Ari Bunim, M.D. Director of Hepatology New York Hospital Queens Assistant Professor of Clinical Medicine Weill Cornell Medical College

Ari Bunim, M.D. Director of Hepatology New York Hospital Queens Assistant Professor of Clinical Medicine Weill Cornell Medical College

New York State Law Goes into Effect January 1, 2014 Hepatitis C Virus Testing (Chapter 425 of the Laws of 2013) This new law requires a hepatitis C virus screening test to be offered to all patients born between 1945 and 1965 who are receiving health services as a hospital inpatient or receiving primary care services and applies to physician, physician assistant, or nurse practitioner. The law further requires that the health care provider refer a patient who receives a positive screening test to another provider to receive confirmatory testing and follow-up care.

Number infected Hepatitis C is Under Diagnosed in the United States 4,000,000 3,000,000 Undiagnosed Diagnosed ~75% 2,000,000 1,000,000 ~21% ~65% 0 HIV HBV HCV HBV=hepatitis B virus; HCV=hepatitis C virus; HIV=human immunodeficiency virus. Institute of Medicine. Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C; 2010.

X1000 persons HCV-Infected Persons in the US: Estimated Rates of Detection, Referral to Care and Cure CDC & USPSTF recommend 1-time testing of baby boomers (born 1945-1965) 3500 3000 2500 2000 50% 1500 1000 500 32-38% 20-23% 7-11% 5-6% 0 Infected Diagnosed Referred HCV RNA Treated Cure to care test Holmberg S, N Engl J Med 2013; 368: 1859

2010 2012 2014 2016 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2038 2040 2042 2044 2046 2048 2050 2052 2054 2056 2058 2060 Number Burden of Hepatitis C Related Morbidity and Mortality in the US Markov model of health outcomes Of 2.7 M HCV infected persons in primary care 1.47 M will develop cirrhosis 350,000 will develop liver cancer 897,000 will die from HCV-related complications 40000 35000 30000 25000 20000 15000 10000 5000 0 Deaths Decompensated cirrhosis HCC Transplants Rein et al. Dig Liver Dis 2010. Year

Cumulative Incidence (%) Cumulative Incidence (%) SVR Reduced HCC and Liver-Related Complications in Patients With Bridging Fibrosis or Cirrhosis HCC (n=307) Liver-Related Complications* (n=307) Follow-Up (years) Follow-Up (years) *Ascites, variceal bleeding. 307 HCV patients with bridging fibrosis (n=127) or cirrhosis (n=180) were evaluated by Cox regression analysis. Non-SVR in 67% of patients treated with pegylated interferon plus ribavirin. Median follow-up: 3.5 years. Cardoso A-C, et al. J Hepatol. 2010;52:652-657.

% patients after 5 years 5-year risk of death (all-cause) by SVR 20 18 16 14 12 10 8 6 4 2 0 General: 18 studies n=29,269 Avg. FU=4.6 years 4.5% 10.5% Cirrhotic: 9 studies n=2,734 Avg. FU=6.6 years 3.6% 11.3% HIV/HCV: 5 studies n=2,560 Avg. FU=5.1 years 1.3% 10.0% General Cirrhotic Co-infected Hill et al AASLD 2014 Abstract 44 SVR No SVR

Simeprevir (Olysio ) 2 nd generation NS 3/4a protease inhibitor Approved for use in patients with genotype 1 HCV with Peg/Riba or with Sofosbuvir Metabolized in the liver and cleared via the biliary system

Sofosbuvir (Sovaldi ) HCV-specific NS5B polymerase inhibitor Approved for Genotypes 1,2,3, and 4 Geno 1 12 weeks with P/R or Simeprevir (non-cirrhotics) 24 weeks with riba if cannot tolerate IFN Geno 2: 12 weeks with riba Geno 3: 24 weeks with riba Geno 4: 12 weeks with P/R Renally Cleared

SVR12 (%) SOF + SMV + RBV for 12 vs 24 Weeks: SVR12 in F0-F2 Patients With Prior Null Response to PEG/RBV (COSMOS) 24 Weeks 12 Weeks 100 90 80 70 60 50 40 30 20 10 0 93 100 96 93 90 79 80 70 60 50 40 30 20 19/24 14/15 10 0 26/27 13/14 SMV/SOF + RBV SMV/SOF SMV/SOF + RBV SMV/SOF Lawitz E et al., Lancet, July 28, 2014, epub (http://dx.doi.org/10.1016/s0140-6736(14)61036-9)

SVR12 (%) SOF + SMV + RBV for 12 vs 24 Weeks: SVR12 in F3-F4 Treatment-naïve Patients (COSMOS) 100 90 80 70 60 50 40 30 20 10 0 24 Weeks 12 Weeks 100 100 100 92 90 86 80 70 60 50 40 30 20 10 13/13 8/8 11/12 6/7 0 SMV/SOF + RBV SMV/SOF SMV/SOF + RBV SMV/SOF Lawitz E et al., Lancet, July 28, 2014, epub (http://dx.doi.org/10.1016/s0140-6736(14)61036-9)

SVR12 (%) SOF + SMV + RBV for 12 vs 24 Weeks: SVR12 in F3-F4 Patients With Prior Null Response to PEG/RBV (COSMOS) 100 90 80 70 60 50 40 30 20 10 0 24 Weeks 12 Weeks 100 100 100 93 88 90 80 70 60 50 40 30 20 10 15/17 8/8 14/15 7/7 0 SMV/SOF + RBV SMV/SOF SMV/SOF + RBV SMV/SOF Lawitz E et al., Lancet, July 28, 2014, epub (http://dx.doi.org/10.1016/s0140-6736(14)61036-9)

Sofosbuvir/Ledipasvir (Harvoni ) Recently approved for genotype 1 chronic HCV infection Most patients treated 8-12 weeks Once daily, oral fixed-dose (90/400 mg) combination tablet No food effect >2000 patients treated

SVR12 (%) SVR12 (%) LDV/SOF + RBV for 12 vs 24 Weeks: SVR12 in GT 1 Treatment-naïve Patients (ION-1) Non-cirrhotic Cirrhotic 179/ 179 178/ 178 181/ 182 179/ 179 32/ 33 33/ 33 31/ 32 36/ 36 LDV/S OF LDV/SOF + RBV LDV/S OF LDV/SOF + RBV LDV/S OF LDV/SOF + RBV LDV/S OF LDV/SOF + RBV 12 Weeks 24 Weeks Afdhal et al. N Eng J Med 2014;370:1889-98 12 Weeks 24 Weeks

SVR12 (%) LDV/SOF + RBV for 8 vs 12 Weeks: SVR12 in GT 1 Treatment-naïve Non-cirrhotic Patients (ION-3) p=0.52 202/215 201/216 206/216 LDV/SOF LDV/SOF + RBV LDV/SOF 8 Weeks 12 Weeks Error bars represent 95% confidence intervals. Kowdley KV et al. N Eng J Med 2014; 370:1879-88

SVR12 (%) Ion 2: Ledipasvir + Sofosbuvir ± RBV Genotype 1 Treatment Experienced 100 94 96 99 99 80 60 40 20 0 102/109 107/111 108/109 110/111 SOF/LDV SOF/LDV+RBV SOF/LDV SOF/LDV+RBV 12 weeks 24 weeks Afdhal N et al, epub April 17, 2014 at NEJM.org

Abbvie 3D (Viekira Pak ) Recently approved for treatment of genotype 1 chronic HCV Including those with compensated cirrhosis, HIV, and post-liver transplant Consists of 4 different drugs Ribavirin also used in geno 1a and those with compensated cirrhosis

SVR12 (%) 3D + RBV for 12 Weeks: SVR12 in GT1a and GT1b Treatment-naïve Noncirrhotic Patients (PEARL-III and PEARL-IV) 100 97.0 GT 1a 90.2 100 GT 1b 99.5 99.0 80 80 60 60 40 40 20 0 20 97/100 185/205 209/210 207/209 3D Regimen + RBV 3D Regimen 0 3D Regimen + RBV 3D Regimen Ferenci P et al. N Engl J Med 2014;370:1983-1992.

SVR12 (%) SAPPHIRE-2 (Placebo-Controlled) Paritaprevir/r-Ombitasvir + Dasabuvir + RBV Genotype 1, treatment experienced, noncirrhotic, 12 weeks, n=394 100 96 96 97 80 60 40 20 0 Overall G1a G1b Zeuzem S et al, N Engl J Med 2014;

Patients (%) with SVR 12 TURQUOISE II: Paritaprevir/r-Ombitasvir + Dasabuvir ± RBV 100 80 92 3D + RBV x 12 Weeks 96 94 89 3D + RBV x 24 Weeks 99 100 60 P=0.089 40 20 0 208 172 Overall GT1a GT1b Relapse/viral breakthrough in 6% (12 wks) and 2% (24 wks) Poordad F et al. N Engl J Med; 2014;370:1973-82

Hepatitis B 800,000-1.4 million cases in the United States Should screen anyone born from an endemic area Asia, Africa, South America, Russia Up to 25% of people with hepatitis B will die prematurely from cirrhosis of liver cancer Not curable Very effective oral medications available to treat with few side effects

New York Hospital Queens

NYHQ 519-bed acute, tertiary care facility Opened in 1957 as Booth Memorial Medical Center Has 1,500 doctors, podiatrists, and dentists on staff Member of New York Presbyterian Healthcare System Affiliate Weill Cornell Medical College

NYHQ Liver Center Provide in-patient and out-patient care for a variety of liver diseases, including decompensated cirrhosis Comprehensive management of hepatocellular carcinoma Drainage of ascites Liver biopsies Liver transplant evaluations and post-transplant care in conjunction with Columbia University Medical Center

Abnormal liver tests Hepatitis B and C Liver lesion or mass Anyone with cirrhosis Portal hypertension Varices Ascites Encephalopathy Who to Refer?

How to Refer Ari Bunim, M.D. 56-45 Main Street Flushing, New York 11355 (718) 670-2399 arb9039@nyp.org