Acute and Chronic Liver Disease Dr. Orla Crosbie Consultant Gastroenterologist, CUH 4th Med, 17th Nov 2010

Contents Investigations Acute Liver disease Chronic Liver Disease

Normal Liver Function Protein synthesis and degradation: albumin, transport proteins, clotting factors, Carbohydrate metabolism Lipid metabolism Bile acid metabolism Bilirubin metabolism Hormone inactivation Drug inactivation and excretion Immunological function

Liver function tests 1 Bilirubin – Conjugated and Unconjugated ALT/AST levels Alkaline Phosphatase gGT Albumin INR FBC

Liver function tests 2 Hepatitis antibodies: A, B, C….D, E EBV, Toxo, CMV, Leptospirosis Ferritin and fasting transferrin saturation, Haemochromatosis genetics Caeruloplasmin and copper (serum), 24 hour urine for copper Autoantibodies: ANA, ASMA, AMA, Coeliac Immunoglobulins: IgG, IgA, IgM Cholesterol, triglycerides, glucose, TFTs a1antitrypsin levels + phenotype a-fetoprotein (cirrhotics only)

Imaging Ultrasound – Liver substance, lesions, gallbladder and biliary tree, vessels (Doppler exam), spleen size and varices CT scan – confirm small lesions, see pancreas MRI of Liver – classify smaller lesions MRCP: Magnetic resonance cholangiopancreatography, to see the biliary tree ERCP: Endoscopic retrograde cholangiopancreatography– diagnostic and therapeutic: stones, strictures etc.

MRCP

ERCP

Liver Biopsy Very useful for confirming a diagnosis, staging degree of inflammation and/or fibrosis, iron content, mass lesions Contraindications: Bleeding disorders, ascites, small liver, uncooperative patient Complications: Bleeding, pain, perforation another viscus, biliary leak, pneumothorax Methods: Percutaneous, transjugular, laparoscopically

Jaundice Pre hepatic Hepatic – any liver disease, acute or chronic Haemolysis Conjugation abnormalities Hepatic – any liver disease, acute or chronic Post hepatic – Obstruction

Gilberts syndrome Deficient glucuronyl transferase Unconjugated hyperbilirubinaemia, other LFTs normal 2-5% population Jaundice when dehydrated Low grade haemolysis Normal liver, life expectancy etc.

Acute Liver Disease Infections Drugs – MANY – HERBALS/OTC Alcohol Viral Hepatitis A, B, C, D, E, EBV, CMV, HSV, Others – Leptospirosis, Toxoplasma, Drugs – MANY – HERBALS/OTC Alcohol Poisons Vascular obstruction (eg. Budd Chiari)

Acute Liver Disease SYMPTOMS SIGNS Nausea & vomiting, diarrhoea, cholestasis, pyrexia, abdominal pain, jaundice Fulminant/acute liver failure rare, patient very unwell coagulopathy and encephalopathic SIGNS Jaundice, hepatomegaly, abdominal tenderness + splenomegaly, flap/foetar

Acute Liver Disease: treatment Supportive mainly Remove precipitating cause if known eg. drugs Treat some cases eg. Leptospirosis, some viral infections in acute phase, Expect complications and treat as they arise eg: Infection Bleeding Outcome Resolve Worsen and develop FLF (? Transplant) Progress to chronic liver disease, may require specific therapy*

Paracetamol toxicity Present in many preparations*** 10gms (20 tablets) can cause fatal liver failure Initial N&V often settles with symptoms of liver failure developing 2-3 days later Coagulopathy and raised ALT Paracetamol levels may be low/neg by this stage High index of suspicion Treat if in any doubt with N-acetylcysteine

Chronic Liver Disease Alcohol Autoimmune – autoimmmune hepatitis, PBC (Primary Biliary cirrhosis), PSC (Primary Sclerosing Cholangitis) Haemochromatosis Chronic Viral hepatitis: B & C Non-alcoholic fatty liver disease (NAFLD) Drugs (MTX, amiodarone) Cystic fibrosis, a1antitryptin deficiency, Wilsons disease, Vascular problems (Portal hypertension + liver disease) Cryptogenic Others: sarcoidosis, amyloid, schistosomiasis

Chronic Liver Disease - symptoms None Fatigue Malnutrition Ascites, ankle oedema, pleural effusions – weight gain Impotence Bleeding Jaundice, itch, steatorrhoea

Alcohol Fatty liver – may have no symptoms Alcoholic Hepatitis – can be unwell with liver and renal failure, jaundice, coagulopathy Cirrhosis and its complications Can present at any stage above ACCURATE ALCOHOL HISTORY Clues: LFTS: gGT, MCV Other problems: medical (pancreatitis, malnutrition, infections, cardiac), social….

Tx. Of Alcoholic Hepatitis Feed (Enterally) Vitamin replacement: Thiamine: IV Pabrinex and multivitamins Treat DTs Corticosteroids if Maddrey’s discriminant function higher than 32: 50% mortality rate mDF= 4.6 x (PT patient-control) + Bilirubin/17.1 umol/L Treat with steroids: Prednisolone 40mg X1/12 Other scoring systems: Glasgow Alcoholic Hepatitis Score, MELD score

Fatty Liver Many Secondary causes of fatty liver, including drugs, alcohol, previous surgery Primary fatty liver or non-alcoholic fatty liver disease (NAFLD) commonly recognised now Some patients in addition to fat on liver biopsy can have inflammation as well (steatohepatitis) and are referred to as NASH (non- alcoholic steatohepatitis), a portion of these will develop scarring and can progress to cirrhosis over time Is associated with obesity, non-insulin dependent diabetes, dyslipidaemia and hypertension; considered part of syndrome X/metabolic syndrome Fatty liver getting more common – obesity increasing.

Hereditary haemochromatosis Commonest genetic problem N. European Progressive iron overload leading to liver disease (cirrhosis and hepatocellular carcinoma), diabetes, pigmentation, arthropathy, hypogonadism, cardiac…. Not always symptomatic at diagnosis

Hereditary haemochromatosis Need high serum ferritin level and fasting transferrin saturations to make diagnosis Fasting Transferrin Saturation > 45% Raised Serum Ferritin > 350ug/L Genetics: C282Y and H63D mutation REMEMBER: MANY CAUSES OF RAISED FERRITIN

Hereditary haemochromatosis If HH confirmed LFTs and ultrasound +/- Liver biopsy to diagnose Cirrhosis Prognosis worse if diabetic or cirrhotic at time of diagnosis If cirrhotic, need tumour surveillance Treatment is phlebotomy to render iron deficient and prevent organ damage, does not remove risk of HCC Life long

Chronic Liver Disease - Decompensation Ascites + renal failure GI bleeding Encephalopathy Jaundice Hepatocellular carcinoma

Ascites Associated with a poor prognosis Often associated with ankle oedema, pleural effusions Diagnostic paracentesis: 1. Biochemistry, 2. Micro & 3. Cytology SAAG: Serum albumin/ascites gradient > 11g/dl Risk of Spontaneous Bacterial Peritonitis Therapy Low salt diet Diuretics: Spironolactone and Frusemide Therapeutic large volume paracentesis – albumin replacement Shunts – TIPS Transplantation DAILY WEIGHTS, WATCH U&Es Don’t fluid restrict

Spontaneous Bacterial Peritonitis Risk: Ascites and Chronic liver disease Often vague symptoms Diagnosis: Diagnostic paracentesis for WCC > 250 cells/mm3 and mainly polymorphs Culture Usually Gram negatives Treat antibiotics +/- albumin Antibiotic prophylaxis

Variceal bleeding Due to portal hypertension Varices at porto-systemic anastomoses Skin – Caput medusa Oesophageal & Gastric Rectal Posterior abdominal wall Stomal Medical emergency

Resuscitate patient Good IV access Cross-match blood and clotting factors Emergency OGD

Band oesophageal varices Can Inject gastric varices with glue Manage in HDU/ITU Terlipressin IV Prophylactic antibiotics U/sound and doppler portal vein Rebleed: Rescope, Balloon tamponade, May need TIPPs shunt, transplant

Prevention of variceal haemorrhage PRIMARY PREVENTION: Have not bled Scope all cirrhotics If large varices: B block with Propranolol or Band varices. SECONDARY PREVENTION: After bleed Repeat banding until varices eradicated +/- propranolol (ideally measure portal pressures)

Encephalopathy Confusion due to liver disease Graded 1-4 Precipitants: GI bleed, infection, constipation, dehydration, medication esp. sedation Flap – asterixis and hepatic foetar Treat underlying cause, Laxatives – phosphate enemas and lactulose Rifaximin-broad non absorbed spectrum antibiotic

Hepatorenal syndrome Progressive renal failure in the setting of advanced liver disease and portal hypertension Rule out other causes for renal failure: Pre-renal, Microscopy, ultrasound Type 1 (acute) and Type 2 (chronic) Very poor prognosis

Hepatocellular Carcinoma (Hepatoma) Primary Liver Cancer Usually in setting of cirrhosis Risk factors: Viral hepatitis B/C, Alcohol, haemochromatosis, a1 anti-trypsin, male PBCs Screen cirrhotics with 6 monthly u/sound and afetoprotein levels Diagnosis made on imaging (u/s, CT or MRI) and aFP levels in cirrhotics – biopsy usually not done Cure: transplant or surgery Palliation: TACE, radiofrequency ablation, Sorafenib po.

Liver transplantation INDICATIONS: Fulminant Liver failure determined by certain clinical criteria (King’s criteria) Paracetamol Overdose: pH, INR, creatinine and Encephalopathy Non-paracetamol: INR, Bilirubin, age, cause, encephalopathy Chronic Liver Disease: Mainly for Decompensation ascites Uncontrolled variceal haemorrhage Encephalopathy Hepatoma – Milan criteria Disease specific criteria: Rising Bilirubin in PBC Need to consider Q of Life and Other illnesses

Liver transplantation WAITING LIST: MELD scoring system Liver Matched by blood group and size Post operative Immunosuppression to prevent rejection eg. Tacrolimus, Mycophenolate and Steroids Prophylaxis against infection eg. CMV, HSV, PCP Can get graft failure, vascular thrombosis, rejection (acute and chronic), infections, disease recurrence…

Liver disease: summary LFTs Causes of jaundice Causes of acute hepatitis Causes of cirrhosis – Risk factors Symptoms and Signs of liver disease – Ascites, encephalopathy & SBP, variceal haemorrhage, HCC and hepatorenal syndrome.