Abstract
BACKGROUND: Occupational acquisition of hepatitis C virus (HCV) among healthcare workers (HCWs) has markedly declined in high-income countries, largely due to improved infection control measures and safety-engineered devices. However, the risk of HCV transmission from HCWs to patients remains insufficiently characterized. METHODS: We conducted a systematic review of studies reporting serological evidence of HCV transmission from infected HCWs to patients. Following PRISMA guidelines, we searched MEDLINE, Scopus, and Cochrane databases for publications up to July 2025. RESULTS: Of 192 studies identified, 24 from eight countries met inclusion criteria. In total, 27 HCWs were implicated as potential sources, and 54,622 patients were tested for HCV RNA. Seventy-six transmissions were confirmed by RNA sequencing; 369 were classified as probable and 15 as possible. Direct provider-to-patient transmission was documented in 18 studies, 12 of which involved exposure-prone procedures (EPP), yielding a mean transmission rate of 0.47% (62/13,224; 95% CI 0.036-0.061%). Viral load data were reported for only eight transmitting HCWs, all with ≥2×10(5) IU/mL, while no measurements were available for the remaining 19. Given the rarity of direct transmission and the absence of validated HCV RNA thresholds, national guidelines (UK, Germany, the Netherlands, Belgium, France, Switzerland, USA) differ considerably regarding restrictions or monitoring of infected HCWs performing EPP. Indirect HCV transmission associated with diversion of opiates and injection-safety breaches by HCWs addicted to morphine accounted for an even higher risk, with a mean rate of 0.94% (389/41,398; 95% CI 0.85-1.04%). CONCLUSIONS: Evidence on HCW-to-patient HCV transmission remains limited and provides only weak guidance for national prevention policies. Indirect transmission through unsafe practices by opioid diversion has emerged as the predominant pathway, underscoring the need for real-time monitoring, tamper-resistant systems, and strict adherence to infection prevention measures in healthcare settings.