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 Death between 35-59 years from cirrhosis and other selected diseases: UK 1952-2009 30 Men 30 Women 25 25 20 20 Coronary heart disease 15 15 Lung 10 cancer 10 Deaths Deaths per 10 000 man-years Coronary Deaths Deaths per 10 000 woman-years heart Stroke disease Breast 5 5 cancer Stroke Cirrhosis Cirrhosis 0 0 1950 1960 1970 1980 1990 2000 2010 1950 1960 1970 1980 1990 2000 2010 Year Year Bhala, Foster & Aithal. BMJ 2013 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?.