Martin Kåberg

Historical epidemiology of hepatitis C virus (HCV) in selected countries

Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV‐infected populations are critical for addressing HCV‐related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.

Strategies to manage hepatitis C virus (HCV) disease burden

The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.

Hepatitis C infection among injection drug users in Stockholm Sweden: Prevalence and gender

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.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

The future disease burden of hepatitis C virus infection in Sweden and the impact of different treatment strategies

Abstract 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.

Knowledge of status and assessment of personal health consequences with hepatitis C are not enough to change risk behaviour among injecting drug users in Stockholm County, Sweden.

This was a multicentre study with risk perception as the theoretical framework, investigating if risk behaviours change when injecting drug users (IDUs) are aware of their hepatitis C virus (HCV) status and had assessed the health consequences with HCV infection. Two hundred and thirteen participants aged 15–40 y were analysed. Sharing of needles and of other injecting equipment were common both among participants who reported HCV-positive status (74%, 95% confidence interval (CI) 65.3–80.1%) and among those who reported HCV status unknown (68%, 95% CI 56.0–78.4%). Participants associating very severe health consequences with HCV infection and those who did not know of any health consequences with HCV infection shared needles at almost the same rate (78%, 95% CI 62.5–87.7 vs 69%, 95% CI 8.0–78.9, respectively). Sharing of other injecting equipment was most common among participants with verified HCV-positive status (adjusted risk ratio 5.64, 95% CI 2.64–12.07). Knowledge of HCV status and assessment of health consequences with HCV infection were not enough to change injecting risk behaviours. Sharing of other injecting equipment was a more important risk factor than sharing needles for participants with verified HCV-positive status. It is suggested that professionals engage IDUs in risk analysis and open a dialogue about assessment in order to identify, quantify and characterize risks.

Model projections on the impact of HCV treatment in the prevention of HCV transmission among people who inject drugs in Europe

BACKGROUND & AIMS Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

Restrictions for reimbursement of interferon-free direct-acting antiviral therapies for HCV infection in Europe

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Prevalence of hepatitis C and pre-testing awareness of hepatitis C status in 1500 consecutive PWID participants at the Stockholm needle exchange program

Abstract Background: People who inject drugs (PWID) are the driving force of the hepatitis C virus (HCV) epidemic. Still, treatment is scarcely offered and the awareness of HCV status in PWID is poor. Prevention includes clean needles, syringes and other paraphernalia. HCV awareness was investigated in 1500 PWID in a needle exchange program (NEP) in Stockholm, Sweden, together with HCV prevalence, and time to HCV infection after start of injection drug use. Methods: 1500 PWID in the Stockholm NEP were consecutively enrolled. At baseline, awareness of the individual pre-test HCV status was measured followed with tests for anti-HCV and HCV RNA if anti-HCV was positive. Results: Mean age of participants was 39 years and the mean time of injection drug use 18 (0–51) years. The overall anti-HCV prevalence was 82% whereof 76% were HCV RNA positive. Within 4 years after start of injection drug use 50% of the participants were anti-HCV positive. Self-awareness of HCV status was low. Hence, 32% who believed that they never have encountered HCV were anti-HCV positive, and 24% were HCV RNA positive. For those who reported not being aware of their HCV status 62% were anti-HCV positive, and 47% were HCV RNA positive. Conclusion: The very high prevalence of chronic HCV in PWID in Stockholm indicates that both measures for prevention with increased awareness of HCV, and a higher antiviral treatment utilisation in combination need to be implemented in order to reduce the HCV prevalence and combat the HCV epidemic.

Incidence and spontaneous clearance of hepatitis C virus (HCV) in people who inject drugs at the Stockholm Needle Exchange-Importance for HCV elimination

The major transmission route for hepatitis C virus (HCV) is through sharing of unsterile injection equipment among people who inject drugs (PWID). The WHO strategy for HCV elimination by 2030 proposes increased efforts to treat PWID populations that drive the HCV epidemic. Among participants in the Stockholm needle exchange programme (NEP), the HCV prevalence is 60%. We aimed to study HCV incidence, spontaneous HCV clearance rate, and predictors associated with new HCV infections and reinfections in NEP participants. All 2320 patients enrolled in the programme between 8 April 2013 and 23 September 2016 were tested for HCV at baseline, and responded to a questionnaire regarding sociodemographic data and injection risk behaviour. Tests for HCV were repeated at an interval of 3‐6 months. The anti‐HCV prevalence in the NEP participants at baseline was 77%, and the prevalence of HCV RNA was 57%. 24% of the anti‐HCV positive were HCV RNA negative with a spontaneously cleared HCV infection. The overall HCV incidence rate was 22/100 PY. The HCV incidence rate in the HCV naive group was 26/100 PY, and in the spontaneously cleared group 19/100. Although there were no significant differences in becoming HCV infected between the two groups (31% vs 29%), the rate of spontaneous HCV clearance was significantly lower in the HCV naive group, 20% vs 44%, (P < 0.05). A high HCV incidence rate was noted among the PWID indicating that treatment needs to be scaled up in conjunction with harm reduction measures to achieve HCV elimination goals set by WHO. This includes high coverage needle exchange programmes and effective addiction treatment for substance users, including opiate substitution treatment.