Drug-induced autoimmune hepatitis: A minireview

Abstract

Drug-induced autoimmune hepatitis (DIAIH) is a specific phenotype of drug-induced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation. Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline, non-steroidal anti-inflammatory drugs, statins as well as anti-tumor necrosis agents. The clinical features of drug-induced liver injury are indistinguishable from idiopathic autoimmune hepatitis (AIH) as both may have positive AIH-related autoantibodies, elevated immunoglobulin G, as well as similar histopathological findings. In patients who show no clinical improvement, or there is progressive liver injury despite cessation of the suspected drug, a liver biopsy should be considered, whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH. Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury. A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper. In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature. Early identification and treatment often lead to a favorable outcome in DIAIH.

Keywords: Autoimmune hepatitis; Drug-induced autoimmune hepatitis; Drug-induced liver injury; Review.

Figure 1

Liver biopsy specimen for patient A. A: Low power view [hematoxylin & eosin (H&E) 100 ×] displays conspicuous portal and lobular inflammation with lobular disarray. Mild steatosis is also noted; B: Higher magnification of the portal tract (H&E 200 ×), zone 1, shows moderate chronic inflammation, lymphoplasmacytic predominantly, and rare eosinophils, with interface damage; C: At similar magnification (H&E 200 ×), the lobule including the perivenular region, e.g., zones 2 and 3, exhibits lobulitis characterized by aggregates of plasma cells, swollen hepatocytes with rosetting, Councilman bodies, and hepatocyte drop-out; D: High power view (H&E 400 ×) demonstrates rosetting of hepatocytes with droplets of orange-brown bile pigment; E and F: Histochemical stains Masson trichrome (E, 40 ×) showing collapse with mild early young fibrosis and Victoria blue (F, 40 ×) revealing paucity of elastic fibers, thus in keeping with subacute injury. Overall, the appearances are supportive of subacute drug-induced liver injury in association with autoimmune hepatitis histological pattern.

Figure 2

Bilirubin and alanine transaminase trend for patients A and B. A: Patient A; B: Patient B.

Figure 3

Liver biopsy findings for patient B. A: Low power view [hematoxylin & eosin (H&E) 100 ×] shows portal and lobular inflammation with lobular disarray and mild steatosis; B: Higher magnification of the portal tract (H&E 200 ×) demonstrates moderate plasma cell-rich chronic inflammation with continuous interface damage; C: Lobulitis with aggregates of plasma cells and rosetting of hepatocytes is present in the lobule (H&E 200 ×); D and E: Masson trichrome (D, 40 ×) and Victoria blue (E, 40 ×) display mild early young fibrosis and paucity of elastic fibers, respectively. The absence of old mature type fibrosis suggested not a chronic injury. The autoimmune hepatitis histological pattern observed was therefore interpreted to be drug related, atorvastatin-induced.