Randomized Placebo-Controlled Trial on the Effect of Corticosteroid on Prolonged Cholestasis due to Acute Hepatitis A

Aim and objective: To determine the efficacy and safety profile of corticosteroid on the clinical course of prolonged intrahepatic cholestasis due to acute hepatitis A. Method: We prospectively studied patients of acute hepatitis A with prolonged cholestasis (more than 12 weeks with debilitating symptoms in the form of anorexia, weight loss and pruritis disturbing night sleep) over a period of five years. The patients were randomly assigned to two groups of ursodeoxycholic acid and prednisolone (Group A) and ursodeoxycholic acid and placebo (Group B). They were assessed for cumulative mean decrease in bilirubin at day 3, 7 and then weekly till normalization of bilirubin. Quality of life was assessed in both groups on the basis of pruritis, anorexia, performance status improvement and work hour loss in days. Results: Out of 84 patients of acute hepatitis A, 21 patients had prolonged cholestatic hepatitis. Eleven patients (group A) were given ursodeoxycholic acid and prednisolone. Ten patients (group B) were given ursodeoxycholic acid and placebo. In group A, male: female ratio was 7:4, with a mean age of 21 years (range 13–30 years). The mean bilirubin was 29.4 mg/dl (range 24.9–34.6 mg/dl), aspartate aminotransferase (AST) 104 (range 84–124 U/L), alanine (ALT) aminotransferase 74 U/L (range 51–98 U/L), alkaline phosphatase (AP) 643 (range 460–870 U/L), prothrombin time (PT) prolongation in seconds 3.09 (range 4–7) and protein/albumin 7.1/4.2 (range 7.6–6.4/3.6–4.7 gm/dl). The decrease in bilirubin in group A (cumulative mean) at day 3, 7, 14, 21, 28, 35, 42, 49 was 20.1%, 45.6%, 58.6%, 64.6%, 71.7%, 76.1%, 80.5% and 86.4%, respectively. The mean time for bilirubin normalization was 44 days (range 28–84 days). In group B, male: female ratio 5:5, with a mean age of 21.5 years (range 11–35 years). The mean bilirulin, AST, ALT, AP, PT prolongation (in seconds) protein-albumin were 28.6 (range 11–35 mg/dl), 81 (range 43–112 U/L), 64 U/L (range 39–91 U/L), 702 (range 326–890 U/L), 3.6 (range 2–7) and 6.57/3.7 (range 7.6–5.8/3.2–4.2 gm/dl), respectively. The decrease in bilirubin at day 3, 7, 4, 21, 28, 35, 42, 49 was 2.1%, 5.9%, 11.9%, 19.1%, 25.1%, 29.3%, 33.3% and 38.5%, respectively. The mean time for bilirubin normalization was 94 days (range 74–138 days). p < 0.05 at day 3, 7, 14, 21, 28, 35, 42 and 49 days. Pruritis responded within a mean of 5 days (range 4–8 days) and 24 days (range 18–45 days) in group A and group B, respectively. Anorexia, performance status improvement occurred early in group A and work hour loss was more in group B. None of the patients developed side-effects to corticosteroid. Conclusion: Both groups of prolonged choleastatic hepatitis A were of comparable severity in term of maximal serum bilirubin and transaminases. Prednisolone resulted in symptomatic relief and a rapid initial drop in serum bilirubin levels followed by a persistent fall. No adverse event was recorded. So, prednisolone can be used in debilitating symptoms due to cholestasis in acute viral hepatitis A.