End of Life Care in Liver Disease Dr Allister Grant Consultant Hepatologist Leicester Liver Unit East Leicestershire and Rutland CCG PLT 3rd Sept.

End of Life Care End of Life Care in Liver Diseasein Liver Disease

Dr Allister GrantDr Allister Grant

Consultant HepatologistConsultant Hepatologist

Leicester Liver UnitLeicester Liver Unit

East Leicestershire and Rutland CCG PLT 3rd SeptEast Leicestershire and Rutland CCG PLT 3rd Sept

Death rates for liver diseaseDeath rates for liver disease

FactsFacts

Liver disease is the 5th largest cause of Liver disease is the 5th largest cause of death in the U.K. death in the U.K.

The average age of death from liver disease The average age of death from liver disease is 59 years, compared to 82-84 years for is 59 years, compared to 82-84 years for heart & lung diseaseheart & lung disease

UK is one of few developed nations with an UK is one of few developed nations with an upward trend in mortality.upward trend in mortality.

Expanded Portal Tracts(Blue)

Prognosis- Child Pugh ScorePrognosis- Child Pugh Score

ScoreScore 1 1 2 2 3 3

EncephalopathyEncephalopathy 0 0 I/II I/II III/IVIII/IV

Ascites Ascites Absent Absent Mild-moderate Mild-moderate SevereSevere

Bilirubin (µmol/l) Bilirubin (µmol/l) <34 <34 34–51 34–51 >51>51

Albumin (g/l) Albumin (g/l) >35>35 28–35 28–35 <28<28

INR INR <1.3 <1.3 1.3–1.5 1.3–1.5 >1.5>1.5

Child-Pugh classChild-Pugh class A A 6 6

B = 7–9B = 7–9

C C 10 10

PrognosisPrognosis

1 Year Survival1 Year Survival

– – Child Pugh A Child Pugh A 80 - 100%80 - 100%

– – Child Pugh B Child Pugh B 60 - 80%60 - 80%

– – Child Pugh C Child Pugh C 35 - 45%35 - 45%

Complications of End Stage Liver Complications of End Stage Liver DiseaseDisease

Decompensated CirrhosisDecompensated Cirrhosis Variceal bleedingVariceal bleeding AscitesAscites EncephalopathyEncephalopathy

Other Other Sepsis (SBP)Sepsis (SBP) Hepatorenal syndromeHepatorenal syndrome Hepatocellular carcinomaHepatocellular carcinoma

Disease ProgressionL

iver

fu

nct

ion

100%

Cirrhosis

Liver FailureTransplantDeathYears

A

B

C

Disease ProgressionL

iver

fu

nct

ion

50%

Cirrhosis

Liver FailureTransplantDeath

Months

Portal Portal CirculationCirculation

Oesophageal varicesOesophageal varices

Management of Bleeding VaricesManagement of Bleeding Varices

PreventionPrevention

ResuscitationResuscitation

Endoscopy -Endoscopy - Band LigationBand LigationSclerotherapySclerotherapy

Pharmacotherapy- TerlipressinPharmacotherapy- Terlipressin

Balloon TamponadeBalloon Tamponade

TIPS/TransplantationTIPS/Transplantation

Oesophageal varicesOesophageal varices

Bleeding Gastric VaricesBleeding Gastric Varices

Variceal BanderVariceal Bander

Variceal Band LigationVariceal Band Ligation

Variceal Band LigationVariceal Band Ligation

Variceal Bleeding in Palliative CareVariceal Bleeding in Palliative Care

May be occult and present as encephalopathyMay be occult and present as encephalopathy--GastricGastric-Duodenal-Duodenal-Colonic-Colonic

Resuscitate if appropriateResuscitate if appropriate Correct coagulopathyCorrect coagulopathy Give Terlipressin if known varicesGive Terlipressin if known varices

As effective as balloon tamponadeAs effective as balloon tamponade As effective as endoscopic therapyAs effective as endoscopic therapy

?Give PPI?Give PPI / sucralfate / tranexamic acid/ sucralfate / tranexamic acid Colonic varices- rectal balloon tamponadeColonic varices- rectal balloon tamponade

AscitesAscites

Causes of Ascites Causes of Ascites

20% of patients with ascites have a non hepatic cause20% of patients with ascites have a non hepatic cause

5% of patients with hepatic ascites have a second cause5% of patients with hepatic ascites have a second cause

Peritoneal disease- carcinomatosis, TBPeritoneal disease- carcinomatosis, TBHeart failureHeart failureDiabetic nephropathyDiabetic nephropathyHypoalbuminaemia of other causesHypoalbuminaemia of other causes

The Development of AscitesThe Development of Ascites

Peripheral arterial dilatation

Reduced effective blood volume Hypoalbuminaemia

Activation of renin-angiotensin-aldosterone systemSympathetic nervous systemADH

Na retention &Water retention

Low urinary NaDilutional hyponatraemia

AscitesSchrier et al Hepatol

Plasma volume expansion

NaCl

Ascites and Oedema

General ManagementGeneral Management

Hepatic Ascites and OedemaHepatic Ascites and Oedema

Salt restrictionSalt restriction

DiureticsDiureticsspironolactonespironolactonefrusemidefrusemide

Water restriction if sodium < 125 mmolWater restriction if sodium < 125 mmol

ParacentesisParacentesisdiagnostic (SBP, tumour)diagnostic (SBP, tumour)therapeutic (Total vs partial + therapeutic (Total vs partial +

colloids)colloids) Daily weightDaily weight

Sampling of AscitesSampling of Ascites

Coagulopathy is not a contraindication to diagnostic paracentesis Coagulopathy is not a contraindication to diagnostic paracentesis (unless clinically evident fibrinolysis or DIC)(unless clinically evident fibrinolysis or DIC)

FFP/platelets are not requiredFFP/platelets are not required

In uncomplicated hepatic ascites request cell count and [Albumin] In uncomplicated hepatic ascites request cell count and [Albumin]

PMN>250 cells/mmPMN>250 cells/mm33 indicates SBP indicates SBP

transudate/exudate <25g/L/>25g/Ltransudate/exudate <25g/L/>25g/L

serum/ascites albumin gradient >11g/L= Portal Hypserum/ascites albumin gradient >11g/L= Portal Hyp

Runyon et al Ann Int Med 1992

Spontaneous Bacterial PeritonitisSpontaneous Bacterial Peritonitis

Definition-Definition-

““SBP is a bacterial infection of ascitic fluid which arises in the SBP is a bacterial infection of ascitic fluid which arises in the absence of any other source of sepsis within the peritoneum absence of any other source of sepsis within the peritoneum or adjacent tissues”or adjacent tissues”

PMN>250 cells/mmPMN>250 cells/mm33

Mortality rate similar to that of a variceal bleed (20-40%)Mortality rate similar to that of a variceal bleed (20-40%)

Secondary prevention of SBPSecondary prevention of SBP Patients who survive SBP have a 1y recurrence rate of 40-Patients who survive SBP have a 1y recurrence rate of 40-

70%70%

Norfloxacin 400mg/day reduces recurrence from 68% to 20% Norfloxacin 400mg/day reduces recurrence from 68% to 20%

Locally we use Septrin 960mg od Mon-FriLocally we use Septrin 960mg od Mon-Fri

Median survival of these patients is 9moMedian survival of these patients is 9mo

These patients should be considered for liver transplantation/ These patients should be considered for liver transplantation/ GSFGSF

Sepsis in CirrhosisSepsis in Cirrhosis

Incidence- Incidence-

1% of 1% of allall admissions to hospital are due to sepsis admissions to hospital are due to sepsis

30-50% of cirrhotic patients admitted to hospital due to 30-50% of cirrhotic patients admitted to hospital due to sepsissepsis

Once admitted 15-35% of cirrhotics develop infection Once admitted 15-35% of cirrhotics develop infection (c.f. 5-7% general hospital population)(c.f. 5-7% general hospital population)

General ManagementGeneral Management

EncephalopathyEncephalopathy

Treat precipitantsTreat precipitants• • SepsisSepsis• • GI bleedGI bleed• • Medications (over-diuresis)Medications (over-diuresis)

• Stop sedatives, hypnotics, opiatesStop sedatives, hypnotics, opiates• ConstipationConstipation

Lactulose (NG/PR/PO)Lactulose (NG/PR/PO)

Metronidazole/ Rifaximin/ neomycin -deafnessMetronidazole/ Rifaximin/ neomycin -deafness

Acute Kidney Injury in CLDAcute Kidney Injury in CLD

Exclude urinary infectionExclude urinary infection Exclude obstructive uropathyExclude obstructive uropathy Trial of volumeTrial of volume Avoid nephrotoxinsAvoid nephrotoxins

• • NSAIDsNSAIDs

• • IV contrastIV contrast Avoid over-diuresisAvoid over-diuresis Avoid hypotensionAvoid hypotension Hepatorenal Failure carries grave prognosisHepatorenal Failure carries grave prognosis

Hepatorenal SyndromeHepatorenal Syndrome Hepatorenal Syndrome is a severe complication of end Hepatorenal Syndrome is a severe complication of end

stage liver disease associated with an 80%-95% stage liver disease associated with an 80%-95% mortality at 2 weeks.mortality at 2 weeks.

The only interventions that have been shown to improve The only interventions that have been shown to improve survival are liver transplantation, the vasopressin survival are liver transplantation, the vasopressin analogues and TIPSanalogues and TIPS

Type 1 (Acute)Type 1 (Acute)

Type 2 (Chronic)Type 2 (Chronic)

HRS SurvivalHRS Survival

Gines et al Lancet 2003

The Development of HRSThe Development of HRS

Reduced effective blood volume

Activation of renin-angiotensin-aldosterone systemSympathetic nervous systemADH

Na retention &Water retention

Low urinary NaDilutional hyponatraemia

AscitesSchrier et al Hepatol

Plasma volume expansion

Renal vasoconstrictionReduced GFR

NSAIDAminoglycosides

Diuretics Sepsis

NaCl

Ascites and OedemaHRS

Increases TerlipressinSplanchnicvasoconstriction

↓↓ ↓

X

Peripheral arterial dilatation

↑Renal Perfusion

Albumin

Hepatocellular CarcinomaHepatocellular Carcinoma

All UK cirrhotic patients undergo 6 monthly All UK cirrhotic patients undergo 6 monthly HCC surveillance with USS and AFPHCC surveillance with USS and AFP

AFP >400 is diagnostic of HCCAFP >400 is diagnostic of HCC

Focal lesion – MRI/triple phase CTFocal lesion – MRI/triple phase CT Arterialised nodule, washout in venous phaseArterialised nodule, washout in venous phase

Surveillance in Cirrhosis Surveillance in Cirrhosis

Surveillance for HepatomaSurveillance for Hepatoma

6 monthly AFP and USS

PruritisPruritis

After exclusion of other causes of Itching considerAfter exclusion of other causes of Itching consider

Biliary ObstructionBiliary Obstruction PBC in the absence of JaundicePBC in the absence of Jaundice Cholestasis/JaundiceCholestasis/Jaundice DrugsDrugs

PruritisPruritis

Biliary ObstructionBiliary Obstruction

StonesStones StrictureStricture 11 or 2 or 2 Tumour Tumour NodesNodes

MRCPMRCP

ERCPERCP

ERCPERCP

Drugs for PruritisDrugs for Pruritis Non-Specific ManagementNon-Specific Management

Lubricants/Topical agentsLubricants/Topical agents Reduce irritationReduce irritation Prevent scratchingPrevent scratching Systemic Anti-pruriticsSystemic Anti-pruritics

• AtaraxAtarax• Fexofenidine etcFexofenidine etc

Liver DiseaseLiver Disease CholestyramineCholestyramine Ursodeoxycholic acidUrsodeoxycholic acid RifampicinRifampicin Opioid antagonists, naloxone , naltrexoneOpioid antagonists, naloxone , naltrexone OndansetronOndansetron

Other TreatmentsOther Treatments

• Ultraviolet light exposureUltraviolet light exposure

• Plasmapheresis Plasmapheresis

• Liver TransplantationLiver Transplantation

FutureFuture Liver disease is an important cause of mortality in the Liver disease is an important cause of mortality in the

U.K. U.K. In 2000 it killed more men than Parkinson’s disease In 2000 it killed more men than Parkinson’s disease and more women than cancer of the cervix.and more women than cancer of the cervix.

~1% of population HCV positive~1% of population HCV positive

Mortality from Alcoholic liver disease doubled in 10 yearsMortality from Alcoholic liver disease doubled in 10 years

Incidence of liver cancer has doubled in 10 yearsIncidence of liver cancer has doubled in 10 years

4% of the population have abnormal liver function4% of the population have abnormal liver function

50% people with colorectal cancer develop liver 50% people with colorectal cancer develop liver metastases, 20% resectablemetastases, 20% resectable

The EndThe End“All right, let's not panic.

I'll make the money by selling one of my livers.I can get by with one “

Doh!