Worldwide Causes of HCC

Jorge L. Herrera, MD, MACG Approach to HCV Treatment in Patients with HCC JORGE LL. HERRERA, HERRERA MD MD, MACG UNIVERSITY OF SOUTH ALABAMA COLLEGE ...
Author: Amy McKinney
7 downloads 0 Views 952KB Size
Jorge L. Herrera, MD, MACG

Approach to HCV Treatment in Patients with HCC JORGE LL. HERRERA, HERRERA MD MD, MACG UNIVERSITY OF SOUTH ALABAMA COLLEGE OF MEDICINE

Worldwide Causes of HCC 60% 50%

54%

40% 30%

31%

20%

15%

10% 0%

Hepatitis B

Hepatitis C

Other

EASL-EORTC Clinical Practice Guidelines. Management of HCC. J Hepatol 2012;56:908-943

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

1

Jorge L. Herrera, MD, MACG

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;62:1190-1200

U.S. Adjusted Rates of Liver/Biliary Cancer

El-Serag HB, Kanwal F. Hepatology 2014;1767-1775

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

2

Jorge L. Herrera, MD, MACG

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 Al h l use Alcohol Obesity Diabetes Genotype

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: 1.1-3.3) Age g 40-59: 3.09 ((CI: 1.04-9.11))

Huang YW, et al. Aliment Pharmacol Ther 2015;42:902-911

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

3

Jorge L. Herrera, MD, MACG

Increased Risk of HCC in Genotype 3 Infection • Observational cohort study of 128,769 HCV patients from the VA HCV Clinical Registry, g y, which compiled p electronic medical records data from 1999 to 2010 GT1 (reference point; n=102,191) GT2 (n=15,113)

Cirrhosis (n=123,988)

GT3 (n=9851) Other (n=1614)

Decompensated cirrhosis (n=128,055) Liver-related hospitalization ( 128 769) (n=128,769) HCC (n=128,481) 0

0.5

1

1.5

2

Hazard Ratio

McCombs J, et al. JAMA Intern Med. 2014;17:204-212.

7

Incidence of HCC According to Genotype VA HCV Clinical Case Registry 2000-2009. 110,484 HCV patients, 8 337 genotype 3 infection 8,337  G3 patients were younger  Adjusted HR for HCC: 1.8 (compared to G1)  Independent of: age Diabetes BMI

Kanwal F, et al. Hepatology 2014;60:98-105

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

4

Jorge L. Herrera, MD, MACG

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 d ffibrosis: b 4.1%

EASL Clinical guidelines recommend HCC screening for FF--3 fibrosis in HCV Lok AS, et al. Gastroenterology 2009;136:138-148

Other Factors Predictive of HCC ADVANCED LIVER DISEASE

PLATELET COUNT

Lok AS, et al. Gastroenterology 2009;136:138-148

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

5

Jorge L. Herrera, MD, MACG

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

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

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

6

Jorge L. Herrera, MD, MACG

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

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 b off ffollow ll up ◦ 16/23 absence of detection

Ultrasound is far from a perfect test! Singal AG et al. Am J Gastroenterol 2013;108:425-432

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

7

Jorge L. Herrera, MD, MACG

What to do with Screening Results

Bruix J, Sherman M. Hepatology 2011;53:1020-1022

Meta-analysis of observational studies

Effects of HCV Therapy on HCC ALL STAGES OF FIBROSIS

ADVANCED FIBROSIS

HR OF HCC AFTER THERAPY

HR OF HCC AFTER THERAPY

Morgan RL, et al. Ann Intern Med 2013;158:329-337

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

8

Jorge L. Herrera, MD, MACG

HCV Cure Does Not Eliminate Risk n=530, advanced fibrosis; 8.4 year follow up post SVR. SVR Europe and Canada

Van der Meer AJ, et al. JAMA 2012;308(24):2584-2593

n=124, biopsy proven cirrhosis; 88-year follow up post SVR. SVR Italy

Ascione A, et al. Hepatology 2007;45:579-587

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 pre-transplant transplant eliminates the possibility of an HCV (+) ( ) organ

◦ Wait time until transplant ◦ The longer the patient is negative pre-transplant, the better

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

9

Jorge L. Herrera, MD, MACG

Sofosbuvir + Ribavirin Pre OLT 61 patients CP-A patients with HCC waiting for OLT Treated with Sofosobuvir + 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;148:100-107

HCV Recurrence vs. Time Undetectable HCV-RNA Sofosbuvir + ribavirin for up to 48 weeks prior to OLT

Curry MP et al. Gastroenterology 2015;148:100-107

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

10

Jorge L. Herrera, MD, MACG

Post Liver Transplantation Sofosbuvir + Ledipasvir + Ribavirin 100%

96%

98%

53/55

55/56 /

90% 80% 70% 60% 50% 40% 30% 20% 10% 0% No Cirrhosis

12 wks

24 wks

AASLD 2015: Ribavirin probably not necessary in post OLT nonnon-cirrhotic patients Charlton M, et al. Gastroenterology 2015;149:649-659

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 4. Aft cure, F3 and d F4 patients ti t remain i att risk i k off HCC 5. Timing of treatment of HCV after HCC diagnosis is evolving

ACG 2015 Nashville Hepatitis School Copyright 2015 American College of Gastroenterology

11