Liver Transplant and Etiology Which of the following is the most - PDF document

10/2/2017 Asian Health Symposium 2017 Liver Transplant and Etiology  Which of the following is the most Liver Transplantation for common indication of liver transplant now in the United States? Hepatocellular carcinoma (HCC)  HCV Francis Yao, M.D.  Alcoholic liver disease Professor of Clinical Medicine and Surgery  Fatty liver disease/ NASH Medical Director, Liver Transplantation  HBV University of California, San Francisco  HCC HCC among Asians Liver Transplant and Etiology  Which of the following is the most  Higher rate of primary liver cancer (HCC) common indication of liver transplant now among the 12 million Asians and Pacific in the United States? Islanders living in the U.S. than the general U.S. population  High prevalence of hepatitis B and C among  HCV  Alcoholic liver disease Asians  Increasing prevalence of obesity, diabetes, and  Fatty liver disease/ NASH  HBV hypertension – risk factors for non-alcoholic steatohepatitis (NASH)  HCC 1

10/2/2017 HCV and HCC HBV and HCC Chronic HCV Chronic HBV Screening Guidelines Cirrhosis Even with SVR after Family history of HCC DAA therapy, patients Cirrhosis Cirrhosis Age > 40 male with cirrhosis are still Age > 50 female at high risk for HCC Active disease HCC HCC Kanwal F et al. Gastroenterology 2017;153:996-1005 HCC – Radiologic Diagnosis HCC – Is Biopsy Necessary? Arterial Phase Portal Venous phase Biopsy is not necessary to confirm HCC diagnosis if the lesion meets radiologic criteria in the appropriate clinical setting False negative biopsy common in clinical practice and may need to delay in diagnosis and treatment Tumor seeding along the biopsy tract in 1-5 % Hyper-enhancement “washout” Biopsy in selected cases if atypical radiologic appearance or lack of strong risk factor for HCC 2

10/2/2017 BCLC Staging Classification Surgical Treatment for Early HCC Cirrhosis, Liver Function, & Portal Hypertension HCC Stage 0 Stage A-C Stage D PST 0, Child-Pugh A Okuda 1-2, PST 0-2, Child-Pugh A-B Okuda 3, PST >2, Child-Pugh C Very early stage (0) Early stage (A) Intermedicate Advanced stage (C) Terminal Non-Cirrhotic Resection Single < 2 cm, Single or 3 nodules stage (B) Poral vein invasion, stage (D) CA in situ < 3 cm, PS 0 Multinodular, PS 0 N1,M1, PS 1-2 5% in Western countries 40% in Asia Single 3 nodules < 3cm (-) portal hypertension Cirrhotic Portal pressure/ bilirubin Increased Associated diseases Portal invasion, N1, Mi Child’s A (+) portal hypertension Normal No Yes Child’s B Liver Transplant Child’s C Resection Liver Transplantation PEI/ RFA TACE New agents Symptomatic Tx 1-yr survival 10-20% 5-yr survival 50-70% 3-yr survival 20-40% Adapted from Llovet JM et al. Lancet 2003;362:1907-17 Liver Transplant for HCC Organ Allocation for HCC Milan Criteria • In the United States, the MELD score (bilirubin, INR, creatinine) ranging from 6 to 40 determines the status 1 lesion ≤ 5 cm 2 to 3, none > 3 cm on the waiting list for liver transplant – “sickest first” policy. • Milan criteria subdivided into T1 (1 lesion < 2 cm) and T2 (1 lesion 2-5 cm, 2-3 lesions up to 3 cm) in the UNOS staging system for liver transplant. • Only patients with HCC meeting T2 criteria are + eligible for receiving priority listing with an adjusted Absence of Macroscopic Vascular Invasion HCC-MELD score and upgrades every 3 months. Absence of Extra-hepatic Spread Mazzaferro et al. N Engl J Med 1996;334: 693-699 3

10/2/2017 Organ Allocation for HCC Local Regional Therapy as “bridge” • Local regional therapy is frequently used to control • Regional disparities in waiting time tumor growth before liver transplant, serving as a • In our region, waiting time for HCC patients receiving bridge to transplant. MELD-exception 18-24 months for blood type O • There is no level I evidence to confirm the benefits (versus < 3 months in many other regions) of local regional therapy in reducing the risk of • In short wait time regions, unfair advantage of HCC dropout from the waiting list or improving outcome versus non-HCC patients in receiving liver transplant after liver transplant. 1,2 • Transplant “tourism” • Local regional therapy is cost-effective if the waiting • “Mandatory wait” of 6 months time is expected to be > 6 months (Markov model). 3 • More changes are coming 1 Lesurtel M, et al. Am J Transpl 2006; 6:2644-50 2 Clavien PA, et al. Lancet Oncology 2012:13;11-22 3 Llovet J, et al. Gut 2000;50:123-128 Trans-catheter Arterial Chemoembolization (TACE) Local Regional Therapies for HCC Chemoembolization (TACE) - Selective embolization of the hepatic arterial supply to tumor Conventional versus Drug-eluting beads via the common femoral artery. Ablations - Cytotoxic agent (Cis-platinum, Doxorubicin, Mitomycin-C, Chemical 5-FU) mixed with lipiodol or Percutaneous ethanol injection (PEI) gelfoam particles. Thermal - Complications include fever, abdominal pain, infection Radiofrequency ablation (RFA) (abscess), hepatic arterial (Laparoscopic, percutaneous or open) injury, hepatic decompensation Microwave/ Cryo- ablation Radioembolization (Yttrium-90) & External Beam Irradiation 4

10/2/2017 Local Regional Therapy for HCC Local Regional Therapy for HCC Choice of Treatment Choice of Treatment Lesion < 5 cm Limitations of percutanoeus RFA – Tumor location Adjacent to diaphram Adjacent to bowel - Percutanoeus RFA Ideal location Most effective when ≤ 3 cm - TACE AFP and Post-transplant Outcome Local Regional Therapy for HCC 100 Choice of Treatment Limitations of percutanoeus RFA – Tumor location 80 67.5 + 2.4% Adjacent to large vessel (heat-sink) Survival rate (%) n=387 60 AFP <=100 ng/L 51.1 + 4.8% n=109 AFP 100-1000 40 AFP > 1000 ng/L 39.1 + 6.3% n=61 20 P < 0.001 0 0 12 24 36 48 60 72 84 96 Months after Liver Transplantation Duvoux et al. Gastroenterology 2012;143:986-94 5

10/2/2017 SURVIVAL WITHOUT HCC RECURRENCE Applying AFP As Exclusion Criterion 80% • Applying an AFP cutoff of >1000 ng/mL to patients with HCC (within Milan) would have AFP <=1000 ng/mL resulted in exclusion of 5% of patients from LT, 52% and a 20% reduction in the rate of post- AFP >1000 ng/mL transplant HCC recurrence • At UCSF, patients with AFP > 1000 ng/mL are required to show decrease in AFP to < 500 with p = 0.026 local regional therapy prior to liver transplant y Hameed B. et al. Liver Transpl 2014;20:945-951 Hameed B. et al. Liver Transpl 2014;20:945-951 The “Ablate and Wait” Concept Applying AFP As Exclusion Criterion • Applying an AFP cutoff of >1000 ng/mL to patients with HCC (within Milan) would have HCC Expanded resulted in exclusion of 5% of patients from LT, (Milan T2) Criteria Down-staging and a 20% reduction in the rate of post- transplant HCC recurrence Ablate and wait • UNOS National policy: Patients with AFP > 1000 ng/mL are required to show decrease in AFP to Dropout Dropout < 500 with local regional therapy prior to liver Liver Transplant transplant Roberts JP, Venook A, Kerlan R, Yao F. Liver Transpl 2010;16:925-9 6

10/2/2017 The “Ablate and Wait” Concept Tumor Down-staging Before Transplant Within Milan Complete necrosis Beyond Milan HCC Expanded (Milan T2) Criteria Down-staging Ablate and wait AFP Dropout Dropout Liver Transplant Roberts JP, Venook A, Kerlan R, Yao F. Liver Transpl 2010;16:925-9 Yao & Fidelman. Hepatology 2016;63:1014-1025 UCSF Down-staging Protocol Down-staging of HCC Inclusion Criteria Updated UCSF Data • No vascular invasion on imaging Meeting Milan criteria (n=41) • 1 lesion >5 cm and ≤ 8 cm Median f/u 3.8 years Dropout - 5 HCC recurrence (8%) • 2 or 3 lesions, each ≤ 5 cm with total - 78% 5-yr survival post-transplant tumor diameter of all lesions ≤ 8 cm - 91% 5-yr recurrence free probability Transplant Down-staging - 56% 5-yr intention- • 4 or 5 lesions, none >3 cm with total (n=64) (n=118) to-treat survival tumor diameter of all lesions ≤ 8 cm UCSF Criteria for Down-staging 1 tumor ≤ 8 cm 2-3 tumor ≤ 5 cm + total diameter ≤ 8 cm 4-5 tumor ≤ 3 cm + total diameter ≤ 8 cm Yao et al. Hepatology 2015;61:1968-1977 Yao et al. Hepatology 2015;61:1968-1977 7