It has been suggested that hepatitis C virus (HCV) infected patients with type II mixed cryoglobulinemia have less extensive liver damage than patients without cryoglobulinemia. We retrospectively evaluated 35 patients with type II mixed cryoglobulinemia associated with HCV infection, seeking for factors associated with normal alanine aminotransferase (ALT) values. The presence of anti-GOR and of other autoantibodies, including the recently described anti-LAG-3.1, was specifically investigated. Fifty-four percent of patients had anti-GOR, 46% anti-LAG-3.1, 40% anti-smooth muscle, 17% anti-nuclear, and 11% anti-liver-kidney microsome 1 antibodies. Anti-GOR was significantly (p = 0.037) associated with anti-LAG-3.1 but not with other autoantibodies. Persistently abnormal ALT levels were observed in 54% of patients. By univariate analyses, abnormal ALT was significantly associated with anti-GOR positivity (p = 0.018) and younger age (p = 0.03). Multivariate regression analysis confirmed that these variables were independently associated with abnormal ALT. Our data suggest that the presence of autoimmune manifestations as well as unidentified age-related host factor(s) may protect from liver injury in HCV-associated cryoglobulinemia.