Macrovascular Invasion Is Not an Absolute Contraindication for Living Donor Liver Transplantation

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1 ORIGINAL ARTICLE LEE ET AL. Macrovascular Invasion Is Not an Absolute Contraindication for Living Donor Liver Transplantation Kwang-Woong Lee, 1 Suk-Won Suh, 1 YoungRok Choi, 1 Jaehong Jeong, 1 Nam-Joon Yi, 1 Hyeyoung Kim, 1 Kyung Chul Yoon, 1 Suk Kyun Hong, 1 Hyo-Sin Kim, 1 Kyung-Bun Lee, 2 and Kyung-Suk Suh 1 Departments of 1 Surgery and 2 Pathology, Seoul National University College of Medicine, Seoul, South Korea The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1-, 3-, and 5-year recurrence-free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha-fetoprotein 3 protein induced by vitamin K absence/antagonist-ii (AP) score (20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (2.1; P < 0.01), and a large original tumor (7cm; P ) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23: AASLD. Received April 3, 2016; accepted August 6, Liver transplantation (LT) is a curative therapeutic option for hepatocellular carcinoma (HCC) because it provides complete oncologic resection and correction of underlying liver dysfunction. However, because recurrence after LT results in a poor prognosis, several Abbreviations: [ 18 F]FDG, [ 18 F]fluorodeoxyglucose; AFP, alpha-fetoprotein; AP, alpha-fetoprotein 3 protein induced by vitamin K absence/antagonist-ii; CR, complete response; CT, computed tomography; GRWR, graft-to-recipient weight ratio; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; LDLT, living donor liver transplantation; LPV, left portal vein; LT, liver transplantation; MC, multinodular confluent; MELD, Model for End-Stage Liver Disease; MMF, mycophenolate mofetil; MoRAL, a model to predict tumor recurrence after living donor liver transplantation; mtor, mammalian target of rapamycin; NBNC, non-b, non-c; P3, segment 3 portal vein; PD, progressive disease; PEIT, percutaneous ethanol injection; PET, positron emission tomography; PIVKAII, protein induced by vitamin K absence/antagonist-ii; PV, portal vein; PVTT, portal vein tumor thrombus; RAPV, right anterior portal vein; RFS, recurrence-free survival; RPPV, right posterior portal vein; RPV, right portal vein; SUV, standardized uptake value; TACE, transarterial chemoembolization; TARE, transarterial radioembolization. preoperative selection criteria including the Milan or University of California San Francisco criteria have been proposed to select patient subgroups to show comparable outcomes with non-hcc patients. (1,2) However, some patients who are not categorized by these criteria can show favorable outcomes. Therefore, patients with advanced HCC who have no other effective treatment modality and who have made a strong request for a living donor liver transplantation (LDLT) are granted a LT, even with the high risk of recurrence. This may be one of the reasons that the indication of LT for HCC is expanding in LDLT. We used significant preoperative biological factors, such as alpha-fetoprotein (AFP), (3) protein induced by vitamin K absence/antagonist-ii (PIVKAII), and positron emission tomography (PET) positivity, (4-7) to predict the prognosis after LDLT. A combination of those biological factors can be used to select a favorable group even in advanced HCC. However, despite of expansion of the indication of LT for advanced HCC, the invasion into the major portal vein (PV) has remained as an absolute contraindication for LT. ORIGINAL ARTICLE 19

2 LEE ET AL. LIVER TRANSPLANTATION, January 2017 At our institution, we provided a LDLT to patients with portal vein tumor thrombus (PVTT) who demonstrated a progressing functional decline, had no other effective treatment modality, and had a strong request for LDLT in order to increase the chance of survival. Furthermore, there have been recent reports on several adjuvant and therapeutic strategies, such as mammalian target of rapamycin (mtor) inhibitors or sorafenib, which may result in a better prognosis. We experienced an unexpectedly good prognosis in selected patients. Therefore, we hypothesized that significant preoperative biological factors will predict prognosis after LDLT with major PVTT and that a combination of biological factors can be used to select favorable groups for a better prognosis in this category. Patients and Methods PATIENTS AND INFORMED CONSENT From January 2009 to December 2013, 282 patients underwent LDLT for HCC at Seoul National University Hospital in Seoul, South Korea. Among them, 11 (3.9%) patients with major PVTT diagnosed radiologically before transplantation were retrospectively reviewed after institutional review board approval (number ). Two patients were excluded from this study because the tumor could not be excised completely during LT due to extensive PVTT down to the PV trunk or superior mesenteric vein. Informed consent including the high-risk nature of this procedure was obtained from both the donor and recipient. High risk of HCC recurrence and short expected survival were manually written in the informed consent. Address reprint requests to Kwang-Woong Lee, M.D., Ph.D., Department of Surgery, Seoul National University College of Medicine, 101 Daehak-no, Jongno-gu, Seoul, , South Korea. Telephone: ; FAX: ; kwleegs@gmail.com This work was supported by the Research Resettlement Fund for the new faculty of Seoul National University ( ). Copyright VC 2016 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI /lt Potential conflict of interest: Nothing to report. DEMOGRAPHICS AND DEFINITIONS Demographics and tumor characteristics were evaluated retrospectively by review of our clinical database and pathology reports of explanted livers. Macrovascular PVTT, defined as a tumor thrombus in the major PV (Vp2, Vp3, or Vp4), was identified by preoperative imaging studies. (8) Each grade is defined as follows: Vp2, presence of a tumor thrombus in the second-order branches of the PV; Vp3, presence of a tumor thrombus in the first-order branches of the PV; and Vp4, presence of a tumor thrombus in the main trunk of the PV or a PV branch contralateral to the primarily involved lobe (or both). Tumor size was measured at the largest diameter of the major tumor (in cm) regardless of viability. The standardized uptake value (SUV) ratio (tumor/ background liver) was calculated in [ 18 F]fluorodeoxyglucose ([ 18 F]FDG) PET scan using the previously described method. (7) A SUV ratio 1.10 was considered as positive. POSTOPERATIVE MANAGEMENT AND FOLLOW-UP PROTOCOL AFTER LT Immunosuppression was a conventional triple regimen including tacrolimus, mycophenolate mofetil (MMF), and steroids after interleukin 2 antagonist induction. The steroid was tapered within 3 months. In some patients, sirolimus was used 1 month after LT. Adjuvant sorafenib was used in selected patients. The serum level of AFP and PIVKAII were measured during every visit. Abdominopelvic computed tomography (CT), chest CT, and a bone scan were performed every 2 or 3 months for the first year and a half after LT and at a 6-month interval thereafter, or in case of increasing level of tumor markers. If routine follow-up imaging studies did not reveal a recurrent lesion despite the suspicion of recurrence, [ 18 F]FDG-PET was performed. RISK FACTOR ANALYSIS Ten variables were analyzed to determine the risk factors for HCC recurrence after LT. The preoperative demographic characteristics included age and sex of the donor and recipient, serum AFP levels (peak and pre-lt), serum PIVKAII levels (peak and pre-lt), alpha-fetoprotein 3 protein induced by vitamin K absence/antagonist-ii (AP) score (peak and pre-lt), SUV ratio between tumor and background liver in 20 ORIGINAL ARTICLE

3 TABLE 1. Baseline and Pathologic Characteristics of 11 HCC Patients With PV Tumor Thrombi Who Underwent LDLT Recipient Donor Pre-LT HCC-Related Characteristics Explant Liver Pathology Postoperative Patient Number Year Age Sex MELD Score Viral Age Sex Relation GRWR Initial Diagnosis To PVTT, Months Transplantation Before PVTT PVTT to LT (mon) Transplantation After PVTT Radiological Response AFP (Peak/ at LT), ng/ml PIVKAII (Peak/ at LT), ng/ml AP Score at LT PET (SUV ratio) Level of PVTT Gross Type of Tumor HCC Size, cm HCC Number (Distribution) ES Grade (Major/ Worst) Viable Tumor Cells in PVTT Adjuvant mtor RFS, Months Survival, Months Male 21 HBV 21 Male Son No 0.5 No 9.8/ Male 9 HBV 20 Male Son TACE and PEIT 1.5 TACE (#1) CR 30.2/ Male 11 HBV 45 Female Wife No 1.5 No 137.8/ Male 6 HBV 27 Male Son No 0.8 No 19.1/ Male 11 HBV 30 Male Son No 0.2 No 18.8/ Male 18 HCV 49 Female Sister No 1.3 TACE (#1) Male 18 NBNC 32 Female Niece TACE 3.0 TACE (#1) PD 340,200.0/ 52, / / 37 17, Vp3 (RPV) Vp3 (RPV) 56/ Vp2 (P3) 173/ / 17 24,000/ 14,360 PD 2.9/1.0 48,000/ 48, Male 10 HBV 22 Male Son No 1.0 No 180.0/ Female 11 HBV 33 Male Son No 0.7 No 36,500.0/ 33, Male 8 HBV 37 Female Wife No 0.7 No / Male 24 HBV 44 Male Brotherin-law No 28.5 TACE (#8) PD / ,880/ 40, / ,520/ 37, / 37, Vp2 (RAPV) Vp2 (RAPV) 750,000, Vp3 (LPV) 48, Vp3 (RPPV and LPV) 7,400, ,000, ,300, 000, ,000, MC (both) II/II Yes Infiltrative 11 1 (Right) III/III Yes MC (both) II/III Yes MC 4 2 (both) IV/IV Yes MC 5.5 >5 (right) III/IV Yes MC with indistinct margin 5.2 >10 (both) II/III No 1 20* 64* MC 7.0 >10 (both) II/III Yes 0 21* 60* 1.5 Vp4 Diffuse 15.0 >5 (both) III/IV Yes 0 2* 10* 2.9 Vp4 MC (both) III/III Yes 1 2* 17* 2.3 Vp4 Diffuse 14.0 >5 (right) III/IV Yes 1 4* 12* 2.6 Vp4 MC 7.5 >5 (left and caudate) II/IV Yes 1 1* 3* *Recurrent patient.

4 LEE ET AL. LIVER TRANSPLANTATION, January 2017 FIG. 1. RFS. (A) Overall, according to (B) pretransplant AP score, (C) level of PV tumor thrombosis, (D) largest tumor size, and (E) SUV ratio (tumor/background liver). [Color figure can be viewed at wileyonlinelibrary.com] PET scan, Model for End-Stage Liver Disease (MELD) score, and pretransplant treatment. Factors related to tumor pathologic characteristics included tumor size, number of tumor lesions, Edmondson- Steiner grade, and viable tumor in PVTT. Factors related to post-lt management included adjuvant use of mtor inhibitors and sorafenib. STATISTICAL ANALYSIS Kaplan-Meier estimates of disease-free survival and survival were calculated and compared with the logrank test. Multivariate analysis was not performed because of the small number of patients. A P value < 0.05 was considered statistically significant. Results DEMOGRAPHICS AND TUMOR CHARACTERISTICS Baseline demographics and tumor characteristics are shown in Table 1. The mean age was years. The majority of patients were men (91%). Among 11 patients, 8 patients were diagnosed as HCC with PVTT at initial diagnosis. One patient (number 5) showed rapid development of PVTT during 1 month without treatment. Therefore, only 2 patients received liver-directed therapy (transarterial chemoembolization [TACE] or percutaneous ethanol injection [PEIT]) before PVTT development and 4 (35.4%) patients received TACE after PVTT development. Among 4 patients who received TACE after PVTT development, 1 patient (number 2) showed compact lipiodol uptake on follow-up CT. The other 3 patients (numbers 6, 7, and 11) showed disease progression. The median preoperative level of serum AFP and PIVKAII were ng/ml (range, ,400.0 ng/ml) and 1760 ng/ml (range, 17-48,000), respectively. PET was positive in all patients. The mean SUV ratio was The mean number of tumors was 3 (range, 1-10). The mean diameter of the largest tumor was cm (range, cm). There were 4 patients where the PVTT reached the main PV (Vp4). A viable tumor was found in the PVTT of the explanted liver in most patients except 1 patient (number 6). All patients were pathologically diagnosed as HCC. Cirrhosis 22 ORIGINAL ARTICLE

5 LIVER TRANSPLANTATION, Vol. 23, No. 1, 2017 LEE ET AL. FIG. 2. Patient survivals. (A) Overall, (B) according to pretransplant AP score, (C) level of PVTT, (D) largest tumor size, and (E) SUV ratio (tumor/background liver). [Color figure can be viewed at wileyonlinelibrary.com] was found in the background liver in most patients except patients 2 and 9. Adjuvant mtor inhibitor was used in 8 (73%) patients. The mtor inhibitor was added at least 1 month after LT. Tacrolimus plus mtor inhibitor or a MMF plus mtor inhibitor combination was a common adjuvant regimen. After recurrence, mtor inhibitor was used in all patients. Adjuvant sorafenib was used in 1 patient (number 2). Mean follow-up duration was 40 months (3-69 months). All currently surviving patients were followed up for more than 40 months. RECURRENCE AND SURVIVAL AFTER LT Recurrence occurred in 6 (54.5%) patients. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 63.6%, 45.5%, and 45.5%, respectively. Mean time to recurrence was months (1-20 months; Fig. 1). All recurrent cases showed a combined type of recurrence (intrahepatic and extrahepatic). However, 3 recurrent cases received resection at the time of the first recurrence. Patient number 6 received a metastatectomy for the abdominal seeding nodules. Patient number 7 received an adrenalectomy for the single adrenal metastasis. Patient number 9 received a repeated pneumonectomy and metastatectomy for abdominal seeding nodule. After surgical resection, new metastatic lesions were developed in intrahepatic and extrahepatic sites. The other 3 patients (numbers 8, 10, and 11) received only sorafenib, TACE, or radiotherapy without resection because of systemic recurrence at the time of recurrence. The 1-, 3-, and 5-year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively. Two patients with delayed recurrence survived approximately 5 years after LT (patients 6 and 7 in Table 1; Fig. 2). RISK FACTORS FOR RECURRENCE AND SURVIVAL In univariate analysis, the pre-lt AP score, a high SUV ratio in the PET scan (>2.1), the level of PVTT, ORIGINAL ARTICLE 23

6 LEE ET AL. LIVER TRANSPLANTATION, January 2017 and the largest tumor of a size 7 cm were identified as significant risk factors for recurrence (Table 2). Pre- LT AP score, level of PVTT, and largest tumor of a size 7 cm were significant risk factors for survival. All 5 patients with pre-lt AP score < 20,000 ng/ml showed no HCC recurrence. All 4 patients with PVTT in the main PV showed recurrence within 4 months after LT. Discussion Tumor recurrence is a significant cause of death in LT patients with HCC (9,10) and is known to have a very poor prognosis. Therefore, selection of a favorable group has been considered to be more important than treatment after recurrence in LDLT for HCC. Recently, biological markers, such as AFP and PIV- KAII, have been suggested as selection criteria. Recent studies reported low recurrence rates after LT in patients with low AFP and PIVKAII even in patients who were outside Milan criteria. (3,4) Combined AP score was also suggested as a significant predictor in LDLT across Milan criteria. (11,12) This concept can be applied in far advanced cases. Also the significance of tumor markers to predict prognosis were reported in resection studies. (13-15) PET scan positivity also has been reported as an important risk factor for HCC recurrence across Milan criteria. (4-7) However, major PVTT has been regarded as a contraindication for LT as well as resection. There have been previous studies which also reported poor outcomes after LT in patients with PVTT. (16,17) According to the Barcelona Clinic Liver Cancer guideline, sorafenib or palliative management is recommend in patients with PVTT. (18) However, we hypothesized that HCC with major PVTT can show good outcomes after LT in selected patients with good tumor biology. In this study, we found that patients with low AP scores demonstrated no recurrence (Table 2). In our earlier study, the suggested cutoff of AFP was 200 ng/ml. (4,7) A recent study reported that those with a model to predict tumor recurrence after LDLT, 11x (MoRAL) score and without extrahepatic metastasis might be potential candidates for LDLT among Milan criteria HCC patients. (12) Optimal cutoff of PIVKA calculated from this equation occurred if AFP was between 200 ng/ml and 700 ng/ml; therefore, MoRAL cutoff (314.8) corresponded to 1,400 of AP score. The suggested AP score cutoff (20,000) for PVTT patients in this study was slightly higher than that from our previous studies (14,000). However, this cutoff of 20,000 was arbitrarily decided and not validated. Further study is needed to select an optimal cutoff in this situation. In our previous studies, the cutoff value of the SUV ratio by receiver operating characteristic analysis was 1.10 (9) or 1.15 (6). All patients in this study were PET positive by these criteria. However, the patients with a higher SUV ratio (>2.1 or 2.2) showed significantly higher recurrence than those with a low SUV ratio. Therefore, if the SUV ratio cutoff is set higher, it can be used to select optimal candidates in PVTT patients. The level of PVTT has been known as an important risk factor for recurrence after resection. Kondo et al. (19) reported higher recurrence in patients with a main PVTT compared with those with a segmental PVTT. Similarly, our study also reports that the level of PVTT affects tumor recurrence after LT. LT can be carefully chosen in patients with segmental or sectional PVTT. In this study, PVTTs were viable in most patients according to the pathological reports. Theoretically, viable PVTT suggests the presence of circulating cancer cells. However, tumor recurrence was not related to the viability of PVTT in our study. Patient 3, who was considered as having no viable tumor in the CT scan after TACE, had a viable portion of PVTT in pathologic examination but did not show recurrence. On the contrary, patient 6, who showed a typical PVTT imaging finding before TACE but showed a complete response (CR) in the PVTT after TACE in preoperative images and no viable portion of the PVTT in pathologic examination, showed early recurrence. Therefore, the viability of PVTT by a preoperative imaging study cannot be used as the exclusion criteria. Instead, other factors such as main tumor progression and tumor marker behavior after local treatment should be considered collectively. For example, patient 3 showed good TACE uptake in the main tumor on pre-lt CT. However, patient 6 (recurrent case) showed main tumor progression, and the tumor marker remained high after TACE (Fig. 3). Treatment response has been known to be a significant factor to assess tumor biology. Not only radiological responsiveness but also AFP behavior have been considered to be important predictors for recurrence after LT. (20) If AFP response is good, even in patients with high AFP before the down-staging procedure, it showed good outcomes after LT. (21) However, the role of down-staging, especially in terms of tumor marker behavior, could not be assessed in this study because 24 ORIGINAL ARTICLE

7 LIVER TRANSPLANTATION, Vol. 23, No. 1, 2017 LEE ET AL. TABLE 2. Risk Factor for Post-LT HCC (A) Recurrence and (B) Survival (Univariate Analysis) RFS (%) Category Factors 1 Year 2 Year 3 Year P Value (A) Risk Factor for Recurrence Pre-LT AP score <20,000 (n 5 5) 5 (100) 5 (100) 5 (100) < ,000 ng/ml (n 5 6) 2 (33.3) 0 0 Pre-LT treatment Yes (n 5 4) 3 (75.0) 1 (25.0) 1 (25.0) 0.43 No (n 5 7) 4 (57.1) 4 (57.1) 4 (57.1) SUV ratio SUV < 2.1 (n 5 7) 6 (85.7) 5 (71.4) 5 (71.4) <0.01 SUV 2.1 (n 5 4) Level of PVTT Vp2 or Vp3 (n 5 7) 7 (100) 5 (71.4) 5 (71.4) <0.01 Vp4 (n 5 4) Largest size of HCC, cm <7.0 (n 5 5) 5 (100) 4 (80.0) 4 (80.0) (n 5 6) 2 (33.3) 1 (16.7) 1 (16.7) Number of HCC 3 (n5 9) 5 (55.6) 4 (44.4) 4 (44.4) 0.66 >3 (n5 2) 2 (100) 1 (50.0) 1 (50.0) Edmonson Grade 3 (n5 6) 5 (83.3) 3 (50.0) 3 (50.0) (n55) 2 (40.0) 2 (40.0) 2 (40.0) Viable tumor portion in PVTT, % 50 (n 5 2) 2 (100) 2 (100) 2 (100) 0.16 >50 (n 5 9) 5 (55.6) 3 (33.3) 3 (33.3) Adjuvant mtor Yes (n 5 9) 6 (66.7) 4 (44.4) 4 (44.4) 0.82 No (n 5 2) 1 (50.0) 1 (50.0) 1 (50.0) Adjuvant sorafenib Yes (n 5 2) 2 (100) 1 (50.0) 1 (50.0) 0.66 No (n 5 9) 5 (55.6) 4 (44.4) 4 (44.4) Overall Survival (%) Category Factors 1 Year 2 Year 3 Year P Value (B) Risk Factor for Survival Pre-LT AP score <20,000 (n 5 5) 5 (100) 5 (100) 5 (100) < ,000 ng/ml (n 5 6) 3 (50.0) 2 (33.3) 2 (33.3) Pre-LT treatment Yes (n 5 4) 3 (75.0) 3 (75.0) 3 (75.0) 0.70 No (n 5 7) 5 (71.4) 4 (57.1) 4 (57.1) SUV ratio SUV < 2.1 (n 5 7) 6 (85.7) 6 (85.7) 6 (85.7) 0.08 SUV 2.1 (n 5 4) 2 (50.0) 1 (25.0) 1 (25.0) Level of PVTT Vp2 or Vp3 (n 5 7) 7 (100) 7 (100) 7 (100) <0.01 Vp4 (n 5 4) 1 (25.0) 0 0 Largest size of HCC, cm <7 (n5 5) 5 (100) 5 (100) 5 (100) (n5 6) 3 (50.0) 2 (33.0) 2 (33.0) Number of HCC 3 (n5 9) 6 (66.7) 5 (55.6) 5 (55.6) 0.30 >3 (n5 2) 2 (100) 2 (100) 2 (100) Edmonson Grade 3 (n5 6) 6 (100) 5 (83.3) 5 (83.3) (n55) 2 (40.0) 2 (40.0) 2 (40.0) Viable tumor portion in PVTT, % 50 (n 5 2) 2 (100) 2 (100) 2 (100) 0.30 >50 (n 5 9) 6 (66.7) 5 (55.6) 5 (55.6) Adjuvant mtor Yes (n 5 9) 7 (77.8) 6 (66.7) 6 (66.7) 0.47 No (n 5 2) 1 (50.0) 1 (50.0) 1 (50.0) Adjuvant sorafenib Yes (n 5 2) 2 (100) 2 (100) 2 (100) 0.30 No (n 5 9) 6 (66.7) 5 (55.6) 5 (55.6) no patient showed good treatment response in terms of tumor marker behavior. The pre-lt AP score or peak AP score similarly affected the outcome of PVTT patients in this study. However, considering previous reports, the pre-lt AP score seems to be a more important selection or exclusion criteria in downstaged patients. In this study, pre-lt TACE did not show tumor marker responsiveness. However, there have been several promising tools such as transarterial radioembolization (TARE) or external beam radiotherapy. (22) TARE was reported as a more effective tool in downstaging from United Network for Organ Sharing T3 to T2 than TACE. (23) And TARE also resulted in good outcomes in PVTT patients. (24) Therefore, outcomes could potentially be improved by the use of these therapies in PVTT patients. Further study is needed to clarify the role of these modalities. ORIGINAL ARTICLE 25

8 LEE ET AL. LIVER TRANSPLANTATION, January 2017 FIG. 3. A representative patient with PVTT (patient 2 in Table 1). The patient received adjuvant sorafenib with rapamycin after transplantation. He showed no recurrence until last follow-up (61 months after transplantation). Pretransplant CT (A) showed infiltrative tumor with PVTT at Vp3 (right PV). Explant liver (B) and PVTT with viable tumor (C). [Color figure can be viewed at wileyonlinelibrary.com] Sirolimus was used as an adjuvant therapy in 8 (73%) patients, and sorafenib was used as an adjuvant therapy in 1 patient. Although our study did not show a significant difference between the adjuvant group and the nonadjuvant group, this may be related to the size discrepancy between the 2 groups. Currently, it is hard to conclude that there is no adjuvant role of sirolimus and sorafenib. We found several significant factors related to no recurrence after LDLT even in patients with major PVTT. If PVTT does not extend into the main PV, and if the AP score is not high, LDLT can be considered to be a curative treatment option. However, because the results of this study are based on a small number of patients, further study is necessary. Acknowledgements: This work was supported by the Research Resettlement Fund for the new faculty of Seoul National University ( ). 26 ORIGINAL ARTICLE

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