20 results on '"Madsen, Lone G."'
Search Results
2. Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark
- Author
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Bollerup, Signe, Hallager, Sofie, Engsig, Frederik, Mocroft, Amanda, Krarup, Henrik, Madsen, Lone G., Thielsen, Peter, Balslev, Ulla, Mens, Helene, Barfod, Toke S., Clausen, Mette R., Hobolth, Lise, Laursen, Alex L., Tarp, Britta, Roege, Birgit T., Hansen, Jesper B., Mygind, Lone, Christensen, Peer B., Gerstoft, Jan, Weis, Nina, Bollerup, Signe, Hallager, Sofie, Engsig, Frederik, Mocroft, Amanda, Krarup, Henrik, Madsen, Lone G., Thielsen, Peter, Balslev, Ulla, Mens, Helene, Barfod, Toke S., Clausen, Mette R., Hobolth, Lise, Laursen, Alex L., Tarp, Britta, Roege, Birgit T., Hansen, Jesper B., Mygind, Lone, Christensen, Peer B., Gerstoft, Jan, and Weis, Nina
- Abstract
The study aimed to determine adjusted all-cause mortality and cause of death in persons with chronic hepatitis B virus (HBV) infection compared with age- and sex-matched persons from the general population. We used nationwide registers to identify persons aged >= 18 years with chronic HBV infection in 2002-2017 in Denmark and included 10 age- and sex-matched controls for each. Follow-up was from 6 months after diagnosis until death, emigration, or 31 December 2017. Mortality rate ratios (MRRs) adjusted for age, sex, employment, origin and comorbidity were calculated using Poisson regression. Unadjusted cause-specific mortality rate ratios with 95% confidence intervals were calculated assuming a Poisson distribution. A total of 6988 persons with chronic HBV infection and 69,847 controls were included. During a median follow-up of 7.7 years (range 0.0-15.5), 315 (5%) persons with-and 1525 (2%) without-chronic HBV infection died. The adjusted all-cause MRR was 1.5 (95% CI 1.2-2.0). Persons with chronic HBV infection had increased mortality due to liver disease including hepatocellular carcinoma (MRR 12.3 [8.6-17.7]), external causes (MRR 3.3 [2.5-4.7]), endocrine disease (MRR 3.2 [1.8-5.4]), genitourinary disease (MRR 3.2 [1.2-7.6]) and neoplasms (except hepatocellular carcinoma; MRR 1.6 [1.2-2.0]). In conclusion, this study showed an increased all-cause mortality in persons with chronic HBV infection in comparison with age- and sex-matched persons without chronic HBV infection which remained after adjustment for several confounding factors. Excess mortality was mainly associated with liver disease, but also external factors, endocrine disease, genitourinary disease and neoplasms (excluding hepatocellular carcinoma).
- Published
- 2022
3. Incidence of Hepatocellular Carcinoma and Decompensated Liver Cirrhosis and Prognostic Accuracy of the PAGE-B HCC Risk Score in a Low Endemic Hepatitis B Virus Infected Population
- Author
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Bollerup, Signe, Engsig, Frederik, Hallager, Sofie, Mocroft, Amanda, Roege, Birgit T., Christensen, Peer B., Laursen, Alex L., Krarup, Henrik, Clausen, Mette R., Thielsen, Peter, Madsen, Lone G., Noerregaard, Lars, Barfod, Toke S., Balslev, Ulla, Tarp, Britta, Hansen, Jesper B., Mygind, Lone H., Gerstoft, Jan, Weis, Nina, Bollerup, Signe, Engsig, Frederik, Hallager, Sofie, Mocroft, Amanda, Roege, Birgit T., Christensen, Peer B., Laursen, Alex L., Krarup, Henrik, Clausen, Mette R., Thielsen, Peter, Madsen, Lone G., Noerregaard, Lars, Barfod, Toke S., Balslev, Ulla, Tarp, Britta, Hansen, Jesper B., Mygind, Lone H., Gerstoft, Jan, and Weis, Nina
- Abstract
Purpose: We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods: In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results: Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring 17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion: We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.
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- 2022
4. Mortality and cause of death in persons with chronic hepatitis B virus infection versus healthy persons from the general population in Denmark
- Author
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Bollerup, Signe, primary, Hallager, Sofie, additional, Engsig, Frederik, additional, Mocroft, Amanda, additional, Krarup, Henrik, additional, Madsen, Lone G., additional, Thielsen, Peter, additional, Balslev, Ulla, additional, Mens, Helene, additional, Barfod, Toke S., additional, Clausen, Mette R., additional, Hobolth, Lise, additional, Laursen, Alex L., additional, Tarp, Britta, additional, Roege, Birgit T., additional, Hansen, Jesper B., additional, Mygind, Lone, additional, Christensen, Peer B., additional, Gerstoft, Jan, additional, and Weis, Nina, additional
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- 2022
- Full Text
- View/download PDF
5. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome
- Author
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Fahnøe, Ulrik, Pedersen, Martin S., Sølund, Christina, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Thielsen, Peter, Madsen, Lone G., Pedersen, Anders G., Schønning, Kristian, Weis, Nina, Bukh, Jens, Fahnøe, Ulrik, Pedersen, Martin S., Sølund, Christina, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Thielsen, Peter, Madsen, Lone G., Pedersen, Anders G., Schønning, Kristian, Weis, Nina, and Bukh, Jens
- Abstract
Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p =.0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs.
- Published
- 2021
6. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non‐target sites, for DAA‐based treatment and retreatment outcome
- Author
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Fahnøe, Ulrik, primary, Pedersen, Martin S., additional, Sølund, Christina, additional, Ernst, Anja, additional, Krarup, Henrik B., additional, Røge, Birgit T., additional, Christensen, Peer B., additional, Laursen, Alex L., additional, Gerstoft, Jan, additional, Thielsen, Peter, additional, Madsen, Lone G., additional, Pedersen, Anders G., additional, Schønning, Kristian, additional, Weis, Nina, additional, and Bukh, Jens, additional
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- 2020
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7. Opioid treatment of painful chronic pancreatitis: Transdermal fentanyl versus sustained-release morphine
- Author
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Niemann, Troels, Madsen, Lone G., Larsen, Steen, and Thorsgaard, Niels
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- 2000
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8. Menetrier's Disease and Helicobacter pylori (Normalization of Gastrointestinal Protein Loss After Eradication Therapy)
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Madsen, Lone G., Taskiran, Mustafa, Madsen, Jan Lysgard, and Bytzer, Peter
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- 1999
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9. Direct acting antiviral treatment of chronic hepatitis C in Denmark:factors associated with and barriers to treatment initiation
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Sølund, Christina, Hallager, Sofie, Pedersen, Martin S, Fahnøe, Ulrik, Ernst, Anja, Krarup, Henrik B, Røge, Birgit T, Christensen, Peer B, Laursen, Alex L, Gerstoft, Jan, Bélard, Erika, Madsen, Lone G, Schønning, Kristian, Pedersen, Anders G, Bukh, Jens, Weis, Nina, Krarup, Henrik, Hansen, Jesper Bach, and Mygind, Lone
- Subjects
hepatitis C virus ,Liver Cirrhosis ,Male ,Sustained Virologic Response ,Denmark ,Hepacivirus ,Liver Cirrhosis/epidemiology ,medicine.disease_cause ,Cohort Studies ,Liver disease ,0302 clinical medicine ,Fibrosis ,Risk Factors ,030212 general & internal medicine ,Treatment Failure ,Antiviral Agents/therapeutic use ,biology ,Gastroenterology ,Middle Aged ,factors associated with treatment ,Hepatitis C, Chronic/complications ,HCV ,Practice Guidelines as Topic ,030211 gastroenterology & hepatology ,Female ,liver disease ,Liver cancer ,Direct acting ,treatment initiation ,Cohort study ,Adult ,medicine.medical_specialty ,Hepatitis C virus ,Hepacivirus/genetics ,Antiviral Agents ,Drug Administration Schedule ,liver cancer ,03 medical and health sciences ,Chronic hepatitis ,Direct Acting Antivirals ,Internal medicine ,medicine ,Humans ,DAA ,business.industry ,Hepatitis C, Chronic ,medicine.disease ,biology.organism_classification ,Denmark/epidemiology ,barriers to treatment ,Logistic Models ,Patient Compliance ,business - Abstract
OBJECTIVES: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark.MATERIALS AND METHODS: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause.RESULTS: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91).CONCLUSIONS: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment.
- Published
- 2018
10. Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark:a nationwide cohort study
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Hallager, Sofie, Ladelund, Steen, Kjaer, Mette S, Madsen, Lone G, Belard, Erika, Laursen, Alex Lund, Gerstoft, Jan, Røge, Birgit T, Grønbaek, Karin E, Krarup, Henrik B, Christensen, Peer B, Weis, Nina, Hallager, Sofie, Ladelund, Steen, Kjaer, Mette S, Madsen, Lone G, Belard, Erika, Laursen, Alex Lund, Gerstoft, Jan, Røge, Birgit T, Grønbaek, Karin E, Krarup, Henrik B, Christensen, Peer B, and Weis, Nina
- Abstract
Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC) and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C and data from national health registries and patient charts were obtained. Tumor stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size and number of lesions combined into stage 0 - 3. We included 1,075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4,988 person years (PY) 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4 - 1.5] in 2002-2003 to 2.9/100 PY [2.4 - 3.4] in 2012-2013. One-year cumulative incidence of at least one AFP or US was 53% among all patients. The positive predictive value of an AFP ≥ 20 ng mL(-1) was 17%. Twenty-three (21%) patients were diagnosed with early stage HCC (stage 0/1) and 84 (79%) with late stage. Median survival after HCC for early stage HCC disease was 30.1 months and 7.4 months for advanced HCC (stage 2/3). The incidence rate of HCC increased over time among patients with hepatitis C and cirrhosis in Denmark. Application of AFP and US was suboptimal and most patients were diagnosed with advanced HCC with a poor prognosis. This article is protected by copyright. All rights reserved.
- Published
- 2018
11. Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections-A Scandinavian real-life study
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Dalgard, Olav, Weiland, Ola, Noraberg, Geir, Karlsen, Lars, Heggelund, Lars, Färkkilâ, Martti, Balslev, Ulla, Belard, Erika, Øvrehus, Anne, Skalshøi Kjær, Mette, Krarup, Henrik, Thorup Røge, Birgit, Hallager, Sofie, Madsen, Lone G, Lund Laursen, Alex, Lagging, Martin, Weis, Nina, Dalgard, Olav, Weiland, Ola, Noraberg, Geir, Karlsen, Lars, Heggelund, Lars, Färkkilâ, Martti, Balslev, Ulla, Belard, Erika, Øvrehus, Anne, Skalshøi Kjær, Mette, Krarup, Henrik, Thorup Røge, Birgit, Hallager, Sofie, Madsen, Lone G, Lund Laursen, Alex, Lagging, Martin, and Weis, Nina
- Abstract
BACKGROUND AND AIMS: Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia.METHODS: Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12-24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-α) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12-16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment.RESULTS: We included 316 patients with a mean age of 55 years (range 24-79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis.In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 (91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004).CONCLUSION: We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.
- Published
- 2017
12. Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark
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Weis, Nina, Cowan, Susan, Hallager, Sofie, Dröse, Sandra, Kristensen, Lena Hagelskjær, Grønbæk, Karin, Jensen, Janne, Gerstoft, Jan, Madsen, Lone G, Clausen, Mette Rye, Lunding, Suzanne, Tarp, Britta D, Barfod, Toke S, Sloth, Stine, Holm, Dorte Kinggaard, Jensen, Jesper, Krarup, Henrik, Weis, Nina, Cowan, Susan, Hallager, Sofie, Dröse, Sandra, Kristensen, Lena Hagelskjær, Grønbæk, Karin, Jensen, Janne, Gerstoft, Jan, Madsen, Lone G, Clausen, Mette Rye, Lunding, Suzanne, Tarp, Britta D, Barfod, Toke S, Sloth, Stine, Holm, Dorte Kinggaard, Jensen, Jesper, and Krarup, Henrik
- Abstract
OBJECTIVE: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission.MATERIALS AND METHODS: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc.RESULTS: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission.CONCLUSION: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.
- Published
- 2017
13. Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections—A Scandinavian real-life study
- Author
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Dalgard, Olav, primary, Weiland, Ola, additional, Noraberg, Geir, additional, Karlsen, Lars, additional, Heggelund, Lars, additional, Färkkilâ, Martti, additional, Balslev, Ulla, additional, Belard, Erika, additional, Øvrehus, Anne, additional, Skalshøi Kjær, Mette, additional, Krarup, Henrik, additional, Thorup Røge, Birgit, additional, Hallager, Sofie, additional, Madsen, Lone G., additional, Lund Laursen, Alex, additional, Lagging, Martin, additional, and Weis, Nina, additional
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- 2017
- Full Text
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14. Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark
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Weis, Nina, primary, Cowan, Susan, additional, Hallager, Sofie, additional, Dröse, Sandra, additional, Kristensen, Lena Hagelskjær, additional, Grønbæk, Karin, additional, Jensen, Janne, additional, Gerstoft, Jan, additional, Madsen, Lone G., additional, Clausen, Mette Rye, additional, Lunding, Suzanne, additional, Tarp, Britta D., additional, Barfod, Toke S., additional, Sloth, Stine, additional, Holm, Dorte Kinggaard, additional, Jensen, Jesper, additional, and Krarup, Henrik, additional
- Published
- 2016
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15. Direct acting antiviral treatment of chronic hepatitis C in Denmark: factors associated with and barriers to treatment initiation.
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Sølund, Christina, Hallager, Sofie, Pedersen, Martin S., Fahnøe, Ulrik, Ernst, Anja, Krarup, Henrik B., Røge, Birgit T., Christensen, Peer B., Laursen, Alex L., Gerstoft, Jan, Bélard, Erika, Madsen, Lone G., Schønning, Kristian, Pedersen, Anders G., Bukh, Jens, Weis, Nina, and The Danhep Group
- Subjects
CHRONIC hepatitis C ,FIBROSIS ,HEPATITIS B ,ODDS ratio ,HEPATOLOGY - Abstract
Objectives: We describe factors associated with and barriers to initiation of Direct Acting Antiviral (DAA) treatment in patients with chronic hepatitis C, who fulfill national fibrosis treatment guidelines in Denmark. Materials and Methods: In this nationwide cohort study, we included patients with chronic hepatitis C from The Danish Database for Hepatitis B and C (DANHEP) who fulfilled fibrosis treatment criteria. Factors associated with treatment initiation and treatment failure were determined by logistic regression analyses. Medical records were reviewed from patients who fulfilled fibrosis treatment criteria, but did not initiate DAA treatment to determine the cause. Results: In 344 (49%) of 700 patients, who fulfilled treatment criteria, factors associated with DAA treatment initiation were transmission by other routes than injecting drug use odds ratio (OR) 2.13 (CI: 1.38-3.28), previous treatment failure OR 2.58 (CI: 1.84-3.61) and ALT above upper limit of normal OR 1.60 (CI: 1.18-2.17). The most frequent reasons for not starting treatment among 356 (51%) patients were non-adherence to medical appointments (n = 107/30%) and ongoing substance use (n = 61/17%). Treatment failure with viral relapse occurred in 19 (5.5%) patients, who were more likely to have failed previous treatment OR 4.53 (CI: 1.59-12.91). Conclusions: In this nationwide cohort study, we found non-adherence to medical appointments and active substance use to be major obstacles for DAA treatment initiation. Our findings highlight the need for interventions that can overcome these barriers and increase the number of patients who can initiate and benefit from curative DAA treatment. [ABSTRACT FROM AUTHOR]
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- 2018
- Full Text
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16. Nationwide experience of treatment with protease inhibitors in chronic hepatitis C patients in denmark:identification of viral resistance mutations
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Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T, Lunding, Suzanne, Barfod, Toke S, Madsen, Lone G, Tarp, Britta, Christensen, Peer B, Gerstoft, Jan, Laursen, Alex L, Bukh, Jens, Weis, Nina, Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T, Lunding, Suzanne, Barfod, Toke S, Madsen, Lone G, Tarp, Britta, Christensen, Peer B, Gerstoft, Jan, Laursen, Alex L, Bukh, Jens, and Weis, Nina
- Abstract
BACKGROUND AND AIMS: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting.METHODS: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy.RESULTS: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively.CONCLUSIONS: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response.
- Published
- 2014
17. Nationwide Experience of Treatment with Protease Inhibitors in Chronic Hepatitis C Patients in Denmark: Identification of Viral Resistance Mutations.
- Author
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Sølund, Christina, Krarup, Henrik, Ramirez, Santseharay, Thielsen, Peter, Røge, Birgit T., Lunding, Suzanne, Barfod, Toke S., Madsen, Lone G., Tarp, Britta, Christensen, Peer B., Gerstoft, Jan, Laursen, Alex L., Bukh, Jens, Weis, Nina, and null, null
- Subjects
CHRONIC hepatitis C ,GENETIC mutation ,PROTEASE inhibitors ,RIBAVIRIN ,POLYMERASE chain reaction ,PATIENTS - Abstract
Background and Aims: The first standard of care in treatment of chronic HCV genotype 1 infection involving directly acting antivirals was protease inhibitors telaprevir or boceprevir combined with pegylated-interferon and ribavirin (triple therapy). Phase III studies include highly selected patients. Thus, treatment response and development of viral resistance during triple therapy in a routine clinical setting needs to be determined. The aims of this study were to investigate treatment outcome and identify sequence variations after triple therapy in patients with chronic HCV genotype 1 infection in a routine clinical setting. Methods: 80 patients, who initiated and completed triple therapy in Denmark between May 2011 and November 2012, were included. Demographic data and treatment response were obtained from the Danish Database for Hepatitis B and C. Direct sequencing and clonal analysis of the RT-PCR amplified NS3 protease were performed in patients without cure following triple therapy. Results: 38 (47%) of the patients achieved cure, 15 (19%) discontinued treatment due to adverse events and remained infected, and 27 (34%) experienced relapse or treatment failure of whom 15 of 21 analyzed patients had well-described protease inhibitor resistance variants detected. Most frequently detected protease variants were V36M and/or R155K, and V36M, in patients with genotype 1a and 1b infection, respectively. Conclusions: The cure rate after triple therapy in a routine clinical setting was 47%, which is substantially lower than in clinical trials. Resistance variants towards protease inhibitors were seen in 71% of patients failing therapy indicating that resistance could have an important role in treatment response. [ABSTRACT FROM AUTHOR]
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- 2014
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18. Value of ultrasound and clinical examination in the diagnosis of liver cirrhosis
- Author
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Madsen, Lone G., primary, Hamberg, Ole, additional, Pedersen, Jan F., additional, Larsen, Vibeke A., additional, and Bytzer, Peter, additional
- Published
- 2000
- Full Text
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19. Global evolutionary analysis of chronic hepatitis C patients revealed significant effect of baseline viral resistance, including novel non-target sites, for DAA-based treatment and retreatment outcome.
- Author
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Fahnøe U, Pedersen MS, Sølund C, Ernst A, Krarup HB, Røge BT, Christensen PB, Laursen AL, Gerstoft J, Thielsen P, Madsen LG, Pedersen AG, Schønning K, Weis N, and Bukh J
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- Drug Resistance, Viral genetics, Drug Therapy, Combination, Genotype, Hepacivirus genetics, Humans, Retreatment, Treatment Failure, Viral Nonstructural Proteins genetics, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Hepatitis C, Chronic drug therapy
- Abstract
Direct-acting antivirals (DAAs) have proven highly effective against chronic hepatitis C virus (HCV) infection. However, some patients experience treatment failure, associated with resistance-associated substitutions (RASs). Our aim was to investigate the complete viral coding sequence in hepatitis C patients treated with DAAs to identify RASs and the effects of treatment on the viral population. We selected 22 HCV patients with sustained virologic response (SVR) to match 21 treatment-failure patients in relation to HCV genotype, DAA regimen, liver cirrhosis and previous treatment experience. Viral-titre data were compared between the two patient groups, and HCV full-length open reading frame deep-sequencing was performed. The proportion of HCV NS5A-RASs at baseline was higher in treatment-failure (82%) than matched SVR patients (25%) (p = .0063). Also, treatment failure was associated with slower declines in viraemia titres. Viral population diversity did not differ at baseline between SVR and treatment-failure patients, but failure was associated with decreased diversity probably caused by selection for RAS. The NS5B-substitution 150V was associated with sofosbuvir treatment failure in genotype 3a. Further, mutations identified in NS2, NS3-helicase and NS5A-domain-III were associated with DAA treatment failure in genotype 1a patients. Six retreated HCV patients (35%) experienced 2nd treatment failure; RASs were present in 67% compared to 11% with SVR. In conclusion, baseline RASs to NS5A inhibitors, but not virus population diversity, and lower viral titre decline predicted HCV treatment failure. Mutations outside of the DAA targets can be associated with DAA treatment failure. Successful DAA retreatment in patients with treatment failure was hampered by previously selected RASs., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2021
- Full Text
- View/download PDF
20. Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark.
- Author
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Weis N, Cowan S, Hallager S, Dröse S, Kristensen LH, Grønbæk K, Jensen J, Gerstoft J, Madsen LG, Clausen MR, Lunding S, Tarp BD, Barfod TS, Sloth S, Holm DK, Jensen J, and Krarup H
- Subjects
- Adolescent, Adult, Child, Child, Preschool, DNA, Viral blood, Databases, Factual, Denmark, Female, Hepatitis B Antibodies blood, Hepatitis B Antigens blood, Hepatitis B virus, Hepatitis B, Chronic epidemiology, Humans, Infant, Infectious Disease Transmission, Vertical prevention & control, Logistic Models, Male, Mass Screening methods, Pregnancy, Risk Factors, Young Adult, Hepatitis B, Chronic transmission, Infectious Disease Transmission, Vertical statistics & numerical data, Vaccination statistics & numerical data
- Abstract
Objective: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission., Materials and Methods: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc., Results: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission., Conclusion: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.
- Published
- 2017
- Full Text
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