| 1. |
- Aleman, Soo, et al.
(author)
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Frequent loss to follow-up after diagnosis of hepatitis C virus infection : A barrier towards the elimination of hepatitis C virus
- 2020
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In: Liver international (Print). - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 40:8, s. 1832-1840
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Journal article (peer-reviewed)abstract
- BACKGROUND: Previous studies on hepatitis C cascade of care have been mainly focused on diagnosis and treatment rate, while less attention has been given to patients lost to follow-up (LTFU) after diagnosis. Analyses of this latter issue on population level are missing.AIMS: In this nationwide study of people with HCV, we aimed to estimate the proportion LTFU after HCV diagnosis, characterize them, and analyze their other healthcare contacts.METHODS: Patients diagnosed with chronic HCV in the Swedish National Patient register during 2001-2011 and still alive December 31, 2013, were included. The number of cured patients without need of follow-up was estimated. Visits to HCV specialist care during 2012-2013 were analysed. For those LTFU, other specialist care contacts were studied.RESULTS: In total 29,217 patients were included, with 24,733 with need of HCV care. 61% (n=15,007) of them were LTFU from HCV care in 2012-2013 and 58% did not attend HCV care during the second year after HCV diagnosis. The departments of surgery/orthopedic or psychiatry/dependency were the most common other non-primary healthcare contacts. Predictors for LTFU were young age, male sex, low education, presence of psychiatric/dependency diagnosis, unmarried, and longer duration since diagnosis of HCV.CONCLUSIONS: This study showed that almost two-thirds of patients were LTFU after HCV diagnosis, with frequent occurrence early after diagnosis. Efforts to link patients back to HCV care, in combination with early and easy access to HCV treatment and harm reduction, are necessary to reach the HCV elimination goal.
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| 2. |
- Batyrbekova, Nurgul, et al.
(author)
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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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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:1, s. 63-70
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Journal article (peer-reviewed)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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| 3. |
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| 4. |
- Blach, S., et al.
(author)
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Hepatitis C Elimination in Sweden : Progress, Challenges and Opportunities for Growth in the time of COVID-19
- 2021
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In: Liver international. - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 41:9, s. 2024-2031
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: In 2014, the burden of hepatitis C virus (HCV) in Sweden was evaluated, to establish a baseline and inform public health interventions. Considering the changing landscape of HCV treatment, prevention, and care, and in light of the COVID-19 pandemic, this analysis seeks to evaluate Sweden's progress toward the WHO elimination targets and identify remaining barriers.METHODS: The data used for modeling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources, and expert input. A dynamic Markov model was employed to forecast population sizes and incidence of HCV through 2030. Two scenarios ("2019 Base" and "WHO Targets") were developed to evaluate Sweden's progress toward HCV elimination.RESULTS: At the beginning of 2019, there were 29,700 (95% UI: 19,300 - 33,700) viremic infections in Sweden. Under the base scenario, Sweden would achieve and exceed the WHO targets for diagnosis, treatment, and liver-related death. However, new infections would decrease by less than 10%, relative to 2015. Achieving all WHO targets by 2030 would require 1) expanding harm reduction programs to reach more than 90% of PWID and 2) treating 90% of HCV+ PWID engaged in harm reduction programs and ≥7% of PWID not involved in harm reduction programs, annually by 2025.CONCLUSIONS: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programs by broadening the setting and base of providers to provide stability and continuity of care during turbulent times.
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| 5. |
- Christensen, P. B., et al.
(author)
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Hepatitis C time trends in reported cases and estimates of the hidden population born before 1965, Denmark and Sweden, 1990 to 2020
- 2022
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In: Eurosurveillance. - : European Centre for Disease Prevention and Control (ECDC). - 1025-496X .- 1560-7917. ; 27:50, s. 30-38
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Journal article (peer-reviewed)abstract
- Background: According to the World Health Organization, hepatitis C virus (HCV) infection should be under control by 2030.Aim: Our aim was to describe the size and temporal changes in reported cases of chronic HCV infection in Denmark and Sweden and to estimate the size of the hidden (undiagnosed) population born before 1965.Methods: We extracted all HCV infections reported to national surveillance systems in Denmark and Sweden from 1990 to 2020. Prediction of the size of the hidden HCV-infected population was restricted to the cohort born before 1965 and cases reported up to 2017. We applied a model based on removal sampling from binomial distributions, estimated the yearly probability of diagnosis, and deducted the original HCV-infected population size.Results: Denmark (clinician-based) reported 10 times fewer hepatitis C cases annually than Sweden (laboratory and clinician-based), peaking in 2007 (n = 425) and 1992 (n = 4,537), respectively. In Denmark, the birth year distribution was monophasic with little change over time. In recent years, Sweden has had a bimodal birth year distribution, suggesting ongoing infection in the young population. In 2017, the total HCV infected population born before 1965 was estimated at 10,737 living persons (95% confidence interval (CI): 9,744-11,806), including 5,054 undiagnosed, in Denmark and 16,124 (95% CI: 13,639-18,978), including 10,580 undiagnosed, in Sweden.Conclusions: The reporting of HCV cases in Denmark and Sweden was different. For Denmark, the estimated hidden population was larger than the current national estimate, whereas in Sweden the estimate was in line with the latest published numbers.
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| 6. |
- Colombe, Soledad, et al.
(author)
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Monitoring the progress towards the elimination of hepatitis B and C in Sweden : estimation of core indicators for 2015 and 2018
- 2022
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In: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 22:1
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Journal article (peer-reviewed)abstract
- INTRODUCTION: To monitor Sweden's progress towards the WHO goal of eliminating viral hepatitis, we estimated the prevalence, notification rate, and liver-related morbidity and mortality for diagnosed hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in 2015 and 2018.METHODS: We identified cases of hepatitis B and C within the National System for Notifiable Diseases and obtained data on treatment and whether the case was deceased or not. We calculated prevalence, notification rates per 100,000, and proportion of newly diagnosed cases of hepatitis with liver disease at the time of diagnosis, and proportion of all deceased cases who died from liver disease. We calculated Poisson 95% confidence intervals (CIs) around the notification rates and Wilson 95% CIs around prevalence and mortality estimates.RESULTS: In 2015 and 2018, the prevalence of diagnosed HBV infections was 0.20% [95% CI: 0.19-0.20] and 0.21% [0.20-0.21]. Notification rates per 100,000 for HBV infections were 13.02 [12.32-13.76] and 7.71 [7.18-8.27]. HBV liver-related morbidity was 2.65% [1.90-3.68] and 2.16% [1.35-3.43]. HBV liver-related mortality was 20.00% [14.81-26.44] and 17.95% [13.20-23.94]. In 2015 and 2018, the prevalence of diagnosed HCV-infections was 0.24% [0.24-0.25] and 0.18% [0.18-0.19]. Notification rates per 100,000 for HCV infections were 15.92 [15.14-16.73] and 13.05 [12.36-13.77]. HCV liver-related morbidity was 8.14% [6.89-9.60] and 3.90% [2.99-5.08]. HCV liver-related mortality was 27.08% [24.54-29.77] and 26.90% [24.12-29.88].CONCLUSIONS: All indicators decreased or remained stable between 2015 and 2018, indicating progress in the elimination of viral hepatitis, especially for HCV infection.
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| 7. |
- Duberg, Ann-Sofi, Docent, 1957-, et al.
(author)
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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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In: Hepatology communications. - : John Wiley & Sons. - 2471-254X. ; 6:9, s. 2418-2430
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Journal article (peer-reviewed)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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| 8. |
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| 9. |
- Gahrton, Caroline, et al.
(author)
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Mortality among amphetamine users with hepatitis C virus infection : A nationwide study
- 2021
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 16:6
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Journal article (peer-reviewed)abstract
- AIMS: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population.METHODS: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086).RESULTS: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals.CONCLUSIONS: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.
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| 10. |
- Kamal, Habiba, et al.
(author)
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Age-specific and sex-specific risks for HCC in African-born persons with chronic hepatitis B without cirrhosis
- 2023
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In: Hepatology communications. - : Wiley Periodicals Inc. on behalf of the American Association for the Study of Liver Diseases. - 2471-254X. ; 7:12
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Journal article (peer-reviewed)abstract
- BACKGROUND: The international recommendations of HCC surveillance for African-born persons with chronic hepatitis B (CHB) without cirrhosis are divergent, probably due to scarce data on incidence rate (IR) for HCC.METHODS: We assembled a cohort with prospectively collected data of Swedish residents of African origin with diagnosed CHB without cirrhosis at baseline from 1990 to 2015. Data from nationwide registers were used to calculate the sex-specific IR and IR ratio (incidence rate ratios) in relation to age, comorbidities, and birth region, using a generalized linear model with a log-link function and Poisson distribution.RESULTS: Among 3865 African-born persons with CHB without cirrhosis at baseline, 31 (0.8%; 77.4% men) developed HCC during a median of 11.1 years of follow-up, with poor survival after HCC diagnosis. The mean age at HCC diagnosis was 46.8 (SD±14.7; range 23-79) in men. HCC IR exceeded the recommended surveillance threshold of 0.2%/year at ages 54 and 59 years in men and women, respectively, and at ages 20-40 years if HCV or HDV co-infection was present. African-born men with CHB had an incidence rate ratios of 10.6 (95% CI 4.4-31.5) for HCC compared to matched African-born peers without CHB, and an incidence rate ratios of 35.3 (95% CI 16.0-88.7) compared to a matched general population.CONCLUSIONS: African-born men with CHB without cirrhosis reached an IR of 0.2%/year between 50 and 60 years, and at younger ages if HCV or HDV co-infection was present. Our findings need further confirmation, and new cost-effectiveness analyses specific for young populations are needed, to provide personalized and cost-effective HCC surveillance.
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| 11. |
- Kamal, H., et al.
(author)
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Long-Term Study of Hepatitis Delta Virus Infection at Secondary Care Centers: The Impact of Viremia on Liver-Related Outcomes
- 2020
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In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 72:4, s. 1177-1190
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Journal article (peer-reviewed)abstract
- Background and Aims Hepatitis delta virus (HDV) infection is associated with fast progression to liver cirrhosis and liver complications. Previous studies have, however, been mainly from tertiary care centers, with risk for referral bias toward patients with worse outcomes. Furthermore, the impact of HDV viremiaper seon liver-related outcomes is not really known outside the human immunodeficiency virus co-infection setting. We have therefore evaluated the long-term impact of HDV viremia on liver-related outcomes in a nationwide cohort of patients with hepatitis B and D co-infection, cared for at secondary care centers in Sweden. Approach and Results In total, 337 patients with anti-HDV positivity, including 233 patients with HDV RNA viremia and 91 without HDV viremia at baseline, were retrospectively studied, with a mean follow-up of 6.5 years (range, 0.5-33.1). The long-term risks for liver-related events (i.e., hepatocellular carcinoma [HCC], hepatic decompensation, or liver-related death/transplantation) were assessed, using Cox regression analysis. The risk for liver-related events and HCC was 3.8-fold and 2.6-fold higher, respectively, in patients with HDV viremia compared with those without viremia, although the latter was not statistically significant. Among patients with HDV viremia with no baseline cirrhosis, the cumulative risk of being free of liver cirrhosis or liver-related events was 81.9% and 64.0% after 5 and 10 years of follow-up, respectively. This corresponds to an incidence rate of 0.04 cases per person-year. Conclusions HDV RNA viremia is associated with a 3.8-fold higher risk for liver-related outcomes. The prognosis was rather poor for patients with HDV viremia without cirrhosis at baseline, but it was nevertheless more benign than previous estimates from tertiary centers. Our findings may be of importance when making decisions about treatment and evaluating potential outcomes of upcoming antivirals against HDV.
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| 12. |
- Kamal, Habiba, et al.
(author)
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Risk of hepatocellular carcinoma in hepatitis B and D virus co-infected patients : A systematic review and meta-analysis of longitudinal studies
- 2021
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In: Journal of Viral Hepatitis. - : John Wiley & Sons. - 1352-0504 .- 1365-2893. ; 28:10, s. 1431-1442
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Research review (peer-reviewed)abstract
- Hepatitis D virus (HDV) infection causes a severe chronic viral hepatitis with accelerated development of liver cirrhosis and decompensation, but whether it further increases the risk of hepatocellular carcinoma (HCC) is unclear. We performed a comprehensive systematic review of the published literature and meta-analysis to assess the risk of HCC in HDV and hepatitis B virus (HBV) co-infected, compared to HBV mono-infected patients. The study was conducted per a priori defined protocol, including only longitudinal studies, thus excluding cross-sectional studies. Random-effects models were used to determine aggregate effect sizes (ES) with 95% confidence intervals (CI). Meta-regression was used to examine the associations among study level characteristics. Twelve cohort studies comprising a total of 6099 HBV/HDV co-infected and 57,620 chronic HBV mono-infected patients were analysed. The overall pooled ES showed that HBV/HDV co-infected patients were at 2-fold increased risk of HCC compared to HBV mono-infected patients (ES = 2.12, 95% CI 1.14-3.95, I2 = 72%, N = 12). A six-fold significant increased risk of HCC was noted among HIV/HBV/HDV triple-infected, compared to HIV/HBV co-infected patients. The magnitude of ES did not differ significantly after adjustment for study design and quality, publication year and follow-up duration in univariable meta-regression analysis. This systematic review and meta-analysis shows that infection with HDV is associated with a 2-fold higher risk of HCC development compared to HBV mono-infection. HCC surveillance strategies taking this increased risk into account, and new treatment options against HDV, are warranted.
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| 13. |
- Kamal, Habiba, et al.
(author)
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The cascade of care for patients with chronic hepatitis delta in Southern Stockholm, Sweden for the past 30 years
- 2024
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In: Liver international. - : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 44:1, s. 228-240
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: Previous studies have shown suboptimal screening for hepatitis D virus (HDV) among patients with chronic hepatitis B (CHB). This study presents the cascade of care for HDV infection in a major secondary referral centre in Southern Stockholm, Sweden.METHODS: HBsAg+ve patients attending Karolinska University Hospital (KUH) from 1992 to 2022 were identified. The prevalence of anti-HDV and/or HDV RNA positivity, interferon (IFN) therapy and maintained virological responses (MVR) after HDV treatment were assessed. Also, time to anti-HDV testing was analysed in relation to liver-related outcomes with logistic regression.RESULTS: Among 4095 HBsAg+ve persons, 3703 (90.4%) underwent an anti-HDV screening; within a median of 1.8 months (range 0.0-57.1) after CHB diagnosis. This screening rate increased over time, to 97.9% in the last decade. Overall, 310 (8.4%) were anti-HDV+ve, of which 202 (65.2%) were HDV RNA+ve. Eighty-five (42%) received IFN, and 9 (10.6%) achieved MVR at the last follow-up. The predictive factors for anti-HDV screening were Asian origin, diagnosis after the year 2012, HIV co-infection (negative factor) and HBV DNA level < 2000 IU/mL in univariable analysis, while HIV co-infection was the only remaining factor in multivariable analysis. Delayed anti-HDV test >5 years was independently associated with worsened liver-related outcomes (adjusted odds ratio = 7.6, 95% CI 1.8-31.6).CONCLUSION: Higher frequency of HDV screening than previously published data could be seen among CHB patients at KUH in a low-endemic setting. Receiving a delayed screening test seems to be associated with worse outcomes, stressing the need of a strategy for timely HDV diagnosis.
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| 14. |
- Kåberg, Martin, et al.
(author)
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High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:5, s. 574-580
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Journal article (peer-reviewed)abstract
- Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.
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| 15. |
- Lybeck, Charlotte, 1979-, et al.
(author)
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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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In: GastroHep. - : Wiley-Blackwell Publishing Inc.. - 1478-1239. ; 3:3, s. 185-195
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Journal article (peer-reviewed)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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| 16. |
- Lybeck, Charlotte, 1979-
(author)
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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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Doctoral thesis (other academic/artistic)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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| 17. |
- Millbourn, Charlotta, et al.
(author)
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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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In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:11, s. 776-785
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Journal article (peer-reviewed)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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| 18. |
- Razavi, Homie A., et al.
(author)
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Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries
- 2023
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In: JOURNAL OF HEPATOLOGY. - : Elsevier. - 0168-8278 .- 1600-0641. ; 79:2, s. 576-580
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Journal article (peer-reviewed)abstract
- Hepatitis D virus (HDV) infection occurs as a coinfection with hepatitis B and increases the risk of hepatocellular carcinoma, decompensated cirrhosis, and mortality compared to hepatitis B virus (HBV) monoinfection. Reliable estimates of the prevalence of HDV infection and disease burden are essential to formulate strategies to find coinfected individuals more effectively and efficiently. The global prevalence of HBV infections was estimated to be 262,240,000 in 2021. Only 1,994,000 of the HBV in-fections were newly diagnosed in 2021, with more than half of the new diagnoses made in China. Our initial estimates indicated a much lower prevalence of HDV antibody (anti-HDV) and HDV RNA positivity than previously reported in published studies. Ac-curate estimates of HDV prevalence are needed. The most effective method to generate estimates of the prevalence of anti-HDV and HDV RNA positivity and to find undiagnosed individuals at the national level is to implement double reflex testing. This re-quires anti-HDV testing of all hepatitis B surface antigen-positive individuals and HDV RNA testing of all anti-HDV-positive in-dividuals. This strategy is manageable for healthcare systems since the number of newly diagnosed HBV cases is low. At the global level, a comprehensive HDV screening strategy would require only 1,994,000 HDV antibody tests and less than 89,000 HDV PCR tests. Double reflex testing is the preferred strategy in countries with a low prevalence of HBV and those with a high prevalence of both HBV and HDV. For example, in the European Union and North America only 35,000 and 22,000 cases, respectively, will require anti-HDV testing annually.
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| 19. |
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| 20. |
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| 21. |
- Simon, Tracey G., et al.
(author)
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Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality
- 2020
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In: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 382:11, s. 1018-1028
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Journal article (peer-reviewed)abstract
- BACKGROUND: More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection.METHODS: Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events.RESULTS: With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4).CONCLUSIONS: In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.).
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| 22. |
- Udumyan, Ruzan, 1971-, et al.
(author)
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Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:5, s. 597-605
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Journal article (peer-reviewed)abstract
- Background: β-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of β-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014.Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures.Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, β-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); p = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); p = .006], β1-receptor selective [0.86 [0.75-1.00); p = .049] and lipophilic [0.78 (0.67-0.90); p = .001] β-blockers. No association was observed for hydrophilic β-blockers [1.01 (0.80-1.28); p = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); p = .062].Conclusion: β-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective β-blocker use.
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| 23. |
- Westin, Johan, 1965, et al.
(author)
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Management of hepatitis B virus infection, updated Swedish guidelines
- 2020
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In: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 52:1, s. 1-22
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Journal article (peer-reviewed)abstract
- Despite access to effective antiviral drugs and vaccines, hepatitis B virus (HBV) infection remains a major health issue worldwide. HBV is highly infectious and may cause chronic infection, progressive liver damage, hepatocellular cancer (HCC) and death. Early diagnosis, proper management and timing of treatment are crucial. The Swedish Reference group for Antiviral Treatment (RAV) here provides updated evidence-based guidelines for treatment and management of HBV infection which may be applicable also in other countries. Tenofovir alafenamide (TAF) has been introduced as a novel treatment option and new principles regarding indication and duration of treatment and characterization of hepatitis B have been gradually introduced which justifies an update of the previous guidelines from 2007. Updated guidelines on HCC surveillance in HBV-infected patients, treatment and prophylaxis for patients undergoing liver transplantation as well as management of pregnant women and children with HBV infection are also provided.
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