Hepatitis C virus micro-elimination: Where do we stand? Mangia, Alessandra; Cotugno, Rosa; Cocomazzi, Giovanna ...
World journal of gastroenterology : WJG,
2021-Apr-28, 2021-4-28, 20210428, Letnik:
27, Številka:
16
Journal Article
Odprti dostop
Hepatitis C virus (HCV) elimination by 2030, using direct-acting antiviral treatments, has been promoted by the World Health Organization. This achievement is not attainable, however, particularly ...after the 2020 pandemic of the coronavirus disease 2019. Consequently, the more realistic objective of eliminating HCV from population segments for which targeted strategies of prevention and treatment are easily attained has been promoted in Europe, as a valid alternative. The underlying idea is that micro-elimination will ultimately lead to macro-elimination. The micro-elimination strategy may target different specific populations and at-risk groups. Different settings, including prisons and hospitals, have also been identified as micro-elimination scenarios. In addition, dedicated micro-elimination strategies have been designed that are tailored at the geographical level according to HCV epidemiology and individual country's income. The main elements of a valid and successful micro-elimination project are reliable epidemiological data and active involvement of all the stakeholders. Community involvement represents another essential component for a successful program.
AIM To review Hepatitis C virus(HCV) prevalence and genotypes distribution worldwide.METHODS We conducted a systematic study which represents one of the most comprehensive effort to quantify global ...HCV epidemiology,using the best available published data between 2000 and 2015 from 138 countries(about 90% of the global population),grouped in 20 geographical areas(with the exclusion of Oceania),as defined by the Global Burden of Diseases project(GBD). Countries for which we were unable to obtain HCV genotype prevalence data were excluded from calculations of regional proportions,although their populations were included in the total population size of each region when generating regional genotype prevalence estimates.RESULTS Total global HCV prevalence is estimated at 2.5%(177.5 million of HCV infected adults),ranging from 2.9% in Africa and 1.3% in Americas,with a global viraemic rate of 67%(118.9 million of HCV RNA positive cases),varying from 64.4% in Asia to 74.8% in Australasia. HCV genotype 1 is the most prevalent worldwide(49.1%),followed by genotype 3(17.9%),4(16.8%) and 2(11.0%). Genotypes 5 and 6 are responsible for the remaining < 5%. While genotypes 1 and 3 are common worldwide,the largest proportion of genotypes 4 and 5 is in lower-income countries. Although HCV genotypes 1 and 3 infections are the most prevalent globally(67.0% if considered together),other genotypes are found more commonly in lowerincome countries where still account for a significant proportion of HCV cases.CONCLUSION A more precise knowledge of HCV genotype distribution will be helpful to best inform national healthcare models to improve access to new treatments.
Despite the great successes achieved in the fields of virology and diagnostics,several difficulties affect improvements in hepatitis C virus(HCV)infection control and eradication in the new era.New ...HCV infections still occur,especially in some of the poorest regions of the world,where HCV is endemic and long-term sequelae have a growing economic and health burden.An HCV vaccine is still no available,despite years of researches and discoveries about the natural history of infection and host-virus interactions:several HCV vaccine candidates have been developed in the last years,targeting different HCV antigens or using alternative delivery systems,but viral variability and adaption ability constitute major challenges for vaccine development.Many new antiviral drugs for HCV therapy are in preclinical or early clinical development,but different limitations affect treatment validity.Treatment predictors are important tools,as they provide some guidance for the management of therapy in patients with chronic HCV infection:in particular,the role of host genomics in HCV infection outcomes in the new era of direct-acting antivirals may evolve for new therapeutic targets,representing a chance for modulated and personalized treatment management,when also very potent therapies will be available.In the present review we discuss the most recent data about HCV epidemiology,the new perspectives for the prevention of HCV infection and the most recent evidence regarding HCV diagnosis,therapy and predictors of response to it.
To analyse the variation of hepatitis C virus (HCV) prevalence and genotype distribution and their determinants in people living with human immunodeficiency virus (HIV) who entered care between 1997 ...and 2015.
HIV-infected patients enrolled in ICONA who were tested for HCV antibodies (HCV-Ab) were included.
Overall 3407 of 12 135 (28.1%) were HCV-Ab+; and 735 of 12 135 (6.1%) were HBsAg+. Among patients whose HCV genotype was known, the most represented were genotypes 1 and 3. The prevalence of HCV infection decreased from 49.2% (2565/5217) during 1997–2002 to 10.2% (556/5466) during 2009–2015. The frequency of genotype 1a increased from 29.0% (264/911) to 43.0% (129/300), whereas genotype 3 decreased from 38.5% (351/911) to 27.0% (81/300). Independent predictors of HCV-Ab+ status were being female (adjusted OR (AOR) 1.23, 95% CI 1.04–1.50, p = 0.01), risk category (versus injecting drug users: men who have sex with men AOR 0.01, 95% CI 0.01–0.01, p <0.001; heterosexuals AOR 0.01, 95% CI 0.01–0.01, p <0.001; other/unknown AOR 0.02, 95% CI 0.01–0.02, p <0.001), being cared for in Central Italy (versus being cared for in Northern Italy: AOR 0.85, 95% CI 0.73–0.98, p <0.001), being Italian-born (AOR 1.44, 95% CI 1.16–1.80, p = 0.001) and being enrolled in less recent calendar years (versus 1997–2002: 2009–2015 AOR 0.23, 95% CI 0.19–0.27, p <0.001; 2003–2008 AOR 0.49, 95% CI 0.41–0.61, p <0.001).
The prevalence of HCV infection in HIV-infected patients entering into care in Italy significantly declined in more recent calendar years. After adjusting for risk factors and calendar years, HCV co-infection was more frequent in females and in those born in Italy.
Objectives
Clinical trials of all‐oral direct‐acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection reported high response rates in HCV/HIV coinfection, similar to those obtained in ...HCV monoinfection. We evaluated the safety and efficacy of these regimens in a clinical practice setting.
Methods
In this prospective observational study, all the HCV‐monoinfected and HCV/HIV‐coinfected patients undergoing HCV treatment with all‐oral DAA regimens in a routine clinical setting from December 2014 to December 2015 were included in the analysis. Sustained virological response 12 weeks after the end of therapy (SVR12) and reported adverse events (AEs) were evaluated. Resistance‐associated variants (RAVs) were analysed in a subgroup of patients at baseline and at the time of viral rebound in those with virological failure.
Results
One‐hundred and nine patients (51 HCV‐infected and 58 HCV/HIV‐coinfected) were enrolled in the study. Sixty per cent had cirrhosis and 52% were pegylated interferon and ribavirin (pegIFN/RBV)‐experienced. Thirty‐six per cent received ombitasvir + paritaprevir/ritonavir + dasabuvir, 25% sofosbuvir + daclatasvir, 16% sofosbuvir + simeprevir, 17% sofosbuvir + ribavirin and 6% sofosbuvir + ledipasvir; ribavirin was used in 57% of subjects. The SVR12 rate was 91% and 96% in HIV‐infected and uninfected patients, respectively (P = 0.44). The 4‐week HCV viral decline was similar in the two groups. RAVs were found at baseline in 23 of 49 patients and did not affect SVR12. No predictors of SVR12 were identified in our cohort.
Conclusions
Treatment with all‐oral DAA combinations of patients infected with HCV and with HCV/HIV under real‐life conditions led to high and similar rates of SVR12. Moreover, the historical factors associated with a sustained virological response to pegIFN/RBV were not predictive of the response to all‐oral DAAs.
Many studies showed insulin resistance amelioration in HCV‐patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to ...assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct‐acting antivirals (DAAs) in HCV‐patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P < 0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV‐patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long‐term.
Evaluating trends in HCV treatment and prevalence is crucial for monitoring elimination. We evaluated the change in current infection and treatment among people who inject drugs (PWID) between ...2018-2019 and 2019-2021.
ETHOS Engage is an observational cohort study of PWID attending drug treatment clinics and needle and syringe programs in Australia. Participant enrolment occurred over two periods, Wave 1 (May 2018-September 2019, 25 sites) and Wave 2 (November 2019-June 2021, 21 sites), with baseline questionnaire completion and point-of-care HCV RNA testing (Xpert® HCV Viral Load Fingerstick). Logistic regression was used to identify factors associated with current HCV infection and historic HCV treatment.
2,395 individuals were enrolled across the two recruitment waves (66% male, median age 43, 72% current opioid agonist therapy, and 65% injecting in the previous month). HCV prevalence decreased from 24% to 17% between 2018-2019 and 2019-2021, respectively (p=0.003). HCV treatment increased from 66% to 74% between 2018-2019 and 2019-2021, respectively (p<0.001). After adjusting, there was a reduction in current HCV infection in 2019-2021 (adjusted odds ratio aOR 0.62; 95% CI, 0.50, 0.77) compared to 2018-2019. Other factors associated with current infection included homelessness (aOR, 1.70; 1.26, 2.30), incarceration (vs. never; historic: aOR 1.69; 95%CI 1.31, 2.19; recent: aOR 1.85; 95%CI, 1.35, 2.54), and recently injecting drugs (vs. >12 months ago; previous month <daily: aOR 2.03; 95%CI, 1.37, 3.02; ≥daily: aOR 2.90; 95%CI, 1.94, 4.32).
The increase in HCV treatment and decrease in prevalence among PWID provides evidence of further progress towards HCV elimination; however, sub-populations may require additional support to enhance elimination.
PWID are a priority population to facilitate HCV elimination and temporal data are crucial to understand trends in HCV infection and treatment in this group. Among a cohort of PWID recruited during two different waves and in an era of unrestricted DAA therapy, prevalence of HCV infection decreased and the proportion who had received HCV treatment increased. Sub-populations of PWID—including people who are homeless, people who have been incarcerated, people who frequently inject drugs, younger people, women, and people not engaged in OAT—may require additional support to enhance HCV elimination efforts.
This study evaluated HCV treatment initiation among people who inject drugs (PWID) following an intervention of campaign days involving peer connection, point-of-care HCV RNA testing, and linkage to ...nursing support. ETHOS Engage is an observational cohort study of PWID attending 25 drug treatment clinics and needle and syringe programs in Australia (May 2018–September 2019). Point-of-care results were provided to the nurse, facilitating confirmatory testing and treatment. The study aimed to evaluate treatment uptake and factors associated with treatment at 24 months post-enrolment. There were 317 people with current HCV infection and eligible for treatment (median age 43, 65% male, 15% homeless, 69% receiving opioid agonist treatment, 70% injected in last month). Overall, 15% (47/317), 27% (85/317), 38% (120/317), and 49% (155/317) of people with current HCV infection had initiated treatment at 3-, 6-, 12-, and 24-months following testing, respectively. Homelessness (adjusted hazard ratio (aHR): 0.40; 95% confidence interval: 0.23, 0.71) and incarceration in the past 12 months (vs. never, aHR:0.46; 0.28, 0.76) were associated with decreased treatment initiation in the 24 months post-enrolment. This testing campaign intervention facilitated HCV treatment uptake among PWID. Further interventions are needed to achieve HCV elimination among people experiencing homelessness or incarceration.
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