Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection.
