Tram T. Tran, MD, FACG Approach to HCV Treatment in Patients with HCC Tram T. Tran, MD, FACG Professor of Medicine Medical Director, Liver Transplant Cedars Sinai Medical Center Natural History of HCV Infection Natural History of HCV Infection Acute Acute Infection Infection Clearance of Clearance of HCV HCV RNA RNA 15%-25% 15%-25% Chronic Chronic Infection Infection 75%-85% 75%-85% Extrahepatic Extrahepatic Manifestations Manifestations %-% %-% over over years years HCC HCC 1%-4% per year 1%-4% per year Decompensated Decompensated 5-yr survival rate 50% 5-yr survival rate 50% %-30% of individuals are symptomatic. %-30% of individuals are symptomatic. HCC=hepatocellular carcinoma. HCC=hepatocellular carcinoma. Adapted from Chen SL, Morgan J MedSci. Sci.06;3:47-52. 06;3:47-52. Adapted from Chen SL, Morgan TR.TR. Int Int J Med Page 1 of 8
HCV Viremia Was Associated With Increased Mortality in a Prospective Taiwanese Cohort Study Cumulative Mortality (%) (%) Anti-HCV+, HCV RNA detectable Anti-HCV+, HCV RNA undetectable Anti-HCV All Causes Liver Cancer Extrahepatic Diseases All Causes Liver Cancer Extrahepatic Diseases (n=2394) (n=115) (n=2199) 35 12 19.8% 30 30.1% 18.4% 16 25 14 8 12 12.2% 11.0% 6 15 12.8% 8 12.4% 4 6 4 5 2 1.6% 2 0 0 0.3% 0 0 2 4 6 8 12 14 16 18 0 2 4 6 8 12 14 16 18 0 2 4 6 8 12 14 16 18 Follow-Up (Years) Follow-Up (Years) Follow-Up (Years) (Years) (Years) (Years) REVEAL HCV: HCV: Risk Risk Evaluation Evaluation of Viral of Load Viral Elevation Load Elevation and Associated and Associated Liver Disease/Cancer Liver Disease/Cancer (1991-08). (1991-08). Anti-HCV seronegative (n=18,541); anti-hcv seropositive (n=95; detectable HCV RNA: 69.4%). Average follow-up: 16.2 years. Among Anti-HCV extrahepatic seronegative causes (n=18,541); of death, anti-hcv 68.5% seropositive and 69.3% (n=95; were detectable noncancer HCV deaths RNA: for 69.4%). HCV Average seronegative follow-up: and 16.2 seropositive, years. respectively. P<.001 Among extrahepatic for comparison causes among of death, all 68.5% 3 groups and and 69.3% P<.001 were noncancer for HCV RNA deaths detectable for HCV seronegative vs undetectable. and seropositive, respectively. Lee P<.001 M-H, for et et al. comparison al. J Infect J Infect Dis. among Dis. 12;6:469-477. all 3 groups and P<.001 for HCV RNA detectable vs undetectable. Regression of Advanced Fibrosis or by Transient Elastography (FibroScan) in SVR12 Patients Retrospective chart review of SVR12 and prospective transient elastography data after SVR12 (n=0) /F3-F4 (65%/35%) Regimens Sofosbuvir-based (45%), telaprevir + PR (29%), PR (16%), clinical trial/other (%) Overall median time to improvement: 2.5 years after SVR versus F3-F4: 3.0 versus 2.5 years Predictor of regression in F3-F4 at baseline: APRI (P<0.05) Surrogate marker of improvement of baseline cirrhosis: decrease in ALT (P=0.03) Crissien AM, et al. Hepatology. 15;62(suppl S1):264A-265A. Abstract 8. Patients (%) 0 80 60 40 0 60% Change in Fibrosis by Transient Elastography Improved No change Worsen 34% Overall (n=0) 6% 69% 14% 17% F3-F4 (n=35) 55% 45% 0% (n=65) Baseline Page 2 of 8
Global Epidemiology of Hepatocellular Carcinoma Global Epidemiology of Hepatocellular Carcinoma 3,000-400,000 deaths related to HCC/year deaths related to HCC/year Represents 5% of all cancer cases Great variability according to gender, age, and geographic areas Represents 5% of all cancer cases Great variability according to gender, age, and geographic areas Kiyosawa K, Jpn. J. Inf. Dis., 55, 69-77, 02 Risk Factors for HCC in Chronic HCV Risk Factors for HCC in Chronic HCV Older age Older age Duration of infection Duration of infection Male sex Race Male sex Alcohol Race Obesity Alcohol Diabetes HBV or HIV co-infection Obesity Absence of treatment Diabetes HBV or HIV co-infection Absence of treatment Page 3 of 8
HCV Related Related HCC HCC Incidence Incidence The Incidence and 5-Year Survival of HCC in United States (1973-07) The Incidence and 5-Year Survival of HCC in United States (1973-07) El-Serag HB. N Engl J Med 11 Page 4 of 8
HCV is the Dominant Risk Factors for HCC in the United States HCV is the Dominant Risk Factors for HCC in the United States HCV is the Dominant Risk Factors for HCC in the United States Di Bisceglie AM, et al.am J Gastroenterol. 03 Sep;98(9):60-3. Di Di BisceglieAM, AM, et et al.amj J Gastroenterol. 03 Sep;98(9):60-3. Hepatocellular Carcinoma Sustained Viral Responders vs. Non-responders Hepatocellular Carcinoma, % % 30 0 0 P<.001 P<.001 Without SVR Without SVR With SVR With SVR 0 1 2 3 4 5 6 7 8 9 Time, y JAMA, Dec 26, 12-vol 308,24,2589 Page 5 of 8
Higher Cancer Rates in HCV Patients: Real-World Evidence from a Large Health Maintenance Organization Higher Cancer Rates in HCV Patients: Real-World Evidence from a Large Health Maintenance Organization Cancer diagnosis diagnosis rate is higher rate is higher for for HCV HCV patients patients vs. non-hcv vs. patients, non-hcv even when patients, excluding even liver cancer when (p<0.001) excluding liver cancer (p<0.001) Univariate analysis analysis shows that shows cancer rates that were cancer significantly rates higher were for significantly liver cancer, higher for liver cancer, nonnon-hodgkin Hodgkin lymphomas, lymphomas, and total and cancer total sites cancer sites Cancer rates are higher in Cancer HCV rates patients; are higher these in HCV patients; results these suggest results suggest another another possible possible manifestation of HCV manifestation of HCV p<0.001; p<0.005 ALL SITES (W/O HCC) ALL SITES (W/ HCC) PROSTATE RENAL LUNG HEAD / NECK NON-HODGKIN LYMPHOMA CRUDE HCV vs. NON-HCV CANCER RATES CRUDE HCV vs. NON-HCV CANCER RATES MYELOMA PANCREAS LIVER COLON / RECTUM STOMACH ESOPHAGUS 0.1 1 0 RATE RATIO (95% CI): HCV vs. NON-HCV Nyberg AH, EASL, 15, O058 Does treatment INCREASE HCC risk? 344 cirrhotic patients Treated with DAA, followed for 24 weeks SVR 91% HCC detected 7.6% overall 28% in those with previous HCC 3% in those with no history of HCC Multivariate analysis: Child-Pugh and prior HCC Conti F J Hepat Oct 16 Page 6 of 8
Abstract FRI-166 E.J. Lawitz 1, P. Ruane 2, C. Stedman 3, G. Foster 4, R.H. Hyland 5, S. Coogan 6, S. Moody 7, H. Dvory-Sobol 8, S.J. Knox 5, D.M. Brainard 5, A. Abergel 9, K. Agarwal, Z. Younes 11, C. Schwabe 12 E-mail: lawitz@txliver.com 1. Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX 2. Ruane Medical and Liver Health Institute, Los Angeles, CA, United States 3. Christchurch Hospital, Christchurch, New Zealand 4. Blizard Institute, Queen Mary University of London, London, United Kingdom 5. Clinical Research, Gilead Sciences, Inc. 6. Clinical Operations, Gilead Sciences Inc., Foster City, CA 7. Pharpoint Research, Inc., Durham, NC 8. Clinical Virology, Gilead Sciences, Inc., Foster City, CA, United States 9. Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France. King s College Hospital, London, United Kingdom 11. Gastro One, Germantown, TN, United States 12. Auckland Clinical Studies, Auckland, New Zealand Objectives and Methods To determine long-term virologic and clinical outcomes in HCV patients treated with DAA regimens using registry study data Patients with chronic HCV treated in a Gilead-sponsored study were eligible for 1 of 2 ongoing 3-year registry studies SVR Registry: patients who achieved a sustained virologic response 12 weeks after treatment end (SVR12) in parent study Sequence Registry: patients with virologic failure in parent study Deep sequencing with 1% cutoff used Page 7 of 8
Outcomes SVR maintained in 99.7% (5414/5433) patients 6 patients (0.1%) virologic evidence of late relapse 12 patients (0.2%) virologic evidence of reinfection HCC was reported in 0.3% (16/5433) and 0.9% (5/536) of patients in the SVR and Sequence registries through Week 96 respectively. Summary Page 8 of 8