Non-alcoholic steatohepatitis with positive ANA Chapter 3 Fatty Liver Diseases 1 Non-alcoholic steatohepatitis with positive ANA Case 3.17

Clinical Presentation 3 Fatty Liver Diseases 2 Clinical Presentation A 65-year-old woman presented with abdominal pain, nausea, and vomiting. She had a history of diabetes mellitus, hypertension, and hyperlipidemia, with no history of alcohol abuse. CT scan showed cirrhosis with splenomegaly.

Laboratory Values Course in Hospital AST: 69 ALT: 49 Alk Phos: 119 3 Fatty Liver Diseases 3 Laboratory Values AST: 69 ALT: 49 Alk Phos: 119 Total Bilirubin: 0.8 Total Protein: 6.9 Albumin: 3.8 Globulin: 3.1 ANA 1:1280 Ceruloplasmin: 29 α1-Antitrypsin: 149 Serologies: Anti-HAV, HBsAg, anti-HCV, SMA, AMA: Negative Course in Hospital Although the enzymes were only minimally elevated, because of the positive high titer ANA an autoimmune hepatitis was suspected and a liver biopsy was performed.

3 Fatty Liver Diseases 4 Pathology A well-established cirrhosis was present (trichrome) (a), the fibrous septa exhibiting a moderate lymphocytic infiltrate. The lobules showed mild steatosis with focal liver cell ballooning, Mallory-Denk body formation, and mild lymphocytic infiltrates (b). No periseptal interface inflammatory activity or plasma cell infiltrates was seen. Figure 3.17(a) Figure 3.17(b)

3 Fatty Liver Diseases 5 Diagnosis Non-alcoholic steatohepatitis (NASH), cirrhotic stage, with positive ANA Note: There was no histologic evidence of autoimmune hepatitis.

3 Fatty Liver Diseases Comment 6 The histologic features in this biopsy are quite characteristic of non-alcoholic steatohepatitis in the advanced stage. Although there was a high titer ANA, no hyperglobulinemia was present, no plasma cells were seen in the portal tracts or parenchyma, and no periportal interface inflammatory activity was present. Because autoimmune hepatitis is associated with some degree of plasma cell infiltrates and periportal activity on biopsy, an autoimmune process in this case example is unlikely. The cause of the ANA positivity in this case is not certain but ANA positivity is seen in about one-third of patients with NASH. Positive ANA can also occur in numerous disorders involving other organ systems such as systemic lupus erythematosus, Sjögren syndrome, and rheumatoid arthritis, but can also be drug related (e.g., nitrofurantoin) or associated with various infections (e.g., chronic hepatitis C). Additionally ANA positivity can also occur in from 3 to 5% in otherwise healthy individuals, although usually the titer is 1:160 or less.