Abstract
Hepatobiliary complications of hypoalimentation and parenteral nutrition (PN) are widely recognised. Hypoalimentation includes conditions such as anorexia nervosa (AN), obesity malnutrition and liver disease following bariatric surgery. Treatment of the underlying condition causing hypoalimentation can result in an improvement in liver dysfunction. Liver function test abnormalities are also commonly found in patients on PN, with the three main complications being steatosis, cholestasis and biliary system sludge/stones. Patients with intestinal failure receiving PN often have multiple possible aetiologies for liver dysfunction (rather than solely caused by the PN); hence, it is now more commonly referred to as intestinal failure-associated liver disease (IFALD). Liver enzyme abnormalities are very common with long-term PN use and do not always help with monitoring progression of IFALD. A systematic approach is required for investigating liver function abnormalities related to PN. The key management in IFALD is through prevention of sepsis, promoting intestinal health and restoring intestinal continuity where possible. A variety of imaging modalities can be used to investigate, and monitor, the liver disease. Most importantly, patients on PN for more than 28 days should be managed in a large centre with experience in managing intestinal failure to minimise the risk of such complications. Early identification of liver dysfunction is essential and, should it progress despite the above measures, early discussion with an intestinal transplant centre should be encouraged.
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References
Peden VH, Witzleben CL, Skelton MA (1971) Total parenteral nutrition. J Pediatr 78:180–181. https://doi.org/10.1016/S0022-3476(71)80289-5
Buchman A (2002) Total parenteral nutrition associated liver disease. J Parenter Enter Nutr 26(Suppl 5):S43–S48. https://doi.org/10.1177/014860710202600512]
Angelico M, Guardia PD (2000) Review article: hepatobiliary complications associated with total parenteral nutrition. Aliment Pharmacol Ther 14(Suppl 2):54–57. https://doi.org/10.1046/j.1365-2036.2000.014s2054.x]
Di Pascoli L, Lion A, Milazzo D et al (2004) Acute liver damage in anorexia nervosa. Int J Eat Disord 36(1):114–117. https://doi.org/10.1002/eat.20002]
Fuhrman MP, Charney P, Mueller CM (2004) Hepatic proteins and nutrition assessment. J Am Diet Assoc 104(8):1258–1264. https://doi.org/10.1016/j.jada.2004.05.213
Fong DG, Nehra V, Lindor KD, Buchman AL (2000) Metabolic and nutritional consideration in non-alcoholic fatty liver. Hepatol 32(1):3–10
Miller KK, Grinspoon SK, Ciampa J, Hier J, Herzog D, Klibanski A (2005) Medical findings in outpatients with anorexia nervosa. Arch Intern Med 165(5):561–566. https://doi.org/10.1001/archinte.165.5.561]
Hanachi M, Melchior JC, Crenn P (2013 Jun) Hypertransaminasemia in severely malnourished adult anorexia nervosa patients: risk factors and evolution under enteral nutrition. Clin Nutr 32(3):391–395. https://doi.org/10.1016/j.clnu.2012.08.020
Jones SC, Pieri LF, Losowsky MS (1999) Abnormalities in liver function in severe anorexia nervosa. Eur Eat Disorders Rev 7:28–36. https://doi.org/10.1002/(SICI)1099-0968(199903)7:1%3C28::AID-ERV274%3E3.0.CO;2-U
Via M (2012) The malnutrition of obesity: micronutrient deficiencies that promote diabetes. ISRN Endocrinol 2012:103472. https://doi.org/10.5402/2012/103472
Kaidar-Person O, Person B, Szomstein S, Rosenthal RJ (2008) Nutritional deficiencies in morbidly obese patients: a new form of malnutrition? Obes Surg 18(8):1028–1034. https://doi.org/10.1007/s11695-007-9350-5
Shaffer EA (2006) Bariatric surgery: a promising solution for non-alcoholic steatohepatitis in the very obese. J Clin Gastroenterol 40(Suppl 1):S44–S50
Ruhl CE, Everhart JE (2004) Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 8(3):501–519. https://doi.org/10.1016/j.cld.2004.04.008
Niswender K (2010) Diabetes and obesity; therapeutic targeting and risk reduction—a complex interplay. Diabetes Obes Metab 12(4):267–287. https://doi.org/10.1111/j.1463-1326.2009.01175.x]
El-Sarag HB, Tran T, Everhart JE (2004) Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterol 126(2):460–468. https://doi.org/10.1053/j.gastro.2003.10.065
NIH conference (1991) Gastro-intestinal surgery for severe obesity. Consensus Development Conference Panel. Ann Intern Med 115(12):956–961
Luyckx FH, Desaive C, Thiry A, Dewe W, Scheen AJ, Gielen JE, Lefebvre PJ (1998) Liver abnormalities in severely obese subjects: effect drastic weight loss after gastroplasty. Int J Obes 22(3):222–226. https://doi.org/10.1038/sj.ijo.0800571
Richardson WS, Plaisance AM, Periou L, Buquoi J, Yillery D (2009) Long-term management of patients after weight loss surgery. Ochsner J 9(3):154–159
Dixon JB, Bhathal PS, Hughes NR, O’Brien PE (2004) Nonalcoholic fatty liver disease: improvement in liver histological analysis with weight loss. Hepatology 39(6):1637–1654. https://doi.org/10.1002/hep.20251
Pironi L, Arends J, Baxter J, Bozzetti F, Pelaez RB, Cuerda C, Forbes A, Gabe S, Gillanders L, Holst M, Jeppesen PB, Joly F, Kelly D, Klek S, Irtun O, Damink SWO, Panisic M, Rasmussen HH, Staun M, Szczepanek K, Van Gossum A, Wanten G, Schneider SM, Shaffer J (2015) ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr 34(2):171–180. https://doi.org/10.1016/j.clnu.2014.08.017
Lloyd DAJ, Gabe SM (2007) Managing liver dysfunction in parenteral nutrition. Proc Nutr Soc 66(4):530–538. https://doi.org/10.1017/S002966510700585X
Lal S, Teubner A, Shaffer JL (2006) Review article: intestinal failure. Aliment Pharmacol Ther 24(1):19–31. https://doi.org/10.1111/j.1365-2036.2006.02941.x
Rodrigues CA, Lennard-Jones JE, Thompson DG, Farthing MJ (1989) Energy absorption as a measure of intestinal failure in the short bowel syndrome. Gut 30(2):176–183. https://doi.org/10.1136/gut.30.2.176]
Cavicchi M, Beau P, Crenn P, Degott C, Messing B (2000) Prevalence of liver disease and contributing factors in patients receiving home parenteral nutrition for permanent intestinal failure. Ann Intern Med 132(7):525–532. https://doi.org/10.7326/0003-4819-132-7-200004040-00003
Richards DM, Deeks JJ, Sheldon TA, Shaffer JL (1997) Home parenteral nutrition: a systematic review. Health Technol Assess 1(1):1–59
Scolapio JS, Fleming CR, Kelly DG, Wick DM, Zinsmeister AR (1999) Survival of home parenteral nutrition-treated patients: 20 years of experience at the Mayo Clinic. Mayo Clin Proc 74(3):217–222. https://doi.org/10.4065/74.3.217]
Baker AL, Rosenberg IH (1987) Hepatic complications of total parenteral nutrition. Am J Med 82(3):489–497. https://doi.org/10.1016/0002-9343(87)90449-9
Grant JP, Cox CE, Kleinman LM, Maher MM, Pittman MA, Tangrea JA, Brown JH, Gross E, Beazley RM, Jones RS (1977) Serum hepatic enzyme and bilirubin elevations during parenteral nutrition. Surg Gynecol Obstet 145(4):573–580
Shaffer JL (1995) Hepatic complications of parenteral nutrition. Clin Nutr 14(Suppl 1):59–64. https://doi.org/10.1016/S0261-5614(95)80286-X
Campos AC, Oler A, Meguid MM, Chen TY (1990) Liver biochemical and histological changes with graded amounts of total parenteral nutrition. Arch Surg 125(4):447–450. https://doi.org/10.1001/archsurg.1990.01410160033006
Meguid MM, Akahoshi MP, Jeffers S, Hayashi RJ, Hammond WG (1984) Amelioration of metabolic complications of conventional total parenteral nutrition. Arch Surg 119(11):1294–1298. https://doi.org/10.1001/archsurg.1984.01390230060014]
Puder M, Valim C, Meisel JA, Lee HD, de Meijer VE, Robinson EM, Zhou J, Duggan C, Gura KM (2009) Parenteral fish oil improves outcomes in patients with parenteral nutrition–associated liver injury. Ann Surg 250(3):395–402. https://doi.org/10.1097/SLA.0b013e3181b36657]
Schmocker C, Weylandt KH, Kahlke L, Wang J, Lobeck H, Tiegs G, Berg T, Kang JX (2007) Omega-3 fatty acids alleviate chemically induced acute hepatitis by suppression of cytokines. Hepatology 45(4):864–869. https://doi.org/10.1002/hep.21626
Macfayden BV, Dudrick SJ, Baquero G, Gum ET (1979) Clinical and biological changes in liver function during intravenous hyperalimentation. JPEN 3(6):438–443. https://doi.org/10.1177/0148607179003006438
Sobotka L, Camilo ME (2011) Metabolic complications of parenteral nutrition. In: Sobotka L, Allison S, Forbes A, Ljungqvist O, Meier R, Pertkiewicz M, Soeters P (eds) Basics in clinical nutrition, 4th edn. Publishing House Galen, Prague, pp 348–418
Tillman EM (2013) Review and clinical update on parenteral nutrition-associated liver disease. Nutr Clin Pract 28(1):30–39. https://doi.org/10.1177/0884533612462900]
Luman W, Shaffer JL (2002) Prevalence, outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition. Clin Nutr 21(4):337–343. https://doi.org/10.1054/clnu.2002.0554
Dibb M, Teubner A, Theis V, Shaffer J, Lal S (2013) Review article: the management of long-term parenteral nutrition. Aliment Pharmacol Ther 37(6):587–603. https://doi.org/10.1111/apt.12209
Beath SV, Booth IW, Murphy MS (1995) Nutritional care in candidates for small bowel transplantation. Arch Dis Child 73(4):348–350. https://doi.org/10.1136/adc.73.4.348]
Capron JP, Gineston JL, Herve MA, Braillon A (1983) Metronidazole in prevention of cholestasis associated with total parenteral nutrition. Lancet 1(8322):446–447
Stout SM, Cober MP (2010) Metabolic effects of cyclic parenteral nutrition infusion in adults and children. Nutr Clin Pract 25(3):277–281. https://doi.org/10.1177/0884533610368701]
Salvador A, Janeczko M, Porat R, Sekhon R, Moewes A, Schutzman D (2012) Randomized controlled trial of early parenteral nutrition cycling to prevent cholestasis in very low birth weight infants. J Pediatr 161(2):229–233. https://doi.org/10.1016/j.jpeds.2012.02.003
Matuchansky C, Messing B, Jeejeebhoy KN, Beau P, Beliah M, Allard JP (1992) Cyclical parenteral nutrition. Lancet 340(8819):588–592. https://doi.org/10.1016/0140-6736(92)92116-W]
Lindor KD, Burnes J (1991) Ursodeoxycholic acid for the treatment of home parenteral nutrition-associated cholestasis. A vase report. Gastroenterology 101(1):250–253
Dawes LG, Greiner MA, Joehl RJ (1999) Altered gallbladder bile acidification with long-term total parenteral nutrition. J Surg Res 81(1):21–26. https://doi.org/10.1006/jsre.1998.5492]
Muller EL, Grace PA, Pitt HA (1986) The effect of total parenteral nutrition on biliary calcium and bilirubin. J Surg Res 40(1):55–62
Messing B, Bories C, Kunstlinger F, Bernier JJ (1983) Does total parenteral nutrition induce gallbladder stasis? Gastroenterology 84(5):1012–1019
Thompson JS (1996) The role of prophylactic cholecystectomy in the short-bowel syndrome. Arch Surg 131(5):556–560. https://doi.org/10.1001/archsurg.1996.01430170102020]
Buchman AL, Dubin MD, Moukarzel A, Jenden DJ, Roch M, Rice KM, Gornbein J, Ament ME (1995) Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology 22(5):1399–1403. https://doi.org/10.1002/hep.1840220510
Buchman AL, Ament ME, Sohel M, Dubin M, Jenden DJ, Roch M, Pownall H, Farley W, Awal M, Ahn C (2001) Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. J Parenter Enter Nutr 25(5):260–268. https://doi.org/10.1177/0148607101025005260
Buchman AL, Dubin M, Jenden D, Moukarzel A, Roch M, Rice K, Gornbein J, Ament ME, Eckhert CD (1992) Lecithin increases plasma free choline and decreased hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology 102(4):1363–1370
Narkewicz MR, Caldwell S, Jones G (1995) Cysteine supplementation and reduction of total parenteral nutrition-induced hepatic lipid accumulation in the weaning rat. J Pediatr Gastroenterol Nutr 21(1):18–24
Gray GE, Landel AM, Meguid MM (1994) Taurine-supplemented total parenteral nutrition and taurine status of malnourished cancer patients. Nutrition 10(1):11–15
Gabe SM, Culkin A (2010) Abnormal liver function tests in the parenteral nutrition fed patient. Frontline Gastroenterol 1:98–104. https://doi.org/10.1136/fg.2009.000521
Sokol RJ, Taylor SF, Devereaux MW, Khandwala R, Sondheimer NJ, Shikes RH, Mierau G (1996) Hepatic oxidant injury and glutathione depletion during total parenteral nutrition in weanling rats. Am J Phys 270(4):G691–G700. https://doi.org/10.1136/fg.2009.000521]
Bawyer BA, Fleming CR, Haymond MW, Miles JM (1989) L-carnitine: effect of intravenous administration on fuel homeostasis in normal subjects and home-parenteral-nutrition patients with low plasma carnitine concentrations. Am J Clin Nutr 49(4):618–623
David S, Hamilton JP (2010) Drug-induced liver injury. US Gastroenterol Hepatol Rev 6:73–80
Clarke PJ, Ball MJ, Kettlewell MGW (1991) Liver function tests in patients receiving parenteral nutrition. J Parenter Enter Nutr 15(1):54–59. https://doi.org/10.1177/014860719101500154]
Woodward JM, Priest AN, Hollingsworth KG, Lomas DJ (2009) Clinical application of magnetic resonance spectroscopy of the liver in patients receiving long-term parenteral nutrition. J Parenter Enter Nutr 33(6):669–676. https://doi.org/10.1177/0148607109332908
Cadranel JF, Rufat P, Degos F (2000) Practices of liver biopsy in France: results of a prospective nationwide survey. For the Group of Epidemiology of the French Association for the Study of the liver (AFEF). Hepatology 32(3):477–481. https://doi.org/10.1053/jhep.2000.16602]
Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, Babb SM (1995) Decreased brain choline uptake in older adults: an in vivo proton magnetic resonance spectroscopy study. JAMA 274(11):902–907. https://doi.org/10.1001/jama.1995.03530110064037
Lim AK, Patel N, Hamilton G, Hajnal JV, Goldin RD, Taylor-Robinson SD (2003) The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C. Hepatology 37(4):788–794
Varghese JC, Liddell RP, Farrell MA, Murray FE, Osborne DH, Lee MJ (2000) Diagnostic accuracy of magnetic resonance cholangiopancreatography and ultrasound compared with direct cholangiography in the detection of choledocholithiasis. Clin Radiol 55(1):25–35. https://doi.org/10.1053/crad.1999.0319
Sandrin L, Fourquet B, Hasquenoph JM, Yon S, Fournier C, Mal F, Christidis C, Ziol M, Poulet B, Kazemi F, Beaugrand M, Palau R (2003) Transient elastography: a new non-invasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 29(12):1705–1713
Castera L, Forns X, Alberti A (2008) Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol 48(5):835–847. https://doi.org/10.1016/j.jhep.2008.02.008
Friedrich-Rust M, Rosenberg W, Parkes J, Herrmann E, Zeuzem S, Sarrazin C (2010) Comparison of ELF, FibroTest and FibroScan for the non-invasive assessment of liver fibrosis. BMC Gastroenterol 10:103
Mardini H, Record C (2005) Detection, assessment and monitoring of hepatic fibrosis: biochemistry or biopsy? Ann Clin Biochem 42:441–447. https://doi.org/10.1258/000456305774538210]
NICE (2016) Non-alcoholic fatty liver disease (NAFLD): assessment and management. 2016 July. Available from: https://www.nice.org.uk/guidance/ng49 [Accessed 15th May 2018]
Ikeda H, Kobayashi M, Kumada H, Enooku K, Koike K, Kurano M, Sato M, Nojiri T, Kobayashi T, Ohkawa R, Shimamoto S, Igarashi K, Aoki J, Yatomi Y (2017) Performance of autotaxin as a serum marker for liver fibrosis. Ann Clin Biochem 1:4563217741509. https://doi.org/10.1177/0004563217741509]
Torres C, Sudan D, Vanderhoof J, Grant W, Botha J, Raynor S, Langnas A (2007) Role of an intestinal rehabilitation program in the treatment of advanced intestinal failure. J Pediatr Gastroenterol Nutr 45(2):204–212. https://doi.org/10.1097/MPG.0b013e31805905f9]
Jawahweer G, Pierro A, Lloyd TA, Shaw NJ (1995) Gallbladder contractility in neonates; effect of parenteral and enteral feeding. Arch Dis Child 72(3):F200–F202
Sitzmann JV, Pitt HA, Steinhorn PA, Pasha ZR, Sanders RC (1990) Cholecystokinin prevents parenteral nutrition induced biliary sludge in humans. Surg Gynecol Obstet 170(1):25–31
Portincasa P, van Erpecum KJ, Jansen A, Renooij W, Gadellaa M, vanBerge-Henegouwen GP (1996) Behaviour of various cholesterol crystals in bile from gallstone patients. Hepatology 23(4):738–748
Spagnuolo MI, Iorio R, Vegnente A, Gaurino A (1996) Ursodeoxycholic acid for treatment of cholestasis in children on long-term total parenteral nutrition: a pilot study. Gastroenterology 111(3):716–719. https://doi.org/10.1053/gast.1996.v111.pm8780577
Beau P, Labat-Labourdette J, Ingrand P, Beauchant M (1994) Is ursodeoxycholic acid an effective therapy for total parenteral nutrition-related liver disease? J Hepatol 20(2):240–244. https://doi.org/10.1016/S0168-8278(05)80064-9
Buchman AL, Scolapio J, Fryer J (2003) AGA technical review on short bowel syndrome and intestinal transplantation. Gastroenterology 124(4):1111–1134. https://doi.org/10.1016/S0016-5085(03)70064-X
Grant D (1999) Intestinal transplantation 1997 report of the international registry. Transplantation 67(7):1061–1064
Buchman AL, Iyer K, Fryer J (2006) Parenteral nutrition-associated liver disease and the role for isolated intestine and intestine/liver transplantation. Hepatology 43(1):9–19. https://doi.org/10.1002/hep.20997
Fishbein TM, Florman S, Gondolesi G, Schiano T, LeLeiko N, Tschernia A, Kaufman S (2002) Intestinal transplantation before and after the introduction of sirolimus. Transplantation 73(10):1538–1542
Goulet O, Brousse N, Revillon Y (1993) Pathology of human intestinal transplantation. In: Grant R, RFM W (eds) Small bowel transplantation. Edward Arnold, London, pp 112–120
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McNeice, A., Scott, R., Rafferty, G.P. et al. The hepatobiliary complications of malnutrition and nutritional support in adults. Ir J Med Sci 188, 109–117 (2019). https://doi.org/10.1007/s11845-018-1836-8
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DOI: https://doi.org/10.1007/s11845-018-1836-8