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1. Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B

Author

Erken, R., Loukachov, V., Dort, K. van, Hurk, A. van den, Takkenberg, R.B., Niet, Anniki de, Jansen, Louis, Willemse, S., Reesink, H., Kootstra, N., Erken, R., Loukachov, V., Dort, K. van, Hurk, A. van den, Takkenberg, R.B., Niet, Anniki de, Jansen, Louis, Willemse, S., Reesink, H., and Kootstra, N.

Abstract

Contains fulltext : 252187.pdf (Publisher’s version ) (Open Access), BACKGROUND AND AIMS: HBV can integrate in the host genome of the hepatocyte and recent findings suggest that integrated HBV contributes to the persistent production of viral proteins. Here, we quantified the levels of integrated HBV in patients with chronic hepatitis B (CHB) and analyzed the relation between HBV integration, virological activity (plasma HBV DNA and HBsAg levels), and clinical outcomes. APPROACH AND RESULTS: We developed and validated a multistep Arthrobacter luteus (Alu)-PCR that specifically amplifies integrated HBV and RT-Alu-PCR detecting mRNA transcripts derived from integrated HBV. Pretreatment liver biopsy samples and baseline characteristics of 124 patients with CHB either treated for 48 weeks with pegylated interferon plus adefovir or tenofovir or receiving no treatment were available for analysis. Integrated HBV sequences containing open reading frame S and X (but not C) and S and X mRNA transcripts derived from integrated HBV could be detected and quantified in liver biopsies. Integrated HBV levels correlated with HBV DNA, HBsAg, alanine aminotransferase plasma levels, and the liver histology activity index but not to levels of intrahepatic covalently closed circular DNA (cccDNA), plasma pregenomic RNA, or hepatitis B core-related antigen. Multivariable logistic regression analysis showed that lower baseline HBV integration levels were independently associated with HBsAg loss (functional cure) within 5 years follow-up. CONCLUSIONS: Integrated HBV levels are strongly correlated with surrogate markers for virological activity but not to cccDNA levels and are predictive for HBsAg loss. Our data suggest that integrated HBV is closely related to HBV replication and may therefore be an important tool in the evaluation and development of treatment modalities aiming to cure CHB.

Published
2022

3. Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis

Author

Willemse, S., Smit, C., Sogni, P., Sarcletti, M., Uberti-Foppa, C., Wittkop, L., Raben, D., D'Arminio Monforte, A., Dabis, F., Van Der Valk, M., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Meyer, L., Murielle, M., Ghosn, J., Leport, C., Reiss, P., Wit, F., Prins, M., Bucher, H., Gibb, D., Fatkenheuer, G., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Perez-Hoyos, S., Hamouda, O., Clinsurv, G., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Prieto, L., Pablo, R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Mussini, C., Tookey, P., Casabona, J., Miro, J. M., Castagna, A., Konopnick, D., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Stephane, D., Jose, M., Costagliola, D., Raffaele, S., Julia, D., Chene, G., Barger, D., Schwimmer, C., Termote, M., Campbell, M., Frederiksen, C. M., Friis-Moller, N., Kjaer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Furrer, H., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Sterne, J., Thiebaut, R., Willemse, S., Smit, C., Sogni, P., Sarcletti, M., Uberti-Foppa, C., Wittkop, L., Raben, D., D'Arminio Monforte, A., Dabis, F., Van Der Valk, M., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Meyer, L., Murielle, M., Ghosn, J., Leport, C., Reiss, P., Wit, F., Prins, M., Bucher, H., Gibb, D., Fatkenheuer, G., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Perez-Hoyos, S., Hamouda, O., Clinsurv, G., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Prieto, L., Pablo, R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Mussini, C., Tookey, P., Casabona, J., Miro, J. M., Castagna, A., Konopnick, D., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Stephane, D., Jose, M., Costagliola, D., Raffaele, S., Julia, D., Chene, G., Barger, D., Schwimmer, C., Termote, M., Campbell, M., Frederiksen, C. M., Friis-Moller, N., Kjaer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Furrer, H., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Sterne, J., Thiebaut, R., Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Infectious diseases, AII - Infectious diseases, Global Health, APH - Aging & Later Life, APH - Global Health, APH - Digital Health, and APH - Personalized Medicine

Subjects
Liver Cirrhosis, Male, Cirrhosis, co‐infection, medicine.disease_cause, 0302 clinical medicine, 80 and over, Mass Screening, 030212 general & internal medicine, Chronic, guideline adherence, Aged, 80 and over, cancer screening, chronic viral hepatitis, co-infection, hepatocellular carcinoma, hepatocellular carcinoma screening, human immunodeficiency virus, liver cirrhosis, Adolescent, Adult, Aged, Carcinoma, Hepatocellular, Coinfection, Female, Guideline Adherence, Hepatitis B, Chronic, Hepatitis C, Chronic, Humans, Liver Neoplasms, Middle Aged, Young Adult, medicine.diagnostic_test, chronic viral hepatiti, virus diseases, Hepatitis C, Hepatitis B, 3. Good health, Infectious Diseases, Hepatocellular carcinoma, Liver biopsy, 030211 gastroenterology & hepatology, medicine.medical_specialty, Hepatitis C virus, Short Communication, Short Communications, 03 medical and health sciences, Virology, Internal medicine, medicine, Mass screening, Hepatitis B virus, Hepatology, business.industry, human immunodeficiency viru, Carcinoma, Hepatocellular, medicine.disease, digestive system diseases, business
Abstract

The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening

Published
2019

4. Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis

Author

Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Willemse S., Smit C., Sogni P., Sarcletti M., Uberti-Foppa C., Wittkop L., Raben D., D'Arminio Monforte A., Dabis F., Van Der Valk M., Judd A., Zangerle R., Touloumi G., Warszawski J., Meyer L., Murielle M., Ghosn J., Leport C., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., ClinSurv G., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., Brockmeyer N., Prieto L., Pablo R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Stephane D., Jose M., Costagliola D., Raffaele S., Julia D., Chene G., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., Thiebaut R., Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Willemse S., Smit C., Sogni P., Sarcletti M., Uberti-Foppa C., Wittkop L., Raben D., D'Arminio Monforte A., Dabis F., Van Der Valk M., Judd A., Zangerle R., Touloumi G., Warszawski J., Meyer L., Murielle M., Ghosn J., Leport C., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., ClinSurv G., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., Brockmeyer N., Prieto L., Pablo R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Stephane D., Jose M., Costagliola D., Raffaele S., Julia D., Chene G., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., and Thiebaut R.

Published
2019

5. Liver stiffness improvement in hepatitis C patients after successful treatment

Author

Brakenhoff, S M, Verburgh, M L, Willemse, S B, Baak, L C, Brinkman, K, van der Valk, M, Graduate School, General Internal Medicine, Gastroenterology and Hepatology, Infectious diseases, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Global Health, APH - Digital Health, and APH - Personalized Medicine

Subjects
Antiviral Agents/therapeutic use, Carcinoma, Hepatocellular, Liver Cirrhosis/diagnostic imaging, Hepatitis C, Chronic/complications, Humans, Liver/diagnostic imaging, Liver Neoplasms/drug therapy, Retrospective Studies
Abstract

BACKGROUND: Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis. METHODS: This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4). RESULTS: Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in 197 patients with pre-treated advanced fibrosis or cirrhosis. In 50.3% of these patients, liver stiffness improved to a value fitting with mild to moderate fibrosis (< 9.5 kPa, F0-F2) after successful treatment. Multivariate analysis demonstrated that a pre-treatment FibroScan® value of ≥ 20.0 kPa was associated with persisting advanced fibrosis or cirrhosis after treatment (OR 29.07, p < 0.001). CONCLUSION: Liver stiffness improves significantly after successful direct-acting antiviral agent treatment in chronic hepatitis C patients with advanced fibrosis or cirrhosis prior to DAA treatment. Long-term outcomes regarding occurrence of hepatocellular carcinoma (HCC) in these patients are required to determine whether they can be safely discharged from HCC surveillance.

Published
2020

6. Retrieval of chronic hepatitis C patients. A manifesto for action to eliminate hepatitis C in the Netherlands: The CELINE project

Author

Dijk, M., Kracht, P. A. M., Arends, J. E., Blokzijl, H., Burger, D. M., Erpecum, K. J., Hoek, B., Knegt, R. J., Posthouwer, D., Ramsoekh, D., Rijnders, B. J. A., Schinkel, J., Willemse, S. B., Marc van der Valk, Drenth, J. P. H., Medical Microbiology and Infection Prevention, AII - Infectious diseases, Gastroenterology and Hepatology, Infectious diseases, Amsterdam Gastroenterology Endocrinology Metabolism, APH - Digital Health, APH - Personalized Medicine, APH - Global Health, Gastroenterology & Hepatology, Internal Medicine, Med Microbiol, Infect Dis & Infect Prev, MUMC+: DA MMI Staf (9), RS: FHML non-thematic output, Gastroenterology and hepatology, and AGEM - Digestive immunity

Subjects
AMSTERDAM, OUTCOMES, DECLINE, elimination, SDG 3 - Good Health and Well-being, HCV, chronic hepatitis C, virus diseases, retrieval
Abstract

Chronic hepatitis C virus (HCV) infection is a global public health issue, which is associated with high rates of morbidity and mortality. The development of direct acting antivirals (DAAs) has transformed treatment: they offer us highly-effective therapy with superior tolerability compared to interferon-containing regimens. In 2016, the World Health Organization (WHO) therefore adopted several ambitious viral hepatitis elimination targets, aiming for a 90% reduction in new infections and a 65% reduction in mortality by 2030. The ultimate goal is to eliminate HCV completely. It is reasonable that these goals may be achieved in the Netherlands due to the low prevalence of chronic HCV, the availability of DAAs, and excellent healthcare infrastructure. This paper describes a national effort to curtail the HCV epidemic in the Netherlands through an HCV retrieval and linkage to care project (CELINE: Hepatitis C Elimination in the Netherlands).

Published
2019

7. Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2

Author

Saraswat, V, Norris, S, de Knegt, Rob, Sanchez Avila, JF, Sonderup, M, Zuckerman, E, Arkkila, P, Stedman, C, Acharya, S, Aho, I, Anand, AC, Andersson, MI, Arendt, V, Baatarkhuu, O, Barclay, K, Ben-Ari, Z, Bergin, C, Bessone, F, Blach, S, Blokhina, N, Brunton, CR, Choudhuri, G, Chulanov, V, Cisneros, L, Croes, EA (Esther), Dahgwahdorj, YA, Dalgard, O, Daruich, JR, Dashdorj, NR, Davaadorj, D, de Vree, M, Estes, C, Flisiak, R, Gadano, AC, Gane, E, Halota, W, Hatzakis, A, Henderson, C, Hoffmann, P, Hornell, J, Houlihan, D, Hrusovsky, S, Jarcuska, P, Kershenobich, D, Kostrzewska, K, Kristian, P, Leshno, M, Lurie, Y, Mahomed, A, Mamonova, N, Mendez-Sanchez, N, Mossong, J, Nurmukhametova, E, Nymadawa, P, Oltman, M, Oyunbileg, J, Oyunsuren, T, Papatheodoridis, G, Pimenov, N, Prabdial-Sing, N, Prins, M, Puri, P, Radke, S, Rakhmanova, A, Razavi, H, Razavi-Shearer, K, Reesink, HW, Ridruejo, E, Safadi, R, Sagalova, O, Sanduijav, R, Schreter, I, Seguin-Devaux, C, Shah, SR, Shestakova, I, Shevaldin, A, Shibolet, O, Sokolov, S, Souliotis, K, Spearman, CW, Staub, T, Strebkova, EA, Struck, D, Tomasiewicz, K, Undram, L, van der Meer, Adriaan, van Santen, D, Veldhuijzen, I, Villamil, FG, Willemse, S, Zuure, FR, Silva, MO, Sypsa, V, Gower, E, Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Infectious diseases, Gastroenterology and Hepatology, Graduate School, Other departments, Gastroenterology & Hepatology, and Epidemiology

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Hepatology, Infant, Newborn, Infant, Hepatitis C, Chronic, Middle Aged, Global Health, Antiviral Agents, Drug Utilization, Liver Transplantation, Young Adult, Infectious Diseases, SDG 3 - Good Health and Well-being, Child, Preschool, Virology, Prevalence, Humans, Female, Child, Aged
Abstract

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8 666 000 cases) and Russia (4 162 000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Published
2015
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8. A single dose of anti-miR-122, RG-101, in CHC patients results in NK cell normalization with no effect on HCV-specific CD8+ T cell function

Author

Stelma, F, van der Ree, M, Sinnige, M, Brown, A, Swadling, L, de Vree, J, Willemse, S, van der Valk, M, Grint, P, Neben, S, Klenerman, P, Barnes, E, Kootstra, N, and Reesink, H

Abstract

MicroRNA-122 (miR-122) is an important host factor for the hepatitis C virus. Treatment with RG-101, a GalNAc conjugated anti-miR-122 oligonucleotide, resulted in a significant viral load reduction in patients with chronic hepatitis C (CHC) infection. Here, we analyzed the effects of RG-101 therapy on antiviral immunity. 32 CHC patients HCV genotype 1, 3 and 4 received a single subcutaneous administration with RG-101 at 2 mg/kg (n=14), 4 mg/kg (n=14) or placebo (n=2 per dosing group). Plasma and PBMCs were collected at multiple time points and comprehensive immunological analyses were performed. Following RG-101 administration, HCV RNA declined in all patients (mean decline at week 2: 3.27 log10 IU/mL). At week 8 HCV RNA was undetectable in 15/28 patients. Plasma IP-10 levels declined significantly upon dosing with RG-101. Furthermore, the frequency of NK cells increased, and the proportion of markers for NK cells expressing activating receptors activity and differentiation normalized and NK cell IFN-γ production decreased after RG-101 dosing. By week 8 post RG-101 injection, fFunctional HCV-specific IFN-γ-T cell responses did not declined significantly change in patients who had undetectable HCV RNA by week 8 post RG-101 injection. No increase in the magnitude of HCV-specific T cell responses was observed at later time points, including 3 patients who were HCV RNA negative 76 weeks post dosing.

Published
2017

9. Advances in guava propagation

Author

PEREIRA, F. M., USMAN, M., MAYER, N. A., NACHTIGAL, J. C., MAPHANGA, O. R. M., WILLEMSE, S., FERNANDO MENDES PEREIRA, MUHAMMAD USMAN, NEWTON ALEX MAYER, CPACT, JAIR COSTA NACHTIGAL, CPACT, OSCAR RANNY MBONGENI MAPHANGA, and SALOMIE WILLEMSE, Institute for Tropical and Subtropical Crops.

Subjects
Cultura de tecidos, Enxertia, Alporquia, Psidium Guajava, Semente, Estaquia
Abstract

Made available in DSpace on 2017-12-08T23:23:40Z (GMT). No. of bitstreams: 1 AlexMayerRBFGUAVAPropagation2017Incluido.pdf: 1009537 bytes, checksum: 1c2de381bab63888d67dea6baf90f3d4 (MD5) Previous issue date: 2017-12-08

Published
2017

11. The present and future disease burden of hepatitis C virus (HCV) infections with today's treatment paradigm - volume 2

Author

Hatzakis, A. Chulanov, V. Gadano, A. C. Bergin, C. and Ben-Ari, Z. Mossong, J. Schreter, I. Baatarkhuu, O. and Acharya, S. Aho, I. Anand, A. C. Andersson, M. I. and Arendt, V. Arkkila, P. Barclay, K. Bessone, F. Blach, S. and Blokhina, N. Brunton, C. R. Choudhuri, G. Cisneros, L. and Croes, E. A. Dahgwahdorj, Y. A. Dalgard, O. Daruich, J. R. Dashdorj, N. R. Davaadorj, D. de Knegt, R. J. de Vree, M. Estes, C. Flisiak, R. Gane, E. Gower, E. and Halota, W. Henderson, C. Hoffmann, P. Hornell, J. and Houlihan, D. Hrusovsky, S. Jarcuska, P. Kershenobich, D. and Kostrzewska, K. Kristian, P. Leshno, M. Lurie, Y. and Mahomed, A. Mamonova, N. Mendez-Sanchez, N. Norris, S. and Nurmukhametova, E. Nymadawa, P. Oltman, M. Oyunbileg, J. and Oyunsuren, Ts. Papatheodoridis, G. Pimenov, N. and Prabdial-Sing, N. Prins, M. Radke, S. Rakhmanova, A. and Razavi-Shearer, K. Reesink, H. W. Ridruejo, E. Safadi, R. and Sagalova, O. Sanchez Avila, J. F. Sanduijav, R. and Saraswat, V. Seguin-Devaux, C. Shah, S. R. Shestakova, I. and Shevaldin, A. Shibolet, O. Silva, M. O. Sokolov, S. and Sonderup, M. Souliotis, K. Spearman, C. W. Staub, T. and Stedman, C. Strebkova, E. A. Struck, D. Sypsa, V. and Tomasiewicz, K. Undram, L. van der Meer, A. J. van Santen, D. Veldhuijzen, I. Villamil, F. G. Willemse, S. and Zuckerman, E. Zuure, F. R. Puri, P. Razavi, H.

Abstract

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.

Published
2015

12. Historical epidemiology of hepatitis C virus (HCV) in select countries - volume 2

Author

Saraswat, V. Norris, S. de Knegt, R. J. Sanchez Avila, J. F. and Sonderup, M. Zuckerman, E. Arkkila, P. Stedman, C. and Acharya, S. Aho, I. Anand, A. C. Andersson, M. I. and Arendt, V. Baatarkhuu, O. Barclay, K. Ben-Ari, Z. and Bergin, C. Bessone, F. Blach, S. Blokhina, N. Brunton, C. R. Choudhuri, G. Chulanov, V. Cisneros, L. Croes, E. A. Dahgwahdorj, Y. A. Dalgard, O. Daruich, J. R. and Dashdorj, N. R. Davaadorj, D. de Vree, M. Estes, C. and Flisiak, R. Gadano, A. C. Gane, E. Halota, W. Hatzakis, A. Henderson, C. Hoffmann, P. Hornell, J. Houlihan, D. and Hrusovsky, S. Jarcuska, P. Kershenobich, D. Kostrzewska, K. Kristian, P. Leshno, M. Lurie, Y. Mahomed, A. and Mamonova, N. Mendez-Sanchez, N. Mossong, J. Nurmukhametova, E. Nymadawa, P. Oltman, M. Oyunbileg, J. Oyunsuren, Ts. and Papatheodoridis, G. Pimenov, N. Prabdial-Sing, N. Prins, M. Puri, P. Radke, S. Rakhmanova, A. Razavi, H. and Razavi-Shearer, K. Reesink, H. W. Ridruejo, E. Safadi, R. and Sagalova, O. Sanduijav, R. Schreter, I. Seguin-Devaux, C. Shah, S. R. Shestakova, I. Shevaldin, A. Shibolet, O. and Sokolov, S. Souliotis, K. Spearman, C. W. Staub, T. and Strebkova, E. A. Struck, D. Tomasiewicz, K. Undram, L. and van der Meer, A. J. van Santen, D. Veldhuijzen, I. Villamil, F. G. Willemse, S. Zuure, F. R. Silva, M. O. Sypsa, V. and Gower, E.

Abstract

Chronic hepatitis C virus (HCV) infection is a leading cause of liver related morbidity and mortality. In many countries, there is a lack of comprehensive epidemiological data that are crucial in implementing disease control measures as new treatment options become available. Published literature, unpublished data and expert consensus were used to determine key parameters, including prevalence, viremia, genotype and the number of patients diagnosed and treated. In this study of 15 countries, viremic prevalence ranged from 0.13% in the Netherlands to 2.91% in Russia. The largest viremic populations were in India (8666000 cases) and Russia (4162000 cases). In most countries, males had a higher rate of infections, likely due to higher rates of injection drug use (IDU). Estimates characterizing the infected population are critical to focus screening and treatment efforts as new therapeutic options become available.

Published
2015

13. Strategies to manage hepatitis C virus (HCV) infection disease burden - volume 2

Author

Gane, E. Kershenobich, D. Seguin-Devaux, C. Kristian, P. and Aho, I. Dalgard, O. Shestakova, I. Nymadawa, P. Blach, S. Acharya, S. Anand, A. C. Andersson, M. I. Arendt, V. and Arkkila, P. Baatarkhuu, O. Barclay, K. Ben-Ari, Z. and Bergin, C. Bessone, F. Blokhina, N. Brunton, C. R. and Choudhuri, G. Chulanov, V. Cisneros, L. Croes, E. A. and Dahgwahdorj, Y. A. Daruich, J. R. Dashdorj, N. R. Davaadorj, D. de Knegt, R. J. de Vree, M. Gadano, A. C. Gower, E. and Halota, W. Hatzakis, A. Henderson, C. Hoffmann, P. and Hornell, J. Houlihan, D. Hrusovsky, S. Jarcuska, P. and Kostrzewska, K. Leshno, M. Lurie, Y. Mahomed, A. and Mamonova, N. Mendez-Sanchez, N. Mossong, J. Norris, S. and Nurmukhametova, E. Oltman, M. Oyunbileg, J. Oyunsuren, Ts. and Papatheodoridis, G. Pimenov, N. Prins, M. Puri, P. and Radke, S. Rakhmanova, A. Razavi, H. Razavi-Shearer, K. and Reesink, H. W. Ridruejo, E. Safadi, R. Sagalova, O. and Sanchez Avila, J. F. Sanduijav, R. Saraswat, V. Schreter, I. and Shah, S. R. Shevaldin, A. Shibolet, O. Silva, M. O. and Sokolov, S. Sonderup, M. Souliotis, K. Spearman, C. W. and Staub, T. Stedman, C. Strebkova, E. A. Struck, D. Sypsa, V. Tomasiewicz, K. Undram, L. van der Meer, A. J. van Santen, D. Veldhuijzen, I. Villamil, F. G. Willemse, S. and Zuckerman, E. Zuure, F. R. Prabdial-Sing, N. Flisiak, R. and Estes, C.

Abstract

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.

Published
2015

14. The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms

Author

Willemse, S. B., Razavi-Shearer, D., Zuure, F. R., Veldhuijzen, I. K., Croes, E. A., Meer, A. J., Santen, D. K., Vree, J. M., Robert De Knegt, Zaaijer, H. L., Reesink, H. W., Prins, M., Razavi, H., Gastroenterology and Hepatology, Other departments, Landsteiner Laboratory, Medical Microbiology and Infection Prevention, Infectious diseases, and Gastroenterology & Hepatology

Subjects
SDG 3 - Good Health and Well-being
Abstract

Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios. Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario. The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2. A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands

Published
2015

15. IP-10 in chronic hepatitis C patients treated with high-dose interferon

Author

Willemse, S. B., Reesink, H. W., Ladee, K., Karlas, J., Gelderblom, H. C., Molenkamp, R., Schinkel, J., Gastroenterology and Hepatology, Other departments, Medical Microbiology and Infection Prevention, and Amsterdam institute for Infection and Immunity

Abstract

Interferon-g-inducible protein-10 (IP-10) serum levels are associated with IL28B genotype and may predict response to interferon÷ribavirin-based therapy in chronic hepatitis C patients. Our aim was to relate IP-10 levels before and during treatment to treatment outcome, viral HCV-RNA kinetics and IL28B genotype. A cohort of chronic hepatitis C patients was treated with high-dose interferon for six weeks, followed by standard peginterferon÷ ribavirin for 24 or 48 weeks. IP-10 and HCV-RNA levels were frequently determined before, during and after treatment. IP-10 levels increased from log2.56 pg÷ml at baseline to log3.48 pg÷ml at Day 1 and gradually diminished thereafter. IP-10 levels at any time point were not statistically different between patients with or without sustained viral response (SVR). Patients with IL28B CC genotype had significantly lower baseline IP-10 levels (p = 0.019) and a higher increase of IP-10 levels from baseline to Day 1 than patients with IL28B non-CC genotypes (p = 0.015). Patients with HCV-RNA decline ≥ 2.28log10 at Day 1 had significantly lower baseline IP-10 levels (p = 0.016) and a higher increase of IP-10 levels from baseline to Day1 (p = 0.047) than patients with HCV-RNA decline of < 2.28log10 at Day 1. In patients treated with high induction dose interferon, IP-10 levels at any time point were not predictive for SVR. Low baseline IP-10 levels and a higher increase of IP-10 levels from baseline to Day 1 were associated with IL28B CC genotype and HCV-RNA decline ≥ 2.28log10 at Day 1. This suggests that, in our cohort, for prediction of SVR the added value of IP-10 to IL28B genotype and early viral kinetics is limited

Published
2014

16. Impurity profiling of trinitrotoluene using vacuum-outlet gas chromatography-mass spectrometry

Author

Brust, H., Willemse, S., Zeng, T., Asten, A. van, Koeberg, M., Heijden, A.E.D.M. van der, Bolck, A., Schoenmakers, P., Brust, H., Willemse, S., Zeng, T., Asten, A. van, Koeberg, M., Heijden, A.E.D.M. van der, Bolck, A., and Schoenmakers, P.

Abstract

In this work, a reliable and robust vacuum-outlet gas chromatography-mass spectrometry (GC-MS) method is introduced for the identification and quantification of impurities in trinitrotoluene (TNT). Vacuum-outlet GC-MS allows for short analysis times the analysis of impurities in TNT was performed in 4. min. This study shows that impurity profiling of TNT can be used to investigate relations between TNT samples encountered in forensic casework. A wide variety of TNT samples were analyzed with the developed method. Dinitrobenzene, dinitrotoluene, trinitrotoluene and amino-dinitrotoluene isomers were detected at very low levels (<1. wt.%) by applying the MS in selected-ion monitoring (SIM) mode. Limits of detection ranged from 6. ng/mL for 2,6-dinitrotoluene to 43. ng/mL for 4-amino-2,6-dinitrotoluene. Major impurities in TNT were 2,4-dinitrotoluene and 2,3,4-trinitrotoluene. Impurity profiles based on seven compounds showed to be useful to TNT samples from different sources. Statistical analysis of these impurity profiles using likelihood ratios demonstrated the potential to investigate whether two questioned TNT samples encountered in forensic casework are from the same source.

Published
2014

18. Liver stiffness improvement in hepatitis C patients after successful treatment.

Author

Brakenhoff SM, Verburgh ML, Willemse SB, Baak LC, Brinkman K, and van der Valk M

Subjects
Antiviral Agents therapeutic use, Humans, Liver diagnostic imaging, Liver pathology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis drug therapy, Retrospective Studies, Carcinoma, Hepatocellular, Hepatitis C, Chronic complications, Hepatitis C, Chronic drug therapy, Liver Neoplasms drug therapy
Abstract

Background: Successful treatment of chronic hepatitis C with direct-acting antiviral agents (DAAs) is expected to lead to improvement in liver fibrosis in most of the patients. However, limited data are available on the improvement of advanced liver fibrosis and cirrhosis, measured by transient elastography after treatment. This study assessed the change in liver stiffness measurements after successful treatment with DAAs in patients with pre-treatment advanced fibrosis or cirrhosis., Methods: This observational retrospective cohort study included 514 mono-infected chronic hepatitis C patients, treated with all possible DAA-regimes in the Amsterdam region, the Netherlands. Liver stiffness was measured using FibroScan® at baseline and during follow-up. Cut-off values for staging liver fibrosis were ≥ 9.5 kPa for advanced fibrosis (F3) and ≥ 14.6 kPa for cirrhosis (F4)., Results: Liver stiffness decreased significantly from a median of 15.6 kPa (IQR 11.4-25.4) to 9.4 kPa (IQR 6.2-17.0) in 197 patients with pre-treated advanced fibrosis or cirrhosis. In 50.3% of these patients, liver stiffness improved to a value fitting with mild to moderate fibrosis (< 9.5 kPa, F0-F2) after successful treatment. Multivariate analysis demonstrated that a pre-treatment FibroScan® value of ≥ 20.0 kPa was associated with persisting advanced fibrosis or cirrhosis after treatment (OR 29.07, p < 0.001)., Conclusion: Liver stiffness improves significantly after successful direct-acting antiviral agent treatment in chronic hepatitis C patients with advanced fibrosis or cirrhosis prior to DAA treatment. Long-term outcomes regarding occurrence of hepatocellular carcinoma (HCC) in these patients are required to determine whether they can be safely discharged from HCC surveillance.

Published
2020

19. Retrieval of chronic hepatitis C patients. A manifesto for action to eliminate hepatitis C in the Netherlands: the CELINE project.

Author

van Dijk M, Kracht PAM, Arends JE, Blokzijl H, Burger DM, van Erpecum KJ, van Hoek B, de Knegt RJ, Posthouwer D, Ramsoekh D, Rijnders BJA, Schinkel J, Willemse SB, van der Valk M, Drenth JPH, and Behalf Of The HepNed Study Group O

Subjects
Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy, Humans, Netherlands epidemiology, Prevalence, Disease Eradication methods, Epidemics, Hepatitis C, Chronic epidemiology, Hepatitis C, Chronic prevention & control, Mass Screening methods
Abstract

Chronic hepatitis C virus (HCV) infection is a global public health issue, which is associated with high rates of morbidity and mortality. The development of direct acting antivirals (DAAs) has transformed treatment: they offer us highly-effective therapy with superior tolerability compared to interferon-containing regimens. In 2016, the World Health Organization (WHO) therefore adopted several ambitious viral hepatitis elimination targets, aiming for a 90% reduction in new infections and a 65% reduction in mortality by 2030. The ultimate goal is to eliminate HCV completely. It is reasonable that these goals may be achieved in the Netherlands due to the low prevalence of chronic HCV, the availability of DAAs, and excellent healthcare infrastructure. This paper describes a national effort to curtail the HCV epidemic in the Netherlands through an HCV retrieval and linkage to care project (CELINE: Hepatitis C Elimination in the Netherlands).

Published
2019

20. In-hospital prescription changes and documentation in the medical records of the primary care provider: results from a medical record review study.

Author

Poldervaart JM, van Melle MA, Willemse S, de Wit NJ, and Zwart DLM

Subjects
Adult, Aged, Female, Humans, Male, Medical Audit, Middle Aged, Netherlands, Reproducibility of Results, Inpatients, Medical Records, Medication Therapy Management, Pharmacy Service, Hospital, Primary Health Care
Abstract

Background: An increasing number of transitions due to substitution of care of more complex patients urges insight in and improvement of transitional medication safety. While lack of documentation of prescription changes and/or lack of information exchange between settings likely cause adverse drug events, frequency of occurrence of these causes is not clear. Therefore, we aimed at determining the frequency of in-hospital patients’ prescription changes that are not or incorrectly documented in their primary care provider’s (PCP) medical record., Methods: A medical record review study was performed in a database linking patients’ medical records of hospital and PCP. A random sample (n = 600) was drawn from all 1399 patients who were registered at a participating primary care practice as well as the gastroenterology or cardiology department in 2013 of the University Medical Center Utrecht, the Netherlands. Outcomes were the number of in-hospital prescription changes that was not or incorrectly documented in the medical record of the PCP, and timeliness of documentation., Results: Records of 390 patients included one or more primary-secondary care transitions; in total we identified 1511 transitions. During these transitions, 408 in-hospital prescription changes were made, of which 31% was not or incorrectly documented in the medical record of the PCP within the next 3 months. In case changes were documented, the median number of days between hospital visit and documentation was 3 (IQR 0–18)., Conclusions: One third of in-hospital prescription changes was not or incorrectly documented in the PCP’s record, which likely puts patients at risk of adverse drug events after hospital visits. Such flawed reliability of a routine care process is unacceptable and warrants improvement and close monitoring.

Published
2017
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21. The estimated future disease burden of hepatitis C virus in the Netherlands with different treatment paradigms.

Author

Willemse SB, Razavi-Shearer D, Zuure FR, Veldhuijzen IK, Croes EA, van der Meer AJ, van Santen DK, de Vree JM, de Knegt RJ, Zaaijer HL, Reesink HW, Prins M, and Razavi H

Subjects
Adolescent, Adult, Aged, Cost of Illness, Disease Progression, Female, Hepatitis C drug therapy, Hepatitis C prevention & control, Hepatitis C, Chronic drug therapy, Hepatitis C, Chronic epidemiology, Hepatitis C, Chronic prevention & control, Humans, Male, Middle Aged, Models, Statistical, Monte Carlo Method, Netherlands, Prevalence, Treatment Outcome, Young Adult, Antiviral Agents therapeutic use, Hepatitis C epidemiology
Abstract

Background & Aims: Prevalence of hepatitis C virus (HCV) infection in the Netherlands is low (anti-HCV prevalence 0.22%). All-oral treatment with direct-acting antivirals (DAAs) is tolerable and effective but expensive. Our analysis projected the future HCV-related disease burden in the Netherlands by applying different treatment scenarios., Methods: Using a modelling approach, the size of the HCV-viraemic population in the Netherlands in 2014 was estimated using available data and expert consensus. The base scenario (based on the current Dutch situation) and different treatment scenarios (with increased efficacy, treatment uptake, and diagnoses) were modelled and the future HCV disease burden was predicted for each scenario., Results: The estimated number of individuals with viraemic HCV infection in the Netherlands in 2014 was 19,200 (prevalence 0.12%). By 2030, this number is projected to decrease by 4 5% in the base scenario and by 85% if the number of treated patients increases. Furthermore, the number of individuals with hepatocellular carcinoma and liver-related deaths is estimated to decrease by 19% and 27%, respectively, in the base scenario, but may both be further decreased by 68% when focusing on treatment of HCV patients with a fibrosis stage of ≥ F2., Conclusions: A substantial reduction in HCV-related disease burden is possible with increases in treatment uptake as the efficacy of current therapies is high. Further reduction of HCV-related disease burden may be achieved through increases in diagnosis and preventative measures. These results might inform the further development of effective disease management strategies in the Netherlands.

Published
2015

22. IP-10 in chronic hepatitis C patients treated with high-dose interferon.

Author

Willemse SB, Reesink HW, Ladee K, Karlas J, Gelderblom HC, Molenkamp R, and Schinkel J

Subjects
Adult, Aged, Cohort Studies, Drug Therapy, Combination, Female, Genotype, Hepatitis C, Chronic genetics, Humans, Interferons administration & dosage, Male, Middle Aged, Treatment Outcome, Viral Load, Young Adult, Chemokine CXCL10 blood, Hepatitis C, Chronic drug therapy, Interferons therapeutic use, Interleukins genetics, RNA, Viral blood
Abstract

Introduction: Interferon-g-inducible protein-10 (IP-10) serum levels are associated with IL28B genotype and may predict response to interferon÷ribavirin-based therapy in chronic hepatitis C patients. Our aim was to relate IP-10 levels before and during treatment to treatment outcome, viral HCV-RNA kinetics and IL28B genotype., Patients and Methods: A cohort of chronic hepatitis C patients was treated with high-dose interferon for six weeks, followed by standard peginterferon÷ ribavirin for 24 or 48 weeks. IP-10 and HCV-RNA levels were frequently determined before, during and after treatment., Results: IP-10 levels increased from log2.56 pg÷ml at baseline to log3.48 pg÷ml at Day 1 and gradually diminished thereafter. IP-10 levels at any time point were not statistically different between patients with or without sustained viral response (SVR). Patients with IL28B CC genotype had significantly lower baseline IP-10 levels (p = 0.019) and a higher increase of IP-10 levels from baseline to Day 1 than patients with IL28B non-CC genotypes (p = 0.015). Patients with HCV-RNA decline &#8805; 2.28log10 at Day 1 had significantly lower baseline IP-10 levels (p = 0.016) and a higher increase of IP-10 levels from baseline to Day1 (p = 0.047) than patients with HCV-RNA decline of < 2.28log10 at Day 1., Conclusions: In patients treated with high induction dose interferon, IP-10 levels at any time point were not predictive for SVR. Low baseline IP-10 levels and a higher increase of IP-10 levels from baseline to Day 1 were associated with IL28B CC genotype and HCV-RNA decline &#8805; 2.28log10 at Day 1. This suggests that, in our cohort, for prediction of SVR the added value of IP-10 to IL28B genotype and early viral kinetics is limited.

Published
2014

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