Asymptomatic abnormal LFTs…..again! ignore, reassure, investigate or refer? Alastair MacGilchrist Laboratory/Primary care Meeting 7 November 2013

Why bother? (1)

Why bother? (2) Liver disease is usually asymptomatic until irreversible…..the classic “silent killer” Most liver disease is due to alcohol, NAFLD or viral hepatitis…..all preventable or reversible in early stages

Price  Consumption  Harm Alcohol kills a Scot every 3 hours 1 in 20 of all deaths in Scotland Twice that of England Doubled in last 15 years 1 in 10 of deaths in Scots aged 35-54 is due to alcoholic liver disease. Enough alcohol is sold in Scotland to enable every adult to exceed safe drinking guidelines almost double that of England Britain’s consumption has doubled since 1960 Alcohol is 70% more affordable than in 1980 Price  Consumption  Harm

NAFLD is a big problem Very common Up to 30% of population Up to 75% if obese 2-5% will develop cirrhosis over 20 years Difficulty distinguishing progressive disease (i.e. fibrosis)

The future of hepatitis C therapy e.g. sofosbuvir, daclatasvir, ledipasvir interferon-free single combi-pill oral short course once-daily dosing minimal side effects

hepatitis C therapy is changing pre 2011 genotype 2 or 3 genotype 1 drugs peg-interferon + ribavirin duration 24 weeks 48 weeks cure up to 80% up to 40% now genotype 2 or 3 genotype 1 drugs peg-interferon + ribavirin peg-interferon + ribavirin + bocepravir or telapravir duration 24 weeks up to 48 weeks cure up to 80% up to 70% 2015 ? genotype 2 or 3 genotype 1 drugs DAAs duration 12 weeks ? cure 100% ?

What are abnormal liver function tests? bilirubin ALT alkaline phosphatase GGT albumin AST prothrombin time FBC creatinine

routine LFTs in primary care: remove GGT and add AST? GGT v AST GGT isolated GGT with raised MCV – consider alcohol in female NAFLD, GGT predicts cirrhosis GGT indicates liver source for ALP ignore GGT alone <100 AST in ALD, AST often > 2 x ALT in NAFLD, suspect significant fibrosis if AST > ALT (AST/ALT > 0.8) APRI score (AST: platelet ratio) >1.5 routine LFTs in primary care: remove GGT and add AST?

The patient with asymptomatic abnormal LFTs NAFLD is not the only diagnosis Pattern and duration are important Consider: Alcohol history Hepatitis risk factors Drugs metabolic syndrome clues Autoimmune disease clues Family history Measure: Viral hepatitis serology HBsAg, anti-HCV Ab HBV, HCV Autoimmune markers ASMA, ANA, AMA AIH, PBC Glucose NAFLD Lipids NAFLD Ferritin haemochromatosis Caeruloplasmin (if <55y) Wilson’s disease Alpha-1-antitrypsin phenotype α-1-Antitrypsin deficiency Ultrasound

Have they got fibrosis/cirrhosis? 1. Primary care Clinical exam Hepatosplenomegaly Spider naevi, etc. LFTs GGT AST/ALT Albumin Platelets Ultrasound

Have they got fibrosis/cirrhosis? 2. Secondary care APRI score Hyaluronic acid Marker panels ELF Fibrotest Elastography Fibroscan ARFI Liver biopsy

“liver screen” Who? ↑ALT/GGT/AP > 2 x ULN 2 occasions > 4 weeks apart What? USS Aetiology HCV Ab, HBsAg ASMA, ANA, AMA ferritin caeruloplasmin (<55y) glucose, lipids (TTG, TFTs) Staging AST platelets albumin Action? Refer if +ve aetiology screen fibrosis/cirrhosis ↓platelets AST/ALT>0.8 splenomegaly unexplained ALD ↓alcohol NAFLD ↓weight

Sub-groups ↑bilirubin alone: usually Gilbert’s (exclude haemolysis) (check unconjugated) ↑GGT alone: think alcohol (think NAFLD) AP alone: probably not liver consider isoenzymes ↑AP + GGT: usually biliary USS for biliary obstruction Check AMA for PBC

So…for the next patient with asymptomatic abnormal LFTs…. investigate? if persistent according to clinical picture don’t miss treatable disease refer? if require treatment, suspect advanced disease or diagnosis unclear reassure? if negative screen and no suspicion of advanced disease ignore? never!

and….. …..a very big thanks to Simon, Sara, Emily and Thulani Your Text Here