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| 2. |
- Duberg, Ann-Sofi, Docent, 1957-, et al.
(författare)
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The incidence of hepatocellular carcinoma in hepatitis B virus infected persons of different origins, living in Sweden
- 2018
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 68:Suppl. 1, s. S488-S488
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Chronic hepatitis B (CHB) is associated with an increased risk of hepatocellular carcinoma (HCC) in both cirrhotic and non-cirrhotic persons. CHB patients with high risk for HCC are therefore recommended to undergo surveillance for HCC, with an estimated cut-off for surveillance in non-cirrhotic patients at incidence rate (IR) of 0.2% per year. People originating from Asia and men from Africa are estimated to have particularly high risks, but the IR for HCC when living in the Western world has not been fully estimated. Therefore, our aim was to study the incidence of HCC by age and origin in persons with CHB who are living in Sweden.Method: In this national population-based study all persons diagnosed with CHB in Sweden during 1990–2015, their country of birth, co-infections, antiviral therapy, liver cancer or death/emigration were identified retrospectively, using the national HBV-surveil-lance register and other national registers. Those co-infected with hepatitis C were excluded. Observation time started at date of reported CHB diagnosis. The IR was calculated for different age groups and by region of birth.Results: In total 16,410 persons (47% women) with CHB were studied. The number of persons and observation time (person-years) by origin were: Western Europe 2,316 (25,415); Eastern Europe 2,349 (26,237); Middle East/North Africa 4,402 (47,320); Sub-Saharan Africa 3,677 (30,565), Asia 3,537 (35,358) and other 129 (1,277). Those from Sub-Saharan Africa were youngest and had the shortest mean time in Sweden, 11.6 years. There were in total 232 diagnosed HCCs (82% in men); 23, 54 and 58 in people from Sub-Saharan Africa ,Asia and Middle East/North Africa, respectively. The corresponding mean ages at HCC diagnoses were 45, 51 and 59 years, respectively. The IRexceeded 0.2% for men from Asia from age-group≥40–49 years (IR 0.63, 95%CI 0.39–1.00), and for men of all other origins from age-group≥50–59 years. Among African men aged <40 yearstherewere 7 HCC, with incidence rate 0.05 and 0.11 in age groups 20–29 and 30–39 years, respectively. In women, HCC was rare but exceeded 0.2% among those aged≥60 years with origins from East Europe, Asia and Middle East/North Africa.Conclusion: In this study only men of Asian origin exceeded the cut-off for HCC surveillance by ages 40–49 years. African men had a few HCCs at youngerages, but did not exceed the cut-off before age 50–59 years. This study confirms the high risk for HCC in especially Asian men living in the Western world, but questions the benefit of surveillance at younger ages for men with African origin who live in a Northern European country
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| 3. |
- Gahrton, Caroline, et al.
(författare)
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Prevalence of Viremic hepatitis C, hepatitis B, and HIV infection, and vaccination status among prisoners in Stockholm County
- 2019
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Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Identification and knowledge of settings with high prevalence of hepatitis C virus (HCV) infection is important when aiming for elimination of HCV. The primary aim of this study was to estimate the prevalence of viremic HCV infection among Swedish prisoners. Secondary aims were to estimate the prevalence of hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), and the proportion who have received hepatitis B virus (HBV) vaccination.METHODS: A cross-sectional study of all incarcerated persons (n = 667) at all prisons (n = 9) in Stockholm County was conducted. All prisoners are routinely offered opt-in screening for HCV antibodies (anti-HCV), HCV RNA, HBsAg, anti-HBs, anti-HBc and HIV Ag/Ab at prison in Sweden. Data on the results of these tests and the number of received HBV vaccine doses were collected from the prison medical records. The parameters of HCV RNA, anti-HCV, and occurrence of testing for HCV were analysed in multiple logistic regression models in relation to age, sex and prison security class.RESULTS: The median age was 35 (IQR 26-44) years, and 93.4% were men. Seventy-one percent (n = 471) had been tested for anti-HCV, 70% (n = 465) for HBsAg and 71% (n = 471) for HIV. The prevalence of anti-HCV, HCV RNA, HBsAg and HIV Ag/Ab was 17.0, 11.5, 1.9, and 0.2%, respectively among tested persons. The proportion of prisoners who had received full HBV vaccination was 40.6% (n = 271) among all study subjects.CONCLUSIONS: The prevalence of viremic HCV infection among Swedish prisoners in Stockholm County was 11.5%, which is high in comparison to the general population. Therefore, when aiming for the WHO goal of HCV elimination, prisons could suit as a platform for identification and treatment of HCV infection. There is a need to increase testing for blood-borne viruses and to improve vaccination coverage against HBV in Swedish prisons.
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| 6. |
- Kileng, Hege, et al.
(författare)
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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
- 2018
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 53:10-11, s. 1347-1353
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Kjellin, Midori, et al.
(författare)
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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
- 2019
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 54:8, s. 1042-1050
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Lagging, Martin, 1965, et al.
(författare)
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Treatment of hepatitis C virus infection for adults and children: updated Swedish consensus guidelines 2017
- 2018
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:8, s. 569-583
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Following the approval of two new therapeutic combinations within the European Union in 2017, the former Swedish recommendations for the treatment of hepatitis C virus (HCV) infection from 2016 were deemed in need of updating. Materials and methods: An expert meeting to this end was held in Stockholm, Sweden in October 2017. Results and conclusions: An interferon-free combination of direct-acting antiviral agents is now recommended for all patients with chronic HCV infection, regardless of liver fibrosis stage, in order to limit morbidity and spread of the disease. An extended discussion of treatment for people who inject drugs in order to diminish transmission is included.
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| 9. |
- Lybeck, Charlotte, 1979-, et al.
(författare)
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A national study of risk for non-liver cancer in people with hepatitis C treated with direct acting antivirals or an interferon-based regimen
- 2018
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Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 68:Suppl. 1, s. S263-S264
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 10. |
- Lybeck, Charlotte, 1979-, et al.
(författare)
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Long-term follow-up after cure from chronic hepatitis C virus infection shows occult hepatitis and a risk of hepatocellular carcinoma in noncirrhotic patients
- 2019
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Ingår i: European Journal of Gastroenterology and Hepathology. - : Lippincott Williams & Wilkins. - 0954-691X .- 1473-5687. ; 31:4, s. 506-513
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Safreed-Harmon, Kelly, et al.
(författare)
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The Consensus Hepatitis C Cascade of Care : standardized reporting to monitor progress toward elimination
- 2019
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 69:12, s. 2218-2227
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 14. |
- Simon, Tracey G., et al.
(författare)
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Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis : Results From a Nationwide Swedish Population
- 2019
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Ingår i: Annals of Internal Medicine. - : American College of Physicians. - 0003-4819 .- 1539-3704. ; 171:5, s. 318-327
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 16. |
- Särnblad, Stefan, 1963-, et al.
(författare)
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Will Early Clinical Training improve the professional skills? : Experience from a New Medical Education in Sweden
- 2018
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Konferensbidrag (refereegranskat)abstract
- Background: The undergraduate medical education in Sweden is 5½ years long (11 semesters), followed by an 18 months internship before license. The university curriculum used to be 6 theoretical semesters followed by 5 “clinical” semesters. Today it is common with integrated curricula with an early introduction of clinical training.Method: School of Medicine at Örebro University started in January 2011 and now admits 70 students every semester. The first students graduated in June 2016. The educational approach is problem-based learning and the curriculum is integrated with six themes based on physiological processes. Biomedicine, clinical medicine and professional development are integrated throughout the entire programme.Results: In total, clinical placement constitutes 74 weeks of which 16 weeks are spread through the first six semesters. The remaining 58 weeks (semester 7-11) are divided into six longer periods related to the themes. The objective of clinical placement during the first 6 semesters is to practice general clinical skills like communication, history-taking and clinical examination, but also to understand the health care system and the tasks of other health care personnel. The clinical placement in semester 6 ends with a seminar for reflection around the professional development and the value of early clinical placement. The students appreciate the early clinical placements. They manage to acquire general professional skills at this early stage and have the possibility to reflect upon their choice of profession. This stimulates theoretical studies and makes them more comfortable when entering the long clinical placements related to the themes. This is beneficial also for the clinical tutors. The first Örebro students that graduated were satisfied with the preparation given “to work as doctors” and gave the University the highest rank in a national survey.Conclusion: Early clinical training is beneficial for the development of professional skills; it motivates and gives the student an early understanding of their future professional role. A challenge may be to find enough placements and the need for coaching adjusted for different stages of professional development.Take-home message: Early clinical training is beneficial for the development of professional skills.
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| 17. |
- Söderholm, Jonas, et al.
(författare)
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ELEVATED RISK FOR LIVER RELATED MORTALITY IN CHRONIC HEPATITIS C PATIENTS BOTH WITH OR WITHOUT ILLICIT SUBSTANCE USE DISORDER : A NATION-WIDE REGISTER STUDY
- 2019
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Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 70:Suppl. 1, s. 366A-366A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hepatitis C is a slowly progressive disease mainly transmitted in people who inject drugs . This cohort has a high mortality from drug related causes, such as overdoses or external causes. We investigated the relative risk for liver related death in chronic hepatitis C (CHC) patients with or without illicit substance use disorders (SUD) .Methods: Patients with CHC were identified using the Swedish National Patient Registry (contains all inpatient, day surgery, and outpatient non-primary care visits) according to the International Classification of Diseases-10 (ICD-10) code B18.2. The baseline observation was set to the first CHC visit from 2001, and person-time continued until death, emigration or December 31, 2013, whichever came first. Patients with ≥2 non-primary care visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have illicit SUD . The underlying cause of death was obtained from the Cause of Death Register . A six months lag-period between CHC diagnosis and death was introduced to reduce surveillance bias. Non-alcoholic liver disease was defined using ICD-10 codes K71–K77, B15–B19, B94.2, R17-R18, I85 .0, I98 .2, and I98 .3 . The relative risk for death was determined using standardized mortality ratio (SMR) where the observed number of deaths was divided by the expected number of deaths taken from five comparators from the general population (matched for age/sex/place of residency) .Results: In total 38,186 patients with CHC were included in the study whereof 11,818 (31%) were considered to have illicit SUD . The CHC patients with SUD were younger (37 .7 vs . 46 .9 years) with a greater proportion of men (72% vs . 62%) than CHC patients without SUD . The SMRs for CHC patients with SUD were 10 .5, 33 .8, 18 .1, 123 .2, 61 .6, and 13 .2, for all-causes, liver cancer, alcoholic or non-alcoholic liver disease, drug-related, or external causes, respectively (Table 1) . The corresponding SMRs for CHC patients without SUD were 4 .1, 52 .8, 18 .0, 69 .4, 11 .2, and 4 .9, respectively (Table 1) .Conclusion: The relative risks for all investigated parameters were elevated for CHC patients whether they had illicit SUD or not . Furthermore, although the CHC patients with SUD had a high relative risk to die from both drug-related and external causes, the relative risk to die from non-alcoholic liver disease was also greatly elevated .
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