45 year old woman presented with abnormal liver function tests Liver Biopsy to r/o autoimmune hepatitis Further down. ANA 1: 160; ASMA 1:80 ANA 1: 160; ASMA 1:80 IgG = 14.5 g/l (upper normal range: 16) ALT 88; AST 76; ALP 132 BMI 31 Hyperlipidemia on Crestor Methotrexate for Psoriasis Viral hepatitis A, B, C serology negative Digital Slides 1
ANA 1: 160; ASMA 1:80 IgG = 14.5 g/l (upper normal range: 16) ALT 88; AST 76; ALP 132 BMI 31 Hyperlipidemia on Crestor Methotrexate for Psoriasis Viral hepatitis A, B, C serology negative 2
: The best representation of these findings is: A. Chronic hepatitis, consistent with autoimmune hepatitis B. Steatohepatitis activity grade 2 /4 C. Chronic hepatitis, consistent with steatohepatitis D. Methotrexate toxicity, recommend drug withdrawal E. None of these is appropriate; I have something else in mind A. Chronic hepatitis, consistent with autoimmune hepatitis There is NO chronic hepatitis, there is steatohepatitis; so it cannot be c/w chronic (autoimmune) hepatitis B. Steatohepatitis activity grade 2 /4 There is NO such grading system for steatohepatitis C. Chronic hepatitis, consistent with steatohepatitis There is NO chronic hepatitis, there is steatohepatitis never the same thing D. Methotrexate toxicity, recommend drug withdrawal Maybe, but the cumulative dose only 0.8 gm : The best representation of these findings is: A. Chronic hepatitis, consistent with autoimmune hepatitis B. Steatohepatitis activity grade 2 /4 C. Chronic hepatitis, consistent with steatohepatitis D. Methotrexate toxicity, recommend drug withdrawal E. None of these is appropriate; I have something else in mind 3
: Steatohepatitis, mildly active, with approx. 50% steatosis and (Kleiner Brunt) fibrosis stage 2 /4: Why mildly active? Why not the NAS score?? Poorly predictive References: 1. Kleiner D.E., Brunt E.M., and The Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41:1313 1321 2. Brunt EM, Kleiner DE, and The NASH Clinical Research Network (CRN). Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810 20 : Steatohepatitis, mildly active, with approx. 50% steatosis and (Kleiner Brunt) fibrosis stage 2 /4: Kleiner Brunt staging system 1A: Delicate perivenular, sub sinusoidal fibrosis 1B: Coarse perivenular, sub sinusoidal fibrosis 1C: Periportal fibrosis with no significant perivenular component 2: Subsinusoidal and periportal fibrosis (with no bridging) 3: Bridging fibrosis 4: Cirrhosis : Learning Point #1 Causes of NASH Steatohepatitis Non alcoholic (hence NASH) Drugs versus non drugs (discuss) Methotrexate reported a cause of NASH, but ALWAYS insist for a clinical search for non drug causes, b/c: Metabolic syndrome is very common and could be overlooked when easily blamed on MTX MTX toxicity is dose dependent and may really not be the culprit but withdrawn wrongly in a patient who really needs it. 4
: Learning Point #2 Beware ANA and ASMA Very (very very) non specific Elevated nonspecifically in at least 21% of NASH patients and has no clinical significance even in this context Vuppalanchi R, et al. Clinical significance of serum autoantibodies in patients with NAFLD: results from the nonalcoholic steatohepatitis clinical research network. Hepatol Int. 2011 10. [Epub ahead of print] Prevalence higher in women and with age with no evidence of AIH : Learning Point #3 Chronic hepatitis connotes something other than steatohepatitis NASH should not be called Chronic Hepatitis NASH mechanism, prognosis, treatment, investigations, etc. are completely different It is Either NASH OR Chronic Hepatitis OR Both overlapping, in which case patient has 2 diseases Lesson from : How to use the term Chronic hepatitis Reserve Chronic Hepatitis for cases in which pathogenesis began with immunemediated inflammation (or pathogens): Autoantigens (autoimmune hepatitis) Viral antigen (viral hepatitis) Drug relate Ag (drug induced hepatitis) Granulomas (granulomatous hepatitis) Hepatitis, etiology uncertain (but NOT when it s NASH) 5
: Learning Point #4 Steatohepatitis is a common disease Reporting system/approach still vary Be sure you and your gastroenterologist understand the same terminologies Try to understand what kinds of treatment response results from your diagnosis Drugs cause steatohepatitis, but be wary about recommending drug withdrawal unless you know or reasonably suspect this is necessary. 6