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Duberg, Ann-Sofi, DocentORCID iD iconorcid.org/0000-0001-7248-0910
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Publications (10 of 47) Show all publications
Kjellin, M., Kileng, H., Akaberi, D., Palanisamy, N., Duberg, A.-S., Danielsson, A., . . . Lennerstrand, J. (2019). Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway. Scandinavian Journal of Gastroenterology
Open this publication in new window or tab >>Effect of the baseline Y93H resistance-associated substitution in HCV genotype 3 for direct-acting antiviral treatment: real-life experience from a multicenter study in Sweden and Norway
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5-10%) at baseline in direct-acting antiviral agents (DAA) treatment-naive genotype (GT) 3a patients when studied by the population-sequencing method (cut-off 20%). This RAS may impair HCV DAA treatment response, since it possesses a high fold in vitro resistance to daclatasvir (DCV) and velpatasvir (VEL) in GT 3. We investigated the effect of baseline Y93H in patients with GT 3a infection on treatment outcome, with or without resistance-based DAA-treatment during 2014-2017.

Patients/Methods: Treatment in the intervention group (n = 130) was tailored to baseline resistance-findings by population-sequencing method. Detection of baseline Y93H above 20% prompted a prolonged treatment duration of NS5A-inhibitor and sofosbuvir (SOF) and/or addition of ribavirin (RBV). Patients without baseline Y93H in the intervention group and all patients in the control group (n = 78) received recommended standard DAA-treatment.

Results: A higher sustained virologic response rate (SVR) in the intervention group was shown compared to the control group at 95.4% (124/130) and 88.5% (69/78), respectively (p = .06). All five patients with baseline Y93H in the intervention group achieved SVR with personalised treatment based on results from resistance testing; either with the addition of RBV or prolonged treatment duration (24w). In the control group, 2/4 patients with Y93H at baseline treated with ledipasvir/SOF/RBV or DCV/SOF without RBV, failed treatment.

Conclusion: The results from this real-life study are in accordance with the findings of the randomised controlled trials in 2015 and the EASL-guidelines of 2016, thus, baseline Y93H impacts on DCV and VEL treatment outcome.

Place, publisher, year, edition, pages
Taylor & Francis, 2019
Keywords
Baseline resistance, NS5A, Y93H, hepatitis C virus, resistance-associated substitution, sustained virologic response
National Category
Infectious Medicine Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-75912 (URN)10.1080/00365521.2019.1652846 (DOI)000481902500001 ()31424972 (PubMedID)
Note

Funding Agencies:

Uppsala-Örebro Regional Research Council  RFR-651021  RFR-744511 

Erik, Karin and Gösta Selander Foundation  

Scandinavian Society for Antimicrobial Chemotherapy  SLS-692951 

Uppsala County Council  

Uppsala University 

Available from: 2019-08-26 Created: 2019-08-26 Last updated: 2019-09-04Bibliographically approved
Simon, T. G., Duberg, A.-S., Aleman, S., Hagström, H., Nguyen, L. H., Khalili, H., . . . Ludvigsson, J. F. (2019). Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Annals of Internal Medicine, 171(5), 318-327
Open this publication in new window or tab >>Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population
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2019 (English)In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 171, no 5, p. 318-327Article in journal (Refereed) Published
Abstract [en]

Background: Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.

Objective: To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.

Design: Prospective propensity score (PS)-matched cohort.

Setting: Swedish registers, 2005 to 2013.

Participants: A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults.

Measurements: Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).

Results: Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The in- verse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -62 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users.

Limitation: Lack of lipid, fibrosis, or HCC surveillance data.

Conclusion: In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.

Place, publisher, year, edition, pages
American College of Physicians, 2019
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-76548 (URN)10.7326/M18-2753 (DOI)000484610900004 ()31426090 (PubMedID)2-s2.0-85072077551 (Scopus ID)
Funder
Stockholm County Council
Note

Funding Agencies:

North American Training Grant from the American College of Gastroenterology  

Research ALF grant from Region Örebro County  OLL-683801 

National Institutes of Health  K23 DK099681  K24 DK078772

Available from: 2019-09-20 Created: 2019-09-20 Last updated: 2019-09-20Bibliographically approved
Lybeck, C., Brenndörfer, E. D., Sällberg, M., Montgomery, S., Aleman, S. & Duberg, A.-S. (2019). Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients. European Journal of Gastroenterology and Hepathology, 31(4), 506-513
Open this publication in new window or tab >>Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
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2019 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 31, no 4, p. 506-513Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Curing hepatitis C virus (HCV) infection primarily aims to prevent severe liver complications. Our objectives were to investigate the long-term presence and impact of occult HCV infection (OCI) and to study the outcomes in terms of liver disease after virological cure.

PATIENTS AND METHODS: A total of 97 patients with achieved sustained virological response (SVR) during 1990-2005 were followed either by a clinical follow-up (FU) visit with blood sampling and liver elastography (n=54) or through national registries for outcomes (n=43). To diagnose OCI among patients with SVR, a highly sensitive method was used to detect HCV-RNA traces in whole blood. The FU duration was a median of 10.5 years, with samples up to 21.5 years after the end of treatment (EOT).

RESULTS: The majority of patients [52 (96%)] were HCV-RNA negative at FU, and regression of fibrosis was statistically significant. OCI was found in two (4%) of them at 8 and 9 years after EOT. These patients had F1 and F2 fibrosis before treatment and F2 at FU, but no other abnormal findings. Three previously noncirrhotic men were diagnosed with hepatocellular carcinoma 8-11 years after EOT.

CONCLUSION: Occult infection could be detected many years after the achievement of SVR but was not associated with the serious liver disease. The majority had persistent viral eradication and regression of fibrosis after SVR. However, an increased risk of hepatocellular carcinoma may persist in the long term after SVR even in noncirrhotic patients. Further studies with FU after direct-acting antiviral therapy and on the long-term impact after cure are needed.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2019
Keywords
chronic hepatitis C, long-term follow-up, sustained virological response
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-70277 (URN)10.1097/MEG.0000000000001316 (DOI)000480690600014 ()30461522 (PubMedID)2-s2.0-85060762793 (Scopus ID)
Funder
Stockholm County CouncilSwedish Research CouncilSwedish Cancer Society
Note

Funding Agency:

Research Committee of Region Örebro County Council  OLL-522501  OLL-590001

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-08-29Bibliographically approved
Safreed-Harmon, K., Blach, S., Aleman, S., Boe Kielland, K., Bollerup, S., Cooke, G., . . . Lazarus, J. V. (2019). The Consensus Hepatitis C Cascade of Care: standardized reporting to monitor progress toward elimination. Clinical Infectious Diseases, Article ID ciz714.
Open this publication in new window or tab >>The Consensus Hepatitis C Cascade of Care: standardized reporting to monitor progress toward elimination
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2019 (English)In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, article id ciz714Article in journal (Refereed) Epub ahead of print
Abstract [en]

Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO's 2030 hepatitis C elimination targets.

Place, publisher, year, edition, pages
University of Chicago Press, 2019
Keywords
Hepatitis C virus, cascade of care, disease elimination, monitoring, policy
National Category
Infectious Medicine
Identifiers
urn:nbn:se:oru:diva-75567 (URN)10.1093/cid/ciz714 (DOI)31352481 (PubMedID)
Available from: 2019-08-09 Created: 2019-08-09 Last updated: 2019-08-09Bibliographically approved
Lybeck, C., Bruce, D., Montgomery, S., Aleman, S. & Duberg, A.-S. (2018). A national study of risk for non-liver cancer in people with hepatitis C treated with direct acting antivirals or an interferon-based regimen. Paper presented at International Liver Congress (ILC), Paris, France, April 11-15, 2018. Journal of Hepatology, 68(Suppl. 1), S263-S264
Open this publication in new window or tab >>A national study of risk for non-liver cancer in people with hepatitis C treated with direct acting antivirals or an interferon-based regimen
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2018 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 68, no Suppl. 1, p. S263-S264Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background and Aims: Direct acting antivirals (DAA) against hepatitis C virus (HCV) have been shown to have an immune modulatory effect, with a possibly decreased tumour specific CD8 T cell response. Reports indicative of a high risk for hepatocellular carcinoma or advanced tumours early after DAA treatment, have raised concerns about whether the risk for non-liver cancer could be increased. Therefore, our aim was to study the early incidence of non-liver cancer after initiation of DAA or interferon (IFN-based) therapy in a national HCV cohort.

Method: All diagnosed HCV-infected persons in Sweden, their antiviral treatments, non-liver cancer or death/emigration were identified retrospectively, using the national HCV-surveillance register and other national registers. Cox regression was used to compare persons treated with DAAs (n = 1,920), IFN-based therapy(n = 2,586) or no HCV therapy (n = 13,872) between 2009 and 2015. Persons with a previous cancer diagnosis (5.7%) were studied separately. Age was used as the time-scale, and the analyses were stratified by sex and adjusted for the Charlson comorbidity index.

Results: In total 492 non-liver cancers were diagnosed, with 222 among persons with no previous cancer and 270 new cancer diagnoses among those with previous cancer. Among persons with no previous cancer, 21, 24 and 177 developed non-liver cancer following DAA, IFN-based and no treatment, respectively. The corresponding numbers for those with previous cancer were 25, 20 and 225, respectively. The hazard ratios (and 95% confidence intervals) for non-liver cancer in the no previous cancer group are 1.35 (0.66–2.76; p = 0.41) for men and 1.75 (0.59–5.18; p = 0.31) for women with DAA treatment, compared with IFN treatment. For those with previous cancer, the corresponding hazard ratios are 1.03 (0.41–2.57; p = 0.95) for men and 0.86 (0.35–2.13; p = 0.75) for women with DAA treatment.

Conclusion: This study did not demonstrate any significantly increased risk for non-liver cancer early after DAA therapy initiation. The hazard ratio was slightly increased among those with outprevious cancer, but the cancers were few and the results were not statistically significant. Further studies with higher numbers of DAA treated patients and longer follow-up are needed to fully explore thisissue.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Gastroenterology and Hepatology Cancer and Oncology
Identifiers
urn:nbn:se:oru:diva-71319 (URN)10.1016/S0168-8278(18)30740-2 (DOI)000461068601132 ()
Conference
International Liver Congress (ILC), Paris, France, April 11-15, 2018
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-03-26Bibliographically approved
Leblebicioglu, H., Arends, J. E., Ozaras, R., Corti, G., Santos, L., Boesecke, C., . . . Salmon, D. (2018). Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries. Antiviral Research, 150, 9-14
Open this publication in new window or tab >>Availability of hepatitis C diagnostics and therapeutics in European and Eurasia countries
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2018 (English)In: Antiviral Research, ISSN 0166-3542, E-ISSN 1872-9096, Vol. 150, p. 9-14Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Treatment with direct acting antiviral agents (DAAs) has provided sustained virological response rates in >95% of patients with chronic hepatitis C virus (HCV) infection. However treatment is costly and market access, reimbursement and governmental restrictions differ among countries. We aimed to analyze these differences among European and Eurasian countries.

METHODS: A survey including 20-item questionnaire was sent to experts in viral hepatitis. Countries were evaluated according to their income categories by the World Bank stratification.

RESULTS: Experts from 26 countries responded to the survey. As of May 2016, HCV prevalence was reported as low (≤1%) in Croatia, Czech Republic, Denmark, France, Germany, Hungary, the Netherlands, Portugal, Slovenia, Spain, Sweden, UK; intermediate (1-4%) in Azerbaijan, Bosnia and Herzegovina, Italy, Kosovo, Greece, Kazakhstan, Romania, Russia, Serbia and high in Georgia (6.7%). All countries had national guidelines except Albania, Kosovo, Serbia, Tunisia, and UK. Transient elastography was available in all countries, but reimbursed in 61%. HCV-RNA was reimbursed in 81%. PegIFN/RBV was reimbursed in 54% of the countries. No DAAs were available in four countries: Kazakhstan, Kosovo, Serbia, and Tunisia. In others, at least one DAA combination with either PegIFN/RBV or another DAA was available. In Germany and the Netherlands all DAAs were reimbursed without restrictions: Sofosbuvir and sofosbuvir/ledipasvir were free of charge in Georgia.

CONCLUSION: Prevalence of HCV is relatively higher in lower-middle and upper-middle income countries. DAAs are not available or reimbursed in many Eurasia and European countries. Effective screening and access to care are essential for reducing liver-related morbidity and mortality.

Place, publisher, year, edition, pages
Amsterdam, Netherlands: Elsevier, 2018
Keywords
Availability of hepatitis C diagnostics, Therapeutics in European and Eurasia countries
National Category
Infectious Medicine Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-63296 (URN)10.1016/j.antiviral.2017.12.001 (DOI)000425078700002 ()29217468 (PubMedID)2-s2.0-85037670440 (Scopus ID)
Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2018-08-16Bibliographically approved
Polaris Observatory, C. (2018). Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study. The Lancet Gastroenterology & Hepatology, 3(6), 383-403
Open this publication in new window or tab >>Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study
2018 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 3, no 6, p. 383-403Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate viral hepatitis by 2030. Although no virological cure exists for hepatitis B virus (HBV) infection, existing therapies to control viral replication and prophylaxis to minimise mother-to-child transmission make elimination of HBV feasible. We aimed to estimate the national, regional, and global prevalence of HBsAg in the general population and in the population aged 5 years in 2016, as well as coverage of prophylaxis, diagnosis, and treatment.

METHODS: In this modelling study, we used a Delphi process that included a literature review in PubMed and Embase, followed by interviews with experts, to quantify the historical epidemiology of HBV infection. We then used a dynamic HBV transmission and progression model to estimate the country-level and regional-level prevalence of HBsAg in 2016 and the effect of prophylaxis and treatment on disease burden.

FINDINGS: We developed models for 120 countries, 78 of which were populated with data approved by experts. Using these models, we estimated that the global prevalence of HBsAg in 2016 was 3·9% (95% uncertainty interval [UI] 3·4-4·6), corresponding to 291 992 000 (251 513 000-341 114 000) infections. Of these infections, around 29 million (10%) were diagnosed, and only 4·8 million (5%) of 94 million individuals eligible for treatment actually received antiviral therapy. Around 1·8 (1·6-2·2) million infections were in children aged 5 years, with a prevalence of 1·4% (1·2-1·6). We estimated that 87% of infants had received the three-dose HBV vaccination in the first year of life, 46% had received timely birth-dose vaccination, and 13% had received hepatitis B immunoglobulin along with the full vaccination regimen. Less than 1% of mothers with a high viral load had received antiviral therapy to reduce mother-to-child transmission.

INTERPRETATION: Our estimate of HBV prevalence in 2016 differs from previous studies, potentially because we took into account the effect of infant prophylaxis and early childhood vaccination, as well as changing prevalence over time. Although some regions are well on their way to meeting prophylaxis and prevalence targets, all regions must substantially scale-up access to diagnosis and treatment to meet the global targets.

Place, publisher, year, edition, pages
Elsevier, 2018
National Category
Clinical Medicine Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-70512 (URN)10.1016/S2468-1253(18)30056-6 (DOI)000436553600019 ()29599078 (PubMedID)2-s2.0-85044540918 (Scopus ID)
Note

Funding Agency:

John C Martin Foundation

Available from: 2018-12-05 Created: 2018-12-05 Last updated: 2018-12-05Bibliographically approved
Simon, T. G., Duberg, A.-S., Aleman, S., Hagström, H., Chung, R. T. & Ludvigsson, J. F. (2018). Lipophilic Statins and Risk of Hepatocellular Carcinoma and Mortality: A Prospective, Nationwide Population with Chronic Viral Hepatitis. Paper presented at Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, San Francisco, CA, USA, November 9-13, 2018. Hepatology, 68(Suppl.1), 59A-60A
Open this publication in new window or tab >>Lipophilic Statins and Risk of Hepatocellular Carcinoma and Mortality: A Prospective, Nationwide Population with Chronic Viral Hepatitis
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2018 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, no Suppl.1, p. 59A-60AArticle in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-69540 (URN)000446020500094 ()
Conference
Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, San Francisco, CA, USA, November 9-13, 2018
Note

Funding Agencies:

AbbVie  

GIlead 

Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2019-01-09Bibliographically approved
Kamal, H., Falconer, K., Westman, G., Duberg, A.-S., Weiland, O. R. H., Wejstal, R., . . . Aleman, S. (2018). Long-Term Liver-Related Outcomes in Hepatitis B and D Co-Infected Patients in Sweden. Paper presented at Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, San Francisco, CA, USA, November 9-13, 2018. Hepatology, 68(Suppl.1), 1190A-1191A
Open this publication in new window or tab >>Long-Term Liver-Related Outcomes in Hepatitis B and D Co-Infected Patients in Sweden
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2018 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 68, no Suppl.1, p. 1190A-1191AArticle in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-69541 (URN)000446020503316 ()
Conference
Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, San Francisco, CA, USA, November 9-13, 2018
Note

Funding Agencies:

Gilead Sciences  

AbbVie  

Abbott  

BMS  

Gilead

Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2019-01-09Bibliographically approved
Kileng, H., Kjellin, M., Akaberi, D., Bergfors, A., Duberg, A.-S., Wesslén, L., . . . Lennerstrand, J. (2018). Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy. Scandinavian Journal of Gastroenterology, 53(10-11), 1347-1353
Open this publication in new window or tab >>Personalized treatment of hepatitis C genotype 1a in Norway and Sweden 2014-2016: a study of treatment outcome in patients with or without resistance-based DAA-therapy
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 10-11, p. 1347-1353Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Resistance-associated substitutions (RASs) may impair treatment response to direct-acting antivirals (DAA) in hepatitis C virus (HCV) treatment. We investigated the effects of baseline NS3-RASs (Q80K and R155K) and clinically relevant NS5A-RASs in patients with HCV genotype (GT) 1a infection on treatment outcome, with or without resistance-based DAA-treatment. This multi-center study was carried out between 2014 and 2016.

PATIENTS/METHODS: Treatment in the intervention group (n = 92) was tailored to baseline resistance. Detection of NS3-RAS led to an NS5A-inhibitor-based regimen and detection of NS5A-RAS to a protease-inhibitor regimen. Patients without baseline RAS in the intervention group and all patients in the control group (n = 101) received recommended standard DAA-treatment.

RESULTS: The sustained virologic response rates (SVR) in the intervention and control groups were 97.8% (90/92) and 93.1% (94/101), respectively (p = .174). A trend toward higher SVR-rate in cirrhotic patients (p = .058) was noticed in the intervention group compared to the control group with SVR-rates 97.5% (39/40) and 83.3% (35/42), respectively. All patients with baseline NS3 (Q80K/R155K) or NS5A-RASs in the intervention group achieved SVR with personalized resistance-based treatment. In the control group, five patients with Q80K or R155K at baseline were treated with simeprevir + sofosbuvir and treatment failed in two of them. Furthermore, one of three patients who failed ledipasvir + sofosbuvir treatment had NS5A-RASs at baseline.

CONCLUSIONS: In line with the findings of the OPTIMIST-2 trial for Q80K and the EASL-guidelines 2016 for NS5A-RASs, baseline RASs appeared to have an impact on treatment outcome albeit a statistical significance was not observed in this low-prevalence population.

Place, publisher, year, edition, pages
Taylor & Francis, 2018
Keywords
Baseline resistance, NS5A, Q80K, hepatitis C virus, resistance-associated substitution, sustained virologic response
National Category
Infectious Medicine Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-70125 (URN)10.1080/00365521.2018.1511824 (DOI)000457980900029 ()30394152 (PubMedID)2-s2.0-85056168923 (Scopus ID)
Note

Funding Agencies:

Uppsala-Örebro Regional Research Council  

Selander Foundation  

Scandinavian Society for Antimicrobial Chemotherapy  

Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2019-02-25Bibliographically approved
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Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7248-0910

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