Abnormal Liver Function Tests (Adults) Dr Allister J Grant Leicester Liver Unit http://hepatologist.eu LIVER FUNCTION TESTS Alanine aminotransferase Aspartate aminotransferase Alkaline phosphatase -Glutamyl transferase Bilirubin Albumin Abnormal LFT’s in well patients 1) Isolated raise in bilirubin 2) ALT rise predominant 3) ALP rise predominant 1) Isolated raise in bilirubin • Differential Gilberts vs Haemolysis • Gilbertsunconjugated hyperbilirubinaemia • HaemolysisUnconjugated hyperbilirubinaemia splenomegaly, anaemia , DCT, haptoglobin, reticulocyte count, film 2) ALT elevated • Hepatitic illness • Acute – – – – – – – – – – – Age Sex Drugs Alcohol Travel Contacts Risky behaviour Autoimmunity Fever AF/BP/CCF Pregnant? • Chronic – – – – – – – – – Age/sex Ethnicity BMI Lipids Diabetes Alcohol Travel Risky behaviour FHx • Autoimmunity • Unexplained Cirrhosis The majority of abnormal LFTs in asymptomatic people occur in those with: • Diabetes or metabolic syndrome (increased risk of NAFLD) • Excessive alcohol intake • Chronic hepatitis B • Chronic hepatitis C • Drugs ALT elevated • Hepatitic illness • Acute – – – – – – Hep A,B,C,E EBV, CMV, TOXO Drugs screen? Immunoglobulins Autoimmune profile Caeruloplasmin (<50) • Chronic – – – – – – – – – – – TFT Diabetic screen Hep B, C Lipids Immunoglobulins Autoimmune profile Ferritin Caeruloplasmin (<50) α-1 antitrypsin TTG ACE 3) ALP Elevated • Cholestatic Illness (With or without jaundice) Differentiate from bony • Acute • Chronic – – – – – – Age/Sex Drugs/Antibiotics FHx gallstones Abdo Pain Red flag symptoms Jaundice? – – – – – – – – – Family Hx Metabolic syndrome Recurrent Fever Itch/lethargy Dry eyes/mouth Colitis Pain SOB/Resp symptoms CCF Liver ALP Elevated • Cholestatic Illness • Acute – – – – – – CBD stones/Gallstones Tumours 1º or 2º Pancreatic pathology Drugs Infiltration SOD • Chronic – PBC – Sclerosing Cholangitis • 1º or 2º – – – – – NASH α-1 antitrypsin Sarcoid Amyloid HIV Drug Induced Cholestasis • Intrahepatic Hepatocellular Cholestasis • Intrahepatic Ductular cholestasis • Ductopenic • Granulomatous • Allopurinol Antithyroid agents Augmentin Azathioprine Barbiturates Captopril Carbamezepine Chlorpromazine Chlorpropamide Clindamycin Clofibrate Diltiazem Erythromycin estolate Flucloxacillin Isoniazid Lisinopril Methyltestosterone Oral contraceptives (containing estrogens) Oral hypoglycemics Phenytoin Trimethoprim-sulfamethoxazole Investigation of Cholestasis Raised ALP Check GT if isolated rise Dilated bile ducts 1) Stop alcohol Consider MRCP ERCP Other imaging 2) Stop hepatotoxic drugs 3) Advise weight loss if BMI>25 Non-dilated bile ducts 4) Recheck LFT’s after an interval Persistently raised ALP Full liver screen Diagnosis madeTreat disease Non diagnostic Ixconsider Liver biopsy 4) -Glutamyl transpeptidase • The high sensitivity and very low specificity seriously hampers the usefulness of this test • If ALP is elevated and GGT is elevated then the raise in ALP is likely to be hepatic in origin • Elevated in – – – – – a whole host of liver diseases Drugs/Alcohol Obesity/ dyslipidaemia/ DM CCF Kidney, Pancreas, Prostate Case 1 Mr X 52 y Admitted to LRI Nov 04 with 6 mo lethargy SOA (8 weeks ↑) Recently returned form USA Had HCV Ab done and found to be + in 2003 Frusemide 1 year Some PR bleeding PMHx RTA 1983 #femur, ankle ,toes PE Hypertension SHx Lived in USA 8 yrs Marriage broken down related to HCV Ab status No risk factors for acquisition Recently returned to UK Construction worker Occasional alcohol Non smoker OE ? Vasculitic rash on legs SR PSM SOA++ Liver edge Splenomegaly ? Ascites Hb 11.9 WCC 4.7 Plt 42 INR 1.7 ALP 146 ALT 31 Bili 54 Alb 32 U&E normal What investigations? USS “Irregular liver, splenomegaly, PV patent” Liver screen HBV sAg HCV Ab Auto Ab IgG IgA and M Ferritin Copper Caeruloplasmin A1AT Endoscopy- OGD Flexi Sig 1 week post admission DSH Waited till after drug round, drew curtains Cut wrists with scissors OD (once previously Oct 04) Suicide note Salicylate ↑ Paracetamol↑ Treated appropriately Transferred to unit. OPD PCR negative x2 A1AT <0.3 Transjugular Liver Biopsy A1AT phenotype Pi ZZ Accumulation Histology and EM Case 2- Mr Y • 53 year old married man presented at GGH -end Aug 09 • Chest Pain/Abdo pain and loose stools • Troponin negative • Abnormal LFT’s ALT 212 ALP 522 Bili 21 ALB 37 Amylase 33 Initial liver screen • IgG slightly elevated • IgM slightly elevated • • • • Caeruloplasmin A1AT level Ferritin TFT Imaging • USS– echogenic mass in left lobe -5x4x2cm – Probably complex haemangioma- some doppler flow and some other small similar lesions By week later ALP>1000 Transferred to Liver Unit • • • • • • HBsAg neg HCV ab neg EBV IgG pos CMV neg Autoantibodies neg Tumour markers neg • CT – Multiple haemangiomata – Multiple enlarged nodes at porta 12mm – ? SB polyp – RMZ consolidation Rash on palms and soles biopsied 9/9/09- non specific Liver biopsy arranged and done 17/9/08periductal fibrosis and biliary inflammation • VDRL/TPHA Positive • Commenced on penicillin • Referred to GUM • LFT’s completely normalised in 2 months The End “All right, let's not panic. I'll make the money by selling one of my livers. I can get by with one “ Doh! Non-Alcoholic Fatty Liver Disease NAFLD • NAFLD is a spectrum of disease which includes Fatty liver disease and NASH, but only NASH is known to progress to cirrhosis. 2nd hit Fatty Liver Obese BMI>28 Centipetal (apple) Bright liver on USS Normal ALT NASH Obese BMI>28 Bright liver on USS Abnormal ALT Features of metabolic syndrome Dyslipidaemia DM HBP Cirrhosis Bright/ small liver on USS + splenomegaly Abnormal ALT Thrombocytopaenia Obesity Poorly controlled DM Poorly controlled lipids Hypertension How common is NAFLD? • The most common cause of abnormal liver function tests in the United States. • Estimated 30.1 million with NAFLD and 8.6 million with NASH • Affects 10-24% of the population • 58-74% of the obese population Age Adjusted Prevalence (%) of Overweight and Obese Americans Aged 20-74y Fatty Liver • Better detected by abdominal imaging than blood tests • Common in individuals who are – Overweight/obese – Type 2 diabetic – Dyslipidaemic – Regular alcohol consumers NAFLD Fatty Liver: Macrovescicular steatosis with nucleus positioning at cell periphery NASH: Mallory bodies, ballooning, degeneration, lobular neutrophil inflammation and perisinusoidal fibrosis AGA Technical Review on Nonalcoholic Fatty Liver Disease. Gastroenterology 2002;123:1705-1725 NASH Steatosis Cirrhosis NASH The rates of progression to cirrhosis have been estimated at between 5% and 20% over 10 years. There aren't any non-invasive means of predicting which patients are at risk of progression, and there are no agreed guidelines on how to monitor progression.