The Prevalence and Risk Factors of Hepatitis B, Hepatitis C, and Hepatitis D Coinfection in Iran's General Population...

Concurrent HBV, HCV, and HDV infections pose a global health challenge, worsening disease, treatment, and patient outcomes, and burdening healthcare. In Iran, no comprehensive review has assessed HBV/HCV and HBV/HDV coinfection rates. This study conducted a systematic review and meta-analysis per PRISMA 2020 guidelines. The study was prospectively registered in PROSPERO (CRD420251007210). A comprehensive search was conducted across international (PubMed, Scopus, Embase, Web of Science, Cochrane Library) and Iranian databases (SID, Magiran), supplemented by Google Scholar, for studies published between January 2000 and March 2025. Eligible studies reported laboratory-confirmed cases of HBV, HCV, and/or HDV coinfections using ELISA, PCR, or real-time PCR. Because HDV replication depends on hepatitis B surface antigen (HBsAg), biologically independent HCV/HDV coinfection cannot occur. Consequently, studies that reported HCV/HDV coinfection without HBV were excluded. Two researchers independently conducted screening and data extraction and assessed study quality using the Newcastle-Ottawa Scale (NOS). To account for variability across studies, a random-effects model was used to estimate the pooled prevalence and its 95% confidence interval. Our analysis included 99 studies, encompassing more than 182,000 participants from regions of Iran. The pooled prevalence rates were 3% for HBV/HCV coinfection, 7% for HBV/HDV coinfection, and 1% for triple HBV/HCV/HDV infection. Due to significant heterogeneity across studies, random-effects models were used to obtain combined estimates. Substantial heterogeneity (I² up to 98%) was observed, attributable to variations in study populations, geographic regions, and diagnostic methods, as confirmed by sensitivity analyses and meta-regression. Publication bias was evident in most analyses. Key risk factors included blood transfusions, injection drug use, incarceration, and chronic liver disease. These findings underscore the urgent need for tailored prevention and surveillance programs. The high prevalence of coinfections in Iran, coupled with marked regional and population-based disparities, calls for standardized diagnostic protocols and targeted interventions that address behavioral and healthcare-associated risk factors.