3Normal Liver Function Protein synthesis and degradation: albumin, transport proteins, clotting factors,Carbohydrate metabolismLipid metabolismBile acid metabolismBilirubin metabolismHormone inactivationDrug inactivation and excretionImmunological function
4Liver function tests 1 Bilirubin – Conjugated and Unconjugated ALT/AST levelsAlkaline PhosphatasegGTAlbuminINRFBC
5Liver function tests 2 Hepatitis antibodies: A, B, C….D, E EBV, Toxo, CMV, LeptospirosisFerritin and fasting transferrin saturation,Haemochromatosis geneticsCaeruloplasmin and copper (serum),24 hour urine for copperAutoantibodies: ANA, ASMA, AMA, CoeliacImmunoglobulins: IgG, IgA, IgMCholesterol, triglycerides, glucose, TFTsa1antitrypsin levels + phenotypea-fetoprotein (cirrhotics only)
6ImagingUltrasound – Liver substance, lesions, gallbladder and biliary tree, vessels (Doppler exam), spleen size and varicesCT scan – confirm small lesions, see pancreasMRI of Liver – classify smaller lesionsMRCP: Magnetic resonance cholangiopancreatography, to see the biliary treeERCP: Endoscopic retrograde cholangiopancreatography– diagnostic and therapeutic: stones, strictures etc.
10Liver BiopsyVery useful for confirming a diagnosis, staging degree of inflammation and/or fibrosis, iron content, mass lesionsContraindications: Bleeding disorders, ascites, small liver, uncooperative patientComplications: Bleeding, pain, perforation another viscus, biliary leak, pneumothoraxMethods: Percutaneous, transjugular, laparoscopically
11Jaundice Pre hepatic Hepatic – any liver disease, acute or chronic HaemolysisConjugation abnormalitiesHepatic – any liver disease, acute or chronicPost hepatic – Obstruction
12Gilberts syndrome Deficient glucuronyl transferase Unconjugated hyperbilirubinaemia, other LFTs normal2-5% populationJaundice when dehydratedLow grade haemolysisNormal liver, life expectancy etc.
13Acute Liver Disease Infections Drugs – MANY – HERBALS/OTC Alcohol Viral Hepatitis A, B, C, D, E, EBV, CMV, HSV,Others – Leptospirosis, Toxoplasma,Drugs – MANY – HERBALS/OTCAlcoholPoisonsVascular obstruction (eg. Budd Chiari)
15Acute Liver Disease: treatment Supportive mainlyRemove precipitating cause if known eg. drugsTreat some cases eg. Leptospirosis, some viral infections in acute phase,Expect complications and treat as they arise eg:InfectionBleedingOutcomeResolveWorsen and develop FLF (? Transplant)Progress to chronic liver disease, may require specific therapy*
16Paracetamol toxicity Present in many preparations*** 10gms (20 tablets) can cause fatal liver failureInitial N&V often settles with symptoms of liver failure developing 2-3 days laterCoagulopathy and raised ALTParacetamol levels may be low/neg by this stageHigh index of suspicionTreat if in any doubt with N-acetylcysteine
20Alcohol Fatty liver – may have no symptoms Alcoholic Hepatitis – can be unwell with liver and renal failure, jaundice, coagulopathyCirrhosis and its complicationsCan present at any stage aboveACCURATE ALCOHOL HISTORYClues: LFTS: gGT, MCVOther problems: medical (pancreatitis, malnutrition, infections, cardiac), social….
21Tx. Of Alcoholic Hepatitis Feed (Enterally)Vitamin replacement: Thiamine: IV Pabrinex and multivitaminsTreat DTsCorticosteroids if Maddrey’s discriminant function higher than 32:50% mortality ratemDF= 4.6 x (PT patient-control) + Bilirubin/17.1 umol/LTreat with steroids: Prednisolone 40mg X1/12Other scoring systems: Glasgow Alcoholic Hepatitis Score, MELD score
22Fatty LiverMany Secondary causes of fatty liver, including drugs, alcohol, previous surgeryPrimary fatty liver or non-alcoholic fatty liver disease (NAFLD) commonly recognised nowSome 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 timeIs associated with obesity, non-insulin dependent diabetes, dyslipidaemia and hypertension; considered part of syndrome X/metabolic syndromeFatty liver getting more common – obesity increasing.
25Hereditary haemochromatosis Commonest genetic problem N. EuropeanProgressive iron overload leading to liver disease (cirrhosis and hepatocellular carcinoma), diabetes, pigmentation, arthropathy, hypogonadism, cardiac….Not always symptomatic at diagnosis
26Hereditary haemochromatosis Need high serum ferritin level and fasting transferrin saturations to make diagnosisFasting Transferrin Saturation > 45%Raised Serum Ferritin > 350ug/LGenetics: C282Y and H63D mutationREMEMBER: MANY CAUSES OF RAISED FERRITIN
27Hereditary haemochromatosis If HH confirmedLFTs and ultrasound +/- Liver biopsy to diagnose CirrhosisPrognosis worse if diabetic or cirrhotic at time of diagnosisIf cirrhotic, need tumour surveillanceTreatment is phlebotomy to render iron deficient and prevent organ damage, does not remove risk of HCCLife long
34Variceal bleeding Due to portal hypertension Varices at porto-systemic anastomosesSkin – Caput medusaOesophageal & GastricRectalPosterior abdominal wallStomalMedical emergency
35Resuscitate patientGood IV accessCross-match bloodand clotting factorsEmergency OGD
36Band oesophageal varices Can Inject gastric varices with glueManage in HDU/ITUTerlipressin IVProphylactic antibioticsU/sound and doppler portal veinRebleed: Rescope,Balloon tamponade,May need TIPPs shunt, transplant
38Prevention of variceal haemorrhage PRIMARY PREVENTION: Have not bledScope all cirrhoticsIf large varices: B block with Propranolol or Band varices.SECONDARY PREVENTION: After bleedRepeat banding until varices eradicated +/- propranolol (ideally measure portal pressures)
39Encephalopathy Confusion due to liver disease Graded 1-4 Precipitants: GI bleed, infection, constipation, dehydration, medication esp. sedationFlap – asterixis and hepatic foetarTreat underlying cause,Laxatives – phosphate enemas and lactuloseRifaximin-broad non absorbed spectrum antibiotic
40Hepatorenal syndromeProgressive renal failure in the setting of advanced liver disease and portal hypertensionRule out other causes for renal failure: Pre-renal, Microscopy, ultrasoundType 1 (acute) and Type 2 (chronic)Very poor prognosis
43Hepatocellular Carcinoma (Hepatoma) Primary Liver CancerUsually in setting of cirrhosisRisk factors: Viral hepatitis B/C, Alcohol, haemochromatosis, a1 anti-trypsin, male PBCsScreen cirrhotics with 6 monthly u/sound and afetoprotein levelsDiagnosis made on imaging (u/s, CT or MRI) and aFP levels in cirrhotics – biopsy usually not doneCure: transplant or surgeryPalliation: TACE, radiofrequency ablation, Sorafenib po.
44Liver transplantation INDICATIONS:Fulminant Liver failure determined by certain clinical criteria (King’s criteria)Paracetamol Overdose: pH, INR, creatinine and EncephalopathyNon-paracetamol: INR, Bilirubin, age, cause, encephalopathyChronic Liver Disease: Mainly for DecompensationascitesUncontrolled variceal haemorrhageEncephalopathyHepatoma – Milan criteriaDisease specific criteria: Rising Bilirubin in PBCNeed to consider Q of Life and Other illnesses
45Liver transplantation WAITING LIST: MELD scoring systemLiver Matched by blood group and sizePost operativeImmunosuppression to prevent rejection eg. Tacrolimus, Mycophenolate and SteroidsProphylaxis against infection eg. CMV, HSV, PCPCan get graft failure, vascular thrombosis, rejection (acute and chronic), infections, disease recurrence…
46Liver disease: summary LFTsCauses of jaundiceCauses of acute hepatitisCauses of cirrhosis – Risk factorsSymptoms and Signs of liver disease – Ascites, encephalopathy & SBP, variceal haemorrhage, HCC and hepatorenal syndrome.