1. Viral Hepatitis Graham R Foster Professor of Hepatology
Queen Marys School of Medicine
Barts Health

2. Standardized Death Rates UK <65 yr (1970 = 100%)
UK Standardised death rates (<65 years)
Standardized Death Rates UK <65 yr (1970 = 100%)
LIVER AND DIGESTIVE HEALTH - UCLPartners

3. Hepatitis
Increased ALT (GGT can be ignored)
Drugs
Bugs
(Autoimmune)

4. Hepatitis Increased ALT (GGT can be ignored) Drugs – ALCOHOL and FAT
Bugs
(Autoimmune)

5. Hepatitis Increased ALT (GGT can be ignored) Drugs – ALCOHOL and FAT
Bugs – VIRAL HEPATITIS
(Autoimmune)

6. Hepatitis Increased ALT (GGT can be ignored) Drugs – ALCOHOL and FAT
Bugs – VIRAL HEPATITIS
(Autoimmune)
These are NOT mutually exclusive

7. Viral Hepatitis Hanging around together
Alcohol and viruses hang around together
Viruses and fat make a great team
A drinker with high ALT remains at risk of viral hepatitis

8. Hepatitis Increased ALT (GGT can be ignored) Drugs – ALCOHOL and FAT
Bugs –VIRAL HEPATITIS - rare in the UK
(Autoimmune)

9. We live on planet earth >= 8% - High HBsAg Prevalence
2-7% - Intermediate
<2% - Low 36

10. We live on planet earth >= 8% - High HBsAg Prevalence
2-7% - Intermediate
<2% - Low 36

11. Planet Earth If it moves VACCINATE IT
Combined HBV and HAV vaccine is best

12. We live on planet earth >= 8% - High HBsAg Prevalence
2-7% - Intermediate
<2% - Low 36

13. Planet Earth
Acute hepatitis is not uncommon
Consider HAV, HBV, HEV

14. Planet Earth
Acute hepatitis is not uncommon
Consider HAV, HBV, HEV

15. Planet Earth Acute hepatitis is not uncommon Consider HAV, HBV, HEV
Think FUNCTION – INR is all that counts
If the INR is high – call us
(Liver SpR or Liver Consultant or My Mobile)

16. Chronic Viral Hepatitis
Chronic HBV
Chronic HCV

17. HBV in East London
HBV is a disease of immigrants

18. HBV in East London

19. Hepatitis B: Natural History
Hepatitis B causes a slowly progressive disease that leads to cirrhosis and liver cancer
At least 30% of people with HBV will die from it

20. HBV in East London Modelling the disease in people from India

21. Hepatitis B: Natural History

22. HBeAg– Virological Response: HBV DNA <400 copies/mL at Year 4‡
Study HBeAg-Negative Patients
100 90 80 70 60 50 40 30 20 10
87%
84%
• TDF-TDF
• ADV-TDF
Percentage %
ITT: LTE-TDF Analysis
100 90 80 70 60 50 40 30 20 10
Weeks on Study
100%
99%
Percentage %
On-Treatment Analysis
Marcellin P, et al. AASLD 2010; Poster #476.
Weeks on Study

23. HBV Therapy We use:- Pegylated Inerferon OR Oral antiviral agents
Monitoring

24. HBV
If we find it – we can control it

25. HBV in Immigrants If we find it – we can control it
If we don’t find it – patients will die

26. HCV Very common in immigrants
Very common in people who have used drugs

27. HCV 45 year old man with diabetes Graphic designer in West London
ALT 160

28. HCV 45 year old man with diabetes Graphic designer in West London
ALT 160
Diabetic clinic asked GP to perform liver screen – no action
Persistently high ALT

29. HCV 45 year old man with diabetes Graphic designer in West London
ALT 160
Diabetic clinic asked GP to perform liver screen – no action
Persistently high ALT
Age 54 tested for HCV - +ve, in hepatology clinic described past drug use
US shows HCC – palliative therapy given

30. Viral Hepatitis in East London Screening for hepatitis in the Mosque
Bangladesh
HCV – 4/726 (0.6%)
HBV – 11/726 (1.5%)

31. Pakistan

32. Age Distribution & Ethnicity of Patients with HCV Admitted over 1 year at RLH5 10 15 20 25 30
<20
20-29
30-39
40-49
50-59
60-69
70-79
White British - Yes
Pakistani - Yes
Bangladeshi - Yes
Count of HCV
Age
Ethnicity
HCV

33. People from Pakistan, living in UK
Female
Male
People from Bangladesh, living in UK
Female
Male

34. HCV in Immigrants HCV is common in immigrants
The number of immigrants with advanced fibrosis is about to explode

35. HCV in Immigrants HCV is common in immigrants
The number of immigrants with advanced fibrosis is about to explode
BUT – we have good treatments

36. Sofosbuvir with PEG-IFN + RBV (NICE approved for August)
NEUTRINO Phase III trial
Sofosbuvir plus PEG-IFN + RBV* for 12 weeks
Treatment naïve, GT1 (89%), 4, 5 or 6 (N=327)
17% had compensated cirrhosis
Primary endpoint: SVR12
Abbreviations:
PEG-IFN + RBV = pegylated interferon and ribavirin
GT = genotype
SVR12 = sustained virological response after 12 weeks of stopping therapy
EOT = end of treatment
RBV administered according to body weight (1000mg/day in patients <75kg; 1200mg/day in patients≥75kg)
*Dose administered according to body weight
†Last observed measurement
Lawitz et al. N Eng J Med 2013;368:1878–87

37. Results: SVR12 in GT 3 by Treatment History and Cirrhosis Status
SOF + RBV 16 weeks
SOF + RBV 24 weeks
SOF + PEG/RBV 12 weeks
SVR12 (%)
DCV+SOF x 12 weeks for comparison: TN NC 97% (73/75), TN C 58% (11/19)
58 70
65 72
68 71
12 21
18 22
21 23
41 54
44 54
49 52
17 36
26 34
30 35
94/112
83/100
10/11
No Cirrhosis
Cirrhosis
No Cirrhosis
Cirrhosis
Treatment Naïve
Treatment Experienced
Error bars represent 95% confidence intervals.

38. HCV – It gets even better
Highly effective all oral therapies are now available
(NICE approval pending)

39. Sofosbuvir/ledipasvir ± RBV for 8 weeks vs 12 weeks in treatment-naive non-cirrhotic G1 HCV-infected patients
LDV/SOF n=216
LDV/SOF n=215
LDV/SOF + RBV n=216
Wk 0
Wk 8
Wk 12
Wk 24
Wk 20
SVR12
Stratified by HCV subtype (1a or 1b)
G1 treatment-naive patients without cirrhosis
LDV/SOF
8 weeks
12 weeks
LDV/SOF + RBV
201/216
202/215
206/216
SVR12 (%)
SVR12 G1 treatment naive
Abstract not available
Kowdley K.V, et al. NEJM 2014;370:1879

40. Baseline Characteristics Patients treated in the UK with cirrhosis
Total
N = 467 G1
N = 235 G3
N = 189
Others
N = 43
Decompensated cirrhosis
(Past or present)
441
(94.4%)
223
(94.9%)
179
(94.7%) 39
(90.7%)
CP-B
309
(66.2%)
161
(68.5%)
121
(64.0%) 27
(62.8%)
CP-C 46
(9.9%) 19
(8.1%) 24
(12.7%) 3
(7.0%)
MELD mean (range)
11.9
(6-36)
11.3
(6-24)
12.6
(6-22)
Active ascites
178
(38.1%) 97
(41.3%) 67
(35.4%) 14
(32.6%)
Previous variceal bleed
127
(27.2%) 61
(26.0%) 55
(29.1%) 11
(25.6%)
Active encephalopathy 80
(17.1%) 41
(17.4%) 34
(18.0%) 5
(11.6%)

41. SVR12 by Genotype and Regime
SVR12 defined as HCV RNA at 12 weeks post-treatment < 30 IU/ml

42. Functional Outcome Change in MELD: Baseline – Follow up week 4
Comparative MELD scores available for 220 patients

43. HCV – Towards a global cure
We now have drugs that allow us to eliminate HCV from the UK
NHS E are working on a policy with regional networks, centrally funded drugs and a prioritisation program

44. HCV – Towards a global cure
We now have drugs that allow us to eliminate HCV from the UK
NHS E are working on a policy with regional networks, centrally funded drugs and a prioritisation program
All we now is to find the patients!

45. HEP-Free (Foster/Griffiths)
NIHR funded grant (£2 million)
90 GP practices –
(Newham, SE London, Bradford, Oxford)
All immigrants will be tested for viral hepatitis and offered therapy

46. HepFREE
If HepFREE is a success screening immigrants for viral hepatitis will become a national priority
We are looking for volunteers
(You will be re-imbursed, supported and will play a role in chaning UK health care)

47. Viral Hepatitis Common –VERY common in East London
(Think DRUGS – ETHNICITY)
Major cause of preventable deaths/cancer
Curable
Test – Refer - Treat