Update on Hepatitis B and Hepatitis C Catherine Stedman Department of Gastroenterology, Christchurch Hospital and University of Otago, Christchurch
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
Hepatitis B Who gets Hep B? Acute Hepatitis B Chronic Hepatitis B Prevention/treatment
Hepatitis B - A Global Problem RoW Asia Pacific 75% 75% of long-term carriers live in Asia Pacific 5 350 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
Estimated >90,000 HBsAg+ living in New Zealand Majority are Maori, Pacific or Asian ethnicity Pacific 295000 Asian, 395,000 Asia-Pacific Maori, 625000 European 2.7million
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: www.cdc.gov/ncidid/disease/hepatitis/b/. Accessed: 2 October 2004; Lee WM. N Engl J Med 1997; 337: 1733 45; Lavanchy D. J Viral Hepat 2004; 11: 97 107.
Hepatitis B: Acute Hepatitis B vs Chronic Hepatitis B
Acute Hepatitis B Incubation Few weeks- 6 months (mean 60-90 days) Prodrome: Serum-sickness like illness (fever, arthralgia, rash 20%) Acute hepatitis: 30% Jaundice ALT typically 1000-2000U/L Fulminant hepatitis <1%
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
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
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
% anti-hbcore+ 1984: NZ Kawerau Community Study Township built in 1953 around paper mill Population 10,000, predominantly Maori 98% of population screened 100 80 60 40 20 Mode of HBV transmission is early horizontal not just vertical 0 0 5 10 15 20 25 30 35 40 45 50 55 Age (years) Milne A et al. I J Epidem 1987; 16: 84-90
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 0.8 0.70 0.8 0.80 0.6 0.57 0.6 0.58 0.4 0.36 0.4 0.34 0.2 0.2 0 1981-86 1986-90 1990-94 0 1981-86 1986-90 1990-94 *Nationwide vaccination in Taiwan, implemented July 1984. Chang MH, et al. N Engl J Med. 1997;336:1855-1859.
Questions to identify people at risk of Chronic Hepatitis B Where were you born? Ethnic background? Is there hepatitis B in your family?
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
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; 921-6.
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
Hepatitis B: Prevention
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 20 30 years
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)
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
Hepatitis C in NZ Estimated 50000 in NZ with Hepatitis C 25% diagnosed Leading cause for liver transplantation Liver cancers increasing 100 80 60 40 20 0 0 1 0 1 1 1 1 1 3 8 8 12 51 38 41 27 12 21 11 13 6 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 74
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
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
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
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
What advice should I give my patient with Hepatitis C? Get your liver assessed Liver biopsy seldom required now
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
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)
Hepatitis C Treatment Is HCV worth treating? What are the treatment options?
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
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
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
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
SVR12 (%) Ledipasvir/Sofosbuvir in HCV Genotype 1 Efficacy: Phase 3: ION-1, ION-2, ION-3 LDV/SOF LDV/SOF+RBV 100 99 97 98 99 94 93 95 94 96 99 99 80 60 40 20 0 211/ 214 211/ 217 212/ 217 215/ 217 202/ 215 201/ 216 12 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/ 216 102/ 109 107/ 111 108/ 109 110/ 111 97% (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
The only problem.. $ 1000 US per tablet $27000 NZ per month
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