Spontaneous Cirrhosis Regression in an IFN-beta-induced AIH-like Syndrome Following Drug Withdrawal: Art of Facts or Artifacts?

Abstract

Autoimmune hepatitis (AIH) is a disease of unknown aetiology with drug-induced AIH being the most complex and not fully understood type. We present the case of a 57-year-old female patient with acute icteric hepatitis after interferon-beta-1b (IFNβ-1b) administration for multiple sclerosis (MS). Based on liver autoimmune serology, histology and appropriate exclusion of other liver diseases, a diagnosis of AIH-related cirrhosis was established. Following discontinuation of IFNβ-1b, a complete resolution of biochemical activity indices was observed and the patient remained untreated on her own decision. However, 3 years later, after a course of intravenous methylprednisolone for MS, a new acute transaminase flare was recorded which subsided again spontaneously after 3 weeks. Liver biopsy and elastography showed significant fibrosis regression (F2 fibrosis). To our knowledge, this is the first report showing spontaneous cirrhosis regression in an IFNβ-1b-induced AIH-like syndrome following drug withdrawal, suggesting that cirrhosis might be reversible if the offending fibrogenic stimulus is withdrawn.

Learning points: Autoimmune hepatitis (AIH) is a very heterogeneous liver disease of unknown aetiology, with drug-induced AIH being the most complex and not fully understood type.Intravenous methylprednisolone pulse administration may reactivate or unmask previously unrecognised or misdiagnosed AIH and therefore liver autoimmune serology should be sought for every patient with acute or chronic hepatitis in the absence of viral, metabolic, genetic and alcoholic causes of liver disease.Spontaneous regression of cirrhosis, although controversial, may occur if the offending fibrogenic stimuli are immediately withdrawn as shown in this case of IFNβ-1b-induced AIH.

Keywords: Autoimmune hepatitis; cirrhosis; drug-induced liver injury; interferon-beta; multiple sclerosis.

Figure 1

(A) Masson’s trichrome ×20. (B) Masson’s trichrome ×200. Representative microphotographs from the first biopsy which was 2.2 cm long and contained incomplete and complete cirrhotic nodules and 14 PT, and also showed extensive portal to portal and portal to central bridging fibrosis. There is a thick diaphragm of connective tissue (thickness 0.75 mm, green arrows) implying the presence of a cirrhotic nodule (modified Hepatic Activity Index stage 5–6). Collagen type I accumulation in the PT and fibrous septa was counted as 73.8±11.8. Blue areas represent collagen type I. (B, C) Representative microphotographs from the second biopsy performed 3 years later which was 2.8 cm long and contained 22 PT. There is portal to portal bridging fibrosis. Green arrows point to thin diaphragms of connective tissue (C: thickness 0.08 mm. D: thickness 0.02 mm). Modified Hepatic Activity Index stage 2 and inflammation grade 8/18. PT: portal tract.