Abnormal Liver Function Tests (Adults)Dr Allister J Grant

Leicester Liver Unit

http://hepatologist.eu

Alanine aminotransferaseAspartate aminotransferase

Alkaline phosphatase-Glutamyl transferase

BilirubinAlbumin

LIVERFUNCTIONTESTS

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

• Gilberts- unconjugated hyperbilirubinaemia

• Haemolysis-Unconjugated 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)

• Acute

– Age/Sex– Drugs/Antibiotics– FHx gallstones– Abdo Pain– Red flag symptoms– Jaundice?

Differentiate from bony

• Chronic

– 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

• AllopurinolAntithyroid agents

AugmentinAzathioprineBarbituratesCaptoprilCarbamezepineChlorpromazineChlorpropamideClindamycin

ClofibrateDiltiazem

Erythromycin estolateFlucloxacillin

Isoniazid

LisinoprilMethyltestosterone

Oral contraceptives (containing estrogens)Oral hypoglycemics PhenytoinTrimethoprim-sulfamethoxazole

Investigation of Cholestasis

Dilated bile ducts

Non-dilated bile ducts

Full liver screen

Raised ALP

Check GT if isolated rise

1) Stop alcohol

2) Stop hepatotoxic drugs

3) Advise weight loss if BMI>25

4) Recheck LFT’s after an interval

Persistently raised ALP

ConsiderMRCPERCP

Other imaging

Diagnosis made-Treat disease

Non diagnostic Ix-consider

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 yAdmitted to LRI Nov 04 with 6 mo lethargySOA (8 weeks ↑)

Recently returned form USA

Had HCV Ab done and found to be + in 2003

Frusemide 1 yearSome PR bleeding

PMHx

RTA 1983 #femur, ankle ,toesPEHypertension

SHx

Lived in USA 8 yrsMarriage broken down related to HCV Ab statusNo risk factors for acquisitionRecently returned to UKConstruction workerOccasional alcoholNon smoker

OE

? Vasculitic rash on legsSRPSMSOA++

Liver edge Splenomegaly

? Ascites

Hb 11.9 ALP 146 U&E normalWCC 4.7 ALT 31Plt 42 Bili 54INR 1.7 Alb 32

What investigations?

USS“Irregular liver, splenomegaly, PV patent”

Liver screen

HBV sAg Endoscopy- OGDHCV Ab Flexi Sig

Auto Ab IgG IgA and MFerritinCopper Caeruloplasmin A1AT

1 week post admission DSH

Waited till after drug round, drew curtainsCut wrists with scissorsOD (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’sALT 212ALP 522Bili 21ALB 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

• CT– Multiple

haemangiomata– Multiple enlarged

nodes at porta 12mm– ? SB polyp– RMZ consolidation

• HBsAg neg• HCV ab neg• EBV IgG pos• CMV neg • Autoantibodies neg• Tumour markers neg

Rash on palms and soles biopsied 9/9/09- non specific

Liver biopsy arranged and done 17/9/08-

periductal fibrosis and biliary inflammation

Rash on palms and soles biopsied 9/9/09- non specific

Liver biopsy arranged and done 17/9/08-

periductal 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.

Fatty Liver

Obese BMI>28Centipetal (apple)Bright liver on USSNormal ALT

NASH

Obese BMI>28Bright liver on USSAbnormal ALTFeatures of metabolic syndrome Dyslipidaemia DM HBP

Cirrhosis

Bright/ small liver on USS + splenomegalyAbnormal ALTThrombocytopaeniaObesityPoorly controlled DMPoorly controlled lipidsHypertension

2nd hit

How common is NAFLD?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 Age Adjusted Prevalence (%) of Overweight and Obese Americans Aged 20-74yOverweight and Obese Americans Aged 20-74y

LEICEST

ER

Fatty LiverFatty Liver

• Better detected by abdominal imaging than blood tests

• Common in individuals who are– Overweight/obese– Type 2 diabetic– Dyslipidaemic– Regular alcohol consumers

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

NAFLDNAFLD

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.