Worldwide Causes of HCC

Transcription

1 Approach to HCV Treatment in Patients with HCC JORGE L. HERRERA, MD, MACG UNIVERSITY OF SOUTH ALABAMA COLLEGE OF MEDICINE Worldwide Causes of HCC 60% 50% 40% 54% 30% 20% 10% 31% 15% 0% Hepatitis B Hepatitis C Other EASL-EORTC Clinical Practice Guidelines. Management of HCC. J Hepatol 2012;56: Page 1 of 13

2 Seroprevalence of HCV and HBV in Patients with HCC - USA Before the year 2000 After the year 2000 De Martel C, et al. Hepatology 2015;62: Age-adjusted incidence of HCC and intrahepatic bile duct cancer Ryerson AB et al. Cancer 2016;122: Page 2 of 13

3 U.S. Adjusted Rates of Liver/Biliary Cancer El-Serag HB, Kanwal F. Hepatology 2014; Liver Cancer Mortality United States Death rates declined for all cancers combined Decrease of 1.5% per year Deaths from liver cancers increased at the highest rate of all cancer sites Men 2x incidence compared to women Highest risk for persons born after 1947 Ryerson AB et al. Cancer 2016;122: Page 3 of 13

4 Age-specific incidence of liver and intrahepatic bile duct cancer from U.S. Ryerson AB et al. Cancer 2016;122: HCV and HCC Connection HCV Infection 15x 20x increased risk for HCC vs. uninfected individuals HCC cumulative risk of 1% to 3% over 25 years After cirrhosis: HCC annual risk 1% to 8%, average 3.5% Risk factors for HCC in HCV cirrhosis Male sex Coinfection with HBV or HIV Alcohol use Obesity Diabetes Genotype Page 4 of 13

5 HCC in HCV and Diabetes Taiwan National Health Insurance Research Database (>99% of the population) Patients with chronic HCV who developed new onset diabetes Adjusted Relative Risks for HCC Study population: 1.9 (CI: ) Age 40-59: 3.09 (CI: ) Huang YW, et al. Aliment Pharmacol Ther 2015;42: Increased Risk of HCC in Genotype 3 Infection Observational cohort study of 128,769 HCV patients from the VA HCV Clinical Registry, which compiled electronic medical records data from 1999 to 2010 Cirrhosis (n=123,988) Decompensated cirrhosis (n=128,055) Liver-related hospitalization (n=128,769) HCC (n=128,481) GT1 (reference point; n=102,191) GT2 (n=15,113) GT3 (n=9851) Other (n=1614) Hazard Ratio McCombs J, et al. JAMA Intern Med. 2014;17: Page 5 of 13

6 Incidence of HCC According to Genotype VA HCV Clinical Case Registry ,484 HCV patients, 8,337 genotype 3 infection G3 patients were younger Adjusted HR for HCC: 1.8 (compared to G1) Independent of: Age Diabetes BMI Kanwal F, et al. Hepatology 2014;60: Fibrosis and Risk of HCC in HCV HCC develops in the setting of advanced fibrosis in HCV HALT-C Study (n=1,005) Stage 3 or 4 fibrosis Median Follow up 4.6 years Cumulative 5y incidence of HCC: 5.2% Cirrhosis: 7.0% Bridging fibrosis: 4.1% EASL Clinical guidelines recommend HCC screening for F-3 fibrosis in HCV Lok AS, et al. Gastroenterology 2009;136: Page 6 of 13

7 Other Factors Predictive of HCC ADVANCED LIVER DISEASE PLATELET COUNT Lok AS, et al. Gastroenterology 2009;136: Identifying Patients at Risk Take Home Messages Risk restricted to advanced fibrosis (F3-F4) Risk is highest in Cirrhosis Males Genotype 3 infection Advanced liver disease Screening for HCC in F0-2 is not recommended Page 7 of 13

8 How to Screen Who to screen Cirrhosis (F4 fibrosis) 1 Bridging fibrosis (F3 fibrosis) 2 Current guidelines: Ultrasound exam every 6 months Alpha-fetoprotein is not recommended Lacks sensitivity and specificity Frequent false positive results Normal levels in up to 40% of documented HCC 1. AASLD & EASL guidelines 2. EASL guidelines If you are using AFP AFP cannot be used as the only screening test Many HCV cirrhosis patients will have elevated AFP The trend is more important than the actual value AFP usually rises as ALT rises A normal AFP should not dissuade you from evaluating a possible abnormality on ultrasound Page 8 of 13

9 Why Screening Fails Only 40% of HCC patients are diagnosed at an early stage 1,005 patients with F3/4 fibrosis, mean follow-up 6.1 years (HALT-C) 69% (692) had consistent surveillance 83 patients had HCC 28% (n=23) were detected beyond Milan Criteria 3/23 had absence of screening 4/23 absence of follow up 16/23 absence of detection Ultrasound is far from a perfect test! Singal AG et al. Am J Gastroenterol 2013;108: What to do with Screening Results Bruix J, Sherman M. Hepatology 2011;53: Page 9 of 13

10 Meta-analysis of observational studies Effects of HCV Therapy on HCC ALL STAGES OF FIBROSIS HR OF HCC AFTER THERAPY ADVANCED FIBROSIS HR OF HCC AFTER THERAPY Morgan RL, et al. Ann Intern Med 2013;158: HCV Cure Does Not Eliminate Risk n=530, advanced fibrosis; 8.4 year follow up post SVR. Europe and Canada n=124, biopsy proven cirrhosis; 8-year follow up post SVR. Italy Van der Meer AJ, et al. JAMA 2012;308(24): Ascione A, et al. Hepatology 2007;45: Page 10 of 13

11 Management of HCV after HCC Diagnosis Eradicate the virus prior to or after the transplant? Factors to consider Severity of liver disease CP-C lower SVR, better served by a transplant Type of donor Pre-transplant strategy works best for living donors Availability of HCV (-) livers Treating HCV pre-transplant eliminates the possibility of an HCV (+) organ Wait time until transplant The longer the patient is negative pre-transplant, the better Sofosbuvir + Ribavirin Pre OLT 61 patients CP-A patients with HCC waiting for OLT Treated with sofosbuvir + ribavirin for up to 48 weeks prior to OLT 49% achieved a cure post-olt 43 patients RNA (-) Pre-OLT SVR post OLT: 70% SVR was inversely related to number of days of undetectable RNA 30 days seems to be the cut-off Sofosbuvir + ribavirin is now considered suboptimal therapy for G1 Curry MP et al. Gastroenterology 2015;148: Page 11 of 13

12 HCV Recurrence vs. Time Undetectable HCV-RNA Sofosbuvir + ribavirin for up to 48 weeks prior to OLT Curry MP et al. Gastroenterology 2015;148: % 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Post Liver Transplantation Sofosbuvir + Ledipasvir + Ribavirin 96% 98% 53/55 55/56 No Cirrhosis 12 wks 24 wks AASLD 2015: Ribavirin probably not necessary in post OLT non-cirrhotic patients Charlton M, et al. Gastroenterology 2015;149: Page 12 of 13

13 HCC in HCV Take Home Points 1. Hepatitis C markedly increases risk of HCC Risk increased in F3 and F4 fibrosis 2. F3 and F4 HCV patients should undergo appropriate HCC screening 3. Cure of HCV markedly reduces risk of HCC in all patients 4. After cure, F3 and F4 patients remain at risk of HCC 5. Timing of treatment of HCV after HCC diagnosis is evolving Page 13 of 13