Digestive Diseases and Sciences

, Volume 64, Issue 10, pp 2780–2783 | Cite as

Don’t Miss the BoAAT: Correctly Diagnosing Acute-on-Chronic Liver Disease

  • Zain A. SobaniEmail author
  • Graziella R. Paniz
  • Morgan Wong
  • Denis M. McCarthy


A 48-year-old male with diabetes and hyperlipidemia was referred to the Hepatology Outpatient Clinic with acute elevation in serum concentrations of liver enzymes. During preoperative evaluation for an elective knee arthroplasty 10 months previously, he had been diagnosed with cirrhosis, based on thrombocytopenia and the finding of a nodular liver as assessed by ultrasound scanning. The cirrhosis was presumed due to nonalcoholic fatty liver disease; his primary care physician managed the patient. Subsequently, he had an acute elevation of serum concentrations of liver enzymes and was referred to the Hepatology Clinic for further evaluation.

The patient complained of having a poorly defined pain in his right upper quadrant for 8 weeks. He recalls having had an upper respiratory tract illness treated with amoxicillin 10–12 weeks before presentation. On review, he had no other symptoms. He was living a relatively normal healthy life, devoid of symptoms or previous illness other than...


Alpha 1 Antitrypsin Deficiency Cirrhosis Acute-on-Chronic Liver Disease Elevated Liver Enzymes 



  1. 1.
    Duvoix A, Roussel BD, Lomas DA. Molecular pathogenesis of alpha-1-antitrypsin deficiency. Rev Mal Respir. 2014;31:992–1002.CrossRefGoogle Scholar
  2. 2.
    Teckman JH, Blomenkamp KS. Pathophysiology of alpha-1 antitrypsin deficiency liver disease. Methods Mol Biol. 2017;1639:1–8.CrossRefGoogle Scholar
  3. 3.
    Teckman JH. Liver disease in alpha-1 antitrypsin deficiency: current understanding and future therapy. COPD. 2013;10(Suppl 1):35–43.CrossRefGoogle Scholar
  4. 4.
    Teckman JH, Jain A. Advances in alpha-1-antitrypsin deficiency liver disease. Curr Gastroenterol Rep. 2014;16:367–368.CrossRefGoogle Scholar
  5. 5.
    Lindblad D, Blomenkamp K, Teckman J. Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model. Hepatology. 2007;46:1228–1235.CrossRefGoogle Scholar
  6. 6.
    Brode SK, Ling SC, Chapman KR. Alpha-1 antitrypsin deficiency: a commonly overlooked cause of lung disease. CMAJ. 2012;184:1365–1371.CrossRefGoogle Scholar
  7. 7.
    Stoller JK, Sandhaus RA, Turino G, Dickson R, Rodgers K, Strange C. Delay in diagnosis of alpha1-antitrypsin deficiency: a continuing problem. Chest. 2005;128:1989–1994.CrossRefGoogle Scholar
  8. 8.
    Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112:18–35.CrossRefGoogle Scholar
  9. 9.
    Campbell E, Scott L. Quantitative isoelectric focusing of alpha1-antitrypsin: grouping and prevalence of unusual alpha1-antitrypsin variants. Chest. 2013;144:705A. Scholar
  10. 10.
    Patel D, Teckman JH. Alpha-1-antitrypsin deficiency liver disease. Clin Liver Dis. 2018;22:643–655.CrossRefGoogle Scholar
  11. 11.
    Hamesch K, Mandorfer M, Pereira VM, et al. Liver fibrosis and metabolic alterations in adults with alpha1 antitrypsin deficiency caused by the Pi*ZZ mutation. Gastroenterology. 2019. Scholar
  12. 12.
    Clark VC, Marek G, Liu C, Collinsworth A, et al. Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort. J Hepatol. 2018;9:1357–1364.CrossRefGoogle Scholar
  13. 13.
    Sarkar S, Floto RA, Berger Z, Imarisio S, et al. Lithium induces autophagy by inhibiting inositol monophosphatase. J Cell Biol. 2005;170:1101–1111.CrossRefGoogle Scholar
  14. 14.
    Hidvegi T, Ewing M, Hale P, Dippold C, et al. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science. 2010;329(5988):229–232.CrossRefGoogle Scholar
  15. 15.
    Kaushal S, Annamali M, Blomenkamp K, Rudnick D, et al. Rapamycin reduces intrahepatic alpha-1-antitrypsin mutant Z protein polymers and liver injury in a mouse model. Exp Biol Med (Maywood). 2010;235:700–709.CrossRefGoogle Scholar
  16. 16.
    Tang Y, Fickert P, Trauner M, Marcus N, et al. Autophagy induced by exogenous bile acids is therapeutic in a model of alpha-1-AT deficiency liver disease. Am J Physiol Gastrointest Liver Physiol. 2016;311:G156–G165.CrossRefGoogle Scholar
  17. 17.
    Carbamazepine in severe liver disease due to alpha-1 antitrypsin deficiency.
  18. 18.
    Lomas DA. New therapeutic targets for alpha-1 antitrypsin deficiency. Chronic Obstr Pulm Dis. 2018;5:233–243.Google Scholar
  19. 19.
    Guo S, Booten SL, Aghajan M, Hung G, et al. Antisense oligonucleotide treatment ameliorates alpha-1 antitrypsin-related liver disease in mice. J Clin Invest. 2014;124:251–261.CrossRefGoogle Scholar
  20. 20.
    A study of an investigational drug, ALN-AAT, in healthy adult subjects and patients With ZZ type alpha-1 antitrypsin deficiency liver disease.
  21. 21.
    Turner AM, Stolk J, Bals R, Lickliter JD, et al. Hepatic-targeted RNA interference provides robust and persistent knockdown of alpha-1 antitrypsin levels in ZZ patients. J Hepatol. 2018;69:378–384.CrossRefGoogle Scholar
  22. 22.
    Safety, tolerability and effect of ARC-AAT injection on circulating and intrahepatic alpha-1 antitrypsin levels.
  23. 23.
    Baligar P, Kochat V, Arindkar SK, Equbal Z, et al. Bone marrow stem cell therapy partially ameliorates pathological consequences in livers of mice expressing mutant human alpha1-antitrypsin. Hepatology. 2017;65:1319–1335.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zain A. Sobani
    • 1
    • 3
    Email author
  • Graziella R. Paniz
    • 2
  • Morgan Wong
    • 1
  • Denis M. McCarthy
    • 1
  1. 1.Division of GastroenterologyUniversity of New Mexico School of MedicineAlbuquerqueUSA
  2. 2.Department of MedicineUniversity of New Mexico School of MedicineAlbuquerqueUSA
  3. 3.Division of Gastroenterology and Hepatology1 University of New MexicoAlbuquerqueUSA

Personalised recommendations