RNA concentrations in each device. It could be seen that viral load concentrations in Cobas Taqman 96 at 2 log through 6 logs were higher than viral load concentrations in GeneXpert but it was not exceeding 1 log limit.

According to the result of qualitative HCV RNA on GeneXpert and Cobas Taqman 96 tools (table 3), there are 9 negative samples in GeneXpert tool also negative by using Cobas Taqman 96. There are 45 positive samples in GeneXpert tool, but there was 1 sample not detected by Cobas Taqman 96 tool, but can be detected by GeneXpert tool. Cobas Taqman 96 is a gold standard PCR. Sensitivity of the Xpert HCV HCV Viral Load assay for HCV RNA was 100% (95% CI: 90% -100%,specificity was 90% (95% CI : 54,1%-99,5%), the positive predictive value (PPV) was 97,7% (95% CI: 86,8%-99,9%), and the negative predictive value (NPV) was 100% (95% CI : 62,9%-100%).

In the Bland-Altman plot analysis results in figure1, it was stated that the HCV RNA tolerance difference that could be tolerated in both devices and they were determined by a limit of <1 log IU / mL. There was a GeneXpert’s sample which had a log difference with the Cobas Taqman 96 tool. In that sample, the lowest viral load value <10 IU / mL could be detected by GeneXpert while in Cobas Taqman 96 the viral load value was undetectable.Based on the correlation analysis in (Table 4) below had shown a significant viral load correlation value between GeneXpert and Cobas Taqman 96 (r = 0.99). With a value of 0.99 it means that there was the strong correlation between two of devices.

Discussion

Hepatitis C has become a health problem in the world. World Health Organization (WHO) states that approximately 130-150 million people in the world suffer from chronic hepatitis infection and some of them develop into cirrhosis or liver cancer. Transmission of hepatitis C virus mainly through exposure to blood media and body fluids contaminated with hepatitis C virus. The incubation period of hepatitis C virus ranges from 14-180 days (±



45 days). The diversity clinical manifestations of acute hepatitis C infection range from asymptomatic (80%) to symptomatic (20%).6,7,8

The frequent investigations used to diagnose acute and chronic hepatitis C are immunological testing (immunoassay enzymes) with hepatitis C virus antibodies but there is a disadvantage of this examination that the acute phase of hepatitis C disease provides negative immunoassay enzyme test results because seroconversion of anti-HCV generally ranges from 5 -10 weeks after exposure. Also in patients with immunodeficiency such as HIV patients, patients undergoing hemodialysis, and the use of immunosuppressant drugs may produce false-negative results. In this study, an evaluation was performed on GeneXpert and with a standard tool for evaluating and comparing HCV viral load measurements. In this study, 54 samples of HCV RNA viral load were analyzed and 9 samples were negative controls.9,10,11

Based on the results of the study in table 1 it was found that the highest GeneXpert viral load was lower than the Cobas Taqman 96 viral load. This condition was clarified in the Bland-Altman plot analysis in figure 1 which showed that the lowest viral load value <10 U / mL can be detected by GeneXpert while in Cobas Taqman the viral load value is undetectable. It was also reinforced by the research M.P. McHugh et al stated that GeneXpert could have the results approximately 4 hours compared to standard tools that take 1-2 days but it also could provide better results in terms of detection and quality control of samples and excel in rapid turn around.12,13,14

In a multicenter study conducted by M.P. Mchugh et al also stated that GeneXpert can provide faster results for routine viral load monitoring in organ donor testing situations, needle injury and patients in prison15. In table 2 above stated that the concentration of HCV RNA in each log obtained average viral load between the two tools were not much different while in table 3 was expressed on 9 negative samples in GeneXpert tool was also negative by Cobas TaqMan 96 while in 45 samples positive in GeneXpert there was a sample that was not detected on Cobas Taqman 96. Based on research conducted by Francois MJ Lamoury et al stated that the use of GeneXpert can give results in an hour. This study demonstrates strong correlations for qualitative and quantitative detection compared with Abbott RealTime HCV and GeneXpert is relatively cost-effective than existing standard tools and is also useful as an early screening and diagnostic tool for hepatitis C infection



because it has high sensitivity and specificity in assessing quantification of HCV RNA. In this study obtained, Sensitivity of the Xpert HCV Viral Load assay for HCV RNA was 100% (95% CI: 90% -100%,specificity was 90% (95% CI: 54,1%-99,5%), the positive predictive value (PPV) was 97,7% (95% CI: 86,8%-99,9%), and the negative predictive value (NPV) was 100% (95% CI : 62,9%-100%). Thus, the use of geneXpert is particularly accurate of the HCV RNA Viral Load test.

Based on research conducted by Jason Grebely’s found the sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in venepunctured plasmawas 100% (95% CI 92·0–100·0) and the specificity was 99·1% (95% CI 94·9–100·0). Whereas the sensitivity of the Xpert HCV Viral Load assay for HCV RNA detection in samples by finger-stick samples was 95·5% (95% CI 84·5–99·4) and the specificity was 98·1% (95% CI 93·4–99·8). In this study showed good sensitivity and specificity of the Xpert HCV Viral Load test for HCV RNA detection in capillary whole blood collected by finger-stick and plasma collected by venepuncture compared with the Abbott RealTime HCV Viral Load RNA assay in people attending drug health and homlessness service in Australia. No adverse events happened while the observation of index test or the reference standard.Examination of HCV RNA with real time-PCR can detect the presence of HCV virus amounts up to a load of <15 IU / mL.16,17,18

In the era of DAA (Direct Acting Antiviral), the need for quantification of RNA to be reduced is preferred for detection and monitoring of treatment response. Thus, the qualitative HCV RNA examination, as well as the examination of the HCV core antigen, has the potential to be used. Table 4 shows there was a strong correlation between GeneXpert and Cobas Taqman 96. It was reinforced by Birgit DA Michelin et al's study which also showed that there was a strong correlation (r = 0.93) between the Abbott RealTime HCV test compared to Cobas TaqMan HCV for measuring a viral load having 93% yield for all samples with positive results by both tests.19,20

Conclusion

There was a strong correlation between GeneXpert and Cobas Taqman to assess HCV RNA viral load. It could calculate the number of viruses in a patient's blood sample that can be done before the treatment process, during treatment monitoring, and after treatment within a certain time. In addition,



GeneXpert could get the results about 4 hours compared to standard tools that take 1-2 days. We investigated the cost-effectiveness than the standard tools available so it will be expected to find in Indonesia. Although the HCV RNA concentrations in each log were found the median viral load between the two devices was not highly differentiation but there were limitations in clinical use because existing HCV viral load tests are complicated to use, require complex technical settings and highly trained technicians to operate. The Xpert HCV Viral Load assay performs well compared to a market-leading HCV viral load test and should be considered for rapid comparable testing is required.

Ethical Approval

The ethical approval for the study was taken from the Institutes Ethical Committee.

Availability Data

The dataset generated during this study are not available from the corresponding author because it include ethical concerns.

References

1. Gupta E, Agarwala P, Kumar G, Maiwall R, Sarin SK. Point-of-care testing (POCT) in molecular diagnostics: performance evaluation of GeneXpert HCV RNA test in diagnosing and monitoring of HCV infection. J Clin Virol. 2017 Mar;88:46-51. doi: 10.1016/j.jcv.2017.01.006.

2. Birgit D.A Michelin, Zsofia Muller, Evelyn Stelzl, Egon Marth, Harald H. Kessler. Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA. J Clin Virol. 2007 Feb;38(2):96-100.

3. Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013 Apr;57(4):1333-42. doi: 10.1002/hep.26141.

4. Michelin BDA, Muller Z, Stelzi E, Marth E, Kessler HH. Evaluation of the Abbott RealTime HCV assay for quantitative detection of hepatitis C virus RNA. J Clin Microbiol. 2009 Feb; 47(2): 385–389.

5. Easterbrook PJ, Group WHOGD. Who to test and how to test for chronic hepatitis C infection—2016 WHO testing guidance for low- and middle-income countries. J Hepatol 2016; 65(suppl 1): S46–66.

6. European Association for the Study of the Liver recommendations on treatment of hepatitis C. 2016. J Hepatol. 2017 Jan;66(1):153-194. doi: 10.1016/j.jhep.2016.09.001.



7. J. Vermehren, A. Aghemo, K. Falconer, S. Susser, G. Lunghi, S. Zeuzem, M.Colombo, O. Weiland, C. Sarrazin, Clinical significance of residual viremia detected by two real-time PCR assays for response-guided therapy of HCV genotype 1 infection. J Hepatol. 2014 May;60(5):913-9. doi: 10.1016/j.jhep.2014.01.002.

8. S. Chevaliez, M. Bouvier-Alias, R. Brillet, J.-M. Pawlotsky, Overestimation underestimation of hepatitis C virus RNA levels in a widely used real-time polymerase chain reaction-based method. Hepatol. Baltim. Md. 46 (2007)22–31, http://dx.doi.org/10.1002/hep.21656.

9. G. Cloherty, A. Talal, K. Coller, C. Steinhart, J. Hackett, G. Dawson, J. Rockstroh, J. Feld, Role of serologic and molecular diagnostic assays in identification and management of hepatitis C virus infection. J Clin Microbiol. 2016 Feb;54(2):265-73. doi: 10.1128/JCM.02407-15.

10. Messina JP, Humphreys I, Flaxman A, Brown A, Cooke GS, Pybus OG, Barnes E. 2015. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology. 2015 Jan;61(1):77-87. doi: 10.1002/hep.27259.

11. Alonso R, Perez-Garcia F, Ampuero D, Reigada E, Bouza E. 2017. New direct-acting antivirals for patients with chronic HCV infection: can we monitor treatment using an HCV core antigen assay? Diagn Microbiol Infect Dis 87:243–246. https://doi.org/10.1016/j.diagmicrobio.2016.11.010.

12. M.P. McHugh, A.H.B.Wu, S. Chevaliez, J.M. Pawlotsky, M. Hallin, K.E. Templeton. Multicenter Evaluation of the Cepheid Xpert Hepatitis C Virus Viral Load Assay. J Clin Microbiol. 2017 May;55(5):1550-1556. doi: 10.1128/JCM.02460-16.

13. Alonso R, Perez-Garcia F, Lopez-Roa P, Alcala L, Rodeno P, Bouza E. HCV core-antigen assay as an alternative to HCV RNA quantification : A correlation study for the assessment of HCV viremia. Enferm Infecc Microbiol Clin. 2018 Mar;36(3):175-178. doi: 10.1016/j.eimc.2016.11.013.

14. Francois M.J Lamoury, Sahar Bajis, Behzad Hajarizadeh, Alison D. Marshall, Marianne Martinello, Elena Ivanova, et all. Evaluation of the Xpert HCV Viral Load Finger-Stick Point-of-Care Assay. The Journal of Infectious Diseases. 2018; 1-6.

15. Matsuura K, Tanaka Y, Hasegawa I, Ohno T, Tokuda H, Kurbanov F, et all. Abbott RealTime hepatitis C virus (HCV) and Roche Cobas Ampliprep/Cobas TaqMan HCV assays for prediction of sustained virological response to pegylated interferon and ribavirin in chronic hepatitis C patients.J Clin Microbiol. 2009 Feb;47(2):385-9. doi: 10.1128/JCM.01753-08.

16. Grebely J, Lamoury FMJ, Hajarizadeh B, Mowat Y, Marshall AD, Bajis S, et all. Evaluation of the Xpert HCV Viral Load point-of-care assay from venepuncture-collected and finger-stick capillary whole-blood samples: a cohort study. Lancet Gastroenterol Hepatol. 2017 July;2(7):514-520. doi: 10.1016/S2468-1253(17)30075-4.

17. Larrat S, Poveda JD, Coudret C, Fusillier K, Magnat N, Signori-Schmuck A, Thibault V, Morand P. Sequencing assays for failed Genotyping with the versant Hepatitis C



Virus Genotype Assay (LiPA), Version 2.0. J Clin Microbiol. 2013 Sep;51(9):2815-21. doi: 10.1128/JCM.00586-13.

18. Zhou K, Fitzpatrick T, Walsh N, et al. Interventions to optimize the care continuum for chronic viral hepatitis: a systematic review and meta-analyses. Lancet Infect Dis 2016; 16:1409–22.

19. Smith BD, Drobeniuc J, Jewett A, et al. Evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus. J Infect Dis 2011; 204: 825–31.

20. Daniel HD, Grant PR, Garson JA, Tedder RS, Chandy GM, Abraham P. Quantitation of hepatitis C virus using an in-house real-time reverse transcriptase polymerase chain reaction in plasma samples. Diagn Microbiol Infect Dis 2008; 61: 415–20.

Table 1. Results of interassay testing

Viral Load GeneXpert (IU/mL) Viral Load Roche Cobas

Taqman 96 (IU/mL)

Median 2,72 x 105 3,04 x 105

Std. Deviation 1,07 x 106 3,60 x 106

Table 2. The averages of viral load values in Genexpert and Cobas Taqman 96

Concentration HCV RNA

(log IU/mL)

Averages of viral load value (log 10 IU/mL)

Genexpert Cobas Taqman 96

1 1,33 1,07

2 2,99 3,22

3 3,38 3,60

4 4,57 4,58

5 5,66 5,77

6 6,34 6,60

Table 3. Results of Qualitative HCV RNA on GeneXpert and Cobas Taqman96

GenexpertCobas Taqman 96

TotalVirus detected Virus not detected

Virus detected 44 1 45

Virus not detected 0 9 9

Total 44 10 54Sensitifitas Genexpert = 44/44 x 100% = 100% (95% CI: 90% -100%) Spesifisitas Genexpert = 9/10 x 100% = 90% (95% CI: 54,1% -99,5%)

PVP Genexpert = 44/45 x 100% = 97,7% (95% CI: 86,8% -99,9%)PVN Genexpert = 9/9 x 100% = 100% (95% CI: 62,9% -100%)



Table 4. Correlation analysis

Log_Genexpert Log_cobas

Log_genexpert Pearson Correlation 1 ,993**

Log_cobas Pearson Correlation ,993** 1**. Correlation is significant at the 0.01 level (2-tailed).

Figure 1. Bland-Altman plot analysis

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NASKAH LENGKAP Liver Update and The Scientific Meeting of …staff.ui.ac.id/system/files/users/rino.gani/publication/... · FKUI/RSCM Dr. Cipto Mangunkusumo Jakarta David Handojo