Statin‐induced autoimmune hepatitis in patients with type 1 diabetes: A report of two cases and literature review

Abstract

Statins are widely used medications for the treatment of hypercholesterolemia, as well as prevention of cardiovascular disease. We report two patients with type 1 diabetes who developed autoimmune hepatitis after the administration of statin. The first patient developed the marked elevation of liver enzymes 6 months into atorvastatin therapy. The second patient developed liver dysfunction 8 months after the initiation of rosuvastatin therapy. Liver biopsies in both patients showed either portal, interface and lobular hepatitis or a piece‐meal necrosis with lymphocytes and plasma cell infiltration that were compatible with autoimmune hepatitis. Then, both patients were started on prednisolone, to which they responded well. Liver biopsy is to be considered for type 1 diabetes patients if there is no improvement of liver dysfunction after discontinuation of statins.

Statin-induced Liver Injury Patterns: A Clinical Review

“… 11 A second patient had an elevated immunoglobulin G level (1,857 mg/dL) along with a liver biopsy significant for lobular, portal and interface hepatitis with lymphocyte and plasma cell infiltration and a IAHG score of 13, suggestive of probable AIH. 11 A third patient with presumed AIH did not have an IAHG score, but was weakly ANA positive and had a positive anti-smooth muscle antibody (ASMA) titer (1:640). 12 The fourth patient initially was only positive for ANA (1:160) 2 weeks after discontinuation of rosuvastatin, but subsequently became ASMA-positive (1:80) on repeat evaluation 1 month after medication discontinuation.…”

“…It is important to note that two of four patients who developed liver injury with autoimmune features had type 1 diabetes mellitus, 11 which is often associated with other autoimmune conditions, but there is literature to support its coexistence with autoimmune hepatitis. 11 The exact mechanism of statin-induced autoimmune hepatitis/immune-mediated DILI is not clear.…”

“…It is important to note that two of four patients who developed liver injury with autoimmune features had type 1 diabetes mellitus, 11 which is often associated with other autoimmune conditions, but there is literature to support its coexistence with autoimmune hepatitis. 11 The exact mechanism of statin-induced autoimmune hepatitis/immune-mediated DILI is not clear. Some studies have suggested that statins may upregulate toll-like receptors on activated dendritic cells, enhance the secretion of proinflammatory cytokines, and could be related to the development of autoimmune hepatitis.…”

“…Using the Scopus, PubMed, and Google Scholar databases, we identified 531 manuscripts using the key words "statin" and "liver injury". Of the 15 manuscripts evaluated, there were nine case reports, [10][11][12][13][14][15][16][17][18] two of which discussed two patients. 11,17 The case reports are summarized in Table 1.…”

Etiopathogenesis and Diagnostic Strategies in Autoimmune Hepatitis

“…AIH etiology is not fully understood. The most important role may be attributed to genetic, environmental, toxic and infective factors, including hepatitis A virus (HAV) [21,22], hepatitis C virus (HCV) [23,24], hepatitis E virus (HEV) [25], measles morbillivirus [26], Epstein-Barr virus (EBV) [16] and herpes simplex virus (HSV) [27] as well as medicines [28,29]. It has been proven that drug metabolites may stimulate the production of antibodies against liver cells.…”