Clinicopathological features of granulomatous hepatitis induced by Bacillus Calmette-Guerin (BCG) bladder instillation: a case series and literature review

Abstract

Abstract: Objective To elucidate the clinicopathological characteristics of hepatitis associated with Bacillus Calmette-Guerin (BCG) bladder instillation. Methods We summarized and documented cases of hepatitis associated with BCG bladder instillation treated at Beijing Friendship Hospital. A systematic review of previously reported cases were conducted. Data were collected and analyzed on variables including gender, age, frequency of BCG bladder instillations, liver biochemical results, liver histopathology, Mycobacterium tuberculosis testing, treatment regimens, and patient outcomes. Results A total of 23 patients, including 2 cases from our center and 21 cases from the literature, were re-evaluated. All patients were male, with a median age of 66 years at onset(range 34-88) and had received a median of 6 BCG bladder instillations (range 1-17). All patients exhibited a significant increase in alkaline phosphatase (ALP) and/or gamma-glutamyl transferase (GGT), with most also demonstrating varying degrees of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, 52.2% (12/23) of the patients had elevated serum total bilirubin (TB). Among the cases, 6 tested positive for Mycobacterium tuberculosis, 14 tested negative and 3 had unclear results. Liver biopsies were performed in 20 cases, revealing granulomatous hepatitis in 19 cases, while 1 case showed expansion and infiltration of inflammatory cells in the portal area without granuloma formation. Seven patients received anti-tuberculosis treatment, 14 were treated with a combination of anti-tuberculosis and glucocorticoid therapy, and 2 received glucocorticoids alone. Outcomes were favorable in 87%(20/23) of cases, with recovery noted in 20 patients; 2 cases improved but were lost to follow-up, and 1patient died. Conclusion Hepatitis resulting from intravesical BCG is rare and typically manifests with elevated ALP and/or GGT levels, often accompanied by jaundice. Most cases present as granulomatous hepatitis, with only a few miniority testing positive for Mycobacterium tuberculosis. While some patients recovered with anti-tuberculosis treatment alone, the majority required a combination of anti-tuberculosis therapy and glucocorticoid, or achieved recovery with glucocorticoids alone, suggesting a significant role of the immune response in the pathogenesis of the disease.

Key words: Granulomatous hepatitis, Calmette-Guerin (BCG) bladder instillation, Bladder cancer, Hepatotoxicity

WANG Yan, WANG Qian-yi, FENG Li-juan, WANG Min, CHEN Sha, WANG Yu, ZHAO Xin-yan. Clinicopathological features of granulomatous hepatitis induced by Bacillus Calmette-Guerin (BCG) bladder instillation: a case series and literature review[J]. Chinese Hepatolgy, 2024, 29(9): 1123-1127.

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