Quantifying transmission dynamics of acute hepatitis C virus infections in a heterogeneous population using sequence data

Opioid substitution and syringes exchange programs have drastically reduced hepatitis C virus (HCV) spread in France but HCV sexual transmission in men having sex with men (MSM) has recently arisen as a significant public health concern. The fact that the virus is transmitting in a heterogeneous population, with different transmission routes, makes prevalence and incidence rates poorly informative. However, additional insights can be gained by analyzing virus phylogenies inferred from dated genetic sequence data. By combining a phylodynamics approach based on Approximate Bayesian Computation (ABC) and an original transmission model, we estimate key epidemiological parameters of an ongoing HCV epidemic among MSMs in Lyon (France). We show that this new epidemic is largely independent of the previously observed non-MSM HCV epidemics and that its doubling time is ten times lower (0.44 years versus 4.37 years). These results have practical implications for HCV control and illustrate the additional information provided by virus genomics in public health.

Acute hepatitis C virus infection and direct-acting antiviral drugs: Perfect combination to eliminate the epidemic?

Early diagnosis and treatment of incident cases of hepatitis C virus (HCV) infection is fundamental to eliminate HCV in HIV-positive patients. From January 2016 to December 2019, we attended 40 episodes of acute HCV infection (AHC) in 35 subjects (9 reinfections) who were coinfected with HIV. The patients were treated with direct-acting antiviral agents (DAAs) in seven hospitals in Andalusia, Spain. All were men who have sex with men (MSM), mean age was 42.9 (±8.3) years and median time of HIV infection was 46.6 months (IQR: 20.4–67.2). All received antiretroviral therapy and had undetectable HIV viral load (except 2 with 65 and 68 copies/mL); median CD4 count was 632 cells/mm3 (IQR: 553–896). Over half (74.3%) also had another concomitant sexually transmitted infection, syphilis (48.6%) being the most common. AHC was asymptomatic in 32 cases (80%). Genotypeic distribution was G1a 65%, G4 32.5% and G1b 3%. Median time to DAA was 6 weeks (IQR: 4.3–18.3) and median baseline HCV RNA was 6.1 Log (IQR: 5.6–6.5). DAA regimens were SOF/LDV (19 episodes), SOF/VEL (14), ELB/GZV (5) and GLP/PIB (2). All presented sustained viral response and none discontinued due to adverse effects. In conclusion, early treatment with DAA in AHC patients proved effective and safe. It could be an excellent strategy to eliminate HCV infection in HIV-coinfected MSM.

Long-lasting Imprint in the Soluble Inflammatory Milieu despite Early Treatment of Acute Symptomatic Hepatitis C

Background Treatment with direct acting antivirals (DAAs) in patients with chronic hepatitis C infection leads to partial restoration of soluble inflammatory mediators (SIMs). In contrast, we hypothesized that early DAA treatment of acute hepatitis C with DAAs may normalize most SIMs. Methods In this study, we made use of a unique cohort of acute symptomatic hepatitis C who cleared HCV with a 6-week course of ledipasvir/sofosbuvir. Plasma samples were used for proximity extension assay (PEA) measuring 92 proteins. Results Profound SIM alterations were observed in acute HCV patients, with marked upregulation of IL-6 and CXCL10 while certain mediators were down-regulated (e.g. MCP-4, IL-7). During treatment and follow-up, the majority of SIMs decreased but not all normalized (e.g. CDCP1, IL-18). Of note, SIMs that were down-regulated before DAA treatment remained suppressed while others that were initially unchanged, declined to lower values during treatment and follow-up (e.g.CD244). Conclusions Acute hepatitis C was associated with marked changes in the soluble inflammatory milieu as compared to both chronic hepatitis patients and healthy controls. Whereas early DAA treatment partly normalized this altered signature, long-lasting imprints of HCV remained. Thus, acute HCV-induced changes in the immune system may persist even after a short duration of viremia.