Another study from Italy detected hepatitis B vaccine escape mutants in 17.7% of patients with genotype D. Of more concern was a rising prevalence of complex mutations (defined as ≥2 vaccine escape mutations) over time from 0.4% in 2005–2009 to 3.0% in 2010–2014 and 5.1% in 2015–2019 [115]. The gene discussed is PPIB; the disease is hepatitis A virus infection.