Deranged LFTs Pathways A H Mohsen Dr A H Mohsen MD (KCL), MRCP, DTM&H Consultant Gastroenterologist

Main causes for progression of liver disease Alcohol consumption Obesity Hepatitis B/C

Common serum liver chemistry tests AST/ALTHepatocellular damage BilirubinCholestasis, impaired conjugation, or biliary obstruction GGTCholestasis or biliary obstruction Alk-PCholestasis, infiltrative disease, or biliary obstruction PT/AlbuminSynthetic function

How common abnormal LFTs? Abnormal LFTs: 1%–4% of the asymptomatic population Those who have LFTs check: >10 are above twice limit of normal abnormal test result resolve spontaneously in 38% of patients Gastroenterology 2002 Ryder, BMJ 2001

149 asymptomatic patients with elevated alanine aminotransferase levels who underwent liver biopsy Cause% Fatty live56 Non-A, Non-B hepatitis22 Alcohol related11 Hepatitis B3 Other diagnosis8 No cause2 Scand J Gastroenterol 1986

1124 consecutive patients with chronic elevations in aminotransferase levels CauseNumber Steatosis41 NASH26 Fibrosis4 Hepatitis B3 Cirrhosis2 Normal8 Am J Gastroenterol no definable cause had LB

Abnormal LFTs Raised ALK-PALT/ASTIsolated rise Bili up to 3x ULN exclude haemolysis and Conjugated bilirubin Probably Gilbert’s

Abnormal LFTs Raised ALK-PALT/ASTIsolated rise Bili up to 3x ULN Check GGT Raised: x2 ULN >3 months Normal: Bone disease USS & AMA abnormal: refer Normal: repeat in 3-6 months Trend not improving

ALT/AST ALT> mod RiskALT<100 Review 1 months Raised: x2.5 ULN >3 months Hep A,E,CMV,EBV USS, liver screen USS & liver screenReferral to Gast Review 1-3 /12 No further action Normal

USS & liver screen Positive screenNegative screen Treat diagnosis Referral to Gast Fat on USS NAFLD + ETOH No fat on USS

Fatty liver (NAFLD/NASH) Fibro-scan Referral to Gast > 7 CriteriaLow riskHigh risk Age<45>45 Diabetes/IFGAbsentPresent BMI<30>30 AST/ALT<1>1 Platelet count>150<150 Albumin>34<34 If > 3 criteria Life style intervention Repeat fibro-scan in 1-2 years GP to monitor < 7

Isolated elevation of GGT Levels > 3 times upper limit of normal: Repeat in 3 months Alcohol intake advice Review medications If trends worsening USS & fibro-scan Levels < 3 times upper limit of normal: Monitor 6-12 monthly Alcohol intake advice Review medications Refer to Gast fibro-scan > 7

Recent case ST, 62 male Presented in March with severe UGIB Stabilised OGD: Likely gastric varices (D/W Addenbrokes) Catastrophic variceal bleed 10 hours later Died PMH: Type II DM (1999) Hypertension IHD

ST, 62 male Current medications: 1. NovoRapid units pre meal 2. Lantus 40 units pre bed 3. Metformin MR 1g bd 4. Bendroflumethiazide 2.5mg 5. Omeprazole 5mg 6. Diltiazem MR 90mg 7. Irbesartan 75mg

Ref. Range 12/03/201422/09/201102/11/201027/10/200831/01/2007 ALP( ) Albumin( ) ALT(0 - 41) Total Bilirubin (0 - 20)

NAFLD prevalence Liver biopsy/post-mortem series 15-39% Third of the population was found to have hepatic steatosis in US (MRI) Obese persons NAFL 60-90%, NASH 20-25%, cirrhosis 2-3% Diabetic : 50 % Morbidly obese and diabetic person NAFL 100%, NASH 50%, cirrhosis 19% Dixon J 2001, silverman J 1989, 1990 Hultcrantz R 1986, Ground K 1982 Hepatology 2004; 40:1387

Examination Process A mechanical pulse is generated at the skin surface, which is propagated through the liver. The velocity of the wave is measured by ultrasound. The velocity is directly correlated to the stiffness of the liver, which in turn reflects the degree of fibrosis. - the stiffer the liver is the greater the degree of fibrosis.

Project Overview A novel diagnostic pathway to detect significant liver disease in the community Amount Won £100,000 Innovation Challenge Prize Winner, November 2013

Summary Clear pathways NAFLD is the most common cause 1/3 of deranged LFTs resolve spontaneously Identify those at risk and refer early