Hepatitis C Global and National Perspective

1
10 Top Tips in Liver Disease Dr Allister J
Grant Consultant Hepatologist University
Hospitals Leicester NHS Trust
2
LIVERFUNCTION TESTS
Alanine aminotransferase Aspartate
aminotransferase Alkaline phosphatase Bilirubi
n Albumin
3
Abnormal LFTs in well patients

• Isolated raise in bilirubin
• ALT rise predominant
• ALP rise predominant

4
1) Isolated raise in bilirubin

• Differential Gilberts vs Haemolysis
• Gilberts-
• unconjugated hyperbilirubinaemia
• Haemolysis-
• Unconjugated hyperbilirubinaemia
• splenomegaly, anaemia ,
• DCT, haptoglobin, reticulocyte count, film

5
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

6
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

7
ALT elevated

• Hepatitic illness
• Acute
• Hep A,B,C,E
• EBV, CMV, TOXO
• Drugs screen?
• Immunoglobulins
• Autoimmune profile
• Caeruloplasmin (lt50)

• Chronic
• TFT
• Diabetic screen
• Hep B, C
• Lipids
• Immunoglobulins
• Autoimmune profile
• Ferritin
• Caeruloplasmin (lt50)
• a-1 antitrypsin
• TTG
• ACE

8
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
• Recurrent Fever
• Itch/lethargy
• Dry eyes/mouth
• Colitis
• Pain
• SOB/afrocarribean
• CCF

9
Liver ALP Elevated

• Cholestatic Illness
• Acute
• CBD stones/Gallstones
• Tumours 1º or 2º
• Pancreatic pathology
• Infiltration
• Drugs
• Flucloxacillin
• Augmentin
• TB drugs

• Chronic
• PBC
• Sclerosing Cholangitis
• 1º or 2º
• Sarcoid
• Amyloid

10
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)

11
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

12
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

13
5) Making a diagnosis of cirrhosis

• Liver Biopsy Percutaneous/Transjugular
• Fibrotest
• Fibroscan

14
6) Surveillance in Cirrhosis

• Surveillance for Hepatoma

6 monthly AFP and USS
15

• Confirm with second mode of imaging
• Triple phase CT
• Contrast enhanced USS
• Avoid biopsy

16
HCC Treatment

• Liver Transplant Milan Criteria
• Resection
• Standard
• Laparoscopic
• Ablation Techniques
• RFA
• MWA
• Alcohol
• TACE

17
Surveillance in Cirrhosis

• Surveillance for Oesophageal Varices

18
Primary prophylaxis

• Propranolol 40mg tds
• Aim to reduce HR by 25
• DEXA Scanning

Surveillance for Bone Disease
19
Case
20
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
21
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
22
OE ? Vasculitic rash on legs SR PSM SOA Liver
edge Splenomegaly ? Ascites Hb
11.9 ALP 146 UE normal WCC 4.7 ALT 31 Plt
42 Bili 54 INR 1.7 Alb 32
23
What investigations?
24
USS Irregular liver, splenomegaly, PV
patent Liver screen HBV sAg Endoscopy-
OGD HCV Ab Flexi Sig Auto Ab IgG IgA and
M Ferritin Copper Caeruloplasmin A1AT
25
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.
26
OPD PCR negative x2 A1AT lt0.3 Transjugular
Liver Biopsy A1AT phenotype Pi ZZ
27
AccumulationHistology and EM
28
7) Making a diagnosis of HCV infection and what
to do about it?
29
HCV- Natural History
100 Infected
Transplantation
30
Prevalence of Hepatitis C virus
2001 WHO
31
Risk Factors Associated withTransmission 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

32
UK HCV Prevalence lt1
IV Drug Use
Blood Donation
200,000
Migration
33
Historical Perspective

• IFN? monotherapy -
• SVR lt20
• IFN? 3MU s/c 3x week Ribavirin po -
• SVR 40

34
Manns M et al Lancet 2001
PEG IFN? 1.5mcg/kg/wk Ribavirin
PEG IFN? 1.5mcg/kg/wk For 4 wks then
0.5mcg/kg/wk Ribavirin
IFN? 3MU 3xwk Ribavirin
1530 pts
35
IFN RibavirinSustained virological responses
gt80
50
36
Mr RP

• 59y Architect
• Type 2 DM 15 yrs on diet alone
• BMI 35
• Hypertension
• Amlodipine , Ramipril
• Minimal Alcohol

37
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

38
Mr RP

• CT abdo
• cirrhotic liver, portal hypertension,
  splenomegaly
• OPD referral
• Alb 28, Pl 65, LFTs normal, INR 1.5
• Imaging compatible with cirrhosis
• Reversal of sleep pattern, lack of concentration
• Daytime somnolence, intermittent confusion
• OGD- varices

39
8) Non-Alcoholic Fatty Liver Disease
40
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 BMIgt28 Centipetal
(apple) Bright liver on USS Normal ALT
41
NASH
Steatosis
Cirrhosis
42
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.

43
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 lt6.5)
• Metformin
• Thiazolidinediones (glitazones)
• Dietician for re-education.
• Diabetologist if glucose control is difficult.
•  
•  

44
NASH Management

• Patients with Hyperlipidaemia and abnormal LFTs
• 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 BMIgt28 with risk factors, or
  gt30 without risk factors, consider treatment with
  Orlistat.
•   Avoid Drugs
• amiodarone, glucocorticoids, methotrexate,
  nifedipine, synthetic estrogens, tamoxifen

45
9) Hepatitis B- the inactive carrier
46
Viral fluctuation patterns are different in
different stages of the disease
47
Prevalence of HBeAg negative Chronic HBV in Italy
HBeAg positive HBeAg negative
1975-85 539 patients
2001 837 patients
10
58
42
90
Giusti et al, 1991
Gaeta et al, 2003
48
HBeAg(-) CHB
Detection limit
Inactive carrier
Detection limit
49
HBV DNA Thresholds
50
How do we manage eAg neg patients in clinic?

• HBV DNA every 3 months in the first year
• If HBV DNA consistently lt103 then see yearly
• If HBV DNA gt104 then consider Rx depending on the
  clinical situation
• Low threshold for biopsy
• If significant fibrosis then treat (whatever the
  DNA)

51
Therapy For HBV is Rapidly Evolving

• Approved Drugs
• Conventional Interferons (IFNs)
• Lamivudine (LMV)
• Adefovir (ADV)
• Pegylated Interferon a-2a (PEG-IFN)
• Future Options
• Entecavir (ETV)
• Tenofovir (TDF)
• Telbivudine (LdT)
• Clevudine
• Pradefovir
• Emtricitabine
• Valtorcitabine
• etc..

Monotherapy Sequential
therapy Combination therapy
52
10) If in doubt - ask
0116 258 6423
Allister.J.Grant_at_uhl-tr.nhs.uk