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

Death rates for liver disease

Facts  Liver disease is the 5th largest cause of death in the U.K.  The average age of death from liver disease is 59 years, compared to years for heart & lung disease  UK is one of few developed nations with an upward trend in mortality.

Expanded Portal Tracts (Blue)

Prognosis- Child Pugh Score Score Encephalopathy 0 I/II III/IV Ascites Absent Mild-moderate Severe Bilirubin (µmol/l) 51 Albumin (g/l) >3528– –35 <28 INR 1.5 Child-Pugh classA  6 B = 7–9 C  10

Prognosis 1 Year Survival – Child Pugh A % – Child Pugh B % – Child Pugh C %

Complications of End Stage Liver Disease  Decompensated Cirrhosis Variceal bleeding Variceal bleeding Ascites Ascites Encephalopathy Encephalopathy  Other Sepsis (SBP) Sepsis (SBP) Hepatorenal syndrome Hepatorenal syndrome Hepatocellular carcinoma Hepatocellular carcinoma

Disease Progression Liver function 100% Cirrhosis Liver Failure Transplant Death Years A B C

Disease Progression Liver function 50% Cirrhosis Liver Failure Transplant Death Months

Portal Circulation

Oesophageal varices

Management of Bleeding Varices  Prevention  Resuscitation  Endoscopy -Band Ligation Sclerotherapy  Pharmacotherapy- Terlipressin  Balloon Tamponade  TIPS/Transplantation

Oesophageal varices

Bleeding Gastric Varices

Variceal Bander

Variceal Band Ligation

Variceal Bleeding in Palliative Care  May be occult and present as encephalopathy - Gastric -Duodenal-Colonic  Resuscitate if appropriate  Correct coagulopathy  Give Terlipressin if known varices As effective as balloon tamponade As effective as balloon tamponade As effective as endoscopic therapy As effective as endoscopic therapy  ?Give PPI/ sucralfate / tranexamic acid  Colonic varices- rectal balloon tamponade

Ascites

Causes of Ascites 20% of patients with ascites have a non hepatic cause 5% of patients with hepatic ascites have a second cause Peritoneal disease- carcinomatosis, TB Heart failure Diabetic nephropathy Hypoalbuminaemia of other causes

The Development of Ascites Peripheral arterial dilatation Reduced effective blood volume Hypoalbuminaemia Activation of renin-angiotensin-aldosterone system Sympathetic nervous system ADH Na retention & Water retention Low urinary Na Dilutional hyponatraemia Ascites Schrier et al Hepatol Plasma volume expansion NaCl Ascites and Oedema

General Management Hepatic Ascites and Oedema  Salt restriction  Diuretics spironolactonefrusemide  Water restriction if sodium < 125 mmol  Paracentesis diagnostic (SBP, tumour) therapeutic (Total vs partial + colloids)  Daily weight

Sampling of Ascites  Coagulopathy is not a contraindication to diagnostic paracentesis (unless clinically evident fibrinolysis or DIC)  FFP/platelets are not required  In uncomplicated hepatic ascites request cell count and [Albumin] PMN>250 cells/mm 3 indicates SBP transudate/exudate 25g/L serum/ascites albumin gradient >11g/L= Portal Hyp Runyon et al Ann Int Med 1992

Spontaneous Bacterial Peritonitis Definition- “SBP is a bacterial infection of ascitic fluid which arises in the absence of any other source of sepsis within the peritoneum or adjacent tissues” PMN>250 cells/mm 3 Mortality rate similar to that of a variceal bleed (20-40%)

Secondary prevention of SBP  Patients who survive SBP have a 1y recurrence rate of 40-70%  Norfloxacin 400mg/day reduces recurrence from 68% to 20%  Locally we use Septrin 960mg od Mon-Fri  Median survival of these patients is 9mo  These patients should be considered for liver transplantation/ GSF

Sepsis in Cirrhosis  Incidence- 1% of all admissions to hospital are due to sepsis 30-50% of cirrhotic patients admitted to hospital due to sepsis Once admitted 15-35% of cirrhotics develop infection (c.f. 5-7% general hospital population)

General Management Encephalopathy Treat precipitants Sepsis Sepsis GI bleed GI bleed Medications (over-diuresis) Medications (over-diuresis) Stop sedatives, hypnotics, opiatesStop sedatives, hypnotics, opiates ConstipationConstipation Lactulose (NG/PR/PO) Metronidazole/ Rifaximin/ neomycin -deafness

Acute Kidney Injury in CLD  Exclude urinary infection  Exclude obstructive uropathy  Trial of volume  Avoid nephrotoxins NSAIDs NSAIDs IV contrast IV contrast  Avoid over-diuresis  Avoid hypotension  Hepatorenal Failure carries grave prognosis

Hepatorenal Syndrome  Hepatorenal Syndrome is a severe complication of end stage liver disease associated with an 80%-95% mortality at 2 weeks.  The only interventions that have been shown to improve survival are liver transplantation, the vasopressin analogues and TIPS  Type 1 (Acute)  Type 2 (Chronic)

HRS Survival Gines et al Lancet 2003

The Development of HRS Reduced effective blood volume Activation of renin-angiotensin-aldosterone system Sympathetic nervous system ADH Na retention & Water retention Low urinary Na Dilutional hyponatraemia Ascites Schrier et al Hepatol Plasma volume expansion Renal vasoconstriction Reduced GFR NSAID Aminoglycosides Diuretics Sepsis NaCl Ascites and Oedema HRS Increases Terlipressin Splanchnic vasoconstriction ↓ ↓↓ X Peripheral arterial dilatation ↑ Renal Perfusion Albumin

Hepatocellular Carcinoma  All UK cirrhotic patients undergo 6 monthly HCC surveillance with USS and AFP  AFP >400 is diagnostic of HCC  Focal lesion – MRI/triple phase CT Arterialised nodule, washout in venous phase Arterialised nodule, washout in venous phase

Surveillance in Cirrhosis  Surveillance for Hepatoma 6 monthly AFP and USS

Pruritis After exclusion of other causes of Itching consider  Biliary Obstruction  PBC in the absence of Jaundice  Cholestasis/Jaundice  Drugs

Pruritis  Biliary Obstruction Stones Stones Stricture Stricture 1  or 2  Tumour 1  or 2  Tumour Nodes Nodes

MRCP

ERCP

ERCP

Drugs for Pruritis  Non-Specific Management Lubricants/Topical agents Lubricants/Topical agents Reduce irritation Reduce irritation Prevent scratching Prevent scratching Systemic Anti-pruritics Systemic Anti-pruritics AtaraxAtarax Fexofenidine etcFexofenidine etc  Liver Disease Cholestyramine Cholestyramine Ursodeoxycholic acid Ursodeoxycholic acid Rifampicin Rifampicin Opioid antagonists, naloxone, naltrexone Opioid antagonists, naloxone, naltrexone Ondansetron Ondansetron

Other Treatments Ultraviolet light exposure Ultraviolet light exposure Plasmapheresis Plasmapheresis Liver Transplantation Liver Transplantation

Future  Liver disease is an important cause of mortality in the U.K. In 2000 it killed more men than Parkinson’s disease and more women than cancer of the cervix.  ~1% of population HCV positive  Mortality from Alcoholic liver disease doubled in 10 years  Incidence of liver cancer has doubled in 10 years  4% of the population have abnormal liver function  50% people with colorectal cancer develop liver metastases, 20% resectable

The 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!