Decompensated cirrhosis Clinical Practice Guidelines - PowerPoint Presentation

Slide1

Decompensated cirrhosis

Clinical Practice Guidelines

Slide2

About these slides

These slides give a comprehensive overview of the EASL clinical practice guidelines on the management of decompensated cirrhosis

The guidelines were first presented at the International Liver Congress 2018 and are published in the Journal of Hepatology

A full copy of the publication can be downloaded from the

Clinical Practice Guidelines

section of the EASL website

Please feel free to use, adapt, and share these slides for your own personal use; however, please acknowledge EASL as the source

Slide3

About these slides

Definitions of all abbreviations shown in these slides are provided within the slide notes

When you see a home symbol like this one: , you can click onthis to return to the outline or topics pages, depending on whichsection you are inPlease send any feedback to: slidedeck_feedback@easloffice.eu

These slides are intended for use as an educational resource and should not be used in isolation to make patient management decisions. All information included should be verified before treating patients or using any therapies described in these materials

Slide4

Guideline panel

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Chair Paolo Angeli PanelCàndid Villanueva, Claire Francoz, Rajeshwar P Mookerjee, Jonel Trebicka, Aleksander Krag, Wim Laleman, Pere Gines, Mauro Bernardi (EASL Governing Board Representative)Reviewers Alexander Gerbes, Thierry Gustot,Guadalupe Garcia-Tsao

Slide5

Outline

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Slide6

Methods

Grading evidence and recommendations

Slide7

Grading evidence and recommendations

1. Guyatt GH, et al. BMJ. 2008:336:924–6;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Grading is adapted from the GRADE system1

Grade of evidenceIRandomized, controlled trialsII-1Controlled trials without randomizationII-2Cohort or case-control analytical studiesII-3Multiple time series, dramatic uncontrolled experimentsIIIOpinions of respected authorities, descriptive epidemiologyGrade of recommendation1Strong recommendation: Factors influencing the strength of the recommendation included the quality of the evidence, presumed patient-important outcomes, and cost2Weaker recommendation: Variability in preferences and values, or more uncertainty: more likely a weak recommendation is warrantedRecommendation is made with less certainty: higher cost or resource consumption

Slide8

Background

Definition and pathophysiology

of decompensated cirrhosis

Slide9

Multi-stage model for the clinical course of cirrhosis

D’Amico G, et al. J Hepatol 2018;68:56376;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Transition from compensated cirrhosis to DC occurs at a rate of ~5–7% per yearDC is a systemic disease, with multi-organ/system dysfunction

Decompensated

Stage

3:

BleedingStage 4: First non-bleeding decompensationStage 5: Second decompensating event

CompensatedStage 0: no varices, mild PHLSM >15 and <20 or HVPG >5 and <10 mmHgStage 1: no varices, CSPHLSM ≥20 or HVPG ≥10 mmHgStage 2: varices (=CSPH)

End stageStage 6: late decompensation:Refractory ascites, persistent PSE or jaundice, infections, renal and other organ dysfunction

ACLF

Death

Slide10

Decompensated

Stage 3: BleedingStage 4: First non-bleeding decompensationStage 5: Second decompensating event

CompensatedStage 0: no varices, mild PHLSM >15 and <20 or HVPG >5 and <10 mmHgStage 1: no varices, CSPHLSM ≥20 or HVPG ≥10 mmHgStage 2: varices (=CSPH)

Multi-stage model for the clinical course of cirrhosis

D’Amico G, et al. J Hepatol 2018;68:56376;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Transition from compensated cirrhosis to DC occurs at a rate of ~5–7% per yearDC is a systemic disease, with multi-organ/system dysfunction

End stage

Stage 6: late decompensation:Refractory ascites, persistent PSE or jaundice, infections, renal and other organ dysfunction

ACLF

Death

Asymptomatic

Median survival: 12 years

Symptomatic

Median survival: 2 years

Slide11

Pathophysiology of DC

Bernardi M, et al. J. Hepatol 2015;63:1272–84;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cirrhosis

Portal hypertension

Liver injury

Bacterial translocation/PAMPs

Activation of innate pattern recognition receptors

Release of pro-inflammatory molecules (ROS/RNS)

Splanchnic arteriolar vasodilation and

cardiovascular dysfunction

Adrenal dysfunction

HE

Kidney dysfunction

HPS

Damaged cells/DAMPs

Other potential mechanisms

++

Slide12

Management strategies for DC

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Management of DC aims to improve outcomes of complications

Complications of DC

Ascites

Bacterial infections

GI bleeding

Increased understanding of DC pathophysiology permits the developmentof more comprehensive therapeutic and prophylactic approachesto prevent or delay disease progression

Hyponatremia

Refractory

Hepatichydrothorax

Uncomplicated

Renal impairment

AKI

CKD

ACLF

RAI

Cardiopulmonary

PPHT

CCM

HPS

Slide13

Key recommendations

Slide14

Overall management of DCSuppression of aetiological factor(s)Treatment of key pathogenic factorsManagement of specific complications of DCAscitesRefractory ascitesHepatic hydrothoraxHyponatremiaGastrointestinal bleedingBacterial infectionsRenal impairment Acute-on-chronic liver failureRelative adrenal insufficiencyCardiopulmonary complications

Topics

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep

.2018.03.024

Click on a topic to skip to that section

Slide15

Overall management of DC

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Management should aim to prevent progression, not treat complicationsNo treatment exists that can act on cirrhosis progression directlyTwo alternative approaches can be taken:Suppress aetiological factor(s) that cause liver inflammation and cirrhosis developmentTarget key factors in the pathogenesis of cirrhosis decompensation and progression

Slide16

Suppression of aetiological factor(s)

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Impact is variableProbably depends on the status of liver disease at the time

RecommendationIn patients with DC the aetiological factor should be removed, particularly alcohol consumption and hepatitis B or C virus infection, as this strategy is associated with decreased risk of decompensation and increased survivalII-21

Grade of evidence

Grade of recommendation

Slide17

Treatment of key pathogenic factors

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Several strategies have been evaluated to prevent disease progression in patients with DCTargeting microbiome abnormalities and bacterial translocation to improve the gut–liver axis (i.e. rifaximin)Improving the disturbed circulatory function (i.e. long-term albumin)Treating the inflammatory state (i.e. statins)Targeting portal hypertension (i.e. β-blockers)

Further clinical research is needed to confirm the safety and potential benefits of these therapeutic approaches toprevent cirrhosis progression in patients with DC

Slide18

Ascites

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Most common complication of decompensation in cirrhosisDevelops in 5–10% of patients with compensated cirrhosis per yearSignificant impact on patientsImpairs patient working and social lifeFrequently leads to hospitalizationRequires chronic treatmentDirect cause of further complicationsPoor prognosis (5-year survival, ~30%)Ascites can be uncomplicated or refractoryAscites is uncomplicated when not infected, refractory or associated with impairment of renal function

Slide19

Uncomplicated ascites:evaluation and diagnosis

*Ascites recurring on ≥3 occasions within a 12-month period despite dietary sodium restriction and adequate diuretic dosage are considered recurrentEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cirrhosis is responsible for 80% of cases of ascitesInitial patient evaluation:HistoryPhysical examinationAbdominal ultrasoundLaboratory assessmentLiver and renal function, serum and urine electrolytes, analysis of ascitic fluidAscites is graded based on amount of fluid in the abdominal cavity

Grading of ascites*Grade 1Mild ascites: only detectable by ultrasound examinationGrade 2Moderate ascites: manifest by moderate symmetrical distension of abdomenGrade 3Large or gross ascites: provokes marked abdominal distension

Slide20

Uncomplicated ascites: evaluation and diagnosis

*Grade of evidence II-2, grade of recommendation 1; †Bedside inoculation blood culture bottles with 10 ml fluid each; ‡A total protein concentration <1.5 g/dl is generally considered a risk factor for SBP;§SAAG ≥1.1 g/dl indicates that portal hypertension is involved in ascites formation with an accuracy of about 97%EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Diagnostic paracentesis is indicated in:*All patients with new-onset grade 2 or 3 ascitesPatients hospitalized for worsening ascites or any complication of cirrhosis

RecommendationNeutrophil count and culture of ascitic fluid culture† should be performed to exclude bacterial peritonitisNeutrophil count >250 cells/µl denotes SBP II-21Ascitic total protein concentration should be performedto identify patients at higher risk of developing SBP‡II-21The SAAG should be calculated when the cause of ascites is not immediately evident, and/or when conditions other than cirrhosis are suspected§II-21Cytology should be performed to differentiate malignancy-related from non-malignant ascitesII-21

Grade of evidence

Grade of recommendation

Slide21

Uncomplicated ascites: prognosis

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Development of ascites in patients with cirrhosis is associated with a poor prognosis1-year mortality: 40%2-year mortality: 50%Patients with ascites should be considered for referral for LTPatients may not receive adequate priority in transplant listsMost commonly used prognostic scores can underestimate mortality riskImproved methods to assess prognosis in these patients are needed

RecommendationSince the development of grade 2 or 3 ascites in patients with cirrhosis is associated with reduced survival, LT should be considered as a potential treatment optionII-21

Grade of evidence

Grade of recommendation

Slide22

Uncomplicated ascites: management

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Grade 1 or mild ascitesNo data on evolution and not known if treatment modifies natural historyGrade 2 or moderate ascitesHospitalization not requiredCorrect sodium imbalance:Dietary restriction and increased renal excretion with diuretics

RecommendationModerate restriction of sodium intake (80–120 mmol/day, corresponding to 4.6–6.9 g of salt) is recommendedI1Generally equivalent to a no added salt diet with avoidance of pre-prepared meals. Adequate nutritional education of patients on how to manage dietary sodium is also recommendedII-21Very low sodium diets (<40 mmol/day) should be avoidedII-21Prolonged bed rest cannot be recommendedIII1

Grade of evidence

Grade of recommendation

Slide23

Uncomplicated ascites:recommended diuretics

*Spironolactone, canrenone or K-canrenoate; †Body weight reduction <2 kg/weekEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Mainstay of medical treatment are anti-mineralocorticoid drugs*Loop diuretics may be added in patients with long-standing ascites

RecommendationFirst episode of grade 2 ascites Anti-mineralocorticoid drug alone (from 100 mg/day with 100 mg stepwise increased every 72 hours to a maximum of 400 mg/day if no response to lower doses)I1In patients who do not respond to anti-mineralocorticoids† or who develop hyperkalaemia, furosemide should be added (from 40 mg/day with 40 mg stepwise increases to a maximum of 160 mg/day)I1Long-standing or recurrent ascites Combination of an anti-mineralocorticoid drug and furosemide (dose increased sequentially according to response)I1Torasemide can be given in patients exhibiting a weak response to furosemideI2

Grade of evidence

Grade of recommendation

Slide24

Uncomplicated ascites: considerations prior to initiating diuretics

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Patients with cirrhosis and ascites are highly susceptible to rapid reductions in extracellular fluid volumeCan lead to renal failure and hepatic encephalopathy

RecommendationGI haemorrhage, renal impairment, hepatic encephalopathy, hyponatraemia, or alterations in serum potassium concentration, should be corrected before starting diuretic therapyIn these patients, cautious initiation of diuretic therapy and frequent clinical and biochemical assessments should be performedIII1Diuretic therapy is generally not recommended in patients with persistent overt hepatic encephalopathyIII1

Grade of evidence

Grade of recommendation

Slide25

Uncomplicated ascites: monitoring of patients receiving diuretics

*Serum sodium <125 mmol/L; †10 mg/day, with a weekly increase of 10 mg/day up to 30 mg/day EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Loop diuretics can lead to potassium and magnesium depletion and hyponatraemiaMuscle cramps can impair quality of life in patients receiving diuretics

RecommendationFrequent clinical and biochemical monitoring during the first weeks of treatment (particularly on first presentation)I1Recommended maximum weight loss: 0.5 kg/day in patients without oedema, 1 kg/day in patients with oedemaII-21Once ascites have largely resolved, the dose of diuretics should be reduced to the lowest effective doseIII1Discontinue diuretics in case of severe hyponatraemia,* AKI, worsening hepatic encephalopathy, or incapacitating muscle crampsIII1Discontinue furosemide for severe hypokalaemia (<3 mmol/L )Discontinue anti-mineralocorticoids for hyperkalaemia (>6 mmol/L)III1Albumin infusion or baclofen administration† are recommended in patients with muscle crampsI1

Grade of evidence

Grade of recommendation

Slide26

Uncomplicated ascites:management of Grade 3 ascites

*Grade of evidence I, grade of recommendation 1EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Grade 3 or large ascitesLVP, under strict sterile conditions, is the treatment of choiceAscites should be completely removed in a single session*Contraindications to LVP include:Uncooperative patient, abdominal skin infection at puncture sites, pregnancy, severe coagulopathy, severe bowel distention

RecommendationLVP should be followed with plasma volume expansionI1Plasma volume expansion should be performed by albumin infusion (8 g/L ascites)For >5 L of ascites: more effective than other plasma expanders For <5 L of ascites (low risk of PPCD): treat with albumin due to concerns about use of alternative plasma expandersI III11After LVP, patients should receive the minimum dose of diuretics necessary to prevent re-accumulation of ascitesI1When needed, LVP should be performed in patients with AKI or SBPIII1

Grade of evidence

Grade of recommendation

Slide27

Uncomplicated ascites: contraindicated drugs

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Patients with DC and ascites are at increased risk of renal impairment from several types of drug

RecommendationNSAIDs should not be used (high risk of developing further sodium retention, hyponatraemia, and AKI)II-21Angiotensin-converting enyzme inhibitors, angiotensin II antagonists, or 1-adrenergic receptor blockers should not generally be used (increased risk of renal impairment)II-21Aminoglycosides are discouraged (increased risk of AKI)Reserved for patients with severe bacterial infections that cannot be treated with other antibioticsII-21Contrast media In patients with preserved renal function: does not appear to be associated with increased risk of renal impairmentIn patients with renal failure: insufficient data, cautious use and preventative measures recommendedIIIII21

Grade of evidence

Grade of recommendation

Slide28

Refractory ascites: definition

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

International Ascites Club:“Ascites that cannot be mobilized or the early recurrence of which (after LVP) cannot be satisfactorily prevented by medical therapy”

Refractory ascites

Diuretic intractable

Diuretic resistant

Ascites that cannot be mobilizedor the early recurrence of whichcannot be prevented because of alack of response to sodiumrestriction and diuretic treatment

Ascites that cannot be mobilizedor the early recurrence of whichcannot be prevented because of thedevelopment of diuretic-inducedcomplications that preclude theuse of an effective diuretic dosage

Slide29

Refractory ascites: diagnostic criteria

*Spironolactone 400 mg/day and furosemide 160 mg/dayEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Diagnostic criteriaTreatment durationPatients must be on intensive diuretic therapy* for at least 1 week and on a salt-restricted diet of less than 90 mmol/dayLack of responseMean weight loss of <0.8 kg over 4 days and urinary sodium output less than the sodium intakeEarly ascites recurrenceReappearance of grade 2 or 3 ascites within 4 weeks of initial mobilizationDiuretic-induced complicationsHE: development of encephalopathy in the absence of any other precipitating factorRenal impairment: increase of serum creatinine by >100% to a value >2 mg/dl (177 µmol/L) in patients with ascites responding to treatmentHyponatraemia: a decrease of serum sodium by >10 mmol/L to a serum sodium of <125 mmol/LHypo- or hyperkalaemia: a change in serum potassium to <3 mmol/L or >6 mmol/L despite appropriate measuresIncapacitating muscle cramps

Slide30

Refractory ascites: diagnosis

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Refractory ascites is associated with a poor prognosisMedian survival around 6 months

RecommendationThe diagnosis of refractory ascites relies on the assessment of the response of ascites to diuretic therapy and salt restrictionEvaluation should be done in stable patients without associated complications, such as bleeding or infection, after ascertaining patient compliance to treatmentIII1Patients with refractory ascites should be evaluated for LTIII1

Grade of evidence

Grade of recommendation

Slide31

Refractory ascites: management

*See also section on gastrointestinal bleedingEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

LVP is a safe and effective treatmentShould be associated with albumin administration to prevent PPCDDrug treatments are controversial or inadequately studied

RecommendationRepeated LVP plus albumin (8 g/L of ascites removed) are recommended as first-line treatment for refractory ascitesI1Diuretics should be discontinued in patients with refractory ascites who do not excrete >30 mmol/day of sodium under diuretic treatmentIII1Although controversial data exist on the use of NSBBs in refractory ascites, caution should be exercised in severe cases*High doses of NSBB should be avoided (i.e. propranolol >80 mg/day)Carvedilol can not be recommended at presentII-2I12

Grade of evidence

Grade of recommendation

Slide32

Refractory ascites: indications for TIPS

*By shunting an intrahepatic portal branch into a hepatic veinEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

TIPS decompresses the portal system*Short term: accentuates peripheral arterial vasodilationWithin 4–6 weeks: improves effective volaemia and renal function to increase renal sodium excretion

RecommendationPatients should be evaluated for TIPS insertion when:There is refractory or recurrent ascites Paracentesis is ineffectiveIIII11TIPS insertion is recommended in patients:With recurrent ascites as it improves survivalWith refractory ascites as it improves the control of ascites II11The use of small-diameter PTFE-covered stents is recommended to reduce the risk of TIPS dysfunction and hepatic encephalopathyI1After TIPS insertion, continue the following until ascites resolution:Diuretics and salt restriction Close clinical follow-upII-2III11

Grade of evidence

Grade of recommendation

Slide33

Hepatic hydrothorax: definition and diagnosis

*Grade of evidence III, grade of recommendation 1EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

DefinitionAccumulation of transudate in the pleural spaceIn the absence of cardiac, pulmonary or pleural diseaseAscites moves through small diaphragmatic defectsNegative intrathoracic pressure induced by inspirationCan lead to respiratory failureCan be complicated by spontaneous bacterial infections (empyema)Associated with poor prognosisMedian survival: 812 monthsDiagnosisOnce pleural effusion has been ascertained, cardiopulmonary and primary pleural diseases should be excluded*Diagnostic thoracentesis is required to rule out bacterial infection*

Slide34

Hepatic hydrothorax: treatment

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

First-line management relies on treatment of ascites with diuretics and/or LVPNot rare for pleural effusion to persist (refractory hepatic hydrothorax)Therapeutic thoracentesis is required to relieve dyspnoea

RecommendationPatients with hydrothorax should be evaluated for LTIII1Diuretics and thoracentesis are recommended as the first-line management of hepatic hydrothoraxIII1Therapeutic thoracentesis is indicated in patients with dyspnoea Chronic pleural drainage should not be performed because of the frequent occurrence of complicationsIIIII-211

Grade of evidence

Grade of recommendation

Slide35

Hepatic hydrothorax: beyond diuretics and thoracentesis

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Other treatments are appropriate in selected patients

RecommendationIn selected patients, TIPS insertion for recurrent symptomatic hepatic hydrothorax is recommendedII-21Pleurodesis can be suggested to patients with refractory hepatic hydrothorax not amenable to LT or TIPS insertionThe frequent occurrence of side effects restricts its use to selected patientsI2Mesh repair of diaphragmatic defects is suggested for the management of hepatic hydrothorax in very selected patientsThe best results are achieved in patients with non-advanced cirrhosis without renal dysfunctionII-22

Grade of evidence

Grade of recommendation

Slide36

Hyponatraemia

*Beyond fluid restriction, hypertonic saline should be limited to rare patients with life-threatening complications. It can be considered in patients with severe hyponatraemia who are expected to undergo LT within days. Correction of serum sodium concentration after attenuation of symptoms should be slow (≤8 mmol/L per day) to avoid irreversible neurological sequelae (II-3;1). Albumin can be administered but data are very limited (II-3;2). Use of vaptans should be limited to clinical trials (III;1)EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Common in patients with advanced cirrhosisArbitrarily defined as serum sodium concentration <130 mmol/LHypo- and hypervolaemic hyponatraemia can occurAssociated with:Increased mortality and morbidity, particularly neurological complicationsReduced survival after LT

RecommendationPatients with cirrhosis who develop hyponatraemia should be evaluated for LTII-21Removal of the cause and administration of normal saline are recommended in the management of hypovolaemic hyponatraemiaIII1Fluid restriction* to 1,000 ml/day is recommended in the management of hypervolaemic hyponatraemia since it may prevent a further reduction in serum sodium levelsIII1

Grade of evidence

Grade of recommendation

Slide37

Variceal haemorrhage: pathophysiology and natural history

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Occurs when variceal wall ruptures due to excessive wall tensionPortal pressure is a key factor in both rupture and severity of bleeding70% of GI bleeding events result from VH in patients with portal hypertensionSecond most common decompensating eventMost severe and immediate life threatening complication

RecommendationPatients with DC are at high risk and should have an OGD to screen for varices, unless previously diagnosed and treatedII-21If OGD is performed, the presence, size and presence of red wale marks should be reportedII-21In patients without varices in whom aetiological factor persists and/or remain decompensated, screening OGD should be repeated yearly In other patients the screening interval could be prolonged, but the exact interval is unclear and more data are required III2

Grade of evidence

Grade of recommendation

Slide38

Variceal haemorrhage: prevention and treatment

*High-risk = small varices with red signs, medium or large varices irrespective of Child–Pugh classification or small varices in Child–Pugh C patientsEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

High risk of death when VH occurs in patients with DCStrategies to adequately treat VH and prevent (re)bleeding and death should be actively pursued

RecommendationPrimary prophylaxis must be initiated upon detection of high-risk varices* because of increased risk of VHI1Patients with small varices with red wale marks or Child–Pugh C should be treated with NSBBsIII1Patients with medium–large varices should be treated with either NSBBs or EBLChoice of treatment can be based on local resources and expertise, patient preference, contraindications and AEsNSBBs could be preferred because in addition to lowering portal pressure, they also exert other potential beneficial effectsIIIIII-2122

Grade of evidence

Grade of recommendation

Slide39

Variceal haemorrhage:prophylaxis with NSBBs and EBL

*Such as bleeding, sepsis, SBP or AKIEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

NSBBs and EBL are equally effective in preventing first bleeding in patients with high-risk varicesChoice between options depends on factors such as patient preference, contraindications or adverse events

Recommendation

Ascites is not a contraindication for NSBBs. However, caution should be exercised in cases of severe or refractory ascitesHigh doses of NSBBs should be avoidedThe use of carvedilol can not be recommended at presentIII-2I112NSBBs should be discontinued in patients with progressive hypotension or those who develop an acute intercurrent condition* After recovery, reinstatement of NSBBs can be attemptedWhen NSBB intolerance or contraindications persist, patient’s bleeding risk should be managed by expeditious EBLIIIIIIIII121

Grade of evidence

Grade of recommendation

Slide40

Variceal haemorrhage:prevention of variceal rebleeding

NSBBs and EBL in combination reduces the risk of re-bleeding compared with monotherapy

*Provided that there are no absolute contraindicationsEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Recommendation

Combination therapy of NSBBs + EBL is recommendedI1Covered TIPS placement is recommended in patients who continue to be intolerant to NSBBs*III1

Slide41

Variceal haemorrhage:

management of acute GI bleeding

*History, physical and blood exam, cultures; †Somatostatin/terlipressin; ‡Ceftriaxone (1 g/24 hours) is the first choice in patients with DC, those already on quinolone prophylaxis, and in hospital settings with high prevalence of quinolone-resistant bacterial infections. Oral quinolones (norfloxacin 400 mg BID) should be used in the remaining patients (I;1)Figure adapted from de Franchis R, et al. J Hepatol 2015;63:74352;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Medical emergency: high rate of complications and mortality in DCRequires immediate treatment and close monitoring

Acute GI bleed + portal hypertension

Initial assessment* and resuscitation

Immediate start of vasoactive drug therapy†Antibiotic prophylaxis (I;1)‡

Early diagnostic endoscopy (<12 hours)

Confirm variceal bleeding

Endoscopic band ligation

Maintain drug therapy for 3–5 days and antibiotics‡

+

Control

(~85% of cases)

Further bleeding

(~15% of cases)

Consider early TIPS in high risk patients

Rescue with TIPS

ENDOSCOPY

ENDOSCOPY

Balloon tamponade or oesophageal stenting

(if massive bleeding)

A

irway

B

reathing

C

irculation

Volume replacement

with colloidsand/or crystalloids should be initiatedpromptly (III;1)Starch should not be used (I;1)Restrictive transfusion is recommendedin most patients (Hb threshold, 7 g/dl; target range 7–9 g/dl) (I;1)

Slide42

Acute variceal haemorrhage: treatment

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Vasoactive drugs and ligation are the primary options for acute VHThere may be a role for TIPS in selected high-risk patients

RecommendationThe combination of vasoactive drugs and ligation is recommended as the first therapeutic option in acute variceal bleedingI1Early pre-emptive covered TIPS (placed within 24–72 hours) can be suggested in selected high-risk patients, such as those with Child–Pugh class C with score <14However, the criteria for high-risk patients, particularly Child–Pugh B with active bleeding, remains debatable and needs further studyI2

Grade of evidence

Grade of recommendation

Slide43

Management of persistent bleeding

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Up to 10–15% of patients have persistent bleeding or early re-bleedingDespite treatment with vasoactive drugs and EBL, and prophylactic antibiotics

RecommendationTIPS should be used as the rescue therapy of choice in cases of persistent bleeding or early re-bleedingI1With the pre-requisite of expertise, balloon tamponade should be used in case of uncontrolled bleeding as a temporary ‘‘bridge” (max 24 hours) until definitive treatment can be instituted Removable, covered and self-expanding oesophageal stents can be used as an alternative to balloon tamponadeIIII12In the context of bleeding, where encephalopathy is commonly encountered, prophylactic lactulose may be used to prevent encephalopathy, but further studies are neededI2β-blockers and vasodilators should be avoided during the acute bleeding episodeIII1

Grade of evidence

Grade of recommendation

Slide44

Bacterial infections

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Risk of bacterial infection in patients with cirrhosis is caused by multiple factorsLiver dysfunctionPortosystemic shuntingGut dysbiosisIncreased BTCirrhosis-associated immune dysfunctionGenetic factorsSpontaneous bacterial peritonitisDefinition: bacterial infection of ascitic fluid without any intra-abdominal surgically treatable source of infectionPrevalence: all patients with cirrhosis and ascites are at risk1.5–3.5% in outpatients; 10% in hospitalized patientsPrognosis: mortality exceeded 90% when first describedReduced to ~20% with early diagnosis and treatment

Slide45

Spontaneous bacterial peritonitis: diagnosis

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Diagnosis is based on diagnostic paracentesis50% of SBP episodes are present at hospital admissionSigns/symptoms of peritonitis: abdominal pain, tenderness, vomiting or diarrhoea, ileusSigns of systemic inflammation: hyper- or hypothermia, chills, altered WBC countWorsening liver function, HE, shock, renal impairment, GI bleeding

However: SPB may be asymptomatic,particularly in outpatients

Slide46

Spontaneous bacterial peritonitis: diagnosis

*Culture should be performed to guide antibiotic therapy (Grade of evidence II-2, grade of recommendation 1)EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Diagnosis is based on diagnostic paracentesis50% of SBP episodes are present at hospital admissionSigns/symptoms of peritonitis: abdominal pain, tenderness, vomiting or diarrhoea, ileusSigns of systemic inflammation: hyper- or hypothermia, chills, altered WBC countWorsening liver function, HE, shock, renal failure, GI bleeding

RecommendationDiagnostic paracentesis should be carried out in:Patients with cirrhosis and ascites, at admission, to rule out SBP Patients with GI bleeding, shock, fever or other signs of systemic inflammation, worsening liver and/or renal function, and HEII-21SBP diagnosed by a neutrophil count in ascitic fluid >250/mm3Neutrophil count is determined by microscopy or flow cytometryNo clear evidence to support routine use of reagent stripsII-21Ascitic fluid culture positivity is not a prerequisite for SBP diagnosis*II-21

Grade of evidence

Grade of recommendation

Slide47

Management of SBP: empirical antibiotics

*Grade of evidence II-2, grade of recommendation 1; †Grade of evidence I, grade of recommendation 1 EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Empirical IV antibiotics should be started immediately following diagnosis*Several factors should guide empirical antibiotic use†Environment (community acquired vs. nosocomial)Local bacterial resistance profilesSeverity of infection

RecommendationThird-generation cephalosporins are recommended as first-line antibiotic treatment for community-acquired SBP in countries with low rates of antibiotic resistanceIn countries with high rates of antibiotic resistance piperacillin/tazobactam or carbapenem should be consideredIII-211Antibiotic resistance is more likely in healthcare-associated and nosocomial SBPPiperacillin/tazobactam: in areas with low prevalence of MDR bacteriaCarbapenem: in areas with high prevalence of ESBL-producing EnterobacteriaceaeCarbapenem + glycopeptides, daptomycin linezolid in areas with high prevalence of gram-positive MDR bacteriaI1

Grade of evidence

Grade of recommendation

Slide48

Management of SBP: empirical antibiotics

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Antibiotic therapy should be carefully controlled and monitored

RecommendationSevere infections by XDR bacteria may require antibiotics known to be highly nephrotoxic in patients with cirrhosis (e.g. vancomycin or aminoglycosides)In these cases, patients’ plasma levels should be monitored in accordance with local policy thresholdsIII1De-escalation according to bacterial susceptibility based on positive cultures is recommended to minimize resistance selection pressureII-21Antibiotic efficacy should be checked with a second paracentesis at 48 hours from starting treatmentSuspect failure of first-line antibiotic if worsening clinical signs and symptoms and/or increase, or no marked reduction in leucocyte count (at least 25%) in 48 hoursII-21The duration of treatment should be at least 5–7 daysIII1Spontaneous bacterial empyema should be managed similarly to SBPII-22

Grade of evidence

Grade of recommendation

Slide49

Management of SBP: use of albumin

1. Sort P, et al. N Engl J Med 1999;341:403–9;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

In patients with SBP treated with a third generation intravenous cephalosporin antibiotic, albumin significantly decreased the incidence of type-1 hepatorenal syndrome and reduced mortality1

RecommendationThe administration of albumin is recommended in patients with SBP1.5 g/kg at diagnosis and1 g/kg on Day 3I1

Grade of evidence

Grade of recommendation

Slide50

Management of SBP: primary prophylaxis

1. Wiest R, et al. Gut 2012;61:297–310;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Patients with cirrhosis and low ascitic fluid protein concentration(<10 g/L) and/or high serum bilirubin levels are at high risk of developing a first episode of SBP1

RecommendationPrimary prophylaxsis with norfloxacin (400 mg/day) is recommended in patients with:Child–Pugh score ≥9 and serum bilirubin level ≥3 mg/dl, andEither impaired renal function or hyponatraemia, andAscitic fluid protein lower than 15 g/LI1Norfloxacin prophylaxis should be stopped in patients with long-lasting improvement of their clinical condition and disappearance of ascitesIII1

Grade of evidence

Grade of recommendation

Slide51

Management of SBP: secondary prophylaxis

1. Rimola A, et al. J Hepatol 2000;32:142–53;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

In patients who survive an episode of SBP, the cumulative recurrence rate at 1 year is approximately 70%1

RecommendationProphylactic norfloxacin (400 mg/day, orally) is recommended in patients who recover from an episode of SBPI1At present, rifaximin cannot be recommended as an alternative to norfloxacin for secondary prophylaxis of SBPAt present, no recommendation can be given to guide prophylaxis of SBP among patients already on rifaximin for the prevention of recurrent HEI2Patients who recover from SBP have a poor long-term survival and should be considered for LTII-21PPIs may increase the risk for the development of SBP, their use should be restricted to those with a clear indicationII-21

Grade of evidence

Grade of recommendation

Slide52

Management of other infections

*Carbapenem alone or in combination with other antibiotics proved to be superior to third-generation cephalosporins in healthcare-associated infections other than SBPEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Non-SBP infections are frequent in patients with cirrhosisAssociated with increased mortality

RecommendationHospitalized patients with cirrhosis should be monitored closely for the presence of infections to enable early diagnosis and treatmentII-11Empirical antibiotic therapy should be commenced promptlyII-11Empirical antibiotic therapy should be based on: environment, local resistance profiles, severity and type of infectionI1In the context of high bacterial resistance to antibiotics, carbapenem alone or in combination with other antibiotics should be preferred*I1Severe infections by XDR bacteria may require antibiotics known to be highly nephrotoxic in patients with cirrhosis (e.g. vancomycin or aminoglycosides)In these cases, patients’ plasma level should be monitored in accordance with local policy thresholdsIII1Routine use of albumin not recommended in infections other than SBPI1

Grade of evidence

Grade of recommendation

Slide53

Assessing severity of infection

1. Singer M, et al. JAMA 2016;315:801–10; Figure adapted from Piano S, et al. Gut 2017; doi: 10.1136/gutjnl-2017-314324.[Epub ahead of print]; EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

qSOFA and Sepsis-3 criteria have been validated in patients with cirrhosis1Can be used to assess severity of infection

Is baseline SOFA score available?

Apply sepsis-3 criteria

Apply sepsis-3 criteria and

qSOFA

Sepsis-3 positive and

qSOFA negative

Good outcome

Grey zone

Monitoring SOFA score is required

Sepsis-3 and

qSOFA

negative

Sepsis-3 and qSOFA positive

Positive

Negative

Good outcome

Poor outcomePatient with need for transfer to ICU

Yes

No

Slide54

Other infections:recommended empirical antibiotic treatment

Adapted from Jalan R, et al. J Hepatol 2013;60:1310–24;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cellulitis

Nosocomial

Healthcare-associated

Community-acquired

3rd-gencephalosporin ormeropemen + oxacillin or glycopeptides ordaptomycin orlinezolid

AREA DEPENDENT:Like nosocomialinfections if highprevalence of MDROsor if sepsis

Piperacillin-tazobactamor 3rd-gencephalosporin +oxacillin

Pneumonia

Nosocomial

Healthcare-associated

Community-acquired

Ceftazidime or

meropemen +

levofloxacin ±

glycopeptides or

linezolid

AREA DEPENDENT:

Like nosocomial

infections if highprevalence of MDROsor if sepsis

Piperacillin-tazobactamor ceftriaxone +macrolide orlevofloxacin ormoxifloxacin

UTI

Nosocomial

Healthcare-associated

Community-acquired

UNCOMPLICATED:

fosfomycin or

nitrofurantoin

IF SEPSIS:

meropemen +

teicoplanin or

vancomycin

AREA DEPENDENT:Like nosocomialinfections if highprevalence of MDROsor if sepsis

UNCOMPLICATED:ciprofloxacin orcotrimoxazoleIF SEPSIS: 3rd-gen cephalosporinor piperacillin-tazobactam

Slide55

Other infections:recommended empirical antibiotic treatment

Adapted from Jalan R, et al. J Hepatol 2013;60:1310–24;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cellulitis

Nosocomial

Healthcare-associated

Community-acquired

3rd-gencephalosporin ormeropemen + oxacillin or glycopeptides ordaptomycin orlinezolid

AREA DEPENDENT:Like nosocomialinfections if highprevalence of MDROsor if sepsis

Piperacillin-tazobactamor 3rd-gencephalosporin +oxacillin

Pneumonia

Nosocomial

Healthcare-associated

Community-acquired

Ceftazidime or

meropemen +

levofloxacin ±

glycopeptides or

linezolid

AREA DEPENDENT:

Like nosocomial

infections if highprevalence of MDROsor if sepsis

Piperacillin-tazobactamor ceftriaxone +macrolide orlevofloxacin ormoxifloxacin

UTI

Nosocomial

Healthcare-associated

Community-acquired

UNCOMPLICATED:

fosfomycin or

nitrofurantoin

IF SEPSIS:

meropemen +

teicoplanin or

vancomycin

AREA DEPENDENT:Like nosocomialinfections if highprevalence of MDROsor if sepsis

UNCOMPLICATED:ciprofloxacin orcotrimoxazoleIF SEPSIS: 3rd-gen cephalosporinor piperacillin-tazobactam

Most clinically relevant

Slide56

Renal impairment: definitions

*Proteinuria/haeamaturia/ultrasonography abnormalities. †Stage 1A (sCr <1.5mg/dl), Stage 1B (sCr ≥1.5mg/dl)EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Definitions of renal impairment and staging of AKI have been updated

RecommendationIn patients with liver diseases, even a mild increase in SCr should be considered since it may underlie a marked decrease of GFRII-21First step is to establish CKD, AKD, AKI or overlapII-21Diagnosis of CKD should be based on a GFR <60 ml/min/1.73 m2 estimated by SCr-based formulas, with or without signs of renal parenchymal damage* for at least 3 monthsII-21The diagnostic process should be completed by staging CKD, which relies on GFR levels, and by investigating its causeNote that SCr-based formulae overestimate GFR in cirrhosisII-21Diagnosis of AKI should be based on adapted KDIGO criteriaEither an increase in SCr of >0.3 mg/dl from baseline within 48 hours, or an increase of ≥50% from baseline within 3 monthsII-21Staging of AKI should be based on an adapted KDIGO system†II-21

Grade of evidence

Grade of recommendation

Slide57

Renal impairment: definitions

*Proteinuria/haeamaturia/ultrasonography abnormalities. †Stage 1A (sCr <1.5mg/dl), Stage 1B (sCr ≥1.5mg/dl)EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Definitions of renal impairment and staging of AKI have been updated

RecommendationIn patients with liver diseases, even a mild increase in SCr should be considered since it may underlie a marked decrease of GFRII-21First step is to establish CKD, AKD, AKI or overlapII-21Diagnosis of CKD should be based on a GFR <60 ml/min/1.73 m2 estimated by SCr-based formulas, with or without signs of renal parenchymal damage* for at least 3 monthsII-21The diagnostic process should be completed by staging CKD, which relies on GFR levels, and by investigating its causeNote that SCr-based formulae overestimate GFR in cirrhosisII-21Diagnosis of AKI should be based on adapted KDIGO criteriaEither an increase in SCr of >0.3 mg/dl from baseline within 48 hours, or an increase of ≥50% from baseline within 3 monthsII-21Staging of AKI should be based on an adapted KDIGO system†II-21

Grade of evidence

Grade of recommendation

Slide58

Renal impairment: definitions of kidney disease

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

KDIGO group definitions

DefinitionFunctional criteriaStructural criteriaAKIIncrease in sCr ≥50% within 7 days,ORincrease in sCr ≥0.3 mg/dl within 2 daysNo criteriaAKDGFR <60 ml/min per 1.73m2 for <3 months,ORdecrease in GFR ≥35% for <3 months,ORincrease in sCr ≥50 % for <3 monthsKidney damagefor <3 monthsCKDGFR <60 ml/min per 1.73 m2 for ≥3 monthsKidney damagefor ≥3 months

Slide59

Renal impairment: definitions of kidney disease

*International Club of Ascites-recommended adaptation of KDIGO group criteriaEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

KDIGO group definitions

DefinitionFunctional criteriaStructural criteriaAKIIncrease in sCr ≥50% within 7 days,ORincrease in sCr ≥0.3 mg/dl within 2 daysNo criteriaAKDGFR <60 ml/min per 1.73m2 for <3 months,ORdecrease in GFR ≥35% for <3 months,ORincrease in sCr ≥50 % for <3 monthsKidney damagefor <3 monthsCKDGFR <60 ml/min per 1.73 m2 for ≥3 monthsKidney damagefor ≥3 months

Increase in sCr ≥50% within 3 months*

Slide60

AKI in patients with cirrhosis: ICA definitions

Angeli P, et al. J. Hepatol 2015;62:96874; EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

SubjectDefinitionBaseline sCrsCr obtained within 3 months prior to admissionIf >1 value within the previous 3 months, the value closest to the admissionIf no previous sCr, the sCr on admission should be usedDefinition of AKIIncrease in sCr ≥0.3 mg/dl (≥26.5 µmol/L) within 48 hours orIncrease sCr ≥50% within the prior 7 daysStaging of AKIStage 1: increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baselineStage 2: increase in sCr >2-fold to 3-fold from baselineStage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 µmol/L) with acute increase ≥0.3 mg/dl (≥26.5 µmol/L) or initiation of renal replacement therapyProgression of AKIProgressionProgression of AKI to a higher stage and/or need for RRTRegressionRegression of AKI to a lower stageResponse to treatmentNo responseNo regression of AKIPartial responseRegression of AKI stage with a reduction of sCr to ≥0.3 mg/dl (≥26.5 µmol/L) above baselineFull responseReturn of sCr to a value within 0.3 mg/dl (≥26.5 µmol/L) of baseline

Slide61

AKI in patients with cirrhosis: ICA definitions

*ICA recommended adaptations of KDIGO group criteriaAngeli P, et al. J. Hepatol 2015;62:96874; EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

SubjectDefinitionBaseline sCrsCr obtained within 3 months prior to admissionIf >1 value within the previous 3 months, the value closest to the admissionIf no previous sCr, the sCr on admission should be usedDefinition of AKIIncrease in sCr ≥0.3 mg/dl (≥26.5 µmol/L) within 48 hours orIncrease sCr ≥50% within the prior 7 daysStaging of AKIStage 1: increase in sCr ≥0.3 mg/dl (≥26.5 µmol/L) or an increase in sCr ≥1.5-fold to 2-fold from baselineStage 2: increase in sCr >2-fold to 3-fold from baselineStage 3: increase of sCr >3-fold from baseline or sCr ≥4.0 mg/dl (353.6 µmol/L) with acute increase ≥0.3 mg/dl (≥26.5 µmol/L) or initiation of renal replacement therapyProgression of AKIProgressionProgression of AKI to a higher stage and/or need for RRTRegressionRegression of AKI to a lower stageResponse to treatmentNo responseNo regression of AKIPartial responseRegression of AKI stage with a reduction of sCr to ≥0.3 mg/dl (≥26.5 µmol/L) above baselineFull responseReturn of sCr to a value within 0.3 mg/dl (≥26.5 µmol/L) of baseline

Stage 1A (sCr <1.5mg/dl)*Stage 1B (sCr ≥1.5mg/dl)*

Slide62

ICA management algorithm for AKI in cirrhosis

*Initial AKI stage is defined as AKI stage at the time of first fulfilment of the AKI criteria;†Treatment of spontaneous bacterial peritonitis should include albumin infusion according to current guidelinesAdapted from Angeli P, et al. J Hepatol 2015;62:968–74;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Investigation and management should begin immediately

Initial AKI* stage 1A

Initial AKI* stage >1A

Close monitoring

Remove risk factors (withdrawal of nephrotoxic

drugs, vasodilators and NSAIDs, taper/withdraw

diuretics and

β

-blockers, expand plasma volume,

treat infections

†

when diagnosed)

Withdrawal of diuretics (if not yet applied) and volume expansion with albumin (1 g/kg) for 2 days

Persistance

Progression

Resolution

Further treatment of AKI decided on a case-by-case basics

Close follow-up

Response

YES

NO

Does AKI meet criteria of HRS?

NO

Specific treatment for other AKI phenotypes

YES

Vasoconstrictors and albumin

Slide63

Differentiating types of AKI

1. Angeli et al. J. Hepatol 2015;62:968–74; EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

All types of AKI can occur in patients with cirrhosisPre-renal, HRS, intrinsic, particularly ATN, and post-renalKey point is to differentiate HRS-AKI from ATNClassification of HRS was recently revised by the ICA1Type 1 HRS now corresponds to HRS-AKIType 2 HRS includes renal impairment that fulfills the criteria of HRS but not of AKI (non-AKI-HRS or NAKI)

RecommendationIt is important to differentiate among types of AKI in patients with cirrhosis II-21The diagnosis of HRS-AKI is based on revised ICA criteria (see next slide)As kidney biopsy is rarely performed in the setting of AKI, biomarkers should be implementedIn clinical practice among the different biomarkers to date, urinary NGAL can be used to distinguish between ATN and HRSII-22

Grade of evidence

Grade of recommendation

Slide64

ICA diagnostic criteria for HRS-AKI

*Patients who fulfil these criteria may still have structural damage such as tubular damageAngeli et al. J. Hepatol 2015;62:96874;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cirrhosis and ascitesDiagnosis of AKI according to ICA-AKI criteriaNo response after 2 consecutive days of diuretic withdrawal and plasma volume expansion with albumin 1 g per kg of body weightAbsence of shockNo current or recent use of nephrotoxic drugs (NSAIDs, aminoglycosides, iodinated contrast media, etc.)No macroscopic signs of structural kidney injury,* defined as:Absence of proteinuria (>500 mg/day)Absence of microhaematuria (>50 RBCs per high power field)Normal findings on renal ultrasonography

Slide65

Management of HRS-AKI: treatment

*Grade of evidence I, grade of recommendation 1;†Continuous IV infusion allows for dose reduction to reduced adverse effects; ‡ Limited data are availableEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

First-line therapy is terlipressin plus albumin*

RecommendationAll patients meeting the current definition of HRS-AKI stage >1A should be expeditiously treated with vasoconstrictors and albumin III1Terlipressin can be administered by IV boluses (1 mg every 4–6 hours) or by continuous IV infusion (2 mg/day)† In case of non-response (decrease in SCr <25% from the peak value) after 2 days, the dose of terlipressin should be increased in a stepwise manner to a maximum of 12 mg/dayI1Albumin solution (20%) should be used at 20–40 g/daySerial measures assessing central blood volume can help to titrate the dose of albumin to prevent circulatory overloadII-21Noradrenaline can be an alternative to terlipressin‡Requires a central venous line often in an ICUMidodrine + octreotide can be an option when terlipressin or noradrenaline are unavailable (but efficacy is much lower)III211

Grade of evidence

Grade of recommendation

Slide66

Management of HRS-AKI: screening and monitoring

*Continuous IV infusion allows for dose reduction to reduced adverse effectsEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Patients receiving treatment for HRS-AKI should be monitored for AEs and treatment responseAEs related to terlipressin or noradrenaline include ischaemic and cardiovascular events

RecommendationCareful clinical screening including ECG before starting the treatment is recommended The decision to treat on a regular ward or transfer to higher dependency care should be case basedClose monitoring of patients for the duration of treatment is importantTreatment should be modified or discontinued according to the type and severity of side effectsI1Response to treatment:CR: final SCr within 0.3 mg/dl (26.5 µmol/L) from baselinePR: regression of AKI stage to a final SCr ≥0.3 mg/dl (26.5 µmol/L) from baselineIII1In case of recurrence a repeat course of therapy should be givenI1

Grade of evidence

Grade of recommendation

Slide67

Management of HRS: TIPS and LT

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

In most patients with HRS-AKI TIPS is contraindicated because of severe degree of liver failure

RecommendationThere is insufficient data to advocate TIPS in HRS-AKIIt could be suggested in selected patients with HRS-NAKIII-22LT is the best therapeutic option for patients with HRS regardless of the response to drug therapyI1The decision to initiate RRT should be based on the individual severity of illnessI2The indication for liver-kidney transplantation remains controversialShould be considered in patients with significant CKD or sustained AKI including HRS-AKI with no response to drug therapyII-21

Grade of evidence

Grade of recommendation

Slide68

Prevention of HRS

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Based on the use of albumin in patients who develop SBP and the prevention of SBP using norfloxacin

RecommendationAlbumin (1.5 g/kg at diagnosis and 1 g/kg on Day 3) should be given in patients with SBP to prevent AKII1Norfloxacin (400 mg/day) should be given as prophylaxis of SBP to prevent HRS-AKII1

Grade of evidence

Grade of recommendation

Slide69

Acute-on-chronic liver failure

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Frequent occurrence in cirrhotic patients30% of admitted patients and 25% of outpatientsMajor cause of death in patients with cirrhosis (50% mortality rate)Develops on a background of acute decompensation Characterized by hepatic and extrahepatic organ failure, highly activated systemic inflammation and a high 28-day mortalityPrecipitating events vary between populations and may include:Bacterial infections (3057% of cases)Active alcohol intake or alcohol bingeReactivation of HBVSuperimposed HAV and HEV infection

Slide70

EASL-CLIF prognostic and diagnostic scores for ACLF

*Age in years, creatinine in mg/dL, WBC in 106 cells/L, sodium in mmol/L; †Bold text indicates the diagnostic criteria for organ failures; ‡Patients submitted to mechanical ventilation due to HE and not to a respiratory failure were considered as presenting a cerebral failure (cerebral score = 3); §Other patients enrolled in the study with mechanical ventilation were considered as presenting a respiratory failure (respiratory score = 3)1. Jalan R, et al. J Hepatol 2014;61:1038–47;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

CLIF-C ACLF score for mortality prediction1*10 x [0.033 x Clif OFs + 0.04 x Age + 0.63 x Ln(WBC) – 2]

Chronic liver failure – organ failure score system1 Organ/system†1 point2 points3 pointsLiver (bilirubin, mg/dl)<6≥6–<12≥12.0Kidney (creatinine, mg/dl)<2.0≥2.0–<3.5≥3.5 or renal replacementBrain/HE (West Haven Criteria)Grade 0Grades 1–2Grades 3–4‡Coagulation (INR, PLT count)<2.0≥2.0–<2.5≥2.5Circulation (MAP, mmHg and vasopressors)≥70<70Use of vasopressorsLungs PaO2/FiO2, or>300≤300–>200≤200§ SpO2/FiO2>357>214–≤357≤214§

Slide71

Classification and grades of ACLF

Moreau R, et al. Gastroenterology 2013;144:1426–37;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Even mild renal or brain dysfunction in the presence of another organ failure, is associated with a significant short-term mortality and therefore defines the presence of ACLF

Grades of ACLFClinical characteristicsNO ACLFNo organ failure, or single non-kidney organ failure, creatinine<1.5 mg/dl, no HEACLF 1aSingle renal failureACLF 1bSingle non-kidney organ failure, creatinine 1.5–1.9 mg/dl and/or HE grade 1–2ACLF IITwo organ failuresACLF IIIThree or more organ failures

Slide72

Diagnosis of ACLF

*Defined as the acute development or worsening of ascites, overt encephalopathy, GI haemorrhage, non-obstructive jaundice and/or bacterial infections; †Note that in a significant proportion of patients, a precipitant factor may not be identifiedEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Diagnosis of ACLF is based on organ failure in the presence of AD in patients with cirrhosis

RecommendationACLF diagnosis: cirrhosis and AD* plus organ failure(s) involving high short-term mortalityII-21Diagnosis and grading should be based using the CLIF-C Organ Failure scoreII-21Potential precipitating factor(s) should be investigated†Hepatic: heavy alcohol intake, viral hepatitis, DILI, autoimmune hepatitisExtrahepatic: infections haemodynamic derangements following haemorrhage, surgeryII-21

Grade of evidence

Grade of recommendation

Slide73

Management of ACLF

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

There is no specific therapy for ACLFTreatment is based on organ support and management of complications

RecommendationTreatment of ACLF should be based on organ support, management of precipitants and associated complications III1Patients should be treated in intermediate care or intensive caresettingsIII1ACLF is a dynamic condition and organ function should be monitored frequently and carefully throughout hospitalizationParticularly, liver, kidney, brain, lung, coagulation, and circulationMonitoring and management should be individualized, mainly according to patients’ age and comorbidities III1

Grade of evidence

Grade of recommendation

Slide74

Management of ACLF

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

The cause of liver injury can be treated in certain situations, e.g. HBVEarly action is crucial to patient survivalTreatment of precipitating factorsReferral for LT before evolution of ACLF makes LT impossible

RecommendationEarly identification and treatment of precipitating factors of ACLF, particularly bacterial infections, is recommended. However, in some patients ACLF progresses despite treatment of precipitating factorsIII1Nucleoside analogues (tenofovir, entecavir) should be instituted as early as possible in patients with HBV-related ACLFI1Early referral of patients with ACLF to LT centres for immediate evaluation is recommendedII-31Withdrawal of intensive care support after 1 week can be suggested in patients who are not LT candidates and have ≥4 organ failuresII-22Administration of G-CSF cannot be recommended at presentI2

Grade of evidence

Grade of recommendation

Slide75

Relative adrenal insufficiency

*Also known as critical illness-related corticosteroid insufficiency (CIRCI)EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Inadequate cortisol response to stress in the setting of critical illness*Pathophysiology in cirrhosis is not well definedDiagnosis is influenced by the method used to measure cortisolIt is not known whether cortisol supplementation in clinically stable cirrhosis with RAI is of any value

RecommendationDiagnosis of RAI<248 nmol/L (9 lg/dl) change in total serum cortisol after 250 lg corticotropin injection, or Random total cortisol of <276 nmol/L (<10 lg/dl)II-21Salivary cortisol determination can be preferredSerum free cortisol concentration can be influenced by reduced serum levels of CBG and albumin, frequently seen in patients with cirrhosisII-22Hydrocortisone treatment (at a dose of 50 mg/6 hours) of RAI cannot be recommendedI2

Grade of evidence

Grade of recommendation

Slide76

Cirrhotic cardiomyopathy

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

CCM occurs in patients with established cirrhosis characterized by:Blunted contractile response to stress (pharmacological/surgery or inflammatory)Altered diastolic left ventricular relaxation or/and increased left atrial volumeElectrophysiological abnormalities e.g. prolonged QTcCardiac output tending to decrease with decompensationSystolic dysfunction: LVEF <55%CCM is largely subclinical but its presence influences prognosis in advanced disease

Slide77

Cirrhotic cardiomyopathy

*Either pharmacologically, or through exercise; †And in the absence of influence of β-blockadeEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Numerous electrocardiographic criteria, along with transmitral Doppler assessment, are used for the evaluation and diagnosis of diastolic dysfunction However, there is the need for more controlled studies and correlation with clinical endpoints

RecommendationECG in patients with cirrhosis should be performed with dynamic stress testing* (systolic dysfunction may be masked by hyperdynamic circulation and reduced afterload)Lack of increased CO after physiological/pharmacological stress† indicates systolic dysfunctionII-11Myocardial strain imaging and assessment of GLS may be useful in the assessment of left ventricular systolic function in patients with DCII-22Cardiac MRI may identify structural changesIII2Diastolic dysfunction may occur as an early sign of CCM in the setting of normal systolic function, and should be diagnosed using ASE criteria:Average E/e’>14Tricuspid velocity >2.8 m/sLAVI >34 ml/m2II-11

Grade of evidence

Grade of recommendation

Slide78

Cirrhotic cardiomyopathy

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Cardiac evaluation in patients with cirrhosis is important since CCM can influence prognosis

RecommendationIn patients with AD, reduced CO (as a manifestation of CCM) is associated with the development of AKI (specifically hepatorenal dysfunction) after infections such as SBPII-11QTc interval prolongation is common in cirrhosis and may indicate a poor outcomeAgents that can prolong the QT interval should be used cautiouslyII-22Detailed functional cardiac characterization should be part of the assessment for TIPS insertionLTII-2II-121Standardized criteria and protocols for the assessment of systolic and diastolic function in cirrhosis are neededII-22

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Slide79

Hepatopulmonary syndrome

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Four main pulmonary complications may occur in patients with chronic liver diseasePneumoniaHepatic hydrotoraxHPSPortopulmonary hypertensionHPS is defined as a disorder in pulmonary oxygenation, caused by intrapulmonary vasodilatation and, less commonly, by pleural and pulmonary arteriovenous communications occurring in the clinical setting of portal hypertensionClinical manifestations of HPS in patients with chronic liver disease primarily involve dyspnoea and platypnoea

Slide80

Pathogenesis of HPS

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Increased ET-1 release

Portosystemic shunt

Hyperdynamic circulationBacterial translocation

Systemic inflammation

Hepatic injury/failurePortal hypertension

ET

B receptor

Endothelial cell

Increased eNOS expression and activity

Increased NO and CO release

VASODILATION

Endothelial activation

of CX3CL1

Genetic

factors

Endothelial cell

Endothelial cell

Endothelial cellproliferation

ANGIOGENESIS

VASODILATION

HEPATOPULMONARY

SYNDROME

Increased adherence of macrophages/

monocytes to endothelial cells

Increased iNOS and HO

expression and activity

Macrophage

recruitment

in the lungs

Pulmonary capillary

CX3CL1

VFG-A release

Slide81

Diagnostic criteria for HPS

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Hypoxia with partial pressure of oxygen <80 mmHg or alveolar–arterial oxygen gradient ≥15 mmHg in ambient air (≥20 mmHg in patients older than 65 years)Pulmonary vascular defect with positive findings on contrast-enhanced echocardiography or abnormal uptake in the brain (>6%) with radioactive lung-perfusion scanningCommonly in presence of portal hypertension, and in particular:Hepatic portal hypertension with underlying cirrhosisPre-hepatic or hepatic portal hypertension in patients without underlying cirrhosisLess commonly in presence of:Acute liver failure, chronic hepatitis

Slide82

Diagnosis of HPS

*For adults ≥65 years a P[A-a]O2 ≥20 mmHg cut-off should be usedEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

In patients with portal hypertension and the clinical suspicion of HPS partial pressure of oxygen (PaO2) in ABG should be assessed

RecommendationIn patients with chronic liver disease, HPS should be suspected and investigated in presence of tachypnoea and polypnoea, digital clubbing and/or cyanosisII-21Screening in adults:If pulse oximetry SpO2 <96% – ABG analysis should be performedIf ABG PaO2 <80mmHg and/or P[A-a]O2 ≥15 mmHg* (in ambient air) – further investigations should be performedII-21The use of contrast (microbubble) echocardiography to characterize HPS is recommendedII-21

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Slide83

Diagnosis of HPS

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

When PaO2 suggests HPS, further investigations are needed to determine the underlying mechanism

RecommendationMAA scan should be performed to quantify the degree of shunting in patients with severe hypoxaemia and coexistent intrinsic lung disease, or to assess the prognosis in patients with HPS and verysevere hypoxaemia (PaO2 <50 mmHg)II-21Neither contrast echocardiography nor MAA scan can definitively differentiate discrete arteriovenous communications from diffuse precapillary and capillary dilatations or cardiac shuntsPulmonary angiography should be performed only in patients with the severe hypoxaemia (PaO2 <60 mmHg), poorly responsive to administration of 100% oxygen, and in whom there is a strong suspicion of arteriovenous communications that are amenable to embolizationII-21Trans-oesophageal contrast-enhanced echocardiography (although associated with risks) can definitively exclude intra-cardiac shuntsII-22

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Slide84

Management of HPS

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

There is no established medical therapy currently available for HPS, the only successful treatment for HPS is LT

Recommendations for medical treatmentLong-term oxygen therapy is recommended in patients with HPS and severe hypoxaemia despite the lack of available data concerning effectiveness, tolerance, cost effectiveness, compliance and effects on survival rates of this therapy II-21No recommendation can be proposed regarding the use of drugs or the placement of TIPS for the treatment of HPSI1Recommendations for liver transplantation Patients with HPS and PaO2 <60 mmHg should be evaluated for LT since it is the only treatment for HPS that has been proven to be effective to dateII-21Severe hypoxaemia (PaO2 <45–50 mmHg) is associated with increased post-LT mortalityABG analysis should be carried out every 6 months to facilitate prioritization to LTII-21

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Slide85

Portopulmonary hypertension

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

PPHT occurs in patients with portal hypertension in the absence of other causes of arterial or venous hypertensionClassification is based on mean pulmonary arterial pressure (mPAP), and assumes high pulmonary vascular resistance (PVR) and normal pulmonary occlusion pressuresMild: mPAP ≥25 and <35 mmHgModerate: mPAP ≥35 and <45 mmHgSevere: mPAP ≥45 mmHgIncidence between 3–10% cirrhosis patients based on haemodynamic criteria; women are at 3x greater risk and it is more common in autoimmune liver diseaseThere is no clear association between the severity of liver disease or portal hypertension and the development of severe PPHT

Slide86

Monitoring and medical management of PPHT

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

The evidence base for pharmacological therapies in PPHT is limited

RecommendationScreening for PPHT should be via TDE in patients deemed potential recipients for TIPS or LTIn those with a positive screening test, right heart catheterization should be performedII-11In patients with PPHT who are listed for LT, echocardiography should be repeated on the waitlist (the specific interval is unclear)III1β-blockers should be stopped and varices managed by endoscopic therapy in cases of proven PPHTII-31Therapies approved for primary pulmonary arterial hypertension may improve exercise tolerance and haemodynamics in PPHT However, endothelin antagonists should be used with caution because of concerns over hepatic impairmentII-21TIPS should not be used in patients with PPHTII-31

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Slide87

Liver transplantation in PPHT

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Although severe PPHT has, historically, been a contraindication for LT, the advent of improved haemodynamic control (with agents such as IV prostacyclin) allows LT to be considered

RecommendationIf mPAP <35 mmHg and right ventricular function is preserved, LT should be consideredmPAP of ≥45 mmHg should be considered an absolute contraindication to LT irrespective of therapy appliedII-2III11Therapy to lower mPAP and improve right ventricular function should be commenced in patients with mPAP ≥35 mmHg Right ventricular function should be periodically evaluatedII-21MELD exception can be considered in patients with proven PPHT in whom targeted therapy fails to decrease mPAP <35 mmHg but does facilitate normalization of PVR to <240 dyn.s/cm-5 and right ventricular functionII-32MELD exception should be advocated in patients with proven PPHT of moderate severity (mPAP ≥35 mmHg) in whom targeted treatment lowers mPAP <35 mmHg and PVR <400 dyn.s/cm-5 II-21

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Slide88

Additional recommendations

Slide89

Portal hypertension gastropathy

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Often presents in patients with DCNatural history significantly influenced by the severity of liver disease and portal hypertension

RecommendationNSBB and iron supplementation and/or blood transfusion, when indicated, are recommended as first-line therapy for chronic haemorrhage from PHGI1In patients with transfusion-dependent PHG in whom NSBBs fail or are not tolerated, covered TIPS placement may be used in the absence of contraindicationsII-32Acute PHG bleeding may be treated with somatostatin analoguesor terlipressin but substantiating data are limitedI2

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Slide90

Gastric varices: classification, prevalence and risk

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

The Sarin classification is most commonly used for risk stratification and management of gastric varices

TypeDefinitionRelative frequencyOverall bleeding risk without treatmentGastro-oesophageal varices (GOV) GOV type 1OV extending below cardia into lesser curvatureOV extending below cardia into lesser curvature70%28%GOV type 2OV extending below cardia into fundusOV extending below cardia into fundus21%55%Isolated gastric varices (IGV) IGV type 1Isolated varices in the fundusIsolated varices in the fundus7%78%IGV type 2Isolated varices else in the stomach Isolated varices else in the stomach 2%9%

Slide91

Management of gastric varices

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Gastric varices are present in about 20% of patients with cirrhosis

RecommendationNSBBs are suggested for primary prevention of VH from GOV type 2 or IGV type 1III2Primary prevention for GOV type 1 follows the recommendations of oesophageal varices III2Acute gastric VH should be treated medically, like oesophageal VHCyanoacrylate is the recommended endoscopic haemostatic treatment for cardiofundal varices (GOV type 2 or IGV type 1)II12TIPS with potential embolization efficiently controls bleeding and prevents re-bleeding in fundal VH (GOV type 2 or IGV type 1) and should be considered in appropriate candidatesII-21Selective embolization (BRTO/BATO) may also be used to treat bleeding from fundal varices associated with large gastro/splenorenal collaterals, although more data is requiredIII2

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Slide92

Diagnosis of SBP

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Both neutrophil count and culture results should be taken into account

RecommendationPatients with bacterascites (neutrophil count <250/mm3 but positive bacterial culture) exhibiting signs of systemic inflammation or infection should be treated with antibioticsOtherwise, the patient should undergo a second paracentesisIf the culture results come back positive again, regardless of the neutrophil count, the patient should be treatedII-2III11Spontaneous bacterial pleural empyema diagnosed by:Positive pleural fluid culture and neutrophil count >250/mm3 orNegative pleural fluid culture and neutrophil count >500/mm3 in the absence of pneumoniaII-21Secondary bacterial peritonitis should be suspected in case of multiple organisms on ascitic culture, very high ascitic neutrophil count and/or high ascitic protein concentration, or in those patients with an inadequate response to therapyPatients with suspected secondary bacterial peritonitis should undergo prompt CT scanning and early considerations for surgeryIII1

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Slide93

Empirical antibiotic treatment of SBP or SBE

*In areas with a high prevalence of vancomycin-resistant enterococciAdapted from Jalan R, et al. J Hepatol 2014;60:1310–24;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

SBP or SBE

NosocomialSBP or SBE

Healthcare-associatedSBP or SBE

Community-acquired SBP or SBE

Carbapenem alone or + daptomycin, vancomycin (or linezolid*) if high prevalence of MDR Gram+ bacteria or sepsis

AREA DEPENDENT:Like nosocomialinfections if highprevalence of MDROsor if sepsis

3rd-gencephalosporin or piperacillin-tazobactam

Slide94

AKI management

EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Investigation and management should begin immediately

Recommendation

Investigate AKI cause as soon as possible to prevent AKI progressionManagement should begin immediately (even absent obvious cause) Screening and treatment of infection are most importantII-21Diuretics and/or β-blockers as well as other drugs that could be associated with the occurrence of AKI such as vasodilators, NSAIDs and nephrotoxic drugs should be immediately stoppedII-21Volume replacement should be used in accordance with the cause and severity of fluid lossesII-21In case of no obvious cause of AKI, AKI stage >1A or infection-induced AKI: 20% albumin solution should be used at a dose of 1 g /kg of body weight (maximum of 100 g of albumin) for 2 consecutive daysIII1In patients with AKI and tense ascites, therapeutic paracentesis should be associated with albumin infusion even when a low volume of ascitic fluid is removedIII1

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Slide95

HRS outside AKI criteria

*Formerly known as HRS type IIEASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

HRS-NAKI has an impaired response to vasorestrictors

RecommendationVasoconstrictors and albumin are not recommended the treatment of HRS outside the criteria of AKI (HRS-NAKI)* Terlipressin plus albumin is effective in the treatment of HRS-NAKI, but recurrence after withdrawal of treatment is the norm, and controversial data exist on the impact of the treatment on long-term clinical outcome, particularly from the perspective of LTI1

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Grade of recommendation

Slide96

Previous CLIF prognostic anddiagnostic scores

*Bold text indicates the diagnostic criteria for organ failures; †μg/kg/min1. Jalan R, et al. J Hepatol 2015;62:831–40;EASL CPG decompensated cirrhosis. J Hepatol 2018;doi: 10.1016/j.jhep.2018.03.024

Sequential Organ Failure Assessment (SOFA) scoreOrgan/system*01234Liver (bilirubin mg/dl)<1.2≥1.2–<2.0≥2.0–<6.0≥6.0–<12.0≥12.0Kidney (creatinine mg/dl)<1.2≥1.2–<2.0≥2.0–<3.5≥3.5–<5.0≥5.0Cerebral (HE grade)NO HEGrade IGrade IIGrade IIIGrade IVCoagulation (INR and PLT count)<1.1≥1.1–<1.25≥1.25–<1.5≥1.5–<2.5≥2.5 or PLT≤20,000/mm3Circulation (MAP mmHg and vasopressors†)≥70<70Dopamine ≤5 or dobutamine or terlipressinDopamine >5 or A ≤0.1 or NA ≤0.1Dopamine >15or A >0.1 or NA >0.1LungsPaO2/FiO2, or>400>300–≤400>200–≤300>100–≤200≤100SpO2/FiO2>512>357–≤512>214–≤357>89- ≤214≤89

CLIF-C Acute decompensation score1*10 x [0.03 x Age + 0.66 x Ln(Creatinine) + 1.71 x Ln(INR) + 0.88 x Ln(WBC) 0.05 x Sodium + 8]