| 1. |
- Batyrbekova, Nurgul, et al.
(författare)
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Hepatitis C virus infection and the temporal trends in the risk of liver cancer : a national register-based cohort study in Sweden
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:1, s. 63-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In many countries, including Sweden, the birth cohorts with the highest prevalence of hepatitis C virus (HCV) infection have now reached the ages with high risk of primary liver cancer (PLC). The aims were to investigate the temporal trends in PLC incidence and the relative risks of PLC among people diagnosed with HCV-infection between 1990 and 2015.METHODS: The HCV-cohort (n: 52,853) was compared with a matched non-HCV comparison-cohort (n: 523,649). Both the Cancer (CR) and Death registers (DR) were used for follow-up. The crude and age-standardised PLC incidence rates were calculated. The relative risk was estimated as standardized incidence ratios (SIR) and as hazard ratios (HR) using stratified Cox hazards regression.RESULTS: There were 1,609 with PLC-diagnosis in the HCV-cohort, the annual number increased continuously with the crude incidence rate reaching 4.56 per 1,000 person-years in 2013, while remaining low and stable in the comparison-cohort. In the HCV-cohort, the age-standardised PLC incidence rates per 1,000 person-years remained relatively constant at 2.64 (95% CI: 1.54, 3.75) in 2000 and 3.31 (2.51, 4.12) in 2014. The highest SIR was 73 (65.9, 79.5) among those infected for 35-40 years; and the highest HR was 65.9 (55.9, 77.6) for men and 62.2 (31.9, 121.1) for women.CONCLUSIONS: There was a considerable increase in PLC-incidence over time and an extremely high relative risk in the population with HCV-infection for more than 35 years.IMPACT: The national HCV-associated PLC-incidence should be monitored in future studies to evaluate the effect of DAA-treatment.
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| 2. |
- Duberg, Ann-Sofi, Docent, 1957-, et al.
(författare)
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Chronic hepatitis B virus infection and the risk of hepatocellular carcinoma by age and country of origin in people living in Sweden : A national register study
- 2022
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Ingår i: Hepatology communications. - : John Wiley & Sons. - 2471-254X. ; 6:9, s. 2418-2430
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), and surveillance is recommended for patients without cirrhosis when risk exceeds an incidence rate (IR) of 0.2%. Populations in Asia and sub-Saharan Africa have been associated with HCC at younger ages, but the risk after immigration to Western countries should be investigated. The aim of this study was to study HCC by age and country of origin in people with chronic HBV infection in Sweden. Through national registers, residents with chronic HBV diagnosis (1990-2015) were identified with information on country of origin, immigration/emigration, death, coinfections, antiviral therapy, and HCC. Observation time started at HBV diagnosis, and IR and hazard ratios for HCC were calculated by sex, age, and region of origin. Among 16,410 individuals (47% women), the origin and observation time (person years) were as follows: Western Europe, 2316 (25,415); Eastern Europe, 2349 (26,237); Middle East/North Africa, 4402 (47,320); sub-Saharan Africa, 3677 (30,565); Asia, 3537 (35,358); and other, 129 (1277). There were 232 individuals with HCC (82% in men). The IR increased with age and exceeded 0.2% for Asian men from age group 40-49 years (IR, 0.63; 95% confidence interval, 0.39-1.00), for men of other origins from age group 50-59 years, and for women aged ≥60 years originating from Eastern Europe, Asia, and Middle East/North Africa. After exclusion of patients with cirrhosis or HBV treatment, the IR still exceeded 0.2% in Asian men aged 40-49 years. This study demonstrates that HBV-infected men of Asian origin should be recommended HCC surveillance at younger ages, but there is a need for further studies of HCC incidence in African-born men without cirrhosis living in the Western world.
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| 3. |
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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Lybeck, Charlotte, 1979-, et al.
(författare)
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Risk of extrahepatic cancer in a nationwide cohort of hepatitis C virus infected persons treated with direct-acting antivirals
- 2021
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Ingår i: GastroHep. - : Wiley-Blackwell Publishing Inc.. - 1478-1239. ; 3:3, s. 185-195
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Direct-acting antivirals (DAAs) against HCV have an immune modulatory effect, this could possibly lead to a decreased tumour control. We, therefore, aimed to assess the risk of extrahepatic cancer (EHC) during and the first years after DAA treatment.Methods and Results: This is a nationwide cohort study with prospectively collected data for 19 685 persons with HCV, 4013 DAA treated, 3071 interferon (IFN) treated and 12 601 untreated, from 2008 to 2016. Follow-up time was maximum 3 years. The risk for EHC was compared between the groups using Cox regression analyses, with adjustment for age and Charlson Comorbidity Index (CCI). The HCV-infected groups were also compared with matched cohorts without HCV from the general population. In total 341 EHCs were identified, 84, 43 and 214 EHC in the DAA, IFN and untreated group respectively. The EHC risk in DAA treated compared with IFN treated was doubled, but when adjusted for age and CCI the HR was 1.07 (95% CI 0.74-1.56). Compared with the general population, the HR of EHC for the DAA group was 1.45 (CI 1.13-1.86), with the difference remaining statistically significant after adjusting for CCI.Conclusion: We found no increased risk for EHC associated with DAA therapy after adjustment for age and CCI. An increased risk of EHC in DAA treated compared with the general population was though seen, and attention should be paid to this association in the ageing population with a history of HCV infection.
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| 8. |
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| 9. |
- Lybeck, Charlotte, 1979-
(författare)
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Towards the elimination of hepatitis C : identifying the infected population, and remaining hepatitis C related risks after successful treatment
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic Hepatitis C virus (HCV) infection can lead to liver fibrosis and cirrhosis with increased risk of hepatocellular carcinoma (HCC) and liver failure. The World Health Organisation (WHO) has set a goal to eliminate viral hepatitis as a global health threat by 2030. To reach this goal for HCV we need to prevent new infections and identify and treat the infected population. Individuals with pre-treatment cirrhosis still have an elevated risk for HCC after HCV cure. This thesis aims to assess the health outcomes after cured HCV infection, study HCV prevalence and find a way to identify undiagnosed infections.In Paper I, 97 patients were followed through clinical visits (n=54) or through national registers (n=43) to study the long-term outcomes after cure from HCV and to assess the presence and impact of occult HCV infection (OCI). Three non-cirrhotic patients were diagnosed with HCC 8-11 years after HCV cure. Two patients had OCI at 8-9 years after cure. They had liver fibrosis stage 2, but no association with HCC. In Paper II, pregnant women (n=4,108) and partners (n=1,027) at antenatal clinics in southern Stockholm and Örebro County were tested for HCV and interviewed about risk factors to assess prevalence and evaluate screening strategies to identify undiagnosed infections. Anti-HCV prevalence was 0.7% and 0.4% were viraemic. The most effective risk factor-based screening was to ask for drug use, country of birth, and having a partner with HCV. Paper III presents a nationwide register study of the risk of extrahepatic cancer (EHC) the first 3 years after HCV treatment with direct acting antiviral (DAAs). We compared 4,013 DAA-treated, with 3,071 interferon-treated and 12,601 untreated patients. No increased risk for EHC was found after adjustments for age and comorbidities. An increased EHC risk in DAA-treated compared with general population was seen. Paper IV presents a register based study of the risk of HCC and association with pre-treatment liver stiffness measurement (LSM) in 7,227 HCV infected patients cured by DAAs. We found that pre-treatment LSM values correlated well with HCC risk. The incidence rate for patients with LSM values ≥12.5 kPa and <12.5 kPa was 1.6 and 0.15/100 person years, respectively.To conclude, cured HCV infection usually leads to regression of fibrosis. The DAAs are safe and highly effective against HCV. However, the HCC risk remains elevated for many years after cure in cirrhotic and sometimes in non-cirrhotic patients. Furthermore, HCV screening of pregnant women and partners is useful to identify patients who would benefit from therapy.
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| 10. |
- Millbourn, Charlotta, et al.
(författare)
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Anti-HCV prevalence and risk factor-based screening for hepatitis C in pregnant women and their partners in Sweden
- 2020
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:11, s. 776-785
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Tidskriftsartikel (refereegranskat)abstract
- Background: The hepatitis C virus (HCV) prevalence in Sweden is estimated to be <0.5%, but unclear in pregnant women. The dominating route of transmission is drug use (DU), blood transfusions constituted a risk before 1992. The aim was to examine the anti-HCV prevalence and risk factors for HCV among pregnant women and their partners to evaluate screening strategies.Methods: Pregnant women and partners in Örebro County and in southern Stockholm were offered HCV-screening when visiting an antenatal clinic in 2013-2016, and completed a questionnaire concerning the country of birth, knowledge of HCV-status and HCV risk factors.Results: In Örebro 2,827 pregnant women and 707 partners, and in Stockholm 1,281 pregnant women and 320 partners participated. Anti-HCV was positive in 34 (0.7%) (25 pregnant women) and the associated risk factors were DU (n = 27), partner with HCV (n = 24) and not born in Sweden (n = 8). HCV RNA was positive in 23 (0.4%), 4 previously unknown and 10 who had been lost to follow-up. The most effective risk factor-based screening model for pregnant women included DU, blood transfusions, born in high prevalence country, partner with HCV, resulting in 538 (13%) pregnant women tested with 96% sensitivity, 87% specificity.Conclusions: In this study of expecting parents in two Swedish regions, the anti-HCV prevalence was 0.7% and 0.4% were viraemic, of which about 60% were previously unknown or lost to follow-up. Awaiting more studies, including cost-benefit analysis evaluating universal screening, we recommend this improved risk factor-based screening model to identify HCV-infected individuals who need follow-up and therapy.
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