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Semin Liver Dis 2011; 31(4): 420-426
DOI: 10.1055/s-0031-1297930
DIAGNOSTIC PROBLEMS IN HEPATOLOGY

© Thieme Medical Publishers

A Maxed-Out Liver: A Case of Acute-On-Chronic Liver Failure

Gene Y. Im1 , Sofia Kazi2 , Swan N. Thung2 , Ponni V. Perumalswami1
  • 1Division of Liver Diseases, The Mount Sinai Medical Center, New York, New York
  • 2The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, The Mount Sinai Medical Center, New York, New York
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Publication History

Publication Date:
21 December 2011 (online)

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ABSTRACT

A 51-year-old man from Puerto Rico with Child-Turcotte-Pugh Class C decompensated cirrhosis due to genotype 1a chronic hepatitis C was referred for worsening jaundice and diuretic-resistant ascites. He began experiencing symptoms of hepatic decompensation 5 months prior to referral with new-onset ascites and spontaneous bacterial peritonitis, evolving into diuretic-resistant ascites, increasing jaundice, and a MELD increase from 12 to 29. During his hospitalization, his MELD score increased to >40 from a rapidly increasing international normalized ratio (INR) and evolving type 1 hepatorenal syndrome. Clinically, the patient appeared quite well despite such a high MELD score. After an extensive pretransplant evaluation and exclusion of infection, he underwent successful orthotopic liver transplantation. After histologic examination of the explanted liver, he subsequently admitted to 5 months of daily use of a detoxifying supplement known as MaxOne®, containing D-ribose-L-cysteine, consistent with a drug-induced acute-on-chronic liver failure. The use of complementary and alternative medicines and its potential for causing drug-induced liver injury and acute-on chronic liver failure requires a high index of suspicion and increased awareness among health care providers.

KEYWORDS

Drug-induced liver injury - acute-on-chronic liver failure - glutathione - hepatitis - liver transplantation

REFERENCES

  • 1 Chalasani N, Björnsson E. Risk factors for idiosyncratic drug-induced liver injury.  Gastroenterology. 2010;  138 (7) 2246-2259
    Search in Google Scholar
  • 2 Larrey D. Epidemiology and individual susceptibility to adverse drug reactions affecting the liver.  Semin Liver Dis. 2002;  22 (2) 145-155
    Search in Google Scholar
  • 3 Bahirwani R, Shaked O, Bewtra M, Forde K, Reddy K R. Acute-on-chronic liver failure before liver transplantation: impact on posttransplant outcomes.  Transplantation. 2011;  92 (8) 952-957
    Search in Google Scholar
  • 4 Ohnishi H, Sugihara J, Moriwaki H, Muto Y. [Acute-on-chronic liver failure].  Ryoikibetsu Shokogun Shirizu. 1995;  (7) 217-219
    Search in Google Scholar
  • 5 Escorsell Mañosa A, Mas Ordeig A. [Acute-on-chronic liver failure].  Gastroenterol Hepatol. 2010;  33 (2) 126-134
    Search in Google Scholar
  • 6 Graziadei I W. The clinical challenges of acute on chronic liver failure.  Liver Int. 2011;  31 (Suppl 3) 24-26
    Search in Google Scholar
  • 7 Francoz C, Glotz D, Moreau R, Durand F. The evaluation of renal function and disease in patients with cirrhosis.  J Hepatol. 2010;  52 (4) 605-613
    Search in Google Scholar
  • 8 Garcia-Tsao G, Parikh C R, Viola A. Acute kidney injury in cirrhosis.  Hepatology. 2008;  48 (6) 2064-2077
    Search in Google Scholar
  • 9 Borzio M, Salerno F, Piantoni L et al.. Bacterial infection in patients with advanced cirrhosis: a multicentre prospective study.  Dig Liver Dis. 2001;  33 (1) 41-48
    Search in Google Scholar
  • 10 Tandon P, Garcia-Tsao G. Bacterial infections, sepsis, and multiorgan failure in cirrhosis.  Semin Liver Dis. 2008;  28 (1) 26-42
    Search in Google Scholar
  • 11 Suriawinata A A, Thung S N. Chronic liver disorders. In: Suriawinata A A, Thung S N, eds. Liver Pathology: An Atlas and Concise Guide. New York, NY: Demos Medical Publishing; 2011: 73-123
    Search in Google Scholar
  • 12 Girelli D, Pasino M, Goodnough J B et al.. Reduced serum hepcidin levels in patients with chronic hepatitis C.  J Hepatol. 2009;  51 (5) 845-852
    Search in Google Scholar
  • 13 Hajdu C H, Lefkowitch J H. Adult polyglucosan body disease: a rare presentation with chronic liver disease and ground-glass hepatocellular inclusions.  Semin Liver Dis. 2011;  31 (2) 223-229
    Search in Google Scholar
  • 14 Jurkowska H, Uchacz T, Roberts J, Wróbel M. Potential therapeutic advantage of ribose-cysteine in the inhibition of astrocytoma cell proliferation.  Amino Acids. 2011;  41 (1) 131-139
    Search in Google Scholar
  • 15 Oz H S, Chen T S, Nagasawa H. Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model.  Transl Res. 2007;  150 (2) 122-129
    Search in Google Scholar
  • 16 Rathbun W B, Killen C E, Holleschau A M, Nagasawa H T. Maintenance of hepatic glutathione homeostasis and prevention of acetaminophen-induced cataract in mice by L-cysteine prodrugs.  Biochem Pharmacol. 1996;  51 (9) 1111-1116
    Search in Google Scholar
  • 17 Lucas A M, Hennig G, Dominick P K, Whiteley H E, Roberts J C, Cohen S D. Ribose cysteine protects against acetaminophen-induced hepatic and renal toxicity.  Toxicol Pathol. 2000;  28 (5) 697-704
    Search in Google Scholar
  • 18 Slitt A M, Dominick P K, Roberts J C, Cohen S D. Effect of ribose cysteine pretreatment on hepatic and renal acetaminophen metabolite formation and glutathione depletion.  Basic Clin Pharmacol Toxicol. 2005;  96 (6) 487-494
    Search in Google Scholar
  • 19 Roberts J C, Nagasawa H T, Zera R T, Fricke R F, Goon D J. Prodrugs of L-cysteine as protective agents against acetaminophen-induced hepatotoxicity. 2-(Polyhydroxyalkyl)- and 2-(polyacetoxyalkyl)thiazolidine-4(R)-carboxylic acids.  J Med Chem. 1987;  30 (10) 1891-1896
    Search in Google Scholar
  • 20 Crankshaw D L, Berkeley L I, Cohen J F, Shirota F N, Nagasawa H T. Double-prodrugs of L-cysteine: differential protection against acetaminophen-induced hepatotoxicity in mice.  J Biochem Mol Toxicol. 2002;  16 (5) 235-244
    Search in Google Scholar
  • 21 Roberts J C, Koch K E, Detrick S R, Warters R L, Lubec G. Thiazolidine prodrugs of cysteamine and cysteine as radioprotective agents.  Radiat Res. 1995;  143 (2) 203-213
    Search in Google Scholar
  • 22 Warters R L, Roberts J C, Wilmore B H, Kelley L L. Modulation of radiation-induced apoptosis by thiolamines.  Int J Radiat Biol. 1997;  72 (4) 439-448
    Search in Google Scholar
  • 23 Waldren C A, Vannais D B, Ueno A M. A role for long-lived radicals (LLR) in radiation-induced mutation and persistent chromosomal instability: counteraction by ascorbate and RibCys but not DMSO.  Mutat Res. 2004;  551 (1-2) 255-265
    Search in Google Scholar
  • 24 Lenarczyk M, Ueno A, Vannais D B et al.. The “pro-drug” RibCys decreases the mutagenicity of high-LET radiation in cultured mammalian cells.  Radiat Res. 2003;  160 (5) 579-583
    Search in Google Scholar
  • 25 Anderson M E, Luo J L. Glutathione therapy: from prodrugs to genes.  Semin Liver Dis. 1998;  18 (4) 415-424
    Search in Google Scholar
  • 26 Saito C, Zwingmann C, Jaeschke H. Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine.  Hepatology. 2010;  51 (1) 246-254
    Search in Google Scholar
  • 27 Yang R, Miki K, He X, Killeen M E, Fink M P. Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity.  Crit Care. 2009;  13 (2) R55
    Search in Google Scholar
  • 28 Uetrecht J. Idiosyncratic drug reactions: current understanding.  Annu Rev Pharmacol Toxicol. 2007;  47 513-539
    Search in Google Scholar
  • 29 Uetrecht J P. New concepts in immunology relevant to idiosyncratic drug reactions: the “danger hypothesis” and innate immune system.  Chem Res Toxicol. 1999;  12 (5) 387-395
    Search in Google Scholar
  • 30 Kaplowitz N. Idiosyncratic drug hepatotoxicity.  Nat Rev Drug Discov. 2005;  4 (6) 489-499
    Search in Google Scholar
  • 31 Aithal G P, Ramsay L, Daly A K et al.. Hepatic adducts, circulating antibodies, and cytokine polymorphisms in patients with diclofenac hepatotoxicity.  Hepatology. 2004;  39 (5) 1430-1440
    Search in Google Scholar
  • 32 Ho R H, Kim R B. Transporters and drug therapy: implications for drug disposition and disease.  Clin Pharmacol Ther. 2005;  78 (3) 260-277
    Search in Google Scholar
  • 33 Pauli-Magnus C, Meier P J. Hepatobiliary transporters and drug-induced cholestasis.  Hepatology. 2006;  44 (4) 778-787
    Search in Google Scholar
  • 34 Zimmerman H. Hepatotoxicity: The Adverse Effects of Drugs and Other Chemicals on the Liver. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 1999
    Search in Google Scholar
  • 35 Lewis J H. The rational use of potentially hepatotoxic medications in patients with underlying liver disease.  Expert Opin Drug Saf. 2002;  1 (2) 159-172
    Search in Google Scholar
  • 36 Russo M W, Watkins P B. Are patients with elevated liver tests at increased risk of drug-induced liver injury?.  Gastroenterology. 2004;  126 (5) 1477-1480
    Search in Google Scholar
  • 37 Wong W M, Wu P C, Yuen M F et al.. Antituberculosis drug-related liver dysfunction in chronic hepatitis B infection.  Hepatology. 2000;  31 (1) 201-206
    Search in Google Scholar
  • 38 Lee B H, Koh W J, Choi M S et al.. Inactive hepatitis B surface antigen carrier state and hepatotoxicity during antituberculosis chemotherapy.  Chest. 2005;  127 (4) 1304-1311
    Search in Google Scholar
  • 39 Patel P A, Voigt M D. Prevalence and interaction of hepatitis B and latent tuberculosis in Vietnamese immigrants to the United States.  Am J Gastroenterol. 2002;  97 (5) 1198-1203
    Search in Google Scholar
  • 40 Ungo J R, Jones D, Ashkin D et al.. Antituberculosis drug-induced hepatotoxicity. The role of hepatitis C virus and the human immunodeficiency virus.  Am J Respir Crit Care Med. 1998;  157 (6 Pt 1) 1871-1876
    Search in Google Scholar
  • 41 Eisenberg D M, Davis R B, Ettner S L et al.. Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.  JAMA. 1998;  280 (18) 1569-1575
    Search in Google Scholar
  • 42 Eisenberg D M, Kessler R C, Foster C, Norlock F E, Calkins D R, Delbanco T L. Unconventional medicine in the United States. Prevalence, costs, and patterns of use.  N Engl J Med. 1993;  328 (4) 246-252
    Search in Google Scholar
  • 43 Graham R E, Gandhi T K, Borus J et al.. Risk of concurrent use of prescription drugs with herbal and dietary supplements in ambulatory care. In: Henriksen K, Battles J B, Keyes M A, Grady ML, eds. Advances in Patient Safety: New Directions and Alternative Approaches (Vol. 4: Technology and Medication Safety). Rockville, MD: Agency for Healthcare Research and Quality (US); 2008
    Search in Google Scholar
  • 44 Sood A, Sood R, Brinker F J, Mann R, Loehrer L L, Wahner-Roedler D L. Potential for interactions between dietary supplements and prescription medications.  Am J Med. 2008;  121 (3) 207-211
    Search in Google Scholar
  • 45 Wold R S, Lopez S T, Yau C L et al.. Increasing trends in elderly persons’ use of nonvitamin, nonmineral dietary supplements and concurrent use of medications.  J Am Diet Assoc. 2005;  105 (1) 54-63
    Search in Google Scholar
  • 46 Peng C C, Glassman P A, Trilli L E, Hayes-Hunter J, Good C B. Incidence and severity of potential drug-dietary supplement interactions in primary care patients: an exploratory study of 2 outpatient practices.  Arch Intern Med. 2004;  164 (6) 630-636
    Search in Google Scholar
  • 47 Bardia A, Nisly N L, Zimmerman M B, Gryzlak B M, Wallace R B. Use of herbs among adults based on evidence-based indications: findings from the National Health Interview Survey.  Mayo Clin Proc. 2007;  82 (5) 561-566
    Search in Google Scholar
  • 48 Gardiner P, Graham R, Legedza A T, Ahn A C, Eisenberg D M, Phillips R S. Factors associated with herbal therapy use by adults in the United States.  Altern Ther Health Med. 2007;  13 (2) 22-29
    Search in Google Scholar
  • 49 Kennedy J, Wang C C, Wu C H. Patient disclosure about herb and supplement use among adults in the US.  Evid Based Complement Alternat Med. 2008;  5 (4) 451-456
    Search in Google Scholar
  • 50 Ang-Lee M K, Moss J, Yuan C S. Herbal medicines and perioperative care.  JAMA. 2001;  286 (2) 208-216
    Search in Google Scholar
  • 51 Kaye A D, Clarke R C, Sabar R et al.. Herbal medicines: current trends in anesthesiology practice—a hospital survey.  J Clin Anesth. 2000;  12 (6) 468-471
    Search in Google Scholar
  • 52 Mehta D H, Phillips R S, Davis R B, McCarthy E P. Use of complementary and alternative therapies by Asian Americans. Results from the National Health Interview Survey.  J Gen Intern Med. 2007;  22 (6) 762-767
    Search in Google Scholar
  • 53 Strader D B, Bacon B R, Lindsay K L et al.. Use of complementary and alternative medicine in patients with liver disease.  Am J Gastroenterol. 2002;  97 (9) 2391-2397
    Search in Google Scholar
  • 54 Cohen M R. Herbal and complementary and alternative medicine therapies for liver disease. A focus on Chinese traditional medicine in hepatitis C virus.  Clin Liver Dis. 2001;  5 (2) 461-478, vii
    Search in Google Scholar
  • 55 Chalasani N, Fontana R J, Bonkovsky H L Drug Induced Liver Injury Network (DILIN) et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States.  Gastroenterology. 2008;  135 (6) 1924-1934, 1934, e1–e4
    Search in Google Scholar
  • 56 Bovill J G. Adverse drug interactions in anesthesia.  J Clin Anesth. 1997;  9 (6, Suppl) 3S-13S
    Search in Google Scholar

Ponni V. PerumalswamiM.D. 

Division of Liver Diseases, The Mount Sinai Medical Center

Box 1104, One Gustave L. Levy Place, New York, NY 10029

Email: ponni.perumalswami@mountsinai.org