Background People who inject drugs have a high prevalence of hepatitis C virus (HCV) and significant disease associated with drug use; however, HCV treatment often occurs in absence of interventions to address opioid use disorder and drug use–related harms. The impact of concurrent initiation of opioid agonist therapy (OAT) on HCV treatment and drug use outcomes is unknown. Methods In this prospective, open-label, observational trial at a harm reduction organization’s drop-in center in Washington, DC, 100 patients with chronic HCV infection, opioid use disorder, and ongoing injection drug use were treated with sofosbuvir-velpatasvir for 12-weeks and offered buprenorphine initiation. The primary end point was sustained virologic response (SVR), and secondary end points included uptake of and retention in OAT, change in risk behavior, and determinants of SVR. Results Eighty-two patients (82%) achieved SVR, which was not associated with baseline OAT status (P = .33), on-treatment drug use (P >.99), or imperfect daily adherence (P = .35) but was significantly associated with completing 2 or more 28-pill bottles of sofosbuvir-velpatasvir (P < .001) and receiving OAT at week 24 (P = .01). Of 67 patients not already receiving OAT at baseline, 53 (79%) started OAT. At week 24, 68 (68%) patients were receiving OAT. Receipt of OAT was associated with fewer opiate-positive urine drug screens (P = .003), lower human immunodeficiency virus risk-taking behavior scores (P < .001), and lower rates of opioid overdose (P = .04). Conclusions The Novel Model of Hepatitis C Treatment as an Anchor to Prevent HIV, Initiate Opioid Agonist Therapy, and Reduce Risky Behavior study demonstrates high uptake of buprenorphine collocated with HCV treatment, and it shows that concurrent initiation of OAT with HCV treatment can result in high rates of SVR while reducing risks associated with drug use. Clinical Trials Registration NCT03221309.

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Hepatitis C virus (HCV) infects 71 million individuals, and barriers to treatment remain. Bacterial translocation is a complication of chronic HCV infection, and this study evaluated circulating microbial components including lipopolysaccharide, peptidoglycan, and β-D-glucan in addition to their pattern recognition receptors and degree of hepatic macrophage uptake. The findings suggest that regulation of serum peptidoglycan and β-D-glucan differs from that of lipopolysaccharide. Additionally, macrophage activation in the liver may be better reflected by the degree of macrophage uptake than by circulating levels of microbial markers. These findings allow for a greater understanding of bacterial translocation and host immune activation during HCV infection.

The gut and liver are connected via the portal vein, and this relationship, which includes the gut microbiome, is described as the gut-liver axis. Hepatitis C virus (HCV) can infect the liver and cause fibrosis with chronic infection. HCV has been associated with an altered gut microbiome; however, how these changes impact metabolism across the gut-liver axis and how this varies with disease severity and time is unclear. Here we used multi-omics analysis of portal and peripheral blood, faeces and liver tissue to characterize the gutliver axis of patients with HCV across a fibrosis severity gradient before (n = 29) and 6 months after (n = 23) sustained virologic response, that is, no detection of the virus. Fatty acids were the major metabolites perturbed across the liver, portal vein and gut microbiome in HCV, especially in patients with cirrhosis. Decreased fatty acid degradation by hepatic peroxisomes and mitochondria was coupled with increased free fatty acid (FFA) influx to the liver via the portal vein. Metatranscriptomics indicated that Anaerostipes hadrus-mediated fatty acid synthesis influences portal FFAs. Both microbial fatty acid synthesis and portal FFAs were associated with enhanced hepatic fibrosis. Bacteroides vulgatus-mediated intestinal glycan breakdown was linked to portal glycan products, which in turn correlated with enhanced portal inflammation in HCV. Paired comparison of patient samples at both timepoints showed that hepatic metabolism, especially in peroxisomes, is persistently dysregulated in cirrhosis independently of the virus. Sustained virologic response was associated with a potential beneficial role for Methanobrevibacter smithii, which correlated with liver disease severity markers. These results develop our understanding of the gut-liver axis in HCV and non-HCV liver disease aetiologies and provide a foundation for future therapies.The gut microbiome is an outsourcing of genes by the host to maximize calorie and environmental exploitation that directly influences host energy regulation, metabolism and immunity 1,2 . The liver is the nexus between the gut and the remainder of the host and is itself vulnerable to perturbations in this complex biology 3,4 . Alterations in the gut-liver axis have been well demonstrated in non-alcoholic fatty liver disease (NAFLD) and chronic liver disease from non-metabolic aetiologies 5 . Viral hepatitis including chronic hepatitis C virus (HCV)

Objective: The ANCHOR program offered buprenorphine treatment to people who inject drugs engaged in hepatitis C (HCV) treatment at a Washington, DC harm reduction organization. This analysis describes the program model and outcomes of the opioid care continuum at 1 year. Methods: Primary outcomes were initiation of buprenorphine and retention in care, defined by an active buprenorphine prescription at given time points. Secondary outcomes included treatment interruptions, reasons for treatment noninitiation and termination, buprenorphine and opiate use, and HIV risk behaviors. Buprenorphine and opiate use were measured by urine toxicology screens and HIV risk behavior was quantified using a validated survey. Results: Of 67 patients receiving HCV treatment not on opioid agonist therapy at baseline, 96% (n ¼ 64) were interested and 73% (n ¼ 49) initiated buprenorphine. Retention was 82% (n ¼ 40), 65% (n ¼ 32), and 59% (n ¼ 29) at months 1, 6, and 12, respectively. Retention at 12 months was associated with selfreported engagement in routine medical care (P < 0.01), but was not associated with gender, stable housing, past opioid agonist therapy, or past overdose. Among retained patients, urine screens positive for opioids were 73% (n ¼ 29), 56% (n ¼ 18), and 79% (n ¼ 23) at months 1, 6, and 12. There was a significant mean decrease in HIV risk-taking behavior scores over the treatment period, primarily driven by reduced injection frequency. Conclusions: Patients engaged in HCV treatment at a harm reduction organization showed a high rate of initiation of buprenorphine treatment, with retention comparable to other treatment settings. Although most patients continued using opioids on treatment, there was a reduced frequency of injection drug use, a significant driver of OUD-related risk. These data support the use of low-threshold buprenorphine access alongside HCV treatment to reduce morbidity and mortality in people with OUD.

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BackgroundEngaging PWID in HCV treatment and monitoring for reinfection is critical to eliminate HCV and improve health in people who use drugs. However, PWID are often marginalized and can be difficult to engage and retain in care. The collocation of HCV treatment with buprenorphine to treat opioid use disorder (OUD) may improve visit adherence in this population.MethodsANCHOR is a single-center study evaluating treatment of HCV in PWID with chronic HCV, OUD, and IDU. Participants receive sofosbuvir/velpatasvir x12 weeks and are offered collocated buprenorphine. HCV visits occur at weeks 4, 12, 24, 48, 72 and 96.ResultsAt screening, the 100 enrolled patients were predominantly male (76%), black (93%), middle-aged (median 57years), injected opioids daily or more (58%), and were not on OAT (67%). Fifty-five (55%) patients were initiated on collocated buprenorphine at some point after day 0.Being on collocated buprenorphine at the time of HCV visit was associated with increased likelihood of visit attendance at weeks 12 (P = 0.002), 24 (P = 0.01), 48 (P = 0.02), 72 (P = 0.003), and 96 (P = 0.04). For patients who attended study visits, being on collocated buprenorphine was associated with a shorter time between planned visit and actual visit at weeks 12 (P = 0.03), 24 (P = 0.04), and 48 (P = 0.04). When looking at patients not on collocated buprenorphine, being on noncollocated opioid agonist therapy vs. not being on OUD treatment did not impact visit adherence.ConclusionEvidence-based treatment of HCV and OUD are critical to improving health in PWID. The collocation of HCV treatment with office-based buprenorphine may improve adherence to visits and visit timing, especially in long-term follow-up. Infectious disease providers should offer collocated buprenorphine as a tool to improve long-term outcomes and engagement in this high-risk population.Disclosures All Authors: No reported Disclosures.

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