Background: Limited empirical evidence exists for hepatitis C virus (HCV) treatment-asprevention. The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study assessed HCV treatment-as-prevention in four Australian prisons.Methods: SToP-C is a non-randomised trial, including a pre/post analysis within a prospective longitudinal cohort of people incarcerated in two maximum-(male) and two medium-security prisons (one male, one female). All prison inmates at least 18 years were eligible for enrolment.Participants were enrolled from late-2014 to 2019. Following HCV testing, participants were monitored for risk behaviors and HCV, among three sub-populations: 1) uninfected (HCV antibody negative); 2) previously infected (HCV antibody positive, HCV RNA negative); 3) infected (HCV antibody and HCV RNA positive). Uninfected and previously infected (at-risk) participants were followed every 3-6 months for HCV primary infection and re-infection, respectively. Infected participants were assessed for treatment, initially standard of care treatment (by prison health services), followed by direct-acting antiviral (DAA) treatment scale-up from mid-2017 (12 weeks sofosbuvir/velpatasvir, through SToP-C). Participants were followed until study closure in November 2019. The primary study outcome was HCV incidence compared between pre-and post-treatment scale-up periods among participants at risk of HCV primary infection or re-infection. The trial was registered with ClinicalTrials.gov (identifier: NCT02064049) Findings: Of 3,691 participants enrolled, 719 (19%) had detectable HCV RNA and 2,965 were at-risk of primary infection (n=2,240) or re-infection (n=725) at baseline. DAA treatment was initiated in 349/499 eligible participants during the treatment scale-up period. Among at-risk population with longitudinal follow-up (n=1,643; median age 33 years; 82% male), 31% reported injecting drug use in prison. HCV incidence declined by 48%, from 8.31 to 4.35/100 person-years between pre-and post-treatment scale-up periods [Incidence Rate Ratio (IRR): 4 0.52, 95%CI: 0.36, 0.78]. Incidence of primary infection declined from 6.64 to 2.85/100 personyears (IRR: 0.43, 95%CI: 0.25, 0.74), while incidence of re-infection declined from 12.36 to 7.27/100 person-years (IRR: 0.59, 95%CI: 0.35, 1.00). Among participants reporting injecting drug use in the current imprisonment, incidence of primary infection declined from 39.08 to 14.03/100 person-years (IRR: 0.36, 95%CI: 0.16, 0.80), and incidence of re-infection declined from 15.26 to 9.34/100 person-years (IRR: 0.61, 95%CI: 0.34, 1.09). Adjusted analysis indicated a significant reduction in HCV risk between pre-and post-treatment scale-up periods (adjusted Hazard Ratio: 0.50, 95% CI: 0.33, 0.76).Interpretation: DAA treatment scale-up was associated with reduced HCV incidence in prison, indicative of HCV treatment-as-prevention. The findings support broad DAA treatment scale-up among incarcerated populations.
Adiponectin demonstrates beneficial effects in various metabolic diseases, including diabetes, and in bowel cancer. Recent data also suggest a protective role in colitis. However, the precise molecular mechanisms by which adiponectin and its receptors modulate colitis and the nature of the adaptive immune response in murine models are yet to be elucidated. Adiponectin knock-out mice were orally administered dextran sulfate sodium for 7 days and were compared with wild-type mice. The severity of disease was analyzed histopathologically and through cytokine profiling. HCT116 colonic epithelial cells were employed to analyze the effects of adiponectin and AdipoR1 interactions in colonic injury following dextran sulfate sodium treatment. Adiponectin knock-out mice receiving dextran sulfate sodium exhibited severe colitis, had greater inflammatory cell infiltration, and an increased presence of activated B cells compared with controls. This was accompanied by an exaggerated proinflammatory cytokine profile and increased STAT3 signaling. Adiponectin knock-out mouse colons had markedly reduced proliferation and increased epithelial apoptosis and cellular stress., adiponectin reduced apoptotic, anti-proliferative, and stress signals and restored STAT3 signaling. Following the abrogation of AdipoR1 , these protective effects of adiponectin were abolished. In summary, adiponectin maintains intestinal homeostasis and protects against murine colitis through interactions with its receptor AdipoR1 and by modulating adaptive immunity.
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