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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. [ABSTRACT FROM AUTHOR]

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 towards the World Health Organization (WHO) elimination targets and identify remaining barriers. Methods: The data used for modelling HCV transmission and disease burden in Sweden were obtained through literature review, unpublished sources and expert input.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 towards HCV elimination. Results: At the beginning of 2019, there were 29 700 (95% uncertainty interval: 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 (i) expanding harm reduction programmes to reach more than 90% of people who inject drugs (PWID) and (ii) treating 90% of HCV + PWID engaged in harm reduction programmes and ≥7% of PWID not involved in harm reduction programmes, annually by 2025. Conclusions: It is of utmost importance that Sweden, and all countries, find sustainability in HCV programmes by broadening the setting and base of providers to provide stability and continuity of care during turbulent times. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The NS5A resistance-associated substitution (RAS) Y93H is found quite frequently (5–10%) at baseline in direct-acting antiviral agents (DAA) treatment-naïve 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. [ABSTRACT FROM AUTHOR]

In a recent expert meeting, Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated. An interferon-free combination of direct-acting antiviral agents is considered and indicated for all patients with chronic HCV infection, but the ability to treat all is limited primarily by high cost of medication. The group of patients prioritized for therapeutic intervention has been extended to also include fertile women desiring to become pregnant. A more thorough discussion of treatment for people who inject drugs (PWIDs) in order to diminish transmission is included, and the clinical significance of baseline NS5A resistance associated variants (RAVs), also known as resistance associated substitutions (RASs), for the treatment of HCV genotype 1a or 3 infection is discussed. [ABSTRACT FROM AUTHOR]

Purpose:The aim of this study was to estimate the prevalence of physician-diagnosed and registered chronic hepatitis C (CHC), and to estimate the reported frequencies of Charlson comorbidities compared with matched comparators from the general population. Materials and methods:Patients were identified according to ICD codes for CHC in the Swedish National Patient Register (1997–2013). Prevalence was estimated according to different patient identification algorithms and for different subgroups. Charlson comorbidities were ascertained from the same register and compared with age/sex/county of residence matched general population comparators. Results:A total of 34,633 individuals with physician-diagnosed CHC were alive in Sweden in 2013 (mean age, 49 years; 64% men), corresponding to a physician-diagnosed prevalence of 0.36%. The prevalence varied by case definition (0.22%-0.36%). The estimate dropped to 0.14% for monitored CHC disease (defined as ≥1 CHC-related visit in 2013). Overall, 41.3% of the CHC patients had ≥1 physician-registered Charlson comorbidity; the most common was liver diseases (22.1%). Compared with matched comparators from the general population (n = 171,338), patients with CHC had more physician-diagnosed and registered diseases such as chronic pulmonary disease (10.2% vs. 4.0%), diabetes (10.6% vs. 5.5%) and liver-related cancer (1.3% vs. 0.2%; allp < .01). No information on behavioural factors, such as smoking, alcohol consumption or on-going illicit drug use, was available. Conclusion:The physician-diagnosed prevalence of CHC was slightly lower than previously reported estimates, and varied by case definition. The additional comorbidities observed in the CHC group should be taken into consideration, as these comorbidities add to the disease burden. [ABSTRACT FROM PUBLISHER]

Introduction Hepatitis C virus ( HCV) infection is common in patients with inherited bleeding disorders treated with clotting factor concentrates prior to the introduction of viral inactivation of these products. The long-term consequences of hepatitis C infection in Swedish patients are not fully understood. Aim To examine the impact of HCV infection on liver-related morbidity and mortality in Swedish patients with inherited bleeding disorders. Methods We retrospectively collected data on 183 patients with inherited bleeding disorders infected with HCV who attended the Coagulation Unit at Karolinska University Hospital, Sweden. Data regarding end-stage liver disease ( ESLD), defined as presence of ascites, encephalopathy, variceal bleeding, hepatocellular carcinoma or liver-related death, were collected from the patient records and the national registers. Results The median follow-up time was 35.9 years ( IQR 29.0-41.2). A total of 41% had achieved sustained virological response ( SVR) after treatment. In total, 14.2% developed ESLD at the median age of 52.6 years ( IQR 46.5-64.7). Nineteen (35.8%) of all deaths were due to liver-related causes. Co-infection with human immunodeficiency virus ( HIV), older age at time of infection and severe form of bleeding disorder was associated with higher risk of developing ESLD, while SVR was a strong protective factor. Conclusions This study demonstrated that liver-related morbidity and mortality was significant in patients with bleeding disorders and HCV infection in Sweden. Patients with HCV-infection should be candidates for treatment with the new highly effective antiviral drugs, since SVR proved to be a strong protective factor. [ABSTRACT FROM AUTHOR]

In a recent expert meeting, Swedish recommendations for the treatment of HCV infection were updated. An interferon-free combination of direct-acting antiviral agents was recommended as the first line standard-of-care treatment for chronic HCV infection. Interferon-based therapy should be considered as a second line option after an individual benefit-risk assessment. Treatment is strongly recommended for HCV infected patients with bridging fibrosis or cirrhosis (Metavir stages F3–4), before and after liver transplantation, and in the presence of extra-hepatic manifestations. Additionally, patients with moderate liver fibrosis (stage F2) as well as women in need of in vitro fertilisation should be prioritised for therapeutic intervention. Treatment indications for people who inject drugs, children, chronic kidney disease and HIV co-infection are also discussed. [ABSTRACT FROM AUTHOR]

Objective. Recently, new highly effective direct-acting antivirals (DAAs) against hepatitis C virus (HCV) were introduced. Whether these will alleviate the anticipated increase of liver disease burden in Sweden is unknown, partly because high costs may restrict the use. The objectives were to model the HCV epidemic in Sweden, the burden of disease, and the potential impact of different treatment strategies. Material and methods. HCV disease progression was modeled to 2030. Scenarios were simulated using new DAAs with sustained annual treatment rate ( n = 1130), reduced treatment rate ( n = 380) to maintain budget, and increased treatment rates ( n = 1430 or 2260) to reduce HCV infections. Results. With today's triple therapies, the estimated number of serious liver complications and death are expected to peak in 2021. Using new DAAs among F0-F4 patients, an unchanged annual treatment rate can reduce the number of HCV infections by 10% by 2030; however, hepatocellular carcinoma (HCC) and mortality will remain unchanged. By reducing to 380 treatments annually and focusing on patients with advanced fibrosis (F3-F4), serious complications will remain constant but the total number of HCV infections will increase. By doubling the number of DAA treatments, HCC-incidence and liver-related deaths would decrease by 65-70% by 2030. Conclusion. Mortality and HCC can be reduced with new DAAs and sustained treatment uptake when restricted to F2-F4 patients, or with increased uptake in F0-F4 patients. Treatment restrictions to limit cost may reduce the positive effects and increase the burden of HCV infection. These results may be important for the future strategies of HCV management. [ABSTRACT FROM AUTHOR]

Swedish recommendations for the treatment of hepatitis C virus (HCV) infection were updated at a recent expert meeting. Therapy for acute HCV infection should be initiated if spontaneous resolution does not occur within 12 weeks. The recommended standard-of-care therapy for chronic HCV genotype 1 infection is an HCV protease inhibitor in combination with peginterferon (peg-IFN) and ribavirin. Treatment is strongly recommended in patients with bridging fibrosis and cirrhosis, whereas in patients with less advanced fibrosis, deferring therapy may be preferential in light of likely therapeutic improvements in the near future. Patients with chronic genotype 2/3 infection should generally be treated with peg-IFN and ribavirin for 24 weeks. In patients with a very rapid viral response (i.e. HCV RNA below 1000 IU/ml on day 7), or favourable baseline characteristics and undetectable HCV RNA week 4, treatment can be shortened to 12-16 weeks, provided that no dose reductions are needed. [ABSTRACT FROM AUTHOR]

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43 000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215 000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) infection is widespread among injection drug users. Young women seem to be at higher risk of acquiring HCV. To optimize future intervention and prevention measures, we studied the epidemiology of human immunodeficiency virus (HIV), hepatitis B (HBV), and HCV infection among men and women. Inclusion criteria for this cross-sectional multicentre study were: history of ever injecting drugs, age > 18 y, and no previous HIV diagnosis. In 310 participants, plasma/serum samples were analysed for HBV, HIV and HCV (anti-HCV, HCV-RNA, and HCV genotype). HCV antibodies were noted in 268 (86.5%) participants, of whom 207 (77.0%) also had detectable HCV-RNA. Genotypes 1 and 3 dominated, at 35.9% and 33.0%, respectively. Women acquired HCV (but not HBV) to a significantly higher degree (RR 2.97, 95% confidence interval 1.11-7.93) during the first y of injecting drugs. They also recovered spontaneously from HCV infection more frequently (RR 2.49, 95% CI 1.28-4.53). The HCV prevalence of about 50% within 2 y after initiation of injection drug use underlines the need for early intervention efforts. Possible causes for higher HCV prevalence and the implications of favourable spontaneous recovery rates among women should be considered when designing intervention and prevention measures. [ABSTRACT FROM AUTHOR]

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.). [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has set a goal to eliminate hepatitis C virus (HCV) infection by 2030, including a 90% reduction of HCV incidence. With the introduction of a needle syringe program (NSP) in Stockholm, Sweden, and unrestricted availability of direct acting antiviral (DAA) treatment, we investigate the change of prevalence and incidence of HCV infection among people who inject drugs (PWID) over time. All persons attending the Stockholm NSP 2013-2021 (n=4,138) were included. The prevalence of viremic HCV infection was investigated yearly. For incidence analysis, PWID at risk with at least one follow-up test were included. Participants were divided into naive defined as anti-HCV negative (n=791), and exposed, defined as anti-HCV positive with a negative HCV RNA (n=1,030). Risk factors for HCV infection were analyzed using parametric exponential proportional hazards regression models. The prevalence of viremic HCV infection decreased from 62% to 30% year 2013-2021 while the prevalence of cured after treatment increased from 0 to 22%, corresponding to 42% cured after treatment out of eligible in 2021. The overall incidence rate in naive was 16.9 (95% CI 15.0-19.0) and in exposed 12.8 (95% CI 11.6-14.2) per 100 person years (PY) and was not significantly reduced years 2013-2015 to 2020-2021 in either group. Risk factors for incident HCV infection in multivariable analysis were sharing needles/syringes, younger age, custody/prison past year, and homelessness, whereas opioid agonist treatment was protective. The prevalence of HCV was halved in PWID as unrestricted DAA treatment became available and NSP was established in Stockholm. However, overall incidence was not reduced. To meet the WHO incidence goal, targeting PWID with high injection risk behaviors for testing and treatment is essential, along with engagement in harm reduction services. [ABSTRACT FROM AUTHOR]