The civil society monitoring of hepatitis C response related to the WHO 2030 elimination goals in 35 European countries.

BACKGROUND: People who inject drugs (PWID) account for the majority of new cases of hepatitis C virus (HCV) infection in Europe; however, HCV testing, and treatment for PWID remain suboptimal. With the advent of direct acting antivirals (DAAs) the World Health Organization (WHO) adopted a strategy to eliminate HCV as public health threat by 2030. To achieve this, key policies for PWID must be implemented and HCV continuum of care needs to be monitored. This study presents results of the first monitoring led by civil society that provide harm reduction services for PWID. METHODS: In 2019, harm reduction civil society organizations representing focal points of Correlation-European Harm Reduction Network in 36 European countries were invited to complete a 27-item online survey on four strategic fields: use/impact of guidelines on HCV testing and treatment for PWID, availability/functioning of continuum of care, changes compared to the previous year and, the role of harm reduction services and non-governmental organizations (NGOs) of PWID. A descriptive analysis of the responses was undertaken. RESULTS: The response rate was 97.2%. Six countries reported having no guidelines on HCV treatment (17.1%). Twenty-three (65.7%) reported having treatment guidelines with specific measures for PWID; guidelines that impact on accessibility to HCV testing/treatment and improve access to harm reduction services in 95.6% and 86.3% of them, respectively. DAAs were available in 97.1% of countries; in 26.4% of them they were contraindicated for active drug users. HCV screening/confirmatory tests performed at harm reduction services/community centers, prisons and drug dependence clinics were reported from 80.0%/25.7%, 60.0%/48.6%, and 62.9%/34.3% of countries, respectively. Provision of DAAs at drug dependence clinics and prisons was reported from 34.3 to 42.9% of countries, respectively. Compared to the previous year, HCV awareness campaigns, testing and treatment on service providers' own locations were reported to increase in 42.9%, 51.4% and 42.9% of countries, respectively. NGOs of PWID conducted awareness campaigns on HCV interventions in 68.9% of countries, and 25.7% of countries had no such support. CONCLUSION: Further improvements in continuum-of-care interventions for PWID are needed, which could be achieved by including harm reduction and PWID organizations in strategic planning of testing and treatment and in efforts to monitor progress toward WHO 2030 elimination goal.

Elimination of hepatitis C in Europe: can WHO targets be achieved?

BACKGROUND: Chronic hepatitis C virus (HCV) infection affects 71 million people worldwide. The availability of highly efficient direct-acting antivirals has revolutionized the treatment landscape with over 95% cure rates. The WHO has launched a global programme to achieve rather ambitious HCV elimination targets for 2030. OBJECTIVES: This article aims to provide a critical overview of the current HCV elimination programmes in Europe highlighting the elements that should be implemented to achieve elimination and those that are already in place to promote this process. SOURCES: Review of the recently published literature and opinion of experts in the field. CONTENT: Elimination of hepatitis C as a public health threat appears to be a difficult task, which should be subdivided into smaller targets, the so-called micro-elimination goals, to increase chances of success. Macro-elimination strategies based on mass-screening are difficult to implement. Evidence supporting the efficacy of micro-elimination comes from key populations, such as people who inject drugs. HCV elimination is proceeding at different speeds in Europe. Some countries are on target with the WHO's objectives whereas others lack economic support and political advocacy, and have insufficient infrastructures to achieve this. The absence of an effective prophylactic vaccine is hampering the process and should be overcome. IMPLICATIONS: Elimination of hepatitis C worldwide appears plausible, but in several countries probably not within the time frame suggested by the WHO. In the absence of vaccination, universal access to HCV treatment would act as a 'therapeutic' option to reduce transmission, especially in high-risk populations.

We know DAAs work, so now what? Simplifying models of care to enhance the hepatitis C cascade.

Globally, some 71 million people are chronically infected with hepatitis C virus (HCV). Marginalized populations, particularly people who inject drugs (PWID), have low testing, linkage to care and treatment rates for HCV. Several models of care (MoCs) and service delivery interventions have the potential to improve outcomes across the HCV cascade of care, but much of the relevant research was carried out when interferon-based treatment was the standard of care. Often it was not practical to scale-up these earlier models and interventions because the clinical care needs of patients taking interferon-based regimens imposed too much of a financial and human resource burden on health systems. Despite the adoption of highly effective, all-oral direct-acting antiviral (DAA) therapies in recent years, approaches to HCV testing and treatment have evolved slowly and often remain rooted in earlier paradigms. The effectiveness of DAAs allows for simpler approaches and has encouraged countries where the drugs are widely available to set their sights on the ambitious World Health Organization (WHO) HCV elimination targets. Since a large proportion of chronically HCV-infected people are not currently accessing treatment, there is an urgent need to identify and implement existing simplified MoCs that speak to specific populations' needs. This article aims to: (i) review the evidence on MoCs for HCV; and (ii) distil the findings into recommendations for how stakeholders can simplify the path taken by chronically HCV-infected individuals from testing to cure and subsequent care and monitoring.

The benefits of hepatitis C virus cure: Every rose has thorns.

To examine mid-term benefits on hepatic complications, extrahepatic clinical syndromes and quality of life associated with HCV cure; to review the few safety issues linked to oral direct-acting antivirals (DAAs); and to discuss the potential population benefits of reducing the burden of HCV infection. DAAs cure HCV infection in more than 95% of patients. The halting of liver inflammation and fibrosis progression translates into both hepatic and extrahepatic benefits and reduces the need for liver transplantation. A reduction in the frequency of extrahepatic manifestations such as mixed cryoglobulinaemia and vasculitis and improvements in quality of life and fatigue have also been described. A few safety issues linked to DAAs such as the potential recurrence of aggressive HCC, the flares of hepatitis B virus in patients with overt or occult HBV infection are been discussed. Curing HCV infection also has a high potential to reduce the burden of HCV infection at the population level. With widespread scaling up of HCV treatment, several modeling studies suggest that major reductions in HCV prevalence and incidence are possible, and that elimination of viral hepatitis is an achievable target by 2030.

Addressing barriers to the prevention, diagnosis and treatment of hepatitis B and C in the face of persisting fiscal constraints in Europe: report from a high level conference.

In the WHO-EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120,000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence-based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost-effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis.

Strategies to manage hepatitis C virus infection disease burden - volume 3.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Ureaplasma parvum and Ureaplasma urealyticum detected with the same frequency among women with and without symptoms of urogenital tract infection.

There is mounting evidence stating that Ureaplasma urealyticum causes non-gonococcal urethritis in males, whereas Ureaplasma parvum does not seem to be of clinical significance. However, the clinical role of U. parvum and U. urealyticum in lower urogenital tract infections in females remains unclear. The aim of the study was to determine the frequency of U. parvum and U. urealyticum among 145 Ureaplasma spp. culture-positive women with symptoms of lower urogenital tract infection (n = 75) and those without (n = 70), and to determine possible associations between the detection of U. parvum and U. urealyticum with selected characteristics. Endocervical, urethral, and vaginal swabs, and first voided urine were obtained. Polymerase chain reaction (PCR) was performed to differentiate ureaplasmas. No significant association between the detection of U. parvum or U. urealyticum and symptom status was found. Significantly more women aged 25 years and younger were infected with U. urealyticum (23.4 %) compared to those aged above 25 years (9.2 %) [odds ratio (OR) 3.0 (1.1; 8.1); p = 0.03] and significantly less women aged 25 years and younger (83.5 %) were infected with U. parvum compared to those aged above 25 years (95.5 %) [OR 0.2 (0.1; 0.9); p = 0.03]. The detection of Chlamydia trachomatis was significantly associated to both U. parvum and U. urealyticum (p = 0.021), and to U. parvum alone with borderline significance (p = 0.063). Although neither U. parvum nor U. urealyticum seem to cause symptoms in females, their role in the female urogenital tract remains unknown, taking into account their ubiquity, possible augmentation of the urogenital microenvironment, and ascending capability to the sterile upper reproductive tract.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Peginterferon alfa-2b plus weight-based ribavirin for 24 weeks in patients with chronic hepatitis C virus genotype 1 with low viral load who achieve rapid viral response.

In chronic hepatitis C (CHC), treatment duration may be individualized according to time to first undetectable hepatitis C virus (HCV) RNA, with patients who attain undetectable HCV RNA early in treatment being candidates for shorter regimens. The aim of this study was to determine the relapse rate in patients with CHC genotype (G) 1 infection and low baseline viral load who achieved undetectable HCV RNA by week 4 [rapid virologic response (RVR)] when treated for 24 weeks. This was an open-label, multicentre, noninterventional study. Adult patients with G1 CHC infection and baseline viral load <600,000 IU/mL who attained RVR were treated with peginterferon alfa-2b (1.5 µg/kg/week) plus ribavirin (800-1200 mg/day) for 24 weeks, then followed for a further 24 weeks. The primary endpoint was relapse rate, defined as the proportion of patients with undetectable HCV RNA at treatment week 24 and detectable HCV RNA at week 24 follow-up. The secondary efficacy endpoint was sustained virologic response (SVR). Overall, 170 patients were included in the efficacy-evaluable population. The relapse rate was 9.7% (16/165, 95% confidence interval: 0.06-0.15), and SVR was attained by 149 of 170 patients (87.6%). Virologic outcomes were consistent regardless of age, gender, body weight and genotype. Seven patients reported treatment-emergent serious adverse events (AEs), and four patients discontinued treatment because of an AE. This study further demonstrates that peginterferon alfa-2b plus weight-based ribavirin for 24 weeks is an effective treatment strategy for treatment-naive patients with G1 CHC and low viral load who attain RVR.

Clinical characteristics of adult patients with influenza-like illness hospitalized in general ward during Influenza A H1N1 pandemic 2009/2010.

OBJECTIVE: To investigate clinical and laboratory features of patients with Influenza A H1N1 virus infection hospitalized during 2009/2010 pandemic. METHODS: Prospective observational study comparing clinical and laboratory characteristics of Influenza A H1N1 positive and negative patients with influenza-like illness (ILI). RESULTS: From October 21, 2009 to February 14, 2010 196 ILI patients were admitted, of which 66 tested positive for Influenza A H1N1. The patients with H1N1 infection were younger (43 years vs. 65 years; P < 0.01), more patients were pregnant (P < 0.01), had allergies (P < 0.05) or, asthma (P < 0.01). H1N1 positive patients were more often febrile (91% vs. 72.9%; P < 0.01) and had a higher prevalence of headache (31.8% vs. 18.5%; P < 0.05). Lower values of C-reactive protein (88 pg/dl vs. 126 pg/dl; P < 0.01), procalcitonine (0.42 µg/l vs. 3.98 µg/l; P < 0.05), leukocyte count (7.4*10(9)/l vs. 11.7*10(9)/l; P < 0.01) and higher values of troponin (0.162 µ/l vs. 0.146 µg/l; P < 0.01) were found in H1N1 positive patients. More bacterial infections were found in H1N1 negative group (68.8% vs. 89.2%; P < 0.05). CONCLUSIONS: In this study patients infected with Influenza A H1N1 differed from H1N1 negative ILI patients in several clinical and laboratory characteristics. The same was observed also by other investigators. The results of the study suggest some other specific features, such as a higher incidence of headache and higher values of troponin in Influenza A H1N1 infected patients.

Lichen planus and other cutaneous manifestations in chronic hepatitis C: pre- and post-interferon-based treatment prevalence vary in a cohort of patients from low hepatitis C virus endemic area.

BACKGROUND: Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. OBJECTIVES: To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)-based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV-seropositive patients and 171 HCV-seronegative age- and gender-matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN-based therapy were assessed. RESULTS: Overall presence of LP in HCV-seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN-based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN-based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post-treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85-53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44-12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. CONCLUSIONS: LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post-compared with pre-treated patients. The role of IFN in post-treatment persistence of skin manifestations needs to be assessed.

Chlamydia trachomatis infections in heterosexuals attending sexually transmitted disease clinics in Slovenia.

This study assessed the age and gender distribution of Chlamydia trachomatis infections among patients attending two clinics for sexually transmitted diseases (STDs) in Slovenia. Between January 1999 and December 2003, 1714 heterosexual male and 892 heterosexual female patients were tested for C. trachomatis. The prevalence of C. trachomatis infection was 19.5% (n = 334) for male patients and 10.7% (n = 96) for female patients, with the highest prevalence in the group aged 15-30 years. The prevalence decreased between 2000 and 2003 among female patients. The results support the implementation of routine screening for C. trachomatis genital infection among male and female patients aged < 30 years attending STD clinics in Slovenia.

Treatment of chronic hepatitis C: our experience.

BACKGROUND/AIMS: While an optimal treatment of chronic hepatitis C has not yet been established, it has been demonstrated that the interferon alpha/ribavirin combination is more effective than interferon alpha monotherapy. METHODOLOGY: One hundred and forty-three patients with chronic hepatitis C received the following treatment: eighty patients an 18-month monotherapy (3-month follow-up) and sixty-three patients a 12-month combined therapy (6-month follow-up). Therapeutic efficacy and adverse effects were compared. RESULTS: In 80 patients in the monotherapy group, complete response was achieved in 49.2%. This was reduced to 27.5% three months after therapy. Significant differences were observed in HCV 3 genotype where complete response was achieved in 12 out of 14 patients (p=0.01). With the combined therapy administered to 63 patients, complete response was achieved in 54.5%. This was reduced to 43.2% after 6 months of follow-up. Among the responders or partial responders, significant differences were observed with regard to age (p=0.0047) and subtype 1b (p=0.012). Comparing the groups of naive patients and relapsers, a statistically significant difference (p=0.027) was found in therapeutic efficacy. CONCLUSIONS: In the treatment of chronic hepatitis C, combined therapy proved more effective than monotherapy. This is, however, not yet a satisfactory solution.

The IgG antibody profile to various antigen regions of hepatitis C virus differs in oral fluid and serum of patients with chronic hepatitis C.

Antibodies to hepatitis C virus (HCV) can be detected not only in serum but also in oral fluid. The aim of the study was to determine IgG antibody reactivity directed to six antigen regions of HCV in oral fluid and to evaluate the significance of the antibody pattern in oral fluid compared to serum. Oral fluid and serum samples of 32 HCV viremic patients were collected to detect antibodies to six antigen regions incorporated as antigen bands into modified commercial updated third generation line immuno-assay. Compared to serum, a significantly lower cumulative antibody response and reactivity to five HCV antigens was found in oral fluid. The significantly highest prevalence of oral fluid reactivity was recorded with antigen C1 (78%), whereas in serum the most significantly frequent reactivity was detected with antigen NS3 (100%). The absence of antibody reactivity with antigen E2 was similar in both body fluids. The discrepancy in antibody pattern to HCV antigens between oral fluid and serum indicates the possible existence of local viral replication, viral mutants, viral inhibitors in oral cavity and, most probably, leakage of the muco-vascular barrier.

Second-generation Hybrid capture test and Amplicor monitor test generate highly correlated hepatitis B virus DNA levels.

The performance of the Digene Hybrid Capture II HBV DNA Test HC II and the Roche Cobas Amplicor Monitor Test (Cobas-HBV) was evaluated on 252 serum samples. One hundred and seventy-three samples were HBV DNA positive and 75 HBV DNA negative by both assays. Four samples were HBV DNA positive by Cobas-HBV only. Linear regression analysis showed that the HBV DNA concentrations obtained from both assays were significantly related (n=173, r=0.976, P<0.0001). The results of the study show that Hybrid capture II and Cobas-HBV could be used equally in the management for patients with chronic HBV infection.

Detection of hepatitis C virus RNA from gingival crevicular fluid and its relation to virus presence in saliva.

BACKGROUND: To search for a possible source of hepatitis C virus (HCV) in saliva, the presence and shedding patterns of HCV in gingival crevicular fluid (GCF) and saliva of HCV viremic patients were assessed based on clinical, biochemical, histological, virological, and oral health parameters. METHODS: Saliva and GCF samples of 50 HCV viremic patients were collected to detect HCV RNA by a modified commercial polymerase chain reaction (PCR) assay. Clinical oral examination was performed and periodontal status at the collection sites was monitored. The results were correlated to specified parameters. RESULTS: HCV RNA was detected in 59% (29/49) of the GCF specimens and in 35% (17/48) of the saliva specimens. In saliva specimens, HCV RNA was detected only in cases which also had detectable HCV RNA in the GCF samples (P=0.00002) and was significantly related to the presence of blood in saliva (P=0.03). Higher, but not significant, values of oral clinical parameters at the sites of fluid collection were found in GCF specimens harboring HCV RNA. In GCF specimens with no blood detected, HCV RNA was more often present in cases with higher plasma viral load (P=0.05). CONCLUSIONS: The results suggest that besides blood, the other most probable source of HCV in saliva is GCF. Unknown endogenous HCV inhibitory mechanisms in the oral cavity may explain the discrepancies in HCV appearance between saliva and GCF. The results provide a biologic basis for further investigation of the role of HCV in the pathogenesis of periodontal disease.

Comparative evaluation of semiautomated COBAS AMPLICOR hepatitis B virus (HBV) monitor test and manual microwell plate-based AMPLICOR HBV MONITOR test.

Comparative evaluation of the semiautomated COBAS AMPLICOR hepatitis B virus (HBV) MONITOR Test (COBAS-HBV) and manual AMPLICOR HBV MONITOR Test (AMPLICOR-HBV) on 208 serum samples revealed no significant difference in the sensitivities of the two assays. Twenty samples tested HBV DNA negative and 183 samples tested HBV DNA positive by both assays. Three samples tested positive by COBAS-HBV only and two samples tested positive by AMPLICOR-HBV only. HBV DNA concentrations determined by the two assays were significantly related (n = 183, r = 0.97, P < 0.0001), which indicates that COBAS-HBV could replace AMPLICOR-HBV. The major inconvenience of COBAS-HBV is the required performance of appropriate predilutions of high-titer samples in order to extend the narrow dynamic range of the assay.

Proviral HIV-1 DNA in gingival crevicular fluid of HIV-1-infected patients in various stages of HIV disease.

The oral cavity is rarely reported to be a site of human immunodeficiency virus (HIV) transmission, despite detectable virus in saliva and relatively frequent prevalence of periodontal disease in HIV-infected persons yielding increased excretion of mononuclear-cell-enriched gingival fluid. To search for possible sources of HIV in saliva, and using the polymerase chain-reaction technique, we sought the presence and shedding patterns of proviral HIV-1 DNA in gingival crevicular fluid in a group of patients previously determined as HIV-1-seropositive. Periodontal status at the collection sites was monitored by several clinical parameters, including Plaque Index, Gingival Index, probing depth, and clinical attachment loss. Gingival crevicular fluid samples were collected by means of paper points. Proviral HIV-1 DNA was detected in the gingival fluid of 17 out of 35 HIV-1-infected patients. Its detection correlated significantly with higher plasma HIV-1 RNA viral load (p = 0.03) and not with peripheral blood CD4+ cell count, the presence of blood in gingival fluid, or oral lesions. There was a significant correlation between clinical attachment loss at the sites of fluid collection and plasma HIV-1 RNA viral load (p = 0.002), and borderline correlation between the latter and probing depth (p = 0.54) in the group of patients harboring proviral HIV-1 DNA in gingival crevicular fluid. The results of our study suggest that mononuclear cells present in gingival crevicular fluid and harboring proviral HIV-1 DNA could represent a potential source of HIV-1 in the presence or absence of local bleeding, especially in persons with advanced HIV infection and increased loss of clinical attachment.