HEPATITIS C DIAGNOSTICS

PRODUCTS AND ORDERING INFORMATION

HCV Antibody
The presence of specific anti-HCV antibodies indicates that an individual has been infected with HCV at some time in the past, may harbour infectious HCV, and may transmit HCV infection. Although the majority of HCV infected individuals is asymptomatic, the infection may develop into chronic hepatitis, cirrhosis and increase the risk of hepatocellular carcinoma.1,2,3,4

Product Name HCV ANTIBODY ARCHITECT Anti-HCV ARCHITECT Anti-HCV Calibrator ARCHITECT Anti-HCV Controls Assay CD-ROM HCV ANTIGEN ARCHITECT HCV Ag ARCHITECT HCV Ag Controls ARCHITECT HCV Ag Calibrators

List Number 6C37 6C37-01 6C37-10 6E59-27 or above 6L47-27 6L47-11 6L47-02 8K30-06 or above

Key Parameters
Specificity 99.60% (95% CI 99.45 99.71%) Sensitivity 99.10% (95% CI 96.77 99.89%) Human serum & plasma (EDTA, LithiumHeparin, Na-Heparin, Na-Citrate, ACD, CPDA-1, CPD, CP2D)

Assay range LLD Precision

3 20.000 fmol/L 3 180.000 fmol/L (autodilution) 3.00 fmol/L 9.5 % CV

HCV Antigen
Detection of HCV Antigen can be applied to differentiate between active and past infection in anti-HCV positive patients. Screening of selected individuals at elevated risk for HCV infections, such as immunocompromised patients, IV drug users, hemodialysis patients and those from areas of high HCV prevalence, may allow detection of an HCV infection during the antibody negative window period and thus reduce the risk of HCV transmission. Quantitation of HCV Antigen in the very early stage of treatment in conjunction with HCV RNA viral load testing may be used as an aid to predict response to antiviral therapy (at Ag levels > 20.000 pg/L).5,6,7

Assay CD-ROM HCV RNA VIRAL LOAD Abbott RealTime HCV Amplification Reagent Kit Abbott RealTime HCV Control Kit Abbott RealTime HCV Calibrator Kit Abbott RealTime HCV Application CD-ROM HCV GENOTYPING

Human serum & plasma (Na-EDTA, K-EDTA, Li-Heparin, Na-Heparin, Na-Citrate, CPD)

4J86-90 4J86-80 4J86-70 1L69

Assay range 1.08 8.00 Log IU/mL LOD 10.5 IU/mL ( 95 % probability) Precision (inter-assay) 0.25 Log IU/mL Human serum & plasma (ACD-A or EDTA)

Abbott RealTime HCV Genotype II Amplification Reagent Kit 8K24-90 Abbott RealTime HCV Genotype II Control Kit Abbott RealTime HCV Genotype II Application CD-ROM 8K24-80 8L36

LOD 500 IU/mL (0.5 ml); 1.250 IU/ml (0.2 ml) Detection of HCV Genotypes 1, 1a, 1b, 2, 3, 4, 5 and 6 Human serum & plasma (ACD-A or K-EDTA, Na-EDTA, CPD)

HCV Genotyping
HCV genotype is predictive of the response of HCV-infected patients to peg-interferon/ ribavirin combination therapy. Determination of the genotype prior to starting combination therapy is recommended and allows application of the most appropriate therapy regimen in terms of duration of treatment and intervals for viral load monitoring.8

SPECIMEN PREPARATION Abbott mSample Preparation System 4J70-24

RNA Extraction Reagent to be used in conjunction with Abbott RealTime HCV assays

REFERENCES
1 2 3 4 5 6

HEPATITIS C PATIENT MANAGEMENT

Dienstag JL. Non-A, Non-B Hepatitis. I. Recognition, Epidemiology, and Clinical Features. Gastroenterology 1983;85:439 62. Gitnick G. Non-A, Non-B Hepatitis: Etiology and Clinical Course. Ann Rev Med 1984;35:265 78. Wick MR, Moore S, Taswell HF. Non-A, Non-B Hepatitis Associated with Blood Transfusion. Transfusion 1985;25:93 101. Hollinger FB. Non-A, Non-B Hepatitis Viruses. In: Fields BN, Knipe DN, editors. Virology. New York: Raven Press, 1990:2239 73. Prof. M. Roggendorf, National Reference Center for Hepatitis C, Institute of Virology, University Essen, Germany (Personal Communication). Aoyagi K, Ohue C, Lida K, Kimura T, Tanaka E, Kiyosawa K, Yagi S. Development of a Simple and Highly Sensitive Enzyme Immunoassay for Hepatitis C Virus Core Antigen. J Clin Microbiol 1999;37:1802 1808. Hayashi K, Hasuike S, Kusumoto K, Ido A, Uto H, Kenji N, Kohara M, Stuver S O, Tsubouchi H. Usefulness of a new immunoreadiometric assay to detect hepatitis C core antigen in a community based population. J Viral Hepat 2005;12:106 110. Sarrazin C, Berg T, Ross S, Schirmacher P, Wedemeyer H, Neumann U, Schmidt HHJ, Spengler U, Wirth S, Kessler HH, Peck-Radosavljevic M, Ferenci P, Vogel W, Moradpour D, Heim M, Cornberg M, Protzer U, Manns MP, Fleig WE, Dollinger MM, Zeuzem S. Prophylaxis, Diagnosis and Therapy of Hepatitis C Virus (HCV) Infection: The German Guidelines on the Management of HCV Infection. Z Gastroenterol 2010, 48: 289 351.

HCV RNA Highly Sensitive and Precise Viral Load

Current guidelines for the management and treatment of Hepatitis C virus infection recommend quantitative and highly sensitive testing for HCV RNA before the start of antiviral therapy, during therapy, and after the conclusion of treatment. The objective of treatment is a sustained virological response (SVR), defined as the absence of HCV RNA detectable by a sensitive test 24 weeks after end of treatment. Monitoring HCV RNA is recommended at weeks 4, 12, 24, end of therapy and 24 weeks after termination of treatment.8

Abbott GmbH & Co. KG Abbott Diagnostics Max-Planck-Ring 2 65205 Wiesbaden, Germany Tel. (+49) 61 22 58 0 Fax (+49) 61 22 58 12 44 www.abbottdiagnostics.com

ARCHITECT, RealTime HCV and Put science on your side are trademarks of Abbott Laboratories in various jurisdictions.

Scientific consultancy: Prof. Dr. med. Christoph Sarrazin Klinikum J. W. Goethe-Universitt Frankfurt, Medizinische Klinik I Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

Put science on your side.

AG2202/uk Hepatitis C Patient Management 03/10/1

HEPATITIS C DIAGNOSTICS AND PATIENT MANAGEMENT

HEPATITIS C DIAGNOSTICS

HEPATITIS C DIAGNOSTICS

HCV RNA

Anti-HCV

Screening / Diagnostics

Chronic hepatitis C virus (HCV) infection affects more than 180 million people worldwide and is one of the major causes of liver cirrhosis, hepatocellular carcinoma, and liver failure leading to transplantation. In the majority of countries HCV infection is under-diagnosed, because acute and chronic infection rarely cause typical symptoms. In contrast, a significant proportion of infected individuals progress to liver fibrosis and cirrhosis. Consequently, screening for HCV infection is a major objective. Highly specific and sensitive HCV antibody tests are available for screening, and differentiation between acute and past HCV infection is established by detection of HCV core antigen or HCV RNA. The current standard treatment of chronic hepatitis C, a combination of pegylated interferon alfa and ribavirin, eradicates the virus in about 50% of patients. Different HCV genotypes exhibit significant differences in response rates to antiviral therapy and mandate determination of the HCV genotype prior to treatment initiation. The key parameter for management of individualized antiviral therapy is HCV RNA. HCV genotype, in combination with baseline viral load and decline of HCV RNA concentration during therapy, are used to terminate treatment early in virologic non-responders and to define the optimal duration of treatment for patients responding to antiviral therapy. New drugs, so called DAA (directly acting antiviral) agents, which directly inhibit HCV replication, have entered phase 1 3 phase clinical trials. These include agents targeting NS3 protease, NS5A replicase, NS5B polymerase as well as compounds causing effects through inter-action with host cell proteins. Sustained virologic response rates will increase with these new therapeutic options. Nevertheless, results from clinical phase 2 studies have revealed that baseline HCV RNA concentration is an excellent predictor of virologic response and tailoring of treatment duration based on initial HCV viral kinetics will continue playing a key role in the era of directly acting antivirals. Highly sensitive HCV RNA assays for detection of minimal residual HCV RNA levels, in combination with highly precise and reliable quantitation of HCV RNA concentration, are essential for optimal management of antiviral therapy in patients with chronic hepatitis C. Monotherapy with DAA agents poses a high risk for selection of resistant variants due to the high genetic heterogeneity of HCV and its rapid replication. HCV resistance testing may be useful to complement viral load and genotype determination in optimization of treatment schedules in the future.

Marker Profile in HCV Infection

Anti-HCV (Immunoassay) Non-Reactive NO HCV Infection
Exception: Acute Hepatitis C and Immunosuppression

Reactive HCV Ag

HCV RNA

Positive

Negative HCV RNA Detectable Undetectable Past HCV Infection

HCV Ag

HCV Core Ag

window period

HCV Infection
0
HCV Ag LLD 3 fmol/L HCV RNA LOD ~ 10.5 IU/mL

20

40

60

80

days

Note: This is a graphic represenation of marker profiles in HCV infection

Pre Treatment

HCV RNA Baseline

HCV Genotyping

Pattern of Virologic Response

7 6 HCV RNA Log10 IU/mL 5 4 3 2 1 0 8 4 2 0 4 8 12 16 20 24 32 40 48 52 60 ETR SVR 72 Relapse

HCV-1 (4, 5, 6)

HCV-2, 3

Peg-Interferon & Ribavirin

RVR Rapid Virologic Response EVR Early Virologic Response DVR Delayed Virologic Response PR Partial Response NR Null Response Lower Level of Detection

Antiviral Treatment 24 72 weeks

Antiviral Treatment 16 48 weeks

Therapy

ETR End Treatment Response SVR Sustained Viral Response

HCV RNA at weeks 4, 12 and 24 HCV RNA undetectable week 4 HCV RNA undetectable week 12 HCV RNA undetectable week 24

< 2 log decline week 12

Weeks after Start of Treatment

HCV RNA detectable week 24

Screening/Diagnostics
HCV Antibody HCV Antigen HCV RNA Detection Detection/Quantitation Detection/Confirmation

Stop Therapy

Pre Treatment Therapy

Resistance Testing*
*In development

Stop Treatment Virologic Non-Response

HCV Genotype Determination HCV RNA Baseline Highly precise Quantitation

Stop Treatment HCV-1 (4 6) LVL 24 weeks

HCV RNA Monitoring Highly sensitive and precise Quantitation HCV Sequencing

Stop Treatment HCV-2, 3 LVL 16 weeks No LVL 24 weeks

Stop Treatment week 48

Stop Treatment week 72

HCV RNA at EOT and week 24 after EOT

LVL = Low baseline viral load < 600.000800.000 IU/mL EOT = End of Treatment