Liver disease in HIV-infected patients may result from the infection itself, antiretroviral treatment or comorbidities. In this study, we analysed liver disease in 79 HIV-infected children and adolescents aged 14.0 ± 5.1 years. All the patients were receiving combination antiretroviral therapy (cART), with a mean duration of 11.5 ± 4.7 years. Six patients (8%) had detectable HIV viral load, and 8/79 (10%) of the participants were coinfected with hepatitis B or C virus (HCV, 6/8 or HBV, 2/8). Liver disease was defined as an elevation of any of the following parameters: alanine or aspartate aminotransferase (ALT and AST), total bilirubin, and gamma glutamyl transferase (GGTP). For the noninvasive evaluation of liver fibrosis, the AST-to-Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) were calculated. Liver disease was diagnosed in 20/79 (25%) of the patients, including 13/71 (18%) of participants without coinfection and 7/8 (88%) with coinfection (p < 0.0001). All of the liver markers except bilirubin were significantly higher in the coinfected group. APRI scores indicated significant fibrosis in 5/8 (63%) of patients with coinfection. HBV or HCV coinfection and detectable HIV viral load were independently positively associated with APRI (p = 0.0001, and p = 0.0001) and FIB-4 (p = 0.001, and p = 0.002, respectively). In conclusion, liver disease in HIV-infected children and adolescents results mainly from HBV or HCV coinfection. Effective antiretroviral treatment is protective against hepatic abnormalities.