Hepatic Biochemical Abnormalities and Clinically Significant Liver Dysfunction during Induction Therapy in Indian Children with B-Cell Acute Lymphoblastic Leukemia: A Prospective Cohort Study

Hepatic dysfunction is frequently encountered during treatment of pediatric acute lymphoblastic leukemia (ALL), particularly during induction chemotherapy. Data from low- and middle-income countries remain limited, where children often present with advanced disease and baseline biochemical abnormalities. This article aims to evaluate the frequency, severity, and temporal trends of hepatic biochemical abnormalities and clinically meaningful hepatic dysfunction during induction chemotherapy in children with ALL. In this prospective cohort study, 62 children aged 1 to 12 years with newly diagnosed B cell ALL treated on the ICiCLe ALL-14 protocol were evaluated. Liver function parameters were assessed serially at predefined time points during induction. Hepatic parameters were analyzed as (1) biochemical abnormalities (including aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], bilirubin, albumin, prothrombin time [PT]/international normalized ratio [INR]) and (2) clinically meaningful hepatic dysfunction, defined using liver-specific indicators (bilirubin and ALT ≥ CTCAE grade 2). At baseline, 88.7% of patients had at least one abnormal biochemical parameter, predominantly elevated AST and ALP, which are not liver-specific in children. Clinically meaningful hepatic dysfunction (based on bilirubin and ALT criteria) was observed in ∼6 to 8% of patients at presentation. During induction, bilirubin and ALT levels increased, while AST abnormalities declined over time. Although biochemical abnormalities were frequent (up to 95.1% by day 29), most were mild (grade: 1–2) and transient. Clinically significant hepatotoxicity remained uncommon, and no patient developed acute liver failure or required permanent modification of chemotherapy. Although hepatic biochemical abnormalities are common during induction therapy in pediatric ALL, they are largely driven by nonspecific parameters such as AST and ALP. When assessed using liver-specific indicators, clinically meaningful hepatic dysfunction is infrequent. These findings highlight the importance of distinguishing nonspecific biochemical abnormalities from true hepatotoxicity to avoid overestimation of liver injury and improve interpretation of liver function tests during therapy.