A vulnerability assessment for the HCV infections associated with injection drug use.

After the 2014-2015 HIV outbreak in Scott County, Indiana, United States Centers for Disease Control and Prevention (CDC) conducted a nationwide analysis to identify vulnerable counties to an outbreak of Hepatitis C Virus (HCV)/Human Immunodeficiency Virus (HIV) and prevent such an outbreak in the future. We developed a jurisdiction-level vulnerability assessment for HCV infections associated with injection drug use (IDU) in Utah. We used three years of data (2015-2017) from 15 data sources to construct a regression model to identify significant indicators of IDU. A ZIP Code, county, or individual-level measure of IDU does not exist, therefore, CDC has suggested using HCV cases as a proxy for IDU. We used the Social Vulnerability Index to highlight vulnerable areas to HCV outbreaks and applied Geographical Information System (GIS) to identify hot spots of HCV infections (i.e. current/ongoing HCV transmissions). Rates of skin infection, buprenorphine prescription, administered naloxone, teen birth, and per capita income were associated with HCV infections. The opioid epidemic is dynamic and over time, it impacts different communities through its sequelae such as HCV outbreaks. We need to conduct this vulnerability assessment frequently, using updated data, to better target our resources. Moreover, we should consider evaluating whether the improvement of HCV screening has an impact on controlling HCV outbreaks. The analysis informs Utah's agencies and healthcare officials to target resources and interventions to prevent IDU-related HCV outbreaks. Our results inform policymakers at the national level on possible indicators of HCV outbreaks as well.

Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy.

BACKGROUND & AIMS: People who inject drugs (PWID) and are on opioid agonist therapy (OAT) might have lower adherence to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) and, therefore, lower rates of sustained virologic response (SVR). Because of this, we compared the SVR rates to interferon-free DAA combinations in individuals receiving OAT and those not receiving OAT in a real-world setting. METHODS: The HEPAVIR-DAA cohort, recruiting HIV/HCV-coinfected patients (NCT02057003), and the GEHEP-MONO cohort (NCT02333292), including HCV-monoinfected individuals, are ongoing prospective multicenter cohorts of patients receiving DAAs in clinical practice. We compared SVR 12 weeks after treatment (SVR12) in non-drug users and PWID, including those receiving or not receiving OAT. Intention-to-treat and per protocol analyses were performed. RESULTS: Overall, 1,752 patients started interferon-free DAA treatment. By intention-to-treat analysis, 778 (95%, 95% CI 93%-96%) never injectors, 673 (92%, 95% CI 89%-93%) PWID not on OAT and 177 (89%, 95% CI 83%-92%) PWID on OAT achieved SVR12 (p = 0.002). SVR12 rates for ongoing drug users (with or without OAT) were 68 (79%) compared with 1,548 (95%) for non-drug users (p <0.001). Among ongoing drug users, 15 (17%) were lost-to-follow-up, and 3 (3.5%) became reinfected. In the per protocol analysis, 97% never injectors, 95% PWID not on OAT and 95% PWID on OAT achieved SVR12 (p = 0.246). After adjustment, ongoing drug use was associated with SVR12 (intention-to-treat) and OAT use was not. CONCLUSIONS: HCV-infected PWID achieve high SVR12 rates with DAAs whether they are on OAT or not, but their response rates are lower than those of patients who never used drugs. This is mainly attributable to more frequent loss to follow-up. Accounting for active drug use during DAA therapy nearly closed the gap in SVR rates between the study groups. LAY SUMMARY: Patients with hepatitis C virus infection who are on opioid agonist therapy can achieve high cure rates with current treatments. The use of illicit drugs during treatment can drive drop-outs and reduce cure rates. However, hepatitis C can be cured in most of those using drugs who complete treatment and follow-up. Clinical trial number: HEPAVIR-DAA cohort, NCT02057003; GEHEP-MONO cohort, NCT02333292.

[Guidelines for the prevention and treatment of hepatitis C (2019 version)].

In order to standardize and update the prevention, diagnosis and antiviral therapy of hepatitis C and to achieve the World Health Organization's goal of eliminating viral hepatitis as a public health threat by 2030, Chinese Medical Association, the Chinese Society of Hepatology, and the Society of Infectious Diseases organized relevant native experts in 2019 to revise the guideline for the prevention and treatment of hepatitis C (2019 version) based on the basic, clinical and prophylactic research progress of hepatitis C infection at home and abroad, combined with the present actual situation of our country, so as to provide an important basis for the prevention, diagnosis and treatment of hepatitis C.

Recovery of Infectious Hepatitis C Virus From Injection Paraphernalia: Implications for Prevention Programs Serving People Who Inject Drugs.

Background: Controlling hepatitis C virus (HCV) transmission among people who inject drugs (PWID) has focused on preventing sharing syringes and drug preparation paraphernalia, but it is unclear whether HCV incidence linked to sharing paraphernalia reflects contamination of the paraphernalia or syringe-mediated contamination when drugs are shared. Methods: In experiments designed to replicate real-world injection practices when drugs are shared, the residual contents of HCV-contaminated syringes with detachable or fixed needled were passed through the "cookers" and filters used by PWID in preparing drugs for injection and then introduced into a second syringe. All items were tested for the presence of infectious HCV using a chimeric HCV with a luciferase gene. Results: Hepatitis C virus could not be recovered from cookers regardless of input syringe type or cooker design. Recovery was higher when comparing detachable needles to fixed needles for residue in input syringes (73.8% vs 0%), filters (15.4% vs 1.4%), and receptive syringes (93.8% vs 45.7%). Conclusions: Our results, consistent with the hypothesis that sharing paraphernalia does not directly result in HCV transmission but is a surrogate for transmissions resulting from sharing drugs, have important implications for HCV prevention efforts and programs that provide education and safe injection supplies for PWID populations.

Solid organ transplantation of viral hepatitis C positive donor organs into viral hepatitis C negative recipients.

PURPOSE OF REVIEW: Strategies are needed to reduce waitlist mortality and increase transplantation rates. Advances in hepatitis C therapy has allowed the transplant community to look toward utilization of grafts from hepatitis C viremic donors to expand the organ pool. Use of such grafts for hepatitis C-negative patients is being evaluated and debated, and early trial data are emerging. RECENT FINDINGS: Both hepatitis C antibody-positive/nucleic acid test-negative and viremic donors are currently underutilized. Outcomes for viral hepatitis C (HCV) viremic transplant recipients are improving in the setting of direct-acting antiviral therapy. Optimization of graft utilization from HCV 'positive' donors and expansion to use of viremic donors for HCV-negative recipients will likely reduce waitlist mortality and result in net overall reduction in healthcare expenditures. SUMMARY: Herein, we provide a review of recent advancements relating to hepatitis C in solid organ transplant and outline future directions. A primary future focus will be data collection of outcomes of transplantation of grafts from HCV 'viremic' donors to nonviremic recipients in formal clinical trial protocols.

[Chronic hepatitis C: achievement, challenge and strategy to eliminate as a public health threat].

The use of direct-acting antiviral agents (DAAs) in the treatment of chronic hepatitis C and its approval in China applying the goal proposed by the World Health Organization is an important step towards eliminating viral hepatitis as public health threat by 2030. However, we also need to create a model that is suitable and short duration therapy for the Chinese patients. On the other hand, it is also essential to study the reverse hepatic fibrosis and the emerging problems of hepatitis C-related liver cancer.

[Clinical value of pegylated interferon-α plus ribavirin-based therapy in antiviral treatment of chronic hepatitis C in China].

Chronic hepatitis C virus (HCV) infection is one of the most common causes of liver cirrhosis and hepatocellular carcinoma in China. The older standard treatment regimen for chronic hepatitis C was the pegylated interferon-alfa plus ribavirin(PR). Now newer oral medications called direct antiviral agents (DAAs) has been gradually changed to PR-based DAAs and interferon-free, oral DAAs; making chronic hepatitis C a curable disease. This article intends to expound the advantages and disadvantages of PR-based therapy and provide reference for the treatment of chronic hepatitis C.

Managing sharps injuries and other occupational exposures to HIV, HBV, and HCV in the dermatology office.

Dermatologists and their staff are at risk for needlestick injuries and exposures to body fluids. Despite the availability of treatment to reduce the risk of blood-borne infection, many exposures go unreported. This paper identifies current recommendations and the specific details for response to occupational exposures to HIV, hepatitis B virus, and hepatitis C virus in the dermatology office. Issues surrounding each virus are discussed individually, and a summary step-by-step algorithm of how to proceed in the event of an occupational exposure is presented. In addition, a focused Practice Improvement Activity that is based on this paper and provides Maintenance of Certification credit has been developed. To view and participate, visit https://secure.dataharborsolutions.com/abdermorg/.

[Hepatitis C-related hepatocellular carcinoma and the treatment with direct-acting antiviral agents].

With the wide use of direct-acting antiviral agents (DAAs), more and more patients with chronic hepatitis C achieve sustained virological response; however, no consensus has been reached on the application of DAAs in the treatment of hepatitis C virus-related hepatocellular carcinoma (HCC). This article summarizes and evaluates related issues in this field, including whether antiviral therapy with DAAs in patients with hepatitis C can increase the incidence or recurrence rate of HCC, as well as whether DAAs can be used for hepatitis C in HCC patients after antitumor treatment and the efficacy of DAAs in such patients.

[A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

ED-based screening programs for hepatitis C (HCV) highlight significant opportunity to identify patients, prevent downstream costs/complications.

New data suggest there is a huge opportunity for EDs to identify patients with the hepatitis C virus (HCV) and link them into care before downstream complications lead to higher medical costs and adverse outcomes. Early results from a pilot study at the University of Alabama Medical Center in Birmingham show that at least 12% of the targeted baby boomer population being screened for HCV in the ED is testing positive for HCV, with confirmatory tests showing that about 9% of the screened population is infected with the disease. Both the Centers for Disease Control in Atlanta and the US Preventive Services Task Force recommend one-time HCV screening for patients who were born between 1945 and 1965. Public health experts say 75% of HCV infections occur in patients born during the baby boomer years, and that roughly half of them are unaware of their HCV status. Researchers at UAB report that so many patients are testing positive for HCV that demand for care can quickly overwhelm the health system if new primary care/specialty resources are not identified. Administrators of ED-based HCV screening programs in both Birmingham and Houston note that EDs with existing screening programs for HIV should have the easiest time implementing HCV screening. They also stress that patients are more accepting of HCV screening, and that the counseling process is easier.

Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial.

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year. METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year. RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence. CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

High-dose silibinin rescue treatment for HCV-infected patients showing suboptimal virologic response to standard combination therapy.

Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies.