Clinical and economic impact of an alert system in primary care for the detection of patients with chronic hepatitis C.

INTRODUCTION: Prevalence of chronic hepatitis C (CHC) is higher in patients born between 1955-1975. The aim was to perform an economic evaluation of an age-based electronic health record (EHR) alert in primary care to detect patients with undiagnosed CHC and its treatment in comparison with non-use of the alert system, in Valencian Community, Spain. MATERIALS AND METHODS: Decision trees and Markov model were used to evaluate the diagnosis and progression of the disease, respectively. CHC was diagnosed by serology and viral load in seropositive subjects. Epidemiological data and diagnostic costs were extracted from public sources of the Valencian Community. Probabilities, utilities and costs of model states were obtained from the literature. The impact on mortality and hepatic complications avoided by the implementation of the alert were estimated, and efficiency was measured as an incremental cost-utility ratio (ICUR) based on quality-adjusted life years (QALYs) and the costs of both alternatives. RESULTS: The EHR alert detected 269,548 patients, of whom 1,331 had CHC (vs. 23 patients with non-alert). Over the patients' lifetime, the alert would prevent 93% of decompensated cirrhosis cases, 87% of hepatocellular carcinomas, 90% of liver transplants, and 89% of liver related deaths compared to non-use of the alert system. In addition, it would obtain an additional 3.3 QALY per patient, with an incremental cost of €10,880 and an ICUR of €3,321. CONCLUSIONS: The implementation of an age-based EHR alert in primary care to detect patients with CHC reduces hepatic complications and mortality and is an efficient strategy.

HCV RNA quantification in capillary dried blood spots with the Xpert® HCV Viral Load test for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection.

BACKGROUND: For patients with difficult venous access after long-term intravenous drug use, rapid point-of-care hepatitis C virus (HCV) RNA quantification in capillary whole blood with the Xpert® HCV Viral Load Fingerstick (VL FS) test (60 minutes) is a convenient and reliable method for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection. However, an expensive GeneXpert® system must be available on site. In decentralised settings with a low case-load, dried blood spot (DBS) testing might be an alternative. METHODS: Between December 2019 and January 2021, patients with an indication for HCV RNA quantification and informed consent provided 100 µl capillary whole blood each for on-site Xpert® HCV VL FS testing (reference) and DBS testing in the laboratory. For the latter, 100 µl blood, collected with an EDTA Minivette®, were transferred to a Whatman® 903 filter card. After drying for at least 1 hour, the DBS sample was packed into a sealable plastic bag with desiccant and sent to the central laboratory of our hospital, where it was stored at -20°C. For HCV RNA extraction, the whole DBS was cut out with an 18-mm puncher and transferred into 1.3 ml guanidinium thiocyanate-containing buffer (provided by Cepheid®). After mixing and incubating at room temperature for 2-3 hours, 1 ml supernatant was analysed with the Xpert® HCV VL test (105 minutes) (filter paper absorbs 0.3 ml). RESULTS: Of 109 paired samples from 67 patients, 38 (34.9%) were positive with the Xpert® HCV VL FS test. Sensitivity and specificity of DBS testing were 89.5% (34/38; 95% confidence interval [CI] 75.9-95.8%) and 97.2% (69/71; 95% CI 90.3-99.2%), respectively. The six (5.5%) discordant results (four false negative, two false positive) all were observed in samples with HCV RNA detectable below the limit of quantification after 2-8 weeks of pan-genotypic direct-acting antiviral treatment or 5 weeks after acute hepatitis C in a patient clearing HCV spontaneously. Quantifiable results (n = 30; 16 genotype 1, 7 genotype 3, 4 genotype 4, 1 genotype 1a and 3a, 2 unknown; HCV RNA range: 2.74-6.66 log IU/ml) correlated well (R2 = 0.981). On average, uncorrected DBS test results were 1.30 ± 0.14 log IU/ml lower than Xpert® HCV VL FS test results (~42 µl instead of the expected 1000 µl plasma used). Storage of DBS samples at room temperature for 7 days before freezing reduced HCV RNA by 0.29 ± 0.12 log IU/ml. CONCLUSION: HCV RNA can reliably be quantified with the Xpert® HCV VL test in capillary dried blood spot samples. Thus, access to capillary HCV RNA quantification for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection can be extended to decentralised settings with a low case load.

Integrated treatment of hepatitis C virus infection among people who inject drugs: A multicenter randomized controlled trial (INTRO-HCV).

BACKGROUND: The standard pathways of testing and treatment for hepatitis C virus (HCV) infection in tertiary healthcare are not easily accessed by people who inject drugs (PWID). The aim of this study was to evaluate the efficacy of integrated treatment of chronic HCV infection among PWID. METHODS AND FINDINGS: INTRO-HCV is a multicenter, randomized controlled clinical trial. Participants recruited from opioid agonist therapy (OAT) and community care clinics in Norway over 2017 to 2019 were randomly 1:1 assigned to the 2 treatment approaches. Integrated treatment was delivered by multidisciplinary teams at opioid agonist treatment clinics or community care centers (CCCs) for people with substance use disorders. This included on-site testing for HCV, liver fibrosis assessment, counseling, treatment, and posttreatment follow-up. Standard treatment was delivered in hospital outpatient clinics. Oral direct-acting antiviral (DAA) medications were administered in both arms. The study was not completely blinded. The primary outcomes were time-to-treatment initiation and sustained virologic response (SVR), defined as undetectable HCV RNA 12 weeks after treatment completion, analyzed with intention to treat, and presented as hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals. Among 298 included participants, 150 were randomized to standard treatment, of which 116/150 (77%) initiated treatment, with 108/150 (72%) initiating within 1 year of referral. Among those 148 randomized to integrated care, 145/148 (98%) initiated treatment, with 141/148 (95%) initiating within 1 year of referral. The HR for the time to initiating treatment in the integrated arm was 2.2 (1.7 to 2.9) compared to standard treatment. SVR was confirmed in 123 (85% of initiated/83% of all) for integrated treatment compared to 96 (83% of initiated/64% of all) for the standard treatment (OR among treated: 1.5 [0.8 to 2.9], among all: 2.8 [1.6 to 4.8]). No severe adverse events were linked to the treatment. CONCLUSIONS: Integrated treatment for HCV in PWID was superior to standard treatment in terms of time-to-treatment initiation, and subsequently, more people achieved SVR. Among those who initiated treatment, the SVR rates were comparable. Scaling up of integrated treatment models could be an important tool for elimination of HCV. TRIAL REGISTRATION: ClinicalTrials.gov.no NCT03155906.

Retrospective Evaluation of Hepatitis C Awareness in Turkey Through Two Decades.

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is the only viral infection that can be treated with oral antiviral agents. However, CHC awareness is a major barrier to the World Health Organization's target of eliminating hepatitis C virus (HCV) by 2030. Here, CHC awareness trends were analyzed in Hacettepe University Hospital, Turkey, between January 2000 and December 2017. MATERIALS AND METHODS: Central laboratory data were retrospectively analyzed for HCV test results (anti-HCV, HCV RNA, HCV genotype). After combining 548,141 anti-HCV test results, 395,103 cases were analyzed. The following two parameters were defined for CHC awareness: (1) the presence of HCV RNA results for anti-HCV positives and (2) the presence of a genotype result for HCV RNA positives. RESULTS: Anti-HCV positives were older than negatives (mean age-years ± SD, 59.4 ± 19.0 vs. 44.0 ± 18.9), and the positivity rate was higher in women than in men (1.4% vs. 1.0%). Anti-HCV positivity decreased from 3.1% to 0.6% from 2000 to 2015 and subsequently stabilized. The overall percentage of RNA testing among anti-HCV positives was 53.1% (range, 20%-70%), which stabilized at approximately 50% after 2010. The genotyping rate for RNA positives varied between 40% and 70%. The main genotype identified was genotype 1 (85.7%). CONCLUSION: In an ideal CHC awareness state, all anti-HCV positives should undergo RNA testing, and genotyping should be performed when RNA tests are positive. However, even in our referral center, the combined rate of RNA and genotype testing was only approximately 50% during the last 10 years.

Monitoring hepatitis C virus treatment rates in an Opioid Treatment Program: A longitudinal study.

BACKGROUND: Direct-acting antivirals (DAAs) are recommended for the treatment of hepatitis C virus (HCV) infection in patients treated with methadone or buprenorphine. AIM: To assess HCV treatment rates in an Opioid Treatment Program (OTP). METHODS: This longitudinal study included 501 patients (81.4% men, median age: 45 years; interquartile range: 39-50 years) enrolled in an OTP between October 2015 and September 2017. Patients were followed until September 2019. Data on socio-demographics, substance use, HCV infection, human immunodeficiency virus (HIV) infection and laboratory parameters were collected at entry. We analyzed medical records to evaluate HCV treatment. Kaplan-Meier methods and Cox regression models were used to analyze the DAA treatment uptake and to identify treatment predictors. RESULTS: Prevalence of HCV and HIV infection was 70% and 34%, respectively. Among anti-HCV-positive (n = 336) patients, 47.2%, 41.3%, and 31.9% used alcohol, cannabis, and cocaine, respectively. HCV-RNA tests were positive in 233 (69.3%) patients. Twentyeight patients (8.3%) cleared the infection, and 59/308 (19.1%) had received interferon-based treatment regimens before 2015. Among 249 patients eligible, 111 (44.6%) received DAAs. Treatment rates significantly increased over time from 7.8/100 person-years (p-y) (95%CI: 5.0-12.3) in 2015 to 18.9/100 p-y (95%CI: 11.7-30.3) in 2019. In a multivariate analysis, patients with HIV co-infection were twice as likely to receive DAAs (HR = 1.94, 95%CI: 1.21-3.12) than patients with HCV mono-infection. Current drug use was an independent risk factor for not receiving treatment against infection (HR = 0.48, 95%CI: 0.29-0.80). CONCLUSION: HCV treatment is evolving in patients with HCV-HIV co-infection. Ongoing drug use while in an OTP might negatively impact the readiness to treat infection.

Cost effectiveness of treatment models of care for hepatitis C: the South Australian state-wide experience.

AIM: The objective was to study the long-term (lifetime) cost effectiveness of four different hepatitis C virus (HCV) treatment models of care (MOC) with directly acting antiviral drugs. METHODS: A cohort Markov model-based probabilistic cost-effectiveness analysis (CEA) was undertaken extrapolating to up to 30 years from cost and outcome data collected from a primary study involving a real-life Australian cohort. In this study, noncirrhotic patients treated for HCV from 1 March 2016 to 28 February 2017 at four major public hospitals and liaising sites in South Australia were studied retrospectively. The MOC were classified depending on the person providing patient workup, treatment and monitoring into MOC1 (specialist), MOC2 (mixed specialist and hepatitis nurse), MOC3 (hepatitis nurse) and MOC4 (general practitioner, GP). Incremental costs were estimated from the Medicare perspective. Incremental outcomes were estimated based on the quality-adjusted life years (QALY) gained by achieving a sustained virological response. A cost-effectiveness threshold of Australian dollar 50 000 per QALY gained, the implicit criterion used for assessing the cost-effectiveness of new pharmaceuticals and medical services in Australia was assumed. Net monetary benefit (NMB) estimates based on this threshold were calculated. RESULTS: A total of 1373 patients, 64% males, mean age 50 (SD ±11) years, were studied. In the CEA, MOC4 and MOC2 clearly dominated MOC1 over 30 years with lower costs and higher QALYs. Similarly, NMB was the highest in MOC4, followed by MOC2. CONCLUSION: Decentralized care using GP and mixed consultant nurse models were cost-effective ways of promoting HCV treatment uptake in the setting of unrestricted access to new antivirals.

Geographically Focused Collocated Hepatitis C Screening and Treatment in Los Angeles's Skid Row.

BACKGROUND: The inequitable prevalence of hepatitis C (HCV) in the homeless is a clinical and public health concern. Prior research estimates, at least one-quarter of homeless persons have been infected with HCV, yet linkage to care and treatment uptake remains marginal. AIM: To evaluate the feasibility of treating HCV in a homeless population. METHODS: Retrospective study of homeless individuals treated for HCV. Demographic information including risk factors was collected. Univariate analyses were performed. The proportion of patients linked to care and sustained viral response at 12 weeks post-treatment (SVR12) was measured. RESULTS: During the study period, 6767 individuals were screened for HCV. A total of 769 (11.4%) were found to have detectable HCV antibodies. Of the individuals with detectable HCV antibodies, 443 (57.6%) were viremic. Of the 443 viremic patients, 375 (84.7%) were linked to care. Among them, 59 patients began antiviral treatment and 95% (56/59) completed the course of therapy. The ITT was 83.1% (49/59), and the per-protocol virologic cure rate was 100% (49/49). CONCLUSION: The favorable linkage to care and cure outcomes in our study suggests that homeless persons may be more likely to engage in HCV screening and treatment when these services are located in the community for their use. Our study further lends support to the efficacy of care coordination programs to encourage movement through the HCV care continuum in vulnerable populations.

Outcomes of Direct-Acting Antiviral Treatment of Psychiatric Patients with Comorbid Hepatitis C Virus Infection.

BACKGROUND: The highest burden of hepatitis C virus (HCV) infection is seen in patients with psychiatric disorders who have been excluded from traditional treatments with Interferon due to treatment-emergent neuropsychiatric adverse effects. The goal of this study is to determine the tolerability, treatment retention, and efficacy of direct-acting antivirals with psychiatric disorders and comorbid substance use disorders in real-life settings. METHODS: This is a retrospective cohort observational study of HCV patients treated with direct-acting antivirals between January 2016 and December 2018. Patients were stratified and sub-stratified based on their psychiatric diagnosis and substance use. The primary assessment was the sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: Among the 291 patients analyzed, patients with psychiatric diagnosis and non-psychiatric patients made up 51.2% (n = 149) and 48.8% (n = 142) respectively. Majority of the patients included in the study were African-Americans (68.7%, n = 200). Overall, 95.3% (142/149) and 94.4% (134/142) of psychiatric and non-psychiatric patients, respectively, achieved SVR12 and treatment response was similar between the groups (p = 0.72). Among psychiatric patients, only the prior treatment status was identified as a predictor of treatment response (OR 0.153, 95% CI 0.03-0.79; p = 0.05). No statistical difference was observed among the patients with SVR12 based on their primary psychiatric diagnoses or by comorbid substance abuse. CONCLUSION: The results of our study show that direct-acting antiviral treatments are well tolerated in psychiatric patients, and an overwhelming majority of patients achieved SVR12. Our study highlights the need to integrate HCV screening with treatment linkage in psychiatry and primary care practice.

Effects of vitamin D supplements in patients with chronic hepatitis C: a randomized, multi-center, open label study.

BACKGROUND/AIMS: We aimed to assess the role of vitamin D supplementation in the response to pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment in patients with chronic hepatitis C (CHC). METHODS: Our study was a multi-center, randomized controlled trial in 11 hospitals. CHC patients were randomly assigned (1:1) to two groups namely, PEGIFN-α plus RBV (control group) or PEG-IFN-α plus RBV + vitamin D (800 IU daily) (vitamin D group). The primary end-point was the rate of sustained virologic response (SVR). RESULTS: One hundred forty eight CHC patients were randomly assigned to two groups. Seventy-one patients received the PEG-IFN-α plus RBV and 77 patients received the PEG-IFN-α plus RBV + vitamin D. A total of 105 patients completed the study (control group, 47 vs. vitamin D group, 58). Baseline characteristics were mostly similar in both the groups. There was a modest but non-significant increase in SVR in the vitamin D group compared to the control group with the intention to treat analysis (64.0% vs. 49.3 %, p = 0.071) as well as in the per protocol analysis (control group vs. vitamin D group: 74.5% vs. 84.5%, p = 0.202). Fifty-two patients (73.2%) in the control group and 63 patients (81.8%) in the vitamin D group experienced at least one adverse event. The drop-out rate due to adverse effects was not different between both groups (control group vs. vitamin D group: 19.7% vs. 10.4%, p = 0.111). CONCLUSION: Vitamin D supplement did not increase SVR in treatment naïve patients with CHC irrespective of genotype.

Rapid point-of-care HCV RNA quantification in capillary whole blood for diagnosing chronic HCV infection, monitoring treatment and detecting reinfection.

BACKGROUND: Rapid point-of-care capillary hepatitis C virus (HCV) RNA quantification could remove barriers to chronic hepatitis C diagnosis and treatment. AIMS: To evaluate the diagnostic accuracy of rapid point-of-care HCV RNA quantification by Cepheid®’s GeneXpert® in 100 µl capillary whole blood using our laboratory-based standard quantitative HCV polymerase chain-reaction (PCR) test (Roche Cobas® Ampliprep/Taqman) with 650 µl venous EDTA plasma as the reference test. METHODS: In a prospective study conducted between November 2016 and May 2019 in the Infectious Diseases Outpatient Clinic of a Swiss tertiary care hospital, all adults with an indication for HCV RNA quantification (including HCV treatment monitoring) and written informed consent provided venous and capillary blood for parallel testing. Up to October 2018, we used the Xpert® HCV Viral Load (VL) test (105 min; developed for 1 ml plasma or serum), for which 1 ml Cepheid® buffer was added to 100 µl finger-stick capillary whole blood (~55% plasma). Thereafter, the Xpert® HCV Viral Load Finger-Stick (VL FS) test (60 min; specifically developed for 100 µl capillary whole blood) was evaluated. RESULTS: (1) Xpert® HCV VL test. Among 194 paired samples from 88 patients, 99 (51.0%) were positive using Cobas® in venous plasma. Sensitivity and specificity of the Xpert® HCV VL test with 100µl capillary whole blood was 97.0% (96/99; 95% confidence interval [CI] 91.5–99.0%) and 94.7% (90/95; 95% CI 88.3–97.7%), respectively. The eight (4.1%) discordant results (three false negative, five false positive) were all under direct acting antiviral (DAA) treatment (week 1–4 or end of treatment), when HCV RNA was near the limit of quantification (highest HCV RNA value missed by Xpert® 68 IU/ml). Quantifiable results (n = 68) correlated well (R2 = 0.9165) irrespective of genotype, sex and HIV status. On average, Xpert® HCV VL test results were 1.32 (±0.34) log IU/ml lower, which corresponds to the ~18-fold smaller plasma volume used (~55 vs 1000µl). (2) Xpert® HCV VL FS test: Among 33 paired samples from 23 patients, 15 (45.5%) were positive using Cobas® in venous plasma. Sensitivity and specificity of the Xpert® HCV VL FS test with 100 µl capillary whole blood was 100% (15/15; 95% CI 79.6–100%) and 88.9% (16/18; 95% CI 67.2–96.9%), respectively. The two (6.1%) discordant results (both false positive) were under DAA treatment (week 3 and 4), when HCV RNA was near the limit of quantification. Quantifiable results (n = 14) correlated well (R2 = 0.9899). On average, Xpert® HCV VL FS test results were 0.10 (±0.17) log IU/ml lower. CONCLUSIONS: Point-of-care HCV RNA quantification in capillary whole blood is a convenient, rapid and reliable method to diagnose active HCV infection, monitor treatment response and detect reinfection. For patients with difficult venous access after long-term intravenous drug use, capillary testing removes a crucial barrier to HCV treatment and reinfection monitoring. Same-day results might improve linkage to care.

Antioxidants benefits in hepatitis C infection in the new DAAs era.

Some of the evidence on whether antioxidant supplements are effective in treatment of liver diseases is contradictory. Here we perform a descriptive analysis of the available data in vivo and in vitro of the possible antiviral action and controversy of several antioxidant molecules against HCV.

Comparative hepatoprotective effect of Nigella sativa pre- and post-treatment to rabbits.

Synthetic drugs are associated with adverse side-effects and rapid increase in resistance to most of them inspires to evaluate plants for their therapeutic values. We have been aimed to suggest the medicinal use of Nigella sativa seed aqueous extract to minimize the severity of liver damage via its antioxidant properties and its role in maintenance of cell ion-homeostasis. Annoyances in serum levels of some antioxidants and trace metals in human hepatitis C infected patients were compared with that from acetaminophen-induced hepatotoxic rabbits. Serum analysis of human patients and that of hepatotoxic rabbits have exhibited the same trend of incidence of liver marker enzymes, antioxidant levels, and trace metal concentrations, except for the serum levels of cobalt. Significance of pre-/ or post-treatment of Nigella sativa to acetaminophen induced-hepatotoxic rabbit has also evaluated. NS post-treatment to rabbits has been found effective in normalizing the levels (P<0.001) of serum liver markers; especially the ALP levels, and the antioxidants; with significant effect on the serum catalase levels. However, NS pre-treatment has shown its role (P<0.001) in maintaining the serum nickel and cobalt concentrations. Therefore, we suggest the use of Nigella sativa seeds as pre-/ or post-treatment therapy, and also as supplement to the normal medications of liver infection to normalize the status of cell antioxidants and trace metal concentrations.

Hepatite C no sistema público de saúde brasileiro: impacto da doença / Hepatitis c in the brazilian public health care system: burden of disease

ABSTRACT BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

RESUMO CONTEXTO: A infecção pelo vírus da hepatite C (HCV) é uma das principais causas de hepatite C crônica e provoca implicações graves para pacientes, familiares e sistema de saúde. OBJETIVO: Os objetivos deste estudo foram: analisar a gravidade da fibrose hepática, comorbidades e complicações da hepatite C; examinar a qualidade de vida relacionada à saúde (QVRS), a perda de produtividade e o uso de recursos e custos no sistema público por pacientes brasileiros com hepatite C crônica, genótipo tipo 1. MÉTODOS: Foi realizado um estudo transversal, multicêntrico em pacientes com hepatite C crônica genótipo-1 para avaliar a carga da doença no sistema público de saúde brasileiro entre novembro de 2014 e março de 2015. Os pacientes foram submetidos a uma elastografia hepática transitória (FibroScan) para avaliar a fibrose e a uma entrevista composta por um questionário desenvolvido para o estudo e cinco questionários padronizados: EQ-5D-3L, HCV-PRO, e WPAI:HepC. RESULTADOS: Foram recrutados 313 pacientes. A amostra foi composta predominantemente por mulheres (50,8%), caucasianos/brancos (55,9%) e indivíduos empregados (39,9%). A média de idade foi 56 (DP=10,4) anos. Em média, os pacientes com HCV esperaram 40,6 (DP=49,6) meses entre o diagnóstico e o primeiro tratamento. Ademais, 42,8% dos pacientes que realizaram o FibroScan tinham cirrose; a comorbidade mais frequente foi doença cardiovascular (62,6%) e a complicação mais comum as varizes esofágicas (54,5%). Os resultados também mostraram que "dor e desconforto" foi a dimensão de QVRS mais afetada (55,0% dos pacientes relataram alguns problemas) e que a média do escore do HCV-PRO foi 69,1 (DP=24,2). Em relação à perda de produtividade, o componente do WPAI:HepC mais afetado foi atividade diária (23,5%) e entre os pacientes empregados, presenteísmo foi mais frequente do que absenteísmo (18,5% vs 6,5%). Os custos diretos médicos totais com essa amostra foi de 12.305,72USD por paciente em um período de dois anos; o tratamento medicamentoso representou 95% desse total. CONCLUSÃO Esse estudo mostrou a maioria dos pacientes possui cirrose, apresenta alta prevalência de doenças cardiometabolicas e varizes esofágicas, QVRS reduzida principalmente em termos de dor/desconforto e dano na produtividade, especialmente presenteísmo. Adicionalmente, nós demonstramos que o HCV impõe uma carga econômica no sistema de saúde brasileiro e que os medicamentos correspondem à maioria dos custos.

Tratamento cirúrgico de lesões císticas do pâncreas: uma experiência unicêntrica / Surgical management of cystic lesions of the pancreas: a single-centre experience

ABSTRACT BACKGROUND: Cystic lesions of the pancreas represent a group of pancreatic diseases with great histological heterogeneity, varying from benign lesions, some of them with malignant potential, to overt malignant lesions. OBJECTIVE: To describe the cases of cystic lesions of the pancreas which underwent surgical intervention at a tertiary university hospital. METHODS: This is a retrospective population-based study (historical cohort) which was carried out enrolling individuals attended at the Outpatient service of Pancreas Surgery of the Hospital de Clínicas of Unicamp. The individuals underwent surgical procedures performed from January 2012 through December 2016. RESULTS: In the period evaluated, 39 cases of cystic lesions of the pancreas which underwent surgery were identified, 26 (66.6%) of which were female. The average age at diagnosis was 47.4±16.4 years (range, 18-73). In regards to symptoms, 35 (89.7%) were symptomatic. The average length of hospital stay was 10 days (range 4-76). Surgeries performed to treat the lesions depended on the localization and type of the lesions: cystojejunostomy (41%), distal pancreatectomy (36%), pancreaticoduodenectomy (15.4%), drainage of ruptured and/or infected pseudocyst (5.2%) and central pancreatectomy (2.6%). CONCLUSION: Cystic lesions of the pancreas are a group of lesions with a highly varying presentation and diagnostic approach and may require an also highly variable surgical treatment. An appropriate preoperative imaging diagnosis is essential for their management.

RESUMO CONTEXTO: As lesões císticas do pâncreas representam um grupo de doenças pancreáticas com grande heterogeneidade histológica, variando desde lesões benignas, algumas com potencial pré-maligno, até outras degeneradas para formas malignas. OBJETIVO: Descrever os casos de LCPs submetidos à intervenção cirúrgica em um hospital universitário terciário. MÉTODOS: Trata-se de um estudo retrospectivo populacional (coorte histórica) realizado com a participação de indivíduos atendidos no Ambulatório de Cirurgia do Pâncreas do Hospital de Clínicas da Unicamp. Os indivíduos foram submetidos a procedimentos cirúrgicos realizados no período de janeiro de 2012 a dezembro de 2016. RESULTADOS: No período avaliado, foram identificados 39 casos de lesões císticas do pâncreas operados, sendo 26 (66,6%) do sexo feminino. A idade média no diagnóstico foi de 47,4±16,4 anos. Em relação aos sintomas, 35 (89,7%) eram sintomáticos. O tempo médio de internação foi de 10 dias (variação de 4-76). As cirurgias realizadas para o tratamento das lesões dependeram da localização e do tipo das lesões: derivação pseudocisto-jejunal (41%), pancreatectomia distal (36%), pancreaticoduodenectomia (15,4%), drenagem de pseudocistos rotos e/ou infectados (5,2%) e pancreatectomia central (2,6%). CONCLUSÃO: As lesões císticas do pâncreas são um grupo de lesões cuja apresentação e abordagem diagnóstica são altamente heterogêneas e que podem requerer um tratamento cirúrgico altamente complexo e variável. Um diagnóstico pré-operatório adequado é essencial para definir o seu tratamento.

Cost-effectiveness of hepatitis C screening and treatment linkage intervention in US methadone maintenance treatment programs.

BACKGROUND: We evaluated the cost-effectiveness of a hepatitis C (HCV) screening and active linkage to care intervention in US methadone maintenance treatment (MMT) patients using data from a randomized trial conducted in New York City and San Francisco. METHODS: We used a decision analytic model to compare 1) no intervention; 2) HCV screening and education (control); and 3) HCV screening, education, and care coordination (active linkage intervention). We also explored an alternative strategy wherein HCV/HIV co-infected participants linked elsewhere. Trial data include population characteristics (67% male, mean age 48, 58% HCV infected) and linkage rates. Data from published sources include treatment efficacy and HCV re-infection risk. We projected quality-adjusted life years (QALYs) and lifetime medical costs using an established model of HCV (HEP-CE). Incremental cost-effectiveness ratios (ICERs) are in 2015 US$/QALY discounted 3% annually. RESULTS: The control strategy resulted in a projected 35% linking to care within 6 months and 31% achieving sustained virologic response (SVR). The intervention resulted in 60% linking and 54% achieving SVR with an ICER of $24,600/QALY compared to no intervention from the healthcare sector perspective and was a more efficient use of resources than the control strategy. The intervention had an ICER of $76,500/QALY compared to the alternative strategy. From a societal perspective, the intervention had a net monetary benefit of $511,000-$975,600. CONCLUSIONS: HCV care coordination interventions that include screening, education and active linkage to care in MMT settings are likely cost-effective at a conventional $100,000/QALY threshold for both HCV mono-infected and HIV co-infected patients.

Recreational Drug and Psychosocial Profile in Chronic Hepatitis C Patients Seeking Antiviral Therapy.

BACKGROUND AND AIMS: Practitioners treating hepatitis C (HCV) provide healthcare to a special population with high rates of substance abuse and psychiatric disorders. We investigated the psychosocial profile in HCV patients and tested what variables affect commencement of antiviral therapy. MATERIAL AND METHODS: Recreational drug use (RDU), marijuana (THC), alcohol use, and psychiatric history were initially investigated with a questionnaire prior to history and physical. Following an educational intervention, we reinterrogated patients for RDU and THC use, and revision of initial statement was documented. Variables affecting commencement of antiviral therapy were analysed with logistic regression. RESULTS: Out of 153 patients, 140 (92%) answered the questionnaire. Intervention increased total yield by 6%, however, 39% (11/28) of those initially denying use revised their statement. Drug screening identified 9 more patients with RDU/THC use. Half of patients consuming alcohol were heavy drinkers, and psychiatric disease was identified in 54%. Only 73 (48%) of 139 patients eligible for antivirals received treatment. Multivariable analysis revealed that younger patients (OR = 1.04, 95% CI 1.01-1.08), and those testing positive on drug screen (OR = 0.41, 95% CI 0.19-0.92) were less likely to be treated. Denial by insurance and loss to follow-up were the most common reasons for not starting antiviral treatment. CONCLUSION: Substance abuse is highly prevalent among HCV patients, and it is difficult to tell prior from current users. Integral care of HCV patients should include a diligent screen for substance abuse and rehabilitation referral, aiming to increase the pool of patients eligible for antiviral therapy. This can only be achieved through a multidisciplinary approach.

Early Successes in an Open Access, Provincially Funded Hepatitis C Treatment Program in Prince Edward Island.

INTRODUCTION: The availability of curative hepatitis C therapies has created an opportunity to improve treatment delivery and access. Local providers, government, industry, and community groups in Prince Edward Island developed an innovative province-wide care model. Our goal was to describe the first year of program implementation. MATERIAL AND METHODS: Using a communitybased prospective observational study design, all chronic hepatitis C referrals received from April 2015 to April 2016 were recorded in a database. Primary analysis assessed the time from referral to assessment/treatment, as well as the number of referrals, assessments, and treatment initiations. Secondary objectives included: (1) treatment effectiveness using intention-to-treat analysis; and (2) patient treatment experience assessed using demographics, adverse events, and medication adherence. RESULTS: During the study period 242 referrals were received, 123 patients were seen for intake assessments, and 93 initiated direct-acting antiviral therapy based on medical need. This is compared to 4 treatment initiations in the previous 2 years. The median time from assessment to treatment initiation was 3 weeks. Eighty-two of 84 (97.6%, 95% CI 91.7 - 99.7%) patients for whom outcome data were available achieved sustained virologic response at 12 weeks post-treatment; 1 was lost to follow-up and 1 died from an unrelated event. In the voluntary registry, 39.7% of patients reported missed treatment doses. CONCLUSION: In conclusion, results from the first 12 months of this multi-phase hepatitis C elimination strategy demonstrate improved access to treatment, and high rates of safe engagement and cure for patients living with chronic hepatitis C genotype 1 infections.

HEPATITIS C IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM: BURDEN OF DISEASE.

BACKGROUND: Infection by hepatitis C virus is one of the leading causes of chronic hepatitis C and cause severe burden for patients, families and the health care system. OBJECTIVE: The aims of this research were to assess the severity of liver fibrosis, comorbidities and complications of hepatitis C virus; to examine health-related quality of life (HRQoL), productivity loss and resource use and costs in a sample of Brazilian chronic hepatitis C, genotype 1, patients. METHODS: This was a cross-sectional multicenter study performed in genotype-1 chronic hepatitis C patients to assess disease burden in the Brazilian public health care system between November 2014 and March 2015. Patients were submitted to a liver transient elastography (FibroScan) to assess liver fibrosis and answered an interview composed by a questionnaire specifically developed for the study and three standardized questionnaires: EQ-5D-3L, HCV-PRO and WPAI:HepC. RESULTS: There were 313 subjects enrolled, with predominance of women (50.8%), caucasian/white (55.9%) and employed individuals (39.9%). Mean age was 56 (SD=10.4) years old. Moreover, 42.8% of patients who underwent FibroScan were cirrhotic; the most frequent comorbidity was cardiovascular disease (62.6%) and the most frequent complication was esophageal varices (54.5%). The results also showed that "pain and discomfort" was the most affected HRQoL dimension (55.0% of patients reported some problems) and that the mean HCV-PRO overall score was 69.1 (SD=24.2). Regarding productivity loss, the most affected WPAI:HepC component was daily activity (23.5%) and among employed patients, presenteeism was more frequent than absenteeism (18.5% vs 6.5%). The direct medical costs in this chronic hepatitis C sample was 12,305.72USD per patient in the 2 years study period; drug treatment costs represented 95.9% of this total. CONCLUSION: This study showed that most patients are cirrhotic, present high prevalence of cardiometabolic diseases and esophageal varices, reduced HRQoL mainly in terms of pain/discomfort, and work productivity impairment, especially presenteeism. Additionally, we demonstrated that hepatitis C virus imposes an economic burden on Brazilian Health Care System and that most of this cost is due to drug treatment.

Modeling the fiscal costs and benefits of alternative treatment strategies in the United Kingdom for chronic hepatitis C.

BACKGROUND: Hepatitis C (HCV) infection causes substantial direct health costs, but also impacts broader societal and governmental costs, such as tax revenue and social protection benefits. This study investigated the broader fiscal costs and benefits of curative interventions for chronic Hepatitis C (CHC) that allow individuals to avoid long-term HCV attributed health conditions. METHODS: A prospective cohort model, assessing the long-term fiscal consequences of policy decisions, was developed for HCV infected individuals, following the generational accounting analytic framework that combines age-specific lifetime gross taxes paid and governmental transfers received (i.e. healthcare and social support costs). The analysis assessed the burden of a theoretical cohort of untreated HCV infected patients with the alternative of treating these patients with a highly efficacious curative intervention (ledipasvir/sofosbuvir [LDV/SOF]). It also compared treating patients at all fibrosis stages (Stages F0-F4) compared to late treatment (Stage F4). RESULTS: Based on projected lifetime work activity and taxes paid, the treated cohort paid an additional £5,900 per patient compared to the untreated cohort. Lifetime government disability costs of £97,555 and £125,359 per patient for treated cohort vs no treatment cohort were estimated, respectively. Lifetime direct healthcare costs in the treated cohort were £32,235, compared to non-treated cohort of £26,424, with an incremental healthcare costs increase of £5,901 per patient. The benefit cost ratio (BCR) of total government benefits and savings relative to government treatment costs (including LDV/SOF) ranged from 1.8-5.6. Treating patients early resulted in 77% less disability costs, 43% lower healthcare costs, and 33% higher tax revenue. CONCLUSION: The ability to cure Hepatitis C offers considerable fiscal benefits beyond direct medical costs and savings attributed to reduced disability costs, public allowances, and improved tax revenue. Changes in parameters, such as productivity, wage growth, and tax rates, can influence the conclusions described here.

Are RA patients from a non-endemic HCV population screened for HCV? A cross-sectional analysis of three different settings / ¿Debe de realizarse un tamizaje de VHC en pacientes con artritis reumatoide pertenecientes a un área no-endémica? Estudio transversal en tres diferentes sistemas de salud

Introduction. In Mexico, other risk factors are associated with hepatitis C virus (HCV): prior heroin users, living alone, widower, and northern region residence. Rheumatoid arthritis (RA) patients are considered immunosuppressed and HCV testing is recommended before treatment. The aim of the study was to describe the characteristics of HCV testing in RA patients in three different medical care settings in a non-endemic area. Methods. A retrospective observational study was performed using medical records from 960 RA patients describing the indications for HCV testing. Results. The test was performed in 28.6% and the HCV overall frequency was 0.36%. Population characteristics were not associated with an increased risk of HCV infection; therefore, anti-HCV positivity was low. The main reason for testing was before starting biological agents. Conclusion. Due to the low pre-test probability, testing for HCV infection should be personalized; i.e., according to disease prevalence in a particular geographical location and the individual risk factors (AU)

Introducción. En México, se han descrito factores de riesgo para virus de hepatitis C (VHC), además de los conocidos como: consumo de heroína, individuos que viven solos, ser viudo y residencia en el norte del país. Los pacientes con artritis reumatoide (AR) son considerados inmunodeprimidos y se recomienda realizar pruebas de VHC antes del inicio del tratamiento. El objetivo fue describir las características de pacientes con AR a quienes se realizaron pruebas de VHC. Material y métodos. Estudio observacional, retrospectivo de 960 registros médicos donde se describieron las indicaciones para las prueba de VHC. Resultados. La prueba se realizó en el 28.6% y la frecuencia global de VHC fue de 0.36%. Las características de la población no se asociaron con un mayor riesgo de infección, por lo tanto la presencia de anti-VHC fue baja. La principal razón para realizar la prueba fue el inicio de tratamiento biológico. Conclusión. Debido a la baja probabilidad pre-test, las pruebas para el VHC deben ser personalizadas, es decir, según la prevalencia de la enfermedad de acuerdo a la zona geográfica y los factores de riesgo individuales (AU)