The ability to make a diagnosis early and appropriately is paramount for the survival of the critically ill ICU patient. Along with the myriad physical examination and imaging modalities available, biomarkers provide a window on the disease process. Herein we review hepatic biomarkers in the context of the critical care patient.
KramerLJordanBDrumlWBauerPMetnitzPG, Austrian. Epidemiologic Study on Intensive Care ASG. Incidence and prognosis of early hepatic dysfunction in critically ill patients – a prospective multicenter study. Crit Care Med. 2007;35
(4):1099–1104.
3.
BrienzaNDalfinoLCinnellaGDieleCBrunoFFioreT. Jaundice in critical illness: promoting factors of a concealed reality. Intensive Care Med. 2006;32
(2):267–274.
4.
StrassburgCP. Gastrointestinal disorders of the critically ill. Shock liver. Best Pract Res Clin Gastroenterol. 2003;17
(3):369–381.
5.
GimsonAE. Hepatic dysfunction during bacterial sepsis. Intensive Care Medicine. 1987;13
(3):162–166.
6.
AronsohnAJensenD. Hepatobiliary manifestations of critically ill and postoperative patients. Clin Liver Dis. 2011;15
(1):183–197.
7.
HarbrechtBGZenatiMSDoyleHR. Hepatic dysfunction increases length of stay and risk of death after injury. J Trauma. 2002;53
(3):517–523.
8.
TragerKRadermacherPGeorgieffM. PEEP and hepatic metabolic performance in septic shock. Intensive Care Med. 1996;22
(11):1274–1275.
9.
ChungCBuchmanAL. Postoperative jaundice and total parenteral nutrition-associated hepatic dysfunction. Clin Liver Dis. 2002;6
(4):1067–1084.
10.
JungermannKKatzN. Functional specialization of different hepatocyte populations. Physiol Rev. 1989;69
(3):708–764.
11.
JungermannKKietzmannT. Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology. 2000;31
(2):255–260.
12.
KoskinasJGomatosIPTiniakosDG. Liver histology in ICU patients dying from sepsis: a clinico-pathological study. World J Gastroenterology. 2008;14
(9):1389–1393.
13.
KooDJChaudryIHWangP. Mechanism of hepatocellular dysfunction during sepsis: the role of gut-derived norepinephrine (review). International J Mol Med. 2000;5
(5):457–465.
14.
ZimmermanHJWestM. Serum enzyme levels in the diagnosis of hepatic disease. Am J Gastroenterol. 1963;40:387–404.
15.
WroblewskiF. The clinical significance of transaminase activities of serum. Am J Med. 1959;27:911–923.
16.
EllisGGoldbergDMSpoonerRJWardAM. Serum enzyme tests in diseases of the liver and biliary tree. Am J Clin Path. 1978;70
(2):248–258.
17.
KirschJFEicheleGFordGC. Mechanism of action of aspartate aminotransferase proposed on the basis of its spatial structure. J Molec Biol. 1984;174
(3):497–525.
18.
BergJMTymoczkoJLStryerL. Biochemistry (6th ed). New York: W.H. Freeman; 2007.
19.
RejR. Aspartate aminotransferase activity and isoenzyme proportions in human liver tissues. Clin Chemistry. 1978;24
(11):1971–1979.
20.
HayashiHWadaHYoshimuraTEsakiNSodaK. Recent topics in pyridoxal 5'-phosphate enzyme studies. Annu Rev Biochem. 1990;59:87–110.
21.
FuhrmannVKneidingerNHerknerH. Hypoxic hepatitis: Underlying conditions and risk factors for mortality in critically ill patients. Intensive Care Med. 2009;35
(8):1397–1405.
22.
KimEEWyckoffHW. Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. J Molec Biol. 1991;218
(2):449–464.
AlvaroDBenedettiAMarucciL. The function of alkaline phosphatase in the liver: regulation of intrahepatic biliary epithelium secretory activities in the rat. Hepatology. 2000;32
(2):174–184.
25.
CourtayCOsterTMicheletF. Gamma-glutamyltransferase: nucleotide sequence of the human pancreatic cDNA. Evidence for a ubiquitous gamma-glutamyltransferase polypeptide in human tissues. Biochem Pharmacol. 1992;43
(12):2527–2533.
26.
LumGGambinoSR. Serum gamma-glutamyl transpeptidase activity as an indicator of disease of liver, pancreas, or bone. Clin Chem. 1972;18
(4):358–362.
27.
GoldbergDM. Structural, functional, and clinical aspects of gamma-glutamyltransferase. CRC Critical Rev Clin Lab Sci. 1980;12
(1):1–58.
28.
ThomsonSJCowanMLJohnstonIMusaSGroundsMRahmanTM. “Liver function tests” on the intensive care unit: a prospective, observational study. Intensive Care Med. 2009;35
(8):1406–1411.
29.
FeldJJDinhHArenovichTMarcusVAWanlessIRHeathcoteEJ. Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and outcome. Hepatology. 2005;42
(1):53–62.
30.
KamathPSWiesnerRHMalinchocM. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33
(2):464–470.
31.
MorenoRVincentJLMatosR. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999;25
(7):686–696.
32.
HarbrechtBGDoyleHRClancyKDTownsendRNBilliarTRPeitzmanAB. The impact of liver dysfunction on outcome in patients with multiple injuries. Am Surg. 2001;67
(2):122–126.
33.
HelftenbeinAWindolfJSangerPHanischE. [Incidence and prognosis of postoperative jaundice in surgical intensive care patients]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen. 1997;68(12):1292–1296.
34.
EstebanAAnzuetoAFrutosF. Mechanical Ventilation International Study G. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002;287
(3):345–355.
35.
FransonTRHierholzerWJJrLaBrecqueDR. Frequency and characteristics of hyperbilirubinemia associated with bacteremia. Rev Infect Dis. 1985;7
(1):1–9.
36.
StehleP. Development of liver dysfunction under artificial nutrition: a reason to modify nutrition therapy in the intensive care unit?Crit Care. 2007;11
(1):112.
37.
KortgenARecknagelPBauerM. How to assess liver function?Current Opin Crit Care. 2010;16
(2):136–141.
38.
KortgenAPaxianMWerthM. Prospective assessment of hepatic function and mechanisms of dysfunction in the critically ill. Shock. 2009;32
(4):358–365.
39.
KrouzeckyARadermacherPMatejovicM. Acute liver injury and biomarkers: a biological lesson from indocyanine green. Shock. 2009;32
(3):340–341.
SakkaSGReinhartKMeier-HellmannA. Comparison of invasive and noninvasive measurements of indocyanine green plasma disappearance rate in critically ill patients with mechanical ventilation and stable hemodynamics. Intensive Care Med. 2000;26
(10):1553–1556.
PaxianMBauerIRensingH. Recovery of hepatocellular ATP and “pericentral apoptosis” after hemorrhage and resuscitation. FASEB J. 2003;17
(9):993–1002.
44.
StockmannMMalinowskiMLockJFSeehoferDNeuhausP. Factors influencing the indocyanine green (ICG) test: additional impact of acute cholestasis. Hepato-Gastroenterology. 2009;56
(91-92):734–738.
45.
SakkaSGReinhartKMeier-HellmannA. Prognostic value of the indocyanine green plasma disappearance rate in critically ill patients. Chest. 2002;122
(5):1715–1720.
46.
InalMTMemisDKargiMSutN. Prognostic value of indocyanine green elimination assessed with LiMON in septic patients. J Crit Care. 2009;24
(3):329–334.
47.
LuetscherJA. Electrophoretic analysis of the proteins of plasma and serous effusions. J Clin Invest. 1941;20
(1):99–106.
48.
IngramGIHillsM. Reference method for the one-stage prothrombin time test on hlman blood. International committee for standardization in hematology. Thromb Haemostasis. 1976;36
(1):237–238.
49.
DensonKWReedSVHaddonMEWoodhamsBBrucatoCRuizJ. Comparative studies of rabbit and human recombinant tissue factor reagents. Thrombosis Res. 1999;94
(4):255–261.
50.
RobertAChazouilleresO. Prothrombin time in liver failure: time, ratio, activity percentage, or international normalized ratio?Hepatology. 1996;24
(6):1392–1394.
51.
HoofnagleJHCarithersRLJrShapiroCAscherN. Fulminant hepatic failure: summary of a workshop. Hepatology. 1995;21
(1):240–252.
52.
O'GradyJGAlexanderGJHayllarKMWilliamsR. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97
(2):439–445.
53.
BellestLEschwegeVPouponRChazouilleresORobertA. A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology. Hepatology. 2007;46
(2):528–534.
54.
TrotterJFBrimhallBArjalRPhillipsC. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation. Liver Transpl. 2004;10
(8):995–1000.
55.
DeitcherSR. Interpretation of the international normalised ratio in patients with liver disease. Lancet. 2002;359
(9300):47–48.
56.
TripodiAChantarangkulVPrimignaniM. The international normalized ratio calibrated for cirrhosis [INR (liver)] normalizes prothrombin time results for model for end-stage liver disease calculation. Hepatology. 2007;46
(2):520–527.
57.
RaurichJMLlompart-PouJAFerreruelaM. Hypoxic hepatitis in critically ill patients: incidence, etiology and risk factors for mortality. J Anesthesia. 2011;25
(1):50–56.
58.
CrouserEDJulianMWHuffJEStruckJCookCH. Carbamoyl phosphate synthase-1: a marker of mitochondrial damage and depletion in the liver during sepsis. Crit Care Med. 2006;34
(9):2439–2446.
59.
StruckJUhleinMMorgenthalerNG. Release of the mitochondrial enzyme carbamoyl phosphate synthase under septic conditions. Shock. 2005;23
(6):533–538.
60.
HoferSBrennerTBoppC. Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction. Crit Care. 2009;13
(3):R93.
61.
JiangDLiangJNoblePW. Hyaluronan in tissue injury and repair. Ann Rev Cell Dev Biol. 2007;23:435–461.
62.
ErikssonSFraserJRLaurentTCPertoftHSmedsrodB. Endothelial cells are a site of uptake and degradation of hyaluronic acid in the liver. Exp Cell Res. 1983;144
(1):223–228.
63.
MartinezSMCrespoGNavasaMFornsX. Noninvasive assessment of liver fibrosis. Hepatology. 2011;53
(1):325–335.
64.
BergSBrodinBHesselvikFLaurentTCMallerR. Elevated levels of plasma hyaluronan in septicaemia. Scand J Clin Lab Invest. 1988;48
(8):727–732.
65.
YagmurEKochAHaumannMKramannRTrautweinCTackeF. Hyaluronan serum concentrations are elevated in critically ill patients and associated with disease severity. Clin Biochem. 2012;45
(1-2):82–87.
66.
BotaDPVan NuffelenMZakariahANVincentJL. Serum levels of C-reactive protein and procalcitonin in critically ill patients with cirrhosis of the liver. J Lab Clin Med. 2005;146
(6):347–351.
67.
IzumiSHughesRDLangleyPGPernambucoJRWilliamsR. Extent of the acute phase response in fulminant hepatic failure. Gut. 1994;35
(7):982–986.
68.
FangCYoonSTindbergNJarvelainenHALindrosKOIngelman-SundbergM. Hepatic expression of multiple acute phase proteins and down-regulation of nuclear receptors after acute endotoxin exposure. Biochem Pharmacol. 2004;67
(7):1389–1397.
69.
SzaboGRomicsLJrFrendlG. Liver in sepsis and systemic inflammatory response syndrome. Clin Liver Dis. 2002;6
(4):1045–1066.
70.
SilvestreJPCoelhoLMPovoaPM. Impact of fulminant hepatic failure in C-reactive protein?J Crit Care. 2010;25(4):657. e7–e12.
71.
WangCShiJSunB. Breath pentane as a potential biomarker for survival in hepatic ischemia and reperfusion injury – a pilot study. PLoS One. 2012;7
(9):e44940.
72.
IkedaHSuzukiYSuzukiM. Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/reperfusion injury to the rat intestinal epithelium. Gut. 1998;42
(4):530–537.
73.
CollardCDGelmanS. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology. 2001;94
(6):1133–1138.
74.
PoezeMLuikingYCBreedveldPMandersSDeutzNE. Decreased plasma glutamate in early phases of septic shock with acute liver dysfunction is an independent predictor of survival. Clin Nutr. 2008;27
(4):523–530.
75.
KochAHornADuckersH. Increased liver stiffness denotes hepatic dysfunction and mortality risk in critically ill non-cirrhotic patients at a medical ICU. Crit Care. 2011;15
(6):R266.
76.
CasteraLFornsXAlbertiA. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48
(5):835–847.
77.
TsochatzisEAGurusamyKSNtaoulaSCholongitasEDavidsonBRBurroughsAK. Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accuracy. J Hepatol. 2011;54
(4):650–659.
78.
Al-ChalabiAMatevossianEAKVT. Evaluation of the Hepa Wash(R) treatment in pigs with acute liver failure. BMC Gastroenterol. 2013;13:83.
79.
BacherA. Extracorporeal liver support with multipass albumin dialysis or plasmapheresis and filtering systems in acute liver failure. Liver Int. 2011;31
(suppl 3):16–18.
80.
WautersJWilmerA. Albumin dialysis: current practice and future options. Liver Int. 2011;31
(suppl 3):9–12.