Transcript Help with Hepatology (Oct 2013)

Help with Hepatology
Dr Allister J Grant
Consultant Hepatologist
Leicester Liver Unit
University Hospitals Leicester NHS Trust
Spire 2013
Abnormal LFT’s in well patients
1)
Isolated raise in bilirubin
2)
γGT raised
1)
ALT rise predominant
2)
ALP rise predominant
1) Isolated raise in bilirubin
 Differential
Gilberts vs Haemolysis
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Gilbertsunconjugated hyperbilirubinaemia
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HaemolysisUnconjugated hyperbilirubinaemia
splenomegaly, anaemia ,
DCT, haptoglobin, reticulocyte count, film
2) -Glutamyl transpeptidase
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The high sensitivity and very low specificity seriously
hampers the usefulness of this test
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If ALP is elevated and GGT is elevated then the raise in
ALP is likely to be hepatic in origin
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Elevated in
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a whole host of liver diseases
Drugs/Alcohol
Obesity/ dyslipidaemia/ DM
CCF
Kidney, Pancreas, Prostate
2) ALT rise predominant
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
Case - Mr Z
59y Architect
Type 2 DM 15 yrs on diet alone
BMI 35
Hypertension
Amlodipine , Ramipril
Minimal Alcohol
Mr RP
 Generally
unwell for 2 years
 Cytopaenia
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Low Hb/platelets
Normal haematological Ix (peripheral
consumption)
 May
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07
LGH admission with ataxia/drowsiness
Extensive Ix
Mr RP
 CT
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abdo
cirrhotic liver, portal hypertension, splenomegaly
 OPD
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referral
Alb 28, Pl 65 LFT’s normal, INR 1.5
Imaging compatible with cirrhosis
Reversal of sleep pattern, lack of concentration
Daytime somnelence, intermittant confusion
OGD- varices
How common is NAFLD?
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The most common cause of abnormal liver
function tests in the United States.
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Estimated 30.1 million with NAFLD and 8.6
million with NASH
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Affects 10-24% of the population
 58-74% of the obese population
 Affects 2.6% of children
 23-53% of obese children
Non Alcoholic Fatty Liver Disease (NAFLD)
Spectrum of Hepatic Pathology
Steatohepatitis
Steatosis
Cirrhosis
Hepatocellular
carcinoma
Diseases Associated with Steatohepatitis
1.Alcoholism
2.Insulin resistance
a.Metabolic Syndrome
i.Obesity
ii.Diabetes
iii.Hypertriglyceridemia
iv.Hypertension
b.Lipoatrophy
c.Mauriac Syndrome
d.PCOS
3.Disorders of lipid metabolism
a.Abetalipoproteinemia
b.Hypobetalipoproteinemia
c.Andersen’s disease
d.Weber-Christian syndrome
4.Total parenteral nutrition
5. HCV (certain genotypes)
6. Untreated coeliac disease
7.Severe weight loss
a.Jejuno-ileal bypass
b.Gastric bypass
c.Severe starvation
8.Iatrogenic
a.Amiodarone
b.Diltiazem
c.Tamoxifen
d.Steroids
e.HAART
f. tetracycline
g.glucosamine
9.Refeeding syndrome
10.Exposure to toxic agents
a.Environment
b.Workplace – Sb,Th,Ba
NASH
Affects 3.5-5% of the population
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.
Natural history
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Simple steatosis: relatively benign “liver” prognosis with
a risk of developing clinical evidence of cirrhosis over
15–20 years in the order of 1%–2%.
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NASH and fibrosis: risk of progress to cirrhosis between
0% at 5 years to 12% over 8 years.
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Cirrhotic: high risk of developing hepatic
decompensation and of dying from a liver-related cause
including HCC.
Initial Investigation
 Look
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BMI, DM, HBP, Lipids,FHx, Drugs, Alcohol
 Liver
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for risk factors
screen (to exclude other diseases)
Including Glc/GTT/HbA1c/Lipids/AST
Pl, Alb, INR
 USS
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Spleen size, fatty liver, collaterals
Fibroscan®
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Electronic platform
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Integrated computer
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Ultrasonic signals acquisition
Numerical signal processing
Stiffness measurement
Examinations database
Dedicated probes with unique
technology
Vibrator (50 Hz)
US Transducer
(3,5 MHz)
Fibroscan® (Echosens, Paris, France)
Position of probe & explored volume
Cylinder of 1 cm wide & 4 cm long
From 25 mm to 65 mm below skin surface
This volume is at least 100 times bigger than a biopsy sample
Results
Stiffness (kPa)
Median value of 10 shots
3.9 Kilo Pascals
 IQR * (kPa)
Interval around median
Contains 50% of valid shots
≤ 25% of median value
 At least 10 shots
 Success Rate: ≥ 60%
NASH Management
1) All patients should be encouraged to exercise, as there is good evidence
that even in the absence of weight loss exercise improves NASH.
Obese Patients
Weight reducing diet (aim for 10%, 1-2lb per week)
In patients with BMI>28 with risk factors, or >30 without risk factors,
consider treatment with Orlistat etc.
2) Diabetic Patients
Good diabetic control (HbA1c <6.5%)
Metformin
Thiazolidinediones
Dietician for re-education.
Diabetologist if glucose control is difficult.
NASH Management
3) Patients with Hyperlipidaemia and abnormal LFT’s
Dyslipidaemia should be aggressively addressed
Dietician Review
Hypercholesterolaemia -Statins
Hypertriglycerideaemia -Fibrate.
Lipid Clinic
Avoid Drugs
amiodarone, glucocorticoids, methotrexate, nifedipine, synthetic
estrogens, tamoxifen
Antioxidants?
Alcohol Related Deaths
E&W 1979-2010
http://www.statistics.gov.uk/cci/nugget.asp?id=1091
Monthly admission rate
UHL Alcohol Admissions 2004-8
Spectrum of Alcoholic Liver Disease
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The most common manifestations of alcoholic
liver disease are:
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Alcoholic steato-hepatitis
Acute alcoholic hepatitis
Cirrhosis due to alcohol
Alcoholic Hepatitis
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Most florid manifestation of ALD
Cholestatic liver disease associated with the long term
heavy use of alcohol
Often a precursor to the development of cirrhosis
More severe forms are associated with a high mortality
1yr mortality after initial hospitalisation is 40%
Best treatment
 Stop drinking
 Resolution occurs within weeks-months +/- cirrhosis
Symptoms
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Fever
Hepatomegaly
Jaundice
Coagulopathy
Features of hepatic decompensation
However, milder forms of alcoholic hepatitis
often do not cause any symptoms
Investigation
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Biochemistry
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AST/ALT ratio >1.5
ALT usually <100 IU/ml
Raised GT (variable)
Raised ALP (variable)
Low Albumin (advanced
disease)
Bilirubin (≥80 mmol/l)
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Haematology
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Prolonged INR
(advanced disease)
Macrocytosis /
anaemia
Leukocytosis
Thrombocytopenia
(advanced disease)
Glasgow Alcoholic Hepatitis Score
Score
1
Age
<50
WCC(109/l) <15
Urea (mmol/l)<5
PT ratio
<1.5
Bili (mol/l) <125
2
3
≥ 50
≥15
≥5
1.5-2.0
125-250
>2.0
>250
Patients score from 5-12 points.
Score >8 was used to define the high risk population
and maximised sensitivity and specificity.
Survival from Alcoholic Hepatitis
Derivation and validation datasets combined – 436 patients
Day 1
GAHS <9
GAHS ≥9
28 day survival (%)
84 day survival(%)
87
46
79
40
93
47
86
37
Day 7
GAHS<9
GAHS ≥9
Corticosteroids
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If the patient has severe alcoholic hepatitis
mDF>32, MELD >11, GAHS>8
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Therapeutic trial of prednisolone 40mg PO
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7 days
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If no improvement in bilirubin then discontinue
Mathurin P Hepatol 2003;38;1363-9
Louvet A Hepatol 2008;45:1348-54
Pentoxifylline
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PTX is a phosphodiesterase inhibitor which modulates
the transcription of the TNFα-gene, lowers blood
viscosity and reduces portal hypertension.
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RCT
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101 patients with severe alcoholic hepatitis (mDF>32).
Given 400mg tds for 28 days vs placebo
Mortality 24% vs 46% at 28 days
Significant reduction in hepatorenal syndrome
Acriviadis E, Gastro 2000 119;1637-48
3) ALP Elevated
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Cholestatic Illness (With or without jaundice)
Differentiate from Bony ALP
GGT, ALP iso-enzymes
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
Liver ALP Elevated
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Cholestatic Illness
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Acute
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CBD stones/Gallstones
Tumours 1º or 2º
Pancreatic pathology
Drugs
Infiltration
SOD
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Chronic
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PBC
Sclerosing Cholangitis
• 1º or 2º
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NASH
α-1 antitrypsin
Sarcoid
Amyloid
HIV
Drug Induced Cholestasis
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Intrahepatic Hepatocellular Cholestasis
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Intrahepatic Ductular cholestasis
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Ductopenic
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Granulomatous
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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
The END
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258 6630
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