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Liver regeneration after adult living donor and deceased donor split-liver transplants
  Abhinav Humar 1 *, Kambiz Kosari 1, Timothy D. Sielaff 1, Brooke Glessing 1, Maria Gomes 2, Charles Dietz 2, Galia Rosen 2, John Lake 1, William D. Payne 11Departments of Surgery, University of Minnesota, Minneapolis, MN2Departments of Radiology, University of Minnesota, Minneapolis, MN
Liver Transplantation
Volume 10, Issue 3, March 2004
As the number of living donor (LD) and deceased donor (DD) split-liver transplants (SLTs) have increased over the last 5 years, so too has the interest in liver regeneration after such partial-liver transplants.
We looked at liver regeneration, as measured by computed tomography (CT) volumetrics, to see if there were significant differences among LDs, right-lobe LD recipients, and SLT recipients. We measured liver volume at 3 months postoperatively by using CT, and we compared the result to the patient's ideal liver volume (ILV), which was calculated using a standard equation.
The study group consisted of 70 adult patients who either had donated their right lobe for LD transplants (n = 24) or had undergone a partial-liver transplant (right-lobe LD transplants, n = 24; right-lobe SLTs, n = 11; left-lobe SLTs, n = 11). DD (vs. LDs) were younger (P < 0.01), were heavier (P = 0.06), and had longer ischemic times (P < 0.01).
At 3 months postoperatively, LDs had attained 78.6% of their ILV, less than the percentage for right-lobe LD recipients (103.9%; P = 0.0002), right-lobe SLT recipients (113.6%; P = 0.01), and left-lobe SLT recipients (119.7%; P = 0.0006). When liver size at the third postoperative month was compared with the liver size immediately postoperatively, LDs had a 1.85-fold increase. This was smaller than the increase seen in right-lobe LD recipients (2.08-fold), right-lobe SLT recipients (2.17-fold), and left-lobe SLT recipients (2.52-fold).
In conclusion, liver regeneration, as measured by CT volume, seems to be greatest in SLT recipients. LD recipients seem to have greater liver growth than their donors. The reason for this remains unclear.
The liver differs from most other organs in its remarkable ability to regenerate after injury or partial resection. This ability has been well documented and studied in animal models of liver resection as well as in human models, the latter usually involving liver resection for an underlying disease process. Recently, the tremendous increase in the number of partial-liver transplants has renewed interest in studies of liver regeneration. Such transplants, which include split-liver transplants (SLTs) from deceased donors (DD) as well as living donor (LD) liver transplants, are now beginning to account for a significant proportion of all liver transplants performed. Recipients of such transplants, as well as the LDs undergoing partial hepatectomy, constitute an ideal group in which to develop clinical models to study liver regeneration.
Liver growth after such transplants occurs at a rapid pace. Most recipients and LDs have near-complete regeneration of their liver volumes within a matter of a few weeks.[4] Both the inability to achieve this degree of regeneration and the ability to perhaps increase this pace would have important clinical implications. Incomplete regeneration may have an impact on long-term liver function for both LDs and recipients. Increasing the rate of regeneration may have benefits for both LDs and recipients. For example, allowing for smaller pieces of the liver to be successfully transplanted might make surgery safer for LDs and more effective for recipients.
The purposes of this study were to measure hepatic regeneration after partial transplants, to compare results in donors and recipients, and to determine the impact of factors such as donor source and graft type on measured liver volumes.
Patients who undergo a partial-liver transplant or a partial hepatectomy offer ideal clinical models for the in vivo study of liver regeneration. Partial-liver transplants are becoming increasingly popular, given the growing organ shortage. To optimally use these partial grafts, to expand the number of such transplants, and to decrease the risks associated with them (both for LDs and for recipients) we need a better understanding of liver regeneration in the clinical situation is required.
In an animal model, the regenerating liver can be removed and its size accurately measured to quantify liver growth. Of course, doing so is not possible in the clinical situation. Other methods are needed to assess liver regeneration in human patients. Liver growth is generally associated with a normalization of synthetic liver function test results (e.g., serum bilirubin and international normalized ratio [INR]); therefore, serial measurements may serve as a crude indicator of liver regeneration. Radiologic imaging with CT scans to obtain volume measurements of the liver has been shown to correlate well with liver size[9] and probably represents the best method at present to measure liver size.
Our analysis of CT scans for measuring liver volume yielded several observations regarding liver growth after surgery. The ability of the liver to rapidly regenerate was well illustrated in all 4 patient groups. By 3 months postoperatively, most patients had almost doubled their liver size, as compared with their residual liver volume immediately postoperatively. This rapid rate of liver growth has been well documented in numerous animal and clinical models. Interestingly, in our study, recipients tended to have a greater increase in liver volume as compared with LDs. By 3 months posttransplant, liver volume increased by a mean of approximately 2.2-fold for all recipients (SLT and LD, right-lobe and left-lobe). For LDs, the mean increase was about 1.8-fold. This difference in growth may be partially due to the different methods used to measure the initial starting volume (i.e., the volume of the liver immediately postoperatively). For donors this was measured from a CT; for recipients this was measured using a scale in the operating room. However, there is generally a good correlation between these two methods for measurement of liver volume.[9] Moreover, other studies of liver regeneration in living donors have reported similar values for liver volume changes after donation.
A similar trend was noted when the liver volume at 3 months postoperatively was expressed as a percentage of the calculated ILV. Again, recipients seemed to have achieved a greater percentage of their ILV (approximately 110%) than did LDs (about 80%). Another interesting finding was that SLT recipients seemed to have somewhat more liver growth than LD recipients, with a higher percentage of ILV achieved. This was, however, not a statistically significant difference.
Admittedly, our liver volume data offer a snapshot only - specifically, at 3 months postoperatively. The majority of patients had only one CT scan after the procedure, so it is not possible to make estimates on the rate of liver regeneration and evaluate how it may differ among the 4 groups. To do so would require multiple CT scans at various times postoperatively, which we felt were not clinically indicated. It is possible that liver volume may continue to change after the 3-month time point, perhaps increasing in LDs as regeneration continues and decreasing in recipients as initial congestion and edema resolve. However, as shown in Table 3, liver volume changed only to a small degree after the first 3 months, at least in the recipients.
In summary, our study demonstrated that liver regeneration occurs at a rapid pace in recipients of partial-liver grafts and in LDs after partial hepatectomy. The liver of LDs seemed to regenerate at a less vigorous pace, as compared with recipients, and may not be as complete. However, it is important to keep in mind that these radiologic findings may not have any clinical impact, at least for LDs. Synthetic liver function was usually completely normal in LDs by 1 week postoperatively, so the fact that they achieve only 80% of their ILV by 3 months may not be of any clinical significance. Nonetheless, studies such as this are important to help solve the mystery of liver regeneration and to ultimately make partial-liver transplants safer for donors and more effective for recipients.
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