Autoimmune-like hepatitis induced by drugs: Still many unanswered questions

Drug-induced autoimmune-like hepatitis (DI-ALH) is an increasingly recognized phenotype within the spectrum of drug-induced liver injury. Several drugs, including nitrofurantoin, minocycline, hydralazine, methyldopa and infliximab, have a well-documented capacity to induce DI-ALH. Distinguishing DI-ALH from classic de novo autoimmune hepatitis (AIH) can be challenging due to overlapping clinical, biochemical, and serological features. Accurate distinction from classic AIH is crucial, as management and prognosis differ. While some DI-ALH cases resolve spontaneously after drug withdrawal, others show persistent or worsening liver injury. Histological studies have shown that fibrosis and cirrhosis are more prevalent in classic AH. Unfortunately, there are no pathognomic clinical, biochemical or immunological features that reliably distinguish DI-ALH from classic AIH. However, most patients with DI-ALH do not relapse after corticosteroid withdrawal, in contrast to the high relapse rate observed in classic AIH. Most patients respond well to corticosteroids, and once liver tests normalize, biochemical parameters should be monitored, and long-term immunosuppression should not be indicated. However, DI-ALH is not exempt from risk of relapse, underscoring the need for long-term follow-up. Most patients with DI-ALH have a favorable prognosis; however, although rare, cases of cirrhosis and, in exceptional instances, acute liver failure have been reported. International collaborative studies are needed to further characterize DI-ALH. In this review, we update current controversies, present emerging concepts, and outline future challenges in the diagnosis and management of this complex condition learned so far.