Transcript Hepatitis C- Global and National Perspective

10 Top Tips in Liver Disease
Dr Allister J Grant
Consultant Hepatologist
University Hospitals Leicester NHS Trust
LIVER
FUNCTION
TESTS
Alanine aminotransferase
Aspartate aminotransferase
Alkaline phosphatase
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
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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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Age/Sex
Drugs/Antibiotics
FHx gallstones
Abdo Pain
Red flag symptoms
Jaundice?
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Recurrent Fever
Itch/lethargy
Dry eyes/mouth
Colitis
Pain
SOB/afrocarribean
CCF
Liver ALP Elevated
• Cholestatic Illness
• Acute
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CBD stones/Gallstones
Tumours 1º or 2º
Pancreatic pathology
Infiltration
Drugs
• Flucloxacillin
• Augmentin
• TB drugs
• Chronic
– PBC
– Sclerosing Cholangitis
• 1º or 2º
– Sarcoid
– Amyloid
Liver ALP Elevated
• Imaging
USS/CT Abdo
MRCP
ERCP
If imaging shows no cause then liver biopsy may be
appropriate
• Auto Ab
– AMA, ANCA
• Immunoglobulins (IgM)
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
5) Making a clinical diagnosis of cirrhosis
• Suspicion- history and clinical findings
• Thrombocytopenia
• Low Alb
• USS/Other Imaging
– irregular liver outline
– splenomegaly
– Collaterals/ recanalisation of umbilical vein
– Ascites
5) Making a diagnosis of cirrhosis
• Liver Biopsy –Percutaneous/Transjugular
• Fibrotest
• Fibroscan
6) Surveillance in Cirrhosis
• Surveillance for Hepatoma
6 monthly AFP and USS
Confirm with second mode of imaging
• Triple phase CT
• Contrast enhanced USS
• Avoid biopsy
HCC Treatment
• Liver Transplant –Milan Criteria
• Resection
– Standard
– Laparoscopic
• Ablation Techniques
– RFA
– MWA
– Alcohol
• TACE
Surveillance in Cirrhosis
• Surveillance for Oesophageal Varices
Primary prophylaxis
• Propranolol 40mg tds
– Aim to reduce HR by 25%
Surveillance for Bone Disease
• DEXA Scanning
Case
Mr M.A
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
7) Making a diagnosis of HCV
infection and
what to do about it?
HCV- Natural History
100 Infected
80 Develop Chronic Hepatitis
20 Clear the HCV
HCV Ab pos
PCR neg
PCR pos
20 No Harmful Effects
60 Signs/symptoms
20% at 20yrs
50% at 30yrs
Transplantation
Liver Failure
3.9% pa
Liver Cancer
1.4% pa
CIRRHOSIS
Age
Gender
Alcohol
Prevalence of Hepatitis C virus
2001 WHO
Risk Factors Associated with
Transmission of HCV
• Injecting drug use
• Transfusion or transplant from infected donor
• Hemodialysis (yrs on treatment)
• Accidental injuries with needles/sharps
• Sexual/household exposure to anti-HCV-positive contact
• Multiple sex partners
• Birth to HCV-infected mother
UK HCV Prevalence <1%
IV Drug Use
Blood Donation
200,000
Migration
Historical Perspective
• IFN monotherapy
SVR <20%
• IFN 3MU s/c 3x week + Ribavirin po SVR ~ 40%
Manns M et al Lancet 2001
1530 pts
PEG IFN
PEG IFN
1.5mcg/kg/wk 1.5mcg/kg/wk
+Ribavirin
For 4 wks then
0.5mcg/kg/wk
+Ribavirin
IFN 3MU
3xwk
+Ribavirin
IFN & Ribavirin
Sustained virological responses
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
>80%
50%
genotype 1
genotype 2 & 3
Mr RP
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
– Low Hb/platelets
– Normal haematological Ix (peripheral
consumption)
• May 07
– LGH admission with ataxia/drowsiness
– Extensive Ix
Mr RP
• CT abdo
– cirrhotic liver, portal hypertension, splenomegaly
• OPD referral
– Alb 28, Pl 65, LFT’s normal, INR 1.5
– Imaging compatible with cirrhosis
– Reversal of sleep pattern, lack of concentration
– Daytime somnolence, intermittent confusion
– OGD- varices
8) 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
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.
NASH Management
All patients should be encouraged to exercise, as there is good
evidence that even in the absence of weight loss exercise improves
NASH.
Diabetic Patients
Good diabetic control (HbA1c <6.5%)
Metformin
Thiazolidinediones (glitazones)
Dietician for re-education.
Diabetologist if glucose control is difficult.
NASH Management
Patients with Hyperlipidaemia and abnormal LFT’s
Dyslipidaemia should be aggressively addressed
Dietician Review
Hypercholesterolaemia -Statins
Hypertriglycerideaemia -Fibrate.
Lipid Clinic
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.
Avoid Drugs
amiodarone, glucocorticoids, methotrexate, nifedipine, synthetic
estrogens, tamoxifen
9) Hepatitis B“the inactive carrier”
Viral fluctuation patterns are different
in different stages of the disease
HBeAg
Anti-HBe
HBV-DNA
ALT
immune immune
tolerance clearance
inactive
carrier
reactivation
Prevalence of HBeAg negative Chronic
HBV in Italy
HBeAg positive
1975-85: 539 patients
HBeAg negative
2001: 837 patients
10%
42%
58%
Giusti et al, 1991
90%
Gaeta et al, 2003
Inactive carrier?
HBeAg(-)
CHB
Detection limit
Inactive
carrier
Detection limit
HBV DNA Thresholds
Serum HBV DNA (copies/ml)
1010
109
108
107
106
HBeAg (+)
CHB
HBeAg (-)
CHB
105
104
103
102
10
Inactive
Carrier
State
How do we manage eAg neg patients in clinic?
• HBV DNA every 3 months in the first year
• If HBV DNA consistently <103 then see yearly
• If HBV DNA >104 then consider Rx depending on the
clinical situation
• Low threshold for biopsy
• If significant fibrosis then treat (whatever the DNA)
Therapy For HBV is Rapidly Evolving
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Approved Drugs
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Conventional Interferons (IFNs)
Lamivudine (LMV)
Adefovir (ADV)
Pegylated Interferon a-2a (PEG-IFN)
Future Options
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Entecavir (ETV)
Tenofovir (TDF)
Telbivudine (LdT)
Clevudine
Pradefovir
Emtricitabine
Valtorcitabine
etc…………..
Monotherapy
Sequential therapy
Combination therapy
10) If in doubt - ask
0116 258 6423
[email protected]