Does a patient who needs portal vein embolization (PVE) to proceed to major hepatectomy (MH) have the same hepatic functional reserve than a patient with no preoperative PVE?
Original Article

Does a patient who needs portal vein embolization (PVE) to proceed to major hepatectomy (MH) have the same hepatic functional reserve than a patient with no preoperative PVE?

Stéphanie Truant1 ORCID logo, Clio Baillet2, Mehdi El Amrani1, Katia Lecolle1, Olivier Ernst3, Sébastien Dharancy4, Anthony Turpin5, Damien Huglo2, François-René Pruvot1

1Department of Digestive Surgery and Transplantation, CHU Lille, Lille, France; 2Department of Nuclear Medicine, CHU Lille, Lille, France; 3Department of Radiology, CHU Lille, Lille, France; 4Department of Hepatogastroenterology, CHU Lille, Lille, France; 5Department of Oncology, CHU Lille, Lille, France

Contributions: (I) Conception and design: S Truant, C Baillet, S Dharancy; (II) Administrative support: K Lecolle, O Ernst, D Huglo; (III) Provision of study materials or patients: FR Pruvot, S Truant; (IV) Collection and assembly of data: M El Amrani, K Lecolle, C Baillet; (V) Data analysis and interpretation: S Truant, FR Pruvot, A Turpin; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Stéphanie Truant, MD, PhD. Department of Digestive Surgery and Transplantation, CHU Lille, F-59000 Lille, France; Hôpital HURIEZ, Rue M. Polonovski, F-59000 Lille, France. Email: stephanie.truant@chu-lille.fr.

Background: While remnant liver function (RLF) gain after portal vein embolization (PVE) was reportedly higher than volume gain, some patients apparently fit for surgery develop post-hepatectomy liver failure (PHLF). This prospective study analyses the hepatic regeneration rates in terms of volume and function following a major hepatectomy (MH) preceded or not by PVE.

Methods: Between 2012 and 2018, all non-cirrhotic candidates for MH had a volumetric-computed tomography evaluation and functional-single photon emission computed tomography (SPECT)-scintigraphy of RL preoperatively and postoperatively at day 7 (POD7) and 1 month (1M). RLF was calculated as intrinsic function (i.e., normalized to volume; %/min), and function/volume changes as relative ones (%). We investigated the impact of PVE on post-hepatectomy regeneration rates and related to 3-month outcome (I) in overall population (II) after excluding more risky patients (biliary drainage, severe complications) and (III) in PVE/no-PVE patients matched on remnant liver volume (RLV)/RLF (as the liver regeneration rate is proportional to the extent of resection).

Results: Among 136 patients, 125 had one-stage MH, preceded by PVE in 33 patients (26.4%). PVE and no-PVE patients were comparable, except for smaller RLV and more frequent biliary drainages in the former, with higher operating times and blood losses. Preoperative intrinsic RLF was comparable between PVE (0.97%/min; range, 0.81−1.4%/min) and no-PVE groups (1.13%/min; range, 0.92–1.44%/min; P=0.30). At POD7, the volumetric gain was strictly comparable between PVE (+48.7%; range, 36.4–71%; P=0.80) and no-PVE patients (+49.8%; range, 26.8–73.3%), but not the functional gain [+10.7% (range, −3.2% to 42.4%) vs. +42% (range, 20.7–78.6%); P=0.002]. PVE patients showed intrinsic RLF drop (0.77%/min; range, 0.63–0.97%/min) in contrast to no-PVE patients (1.1%/min; range, 0.75–1.3%/min; P=0.001), persisting at 1M (0.93%/min; range, 0.73–1%/min) vs. overcompensation in no-PVE patients (1.27%/min; range, 1–1.5%/min; P=0.001). This was associated with significantly increased PHLF and morbi-mortality rates. Findings were similar after excluding patients with biliary drainage or severe complications or after matching patients on RLV or RLF.

Conclusions: The current findings showed that some patients apparently fit for surgery after PVE are going to hepatic resection with some degree of disadvantage, displaying lower hepatic reserve and delayed functional recovery than no-PVE patients.

Keywords: Major hepatectomy (MH); liver regeneration; hepatobiliary scintigraphy (HBS); remnant liver volume (RLV); remnant liver function (RLF)

Submitted Aug 29, 2024. Accepted for publication Dec 18, 2024. Published online Jun 13, 2025.

doi: 10.21037/hbsn-24-478

Highlight box

Key findings

• Patients who need portal vein embolization (PVE) to proceed to major hepatectomy have a lower hepatic functional reserve than patients with no need for PVE.

What is known and what is new?

• Increase in future remnant liver (RL) function after PVE is reportedly higher than the RL volume increase; despite this, some patients apparently fit for surgery after PVE develop post-hepatectomy liver failure, with 3-month mortality rate above 10% in a literature review.

• Patients apparently fit for surgery after PVE are going to hepatic resection with some degree of disadvantage and with lower hepatic functional reserve than no-PVE patients.

What is the implication, and what should change now?

• Special attention should be paid to such patients in the early perioperative period, considering their altered functional regenerative capacities with subsequent higher rates of morbi-mortality.

Introduction

Liver regeneration makes extensive liver resection for liver tumors possible. Nevertheless, in the case of insufficient remnant liver volume (RLV), patients are at risk of developing post-hepatectomy liver failure (PHLF), a severe complication for which only supportive treatment options are currently available (1). The incidence of PHLF after such extended hepatectomy is estimated to reach up to 10% according to the definition used (2), being the main cause of mortality. Preoperative portal vein embolization (PVE) or ligation (PVL) is a widely accepted technique to increase both RLV and remnant liver function (RLF) in patients with future RLV deemed insufficient, in particular in cases of injured liver (e.g., heavy neoadjuvant chemotherapy, steatosis, cholestasis). PVE-primed liver can manage sequentially the numerous tasks that stress simultaneously the RL after an unprepared hepatectomy, with ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) (3,4) or LVD (i.e., liver venous deprivation consisting in simultaneous hepatic and PVE) (5) as alternatives for extended resection.

Using HIDA or GSA single photon emission computed tomography (SPECT)-hepatobiliary scintigraphy (HBS), two teams reported that the post-PVE increase in RLF was higher than the RLV increase (6,7); despite this, some patients apparently fit for surgery after PVE develop PHLF, with 3-month mortality rate above 10% in a systematic review (8). Regarding hepatic resection, our team previously showed that RLF gain after a major hepatectomy (MH) is slower than volume gain (9), contrasting with PVE. Accordingly, in an experimental study, Tashiro et al. (10) showed that the mechanism of liver regeneration after PVL/PVE is different from that after hepatectomy. Besides, considering the role that portal blood flow plays in liver regeneration, its modulation may potentially impact liver regeneration capacities (11).

Considering the beneficial effect of both the rise in portal flow and parenchymal transection on liver regeneration, this prospective monocentric study aimed to analyse the hepatic regeneration rate both in terms of volume and function via sequential computed tomography (CT) and HBS following a MH preceded or not by a PVE, and in relation with the postoperative outcome. We present this article in accordance with the STROCSS reporting checklist (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-478/rc).

Methods

Between 2012 and 2018, all non-cirrhotic patients scheduled for one-stage MH [≥3 Couinaud’s segments (12)] preceded or not by a PVE in our University Hospital were enrolled in this prospective case-control study after obtaining patient’s written consent and institutional review board approval of the “Comité de Protection des Personnes”. After inclusion phase, each patient had a volumetric CT evaluation as previously described (13) and functional SPECT scintigraphy of remnant liver (RL) preoperatively and postoperatively at day 7 (POD7) and 1 month (1M). In all cases, examinations were carried out after PVE [performed for RLV <25% of total liver volume or RL to body weight ratio (RLVBWR) <0.5% (13-16)] and after biliary drainage in jaundiced patients due to the competition between mebrofenin and bilirubin on hepatic receptors (17). Patients were mostly operated on 3 to 5 weeks after PVE. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Hepatic resection

Surgical technique of liver resection and different methods of vascular control to reduce intraoperative bleeding were performed as previously reported (13,18). For each resected specimen, an experienced pathologist performed a specific histological analysis of representative sections of non-neoplastic hepatic parenchyma. Macrovesicular steatosis was considered pathologic for a hepatic fat content involving 30% or more of hepatocytes (19). Liver fibrosis was quantified according to the METAVIR score (20) (exclusion of F4 fibrosis).

HBS

After injection of 130 MBq of 99mTc mebrofenin, a dynamic acquisition was performed (45 frames of 10 s) with a gamma camera SYMBIA S (Siemens Healthcare GmbH, Erlangen, Germany) in anterior and posterior views. The liver uptake phase was followed by a tomographic study (32 projections of 10 s each). Activity curves were obtained from the dynamic acquisition after drawing regions of interest (ROI) on the parenchymal liver, heart and total field-of-view. The total liver uptake (TLU; i.e., function) rate was calculated between 150 and 350 s after injection as described by Ekman et al. (21). The future RL was outlined on the SPECT co-registered with the contrast-enhanced CT. The future RL uptake (RLU) or function was calculated by multiplying TLU by the ratio of the counts of future RL drawn on the preoperative acquisition to the ones of the total liver. Intrinsic RLF was calculated as RLF normalized to RLV (uptake per 100 g of liver in %/min).

Endpoints

As primary endpoint, we investigated the influence of PVE on post-hepatectomy regeneration rate (i.e., function/volume changes expressed as either relative ones: (postoperative − preoperative)/preoperative in percentage or changes in intrinsic RLF and in relation to 3-month outcome rated according to Clavien-Dindo classification (22), in particular PHLF according to International Study Group of Liver Surgery (ISGLS) definition (23). As secondary endpoints, results were compared between PVE and no-PVE patients (I) in subgroup analyses to consider the influence of additional risk factors related to the PVE setting (i.e., preoperative biliary drainage, postoperative severe complications Clavien ≥IIIb) on liver functional recovery and (II) in patients matched on RLVBWR (±0.04) or on RLU (±0.3), considering that the regeneration rate is proportional to the extent of resection.

Statistical analysis

Continuous variables were expressed as median and interquartile range (IQR) and compared using the Mann-Whitney U test, or Wilcoxon test, or Student’s t-test for paired samples, as appropriate. Categorical variables were compared using χ2 tests or Fisher exact tests, as appropriate. The threshold for statistical significance was set to P<0.05. All analyses were performed using SPSS version 22 (SPSS, Chicago, IL, USA).

Results

Among 136 patients, 125 had one-stage MH, preceded by PVE in 33 patients (26.4%). A majority of patients (n=118; 94.4%) were operated on for a malignant tumour, including 62 for colorectal cancer liver metastases (Table 1). Fifty-six patients (44.8%) received neoadjuvant chemotherapy. After PVE, the median degree of RL hypertrophy was +55% (range, +30% to +80.5%) and the median delay before hepatic resection was 37 (range, 24–44) days. Preoperatively, PVE and no-PVE patients showed similar clinico-biological characteristics, except for smaller RLV (P=0.02), higher cytolysis (P=0.009) and more frequent biliary drainages (P<0.001) in PVE group because of a higher rate of cholangiocarcinoma compared to no-PVE patients (24.2% vs. 3.3%; P=0.001). Nevertheless, groups were comparable in terms of preoperative bilirubinemia (P=0.70) as a potential competitor with mebrofenin on hepatic receptors. There was no difference regarding histological examination of extra-tumoral liver (P=0.80 for steatosis ≥30%, P=0.30 for fibrosis > F1). Regarding intra-operative data, PVE patients expectedly underwent more extended and complex hepatic resection (P<0.001), with more frequent vascular and/or biliary reconstruction (P<0.001) with increased operating times (P=0.007), blood losses (P=0.02) and transfusion requirements (P=0.20), though non-significant for the latter.

Table 1

Clinicopathological, operative and postoperative data for all patients and for groups with vs. without PVE

Characteristics All patients (n=125) No PVE (n=92) PVE (n=33) P
Age (years) 65 [57–71] 65 [56–71] 68 [59–71] 0.49
ASA score 2 [2–3] 2 [2–3] 2 [2–2.5] 0.28
Gender (female/male) 53/72 35/57 18/15 0.10
BMI, kg/m2 25 [23–29] 25 [23–29] 25.5 [20–27.8] 0.56
   >30 23 (18.4) 17 (18.5) 6 (18.8) 0.97
Preoperative chemotherapy 56 (44.8) 40 (43.5) 16 (48.5) 0.38
   Number of courses 9 [4.5–12] 7 [4–12] 11.5 [5–17] 0.43
   >12 cycles 12 (9.6) 7 (7.6) 5 (15.2) 0.29
Preoperative biliary drainage 15 (12) 4 (4.3) 11 (33.3) <0.001*
Preoperative laboratory values
   Total bilirubin, mg/dL 5 [3–7] 5 [3–7] 4 [3–8] 0.66
   AST, U/L 29 [22–41] 27 [22–38] 33 [27–56] 0.009*
   ALT, U/L 27 [20–42] 25 [18–34] 36 [26–66] 0.002*
   PT, % 100 [88–100] 100 [89–100] 97 [88–100] 0.20
   Serum albumin, g/L 42 [39–44] 43 [40–45] 40 [36–41] 0.12
Tumor type 0.36
   Benign tumor 7 (5.6) 7 (7.6) 0
   Malignant tumor 118 (94.4) 85 (92.4) 33 (100)
   Primary 56 40 16
   Secondary 62 45 17
   Tumor number 1 [1–4] 1 [1–3] 2 [1–4] 0.08
Extra-tumoral liver
   % steatosis 0 [0–20] 0 [0–20] 0 [0–10] 0.19
   Steatosis ≥30% 18 (14.4) 14 (15.2) 4 (12.1) 0.78
   Fibrosis >F1 (F4 excluded) 12 (9.6) 7 (7.6) 5 (15.2) 0.29
Intra-operative data
   Number of resected segments 4 [4–5] 4 [4–5] 5 .5 [5–6] <0.001*
   Vascular and/or biliary reconstruction 18 (14.4) 3 (3.3) 15 (45.4) <0.001*
   Operating time, min 336.5 [247.5–440] 325 [240–390] 410 [330–500] 0.007*
   PTC 75 (60) 54 (58.7) 21 (63.6) 0.62
   Blood loss, mL 600 [350–1,000] 500 [337–825] 825 [500–1,040] 0.02*
   Transfusion 14 (11.2) 8 (8.7) 6 (18.2) 0.14
Postoperative laboratory values
   On POD7
    Total bilirubin, mg/dL 14 [8–32] 10 [8–21] 28 [14–51.7] <0.001*
    PT 81 [66–93] 88 [75–98] 67 [55.5–81] <0.001*
   At 1M
    Total bilirubin, mg/dL 6 [4–10] 5 [3–6] 10.5 [5.25–108] 0.001*
    PT 91 [82–100] 93 [82–100] 84 [64–92.5] 0.008*
Postoperative course
   3-month mortality 8 (6.4) 2 (2.2) 6 (18.2) 0.004*
   3-month morbidity
    Overall 73 (58.4) 48 (52.2) 25 (75.8) 0.02*
    Severe (grades IIIb-IV) 25 (20) 12 (13) 13 (39.4) 0.02*
   PHLF 23 (18.4) 9 (9.8) 14 (42.4) <0.001*
   Length of stay, days 10 [8–18] 10 [8–14] 18 [10–28] 0.001*
   Intensive care unit, days 3 [2–6] 3 [2–4.75] 5 [3–9] 0.001*

Continuous variables are presented as median [range]. Categorical variables are presented as n (%) or n. *, statistically significant. 1M, 1 month postoperative; ALT, alanine aminotransferase; ASA, American Society of Anesthesiologists; AST, aspartate aminotransferase; BMI, body mass index; PHLF, post-hepatectomy liver failure (according to ISGLS criteria); POD, postoperative day; PT, prothrombin time was expressed as a percentage of the normal level of prothrombin activity; PTC, portal trial clamping; PVE, portal vein embolization.

Hepatic volume and function in PVE vs. no-PVE patients in the overall study population

Before surgery, the median RLV/total liver volume (TLV) was 37% (range, 29–50.3%) and RLVBWR was 0.93% (range, 0.68–1.18%) (Table 2). Postoperatively, there was a delayed functional recovery compared to volumetric gain in the overall population, as previously reported (9).

Table 2

Pre- and postoperative volumes and function in the overall population and in patients with and without preoperative PVE

Hepatic volume and function All patients
(n=125)		 Overall population Patients with no biliary drainage
No PVE (n=92) PVE (n=33) P No PVE (n=88) PVE (n=22) P
Preoperative volume and function
   TLV (cm3) 1,739 (1,415–2,067) 1,700 (1,413–2,044) 1,822 (1,380.5–2,229) 0.33 1,694 (1,410–2,025) 1,827 (1,309.7–2,279.7) 0.27
   RLV (cm3) 650 (485–855) 702 (503–1,007.2) 566 (473–668) 0.02* 698 (503–1,054) 560 (474.7–652) 0.06*
   RLV/TLV (%) 37 (29–50.3) 38.5 (30.5–60.9) 31.9 (26.6–37.1) 0.001* 38.7 (30.5–61.9) 32.1 (26.6–38.1) 0.007*
   RLVBWR (%) 0.93 (0.68–1.18) 0.98 (0.7–1.32) 0.78 (0.65–0.97) 0.02* 0.97 (0.7–1.3) 0.74 (0.66–0.89) 0.01*
   TLU (%/min·m2) 9.9 (8.4–11.7) 10.2 (8.7–11.9) 9.1 (7–11.2) 0.03* 10.3 (9–11.9) 9 (7.4–11.4) 0.046*
   RLU (%/min·m2) 3.8 (2.9–5.4) 4 (3–6) 3.1 (2.6–4.3) 0.005* 4 (3–6) 3.3 (2.6–4.4) 0.03*
   Intrinsic RL function (%/min) 1.07 (0.87–1.43) 1.13 (0.92–1.44) 0.97 (0.81–1.4) 0.29 1.14 (0.91–1.45) 1 (0.81–1.4) 0.47
Volume and function on POD7
   RLV (%/min·m2) 983 (889–1,219) 1,054 (855–1,355.5) 860 (748–1,033.5) 0.008* 1,054 (857–1,369) 867 (784–1,095) 0.10
   RLU (%/min·m2) 5.5 (3.9–7.3) 5.9 (4.5–8.2) 4 (2.5–4.4) <0.001* 6 (4.6–8.2) 4.1 (2.6–5.5) <0.001*
   RL volume increase
    Relative gain (%) 49.4 (30.6–73.2) 49.8 (26.8–73.3) 48.7 (36.4–71) 0.77 49.8 (28–76.3) 59 (41.7–75.5) 0.28
   RL function increase
    Relative gain (%) 38.8 (7.9–72.3) 42 (20.7–78.6) 10.7 (−3.2–42.4) 0.002* 42.1 (22.3–79.3) 8.7 (−3.5–47.5) 0.003*
   Intrinsic RL function (%/min) 0.98 (0.72–1.3) 1.1 (0.75–1.3) 0.77 (0.63–0.97) 0.001* 1.1 (0.78–1.34) 0.76 (0.58–1.08) 0.003*
Volume and function at 1M
   RLV (%/min·m2) 1,118 (927–1,393) 1,135 (996–1,445) 941.5 (826–1,321) 0.02* 1,135 (992–1,433) 941.5 (874.2–1,374.5) 0.08
   RLU (%/min·m2) 7.4 (6.1–9.8) 8 (6.4–10.4) 5.5 (3–6.7) <0.001* 8 (6.4–10.5) 5.5 (2.8–7.2) <0.001*
   RL volume increase
    Relative gain (%) 73 (34.5–104.1) 65.1 (28.7–104.8) 85 (50–96.6) 0.27 61.3 (28.1–104.8) 81.1 (54.6–101.2) 0.27
   RL function increase
    Relative gain (%) 78.1 (37.9–123.6) 87.4 (49.8–133.9) 41.4 (13.1–112.2) 0.005* 87.6 (50.6–135.5) 41.4 (21.7–107.7) <0.001*
   Intrinsic RL function (%/min) 1.2 (0.94–1.5) 1.27 (1–1.5) 0.93 (0.73–1) <0.001* 1.27 (1–1.5) 0.9 (0.7–1.36) 0.001*

Continuous variables are presented as median (range). Intrinsic RL function was calculated by dividing the quantitative liver function data by the respective liver weight and expressed as uptake per 100 g of liver. Relative gains in RL function and volume were calculated as follows: (postoperative RL − preoperative RL)/preoperative RL. *, statistically significant. 1M, 1 month postoperative; POD, postoperative day; PVE, portal vein embolization; RL, remnant liver; RLU, remnant liver uptake; RLV, remnant liver volume; RLVBWR, RLV to body weight ratio; TLU, total liver uptake; TLV, total liver volume.

When comparing PVE to no-PVE patients, the RLV and RLF (as measured by RLU) were expectedly lower in the former. Nevertheless, the intrinsic RLF (i.e., RLF normalized to RLV) was preoperatively comparable between PVE (0.97%/min; range, 0.81–1.4%/min) and no-PVE (1.13%/min; range, 0.92–1.44%/min; P=0.30) groups (Table 2). At POD7 of MH, the volumetric gain was comparable between PVE (+48.7%; range, 36.4–71%) and no-PVE patients (+49.8%; range, 26.8–73.3%; P=0.80). By contrast, the functional gain was significantly lower in PVE patients than in no-PVE patients [+10.7% (range, −3.2–42.4%) vs. +42% (range, 20.7–78.6%); P=0.002]. Compared to baseline, PVE patients showed a significant drop in intrinsic RLF (0.77%/min; range, 0.63–0.97%/min), contrary to no-PVE (1.1%/min; range, 0.75–1.3%/min; P=0.001). This inter-group difference persisted at 1M with a return to near-baseline values in PVE patients (0.93%/min; range, 0.73–1%/min) contrasting with functional overcompensation in no-PVE patients (1.27%/min; range, 1–1.5%/min, P=0.001). This delayed functional recovery in PVE patients was paralleled by significantly increased serum bilirubin levels and lower prothrombin time (PT) values at POD7 and 1M and with higher rates of 3-month PHLF and PHLF-related morbi-mortality (Table 1).

Hepatic volume and function in PVE vs. no-PVE patients in subgroup analyses

Subgroup analyses were performed to consider the influence of additional PVE-related risk factors on liver functional recovery, such as preoperative biliary drainage or postoperative severe complications that were more frequent in these patients (Table 1). Similar differences between PVE and no-PVE patients were observed after excluding (I) more risky patients with preoperative biliary drainage (Table 2) and (II) patients with complications Clavien ≥IIIb (data not shown), as severe complications are known to impact RL functional recovery. In these subgroup analyses, the drop in intrinsic RLF persisted in PVE patients at POD7 and 1M, contrasting with a functional overcompensation in no-PVE patients.

As PVE patients showed initially smaller RLV/RLF, which differently impacts the regeneration rates, each patient in the PVE group was paired with one or more patients in the no-PVE group on either the RLV or RLF.

Hepatic volume and function in PVE vs. no-PVE paired patients

Overall, 32 out of 33 PVE patients could be paired with 49 no-PVE patients on the RLVBWR (±0.04), displaying comparable future RLV and RLF (Table 3). Postoperatively, findings on volume and function gains in matched patients were similar to those observed in the overall population. Indeed, despite a similar volume gain, there was a lower function increase in PVE patients [+10.7% (−3.2% to 42.4%)] than in no-PVE patients [+40.1% (6.9–79.8%); P=0.02] at POD7. This resulted in a significant drop in intrinsic RLF in PVE patients compared to baseline values in this group and to no-PVE patients. At the end of the first month of RL regeneration, intrinsic RLF was still near-baseline values in PVE patients, contrasting with a functional overcompensation in no-PVE patients (Figure 1). Very similar results were observed after pairing PVE and no-PVE patients on the RLU (±0.3) (Table 3).

Table 3

Pre- and postoperative volumes and function in patients with and without preoperative PVE paired on either RLVBWR (±0.04) or on RLU (±0.3)

Hepatic volume/function in paired patients Patients paired on RLVBWR Patients paired on RLU
No PVE (n=49) PVE (n=32) P No PVE (n=65) PVE (n=30) P
Preoperative volume and function
   RLV (cm3) 591 (436–737.5) 563 (473.2–669.5) 0.48 667 (436–803.5) 560 (461–659) 0.13
   RLVBWR (%) 0.85 (0.64–1) 0.78 (0.65–0.97) 0.84 0.9 (0.63–1.06) 0.75 (0.64–0.93) 0.12
   RLU (%/min·m2) 3.4 (2.9–4.3) 3.2 (2.6–4.3) 0.27 3.4 (2.9–4.35) 3.15 (2.6–4.3) 0.47
   Intrinsic RL function (%/min) 1.1 (0.94–1.4) 0.97 (0.81–1.4) 0.42 1.04 (0.87–1.3) 0.97 (0.81–1.4) 0.85
Volume and function on POD7
   RLVBWR (%) 1.29 (1.2–1.5) 1.23 (1–1.38) 0.19 1.32 (1.17–1.58) 1.23 (1–1.4) 0.04*
   RLU (%/min·m2) 5.2 (3.8–7) 4 (2.6–4.45) 0.003* 5.45 (3.9–7) 4 (2.65–4.45) <0.001*
   RL volume increase
    Relative gain (%) 60.1 (36.1–96) 53.3 (36.4–72.4) 0.26 54.7 (31.6–93.6) 53.3 (36.2–72.4) 0.82
   RL function increase
    Relative gain (%) 40.1 (6.9–79.8) 10.7 (−3.2–42.4) 0.02* 54.6 (25.45–80.5) 10.7 (−3.2–42.4) 0.001*
   Intrinsic RL function (%/min) 1 (0.72–1.3) 0.76 (0.63–0.96) 0.01* 1 (0.72–1.3) 0.76 (0.63–0.97) 0.008*
Volume and function at 1M
   RLVBWR (%) 1.54 (1.46–1.6) 1.4 (1.2–1.7) 0.10 1.54 (1.43–1.7) 1.4 (1.2–1.7) 0.052
   RLU (%/min·m2) 6.9 (6.2–8.7) 5.5 (3–6.7) 0.01* 7.2 (6.2–8.7) 5.5 (3–6.75) <0.001*
   RL volume increase
    Relative gain (%) 83.9 (53.1–121.5) 85 (50–96.6) 0.20 83 (48.5–120.5) 85 (50–96.6) 0.90
   RL function increase
    Relative gain (%) 96.5 (61.4–145.6) 41.4 (13.1–112.2) 0.02* 105.8 (69–155.6) 41.4 (13.1–112.2) <0.001*
   Intrinsic RL function (%/min) 1.2 (0.99–1.42) 0.93 (0.73–1) 0.01* 1.2 (0.99–1.44) 0.93 (0.73–1) 0.001*

Continuous variables are presented as median (range). Intrinsic RL function was calculated by dividing the quantitative liver function data by the respective liver weight and expressed as uptake per 100 g of liver. Relative gains in RL function and volume were calculated as follows: (postoperative RL − preoperative RL)/preoperative RL. *, statistically significant. 1M, 1 month postoperative; POD, postoperative day; PVE, portal vein embolization; RL, remnant liver; RLU, remnant liver uptake; RLV, remnant liver volume; RLVBWR, RLV to body weight ratio.

Figure 1 Kinetics of (A) RLV, (B) RLF (in absolute value, namely RL uptake), and (C) RLF normalized to volume (i.e., intrinsic RLF) in patients with PVE compared to compared to those without PVE. Data are expressed as median. 1M, 1 month postoperative; POD, postoperative day; PVE, portal vein embolization; RL, remnant liver; RLF, remnant liver function; RLV, remnant liver volume.

Discussion

PVE is considered as a “functional” test allowing selecting best candidates for major resection on a volume basis. Herein, we aimed evaluating the behavior of PVE patients in terms of volumetric and functional liver regeneration early after an MH, namely in the first postoperative month, a crucial period for patient outcome. Through a systematic sequential CT and HBS protocol, we showed a delayed postoperative functional recovery in patients who need PVE to proceed to surgery compared to no-PVE patients, despite comparable RL intrinsic function at baseline and similar kinetics of volume in the early postoperative period. This delayed functional recovery in PVE patients was paralleled by significantly increased serum bilirubin levels and lower PT values at POD7 and 1M and with higher rates of PHLF and morbi-mortality. This was true even after excluding more risky patients with preoperative biliary drainage, mainly for Klatskin tumours, or after matching PVE and no-PVE patients either on the RLV or RLF (as the liver regeneration rate is proportional to the RLV). Overall patients who were rendered resectable at the cost of preoperative PVE showed a lower functional hepatic reserve.

Of note regarding the functional recovery after MH, the PVE patients did not reach the baseline preoperative values at POD7 but only at 1M, whatever the parameter used for function analysis. This contrasted with no-PVE patients who had a sustained intrinsic function at the early regeneration phase on POD7, followed by a late overcompensated RLF at 1M. Besides, there was no difference regarding volumetric gain between groups, in line with previous studies (24,25). To our knowledge, there has been only one similar case-control study (24) that compared retrospectively liver regeneration in PVE (n=10) vs. no-PVE (n=13) patients displaying similar future RLV and RLF at baseline. At POD90, the mean RLV was 81.9%±8.9% of the initial TLV in the PVE group and 79.4%±11.0% in the control group, while RLF increased up to 88.1%±17.4% and 83.3%±14% of the original total liver function, respectively (both P>0.05), contrasting with the current results. Nevertheless, in addition to its retrospective design, this study was limited by the low number of patients in each group. The analysis at 3 months also placed the authors beyond the critical period of liver regeneration at risk for liver failure. Last, considering the total liver volume/function as the reference was questionable as including the diseased liver segments with varying degrees of tumoral infiltration, vascular and/or biliary obstruction and heterogeneously-distributed function (26). To avoid these drawbacks, we considered herein only the RLV and RLF as a reference.

Regarding potential explanations for delayed functional recovery in PVE patients, there was first a decreased total liver function (TLU) compared to no-PVE patients, despite comparable TLV. This resulted in lower intrinsic liver function at baseline in these patients (in both the total liver and future RL), though not statistically significant. Factors of pre-existing hepatic injuries came from slightly higher cytolysis and more frequent jaundice in PVE patients. There is a well-established deleterious effect of biliary obstruction and drainage-related sepsis on the liver regenerative capacity, both in PVE and liver resection settings (27). Nevertheless, the current study showed a delayed functional recovery in PVE patients even after excluding those with preoperative biliary drainage (Table 2). Second, PVE patients are globally subjected to more difficult and more bloody hepatectomies due to parenchymal collaterals, hyper arterialisation, larger transection surface, and more frequent biliary and/or vascular reconstructions. This resulted in longer operating times and higher blood transfusion requirements compared with no-PVE patients, in accordance with previous studies (28). This could also explain the higher rate of postoperative complications in PVE patients, which could have in turn altered functional recovery. Nevertheless, the drop of intrinsic RLF was still observed in PVE patients after excluding patients with severe complications (data not shown). Third, these patients, who had more extended hepatectomy, were more likely to suffer postoperatively from accelerated (too fast) liver regeneration as previously reported in case of very small RLV due to the abrupt and disorganized regenerative response (i.e., asynchronism in hepatocytes-liver sinusoidal endothelial cells proliferation) (29). Nevertheless, the delayed function recovery in PVE patients was observed even after matching with no-PVE patients on RLV.

It is established that MH results in a significant increase in portal vein pressure (PVP), whereas it reduces hepatic arterial flow (HAF) and has mild effects on overall portal vein flow (PVF) (30,31). Besides, there are only scarce literature data regarding the impact of PVE on post-resection portal blood flow, which plays a crucial role in liver regeneration. In a recent series of 67 consecutive patients who had intraoperatively pre- and postresection hemodynamics measurements (32), MH with and without preoperative PVE resulted in similar changes of PVF and HAF that confirm the importance of relative portal hyperperfusion as a trigger for liver regeneration, even in the setting of previous PVE (32). The only marked difference between patients with and without preoperative PVE was found for PVP that was already elevated pre-resection in PVE patients but did not further increase post-resection (32). In contrast, PVP significantly increased post-resection in patients without PVE, with the extent of PVP increase being a strong and independent predictor of PHLF (32). Two clinical studies on microcirculatory assessment of the liver after PVE (33,34) reported an increase in microvascular density and concomitant neoangiogenesis in the non-embolized lobe, which may limit the increase in PVP secondary to disruption of post-PVE intrahepatic portal collaterals during liver transection (35). As such, PVE is considered a pre-conditioning modality avoiding an acute PVP increase, albeit still enabling changes in PVF required for initiation of the regenerative response.

This study showed some limitations. First, there was a potential patient selection bias as PVE patients had more frequent preoperative biliary drainage and/or vascular/biliary reconstruction. Nevertheless, all HBS studies were performed after biliary drainage, while mebrofenin is the HBS tracer whom uptake is the least sensitive to high bilirubin plasma levels. Moreover, in a comparison excluding patients with preoperative biliary drainage, the delayed functional recovery was still observed in PVE compared to no-PVE patients; the same was true after matching patients on RLV or RLF, allowing to obtain comparable groups at baseline. A multivariate analysis with PVE as one of the variables would be ideal, although not feasible because of the direct link (and potential collinearity) between PVE and most of the other variables of interest. As another limitation, the analysis was retrospectively conducted. Nevertheless, this pilot study was carried out on a prospective cohort of patients that is so far the unique and largest one, entailing three sequential perioperative HBS. Lastly, the potential impact of mini-invasive approach could not be analyzed as all patients had an open hepatectomy.

Conclusions

In conclusion, the current findings showed that some patients apparently fit for surgery after PVE are going to hepatic resection with some degree of disadvantage and with lower hepatic functional reserve than no-PVE patients. Special attention should be paid to such patients in the perioperative period, considering their altered functional regenerative capacities. A particular focus should be made in optimizing the future RLV [e.g., >30–40% as for patients with extensive preoperative chemotherapy (36)] and in avoiding additional severe intra- and/or postoperative events (e.g., massive blood losses or severe biliary complications) that increase significantly the risk of fatal PHLF (1). In the future, artificial intelligence surgery could be of high interest in such risky patients as suggested by recent studies (37).

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROCSS reporting checklist. Available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-478/rc

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Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-24-478/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study has obtained informed consent from patients and institutional review board approval of the “Comité de Protection des Personnes”.

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Cite this article as: Truant S, Baillet C, El Amrani M, Lecolle K, Ernst O, Dharancy S, Turpin A, Huglo D, Pruvot FR. Does a patient who needs portal vein embolization (PVE) to proceed to major hepatectomy (MH) have the same hepatic functional reserve than a patient with no preoperative PVE? Hepatobiliary Surg Nutr 2026;15(2):38. doi: 10.21037/hbsn-24-478

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