Update on Hepatitis B and Hepatitis C

Transcription

1 Update on Hepatitis B and Hepatitis C Catherine Stedman Department of Gastroenterology, Christchurch Hospital and University of Otago, Christchurch

2 Disclosures I have the following financial relationships to disclose within the past 12 months: Advisory board committees or speaking for Gilead Sciences, Janssen, MSD 2

3 Hepatitis B Who gets Hep B? Acute Hepatitis B Chronic Hepatitis B Prevention/treatment

4 Hepatitis B - A Global Problem RoW Asia Pacific 75% 75% of long-term carriers live in Asia Pacific million long-term carriers worldwide 1 Up to 25% will die due to hepatitis B or related complications 2 ~ 1 million die each year from HBV infection 3 (9th leading cause of death worldwide 4) 1 WHO 1998; 2 Mast 1993; 3 Lee 1997; 4 Boag 1991; 5 Gust 1996

5 Estimated >90,000 HBsAg+ living in New Zealand Majority are Maori, Pacific or Asian ethnicity Pacific Asian, 395,000 Asia-Pacific Maori, European 2.7million

6 Transmission of HBV Vertical transmission Horizontal transmission Mother Host Recipient Infant Perinatal 90% of infected infants become chronically infected Child-to-child (playground) Contaminated needles Sexual Healthcare worker Transfusion Rate of chronicity dependent on age CDC Fact Sheet. Available at: Accessed: 2 October 2004; Lee WM. N Engl J Med 1997; 337: ; Lavanchy D. J Viral Hepat 2004; 11:

7 Hepatitis B: Acute Hepatitis B vs Chronic Hepatitis B

8 Acute Hepatitis B Incubation Few weeks- 6 months (mean days) Prodrome: Serum-sickness like illness (fever, arthralgia, rash 20%) Acute hepatitis: 30% Jaundice ALT typically U/L Fulminant hepatitis <1%

9 How is Acute Hepatitis B Acquired? (Western Countries) Transfusion and transplant recipients Newborns of long-term carriers sexual partners Intravenous drug users Healthcare workers Prisoners and other institutionalised people

10 Acute Hepatitis B: Management 1. Monitor LFTs, INR, creatinine, albumin twice weekly until improving Refer if INR/creatinine or albumin 2. Screen/vaccinate contacts; notify Department of Health 3. Follow up: HBsAg, anti-hbs HBsAg negative by 12 weeks in 80% of cases Refer if HBsAg remains positive Most Acute Hep B is self-limited Acute liver failure 5% develop chronic HepB

11 How is Chronic Hepatitis B Acquired? Transfusion and transplant recipients Individuals with multiple sexual partners Early childhood/ Newborns of long-term carriers Chronic hepatitis B Intravenous drug users Healthcare workers Prisoners and other institutionalised people

12 % anti-hbcore+ 1984: NZ Kawerau Community Study Township built in 1953 around paper mill Population 10,000, predominantly Maori 98% of population screened Mode of HBV transmission is early horizontal not just vertical Age (years) Milne A et al. I J Epidem 1987; 16: 84-90

13 Per 100,000 Children (6-14 Yrs) Per 100,000 Children (6-14 Yrs) HBV Vaccination: Reduces HCC Incidence and Mortality* 1 Incidence 1 Mortality *Nationwide vaccination in Taiwan, implemented July Chang MH, et al. N Engl J Med. 1997;336:

14 Questions to identify people at risk of Chronic Hepatitis B Where were you born? Ethnic background? Is there hepatitis B in your family?

15 Maori Cook Is Niuean Tongan Indian (50,000) SE Asian (20,000) Chinese (72,500) % HBsAg+ NZ National HBV Screening Programme Prevalence according to Ethnicity 20% 15% 13.3% 10% 5.8% 7.4% 9.1% 9.3% 9.4% 5% 0% 0.6% Robinson T, et al. NZ Med J. 2005; 118: No. 1211

16 Hepatitis B in Pregnancy Prevention of Vertical Transmission 262 HBsAg+ Hong Kong women» Randomised to 4 post-partum regimens» 47% were HBeAg+» 33 babies were infected % babies HBsAg+ at 6 mths 80% 60% 40% 20% 0% 73% Protective Efficacy Rates 71% 21% 7% Placebo Vaccine Vaccine +1xHBIG 91% 97% 3% Vaccine +>1xHBIG Wong VCW et.al Lancet 1984;

17 Prevention of in-utero HBV transmission For high risk women (HBeAg +ve with high viral loads) Antiviral therapy with tenofovir in 3 rd trimester reduces in-utero transmission

18 Hepatitis B: Prevention

19 Consequences of chronic HBV infection 60% Liver stays normal for many years Normal Chronic HBV infection 40% Liver damage = the result of unsuccessful attempts to clear infected hepatocytes in the immunoclearance stage of disease CIRRHOSIS CIRRHOSIS/ ESLD HCC years

20 Practical aspects of Hep B treatment Goal: good immune control or undetectable HBV DNA on drugs Interferon: specialist hepatitis nurses monitor patients Direct acting antivirals (entecavir/tenofovir) Continuous drug supply is crucial Avoid interrupted dosing (mutations/ resistance) Never stop abruptly (risk of fatal flares) Pregnancy: discuss with specialist (switch to tenofovir)

21 Hepatitis B: Key Points 1. Hepatitis B major cause of morbidity and mortality 2. Vaccinate! 3. Screen NZ Maori, people from Asia-Pacific and known contacts for HBsAg 4. Educate pregnant women with HBV 5. All Hepatitis B carriers require lifelong monitoring 6 monthly LFT and AFP Hepatitis Foundation NZ can assist with monitoring

22 Hepatitis C in NZ Estimated in NZ with Hepatitis C 25% diagnosed Leading cause for liver transplantation Liver cancers increasing

23 Risk factors for Hepatitis C Injecting drug use (even once!) Tattoos Blood transfusion pre 1992 Overseas healthcare Time in prison Sexual partner with HCV Mother with HCV Especially baby boomers

24 Risk factors for Hepatitis C Injecting drug use (even once!) Tattoos You cannot tell by looking at the Blood transfusion pre 1991 patient Overseas healthcare Check the HCV Antibody Time in prison Sexual partner with HCV Mother with HCV Especially baby boomers

25 Hepatitis C Initial tests Screening: HCV antibody test Confirmation: HCV viral load (PCR/RNA) If viral load negative - repeat in 3-6 months (exclude false negatives) If persistently negative then patient has cleared virus spontaneously If viral load positive check genotype Consider referral for fibroscan and treatment

26 What advice should I give my patient with Hepatitis C? Reduce alcohol NO alcohol if advanced liver fibrosis Reduce cannabis Cannabis increases liver fibrosis Encourage coffee Protective effect on liver Healthy weight - avoid additive effect of fatty liver Women with HCV - test their children

27 What advice should I give my patient with Hepatitis C? Get your liver assessed Liver biopsy seldom required now

28 What advice should I give my patient with Hepatitis C? Get your liver assessed Fibroscan now allows non-invasive assessment of liver fibrosis for patients with hepatitis C

29 Fibroscan for HCV: non invasive assessment of liver fibrosis Excellent at separating: Normal liver (F0/F1) No rush to treat HCV No need for USS surveillance From: Advanced fibrosis (F3/F4) HCV Treatment more urgent and difficult Requirement for HCC surveillance (USS)

30 Hepatitis C Treatment Is HCV worth treating? What are the treatment options?

31 Is Hep C worth Treating? YES HCV is potentially curable SVR = sustained virological response = cure Benefits: Mild liver disease: prevent liver damage Advanced liver fibrosis: marked reduction in morbidity and mortality

32 HCV Treatment Options: (1) Interferon based therapy Peginterferon +ribavirin +/- boceprevir Cure rates 30-80% Adverse effects ++ Flu-like syndrome Anorexia, weight loss Insomnia Bone marrow suppression Depression Contraindicated in some patients Refused by many patients Can t be used in patients with decompensated liver disease: risk of liver failure

33 HCV Treatment Options: (1) Interferon based therapy Peginterferon +ribavirin +/- boceprevi The only currently funded Cure rates 30-80% treatment in New Zealand Adverse effects ++ Flu-like syndrome Anorexia, weight loss Insomnia Bone marrow suppression Depression Contraindicated in some patients Refused by many patients

34 Hepatitis C New Direct Acting Antiviral Treatments Hepatitis C is now curable in 12-week alloral interferon-free regimens that are relatively free of side effects 34

35 SVR12 (%) Ledipasvir/Sofosbuvir in HCV Genotype 1 Efficacy: Phase 3: ION-1, ION-2, ION-3 LDV/SOF LDV/SOF+RBV / / / / / / Weeks 24 Weeks 8 Weeks 12 Weeks 12 Weeks 24 Weeks ION-1 GT 1 treatment-naïve including cirrhotics ION-3 GT 1 treatment-naïve non-cirrhotic ION-2 GT 1 treatment-experienced including cirrhotics and PI failures 206/ / / / / % (1886/1952) overall SVR rate Error bars represent 95% confidence intervals. Afdhal N, et al. N Engl J Med 2014; 2014 Apr 12 [Epub ahead of print] Kowdley K, et al. N Engl J Med 2014; 2014 Apr 11 [Epub ahead of print] Afdhal N, et al. N Engl J Med 2014; 2014 Apr 12 [Epub ahead of print

36 The only problem.. $ 1000 US per tablet $27000 NZ per month

37 Hepatitis C: Treatment Currently the only funded therapy for chronic HCV is interferon-based therapy Interferon-based treatment still has a role in many patients, particularly those who can t afford to wait Clinical Trials provide access to new direct acting antiviral drugs