Hepatitis C- Global and National Perspective

Report
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
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–
–
–
–
–
–
Age
Sex
Drugs
Alcohol
Travel
Contacts
Risky behaviour
Autoimmunity
Fever
AF/BP/CCF
Pregnant?
• Chronic
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–
–
–
–
–
–
–
–
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
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–
–
–
–
–
–
–
–
–
–
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
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–
–
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Age/Sex
Drugs/Antibiotics
FHx gallstones
Abdo Pain
Red flag symptoms
Jaundice?
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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
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–
–
–
–
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
–
–
–
–
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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.

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