David F. Dies, MD, MBA

Transcription

1 David F. Dies, MD, MBA Medical Director, Liver Transplantation John C McDonald Regional Transplant Center Willis Knighton Shreveport The Liver Center at GastroIntestinal Specialists AMeltingPotofPearls of Pearls for the Practicing Gastroenterologist 1

2 No Financial disclosures Will discuss off label use of drugs Will discuss drugs in development 55 yo WM presents for second opinion. He was hospitalized for an UGI bleed. EGD found blood but no lesion. He was discharged d on a PPI. Lab: Normal LFT and renal function WBC = 8,000 Hg = 18 gm/dl and HCT = 54% Platelets = 100K 2

3 These are Duodenal Varices What Do They Imply? Always think PVT with duodenal varices PVT accounts for 5-10% of portal HTN Thrombophilic disease identified in >2/3 Diagnosis with Doppler U/S Other Manifestations: Esophago-gastric gastric varices Tortuous vessels around PVT called cavernoma Portal biliopathy and GB varices Splenomegaly 3

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5 Scarce (if any) data on use of beta blockers Banding done in acute bleed setting Octreotide recommended in acute bleed BAVERNO IV Consensus J Hepatol 2005;43(1):

6 SeminLiver Dis 2008;28: New Crohn s patient with active disease. Prior to steroids and infliximab you obtain lab: normal LFT HBsAg- HBcAb IgM+ HBsAb- 6

7 You recommend: A) Begin entecavir B) HBV DNA q3-6 months, Tx if positive C) Recheck Serology in 6 months There is no Window HBcAB+, HBsAg- means prior HBV 7

8 Prednisone Azathioprine, methotrexate, mycophenolate Anti-TNF drugs (ex: infliximab, adalimumab) Abatacept, Natalizumab Other: Rituximab Chemotherapy Transplantation Rituximab or Bone Marrow transplant: Treat HBsAg+ Treat HBsAG-/HBcAb HBcAb+ (+/-HBsAb HBsAb) Do not treat isolated HBsAb+ 8

9 Other than Rituximab or BM transplant: If HBsAg+ Begin treatment with entecavir or tenofovir Continue until 6-12 months after last dose If HBsAg- and HBcAb+ Begin treatment if there cannot be followup OR measure HBV DNA now and q3-6 months Treat if HBV DNA+ Baseline Liver Function Tests Not Relevant In the World of PSC, What is a Dominant Stricture? 9

10 A width of: 1.5 mm in CBD 1mm in Hepatic Duct 10

11 Per AASLD Guidelines: Biliary Stenting is associated with increased complications as associated with balloon dilation Biliary sphincterotomy with balloon dilation has been shown to be of value. Per ACG Guidelines: Biliary balloon dilation is associated with fewer episodes of cholangitis, improvement of cholangiography and biochemical tests 11

12 35 yo woman presents with small amount of BRBPR after a hard BM. She wants a colonoscopy because cancer runs in my family. Fam Hx: Father had transitional cell cancer of the ureter Mother had cancer of the uterus Colonoscopy reveals a 9 mm polyp in the right colon and small internal hemorrhoids. On followup visit you tell the patient the polyp was a tubulovillous adenoma with no signs of cancer and recommend a 3 year followup. She starts crying and says I have a BABY at home and cancer runs in my family. Is that IT? How can you be so sure about that polyp. I want that polyp sent off for additional tests! What should you do for this 35 year old woman? 12

13 She is at increased risk of LYNCH or HNPCC as there are two family members with LYNCH cancers and you diagnosed an adenoma in her prior to age 40 By ACG position statement t t you should send the adenoma for MSI and if positive should test her for HNPCC genetics HNPCC = Hereditary Non-Polyposis Colon Cancer MSI = Microsatellite Instability Colon Endometrial Ovarian Transitional Cell or renal pelvis or ureter Gastric Hepatobiliary Small Bowel Glioblastoma Pancreatic 13

14 Amsterdam criteria (3 relatives affected) One relative with two cancers (or metachronous) Any individual with adenoma prior to age 40 Anyone with colon or endometrial cancer < 50. MSI If positive then do genetic test for LYNCH MLH1 MSH2, MSH6, PMS2 Caveat 15% of sporadic colon cancer +MSI 14

15 Screening Guidelines 15

16 Adults born during should receive one-time testing for HCV without prior ascertainment of HCV risk All persons identified with HCV infection should receive a brief alcohol screening and intervention as clinically indicated, followed by referral to appropriate care and treatment services for HCV infection and related conditions Smith BD, et al. MMWR Recomm Rep. 2012;61:

17 Simeprevir A 2 nd generation NS3/4A protease inhibitor Marketed to be used with hi interferon Approved GN 1 only 24 weeks for naïve and relapsers 48 weeks for partial and null responders Sufosbuvir A nucleotide polymerase inhibitor NS5B Can be used with or without interferon Approved PanGenotypic 12 weeks for genotype 1, 2 or 4 24 weeks for genotype 3 17

18 100% 90% 84% 85% 80% 70% 60% 58% 50% 40% 30% 20% 10% 0% 1a with Q80K 1a without Q80K 1b Quest Trials, package insert 48% of US Subjects Labcorp = GENOSURE QUEST = NS3 Genotype 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 84% 82% 88% 68% 67% 25% F0-2 vs F3-4 Black vs white EVR vs not Quest Trials, package insert EVR = virus neg by week 4 18

19 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 47% 78% 86% 0% 1a with Q80K 1a without Q80K 1b Promise Trial, package insert 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 77% 44% 41% 47% 1a 1b 1a 1b Prior Partial Responders Prior Null Responders Aspire Trial, package insert 19

20 100% 96% 92% 92% 89% 90% 82% 80% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1b vs 1a Cirrhosis vs not >10 6 vs < 10 6 Neutrino Trial, package insert 20

21 Summary of Sofosbuvir SVR12 Data GN 1 Treatment Naïve 24 weeks of SOF/Riba 54% 82% Photon Trial Not fully published NO DATA IN PACKAGE INSERT! 21

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27 2013: IFN-Free DAA Regimens in Phase 3 Trials PI NS5A Nonnucleoside polymerase Ledipasvir Nucleo(t)ide polymerase Ribavirin +/- RBV ABT450/r ABT267 ABT333 +/- RBV Faldaprevir Deleobuvir RBV Asunaprevir Daclatasvir Asunaprevir Daclatasvir BMS Genotype 1b only 27

28 ABT-450/ritonavir (150/100 mg) A boosted protease inhibitor ABT-267 (25 mg) Non-nuclosidenucloside NS5B Polymerase inhibitor ABT-333 (250 mg) NS5A inhibitor 28

29 N Engl J Med 2014;370: Daclatasvir + Sofosbuvir 3 arms GN 2/3 (naïve) With and without t Riba 1 week lead in with SOF 5 arms GN 1 (naïve) With and without Riba 12 vs 24 weeks 1 week lead in with SOF 44 pts 126 pts 2 arms GN 1 (prior protease failure) 41 pts With and without Riba N Engl J Med 2014;370:

30 Daclatasvir + Sofosbuvir Riba did not matter Lead in did not matter 12 weeks did as well (small numbers) SVR-12 GN 2 naïve 92% GN 3 naïve 93% GN 1 naïve 98% GN 1 PI failure 98% 30

31 Sofosbuvir and Ledipasvir Sofosbuvir and Ledipasvir 31

32 Sofosbuvir and Ledipasvir Sofosbuvir and Ledipasvir 32

33 Summary Hepatitis C 2014 Identification of infected patients via screening Risk of exposure and elevated ALT 2012 plus birth cohort Management Alcohol, obesity, prevention of transmission and HAV/HBV vaccination Determine need for treatment (liver disease) Treatment 2014: 2nd generation HCV PI and nucleotide analogue polymerase inhibitor 12 week oral, IFN-free regimen: SOF/RBV for HCV genotype 2 24 week oral IFN-free regimen: SOF/RBV for HCV genotype 3 Late ?: 8-12 week oral regimens for genotype 1 New Device for Endoscopic Therapy of Pancreatic Necrosis 33

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39 David F. Dies, MD, MBA Medical Director, Liver Transplantation John C McDonald Regional Transplant Center Willis Knighton Shreveport The Liver Center at GastroIntestinal Specialists 39