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Acquired Metabolic Disorders

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Liver Diseases

Abstract

The liver is a complex and critically important organ involved in both the biosynthesis of as well as the metabolism of numerous biochemical products. Acquired metabolic liver disorders result from the loss of this hepatic homeostasis. It is thought that the first recognition of a metabolic liver disorder was the description of porphyria by Hippocrates. The focus of this chapter is the potential origins for, diagnosis of, and treatment of acquired metabolic liver disorders, which include ornithine transcarbamylase deficiency, porphyria, hemochromatosis, and alpha 1 antitrypsin deficiency. Origins for acquired metabolic liver disorders include bariatric surgery with regards to ornithine transcarbamylase deficiency, organic chemical exposure with regards to porphyria, alcohol use/repeated blood transfusions/excessive oral iron supplements/hepatitis C with regards to hemochromatosis, and infectious Tropical Pulmonary Eosinophilia with regards to alpha 1 antitrypsin deficiency. Wilson disease is an additional, important genetic metabolic liver disease. In future work, pathophysiological mechanisms of disease and preventing the development of acquired metabolic liver disorders remain areas of focus for clinical research in this field.

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References

  1. Häberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, Karall D, Martinelli D, Crespo PS, Santer R, Servais A, Valayannopoulos V, Linder M, Rubio V, Dionisi-Vici C. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J Rare Dis. 2012;7:32.

    Article  Google Scholar 

  2. Brassier A, Gobin S, Arnoux JB, Valayannopoulos V, Habarou F, Kossorotoff M, Servais A, Barbier V, Dubois S, Touati G, Barouki R, Lesage F, Dupic L, Bonnefont JP, Ottolenghi C, De Lonlay P. Long-term outcomes in ornithine transcarbamylase deficiency: a series of 90 patients. Orphanet J Rare Dis. 2015;10:58. https://doi.org/10.1186/s13023-015-0266-1.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Acharya G, Mehra S, Patel R, Frunza-Stefan S, Kaur H. Fatal non hepatic hyperammonemia in ICU setting: a rare but serious complication following bariatric surgery. Case Rep Crit Care. 2016;2016:8531591.

    PubMed  PubMed Central  Google Scholar 

  4. Becker D, Balcer L, Galetta S. The neurological complications of nutritional deficiency following bariatric surgery. J Obes. 2012;2012:608534. https://doi.org/10.1155/2012/608534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Fenves A, Shchelochkov O, Mehta A. Hyperammonemic syndrome after Roux-en-Y gastric bypass. Obesity. 2015;23(4):746–9.

    Article  Google Scholar 

  6. Kromas ML, Mousa OY, John S. Hyperammonemia-induced encephalopathy: a rare devastating complication of bariatric surgery. World J Hepatol. 2015;7(7):1007–11.

    Article  Google Scholar 

  7. Bissell DM, Anderson KE, Bonkovsky HL. Porphyria. N Engl J Med. 2017;377(9):862–72.

    Article  CAS  Google Scholar 

  8. Stein P, Badminton M, Barth J, Rees D, Stewart MF, British and Irish Porphyria Network. Best practice guidelines on clinical management of acute attacks of porphyria and their complications. Ann Clin Biochem. 2013;50(Pt 3):217–23.

    Article  Google Scholar 

  9. Balwani M, Wang B, Anderson KE, Bloomer JR, Bissell DM, Bonkovsky HL, Phillips JD, Desnick RJ, Porphyrias Consortium of the Rare Diseases Clinical Research Network. Acute hepatic porphyrias: recommendations for evaluation and long-term management. Hepatology. 2017;66(4):1314–22.

    Article  Google Scholar 

  10. Smith AG, Foster JR. The association between chemical-induced porphyria and hepatic cancer. Toxicol Res (Camb). 2018;7(4):647–63.

    Article  CAS  Google Scholar 

  11. Salameh H, Sarairah H, Rizwan M, Kuo YF, Anderson KE, Singal AK. Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis. Br J Dermatol. 2018. https://doi.org/10.1111/bjd.16741.

    Article  CAS  Google Scholar 

  12. Ulvik RJ. Hereditary haemochromatosis through 150 years. Tidsskr Nor Laegeforen. 2016;136(23–24):2017–21.

    Article  Google Scholar 

  13. Zou D-M, Sun W-L. Relationship between hepatitis C virus infection and iron overload. Chin Med J. 2017;130(7):866–71.

    Article  Google Scholar 

  14. Golfeyz S, Lewis S, Weisberg IS. Hemochromatosis: pathophysiology, evaluation, and management of hepatic iron overload with a focus on MRI. Expert Rev Gastroenterol Hepatol. 2018;12(8):767–78.

    Article  CAS  Google Scholar 

  15. Rostoker G, Vaziri ND. Iatrogenic iron overload and its potential consequences in patients on hemodialysis. Presse Med. 2017;46(12 Pt 2):e312–28.

    Article  Google Scholar 

  16. Townsend SA, Edgar RG, Ellis PR, Kantas D, Newsome PN, Turner AM. Systematic review: the natural history of alpha-1 antitrypsin deficiency, and associated liver disease. Aliment Pharmacol Ther. 2018;47(7):877–85.

    Article  CAS  Google Scholar 

  17. Mitchell EL, Khan Z. Liver disease in alpha-1 antitrypsin deficiency: current approaches and future directions. Curr Pathobiol Rep. 2017;5(3):243–52.

    Article  CAS  Google Scholar 

  18. Renjen PN, Khanna L, Rastogi R, Khan NI. Acquired hepatocerebral degeneration. BMJ Case Rep. 2013. https://doi.org/10.1136/bcr-2013-009387. pii: bcr2013009387.

    Google Scholar 

  19. Li H, Liu L, Li Y, He S, Liu Y, Li J, Tao R, Li W, Shang S. Familial screening of children with Wilson disease: necessity of screening in previous generation and screening methods. Medicine. 2018 Jul;97(27):e11405. https://doi.org/10.1097/MD.0000000000011405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ferenci P, Czlonkowska A, Stremmel W, Houwen R, Rosenberg W, Schilsky M, Jansen P, Moradpour D, the European Association for Study of Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol. 2012;56(3):671–85.

    Article  Google Scholar 

  21. Santiago R, Gottrand F, Debray D, et al. Zinc therapy for Wilson disease in children in French pediatric centers. J Pediatr Gastroenterol Nutr. 2015;61(6):613–8.

    Article  CAS  Google Scholar 

Further Readings

    Ornithine Transcarbamylase Deficiency

    • Russell A, Levin B, Oberholzer VG, Sinclair L. Hyperammonemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea. Lancet. 1962;2(7258):699–700.

      Article  CAS  Google Scholar 

    • Chikwava K, Finegold D. Final diagnosis-partial ornithine transcarbamylase (OTC) deficiency. Case presentation at UPMC pathology: Case. p. 335.

      Google Scholar 

    • Hu WT, Kantarci OH, Merritt JL, McGrann P, Dyck PJB, Lucchinetti CF, Tippmann-Peikert M. Ornithine transcarbamylase deficiency presenting as encephalopathy during adulthood following bariatric surgery. Arch Neurol. 2007;64(1):126–8.

      Article  Google Scholar 

    • Levy H, Picker J. New England Consortium of Metabolic Programs. Ornithine transcarbamylase deficiency (OTC deficiency).

      Google Scholar 

    • Gyato K, Wray J, Huang ZJ, Yudkoff M, Batshaw M. Metabolic and Neuropsychological phenotype in women heterozygous for ornithine transcarbamylase deficiency. Ann Neurol. 2004;55:80–6.

      Article  Google Scholar 

    Porphyria

    • Downey DC. Porphyria and chemicals. Med Hypotheses. 1999;53(2):166–71.

      Article  CAS  Google Scholar 

    • Jarrell JF, Gocmen A, Akyol D, Brant R. Hexachlorobenzene exposure and the proportion of male births in Turkey 1935-1990. Reprod Toxicol. 2002;16(1):65–70.

      Article  CAS  Google Scholar 

    Hemochromatosis

    Alpha 1 Antitrypsin Deficiency

    • Ray D, Harikrishna S, Immanuel C, Victor L, Subramanyam S, Kumaraswami V. Acquired alpha 1-antitrypsin deficiency in tropical pulmonary eosinophilia. Indian J Med Res. 2011;134:79–82.

      CAS  PubMed  PubMed Central  Google Scholar 

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    Author information

    Authors and Affiliations

    1. Center for Advanced Laparoscopic General & Bariatric Surgery, Washington, DC, USA

      Ivanesa L. Pardo Lameda & Timothy R. Koch

    2. MedStar Washington Hospital Center and Georgetown University School of Medicine, Washington, DC, USA

      Timothy R. Koch

    Authors
    1. Ivanesa L. Pardo Lameda
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    2. Timothy R. Koch
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    Corresponding author

    Correspondence to Timothy R. Koch .

    Editor information

    Editors and Affiliations

    1. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

      Florentina Radu-Ionita

    2. New Jersey Medical School, Rutgers University New Jersey Medical School, Newark, NJ, USA

      Nikolaos T. Pyrsopoulos

    3. Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

      Mariana Jinga

    4. Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania

      Ion C. Tintoiu

    5. Medical Radiation Sciences, Curtin University, Perth, WA, Australia

      Zhonghua Sun

    6. “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania

      Ecaterina Bontas

    Self Study

    Self Study

    1.1 Questions

    1. 1.

      Which statements are true?

      1. (a)

        Ornithine Transcarbamylase deficiency is the most common urea cycle disorder.

      2. (b)

        Hyperammonemia causes symptoms of peripheral neuropathy beginning with paresthesias of the extremities, progressing to numbness, and then to a constant burning sensation.

      3. (c)

        Patients with Ornithine Transcarbamylase deficiency present with a decreased urine orotic acid.

      4. (d)

        Initial treatment of ornithine transcarbamylase deficiency involves a reduction in the production of nitrogenous waste as well as increased excretion of nitrogenous waste.

    2. 2.

      Which statement is true?

      1. (a)

        Porphyrias result from a urea cycle disorder.

      2. (b)

        The development of blistering and thinning of areas of sun-exposed skin can result from exposure to a mixture of two phenoxy herbicides: 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid.

      3. (c)

        The avoidance of alcohol does not prevent development of porphyria cutanea tarda.

      4. (d)

        Individuals receiving chloroquine or hydroxychloroquine should undergo periodic examination of renal or kidney function.

    3. 3.

      Which statement is true?

      1. (a)

        Hereditary hemochromatosis is an autosomal dominant disorder that involves the HFE gene.

      2. (b)

        Symptoms/findings of hemochromatosis include liver enlargement, cirrhosis, “bronze” skin color, diabetes mellitus, arthropathy, cardiomyopathy, or hypogonadism.

      3. (c)

        In individuals without HFE gene mutations, computerized tomography imaging of the liver is generally useful for supporting a diagnosis of hemochromatosis.

      4. (d)

        Phlebotomy is the initial treatment for hereditary hemochromatosis and the pretreatment hemoglobin should be >10 g/dl with a serum ferritin of <50 ng/ml.

    4. 4.

      Which statements are true?

      1. (a)

        Alpha 1 antitrypsin is a protease inhibitor mainly biosynthesized by hepatocytes that protects tissues from proteolytic enzyme damage.

      2. (b)

        Upon genetic testing for alpha 1 antitrypsin, three alleles have been described, M, S, and Z.

      3. (c)

        There have been sporadic reports of acquired alpha 1 antitrypsin deficiency, especially in individuals with Tropical Pulmonary Eosinophilia and the homozygote ZZ alleles.

      4. (d)

        Alpha 1 antitrypsin deficiency-related liver disease is treated with augmentation therapy using alpha 1 antitrypsin protein purified from plasma of healthy humans.

    5. 5.

      What is the most effective initial treatment for Wilson Disease?

      1. (a)

        Low copper diet.

      2. (b)

        Oral zinc supplements.

      3. (c)

        Decoppering with penicillamine

      4. (d)

        Decoppering with trientine

    1.2 Answers

    1. 1.

      Which statements are true?

      • (a) Ornithine Transcarbamylase deficiency is the most common urea cycle disorder with a prevalence of 1:14,000–70,000.

      • (b) Untreated hyperammonemia will manifest as neurological symptoms that may range from mild cognitive and psychomotor changes, to altered level of consciousness and coma.

      • (c) Patients with Ornithine Transcarbamylase deficiency present with an increased urine orotic acid.

      • (d) Ornithine transcarbamylase deficiency must be considered early in individuals with suspected hepatic encephalopathy because rapid reduction in the production of nitrogenous waste and increased excretion of nitrogenous waste are required to prevent neurological damage.

    2. 2.

      Which statement is true?

      • (a) Porphyrias are the result of defective enzymatic activity in the heme biosynthetic pathway in erythroid and nonerythroid tissues.

      • (b) The classic acquired porphyria is the development of porphyria cutanea tarda (Type 1) following exposure to Agent Orange (two phenoxy herbicides: 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid containing a trace of a toxic dioxin). Clinical features of this disorder include the development of blistering and thinning of areas of sun-exposed skin.

      • (c) The initial treatment of porphyria cutanea tarda is prevention, e.g. the avoidance of alcohol and avoiding exposure to estrogen.

      • (d) Medical Providers should consider obtaining periodic retinal examinations in those individuals receiving chloroquine or hydroxychloroquine. The protective effect of hydroxychloroquine in retarding renal damage occurrence in individuals with autoimmune disorders has been reported.

    3. 3.

      Which statement is true?

      • (a) Hereditary hemochromatosis is an autosomal recessive disorder that involves the HFE gene, and causes abnormal iron storage as the result of association of HFE protein with the transferrin receptor in the duodenum.

      • (b) The classic description of an individual with hereditary hemochromatosis is presentation with liver enlargement or cirrhosis in combination with “bronze” skin color and diabetes mellitus. Individuals can present with symptoms/findings of arthropathy, cardiomyopathy, or hypogonadism, or they can simply present with cirrhosis.

      • (c) In the 15% of individuals without the HFE gene mutations, patients can be sent for magnetic resonance imaging of the liver or proceed to the historical “gold standard” for diagnosis, which is performance of a liver biopsy with iron quantification.

      • (d) Phlebotomy is the initial effective treatment for hereditary hemochromatosis and, if begun early in the course of this metabolic disease, can prevent the development of cirrhosis. The pretreatment hemoglobin should be >12 g/dl. Phlebotomy to remove 500 ml of whole blood once weekly is performed to produce a transferrin saturation of <50% or a serum ferritin of <50 ng/ml.

    4. 4.

      Which statements are true?

      • (a) Alpha 1 antitrypsin is a protease inhibitor that is mainly biosynthesized by hepatocytes. This protein protects tissues from proteolytic enzyme damage, and this benefit appears to be protective with regards to white blood cells that produce neutrophil elastase. This defect can lead to tissue damage involving connective tissue in the lung and liver.

      • (b) Upon genetic testing for alpha 1 antitrypsin, three alleles have been described, M, S, and Z. In examining the Proteinase inhibitor (Pi) locus, normal individuals have the MM alleles, heterozygotes have an M allele and a Z allele, while the presence of the homozygote ZZ alleles leads to the more severe form of protein misfolding. Individuals who are PiSZ have an increased risk of liver or lung disease.

      • (c) There have been sporadic reports of acquired alpha 1 antitrypsin deficiency, especially in Tropical Pulmonary Eosinophilia. In individuals with Tropical Pulmonary Eosinophilia due to intestinal worm infestation, low levels of the protein, alpha 1 antitrypsin, have been reported. These individuals have normal M1 or M2 alleles.

      • (d) Alpha 1 antitrypsin deficiency-related liver disease cannot be treated with augmentation therapy (using alpha 1 antitrypsin protein purified from plasma of healthy humans).

    5. 5.

      What is the most effective initial treatment for Wilson Disease?

      • (a) A low copper diet is not effective for decoppering an individual with Wilson disease.

      • (b) The United States Food and Drug Administration did not approve zinc supplements for the initial decoppering of individuals with Wilson disease.

      • (c) Penicillamine is the preferred treatment for the initial decoppering of an individual with Wilson disease.

      • (d) Trientine is used for decoppering individuals with Wilson disease who are intolerant of penicillamine.

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    Pardo Lameda, I.L., Koch, T.R. (2020). Acquired Metabolic Disorders. In: Radu-Ionita, F., Pyrsopoulos, N., Jinga, M., Tintoiu, I., Sun, Z., Bontas, E. (eds) Liver Diseases. Springer, Cham. https://doi.org/10.1007/978-3-030-24432-3_10

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    • DOI: https://doi.org/10.1007/978-3-030-24432-3_10

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    • Publisher Name: Springer, Cham

    • Print ISBN: 978-3-030-24431-6

    • Online ISBN: 978-3-030-24432-3

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