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Volume regeneration after right liver donation
Article first published online: 6 JAN 2004
Copyright © 2004 American Association for the Study of Liver Diseases
Volume 10, Issue 1, pages 65–70, January 2004
How to Cite
Hata, S., Sugawara, Y., Kishi, Y., Niiya, T., Kaneko, J., Sano, K., Imamura, H., Kokudo, N. and Makuuchi, M. (2004), Volume regeneration after right liver donation. Liver Transpl, 10: 65–70. doi: 10.1002/lt.20006
- Issue published online: 6 JAN 2004
- Article first published online: 6 JAN 2004
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor and Welfare of Japan
After right hepatectomy with the middle hepatic vein trunk for a graft, the venous outflow in segment IV is disturbed. There are limited data, however, regarding the effect of middle hepatic vein deprivation on liver regeneration or functional recovery. Living donors who underwent right hepatectomy with preservation of the middle hepatic vein (Group A, n = 58) and those deprived of the middle hepatic vein (Group B, n = 13) were reviewed. When the donor was under 50 years old and the remnant left liver was estimated to be more than 35% of the whole liver, right liver graft harvesting with the middle hepatic vein trunk was considered. Volume regeneration of segments I–III, segment IV, and overall liver volume was assessed at the third postoperative month using computed tomography. The regeneration rate of segment IV was significantly impaired in Group B donors compared with that in Group A donors (125% vs. 45%, P = 0.008). In contrast, the regeneration rate of segments I –III was significantly higher than that in Group A (208% vs. 263%, P = 0.004). There was no significant difference in the regeneration rate of the whole left liver or functional recovery between groups. Multivariate analysis revealed that the resection type (group) was a significant predictive factor for the regeneration rate of segments I–III and segment IV. When deprived of the middle hepatic vein, liver regeneration of segment IV was impaired but was compensated for by the regeneration of segments I–III. In conclusion, extended right hepatectomy can be safely performed with careful preoperative consideration using these criteria. (Liver Transpl 2004;10:65–70.)
The shortage of cadaveric donors has led to an increase in the practice of living donor liver transplantation (LDLT).1 A vital issue in LDLT is the preservation of a satisfactory blood supply and venous return in both the right and left livers to maximize donor safety and graft function. When splitting the liver along the main portal fissure to harvest a hemiliver graft, however, it is impossible to maintain complete venous outflow in both of the bisected livers, because the middle hepatic vein (MHV) can be preserved on only one side.
An extended right liver graft,2 which includes the MHV trunk, was devised by the Hong Kong group. This method is beneficial with regard to venous drainage of the graft. On the donor side, however, the venous outflow disturbances in segment IV are a concern, and they might disrupt the function of the relevant hepatic region.3 Consequently, this type of graft is less commonly used than a right liver graft without the MHV trunk.4
In our institution, we adopted right hepatectomy with or without MHV as the donor procedures for LDLT in selected donor-recipient combinations. The aim of the present study is to clarify whether deprivation of the MHV truly causes adverse effects in donors, including disturbances in liver regeneration of segment IV or functional recovery.
Materials and Methods
From March 2000 through March 2003, 138 consecutive living donors underwent hepatectomy at the University of Tokyo Hospital. Of these, 71 donors with right hepatectomy were investigated. Details regarding selection criteria and evaluation are described elsewhere.5 All of the donors were related to the recipients. The relationships of the donors to the patients were 29 children, 20 siblings, 10 spouses, eight parents, and four nephews. Preoperative liver biopsy was indicated when the body mass index was over 25, and candidates with more than 30% steatosis on biopsy were rejected as donors.6 All donors and patients provided written informed consent.
Right liver volume was preoperatively estimated using computed tomography (CT) as described previously.7 Candidates in whom the right liver comprised more than 70% of the whole liver were rejected as prospective donors. The estimated ratio of graft volume to recipient standard liver volume was 40%, which was the lower limit for right liver transplantation. The number and diameter of thick MHV tributaries draining the right paramedian sector were evaluated on CT. When the donor was under 50 years old and the remnant left liver was estimated to be more than 35% of the whole liver, extended right liver graft harvesting was considered. Otherwise, right liver graft harvesting without the MHV trunk was indicated.
The donors were divided into two groups. Group A (control group) included 58 donors who underwent resection of the right liver (segments IV–VIII). In this group, the MHV trunk was preserved in the remnant donor liver, and venous drainage of the right paramedian sector was thoroughly maintained after hepatectomy. Group B consisted of 13 donors with right liver resection involving the MHV. In this group, venous drainage of segment IV was interrupted after hepatectomy. Group A was comprised of 34 men and 24 women with a median age of 38 years (range, 36–61 yr), and Group B was comprised of two men and 11 women with a median age of 37 years (24–54 yr). Postoperative CT with contrast enhancement was routinely conducted 3 months after hepatectomy for evaluation of postoperative liver volume regeneration.
Surgical Technique and Postoperative Care
The surgical techniques of donor hepatectomy were described previously.9 Briefly, a J-shaped incision was made to enter the abdominal cavity. Hepatectomy started with a careful hilar dissection. Intraoperative ultrasound was then performed to confirm the hepatic vein anatomy and to verify the transection plane. For right liver harvesting without the MHV trunk, the transection line was set at a plane to the right of the MHV. In this type of hepatectomy, MHV tributaries, if present and greater than 5 mm in diameter, were isolated and preserved. In contrast, for right liver harvesting with the MHV trunk, the transection line was set at a plane to the left of the MHV. Attention was paid to preserve a hepatic vein branch draining segment IV.
Parenchymal transection was performed using a combination of the clamp fracture technique and a Cavitron Ultrasonic Surgical Aspirator (SNOP 5000; Aloka Co., Tokyo, Japan). All sizable vascular and biliary structures were divided between ligatures. During transection, the inflow was intermittently occluded by Pringle's maneuver and sometimes selectively to the right portal vein and the paramedian branch of the right hepatic artery.10 After the transection, the portal flow to segment IV was confirmed by Doppler ultrasound.
Postoperatively, all donors were observed in the intensive care unit for one night. Total bilirubin level, aspartate aminotransferase level, and prothrombin time were measured every day after the operation for 1 week and every other day for the next week.
Volume Regeneration Rate
The term “volume regeneration rate” is defined as “increasing percentage per 3 months,” as defined previously11 Accordingly, the volume regeneration rate of segments I–III and segment IV during the initial 3 postoperative months was calculated using the following formulas:
RRI–III = (V2I–III − V1I–III) / V1I–III × 100 (%)
RRIV = (V2IV − V1IV) / V1IV × 100 (%)
RRI–IV = (V2I–IV − V1I–IV) / V1I–IV × 100 (%)
Abbreviations are as follows: RRn, volume regeneration rate (%) of segment(s) n during the first three postoperative months; V1n, volume (ml) of the segment(s) n on preoperative CT; V2n, volume (ml) of the segment(s) n on CT at the third postoperative month.
The ratio of the remnant liver volume at the third postoperative month to the preoperative whole liver volume (RV), which is another index of liver mass restoration, was also calculated in both groups using the following formula:
RV = V2I–IV / V1I–VIII ×100 (%)
The clinical parameters were defined as follows: resection type (group), donor age, volume of blood loss during the operation, total ischemia time during hepatectomy, preoperatively estimated volume ratio to whole liver, and volume of the segment. These variables, except for resection type, were compared between groups using the Student t test. Multiple regression analysis was then performed to identify predictive factors independently associated with the regeneration rate. The clinical parameters were used as independent factors.
Intergroup comparison of intraoperative data was performed using the Student t test. Postoperative alanine aminotransferase level, total bilirubin level, and prothrombin time of the groups were compared using a two-way repeated measures analysis of variance. Differences were considered significant at a P value of less than 0.05. Values of measured variables were expressed as median and range or mean ± standard deviation.
The median volume of blood loss was 420 ml (range, 110–1,537 ml), which was replaced by 320 ml (range, 0–1,200 ml) of each donor's own fresh frozen plasma or whole blood. The operation lasted 505 minutes (range, 355–1,495 min). The arterial blood supply was maintained, and venous congestion was not apparent on the remnant right liver surface at the time of hepatectomy. Intraoperative ultrasound, however, revealed hepatofugal portal flow to segment IV in 10 of 13 Group B donors (Fig. 1). In these cases, liver surface discoloration in a part of segment IV was observed after five minutes of clamping of the middle hepatic artery. There was no significant difference between the groups in any of the intraoperative parameters (Table 1).
|Group A (n = 58)||Group B (n = 13)||P Value|
|Duration (min)||533 ± 159 (505-1495)||491 ± 75 (395-650)||0.36|
|Blood Loss (ml)||449 ± 230 (250-1537)||563 ± 268 (165-1125)||0.12|
|Autologous Blood transfusion (ml)||358 ± 307 (0-1200)||215 ± 289 (0-600)||0.42|
|Ischemic Time (min)||53 ± 17 (45-89)||59 ± 18 (40-95)||0.23|
Postoperative Course and Complications
All donors survived the operation. Postoperative bile leakage occurred in seven donors in Group A and in one donor in Group B. Of these, four donors in Group A required reoperation for repair. Bile leakage was seen from the stump of the right bile duct branch in three and dissection plane of the liver was seen in one, which was closed meticulously. Another donor in Group A was complicated with abscess formation in the dissection plane of the liver and underwent reoperation for drainage.
In both groups, total bilirubin level, alanine aminotransferase level, and prothrombin time peaked on the first postoperative day and gradually decreased thereafter (Fig. 2). There was no significant difference between the groups in any of these parameters.
Liver Volumetric Regeneration
The volumetric data are summarized in Table 2 and the volume regeneration rate of each sector is illustrated in Figure 3. There was a significant difference in the ratio of remnant liver volume between the groups. In Group B, RRIV (45 ± 33%) was lower than RRI–III (263 ± 48%, Fig. 4). In Group A, the regeneration rate was more proportional. RRIV in Group B was significantly lower than that in Group A (P = 0.008), whereas RRI–III in Group B was significantly higher than that in Group A (P = 0.004). There was no significant difference between the groups in RRI–IV or RV (P = 0.19 or P = 0.98, respectfully).
|Group A (n = 58)||Group B (n = 13)||P Value|
|V1I-IV/V1I-VIII (%)||34 ± 2 (30-39)||37 ± 2 (35-41)||0.04|
|V1I-III (ml)||228 ± 55 (131-381)||200 ± 38 (141-263)||0.17|
|V1IV (ml)||136 ± 38 (85-205)||134 ± 37 (83-194)||0.91|
|V2I-III (ml)||506 ± 124 (348-849)||557 ± 157 (423-935)||0.32|
|V2IV (ml)||300 ± 105 (150-659)||194 ± 72 (118-343)||0.008|
|RRI-III (%)||208 ± 32 (149-280)||263 ± 48 (205-337)||0.004|
|RRIV (%)||125 ± 62 (50-307)||45 ± 33 (9-101)||0.008|
|RRI-IV (%)||125 ± 38 (72-218)||124 ± 37 (70-180)||0.98|
|RV (%)||75 ± 10 (56-98)||80 ± 12 (63-98)||0.19|
The results of multiple regression analysis are shown in Table 3. The resection type was the sole significant predictive factor for the regeneration rate of segments I–III and segment IV. In contrast, the preoperative volume percentage rate to the left liver (segments I–IV), but not the graft type, affected the regeneration rate of the remnant liver.
|Group||Age||Blood Loss||Ischemic Time||Preoperative Volume Ratio to Whole*||Preoperative Volume*|
The present study demonstrated effects of outflow deprivation on liver regeneration. The regeneration rate of segments I–III and that of segment IV after right hepatectomy was proportional when the blood circulation was maintained. In contrast, segment IV without the MHV had impaired volume regeneration compared with cases in which the MHV was preserved. Conversely, in such cases, segments I–III underwent accelerated volume regeneration, probably due to a compensatory mechanism. The results are consistent with those of a recent report.11, 12 on the volumetric changes of the right liver after left or right liver donation.
Deprivation of the MHV tributaries induces hepatofugal portal flow of a part of segment IV.13 Poor portal blood supply leads to unsatisfactory regeneration of segment IV, because portal blood is the most important nutritional supply for the liver parenchyma, and suspension of partial portal blood inflow results in impaired regeneration of the corresponding hepatic area.14 Cheng et al.15 reported that in LDLT using the extended right lobe graft (segments II, III, and a part of segment IV), a part of segment IV decreased in volume when the MHV tributaries were not reconstructed. This observation can be explained by the hepatofugal flow of the portal branch of segment IV induced by deprivation of the MHV tributaries. A previous report16 revealed that in LDLT, venous flow of the ligated MHV tributaries drained into the right hepatic vein by way of the venous collaterals that rapidly develop approximately 1 week after transplantation, which was confirmed by Doppler ultrasonography. Liver regeneration generally begins during the first 3 to 5 days after hepatectomy.17
Volume regeneration of segment IV without MHV drainage was not uniform among the individuals, ranging from 9 to 101%. The left medial vein draining the left part of the medial segment is close to the confluence of the middle and left hepatic veins.18 This tributary flows into the left hepatic vein in the majority of cases, but sometimes it flows into the MHV. The variation in volume enlargement of segment IV might reflect an anatomic difference in left medial vein bifurcation. Thus, detailed recognition of the venous territory pattern on preoperative CT and ultrasonography in individual donors is essential.
As for whole remnant liver regeneration, the ratio of the preoperative left liver to the whole liver was a significant predictor. The results indicate that smaller livers will regenerate more quickly, which is consistent with previous data that regeneration of the partial liver converges to the standard liver volume.19 In addition, partial venous disruption did not lead to overall retardation of mass restoration with the balance between impaired and accelerated regeneration of respective segments. Additionally, postoperative liver functional recovery was comparable between groups. These results suggest that extended right hepatectomy can be safely performed using our criteria. The procedure may be more frequently adopted, because it was not as risky for donors as previously estimated and could prevent a complex reconstruction strategy in MHV reconstruction in recipients. A previous report20 suggested that a residual liver volume of 30% of the total volume is the lower limit. We believe, however, that a larger safety margin should be added to the limitation. We made a limitation of age less than 50 years for the donor for extended right hepatectomy. Previous studies reported that liver grafts from older donors had an inferior ability to regenerate.21, 22 The present multivariate analysis, however, failed to support the theoretical background of the age limitation. Nonetheless, without more data we will continue to employ the present criteria for donor selection for extended right hepatectomy.
Although the multivariate analysis revealed that the total blood-loss volume was not a significant predictor for liver regeneration, minimizing blood loss is clearly important for donor safety. Severe bleeding is associated with decreased hepatic blood flow and ischemic injury.20 Although the upper limitation on ischemic duration should be discussed, previous data10 indicated a beneficial effect of Pringle's maneuver on graft outcome. As the application of Pringle's maneuver requires no specific skills, surgeons should not hesitate to apply this technique to donor hepatectomy.
In summary, the present data indicated that right hepatectomy with MHV resection was associated with latent impairment in postoperative liver regeneration of segment IV. However, we could perform extended right hepatectomy with low postoperative morbidity when the donor was under 50 years of age, and the remnant left liver was estimated to be more than 35% of the whole liver. For donor safety, careful preoperative consideration should be given on a case-by-case basis to the extent of right liver harvesting.