Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Upper GI & Hepatobiliary Disorders Dylan Leon Thursday 1 February @BRITISHINDIANMEDICASSOC@BINDIANMEDICS @BIMA N BIMA Clinical Crash CourseTOPICS TO BE COVERED • Hepatitis - Viraland Autoimmune • FattyLiverdisease: • Alcoholic liver disease • Non AlcoholicFatty liver disease • Liver Cirrhosis • LFT interpretation • Primary biliary cholangitis • Gilbert's syndromeCase1 A 45-year-old woman presents with insidiousonset of fatigue,malaise,lethargy,anorexia,nausea,abdominal discomfort, mildpruritus,andarthralgiainvolving the smalljoints. Her pastmedicalhistory includes coeliac disease.Physicalexaminationrevealshepatomegalyand spider angiomata.Case1 A 45-year-old woman presents with insidious onset of fatigue,malaise,lethargy,anorexia,nausea,abdominal discomfort, mildpruritus,andarthralgiainvolvingthe smalljoints. Her pastmedicalhistory includes coeliac disease.Physicalexaminationrevealshepatomegalyand spider angiomata.Autoimmune Hepatitis Definition: Chronicinflammatorydiseaseof the liverof unknownaetiology,whichif left untreatedoften leadsto cirrhosis,liverfailure,anddeath Epidemiology: F > M 3-4x Associations: Otherautoimmunediseases, Hypergammaglobulinaemia,HLAB8,DR3 Commonly: Thyroiditis, T1DM, Coeliac Disease, UC, RA, HaemolyticAnaemia, or ITP ClinicalFeatures • Maypresentwithsignsof chronicliverdisease • Acute hepatitis:fever, jaundice(~ 25%) • Amenorrhoea (common) Autoimmune Hepatitis Investigations Bloods Type I Type II Type III • ↑ serum ALTand AST activity ANA LKM1 Soluble liver- • ↑ serum IgG kidneyantigen • ↑ titres of circulatingautoantibodies (titres of >1:40) SMA • ANA/SMA/LKM1 antibodies Management: Liver Biopsy • Typicalfeature: Interface hepatitis(inflammation of Immunosuppression hepatocytes at thejunctionof the portal tract and • Steroids+/- hepatic parenchyma) • Azathioprine • 'piecemeal necrosis', bridgingnecrosis Liver Transplant Acute:symptomatic Hepatitis Chronic:> 6 months, asymptomatic AcuteHepatitis ChronicHepatitis • AcuteViralHepatitis • ChronicViral Hepatitis - HBV,HCV HAV,HBV,HCV,HDV,HEV,CMV, • AutoimmuneLiver Disease EBV - AI Hepatitis: ANA/ ASMA/ LKM • AutoimmuneLiverDisease - Primary Biliary Cholangitis: AMA - ANA/ ASMA/ LKM • MetabolicLiverDisease • Drug induced - Ferritin(Haemochromatosis) - Ceruloplasmin(Wilson’sDisease) - Paracetamol - α1 antitrypsindeficiency Non Specific Symptoms: RUQ pain, dark urine, jaundice,malaise, fever,headache, anorexia, N&V Viral Lab Results • ↑ ALT/AST/Bilirubin Hepatitis • ClottingDerangement • IgM (acute) or IgG (chronic) • Viral nucleicaciddetection (DNA/RNA) • AntigenDetection(HBV/HCV) Transmission ViralHepatitis • FoecalOral:HepA/E • BloodBorne:Hep B/C/D Hepatitis A • RNA picornavirus • Transmission: Foeco-Oral • Incubation Period = 2 – 4 weeks • Clinical Features: fever,anorexia, n/v/j, RUQ pain • Severitydependenton age • < 5 yrs:mostly asymptomatic • > 50yr: mortality rate 1.5% • Diagnosis: • Acute infection: HAV-IgM in serum by EIA • Chronic infection: HAV-IgG in serum by EIA • Treatment:UsuallySelf Limiting. Maintain hydration, avoid alcohol • Asymptomatic in children < 5 • Mortality 1.5% if age > 50 • No Chronic Hepatitis/ No predisposition toHCC • Vaccine Hepatitis B • DNAVirus • Common • VaccinePreventable • Transmission:Transfusion, Fluids (Blood/Semen), Organs/Tissue transplantation, Vertical transmission, Contaminated needles/syringes • Incubation: 6 – 20 weeks • Features: fever,jaundice, elevated transaminases • Age determines severity &risk ofchronicHBV • Birth/youngchild: asymptomatic+ chronic infection • Adult:symptomatic but clear • 25%develop chronicHBVwhichcarryariskof • Cirrhosis • Decompensationwithascites • HepatocellularCarcinoma(HCC) Hepatitis B HBV isdiagnosed if sAg andDNA are detectable Treatment • Acute: None Markerofinfection • Chronic:only if there is evidence of liver inflammation or fibrosis Suggestshighinfectivity • SuppressViral Replication + Prevent further damage • Pegylated Interferon-alpha cAb– marker of current/prev infection • Tenofovir + Entecavir Measure treatment response Prevention • Education • Vaccination • Preventionof Motherto Child TransmissionHepatitis B Hepatitis C • RNAFlavivirus, affects 170million people worldwide • Transmission: IVDU, Blood Transfusion/Transplant,Sexual/Vertical Transmission, Needle stick • Novaccine, no immunity, no protective antibody response identified • Incubation period: ~ 6 – 7 weeks • High rate ofprogression chronicdisease (70%), eventual cirrhosis(25%) &HCC (1 – 5%) • Rate of progression related to: Male, age > 40, alcohol > 50g/week • Clinical features: mostly asymptomatic, only 30% pt will develop jaundice, transient rise in serumaminotransferases, fatigue, arthralgia • Investigations • HCV RNA(PCR) orAntigen positive: currentinfection • Anti HCVIgG positive: chronicinfection/ cleared infection • Aim oftreatment: Treatinfection • Direct Acting Antiviral (DAA)for8 –12 weeks, depending onthe viral genotype • Cure rates of > 95%Hepatitis D • ssRNA virus • Transmittedparentally-entersvia • Superinfection of chronic HBVcarriers skin/mucosa/bloodstream liver • UsuallydevelopchronicHDV infection • Defective virus: Replicates onlyin • High riskof severechronic liver disease, presenceof HBV fulminant hepatitis, andcirrhosis • Maypresentasan acute hepatitis • Co-infection withHBV • Severeacute disese • Low riskof chronic infection • Treatment: Interferon HepatitisE • Virus replicates in GI tract --> blood streamliver • RNA Virus • Clinical course : 2-4 weeks • Mostinfections are • Transmission:Faeco-oral, Undercooked meat(pork), asymptomatic/mild associated withlarge water-borne outbreaks • Infectionclearedcompletely • No chronic infection, no carrier • Incubation = 3 – 8 weeks • Treatment: Supportive (Maintain hydration, IV fluids) • No vaccine • Neurological complications • Chronicinimmunosuppressed patients(TxRibavirin) FattyLiverDisease 1. AlcoholicLiverDisease 2.NonAlcoholicFatty Liver Disease Macrovesicular SteatosisolicSteatosis Steatosis Steatohepatitis AlcoholicHepatitis Non AlcoholicSteatohepatitis(NASH) Pericellular FibrosiAlcoholicCirrhosis NAFLD CirrhosisCase – The newly jaundiced patient A 38-year-old man presentsto the emergency vomiting. He hasa significantmedical history of chronic heavyalcohol consumptionof about one bottle of wine each dayfor about 5 yearsuntil 1 year ago; since thenhe reports no other significant medical problems. Thepatient isconfusedand slightlylethargic, andhepatomegalyis discoveredon physical exam. His BMI is 22. Pertinent positivelaboratory valuesshow low haemoglobin,AST highserumalcohol level.Ultrasoundof the abdomenvery showsfattyinfiltration in theliver.Case – The newly jaundiced patient A 38-year-old man presentsto the emergency vomiting. He has a significant medical history of chronic heavyalcohol consumptionof about one bottle of wine each dayfor about 5 yearsuntil 1 year ago; since thenhe reports no other significant medical problems. Thepatient isconfusedandslightly lethargic, andhepatomegalyis discoveredon physical exam. His BMI is 22. Pertinent positivelaboratory valuesshow low haemoglobin,AST highserumalcohol level.Ultrasoundof the abdomen very shows fattyinfiltration in theliver. 3 Stages AlcoholicLiverDisease FattyLiver (Steatosis) • Accountsfor3 milliondeathsannuallyworldwide Cause AlcoholicHepatitis (inflammation • Chronicheavy alcohol ingestion and necrosis) • ~ 40 - 80 g/day (M) • ~ 20 - 40 g/day (F) Clinical Spectrum: - Malaise AlcoholicCirrhosis - Nausea - Hepatomegaly - Sepsis - Fever - Encepalopathy - Jaundice - Ascites - Death AlcoholicLiverDisease ‘ClinicallyRelevant’ Alcoholic Hepatitis Investigations Essentialfeatures • ↑ Bilirubin (80 umol/l) forless than 2 months Bloods • Exclusion ofother liver disease • Gamma-GT is characteristically ↑ • ↑ AST,↑ ALT • Treatment of Sepsis/ GIBleeding • AST:ALTratiois> 2 • AST < 500 (AST:ALT ratio > 1.5) Characteristic Features - Ratioof > 3 strongly suggestive of acute alcoholic hepatitis • Hepatomegaly • ↑ Urea, ↑ PT ratio/ INR, ↑ Bilirubin, ↑ WCC • Fever • Leucocytosis Imaging: Ultrasound • Hepaticbruit Liver Biopsy: Diagnostic, notindicated in all patientsAlcoholicLiverDisease Management • Alcohol abstinence ** • Periodicliver enzyme tests(monitor ongoingliver damage) • Glucocorticoids(e.g.prednisolone) Complications • Oesophagealor gastric variceal bleeding • Ascites • Coagulopathy Mortalityas • Hepaticencephalopathy high as 60% • Liver cancer Case A 42-year-old man is referred to the liver clinic with mild elevation in aminotransferasesfor several years.He has a medical historysignificant for obesity, hypertension, and hypercholesterolaemia. He does not smoke or drink alcohol and there is no high-risk behaviour.He has a family history of premature cardiacdisease. He istakinga diureticand, because ofhis elevated liver tests,wasrecommended todiscontinue his statinmedicationseveral monthsago.Other thancomplaintsof mildfatigue, the patient feels well.Examination isnotable for a BMI of 37 kg/m², truncal obesity, and mild hepatomegaly. Case A 42-year-old man is referred to the liver clinic with mild elevation in aminotransferasesfor several years.He has a medical historysignificant for obesity, hypertension, and hypercholesterolaemia. He does not smoke or drink alcohol and there is no high-risk behaviour.He has a family history of premature cardiacdisease. He is takinga diuretic and, because ofhis elevated liver tests,wasrecommended todiscontinue his statinmedicationseveral monthsago.Other thancomplaintsof mildfatigue, thepatientfeels well. Examination isnotablefor a BMI of 37 kg/m², truncal obesity, and mild hepatomegaly. Non AlcoholicFatty LiverDisease • Commonest cause ofliverdisease in thedevelopedworld • Associatedwith:Obesity,T2DM,Hyperlipidaemia, Metabolic Syndrome,HTN • Describesa spectrum ofdiseases Steatosis (non progressive) Non AlcoholicSteatohepatitis (NASH) Steatosis,lobularinflammation, and (may progress to fibrosis ballooningdegeneration cirrhosisand liver failure) Steatosis,ballooningdegeneration, and NAFLDCirrhosis fibrosisor Mallory bodies Non AlcoholicFatty LiverDisease ClinicalFeatures: usuallyasymptomatic Investigations • ClinicalExamination:Hepatomegaly Imaging • Bloods: ALT > AST Ultrasound:increasedechogenicity -typicallyasymptomatic liver fatty changes - ALT ↑ or normal - AST normal Liver Biopsy– goal standard - AST/ALT ratio < 0.8 (> 0.8 inmore advanceddisease) - GGT ↑ or normal - Triglycerides ↑ Management - HDL-cholesterol ↓ • Weightloss • Lifestyle modification(diet &exercise) - HbA1c ↑FattyLiverDisease Characteristic NAFLD ALD Weight ↑ Variable FastingPlasmaGlucose/HbA1c Often Usually normal Reporteddailyalcoholintake M < 30g, F < 20g M > 30g, F > 20g ALT ↑ or normal ↑ or normal AST Normal AST/ALTratio GGT ↑ or normal Markedly↑ Triglycerides Variable, maybe markedly↑ HDL- cholesterol ↓ ↑ Mean corpuscular volume Normal ↑ Case A 56-year-old man with a remote history of intravenousdrug use presentsto an initial but deniesjaundice.He drinks about 2 to 4irth glassesof wine with dinner and recalls having had abnormal liver enzymesin the past. Physical examination revealsspidernaevi,a shifting dullnessconsistent with the presence of ascites.Liverfunctionis foundto be derangedwith elevatedaminotransferases (aspartate aminotransferase[AST]: 90 U/L, the patient is positive for anti-hepatitisC antibody. Case A 56-year-oldman with a remote history of intravenousdrug usepresentsto an initial visit complaining of increasedabdominal girth but deniesjaundice. He drinks about 2 to 4 glassesof wine with dinnerand recallshaving had abnormal liver enzymesin the past. Physical examination revealsspidernaevi,a palpable firm liver,mild splenomegaly,and of ascites.Liverfunctionis found to beresence derangedwith elevatedaminotransferases (AST:90 U/L, ALT:87 U/L), and the patient is positive for anti-hepatitisC antibody. Cirrhosis • Pathologicalend-stage of anychronicliverdisease • Progressive destructionofhepatocytes andreplacement by fibroustissue --> complete lossof liverlobulararchitecture Causes 1. ViralHepatitis B andC 2. Alcohol 3. Non-alcoholicfatty liverdisease • ProgressivefibrosisDisruptsportal bloodflow (portal Oncea patient with cirrhosisdevelops signs oftension) decompensation, survival is significantly impaired General: fatigue, anorexia, malaise, weightloss, musclewasting, fever Haematological: anaemia, thrombocytopenia, leukopenia, impaired coagulation, Cirrhosis DIC, haemosiderosis Renal: secondary hyper aldosteronismleads toNa+ and water retention Pulmonary: decreased 02 saturation,altered ventilationperfusion Clinical Features • Stigmata • Spider Naevi • FoetorHepaticus • Encephalopathy • Malnutrition • Blood test • low albumin & clotting factors • Prolonged PTtime • BleedingCirrhosis Portalhypertension • Ascites • Porto-systemicshunts:OesophagealVarices,Caput Medusae,Haemorrhoids • HepaticEncephalopathy(confusion,stupor,coma) • Hepatorenal Syndrome • SplanchnicVasodilation • HyperdynamicCirculation Hypersplenism • Congestive Splenomegaly • Thrombocytopenia PortalHypertension CIRRHOSIS RAISEDPORTALPRESSURE HYPERSPLENISM (thrombocytopenia) SPLANCHNIC VASODILATATION PORTO-SYSTEMICSHUNTING OESOPHAGO-GASTRIC VARICES VASODILATATION ENCEPHALOPATHY (nitric oxide) REDUCEDEFFECTIVE HYPERDYNAMIC CIRCULATING VOLUME CIRCULATION ASCITES SODIUM RETENTION COMPENSATORYVASOPRESSORS (RAAS; catecholamines) RENAL HEAPTO-RENAL VASOCONSTRICTION SYNDROMECirrhosis Diagnosis Imaging • Fibroscan • transientelastography • measures the 'stiffness' of the liverwhichisa proxyforfibrosis Bloods • EnhancedLiverFibrosisTest (ELC) • Fibrotest • HepC • M > 50u/ F > 35u alcoholper week • Alcohol-related liver diseaseCirrhosis Management Complications • Treatunderlyingliverdisease • Spontaneous bacterial • Avoiding superimposed injury, peritonitis • Managing complications • HepaticEncephalopathy • Liver transplantation : only curative treatment option • Cerebraloedema for patients withdecompensated cirrhosis • Renalfailure • Sepsis Further Investigations • Metabolic disorder: • Liver USS every 6 months (+/- AFP) assess for HCC Hypoglycaemia, Acidosis, Hypoxemia • Upper endoscopy (?Varices) inpt withnew diagnosis • CoagulopathyAscites Management Assessment: Diagnostictap • Low salt diet Cell count • SpontaneousBacterial Peritonitis:>500WBC/cm and/or>250 • Diuretics neutrophils/cm • Spironolactone • High mortality unlesstreated appropriately • Treatment:IV Antibiotics & Albumin • +/- Furosemide • Tb/Peritoneal carcinoma: lymphocytosis • Paracentesis • Inflammatory conditions:RaisedWCC • TIPSS Albumin • Prophylactic Abx (↓ risk of SBP) • Serum ascites albumin gradient (SAAG)= serumalbumin – ascitic albumin g/l • Liver transplant • Portal hypertension = SAAG > 11g/l Aim for weight loss of 0.5 – 1 kg/day Cirrhosis Scoring System ModelforEnd-StageLiver Child-Pugh classification Disease(MELD) - Used to allocatedonor organsin USA forliver transplantLiver Function TestsInterpretation LFTs:Panel of biochemicaltestsoftenderangedin patientswith liver disease TypicalLiver FunctionTestPanel Liver Functionindicated by • Albumin - Bilirubin • Bilirubin - AlkalinePhosphatase • Prothrombin Time - Gamma Glutamylytransferase(GGT) - AspartateAminotransferase (AST) - AlanineAminotransferase(ALT) - AlbuminLiver Function TestsInterpretation LFTs:Panelofbiochemicaltestsoftenderangedin patientswithliver disease TypicalLiverFunctionTestPanel Uses of LFTs - Bilirubin - Screening: non invasive - Isolatedraisedbilirubin may behaemolysis - AlkalinePhosphatase - Recognize different type of liver disease - Found in liverand other tissues like bone, intestine, placenta (differentiate acute viralhepatitis/cholestatic - Located in the cells lining the billiary ducts in the liver disorders) - ALP is a markerof cholestasis - AssessSeverity of certaindiseases - Gamma Glutamylytransferase(GGT) - Evaluatingresponse to therapy - AspartateAminotransferase(AST) • Also present inheart, muscle, kidney and brain. - May be raised in hepatocellular disease, MI, muscle injury Limitations - AlanineAminotransferase(ALT) - Lacksensitivity(LFT may be normal in certain - Albumin liverdiseases) - Decreased inchronic liver disease - Lackspecificity - Hypoalbuminemia not specific for liver disease - May occur in protein malnutrition, nephrotic syndrome Bilirubinraised (isolated): haemolysis ASTandALTare raisedmainly in hepatocellular disease (where there isdamage to the hepatocytes) AlkalinePhosphataseand GGT levelsare raised mainly in obstructive (cholestatic) disease: damage to bile ducts Case 1 A 40year – oldhousewife complainedto her general practitionerof generalized severe itchingduringthe previousninemonths.She hadno threeunitsperweek). Onclinicalexaminationshe was slightlyjaundiced, andbilirubinwas detected inthe urine.The resultsof the liverfunction testswere asfollows Plasma analysis Result Referencerange Whatisthe most likely cause of the jaundice? • Albumin 38 36 – 47 a. Alcoholichepatitis • ALP activity 450 40 – 125 • ALTactivity 60 10 – 40 b. CBD stone c. Paracetamol overdose • TotalBilirubin 60 2 – 17 d. Haemolyticanaemia • GGT activity 150 10 – 55 e. ViralHepatitis Case 1 A 40year – oldhousewife complainedto her general practitionerof generalized severe itchingduringthe previousninemonths.She hadno threeunitsperweek). Onclinicalexaminationshe was slightlyjaundiced, andbilirubinwas detected inthe urine.The resultsof the liverfunction testswere asfollows Plasma analysis Result Referencerange Whatisthe most likely cause of the jaundice? • Albumin 38 36 – 47 a. Alcoholichepatitis • ALP activity 450 40 – 125 • ALTactivity 60 10 – 40 b. CBD stone c. Paracetamol overdose • TotalBilirubin 60 2 – 17 d. Haemolyticanaemia • GGT activity 150 10 – 55 e. ViralHepatitis Case 2 • 52 year old M Plasma analysis Result Refencerange • Bilirubin 65 (<20) • PC: Tiredfora fewweeks, then jaundiced • Drinksalcohol 25 units/week for“years” • Albumin 29 (35 – 46) • AST 210 (< 50) • History of Bloodtransfusion (1980) fora RTA • Cousin had “iron in body” • ALT 101 (<50) • PT time 16 (9 – 12) • Signsof ChronicLiver Disease &Ascites Whatisthemost likelydiagnosis? • Ferritin 450 (20 – 270) A. AlcoholicLiver Disease B. HepatitisC C. Haemochromatosis D.Primary Biliary Cirrhosis E. Autoimmune Hepatitis Case 2 • 52 year old M Plasma analysis Result Refencerange • Bilirubin 65 (<20) • PC: Tiredfora fewweeks, then jaundiced • Drinksalcohol25units/week for“years” • Albumin 29 (35 – 46) • AST 210 (< 50) • History of Bloodtransfusion (1980)for a RTA • Cousin had “iron inbody” • ALT 101 (<50) • PT time 16 (9 – 12) • Signsof ChronicLiver Disease &Ascites Whatisthemost likelydiagnosis? • Ferritin 450 (20 – 270) A. AlcoholicLiver Disease B. HepatitisC C. Haemochromatosis D.Primary Biliary Cirrhosis E. Autoimmune HepatitisCase 3 70 y/o M with cirrhosis has a rising AFP and focal liverlesion on ultrasound scan. What is the probable diagnosis? Whatisthe most likely diagnosis? A. Nodularregenerative hyperplasia B. Hepatocellular Carcinoma C. Hepatichaemangioma D.Nodularregenerative hyperplasia E. HepaticAdenomaCase 3 70 y/oM withcirrhosis has a rising AFP and focal liverlesion on ultrasound scan. What is the probable diagnosis? Whatisthe most likely diagnosis? A. Nodularregenerative hyperplasia B. Hepatocellular Carcinoma C. Hepatichaemangioma D.Nodularregenerative hyperplasia E. HepaticAdenoma Primary Biliary Cholangitis Autoimmune disease with serum anti-mitochondrial antibodies (AMA)and high IgM Classicpresentation: itchingin a middle aged women (F:M9:1) Associations • Sjogren'ssyndrome (seen Management in up to 80% of patients) • Rheumatoidarthritis • No cure • Systemic Sclerosis • Ursodeoxycholic acid eases symptoms, slows progression • Thyroid disease • Endstage: Liver Transplant Despitethe name, PBC is not cirrhotic from the onset. Complications Progressesto fibrosis,then cirrhosis overthe years • Cirrhosis→ portal hypertension →ascites,variceal haemorrhage Interlobular bile ducts become damaged by a chronicinflammatory processcreasedriskofHCC causing progressive cholestasis which may eventually progress to cirrhosis. GilbertSyndrome • Autosomalrecessive • Common,~8%GeneralPopulation unconjugated bilirubinencyof UDP glucuronosyltransferaseleadsto decreasedconjugationof • Bilirubinclearancereducedby60% • Liver functionisotherwise normal Presentation: asymptomatic, mildicterus(jaundice)duringtimes of fasting/physiological stress (intercurrentillnessor exercise) Investigation: - Unconjugated hyperbilirubinaemia (i.e.not in urine) - Rise inbilirubinfollowingprolongedfastingor IVnicotinicacid Management: Notreatment required,noliverinjury/progressionto ESLDQuestions? Thank you Dylan.leon19@imperial.ac.uk