Acute Liver Problems

Dr. Martin James PhD FRCP Nottingham University Hospitals HST GIM Teaching December 2016 Priorities for liver disorders?

• What will I see on the acute take?

• Which patients need urgent management?

• What are the priorities for treatment?

• What’s new in liver disease? Clinical Priorities

• Decompensated chronic liver disease - 80% – Variceal haemorrhage – Ascites & infection – Encephalopathy – Hepatorenal syndrome • Acute liver failure - <5% • Biliary sepsis - 15% BACKGROUND Lifestyle & liver disease?

Alcohol NAFLD

Viral Hepatitis Hepatitis C virus (HCV) Annual diagnosis

SVR (cure) in 2016 1700 440 Annual Treatment 16,000 460

250 Annual Incidence 900 Cure 2012

Adapted from HPA/Roche 2012 New HCV therapies Accessing HCV therapy? Alcohol consumption

Caner Research UK 2010 Deaths per 10 000 man-years 10 15 20 25 30 Death between fromother and Death years 35-59cirrhosis between 0 5 1950 cancer Lung Cirrhosis 1960 Stroke 1970 Men Year 1980 1990 disease heart Coronary 2000 2010 1952-2009

Deaths per 10 000 woman-years 20 25 30 10 15 0 5 1950 Cirrhosis Bhala, FosterBhala,2013 BMJ & Aithal. 1960 disease heart Coronary Stroke 1970 selected diseases: UKdiseases: selected W omen Year 1980 1990 cancer Breast 2000 2010 Silly Money?

Prevention

Cure Preventing liver deaths?

NHS Atlas of Liver disease 2013 WHICH PATIENTS NEED URGENT MANAGEMENT? In-patient jaundice

Biliary obstruction

Alcohol-related liver disease

Other liver diseases, drugs, infection, cancers Clinical Priorities

• Decompensated chronic liver disease – Variceal haemorrhage – Ascites & infection – Encephalopathy – Hepatorenal syndrome • Acute liver failure • Biliary sepsis Decompensated Cirrhosis

• Jaundice

• Bleeding Cirrhosis • Ascites “bundle” & consider assessment for • Encephalopathy transplantation • Hepatorenal syndrome Cause of decompensation?

• Sepsis • Also consider: – Ascites – Head injury – biliary – Drug ingestion/ toxicity – chest – diuretics – UTI – Electrolytes disturbance – CNS – Hypoglycaemia – skin – Constipation • GI Bleeding – dehydration • Progression of CLD – HCC development DKA, MI etc – PV thrombosis – The golden 24 hours

• Implementation of the BSG/BASL Decompensated Cirrhosis Care Bundle in acute medicine:

• NUH local experience feedback

• P.Thiagarajan, C.Peal, D.Gunn, M.James • October 2015

Chronic Liver Disease by Aetiology

Baseline Audit: Post-intervention Audit: June 2015 September 2015 3% 3% 4% 4% 7% 7%

Alcohol Excess Alcohol Excess, n (%) NAFLD NAFLD, n (%) 14% Viral Hepatitis 17% Viral Hepatitis, n (%) 69% Autoimmune Autoimmune 72% Unknown Unknown Cause for decompensation Sepsis, n (%)

23% Upper GI bleeding, n (%)

Dehydration, n (%) 0% 3% 47% Baseline (n=30) Drugs, n (%) 7% Hepatocellular carcinoma, n (%) 20% Unknown, n (%)

Sepsis, n (%)

24% Upper GI bleeding, n (%)

Post-intervention (n=29) 41% Dehydration, n (%)

3% Drugs, n (%) 4% 4% Hepatocellular carcinoma, n (%) Unknown, n (%) 24% Septic Screen Parameters

100.0 P=0.02 90.0

80.0 P=0.002 70.0

60.0

50.0 Percentage 40.0

30.0

20.0 +39% +15% +22% +65%

10.0

0.0 Blood cultures Urine Dipstick CXR Ascitic tap Baseline 26.7 53.3 53.3 23.5 Post-intervention 65.5 68.9 75.9 88.2 Suspected Variceal Haemorrhage 120.0

P=0.03 P=0.03 100.0

80.0

60.0 Percentage

+13% +16% +26% +21% 40.0 +33%

20.0

0.0 Terlipressin Antibiotics Fluid resuscitation Restrictive Transfusion Lactulose Baseline 66.7 60.0 66.7 60.0 68.0 Post-intervention 80.0 85.7 100.0 85.7 89.3 Bleeding & liver disease

• Resuscitation

• Vasopressors and antibiotics

• Correct coagulation (Platelets <50, INR>1.5, Fibrinogen <1.0) – biliary obstruction vs liver failure

• Identify source of bleeding

• Endoscopic therapy GI bleeding, antibiotics & mortality Soares-Weiser Cochrane Review 2002 Model for Endstage Liver Disease

MELD: Bilirubin, PT (INR) and creatinine Gut 2007 TIPS for varices

Hepatic vein

coils

TIPS

Portal vein

Early (≤72 hours) TIPS

Garcia-Pagan et al NEJM 2010 SX-Ella Danis Stent

Wright G et al Gastrointestinal Endoscopy 2010 Danis Stent Oesophagus post stent removal Secondary prophylaxis – oesophageal varices

Sharara et al NEJM 2001 Diagnostic ascitic tap

• Sterile • Anterior axillary line • 50mm cephalic from anterior superior iliac spine

• Samples for: WCC MC&S

(SAAG, cytology)

Serum-ascitic albumin gradient (SAAG)

• SAAG serum minus ascitic albumin

• High SAAG >11g/L

– LR+ for portal hypertension 4.6 (1.6-12.9)

– LR- for portal hypertension 0.06 (0.02-0.2) Wong JAMA 2008

Gines NEJM 2006 Spontaneous bacterial peritonitis (SBP)

• Increased bacterial translocation in cirrhosis – Usually gut organisms

• High ascitic neutrophils/ WCC (even without organism identified)

• Sample ascitic fluid aseptically – Neutrophils >250/mm 3, Total WCC>500/mm 3 – Culture fluid in blood culture bottles. GI bleed PPI? lung

urine ascites

TNF ααα LN IL-1 IL-6, IL-8 vasodilatation endotoxin nitric oxide Reduced renal perfusion

Hepatorenal syndrome Resistance C. difficile death Cefotaxime vs Cefotaxime & HAS Sort et al NEJM 1999

Outcome Cefotaxime Cefotaxime & 20% p value albumin Infection resolution 94% 98% 0.36 Urea (day 6) 12.8 7.8 0.03 Creatinine (day 6) 114.9 88.4 0.03 Sodium (day 6) 130 134 <0.001 MAP (mmHg) 79 80 0.71

Renal failure 33% 10% 0.002 Mortality In hospital 29% 10% 0.01

3 months 41% 22% 0.03

Clinical Priorities

• Decompensated chronic liver disease – Variceal haemorrhage – Ascites & infection – Encephalopathy – Hepatorenal syndrome • Acute liver failure • Biliary sepsis Acute liver failure (ALF)

• Potentially reversible consequence of severe liver injury

• Encephalopathy within weeks of the onset of first symptoms

• Absence of pre-existing liver disease Causes of acute liver failure

• Paracetamol 50%

• Hepatitis B 10%

• Hepatitis A/E 5%

• Other drugs 10%

• Cryptogenic (non-A, non-B) 20% Drugs associated with liver injury

• Paracetamol • Amoxycillin-clavulinic acid • Flucloxacillin • Nitrofurantoin • Statins • Isoniazid • Propythiouricil Other causes of ALF

• Vascular liver diseases – Budd Chiari syndrome – Ischaemic liver injury • Malignant infiltration • Autoimmune hepatitis • Acute fatty liver of pregnancy • Wilson’s disease Clinical case

ALT Clinical case - ALT

Bili PT

Albumin Outcome Prediction - KCH criteria Paracetamol pH <7.3 (alone)

Or all 3 of: Grade III to IV encephalopathy PT>100 seconds Creatinine >300 µmol/L

(lactate >3.0 mmol/L after resuscitation)

Non-paracetamol PT>100 seconds

Or any 3 of: Age <10 or >40 years Bad aetiology (NANB, Drugs) Jaundice to encephalopathy >7 days PT > 50s Bilirubin > 300 µmol/L Take home messages - ALF

• Sick patients; may deteriorate rapidly

• Resuscitate, assess patient and numbers

• Transfer to AICU/ liver unit – encephalopathy, rising INR, hypotension or ARF, sepsis, hypoglycaemia or bleeding

• Suspicion of paracetamol; use NAC Transplant indications

Gut 2011Gut 2007 Transplant; 5-year survival

Gut 2007 Clinical Priorities

• Decompensated chronic liver disease – Variceal haemorrhage – Ascites & infection – Encephalopathy – Hepatorenal syndrome • Acute liver failure • Biliary sepsis Biliary obstruction Management; ascending cholangitis

• Resuscitation and renal support • Check & correct coagulation

• Biliary drainage

• Antibiotics (e.g. iv tazoxin, cefuroxime) – Organisms: E. Coli, Klebsiella, Streptococcus

• Analgaesia Relieve obstruction Malignant obstruction Liver abscess Biliary MDT Summary

• Decompensated liver disease increasing – prevention critical – treat complications & consider transplantation • Acute Liver Failure – rare, but early recognition critical • Biliary sepsis – clinical history, imaging, treat sepsis and achieve drainage – MDT approach QUESTIONS?