Granulomatous hepatitis: case reportA 79-year-old man developed granulomatous hepatitis during treatment with BCG for bladder cancer. The man presented with a history of dyslipidaemia medicated with unspecified statins, moderate alcohol consumption and ischaemic heart failure. He was diagnosed with high-grade papillary urothelial carcinoma back in 2016, and received immunotherapy with intravesicular instillation of BCG [dosage not stated] for a full year with the last instillation in February 2018. Routine bloodwork showed a hepatic cytolysis and cholestasis for the first time in January 2018 with an elevated level of aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, alkaline phosphatase, and without hyper-bilirubinaemia. He also reported fatigue and diminished appetite. On physical examination, the liver was found palpable 4cm bellow the right costal margin. Blood tests revealed a mild hepatic cytolysis. Three months later, he had aggravated liver enzymes, with elevated level of AST, ALT and cholestasis and normal bilirubin. At that time, he stopped statin therapy and alcohol consumption. An abdominal ultrasound performed in November 2018 revealed a globous hepatic parenchyma with no focal lesions. In April 2019, he reported weight loss in the previous few months and colangio-MRI was performed, which revealed homogeneous mild hepatomegaly and splenomegaly, without nodules or other lesions, and the absence of biliary duct dilatation. In November 2019, he electively admitted for a hepatic biopsy. Histology revealed a granulomatous hepatitis and fibrotic septation of the parenchyma, with some multinucleated cells but without the typical aspects of Langhans cells and a negative Ziehl-Neelsen stain. A polymerase chain reaction (PCR) of Mycobacterium tuberculosis complex was found to be negative in the liver biopsy paraffined specimen. The HIV and viral hepatitis serologies were also found negative. Serology and PCR for Coxiella burnetii and Brucella spp., as well as mycobacterial examination of urine, were also found negative. Thoracic CT revealed multiple mediastinal and hilar lymph nodes without adenomegaly criteria, some with gross calcifications, and lung parenchyma with evident emphysema, without masses, nodules or consolidations. An immune panel for autoimmune hepatitis was normal, and the serum angiotensin conversion enzyme (ACE) was found negative. He was then referred to the infectious disease outpatient clinic, where he was first observed in June 2020. With the complaints of anorexia and weight loss, a diagnosis of granulomatous hepatitis secondary to BCG was made. The hepatic cytolysis and cholestasis started 1-2 months after the discontinuation of the BCG, which was consistent with the suspected diagnosis.The man received empirical treatment with isoniazid and rifampicin in late June. After the treatment initiation, there was a progressive improvement of the liver enzymes was observed, with full normalisation of the cytolysis and a considerable decrease in cholestasis in November. ...
