Asynchronous electronic consultation between primary care and specialized care proved effective for continuum of care for viraemic hepatitis C patients.

INTRODUCTION: It has been proposed that primary care diagnose and treat hepatitis C virus (HCV) infection. However, a care circuit between primary and specialized care based on electronic consultation (EC) can be just as efficient in the micro-elimination of HCV. It is proposed to study characteristics and predictive factors of continuity of care in a circuit between primary and specialized care. METHODS: From February/2018 to December/2019, all EC between primary and specialized care were evaluated and those due to HCV were identified. Variables for regression analysis and to identify predictors of completing the care cascade were recorded. RESULTS: From 8098 EC, 138 were performed by 89 (29%) general practitioners over 118 patients (median 50.8 years; 74.6% men) and were related to HCV (1.9%). Ninety-two patients (78%) were diagnosed>6 months ago, and 26.3% met criteria for late presentation. Overall, 105 patients required assessment by the hepatologist, 82% (n=86) presented for the appointment, of which 67.6% (n=71) were viraemic, 98.6% of known. Finally, 61.9% (n=65) started treatment. Late-presenting status was identified as an independent predictor to complete the care cascade (OR 1.93, CI 1.71-1.99, p<0.001). CONCLUSION: Communication pathway between Primary and Specialized Care based on EC is effective in avoiding significant losses of viraemic patients. However, the referral rate is very low, high in late-stage diagnoses, heterogeneous, and low in new diagnoses. Therefore, early detection strategies for HCV infection in primary care are urgently needed.

Expectations of patients with hepatitis C from family physicians - a Polish example.

INTRODUCTION: In Poland, approximately 1.9% of the general population is infected with Chronic hepatitis C (HCV), which develops in about 70-80% of infected patients who require constant care from family physicians. OBJECTIVE: The aim of the study was to define the kinds of expectations of patients with chronic HCV from family physicians. MATERIAL AND METHODS: The study included 220 patients with HCV, and was conducted using a dignostic survey, the Patient Request Form (PRF) and an author-constructed questionnaire. RESULTS: The respondents most often expected from a family physician, an explanation of the disease (9.67 scores), and obtaining information concerning examinations and treatment (9.65 scores), while to a lesser degree, emotional support (6.92 scores). Respondents with higher education to a significantly higher degree expected an explanation of the essence of the disease. Patients who were inactive occupationally significantly more frequently expected emotional support and information concerning examinations and treatment. Respondents who considered themselves disabled due to HCV, to a significantly higher degree expected emotional support and information concerning examinations and treatment. The remaining variables: age, gender, place of residence, marital status, self-reported state of health and ordered, diet had no significant effect on the expectations of patients with chronic hepatitis C from family physicians. CONCLUSIONS: Patients with HCV, to the highest degree expected an explanation of the disease and information concerning examinations and treatment, and to a lower degree - emotional support during consultations.

Serum neutralization activity declines but memory B cells persist after cure of chronic hepatitis C.

The increasing incidence of hepatitis C virus (HCV) infections underscores the need for an effective vaccine. Successful vaccines to other viruses generally depend on a long-lasting humoral response. However, data on the half-life of HCV-specific responses are lacking. Here we study archived sera and mononuclear cells that were prospectively collected up to 18 years after cure of chronic HCV infection to determine the role of HCV antigen in maintaining neutralizing antibody and B cell responses. We show that HCV-neutralizing activity decreases rapidly in potency and breadth after curative treatment. In contrast, HCV-specific memory B cells persist, and display a restored resting phenotype, normalized chemokine receptor expression and preserved ability to differentiate into antibody-secreting cells. The short half-life of HCV-neutralizing activity is consistent with a lack of long-lived plasma cells. The persistence of HCV-specific memory B cells and the reduced inflammation after cure provide an opportunity for vaccination to induce protective immunity against re-infection.

Comment on review article: Chronic hepatitis C virus infection cascade of care in pediatric patients.

An enhanced cascade of care should include a younger population, helping to achieve the goal of the World Health Organization with a focus on elimination in the pediatric population. Furthermore, enhanced screening and awareness efforts and continued education of health care providers will improve the outcomes of chronic hepatitis C virus (HCV) infection in the pediatric population. The present work discusses and comments on the topic "cascade of care in HCV chronic pediatric patients".

Itemization difference of patient-reported outcome in patients with chronic liver disease.

BACKGROUND AND AIMS: The itemization difference of patient-reported outcome (PRO) in hepatitis patients with different etiologies remains elusive in Asia. We aimed to assess the characteristics and the difference of health-related quality of life (HRQoL) in chronic hepatitis B (CHB), chronic hepatitis C (CHC), and non-alcoholic fatty liver disease (NAFLD) patients. METHODS: We conducted the study in an outpatient setting. The 36-Item Short Form Health Survey (SF-36) was completed by the patients upon the initial diagnosis and recruitment for a long-term follow-up purpose. The PRO results were also assessed by disease severity. RESULTS: There were 244 patients (198 males) of CHB, 54 patients (29 males) of CHC, and 129 patients (85 males) of NAFLD, respectively. CHC patient had the mean score of 67.1 ± 23.3 in physical component summary (PCS) of the SF-36 health survey, which was significantly lower than CHB patients (76.4 ± 19.5), and NAFLD patients (77.5 ± 13.7), respectively (p = 0.001). The significantly lower performance of PCS in CHC patients was mainly attributed to the lower performance in physical functioning and bodily pain components. Higher fibrosis 4 index scores were significantly associated with lower PCS scores in all patient groups. There was no significant difference of mean mental component summary (MCS) between groups. However, NAFLD patients had significantly lower mental health scores than other groups (p = 0.02). CONCLUSIONS: The significant difference of HRQoL exists in hepatitis patients with different etiologies. Disease severity leads to a lower PCS performance.

Time Costs and Out-of-Pocket Costs in Patients With Chronic Hepatitis C in a Publicly Funded Health System.

OBJECTIVES: Chronic hepatitis C (CHC) infection affects more than 70 million people worldwide and imposes considerable health and economic burdens on patients and society. This study estimated 2 understudied components of the economic burden, patient out-of-pocket (OOP) costs and time costs, in patients with CHC in a tertiary hospital clinic setting and a community clinic setting. METHODS: This was a multicenter, cross-sectional study with hospital-based (n = 174) and community-based (n = 101) cohorts. We used a standardized instrument to collect healthcare resource use, time, and OOP costs. OOP costs included patient-borne costs for medical services, nonprescription drugs, and nonmedical expenses related to healthcare visits. Patient and caregiver time costs were estimated using an hourly wage value derived from patient-reported employment income and, where missing, derived from the Canadian census. Sensitivity analysis explored alternative methods of valuing time. Costs were reported in 2020 Canadian dollars. RESULTS: The mean 3-month OOP cost was $55 (95% confidence interval [CI] $21-$89) and $299 (95% CI $170-$427) for the community and hospital cohorts, respectively. The mean 3-month patient time cost was $743 (95% CI $485-$1002) (community) and $465 (95% CI $248-$682) (hospital). The mean 3-month caregiver time cost was $31 (95% CI $0-$63) (community) and $277 (95% CI $174-$380) (hospital). Patients with decompensated cirrhosis bore the highest costs. CONCLUSIONS: OOP costs and patient and caregiver time costs represent a considerable economic burden to patient with CHC, equivalent to 14% and 21% of the reported total 3-month income for the hospital-based and community-based cohorts, respectively.

HCV infection in hemophilia A patients is associated with altered cytokines and chemokines profile and might modulate the levels of FVIII inhibitor.

Prevalence of hepatitis C virus (HCV) is high in hemophilia A patients and the development of FVIII inhibitor is another challenge in the management of these individuals. The influence of HCV infection in the occurrence of inhibitors was investigated by the comparison of clinical and laboratory data from noninfected (NI, n = 96) and chronically HCV-infected (HCV, n = 58) hemophilia A patients. Concentrations of plasmatic cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A) and chemokines (CCL2, CCL5, CXCL8, CXCL9, and CXCL10) were quantified from patients' samples. The results showed that older age, use of cryoprecipitate and fresh frozen plasma, and severe hemophilia were associated with HCV infection, whereas exclusive use of virus inactivated clotting factors was a protector factor to acquiring HCV infection. HCV infection was strongly associated with low levels of inhibitor (OR = 20.53, p < 0.001). Patients with a history of inhibitor (INB+) presented a mixed immune profile characterized by higher levels of pro-and anti-inflammatory cytokines than those without a history of inhibitor (INB-). The highest levels of CCL2 and CXCL8 were seen in HCVINB- , whereas CXCL9 and CXCL10 in HCVINB+ . Heatmap analysis of the set of cytokines and chemokines concentration distributed HCV patients into two distinct clusters, HCVINB+ and HCVINB- , both characterized by low concentrations of IL-4, while noninfected patients were grouped in a single block regardless of inhibitor development history (NIINB-/INB+ ). This finding suggests that the strong association between HCV infection and low levels of factor VIII inhibitors might be due to the modulation of the cytokine and chemokine network established by the antiviral response.

Viral hepatitis amidst COVID-19 in Africa: Implications and recommendations.

Hepatitis, a significant cause of mortality worldwide, results in around 1.34 million deaths each year globally. Africa is not exempt from the plague of Hepatitis. Around 100 million estimated individuals are infected with Hepatitis B or C. Egypt has the highest prevalence of cases of Hepatitis followed by Cameroon and Burundi. The continent is severely affected by the onset of the COVID-19 pandemic, as the virus has added an additional burden on the already fragile continent. With the pandemic, it is presumable that Hepatitis like other viral diseases will pose a threat to collapsing healthcare system. Therefore, for Africa to become more resilient in the face of such menaces, including Hepatitis, further prevention policies are required to be implemented.

Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.

Cirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression.

Late presentation of chronic HBV and HCV patients seeking first time specialist care in Spain: a 2-year registry review.

Chronic viral hepatitis infection affects an estimated 325 million people globally. People who initiate treatment after significant disease progression face increased risk of severe liver complications and death. Data are scarce on the characteristics and risk factors of people who present late to care in Spain and globally. Data were collected from January 2018 to December 2019 to report late presentation (LP) to specialist care at 11 large university hospitals in Spain to assess related risk factors using a multivariable logistic regression model. 2290 (CHB = 505, CHC = 1785) patients were analysed, with 581 (25.2%) presenting late. Hepatitis C patients more frequently reported LP compared to hepatitis B patients (28.1% vs 15.0%; p < 0.001). Older age (p < 0.001), being male (p < 0.001), being Spanish-born (p < 0.001), and having an unknown origin of referral (p = 0.08) were associated with a higher likelihood of LP. Advanced liver disease was identified in 533 (23%) patients and late-stage liver disease in 124 (5.4%). LP, including with irreversible liver damage, to viral hepatitis specialist care is frequent in Spain, despite being a country with unrestricted treatment access. Initiatives to reduce LP should specifically target men, older individuals, foreign-born populations for CHB, and Spanish nationals for CHC.

Study of Quasispecies Complexity and Liver Damage Progression after Liver Transplantation in Hepatitis C Virus Infected Patients.

Cirrhosis derived from chronic hepatitis C virus (HCV) infection is still a common indication for liver transplantation (LT). Reinfection of the engrafted liver is universal in patients with detectable viral RNA at the time of transplant and causes fast progression of cirrhosis (within 5 years) in around one-third of these patients. To prevent damage to the liver graft, effective direct-acting antiviral (DAA) therapy is required as soon as possible. However, because of post-LT clinical instability, it is difficult to determine the optimal time to start DAAs with a low risk of complications. Evaluate changes in quasispecies complexity following LT and seek a predictive index of fast liver damage progression to determine the timing of DAA initiation. HCV genomes isolated from pre-LT and 15-day post-LT serum samples of ten patients, who underwent orthotopic LT, were quantified and sequenced using a next-generation sequencing platform. Sequence alignments, phylogenetic trees, quasispecies complexity measures, biostatistics analyses, adjusted R2 values, and analysis of variance (ANOVA) were carried out. Three different patterns of reinfection were observed (viral bottlenecking, conserved pre-LT population, and mixed populations), suggesting that bottlenecking or homogenization of the viral population is not a generalized effect after liver graft reinfection. None of the quasispecies complexity measures predicted the future degree of liver damage. Higher and more uniform viral load (VL) values were observed in all pre-LT samples, but values were more dispersed in post-LT samples. However, VL increased significantly from the pre-LT to 15-day post-LT samples in patients with advanced fibrosis at 1-year post-LT, suggesting that a VL increase on day 15 may be a predictor of fast liver fibrosis progression. HCV kinetics after LT differ between patients and are not fibrosis-dependent. Higher VL at day 15 post-LT versus pre-LT samples may predict fast liver fibrosis progression.

Safe use of livers from deceased donors older than 70 years in recipients with HCV cirrhosis treated with direct-action antivirals. Retrospective cohort study.

INTRODUCTION: There is controversy regarding the use of older grafts for liver transplantation (LT) in HCV-infected patients, but the introduction of direct-acting antivirals (DAA) can radically change that debate. METHODS: The aim of this retrospective cohort study was to evaluate outcomes of the use of liver grafts from donors older than 70 years in recipients with HCV infection who underwent pre- or post-LT treatment with DAA. We compared two groups of patients who underwent LT using livers >70 years; the groups were defined according to antiviral therapy: non-DAA therapy group (n = 62; LT between May 1996 and December 2013), and DAA therapy group (n = 31; LT between January 2014 and December 2019). RESULTS: Thirty (96.8%) patients of DAA therapy and nine (14.5%) of non-DAA therapy (21 patients underwent complete therapy with interferon-ribavirin) achieved sustained viral response (SVR). One, 3-, and 5-year patient survival were 83.9%, 67.7%, and 56.5% in the non-DAA group vs 93.5%, 88.4%, and 88.4% in the DAA group (P = 0.04); the 1-, 3-, and 5-year graft survival were 77.4%, 62.9%, and 51.6% in the non-DAA group vs. 88.6%, 83.7%, and 83.7% in the DAA group (P = 0.03). Multivariate analysis demonstrated donor female sex and DAA therapy as protective factors of graft survival. CONCLUSIONS: Pre- or post-LT therapy with DAA in HCV-infected patients has achieved an almost overall SVR. The use of liver grafts >70 years in these patients treated with DAA was associated with significantly higher 5-year patient and graft survival in DAA group compared to non-DAA group. Thus, the introduction of DAA therapy has allowed the safe use of livers >70 years in HCV-positive recipients.

Mandatory multidisciplinary management of hepatocellular carcinoma: Need of the hour in a country with high prevalence of hepatitis C virus infection.

Hepatocellular carcinoma is the sixth common cancer diagnosed and fourth leading cause of cancer-related deaths worldwide. Its incidence is on rise due to increasing prevalence of chronic hepatitis C virus infection. Pakistan is ranked second in countries burdened by hepatitis C virus in the world. Management of hepatocellular carcinoma is complex as it develops on the back of liver cirrhosis, and the risk of mortality is an accumulation of both tumour-related factors as well as liver decompensation. A multidisciplinary tumour board is an ideal approach to improve the outcomes of hepatocellular carcinoma since this ensures assimilation of input from a diverse group of care-providers, including hepatobiliary and transplant surgeons, gastroenterologists, interventional radiologists, oncologists and palliative care specialists. A multidisciplinary tumour board provides tailored approach to individual cases in a timely fashion to avoid treatment delays and communication gaps to improve the overall outcomes.

Society for Maternal-Fetal Medicine Consult Series #56: Hepatitis C in pregnancy-updated guidelines: Replaces Consult Number 43, November 2017.

In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy. The following are the Society for Maternal-Fetal Medicine's recommendations: (1) We suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of hepatitis C virus diagnosis alone (GRADE 2C); (2) we suggest screening for viral hepatitis in patients with a diagnosis of intrahepatic cholestasis of pregnancy at an early gestational age or with high levels of bile acids (GRADE 2C); (3) we recommend that obstetrical providers screen all pregnant patients for hepatitis C virus by testing for anti-hepatitis C virus antibodies in every pregnancy (GRADE 1B); (4) we suggest that obstetrical care providers screen hepatitis C virus-positive pregnant patients for other sexually transmitted infections (if not done previously), including human immunodeficiency virus, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 2C); (5) we recommend vaccination against hepatitis A and B viruses (if not immune) for patients with hepatitis C virus (GRADE 1B); (6) we recommend that direct-acting antiviral regimens only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a direct-acting antiviral should be counseled in a shared decision-making framework about the risks and benefits of continuation (GRADE 1C); (7) we suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited (GRADE 2C); (8) we recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B); (9) we suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with hepatitis C virus unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery) (GRADE 2B); (10) we recommend that hepatitis C virus status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding (GRADE 1A).

Health care costs associated with chronic hepatitis C virus infection in Ontario, Canada: a retrospective cohort study.

BACKGROUND: High-quality estimates of health care costs are required to understand the burden of illness and to inform economic models. We estimated the costs associated with hepatitis C virus (HCV) infection from the public payer perspective in Ontario, Canada. METHODS: In this population-based retrospective cohort study, we identified patients aged 18-105 years diagnosed with chronic HCV infection in Ontario from 2003 to 2014 using linked administrative data. We allocated the time from diagnosis until death or the end of follow-up (Dec. 31, 2016) to 9 mutually exclusive health states using validated algorithms: no cirrhosis, no cirrhosis (RNA negative) (i.e., cured HCV infection), compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, both decompensated cirrhosis and hepatocellular carcinoma, liver transplantation, terminal (liver-related) and terminal (non-liver-related). We estimated direct medical costs (in 2018 Canadian dollars) per 30 days per health state and used regression models to identify predictors of the costs. RESULTS: We identified 48 239 patients with chronic hepatitis C, of whom 30 763 (63.8%) were men and 35 891 (74.4%) were aged 30-59 years at diagnosis. The mean 30-day costs were $798 (95% confidence interval [CI] $780-$816) (n = 43 568) for no cirrhosis, $661 (95% CI $630-$692) (n = 6422) for no cirrhosis (RNA negative), $1487 (95% CI $1375-$1599) (n = 4970) for compensated cirrhosis, $3659 (95% CI $3279-$4039) (n = 3151) for decompensated cirrhosis, $4238 (95% CI $3480-$4996) (n = 550) for hepatocellular carcinoma, $8753 (95% CI $7130-$10 377) (n = 485) for both decompensated cirrhosis and hepatocellular carcinoma, $4539 (95% CI $3746-$5333) (n = 372) for liver transplantation, $11 202 (95% CI $10 645-$11 760) (n = 3201) for terminal (liver-related) and $8801 (95% CI $8331-$9271) (n = 5278) for terminal (non-liver-related) health states. Comorbidity was the most significant predictor of total costs for all health states. INTERPRETATION: Our findings suggest that the financial burden of HCV infection is substantially higher than previously estimated in Canada. Our comprehensive, up-to-date cost estimates for clinically defined health states of HCV infection should be useful for future economic evaluations related to this disorder.

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

Age and gender-specific hepatitis C continuum of care and predictors of direct acting antiviral treatment among persons who inject drugs in Seattle, Washington.

BACKGROUND: Direct acting antivirals (DAAs) have revolutionized management of hepatitis C virus (HCV), but treatment uptake remains low among persons who inject drugs (PWID). We report the continuum of care for HCV and describe predictors of treatment with DAAs among PWID in Seattle. METHODS: We analyzed data from the 2018 Seattle area National HIV Behavioral Surveillance (NHBS) survey of PWID. Persons ≥18 years of age who injected drugs in the past year and completed the core NHBS survey, a local survey supplement, and rapid HCV antibody testing were included. Among those who screened HCV antibody positive, we calculated proportions and 95 % confidence intervals for self-reported steps along the HCV care continuum. Multivariable logistic regression was used to calculate the adjusted odds (AOR) of having received DAA therapy. RESULTS: The sample included 533 PWID, 376 (71 %) of whom tested positive for antibodies to HCV. Among those who were HCV antibody positive, 94 % reported any prior HCV test, 81 % reported a prior confirmatory test, and 68 % reported a prior HCV diagnosis. Of those diagnosed, 26 % had undergone treatment and 18 % had been cured. In a multivariate model, being one year older (AOR 1.05 per year, 1.01-1.08) was predictive of DAA treatment, while homelessness (AOR 0.39, 0.19-0.80) and female gender (AOR 0.36, 0.16-0.78) were associated with a lower odds of DAA therapy. CONCLUSIONS: Despite widespread HCV testing among PWID in Seattle, treatment uptake remains low in the DAA era. In particular, treatment of women, younger adults and persons living homeless is lagging behind.

Chronic hepatitis C patients lost in the system: predictive factors of non-referral or loss of follow-up in Hepatology units.

INTRODUCTION: several barriers remain in the hepatitis C care cascade, which need to be removed in order to eliminate chronic hepatitis C. These barriers include deficiencies in screening and confirmatory diagnosis as well as difficulties in accessing treatment. AIMS: to identify factors associated with the non-referral of patients with positive hepatitis C virus (HCV) antibodies and to identify factors associated with loss of follow-up or non-attendance of these patients to specialist consultation after referral. METHODS: observational and retrospective single-center-study, including all positive HCV serology tests performed between January 2013 and May 2018, in the Virgen Macarena health area (Seville, Spain) before implementing the one-step diagnosis. Non-referred patients and patients who were lost to follow-up after being referred were identified. RESULTS: a total of 54 (77.4 %) patients diagnosed in Primary Care (PC) and 54 (22.2 %) from hospital specialists were not referred (p < 0.001). Predictors for non-referral were: stay in prison/institutionalization (p = 0.04), suffering chronic obstructive pulmonary disease (COPD) (p = 0.07), a normal AST value (p = 0.034) or test requested by Primary Care physician (PCP) (p = 0.004). Patients referred from PC were more likely to be lost to follow-up than those referred from hospital specialists (p < 0.001). Predictors of follow-up loss included: opioid replacement therapy (p = 0.034), absence of high blood pressure (p = 0.039) and test requested by PCP (p = 0.049). CONCLUSIONS: a high percentage of patients with positive HCV serology were not referred or were lost to follow-up, mainly those belonging to high risk social groups or those with associated comorbidities. Patients with average values of transaminases or those diagnosed in PC were also less frequently referred.

Treatment of Chronic Hepatitis C in Young Children Reduces Adverse Outcomes and Is Cost-Effective Compared with Deferring Treatment to Adulthood.

OBJECTIVE: To evaluate the cost-effectiveness of treating young children with chronic hepatitis C virus (HCV) with new direct-acting antivirals. STUDY DESIGN: A state-transition model of chronic HCV was developed to conduct a cost-effectiveness analysis comparing treatment at age 6 years vs delaying treatment until age 18 years. Model inputs were derived from recently conducted systematic reviews, published literature, and government statistics. Medical care costs were obtained from linked population level laboratory and administrative data (Ontario, Canada). Outcomes are expressed in expected quality-adjusted life-years and costs (CAD$). Analysis included a base-case to estimate the expected value and one-way and probabilistic sensitivity analyses to evaluate the impact of uncertainty of the model inputs. RESULTS: After 20 years, treating 10 000 children early would prevent 330 cases of cirrhosis, 18 cases of hepatocellular carcinoma, and 48 liver-related deaths. The incremental cost-effectiveness ratio of early treatment compared to delayed treatment was approximately $12 690/quality-adjusted life-years gained and considered cost-effective. Model results were robust to variation in fibrosis progression rates, disease state-based costs, treatment costs, and utilities. CONCLUSIONS: Delaying treatment until age 18 years results in an increased lifetime risk of late-stage liver complications. Early treatment in children is cost effective. Our work supports clinical and health policies that broaden HCV treatment access to young children.