Appleyard et al. Journal of Medical Case Reports 2010, 4:311 http://www.jmedicalcasereports.com/content/4/1/311 excess alcohol intake. An ultrasound scan showed an irregular liver contour, her previous cholecystectomy and no evidence of any biliary obstruction. Clinical examination revealed palmar erythema, a palpable liver edge, cholecystectomy and nephrectomy scars. Blood tests on admission showed unremarkable full blood count (FCB), although mean corpuscular volume (MCV) was 100, bilirubin 394 μmol/L, alanine amino- transferase (ALT) 1423 U/L, alkaline phosphatase 207 U/L. Albumin was 29 g/L, international normalized ratio (INR) 1.2. A computed tomography (CT) scan of the abdomen showed no focal lesion within the liver and no evidence of any biliary dilatation. Serological tests were negative for hepatitis A, hepatitis B, hepatitis C, hepatitis E, cytomegalovirus, Epstein-Barr virus and human immunodeficiency virus (HIV). Immunoglobulin levels showed high IgG at 22.3 g/L and IgA slightly elevated at 4.4 g/L. Anti-nuclear antibody was strongly positive at 1:640, but smooth muscle antibody and liver/ kidney microsomal antibodies were negative as was the rest of the auto-antibody screen including serologi- cal markers for systemic lupus erythematosus. Tissue transglutaminase antibody was negative. A liver biopsy showed striking lobular inflammation, confluent and bridging necrosis. In addition there were some syncytial giant cells. There was minimal portal inflammation and minimal plasma cells. Features were consistent with an acute hepatitis with an autoimmune component and some features of a syncytial giant cell hepatitis (Figure 3). Nitrofurantoin was stopped. Prednisolone 30 mg daily was commenced, but failed to improve her clinical or biochemical picture. The dose was increased to 50 mg Figure 3 Liver biopsy in Case 3: syncitial hepatocyte giant cell (arrowed) with surrounding severe hydropic degenerative change of hepatocytes and numerous neutrophils (hematoxylin and eosin × 40). Page 3 of 5 daily, and she remained hospitalized as she became more unwell with bilirubin reaching 430 μmol/L and albumin dropping to16 g/L. Mycophenolate 1 g twice daily was added. Over a period of four months her jaun- dice subsided and at seven months after initial presenta- tion her liver biochemistry had returned to normal, while taking prednisolone 10 mg daily and mycopheno- late 1 g twice daily. Discussion Three cases of hepatitis in women who were taking long-term nitrofurantoin as prophylaxis against recur- rent urinary tract infection are described. In all three cases the serology, liver histology and clinical response to immunosuppressive drugs were consistent with auto- immune hepatitis. Nitrofurantoin is widely used for both acute and chronic management of urinary tract infections. It is cheap and effective, with a low incidence of resistance in common urinary pathogens; it is also safe in preg- nancy [3]. Nitrofurantoin has been linked to autoim- mune hepatitis, but in view of the rarity of the association, almost all reports of the association have been single case reports or small series [4-9]. Further information has been obtained from national adverse drug reaction monitoring agencies in the Netherlands [10] and Denmark [11] and it has been estimated that the incidence of nitrofurantoin-induced hepatic injury is low at about three cases in 1,000,000 [12]. Liver injury secondary to nitrofurantoin has been reported after both acute and chronic exposure and the patterns of hepatotoxity are different. Case reports have often reported heterogeneous patients [7], including both acute and chronic nitrofurantoin associated liver injury. Acute injury, which may be via a hypersensitivity type reaction, tends to occur within weeks of drug intro- duction [8]. Chronic hepatitis is associated with long- term antimicrobial prophylaxis. It occurs after at least six months treatment in 85% of cases [10], and in many cases treatment has been ongoing for years before pro- blems present. Anti-nuclear antibodies and anti-smooth muscle antibodies are often present in the chronic form of hepatitis [6] and the liver histology resembles that of ‘idiopathic’ autoimmune hepatitis. When hepatotoxicity is a consequence of direct drug injury, drug withdrawal alone may lead to liver recovery. However, the chronic liver disease associated with nitro- furantoin is likely to be mediated via an immunoaller- genic route. Evidence for this includes the increase incidence in women, presence of auto-antibodies and histological appearances. Risk factors for nitrofurantoin- triggered liver injury have been postulated and these include advanced age (possibly related to reduced creati- nine clearance), female sex - in common with many