Brilliant Answers Brilliant Answers Jennifer Price, MD, PhD - PDF document

12/8/17 10 Important Liver Care 10 Important Liver Care Questions and 10 Questions and 10 × Brilliant Answers Brilliant Answers Jennifer Price, MD, PhD Jennifer Price, MD, PhD UCSF Hepatology UCSF Hepatology December 8, 2017 December 8, 2017 Disclosures Outline • Grant support: Gilead, Merck • Complications of cirrhosis – Surveillance for hepatocellular carcinoma (HCC) • Advisory board: Intercept – Risk of HCC with DAA’s • Ownership interest: Bristol-Myers Squibb, – Surveillance for esophageal varices Johnson and Johnson, Merck, Abbvie • Timing of HCV treatment in transplant candidates • Hepatitis B virus – Isolated HBcAb+ – New treatments • Nonalcoholic fatty liver disease (NAFLD) – Diagnosis and management 1

12/8/17 Natural History of Chronic Liver HCC Surveillance: U/S +/- AFP Disease (HCV example) every 6 months Acute hepatitis C • Rising incidence over past 20 years 55 - 85% – Estimated 39,230 cases and 27,170 deaths in 2016 Chronic infection – Aging HCV+ population, increasing NAFLD – Incidence expected to rise until 2030 70% • High risk groups: Chronic hepatitis 1-4%/yr – Cirrhosis Hepatocellular 20% Carcinoma – Chronic HBV Cirrhosis – F3 fibrosis Decompensation 4-5%/yr • Observational studies in cirrhosis: screening associated Time with improved survival, detection of early-stage HCC (yr) 20 10 30 Heimbach J, AASLD Practice Guidelines, 2017. HCC Surveillance: Chronic HBV HCC Surveillance: Chronic HBV 1. How should we approach HCC screening in patients 1. How should we approach HCC screening in patients with HIV/HBV? with HIV/HBV? Surveillance recommended HBV Population Group Threshold incidence for Incidence of HCC efficacy of surveillance Cirrhosis 0.2-1.5%/yr 3-8%/yr Family h/o HCC 0.2%/yr Incidence higher than without family history Asian male >40 years 0.2%/yr 0.4-0.6%/yr Asian female >50 years 0.2%/yr 0.3-0.6%/yr African/North American Blacks 0.2%/yr Occurs at earlier age Benefit uncertain Males <40, Females <50 0.2%/yr <0.2%/yr Bruix J, AASLD Practice Guidelines, 2011. 2

12/8/17 HCC Surveillance: Chronic HBV HCC Surveillance: Chronic HBV 1. How should we approach HCC screening in patients 1. How should we approach HCC screening in patients with HIV/HBV? with HIV/HBV? What about Caucasian pts? What about Caucasian pts? Surveillance recommended Surveillance recommended ─ If no cirrhosis and chronic inactive HBV HBV Population Group HBV Population Group (long-term normal ALT, low HBV DNA) “the incidence of HCC is probably too Cirrhosis Cirrhosis low to make surveillance worthwhile” Family h/o HCC Family h/o HCC ─ However… “additional risk factors have to be taken into account including older Asian male >40 years Asian male >40 years age, persistence of viral replication, co- Asian female >50 years Asian female >50 years infection with HCV or HIV, or presence of other liver disease” African/North American Blacks African/North American Blacks ─ …“Caucasian pts with active HBV are Benefit uncertain Benefit uncertain likely at risk for HCC and should be Males <40, Females <50 Males <40, Females <50 screened” Bruix J, AASLD Practice Guidelines, 2011. Bruix J, AASLD Practice Guidelines, 2011. HCC Surveillance: Chronic HBV HCC Surveillance: Chronic HBV 1. How should we approach HCC screening in patients 2. How should we approach HCC screening in non- with HIV/HBV? cirrhotic pts with isolated HBcAb+: What about Caucasian pts? • Isolated HBcAb+: Surveillance recommended ─ If no cirrhosis and chronic inactive HBV HBV Population Group • Isolated HBcAb+ associated with increased HCC risk in Japanese (long-term normal ALT, low HBV DNA) pts with non-HBV, non-HCV cirrhosis 1 “the incidence of HCC is probably too Cirrhosis • High prevalence of HBcAb+ in Korean pts with non-HBV, non- low to make surveillance worthwhile” Family h/o HCC HCV HCC 2 ─ However… “additional risk factors have to be taken into account including older • HBcAb+ not associated with HCC in U.S. HCV cohort 3 Asian male >40 years age, persistence of viral replication, co- • Systematic review suggested increased risk of HCC 4 Asian female >50 years infection with HCV or HIV, or presence of other liver disease” ─ Mostly case/control, few adjustments for confounders, only 1 in US African/North American Blacks ─ …“Caucasian pts with active HBV are • Insufficient evidence to support surveillance in this group Benefit uncertain likely at risk for HCC and should be Males <40, Females <50 screened” Bruix J, AASLD Practice Guidelines, 2011. 1 Ikeda K, J Viral Hepat, 2009. 2 Lee SB, Liver Int, 2016. 3 Lok AS, Hepatology, 2011. 4 Lee SB, Liver Int, 2016. 3

12/8/17 HCC Surveillance: Chronic HBV HCC Surveillance: HCV 2. How should we approach HCC screening in non- 3. Should we screen in HCV+ pts with F3 fibrosis? cirrhotic pts with HBsAg loss (spontaneous or due to tx)? • HBsAg loss • HBV tx reduces (but does not eliminate) risk of HCC 1 • HCC still occurs in pts who lose HBsAg spontaneously or with tx 2,3 • Factors predicting HCC: age ≥50 at seroclearance, cirrhosis, low albumin, male sex 3 • Continue surveillance in pts at risk due to baseline factors 4 1 Sung JJY, Aliment Pharmacol Therp, 2008. 2 Hung CH, J Viral Hepat, 2017. 3 KimGA, J Hepatol, 2015. 4 EASL-EORTC Guidelines, 2012. HCC Surveillance: HCV HCC Surveillance: HCV 3. Should we screen in HCV+ pts with F3 fibrosis? 3. Should we screen in HCV+ pts with F3 fibrosis? • HCV+ pts with F3 fibrosis have elevated HCC risk • HCV+ pts with F3 fibrosis have elevated HCC risk • HCC guidelines are conflicting – Recommended for F3 fibrosis in HCV by EASL (2012) – Benefit uncertain in AASLD guidelines (2010) • Post-SVR Treatment guidelines are consistent and recommend surveillance in pts with F3 fibrosis Lok AS, Gastroenterology, 2009. Lok AS, Gastroenterology, 2009. 4

12/8/17 HCC Surveillance: HCV HCC Surveillance: HCV 3. Should we screen in HCV+ pts with F3 fibrosis? 3. Should we screen in HCV+ pts with F3 fibrosis? AASLD/IDSA HCV Guidelines, 2017. EASL HCV Guidelines, 2017. HCC Surveillance: HCV HCC Risk with HCV DAA’s 3. Should we screen in HCV+ pts with F3 fibrosis? 4. Do DAA’s increase the risk of HCC? Yes! • Essential to adequately stage fibrosis prior to HCV tx – Nearly 50% of pts with F3 fibrosis on pre-treatment Fibroscan (≥9.5 kPa) will have post-SVR Fibroscan <9.5 kPa – Fibroscan and other non-invasive fibrosis surrogates have not been validated in post-SVR pts – Limited evidence comparing post-SVR biopsy with Fibroscan shows you will underestimate fibrosis stage if you rely on post-SVR results • 5 UCSF pts with ≥F3 fibrosis on post-SVR biopsy: 3 (60%) had post- SVR Fibroscan <9.5; 1 of these developed HCC post-SVR 5

12/8/17 HCC Risk with HCV DAA’s HCC Risk with HCV DAA’s 4. Do DAA’s increase the risk of HCC? Incident HCC risk 4. Do DAA’s increase the risk of HCC? Incident HCC risk • High de novo HCC occurrence rates within 12 months of DAA cessation reported in 3 early studies HCC Risk with HCV DAA’s HCC Risk with HCV DAA’s 4. Do DAA’s increase the risk of HCC? Incident HCC risk 4. Do DAA’s increase the risk of HCC? Incident HCC risk • High de novo HCC occurrence rates within 12 months • High de novo HCC occurrence rates within 12 months of DAA cessation reported in 3 early studies of DAA cessation reported in 3 early studies • Subsequent larger studies showed no increased risk • Subsequent larger studies showed no increased risk • Large VA study of 22,500 HR 0.28 (95% CI 0.22-0.36) pts (39% with cirrhosis): SVR after DAAs reduced risk of HCC Kanwal F, Gastroenterology, 2017. 6

12/8/17 HCC Risk with HCV DAA’s HCC Risk with HCV DAA’s 4. Do DAA’s increase the risk of HCC? Incident HCC risk 4. Do DAA’s increase the risk of HCC? Recurrence risk SVR (DAA-based tx) 1.5-4% per year • W e are now treating older pts with more advanced liver disease (higher risk for HCC) DAAs are not associated with increased INCIDENT HCC Llovet JM, Nat Rev Gastro Hepatol, 2016. HCC Risk with HCV DAA’s HCC Risk with HCV DAA’s 4. Do DAA’s increase the risk of HCC? Recurrence risk 4. Do DAA’s increase the risk of HCC? Recurrence risk • Some data suggests possibility of early recurrence of • Some data suggests possibility of early recurrence of HCC with DAA therapy HCC with DAA therapy • Several studies show no increased risk ANRS Study Group, J Hepatology, 2016. 7