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Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2899_Библиотеки_им_академика_М_И_Перельмана

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Table33.1TimeframeofdifferentALFpresentations
Aetiologieswhichmayalsopresenthyperacutelyareitalicized.
Category Acute Acuteandsubacute
Viral HepatitisAandE
HepatitisB CMV HSV VZV Dengue
Drugsortoxins Ecstasy
Chemotherapy NSAIDs Antiepileptics,e.g.phenytoin,carbamazepine Statins Flucloxacillin Anti-TBtreatments
Paracetamoloverdose
Vascular Hypoxichepatitis Budd–Chiarisyndrome
Pregnancy Pre-eclampsia
HELLP Fattyliverofpregnancy
Other Wilsondisease
Autoimmune Malignancy,includinglymphoma
CMV,cytomegalovirus;HELLP,haemolysis,elevatedliverenzymesandlowplatelets(syndrome);HSV, herpessimplexvirus.
ReproducedfromWendonJ,CordobaJ,DhawanA,LarsenFS,MannsM,SamuelD,SimpsonKJ, YaronI,BernardiM.EASLClinicalPracticalGuidelinesonthemanagementofacute(fulminant)liver failure.JHepatol.2017May;66(5):1047–1081withpermissionfromElsevier.
The most common causes of ALF worldwide are hepatitis A, B, and E. In Europe, drug-inducedALFisthemostcommoncause.
Examination
Beginwithageneralinspection,lookinginparticularforjaundice,ascites,andevidence ofHE.TakenoteofcluesthatmaypointtospecificcausesofALF,includingevidenceof self-harm (overdose), tattoos or injection sites (hepatitis B), Kayser–Fleischer rings (Wilson disease), combination of RUQ pain, hepatomegaly, and ascites(typicaltriad of Budd–Chiarisyndrome).
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Signsofliverfailureinclude:
Asterixis Jaundice(examineskinandsclera) Ascites Bruisingorbleeding HE(Table33.2).
Table33.2Gradesofhepaticencephalopathy
Grade Presentation
Grade1 Alteredmood,reducedattentionspan,sleepdisturbance
Grade2 Increasingdrowsiness,timedisorientation,personalitychange,asterixis,inappropriatebehaviour
Grade3 Stupor,bizarrebehaviour,significantconfusion
Grade4 Coma
Source:datafromHepaticEncephalopathyinChronicLiverDisease:2014PracticeGuidelinebythe EuropeanAssociationfortheStudyoftheLiverandtheAmericanAssociationfortheStudyofLiver Diseases(September2014)ClinicalPracticeGuidelines61(3):642–659.
Investigations
Useinvestigationstodecideonappropriatetreatmentandwhetherreferraltoaspecialist centreisrequired(Table33.3).
Bedside
Urinalysis ECG.
Bloods
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FBC,U&E,LFT,coagulationprofile(INRand/orPT,fibrinogen),glucose ABG(monitorforacidosisandlactatelevel) Arterialammonia(sampleoftenrequiresdeliverytolaboratoryonice) Paracetamollevel Viral screen (hepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) IgM (consider hepatitisBvirusDNA),anti-hepatitisAvirusIgM,anti-hepatitisEvirusIgM,anti-HSVIgM,anti­VZVIgM,CMV,HSV,EBV,parvovirus,andVZVpolymerasechainreaction(PCR)) Autoimmune screen (antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti­soluble liver antigen (SLA), anti-liver kidney microsomal antibody (LKMA), immunoglobulin profile,antineutrophilcytoplasmicantibody(ANCA),HLAtyping) Bloodcultures.
Imaging
ChestX-ray(baseline) UltrasoundliverwithDopplerexaminationofhepaticvessels CTabdomenmayberequiredforfurtherlivercharacterization.
Other
Ascitictapifascitespresent(>250neutrophils/mm3suggestsspontaneousbacterialperitonitis) Liverbiopsymaybeusefultoexcludecirrhosis,malignancy,oralcohol-inducedacuteliverinjury.
Table33.3Criteriaforreferraltoaspecialistcentre
ALFsecondarytoparacetamoloverdose,orhyperacute presentation
ALFsecondarytoanyothercause
pH<7.3orHCO3<18
Hypoglycaemia
INR>3onday2,orINR>4afterday2 INR>1.8
Oliguriaand/orraisedcreatinine Oliguria,renalfailure,orNa
<130mmol/L
Changeinlevelofconsciousness Encephalopathy
Highlactatenotrespondingtofluids Metabolicacidosis
Bilirubin>300μmol/L
Decreasingliversize
ReproducedfromWendonJ,CordobaJ,DhawanA,LarsenFS,MannsM,SamuelD,SimpsonKJ, YaronI,BernardiM.EASLClinicalPracticalGuidelinesonthemanagementofacute(fulminant)liver failure.JHepatol.2017May;66(5):1047–1081withpermissionfromElsevier.
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Management
Acutemanagement
Theacutemanagementofliverfailurerequiresasystemicapproach,reflectingthebroad presentationandmultiorganinvolvement(Table33.4).ConsiderICUreferralearly.
Table33.4AcutemanagementofALF
A
Protect airway if necessary due to HE or reduced consciousness (HE grade 3 or above is typically an indicationforintubation)
C
Patientsareusuallyvolumedepleted ConsiderIVfluidresuscitationandurinarycatheterizationtoaccuratelymeasurefluidinputandoutput Ifbloodtransfusionisrequired,aimforatargethaemoglobinof70g/L
D
Monitorneurologicalstatus2-hourlyforsignsofworseningHE.DevelopmentofHEgrade2ormoreshould leadtoICUtransfer Donotgivesedativeagents Patientsshouldhave2-hourlyCBGmonitoring Consider IV dextrose to avoid hypoglycaemia (commonly associated with ALF, especially paracetamol overdose)
E
Antibiotics: low threshold if haemodynamically unstable, or worsening HE which might have an infective
cause
N-acetylcysteine:giveeveninnon-paracetamolcases Nutrition: involve dieticians early, ideally continue enteral feeding but may require parenteral
supplementation.Replacedepletedelectrolytes
Medicationreview:avoiddrugsthatarehepaticallymetabolized Alcoholwithdrawal:ifconcernedaboutalcohol withdrawal,trytousealternativestochlordiazepoxide,e.g.
oxazepamorlorazepam Renal replacement therapy (RRT): consider need for RRT if worsening AKI, hyperammonaemia, hyponatraemia,orpersistentacidosis Coagulopathy:LMWHmaybecontinuedbutshouldberegularlyreviewedalongwithbleedingrisk.Hepatic coagulopathyisassociatedwith↑ thrombosisratherthan bleedingrisk,butconsiderneedforvitamin Kand plateletsifactivelybleeding
Discuss other management with a hepatology specialist including whether to start steroids in suspected autoimmune hepatitis. Pregnancy-related ALF may require promptdeliveryofthebabybyanobstetrician.
Specialconsiderations
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Livertransplant
Early assessment of the patient for liver transplant is important. The King’s College criteriafortransplant(Table33.5)arewidelyaccepted.
Table33.5King’sCollegecriteriaforlivertransplant
ALFsecondarytoparacetamol ALFsecondarytoacauseotherthanparacetamol
ArterialpH<7.3afterresuscitation(>24hourssince ingestion) OR All3of: HEgrade3or4 AND Serumcreatinine>300μmol/L AND INR>6.5
INR>6.5 OR Any3outof5variables:
Indeterminateaetiologyordrug-inducedhepatitis Age<10yearsor>40years Interval between jaundice and encephalopathy onset >7days Bilirubin>300μmol/L INR>3.5
Source:datafromO’GradyJG,AlexanderGJ,HayllarKM,WilliamsR.Earlyindicatorsofprognosis infulminanthepaticfailure.Gastroenterology.1989Aug;97(2):439–45.doi:10.1016/0016­5085(89)90081-4.PMID:2490426.
Furtherreading
1.EuropeanAssociationfortheStudyoftheLiverandtheAmericanAssociationfortheStudyofLiver Diseases (2014). Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the EuropeanAssociationfortheStudyoftheLiverandtheAmericanAssociationfortheStudyofLiver Diseases.Availableat:https://www.journal-of-hepatology.eu/article/S0168-8278(14)00390-0/fulltext
2. Bloom S, Webster G, Marks D (2011). Acute liver failure (ALF). Oxford Handbook of Gastroenterologyand Hepatology, 2nded (pp. 572–7).Oxford: Oxford University Press.Available at:https://doi.org/10.1093/med/9780199584079.003.0150
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Chapter34
Alcohol-relatedliverdisease
Guideline: European Association forthe Studyof the Liver(EASL clinical
practice guidelines: management of alcohol-related liver disease):
https://www.journal-of-hepatology.eu/article/S0168-8278(18)30214-9/fulltext
OUPdisclaimer:OxfordUniversity Press makesno representation, express or implied, that the drugdosagesarecorrectand thatthe recommendations are an exclusive or mandatory course of care. All health professionals readingthistexthavearesponsibilitytoevaluateitsappropriatenessandtake theindividualneedsofthepatientintoaccount.
Localtrustguideline:pleaserefertoyourlocalguidelinesasnecessary.
Overview
Alcoholmisuseisamajorcauseofpreventableliverdiseaseworldwide.Alcohol-related liverdisease(ArLD)representsaspectrumfromsimplesteatosistolivercirrhosiswhich canleadtoliverfailureandhepatocellularcarcinoma(HCC).ThecourseofArLDcanbe affected by inherited and environmental causes. The coexistence of other factors can accelerateliver injury,suchas metabolicsyndrome, ironoverload,and chronichepatitis virus.
The successful management of ArLDisdependent on reducing alcohol consumption
andthesecondarypreventionofalcohol-associatedcomplications.
Liverterminology
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Alcoholic hepatitis: recent onset of jaundice with or without other signs of hepatic decompensation,duetoprolonged,excessiveconsumptionofalcohol Alcohol-relatedliverdisease(ArLD):umbrellatermtoincludeallliverdiseasesecondaryto excessalcoholintake Cirrhosis: advanced fibrotic chronic liver disease characterized histologically by bands of bridgingfibrosisandthepresenceofregenerativenodulesofhepatocytes Compensatedchronicliverdisease(CLD):CLD(>6months)withmaintainedliverfunction. TheChild–PughscoreforpatientswithCLDisbasedonbiochemicalandclinicalfeaturesand predictsprognosis DecompensatedCLD: development of features of liver failure including jaundice, ascites and/orencephalopathyinapatientwithCLD Acute-on-chronicliverfailure: Acute worseningof liver functionwith decompensationand multipleorganfailureinapatientwithCLD.
Diagnosis
History
Mostareasymptomatic,thereforeanyhigh-riskpatientshouldundergoscreening ArLDissuggestedby:
Hazardousorharmfulalcoholconsumption(seeChapter35) Presenceofclinicaland/orbiologicalabnormalitiessuggestiveofliverdisease Imagingfindings
Alcoholichepatitisissuggestedby:
Recent-onsetprogressivejaundice,withorwithoutdecompensation Maybeassociatedwithfever(evenifthereisnoinfection),malaise,andweightloss.
Examination
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Mayrangefromnormaltosignssuggestiveofcirrhosis Mostphysicalsignsarenotspecificoftheaetiology:
Jaundice Rightupperquadrantpain Abdominaldistensionduetoascites
Palmarerythema Signsofalcoholwithdrawal/deliriumtremens Signssuggestiveofharmfulalcoholintake:
Bilateralparotidglandhypertrophy
Musclewasting
Malnutrition
Dupuytren’scontracture
Symmetricalperipheralneuropathy
Splenomegaly
Gynaecomastia
Extensivespiderangiomas
Caputmedusae.
Investigations
Bloods
There are a number of prognostication tools that can be used in ArLD based on biochemicalandclinicalparameters.
Alcoholichepatitis
Glasgowalcoholichepatitis(GAH)score Maddrey’sDiscriminantFunction(MDF).
Thesepredictmortalityandguidewhichpatientsmaybenefitfromsteroidtherapy.
Chronicliverdiseaseorsuspectedcirrhosis
Child–Pughscore UnitedKingdomModelforEnd-StageLiverDisease(UKELD)score.
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Table34.1BloodsinArLD
Test Significance
FBC
Macrocyticanaemia Thrombocytopaenia Lymphopenia NeededforGAHscore
U&E
Sodiumandrenalfunctionmonitoringinascites/hepatorenalsyndrome UreainGIbleed NeededforGAHscore
LFT
RaisedGGT,AST,ALT HyperbilirubinaemiaandhypoalbuminaemiainadvancedArLD InvertedAST:ALTofapproximately2:1inArLD NeededforGAHandMDFscores
Carbohydratedeficient transferrin(CDT)
Maybeusefulinpatientswherealcoholhistoryisunclear Positive when ethanol intake of 50–80g/day is sustained over 1–2 weeks, normalizesafter2–3weeksofabstinence
Magnesium,calcium, phosphate,andglucose
Refeedingbloods Hypoglycaemiacanbeacomplicationofalcoholwithdrawal
PTandINR
Indicative of liver synthetic function—both may be prolonged, but does not implyincreasedbleedingrisk NeededforGAHandMDFscores
Before attributingliverdiseaseto alcoholmisusealone,perform anon-invasiveliver screentoexcludealternativecauses/hepaticcomorbidity.SeeTable36.1inChapter36.
Ascitictap
Whenascitesispresentonadmission,anascitictapshouldalwaysbeperformedtoconfirmthatit isrelatedtoportalhypertensionandtoexcludespontaneousbacterialperitonitis:
Neutrophil count and culture (in blood culture bottles) should be performed to exclude
spontaneousbacterialperitonitis(SBP)
Neutrophilcount>250cells/mm3isdiagnosticofSBP.SeeChapter36. Calculateserum-ascitesalbumingradient(SAAG)wheninvestigatingthecauseofascites:
>11g/Lisindicativeofportalhypertensionasacauseofascites Cytology should be performed on presentation to differentiate between malignant and non­malignantascites.
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Imaging
Contributestoassessmentbutcannotconfirmalcoholastheunderlyingcause LiverdiseasemaybesuggestedbyUSS,CT,orMRI
Transient elastography (‘Fibroscan®’) uses liver stiffness measurement to assess for fibrosis althoughitisnottechnicallypossibleinthecontextofascites.
Liverbiopsy
Invasive procedurewithpotential forsevere complicationsinapproximately1:300–1:500 (such asintra-abdominalbleeding,pneumothorax) Considerifdoubtregardingunderlyingdiagnosisortodeterminethepresenceofcirrhosis Percutaneous approach is appropriate in most patients; a transjugular approach is safer if low platelets/prolonged PT,andallowstheassessmentofportal hypertensionbymeasurementofthe hepaticvenouspressuregradient.
Uppergastrointestinalendoscopy
Ifevidenceofcirrhosis,considerscreeningforoesophagealvarices.
Management
Lifestyleandsimpleinterventions
Abstinence:
ThemostimportantinterventioninArLD
ImprovessurvivalatallstagesintheArLDspectrum Nutrition:
Proteinmalnutritionisassociatedwithincreasedriskofcomplications
Get early dietetic input. Consider enteral nutrition in severe alcoholic hepatitis: protein-
caloricintakeoftendifficulttoachieveorally.
Psychologicalinterventions
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