Progestin-induced liver injury in an asymptomatic patient

We report a case of a female in her mid-40s diagnosed as norethisterone-induced liver injury. Our patient presented to the medical gastroenterology clinic with an incidental finding of progressively increasing transaminases. A detailed evaluation strongly supported our suspicion of progestin-induced liver disease with prompt reversal after discontinuation of norethisterone. Various clinical trials on the safety and efficacy of norethisterone suggest that liver injury is not a common adverse event associated with norethisterone use. Oestrogens are more commonly, and progestogens are less frequently,associated with a spectrum of liver abnormalities, including hepatocellular or cholestatic types of injury, peliosis hepatitis and sinusoidal obstruction syndrome. It may be a completely incidental finding, as in our patient. Our patient lacks cardiometabolic risk factors such as obesity, diabetes mellitus and dyslipidaemia, which are typically associated with metabolic dysfunction-associated steatotic liver disease (MASLD), or alcohol use. Awareness of rare adverse drug reactions, as in this case with norethisterone, is vital for prompt diagnosis and effective management and hence prevention of potential morbidity and mortality. We discuss the various aspects of evaluating suspected drug-induced liver injury, combining clinical assessment with the use of diagnostic tools such as Roussel Uclaf Causality Assessment Method to aid in identifying the offending agent.