Aim: This study aimed to analyze biochemical changes in liver enzyme levels during pharmacological treatment of chronic hepatitis and to evaluate treatment adherence and safety. Materials and Methods: A prospective observational study was conducted on 120 patients diagnosed with chronic hepatitis who received Tenofovir Disoproxil Fumarate (300 mg once daily) for 48 weeks. Liver enzyme levels, including ALT, AST, ALP, and GGT, were measured at baseline and at 4-week intervals to monitor treatment efficacy. Total bilirubin and albumin levels were also evaluated. Adherence and adverse events were assessed throughout the study. Data were analyzed using repeated-measures ANOVA and paired t-tests, with significance set at p < 0.05. Results: At baseline, the cohort demonstrated significant hepatic dysfunction, with elevated ALT (80.5 ± 28.3 U/L), AST (70.2 ± 24.1 U/L), ALP (96.7 ± 30.5 U/L), and GGT (90.4 ± 33.2 U/L). ALT normalized within 16 ± 4 weeks, while AST normalized within 20 ± 6 weeks. ALP and GGT levels significantly decreased to 46.7 ± 18.9 U/L and 39.5 ± 18.2 U/L, respectively, by 48 weeks. Total bilirubin reduced from 1.7 ± 0.5 mg/dL to 0.9 ± 0.3 mg/dL, and albumin increased from 3.8 ± 0.6 g/dL to 4.5 ± 0.3 g/dL (p < 0.001). High adherence (93.33%) resulted in enzyme normalization for 90.00% of patients. Adverse events were minimal (6.67%), with no severe events reported. Conclusion: Pharmacological treatment of chronic hepatitis effectively normalized liver enzyme levels, reduced hepatic inflammation, and improved synthetic liver function. High adherence was critical to achieving favorable outcomes, and the treatment was well-tolerated with minimal adverse events. Continuous biochemical monitoring is essential for optimizing therapy and improving patient outcomes.