FINANCIAL DISCLOSURE

Transcription

1 FINANCIAL DISCLOSURE People who work at NIH only dream about having financial disclosures Wait, this just in. The US government has now banned dreaming

2 CRITICAL NON-FINANCIAL DISCLOSURES Nothing I say reflects the position of the US government ---- which instantly gives it great credibility and relevance Because light travels faster than sound I will appear bright Until you hear me speak My guiding scientific principle is that to steal from one is plagiarism.. but to steal from many is research

3 TIMELINE OF HEPATITIS HISTORY First to Describe: Ikterus Kirros Campaign jaundice Vaccine jaundice Hep A vs. Hep B 2000 YEARS BC THE OATH Physician, first, do no harm Physician, second, get paid upfront and do not take Medicare 1960 s

4 HEPATITIS B: THE INFANT YEARS Baruch S. Blumberg, Harvey J. Alter, Sam Visnich JAMA 1965;191:541

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6 LANDMARK HBV EVENTS THAT FOLLOWED DISCOVERY OF THE AUSTRALIA ANTIGEN 1968: Prince shows Au specific for hep. B; names it SH : Okochi (Japan), Gocke (US), Holland, Alter, Purcell (NIH) link HAA to PTH 1970: Dane observes complete HBV virion by IEM ; HAA renamed HBsAg : Universal donor screening for HBsAg implemented in US and Japan 1972: Magnius and Espmark describe HBeAg 1976: Hilleman (Merck) develops sub-unit HBV vaccine 1977: Rizzetto, et al discover the Delta agent 1980: Szmuness and Stevens conduct clinical trial that establishes efficacy of HBV sub-unit vaccine 1981: Beasley in Taiwan and Kew in SA demonstrate strong link between HBV infection and HCC.

7 HEPATITIS HISTORY: THE NIH YEARS NANB EMERGES IN THE WAKE OF INVESTIGATIONS INTO POST-TRANSFUSION HEPATITIS

8 Post-Transfusion Hepatitis at NIH-1

9 Hepatitis Outcome in Prospectively Followed Patients Transfused with Unscreened Blood Total Patients (N=66) Hepatitis N=30 (45%) No Hepatitis N=36 (54.5%) HBV N=4 HCV N=20 HBV+ HCV N=6 HBV N=9 HCV N=4 HBV+ HCV N=1 100% d/t HBV or HCV 39% without ALT HBV or HCV infected NOTE: 44/66 (67%) infected. No Non-A, Non-B, Non-C

10 Biomarkers of Hepatitis Viruses in Unscreened Pooled Normal Human Plasma MARKER LOT #1 LOT #2 HBsAg + + Anti-HBc + + Anti-HBs - - HBV DNA 5.4** - Anti-HCV + + HCV RNA 3.5** 4.5** HDV RNA 2.1** - HEV RNA - - ** geq/ml

11 Post-Transfusion Hepatitis at NIH-2

12 Post-Transfusion Hepatitis at NIH-3 Transmitted From Patients with acute and chronic hepatitis Asymptomatic implicated donors

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15 WHAT WE KNEW BEFORE WE KNEW WHAT WE KNOW NOW NANB agent is small and lipid enveloped and unrelated to HAV, HBV and delta agent Agent likely to be in the family of small RNA flaviviruses Infection most often results in a persistent carrier state Agent transmitted by blood and primary cause of TAH. Transmitted not only from patients with acute hepatitis, but more commonly from chronic asymptomatic carriers Unknown: How serious is chronic NANB hepatitis?

16 Berman M, et al (1997);91:1-6

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18 There Is No Sense Chiron Over Spilt Milk

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20 Post-Transfusion Hepatitis at NIH-5

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24 After A Brief Stay in America, David Returns to Florence

25 Kiyosawa, et al Hepatology 1990

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27 Assuming no change in standard of care, cases of decompensated cirrhosis, HCC and need for tspl. will inc.>4-fold in next yrs.

28 100 Peginterferon Direct-acting antivirals Standard interferon 1991 Ribavirin Month s IFN 16 IFN IFN/RBV IFN/RBV PegIFN PegIFN/ RBV PegIFN/RBV /DAA

29 IFN-Free Oral Therapy with Combined NS-5a and NS-5b Inhibitors in Treatment Naïve Patients Patient characteristics: GT1a (73%), male (52%), black (20%), IL28B CT/TT (64%); advanced liver disease (non-cirrhotic): 14%; Mean HCV RNA: 6.6 logs GT1a or 1b (n = 44) GT2 or 3 (n = 44) Sofosbuvir Wk 1 Wk 24 Daclatasvir + Sofosbuvir (NS-5a) (NS-5b) Daclatasvir + Sofosbuvir Daclatasvir + Sofosbuvir + RBV SVR 24 93% 100% 100% Sulkowski M, et al. AASLD Abstract LB-2.

30 Hepatitis C: Paradoxes & Economics Although efficacy of new treatments will be high, more than half of HCV carriers remain unidentified and, even if identified, many do not receive proper therapy; greatly magnified in developing nations Because of high global HCV prevalence, the absolute number of potential HCV-related dire events is staggering, even if the proportion who suffer these events is relatively small The cost of treating 3.2 million is 270 billion, roughly 10% of the total US health care budget; 50-fold higher if include the 150 million infected globally unless price adjusted

31 HCV Economics 101 Despite the high cost, all models show IFN-free DAA therapy to be cost effective because: Treatment is short term Treatment is curative in almost all patients It markedly reduces the national cost of treating cirrhosis and HCC ($30,000-70,000 annual cost x 5-10 years/patient) It markedly reduces need for liver transplantation ($350,000/transplant) It prevents secondary transmissions that add to the disease burden

32 HCV THERAPEUTIC OPTIONS FROM AN ECONOMIC PERSPECTIVE Treat all identified cases with an optimal DAA (IFN-free) regimen Maximal cures Minimal side effects High adherence Allows treatment by PCP Treat first with regimens that include IFN to capture easy cures and use DAAonly for Tx failures Prioritize cases to spread costs; only treat those with stage >2 fibr. Reduces cure rate Maximizes side effects Lowers adherence Requires specialist Requires 2 nd Tx for some Only reduces cost by 20% Raises major ethical issue Saves money but defers >costs Reduces early cures/ 2 nd trans Staging adds costs/bx risk Risks missing fibrosis progression

33 WITH GREAT POWER COMES GREAT RESPONSIBILITY FROM THIS TIME FORWARD, ONCE AN HCV CARRIER IS IDENTIFIED, NONE SHOULD DEVELOP CIRRHOSIS OR DIE FROM HEPATITIS C WHO WILL TAKE RESPONSIBILITY?

34 A PHILOSOPHIC PERSEPECTIVE OF LIFE VERSUS AGE G I V E A D A M N ME AGE

35 ODE TO HCV

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