In contrast, adding a CTLA-4 inhibitor to a PD-1 inhibitor resulted in a markedly higher incidence and severity of hepatitis: elevated AST levels in 16.7% of patients (grade ≥ 3 in 5.9%) and elevated ALT levels in 18.2% (grade ≥ 3 in 8.4%) [31]. This evidence concerns the gene PDCD1 and hepatitis A virus infection.