Post on 24-Dec-2015
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.