Presentation title and subject Dying for a drink:

alcohol and the liver Dr. Talal Valliani Consultant Hepatologist/Gastroenterologist Southmead Hospital, North Bristol NHS Trust

Outline  Prevalence  Impact  On the liver  On the patient  On the service

 Management  Alcoholic hepatitis  Liver care bundle  ACLF

Prevalence NHS Atlas of Variation in Healthcare for people with liver disease, 2013

“the only major cause of mortality and morbidity which is on the increase in England...” CMO, 2011

Prevalence

NHS Atlas of Variation in Healthcare for people with liver disease, 2013

“…whilst decreasing amongst our European neighbours” CMO, 2011

Prevalence - alcohol attributable DALYs

Rehm, Lancet 2009

Prevalence in the UK: alcohol-related deaths

Prevalence: top 5 alcohol related causes of death

England and Wales, 2012 Office for National Statistics, Feb 2014

:Prevalence All ages, DSR per 100,000 population – Males & Females – 2009/10 – by SHA 2,000

1,888

1,807

1,800 1,600 1,423 1,417 1,415 1,400

All Ages DSR per 100,000

1,400 1,200

1,346 1,284 1,207 1,201

1,076

1,053

1,045

1,000 812

800

799

790

783

742

725

691

672 609

600 400 200

Females

Source: Local Alcohol Protocols for England. NWPHO, 2011

Males

South Central

East Of England

South East Coast

South West

East Midlands

England

Yorkshire & Humber

West Midlands

London

North West

North East

South Central

East Of England

South East Coast

South West

London

East Midlands

England

Yorkshire & Humber

West Midlands

North West

North East

0

Prevalence: impact of age

Liver transplant for ALD in the UK

April 2011-March 2012, NHSBT data

Impact  Pathogenesis  Symptoms  Screening

Normal liver

Steatosis Alcoholic hepatitis

Fibrosis

Cirrhosis

HCC Death

‘Environmental’ susceptibility  Dose-relationship (Becker et al, Hepatology 1996; Bellentani et al, Gut 1997)  >60g/d; >120g/d

 Type of drink? Debated/Unclear  Pattern  Binge/heavy drinking; Outside mealtimes

 Diet-related? Obesity is most significant factor  Single most important risk factor for progression in heavy drinkers (Naveau et al, 1997; Raynard et al 2002)

Identifying those with advanced ALD  Liver disease is “silent” until end-stages  Signs/symptoms of cirrhosis

 Abnormal liver tests (↑ALT/AST, ↑GGT) – not particularly helpful/prognostic in ALD  Prognostic markers (↓Alb, ↓plt, ↑BR, ↑PT) – usually endstage/advanced cirrhosis  Abnormal liver imaging ?fatty liver ??cirrhosis  Recent interest in identifying those who have progressive liver disease, before end-stage

Screening & Brief Intervention  Screening adult population for risky alcohol consumption and providing feedback and brief advice results in a reduction in the amount of alcohol they consume (Kaner et al 2013)  NICE PH 24 recommends alcohol screening should be integral part of healthcare practice  Best current evidence from studies in primary care and ED with less evidence on the feasibility of routine implementation in other healthcare settings

How many units in….

Screening Tool

Management  Alcohol withdrawal  Nutrition

 Alcoholic hepatitis  Acute on chronic liver failure

Schematic Diagram of Alcohol Withdrawal Syndrome (McKinley, 2005)

CNS excitation

DTs Short term effect of alcohol

Long -term effect of alcohol

Seizures

(Mild) AWS

Withdrawal

Cessation of drinking

120 hours

96 hours

72 hours

48 hours

24 hours

0 hours

Time line

Pharmacological alcohol withdrawal   

Meta-analyses: BDZ are effective in reducing withdrawal severity, incidence of DTs and seizures Cochrane systematic review: BDZ better than placebo in preventing seizures; trend in favour BDZ vs others Fixed dosing – predetermined over specified number of days; ‘conventional wisdom’  but many patients undergo withdrawal with no pharmacotherapy  may involve unnecessary sedation and hospitalisation



Symptom triggered – by signs/symptoms  Allows individualised approach  Regular assessment and monitoring using clinical experience or a clinical tool (eg CIWA-Ar)

Pharmacological management Acamprosate, naltrexone and disulfiram – all in NICE CG115.  Acamprosate – avoid in severe hepatic impairment.  Naltrexone – avoid in acute hepatitis, hepatic failure or severe impairment.  Disulfiram – use with caution in hepatic impairment

Alcohol Guideline  Screen all admissions with AUDIT-C  If ≥ 5, refer to the ASN team (Brief intervention and full AUDIT) and complete the alcohol protocol     

History as per NCEPOD recommendations FAST score to determine who needs pharmacological detoxification CIWA vs. symptom triggered Lorazepam vs. Chlordiazepoxide Thiamine guideline

Alcoholic hepatitis  Progressive inflammatory liver injury associated with long-term heavy intake of ETOH  Prevalence in Western society - approximately 25-30%  20-60 yrs  F>M

Alcoholic hepatitis     

Mild alcoholic hepatitis benign disorder Moderate/Severe Alcoholic hepatitis (hepatic encephalopathy, jaundice, or coagulopathy)  High mortality 30-day mortality rate in patients hospitalized  15%  Maddrey > 32 (severe) – up to 50% On-going ETOH  persists and progresses to cirrhosis ETOH cessation  Resolves slowly over weeks to months  Sometimes without permanent sequelae  Often with residual cirrhosis

Alcoholic hepatitis  Maddrey score    

Predicts the prognosis of alcoholic hepatitis Prothrombin Time/Bilirubin (> 80) DF = (4.6 × PT prolongation) + total serum bilirubin in mg/dL Value >/=32  Indicates severe hepatitis  Mortality 30-50%  Indication for treatment with ???

Alcoholic hepatitis  STOPAH trial  Prednisolone improves 28 day mortality (13.9% compared to 18%) but no further impact  Infections twice as common in people who start Prednisolone  Reducing alcohol misuse just as bad as continuing to misuse

 Future….  GCSF  NAC/Pred  NAC/GCSF

Acute Decompensation  In somebody with chronic liver disease  Ascites/variceal haemorrhage/HE/bacterial infection  No organ failure

Acute on chronic liver failure  ‘Acute deterioration (jaundice, HE +/- or HRS) of pre-existing, well compensated, chronic liver disease, usually related to a precipitating event and associated with increased mortality at 3 months due to multisystem organ failure (renal)’  Liver/Kidney/CVS/CNS/Haem/Resp

Management - Liver Care Bundle  Decompensation      

Jaundice Increasing ascites HE Renal impairment Sepsis/hypovolaemia GI bleeding

Management - Liver Care Bundle 

Causes         

GIB (variceal and non variceal) - antibiotics Infection (SBP) Alcoholic hepatitis PVT HCC Drugs (alcohol/opiates/NSAIDS) Ischaemia Dehydration Constipation

Management - Liver Care Bundle

Management - Liver Care Bundle

Management - NCEPOD  

  

Deterioration in renal function should not be assumed to be hepatorenal syndrome, as other potential causes are often present and should be actively excluded Patients with ARLD who have deteriorating renal function should have diuretics stopped and have IV fluids even if peripheral oedema and ascites are present If ascites is present in patients presenting with decompensated ARLD, a diagnostic ascitic tap should be performed - coagulopathy is not a contraindication All patients with ARLD, who present with gastrointestinal bleeding, should be offered antibiotics and terlipressin until the outcome of the endoscopy is known Escalation of care should be actively pursued for patients with ARLD, who deteriorate acutely and whose background function is good

Scores  Hospital mortality of cirrhotic patients in ICU variable  40% - > 80%  Policies about admission to ICU  Access to salvage transplantation

 Need to identify patients who are most likely to benefit from aggressive treatment

Scores  MELD (Bili/INR/Creatinine)  CTP (Bili/albumin/INR/ascites/HE)  Don’t take into account other organ/system failures (apart from renal)  Not accurate at identifying sub group of patients who are likely to survive ICU admission

Scores 

CLIF organ failure score  Based on organ failures with cut off values specifically identified in cirrhotic patients  Used to define grade of ACLF      

Liver (Bilirubin) Renal (Creatinine/RRT/HRS) Neuro (grade of HE) Haem (INR) CVS (MAP/inotropes) Resp (SpO2)

CLIF Organ Failure score  Helps to determine grade of ACLF      

Liver (Bilirubin) Renal (Creatinine/RRT/HRS) Neuro (grade of HE) Haem (INR) CVS (MAP/inotropes) Resp (SpO2)

ACLF classification No ACLF

28 and 90 day mortality

No organ failure Single organ failure with Cre