Drug Liver Injury Induced by Olmesartan Mediated by Autoimmune-Like Mechanism: A Case Report.

Autoimmune hepatitis (AIH) was the first liver disease for which an effective therapeutic intervention was carried out, using prednisolone; its usefulness was demonstrated in several clinical trials. Nevertheless, AIH still remains a difficult diagnosis in some cases, because it is necessary to dismiss other possible diagnoses, and perhaps due to it being a heterogeneous disease. The relationship between drug-induced liver injury (DILI) and AIH is complex and not fully understood. There are three possible scenarios: (1) DILI with a strong immunoallergic component mimicking AIH; (2) AIH mimicking a DILI due to drug exposure and (3) AIH triggered by exposure to an offending drug (drug-induced AIH). Drug-induced AIH is well described and documented for some drugs such as nitrofurantoin and minocycline. Histologically distinguishing DILI from AIH remains a challenge. We present an interesting case report which met serologic criteria and histological confirmation to establish AIH, but discontinuation of a suspected drug resolved hypertransaminasaemia. LEARNING POINTS Idiosyncratic drug-induced liver injury is one of the most challenging liver disorders. Diagnosis of drug-induced liver injury is a complex question; this can evolve to severe hepatotoxicity if it is not diagnosed promptly. Usually, olmesartan and similar anti-hypertensive drugs are not considered drugs with the potential to cause liver damage. Keywords: Olmesartan, drug-induced liver injury, autoimmune-like mechanism, hypertransaminasaemia CASE DESCRIPTION The patient was an 80-year-old woman with a history of hypertension being treated with olmesartan/amlodipine since 2015, dyslipidaemia, sigmoid diverticulosis and serous papillary peritoneal adenocarcinoma diagnosed on November 2015, treated by surgery and chemotherapy with carboplatin-paclitaxel, receiving 6 cycles (the last cycle was received in June 2016). A complete response was confirmed in December 2016, with tumour markers within the normal range and no findings suggestive of neoplasm in PET-CT. In July 2017 the patient was referred to the Liver Unit due to alterations found during liver tests: aspartate aminotransferase (AST) 207 IU/L (N<33), alanine aminotransferase (ALT) 213 IU/L (N<33), gamma-glutamyl transpeptidase (GGTP) 21 IU/L (N<40), alkaline phosphatase (ALP) 116 IU/L (N<105), total bilirubin 0.5 mg/dl (N<1.2) and international normalized ratio 1.2. These findings were discovered during follow-up of the tumoural disease. No tumour marker elevation or CT alterations were observed. Liver tests were normal before starting treatment with olmesartan. The patient did not take herbal products, or other potentially hepatotoxic drugs. She had not travelled outside Europe recently. She had no history of abusive alcohol consumption and her body mass index was 26.6 kg/m2. Physical examination was normal. No fever, rash, eosinophilia, jaundice or coagulopathy was observed during follow-up, and she did not require hospitalization during the course of the disease. We repeated the liver tests 1 week later, with alterations persisting at 5 times the upper limit of normal values. An extensive evaluation was carried out, which ruled out serological viral hepatitis (hepatitis A, B and C) and metabolic liver disease, as well as Wilson disease or haemochromatosis; there was a normal blood count, normal gamma globulin, thyroid and lipid profiles, and no other relevant biochemistry alterations. Testing for antinuclear antibodies (ANA) was positive with a higher titre of 1/2,560 and a homogeneous pattern; testing for ASMA, anti-LKM1 antibodies and AMA was negative. In view of these findings and the persistent alterations seen in liver tests, we conducted a liver biopsy that showed the preserved architecture of liver parenchyma, with a portal polymorphic inflammatory infiltrate with occasional plasma cells (Fig. 1), lymphoplasmacytic patchy infiltrate in the lobule and mild portal fibrosis (Fig. 2). Occasional nuclear pseudoinclusions in hepatocytes were found. No signs suggestive of viral aetiology, abnormal iron deposits or Mallory’s hyaline were found with the corresponding techniques. Based on those results, we decided to stop olmesartan but without introducing prednisolone or other immunosuppressive therapy. Open in a separate window Figure 1 Histological results from liver biopsy showing an inflammatory infiltrate in the portal space with some plasmatic cells. These are the typical findings in patients with autoimmune hepatitis (images have been provided by Dra. M. Abengozar, Department of Pathology, Clinica Universidad de Navarra)