Table S1A: Patient demographics, tumour characteristics, and laboratory values in patients with hepatocellular carcinoma (with vs. without PVTT) who underwent living donor liver transplantation. HCC-cirr – patients with cirrhosis and hepatocellular carcinoma, PVTT – portal vein tumour thrombus, LDLT – living donor liver transplantation, SD – standard deviation, MELD – model for end stage liver disease, HCC- hepatocellular carcinoma, UCSF – University of California, San Francisco, RT – radiotherapy, DS – downstaged, AFP – alpha feto-protein, 18-FDG PET – 18-fluorodeoxy glucose positron emission tomography, NLR- neutrophil lymphocyte ratio, PLR – platelet lymphocyte ratio

CategoryofpatientCharacteristics

HCC‐cirr,PVTT,LDLTpostdownstaging

N=25

HCC‐cirr,PVTT,LDLTwithoutdownstaging

N=21

pvalue

Demographics Age Mean ± SD 51±8 58±7 <0.01 Sex Male:Female (%) 23 (92%):2 (8%) 19 (90%):2(10%) 0.81 Etiology

Hepatitis C virus (n/%) 9 (32%) 10 (48%) 0.27

Hepatitis B virus (n/%) 11 (44%) 3 (14%) 0.03

Ethanol (n/%) 2 (8%) 3 (14%) 0.52 Non alcoholic fatty liver disease

(n/%) 0 (0) 1 (5%) 0.26

MELD (median/range) 10 (6-21) 11 (6-25) 0.33 HCCcharacteristics Largest tumour median (range) 5.2 cm (1.7-27.5 cm) 4 cm (2.3-16 cm) 0.31

Number of tumours median (range)

3 (1-6) 2 (1-7) 0.82

Milan In vs. Milan Out at diagnosis n (%) [tumour number/size]

4 (16%):21 (84%) 8 (38%) vs. 13 (62%) 0.09

UCSF In vs. UCSF Out at diagnosis n (%) [tumour no./size]

6 (24%) vs. 19 (76%) 9 (43%) vs. 12 (57%) 0.18

Post-RT/pre LDLT AFP (median, range in IU), (mean ±SD) in DS

55 (2-7320)774 ± 1909

271 (4-17104) 2483±4646

0.09

Tumour FDG-18 PET avidity Avid vs. Non avid

21 (84%) vs. 4 (16%) 13 (62%) vs. 8 (38%) 0.09

NLR before LDLT Mean ± SD

6.13 ± 3.8 2.98 ± 1.95 <0.01

PLR before LDLT Mean ± SD

1094±1054

615 ± 426 0.06

Table S1B: Patient demographics, tumour characteristics, and laboratory values in patients with hepatocellular carcinoma with vs. without PVTT who underwent living donor liver transplantation. HCC-cirr – patients with cirrhosis and hepatocellular carcinoma, PVTT – portal vein tumour thrombus, LDLT – living donor liver transplantation, SD – standard deviation, MELD – model for end stage liver disease, HCC- hepatocellular carcinoma, UCSF – University of California, San Francisco, RT – radiotherapy, DS – downstaged, AFP – alpha feto-protein, 18-FDG PET – 18-fluorodeoxy glucose positron emission tomography, NLR- neutrophil lymphocyte ratio, PLR – platelet lymphocyte ratio

CategoryofpatientCharacteristics

HCC‐cirr,PVTT,LDLTpostdownstaging

N=25

HCC‐cirr,noPVTT,LDLTN=405

pvalue

Demographics Age Mean ± SD 51±8 55 ± 8 0.02 Sex Male:Female (%) 23 (92%):2 (8%) 322(80%):83(20%) 0.24 Etiology

Hepatitis C virus (n/%) 9 (32%) 183 (45%) 0.20

Hepatitis B virus (n/%) 11 (44%) 104 (26%) 0.05

Ethanol (n/%) 2 (8%) 40 (10%) 0.74 Non alcoholic fatty liver disease

(n/%) 0 (0) 35 (9%) 0.12

MELD (median/range) 10 (6-21) 19 (6-38) <0.01HCCcharacteristics Largest tumour median (range) 5.2 cm (1.7-27.5 cm) 3.1 cm (0.8-18 cm) <0.01

Number of tumours median (range)

3 (1-6) 1 (1-6) 0.04

Milan In vs. Milan Out at diagnosis n (%) [tumour number/size]

4 (16%):21 (84%) 197(49%):208 (51%)

<0.01

UCSF In vs. UCSF Out at diagnosis n (%) [tumour no./size]

6 (24%) vs. 19 (76%) 231(57%):174 (43%)

<0.01

Post-RT/pre LDLT AFP (median, range in IU), (mean ±SD) in DS

55 (2-7320)774 ± 1909

23.7 (1-17500)551±1849

0.32 0.69

Tumour FDG-18 PET avidity Avid vs. Non avid

21 (84%) vs. 4 (16%) 149( 47%):170 (53%)

<0.01

NLR before LDLT Mean ± SD

6.13 ± 3.8 3.32 ± 2.92 <0.01

PLR before LDLT Mean ± SD

1094±1054

622 ± 731 <0.01

Table S2A: Tumour pathology and recurrence patterns in in patients with hepatocellular carcinoma with PVTT who underwent living donor liver transplantation with vs. without downstaging therapy HCC-cirr – patients with cirrhosis and hepatocellular carcinoma, PVTT – portal vein tumour thrombus, LDLT – living donor liver transplantation, SD – standard deviation

CategoryofpatientCharacteristics

HCC‐cirr,PVTT,LDLTpostdownstaging

N=25

HCC‐cirr,PVTT,LDLTwithoutdownstaging

N=21

pvalue

Explanthistopathology Largest tumor mean±SD (range) 6.3±5.2 5.1±3.2 0.36 Number of tumors mean±SD (range) 2.9±1.6 (1-multiple) 2.9±1.9 (1-multiple) 1.00 Microvascular invasion 21 (84%) 17 (81%) 0.79 Hepatic venous branch involvement 6 (24%) 8 (38%) 0.31 RecurrencePatterns Number of patients (%) 6 (24%) 10 (48%) 0.09 Time to recurrence [months] Mean ± SD

9 ± 15

13 ± 13

0.34

Recurrence type n (single or multiple sites)

Hepatic 3 (50%) 2 (20%) 0.04

Lung 5 (83%) 7 (70%) 0.42 Bone 2 (33%) 4 (40%) 0.63 Lymph nodes, soft tissue - 3 (30%) <0.01 Brain - 1 (10%) 0.11

Table S2B: Tumour pathology and recurrence patterns in patients with hepatocellular carcinoma with vs. without PVTT who underwent living donor liver transplantation. HCC-cirr – patients with cirrhosis and hepatocellular carcinoma, PVTT – portal vein tumour thrombus, LDLT – living donor liver transplantation, SD – standard deviation

CategoryofpatientCharacteristics

HCC‐cirr,PVTT,LDLTpostdownstaging

N=25

HCC‐cirr,noPVTT,LDLTN=405

pvalue

Explanthistopathology Largest tumor mean±SD (range) 6.3±5.2 4.3±3.2 <0.01Number of tumors mean±SD (range) 2.9±1.6 (1-multiple) 2.0±1.3 (1-multiple) <0.01 Microvascular invasion 21 (84%) 164 (50%) <0.01Hepatic venous branch involvement 6 (24%) 20 (5%) <0.01 RecurrencePatterns Number of patients (%) 6 (24%) 95 (23%) 0.91 Time to recurrence [months] Mean ± SD

9 ± 15

19 ± 17

Recurrence type n (single or multiple sites)

Hepatic 3 (50%) 31 (33%) 0.08

Lung 5 (83%) 42 (44%) <0.01 Bone 2 (33%) 12 (13%) <0.01 Lymph nodes, soft tissue - 8 (8%) 0.15 Brain - 2 (2%) 0.48

Figure S1

A: Overall survival in patients with hepatocellular carcinoma and portal vein tumor

thrombus undergoing living donor liver transplantation after successful downstaging

(n=23), after censoring postoperative deaths

B: Recurrence-free survival in patients with hepatocellular carcinoma and portal vein

tumor thrombus undergoing living donor liver transplantation after successful

downstaging (n=23), after censoring postoperative deaths

Figure S2

A: Overall survival in patients with hepatocellular carcinoma and portal vein tumor

thrombus undergoing living donor liver transplantation with/without downstaging

(n=43), after censoring postoperative deaths

B: Recurrence-free survival in patients with hepatocellular carcinoma and portal vein

tumor thrombus undergoing living donor liver transplantation with/without

downstaging (n=43), after censoring postoperative deaths

Figure S3 - Overall survival in patients with hepatocellular carcinoma and portal vein

tumor thrombus who were treated with transarterial readioembolization or

stereotactic body radiation with/without Sorafenib or those who received no

intervention, or Sorafenib alone.

Figure S4 - Comparison of OS between HCC patients with Vp3/Vp4 PVTT receiving DS

before LDLT (n=12) vs. Vp3 PVTT who underwent upfront LDLT without DS (n=3)

Figure S5A - Comparison of OS between HCC patients with Vp3/Vp4 PVTT receiving DS

before LDLT (n=12) vs. HCC patients without PVTT undergoing upfront LDLT (n=382)

Figure S5B - Comparison of OS between HCC patients with Vp3/Vp4 PVTT receiving DS

before LDLT (n=12) vs. HCC patients with PVTT receiving only palliative treatment and

no transplant (n=44)