[PDF] - Liver Transplant and Etiology Which of the following is the most PDF Document

SLIDE 1

10/2/2017 1 Liver Transplantation for Hepatocellular carcinoma (HCC)

Francis Yao, M.D.

Professor of Clinical Medicine and Surgery Medical Director, Liver Transplantation University of California, San Francisco

Asian Health Symposium 2017

Liver Transplant and Etiology

Which of the following is the most

common indication of liver transplant now in the United States?

HCV
Alcoholic liver disease
Fatty liver disease/ NASH
HBV
HCC

Liver Transplant and Etiology

Which of the following is the most

common indication of liver transplant now in the United States?

HCV
Alcoholic liver disease
Fatty liver disease/ NASH
HBV
HCC

HCC among Asians

Higher rate of primary liver cancer (HCC)

among the 12 million Asians and Pacific Islanders living in the U.S. than the general U.S. population

High prevalence of hepatitis B and C among

Asians

Increasing prevalence of obesity, diabetes, and

hypertension – risk factors for non-alcoholic steatohepatitis (NASH)

SLIDE 2

10/2/2017 2 HCV and HCC

Chronic HCV Cirrhosis HCC

Even with SVR after DAA therapy, patients with cirrhosis are still at high risk for HCC

Kanwal F et al. Gastroenterology 2017;153:996-1005

HBV and HCC

Chronic HBV Cirrhosis HCC

Cirrhosis Family history of HCC Age > 40 male Age > 50 female Active disease Screening Guidelines

Arterial Phase Portal Venous phase Hyper-enhancement “washout”

HCC – Radiologic Diagnosis HCC – Is Biopsy Necessary?

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%

Biopsy in selected cases if atypical radiologic appearance or lack of strong risk factor for HCC

SLIDE 3

10/2/2017 3

HCC

Stage A-C

Okuda 1-2, PST 0-2, Child-Pugh A-B

BCLC Staging Classification

Adapted from Llovet JM et al. Lancet 2003;362:1907-17

Stage D

Okuda 3, PST >2, Child-Pugh C

Stage 0

PST 0, Child-Pugh A Very early stage (0) Single < 2 cm, CA in situ Single Portal pressure/ bilirubin Normal

Resection Liver Transplantation PEI/ RFA

Terminal stage (D)

5-yr survival 50-70% TACE New agents 3-yr survival 20-40% Symptomatic Tx 1-yr survival 10-20%

Early stage (A) Single or 3 nodules < 3 cm, PS 0 Intermedicate stage (B) Multinodular, PS 0 3 nodules < 3cm Increased Associated diseases No Yes Advanced stage (C) Poral vein invasion, N1,M1, PS 1-2 Portal invasion, N1, Mi

Surgical Treatment for Early HCC

Cirrhosis, Liver Function, & Portal Hypertension

Resection Non-Cirrhotic

5% in Western countries 40% in Asia

Cirrhotic

Child’s A Child’s B Child’s C

Liver Transplant

(-) portal hypertension (+) portal hypertension

Liver Transplant for HCC

Milan Criteria

+ Absence of Macroscopic Vascular Invasion Absence of Extra-hepatic Spread 1 lesion ≤ 5 cm 2 to 3, none > 3 cm

Mazzaferro et al. N Engl J Med 1996;334: 693-699

In the United States, the MELD score (bilirubin, INR,

creatinine) ranging from 6 to 40 determines the status

n 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 HCC-MELD score and upgrades every 3 months.

Organ Allocation for HCC

SLIDE 4

10/2/2017 4

Regional disparities in waiting time
In our region, waiting time for HCC patients receiving

MELD-exception 18-24 months for blood type O (versus < 3 months in many other regions)

In short wait time regions, unfair advantage of HCC

versus non-HCC patients in receiving liver transplant

Transplant “tourism”
“Mandatory wait” of 6 months
More changes are coming

Organ Allocation for HCC

Local regional therapy is frequently used to control

tumor growth before liver transplant, serving as a bridge to transplant.

There is no level I evidence to confirm the benefits
f local regional therapy in reducing the risk of

dropout from the waiting list or improving outcome after liver transplant.1,2

Local regional therapy is cost-effective if the waiting

time is expected to be > 6 months (Markov model).3

Local Regional Therapy as “bridge”

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

Local Regional Therapies for HCC

Chemoembolization (TACE)

Conventional versus Drug-eluting beads

Ablations

Percutaneous ethanol injection (PEI)

(Laparoscopic, percutaneous or open)

Radiofrequency ablation (RFA) Chemical Thermal Radioembolization (Yttrium-90) & External Beam Irradiation Microwave/ Cryo- ablation

Trans-catheter Arterial Chemoembolization (TACE)

Selective embolization of the

hepatic arterial supply to tumor via the common femoral artery.

Cytotoxic agent (Cis-platinum,

Doxorubicin, Mitomycin-C, 5-FU) mixed with lipiodol or gelfoam particles.

Complications include fever,

abdominal pain, infection (abscess), hepatic arterial injury, hepatic decompensation

SLIDE 5

10/2/2017 5

Local Regional Therapy for HCC Choice of Treatment

Lesion < 5 cm

Percutanoeus RFA

Ideal location Most effective when ≤ 3 cm

TACE

Limitations of percutanoeus RFA – Tumor location Adjacent to bowel Adjacent to diaphram

Local Regional Therapy for HCC Choice of Treatment

Limitations of percutanoeus RFA – Tumor location Adjacent to large vessel (heat-sink)

Local Regional Therapy for HCC Choice of Treatment

0 12 24 36 48 60 72 84 96 Months after Liver Transplantation

67.5 + 2.4% 51.1 + 4.8% 39.1 + 6.3%

100 80 60 40 20

AFP <=100 ng/L AFP 100-1000 AFP > 1000 ng/L

P < 0.001

Duvoux et al. Gastroenterology 2012;143:986-94 n=109 n=387 n=61

Survival rate (%)

AFP and Post-transplant Outcome

SLIDE 6

10/2/2017 6

80% 52% y

AFP <=1000 ng/mL AFP >1000 ng/mL

p = 0.026

Hameed B. et al. Liver Transpl 2014;20:945-951

SURVIVAL WITHOUT HCC RECURRENCE

Applying an AFP cutoff of >1000 ng/mL to

patients with HCC (within Milan) would have resulted in exclusion of 5% of patients from LT, and a 20% reduction in the rate of post- transplant HCC recurrence

At UCSF, patients with AFP > 1000 ng/mL are

required to show decrease in AFP to < 500 with local regional therapy prior to liver transplant

Hameed B. et al. Liver Transpl 2014;20:945-951

Applying AFP As Exclusion Criterion

Applying an AFP cutoff of >1000 ng/mL to

patients with HCC (within Milan) would have resulted in exclusion of 5% of patients from LT, and a 20% reduction in the rate of post- transplant HCC recurrence

UNOS National policy: Patients with AFP > 1000

ng/mL are required to show decrease in AFP to < 500 with local regional therapy prior to liver transplant

Applying AFP As Exclusion Criterion

Liver Transplant HCC (Milan T2) Expanded Criteria

The “Ablate and Wait” Concept

Dropout Dropout

Roberts JP, Venook A, Kerlan R, Yao F. Liver Transpl 2010;16:925-9

Ablate and wait

Down-staging

SLIDE 7

10/2/2017 7

Liver Transplant HCC (Milan T2) Expanded Criteria

The “Ablate and Wait” Concept

Dropout Dropout

Roberts JP, Venook A, Kerlan R, Yao F. Liver Transpl 2010;16:925-9

Ablate and wait

Down-staging

AFP

Tumor Down-staging Before Transplant

Beyond Milan Within Milan Complete necrosis

Yao & Fidelman. Hepatology 2016;63:1014-1025

No vascular invasion on imaging
1 lesion >5 cm and ≤ 8 cm
2 or 3 lesions, each ≤ 5 cm with total

tumor diameter of all lesions ≤ 8 cm

4 or 5 lesions, none >3 cm with total

tumor diameter of all lesions ≤ 8 cm

UCSF Down-staging Protocol

Inclusion Criteria

Yao et al. Hepatology 2015;61:1968-1977

Down-staging of HCC Updated UCSF Data

Down-staging Transplant

Meeting Milan criteria Dropout (n=118) (n=41) (n=64)

5 HCC recurrence (8%)
78% 5-yr survival

post-transplant

91% 5-yr recurrence

free probability

56% 5-yr intention-

to-treat survival Yao et al. Hepatology 2015;61:1968-1977 Median f/u 3.8 years