The effect of donor weight reduction on hepatic steatosis for living donor liver transplantation

Authors

  • Shin Hwang,

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Sung-Gyu Lee,

    Corresponding author
    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    • Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea
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    • Telephone: 82-2-3010-3485; FAX: 82-2-474-9027

  • Se-Jin Jang,

    1. Department of Diagnostic Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Sung-Hun Cho,

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Ki-Hun Kim,

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Chul-Soo Ahn,

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Deok-Bog Moon,

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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  • Tae-Yong Ha

    1. Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Abstract

Hepatic steatosis is often associated with overweight, so we tried body-weight reduction in potential living donors with fatty liver and/or obesity to alleviate hepatic steatosis. We advised to reducing the body weight by 5% for 9 potential living donors showing hepatic steatosis of 25–95% on initial percutaneous needle biopsy (PCNB). They lost 5.9 ± 2.0% of the initial body weight during 2–6 months and their body mass index changed from 25.3 ± 3.8 to 23.7 ± 3.4. Total amount of hepatic steatosis changed significantly from 48.9 ± 25.6% to 20.0 ± 16.2% before and after weight reduction. The proportional reduction in microvesicular steatosis was more obvious than in macrovesicular fatty changes. Six right lobe and 3 left lobe grafts were procured uneventfully from these 9 donors. All donors recovered uneventfully, and all 9 recipients survived more than 15 months to date. In conclusion, we think that short-term weight reduction of living donors will be helpful to alleviate excessive hepatic steatosis, especially in microvesicular type and can contribute to expand the pool of marginal living donors. (Liver Transpl 2004;10:721–725.)

Living donors with excessively steatotic livers have been excluded for donation for fear of poor graft function and donor risk. The acceptable degree of hepatic steatosis for living donor liver transplantation (LDLT) has been changeable, but there is a consensus that total steatosis of more than 30% may be not acceptable for transplantation.1 However, if one living donor is excluded due to fatty liver or any other reasons, the recipient candidate will have little chance to undergo LDLT because the number of living donors to a recipient is usually very limited. Excessive hepatic steatosis is often associated with obesity unless there are other medical diseases or intemperate alcohol intake. A series of ideas about the limited availability of living donors and the interrelation between fatty liver and overweight led us to try body-weight reduction in potential living donors with fatty liver and/or obesity. During the preoperative evaluation period of living donors, some potential living donors who had revealed mild-to-severe hepatic steatosis reduced their weight noticeably. These volunteers have finally donated their partial livers uneventfully. In this study, we evaluated the effect of donor weight reduction on hepatic steatosis with the goal of alleviating the fatty change and expanding the living donor pool.

Abbreviations

PCNB, percutaneous needle biopsy; LDLT, living donor liver transplantation.

Patients and Methods

From January 2001 to December 2002, 288 healthy volunteers underwent liver donation for 248 cases of adult-to-adult LDLT in our institution. Forty cases of dual LDLT were included.2 Percutaneous needle biopsy (PCNB) to the right liver has been carried out in all of the living donors as a preoperative evaluation procedure for hepatic steatosis, in addition to abdominal ultrasonography and triphasic computed tomogram. We have principally excluded potential living donors who revealed steatosis of more than 30% as a sum of macro- and microvesicular fatty changes and definite evidences of moderate-to-severe hepatic steatosis on ultrasonography or computed tomography. During the study period of 2 years, there were 9 (3.1%) volunteers whose liver donation had been withheld due to histological finding of excessive hepatic steatosis and/or overweight. Four of them were nondrinkers and other 5 were social drinkers only, with occasional alcohol intake (< 40 gm/week). They denied any medication of drugs or herbs during the last 12 months as well as a medical history of diabetes mellitus. They were advised to reduce their body weight by 5% before revisit for further evaluation. Details on dietary control and exercise regimen were described elsewhere.3 Low-calorie balanced diet (25–30 calories × ideal body weight [Kg] per day), aerobic exercise, and total abstinence from alcohol were recommended. They also consulted with a dietician for dietary control. All of the 9 volunteers reduced their weight through diet and exercise for 2–6 months (Table 1). After confirmation of significant reduction of the body weight, they again underwent radiological study (ultrasonography and/or computed tomography) and PCNB of the liver. All of these volunteers have finally donated their partial livers at 1–3 weeks after completion of the preoperative evaluation. Initial and repeated core biopsy specimens as well as wedge biopsy specimens from the right and left lobes during donor operation were compared, to evaluate the degree of steatosis. These pathologic specimens were collectively reviewed by a pathologist (SJJ) in a blind fashion. The results were also compared with the previous formal reports that were issued before or during donor hepatectomy. Body mass index was obtained from weight (Kg)/height (m)2. Numeric data were expressed as mean ± standard deviation, and paired t-test was used for analysis. Primary diagnoses of the 9 adult recipients were hepatitis B–associated liver cirrhosis, with hepatocellular carcinoma (n = 4), and without hepatocellular carcinoma (n = 5).

Table 1. Profiles of 9 Living Donors Who Reduced Their Body Weight for Liver Donation
Case No.Gender/AgeWeight (Kg)Interval (mos)BMIDegree of Hepatic Steatosis
Radiological StudyHistological Study
1st2nd1st2nd1st2nd1st2nd
  1. Abbreviation: BMI, body mass index.

  2. Interval means the intervening period between the first and second percutaneous liver biopsies. Radiological study included ultrasonography and triphasic computed tomogram. Data of histological study were expressed as “the sum of steatosis (macrovesicular steatosis + microvesicular steatosis).”

1M/20625952120ModerateNo95% (15 + 80)20% (10 + 10)
2M/39797432725SevereModerate70% (55 + 15)60% (40 + 20)
3M/31737022322NoNo25% (5 + 20)5% (5 + 0)
4M/22787652625MildMild25% (15 + 10)20% (15 + 5)
5M/25666032119MildNo35% (15 + 20)10% (10 + 0)
6M/18736862422ModerateMild75% (15 + 60)15% (10 + 5)
7M/43686522423MildNo40% (10 + 30)10% (10 + 0)
8M/42807443128MildNo25% (10 + 15)15% (10 + 5)
9M/25918523129ModerateMild50% (30 + 20)25% (20 + 5)

Results

All of the 9 donors were close relatives of the recipients and there was no pure volunteer donor. Their preoperative profiles were summarized in Table 1. The pathological results from a blind collective review and those described in the previous formal reports were quite similar each other. We presented only the data from the blind review in this study. Radiological and histological findings of donor case 1 are depicted in Fig. 1. In the 9th donor, the initial level of serum alanine transaminase was slightly higher than the reference value of 40 IU/L, but it decreased below the reference value after weight reduction. The other 8 donors did not show any abnormalities in the profiles of liver function before and after weight reduction. The goal of weight reduction by nearly 5% of the initial body weight was achieved in 6 donors, and the mean proportion of weight reduction in 9 donors was 5.9 ± 2.0%3 of the initial body weight. Their body mass index before and after weight reduction were 25.3 ± 3.8 and 23.7 ± 3.4, respectively (P = .0001). Total amount of hepatic steatosis was significantly changed from 48.9 ± 25.6% before weight reduction and to 20.0 ± 16.2% after weight reduction (Fig. 2, P = .006). The proportional change in microvesicular steatosis was more obvious than in macrovesicular fatty changes (Fig. 3). All 9 donors underwent laparotomy for liver donation. Total steatosis of the wedge biopsy specimens from each right lobe and left lobe are also depicted in Figure 2. There was no evidence of fibrosis, ballooning, or lobular inflammation, except for mild portal inflammation only in 2 donors. Right lobe grafts without middle hepatic vein trunk were procured from 6 donors and implanted as a single graft with reconstruction of the middle hepatic vein. The left lobe graft was procured from donor cases 2, 8, and 9. Donor case 2, in whom the fatty change was 60% in the repeated PCNB and 55% in the intraoperative wedge biopsy, afforded the left lobe that was equivalent to 33% of the whole liver volume. The small, fatty, left lobe graft was used for dual LDLT. In donor case 8, the left lobe was procured due to its disproportionately small size, and it was also implanted as a graft for dual LDLT. In donor case 9, the left lobe with caudate lobe was procured and implanted as a single graft. All of these 9 donors recovered uneventfully after liver donation, and all 9 recipients have survived more than 15 months to date.

Figure 1.

Histological and radiological changes of hepatic steatosis in donor case 1, who reduced his body weight by nearly 5% during 5 months. An initial preenhanced computer tomography image revealed moderate steatosis (C), and initial percutaneous core biopsy of the liver also demonstrated severe steatosis (A, hematoxylin and eosin stain, 400×). After weight reduction, repeated histological and radiological studies revealed obvious reduction of hepatic steatosis (B and D).

Figure 2.

Comparison of the changes in total hepatic steatosis from different sampling times and sites. Transverse bars indicate maximum-minimum range and boxes with symbols presenting standard error and mean values. Total steatosis means the sum of macro- and microvesicular fatty changes. A: Steatosis from the initial percutaneous liver biopsy at the deep portion of the right lobe. B: Steatosis from the second percutaneous liver biopsy after weight reduction. There was a significant difference in the amount of steatosis between A and B. C: Steatosis from intraoperative wedge biopsy at the edge of the right lobe. D: Steatosis from intraoperative wedge biopsy at the edge of the left lobe. There were no statistical differences among B, C, and D.

Figure 3.

Comparison of the hepatic steatosis before and after weight reduction in separate aspects of macrovesicular and microvesicular fatty changes. Transverse bars indicate maximum-minimum range and boxes with symbols presenting standard error and mean values. A: Macrovesicular steatosis from the initial percutaneous liver biopsy at the deep portion of the right lobe. B: Macrovesicular steatosis from the second percutaneous liver biopsy after weight reduction. There was a significant difference in the amount of macrovesicular steatosis between A and B. C: Microvesicular steatosis from the initial percutaneous liver biopsy. D: Microvesicular steatosis from the second percutaneous liver biopsy. The difference between C (mean 30%) and D (mean 5.6%) was much greater than that between A (mean 18.9%) and B (mean 14.4%).

Discussion

Fatty change of a partial liver graft has been a major concern in LDLT due to its influence on evaluation of the graft size and posttransplant recovery of the graft function. In fact, the detrimental effect of hepatic steatosis on preservation-reperfusion injury in LDLT must be much milder than in cadaveric donor liver transplantation because in most LDLT operations, there would be no prolonged preservation.1, 4 Instead, the functional graft mass excluding fat has been emphasized for accurate assessment of the graft size in LDLT.5 In evaluation of hepatic steatosis, noninvasive imaging studies such as abdominal ultrasonography and preenhanced computed tomography scan have been primarily used in most LDLT centers. However, these indirect methods do not always reliably reflect the degree of hepatic steatosis.6 We experienced 2 potential donors revealing severe fatty changes without corresponding radiological evidences of hepatic steatosis in our early series. Thereafter, we adopted ultrasonography-guided PCNB as a routine procedure for preoperative evaluation of living donors. The rate of procedure-related complications has been reported as 1% in various states of the livers,7, 8 but we have not experienced any complication yet in over 700 living donors to date. We think that PCNB is quite safe in normal donor livers.6 Fatty changes are often unevenly distributed in the hepatic parenchyma, so PCNB from 2 or 3 sites would not always reflect the state of the whole liver.9 However, PCNB is the only quantitative evaluation method as far as we know. The outcomes of PCNB were much similar to those from the wedge biopsies in this study, not to mention those of our data series from 700 living donors.

In our institution, the degree of hepatic steatosis in living donors has been evaluated preoperatively by the combination of PCNB and imaging studies. Our criteria to exclude fatty donor liver from right lobe procurement is steatosis of more than 30% as a sum of macro- and microvesicular fatty changes in PCNB. For procurement of the left lobe graft, they become slightly more loose case by case, because there is a general tendency of lessened steatosis in the left liver. In addition, we actually do not set any limitation to donor livers that are destined for dual LDLT. The fatty liver graft from donor case 2 revealed progressive alleviation of steatosis in weekly computed tomography follow-up. The radiological evidence of steatosis disappeared after 3 weeks. Although uneventful recovery was achieved in the recipient, there was an exceptionally high rise of liver enzymes and delayed liver regeneration. We have not dared to use such a severely steatotic liver as a single graft instead of dual LDLT.

In this study, we advised the potential donors to reduce their weight by 5% to control hepatic steatosis and/or overweight. In practice, there was no theoretical target weight because more than half of them were not classified as obese (i.e., with body mass index greater than 25). However, presentation of an achievable target value such as reduction of 5% seemed to be helpful for the potential donors to carry out weight control.

Our result proved that microvesicular steatosis was markedly reduced by a small reduction in body weight. However, the effect from weight control on macrovesicular steatosis seemed to be less evident than in microvesicular steatosis. These results imply that microvesicular steatosis is vulnerable to the change of body weight. At this point, we mention a living donor who had undergone severe nonalcoholic steatohepatitis after extended right lobe donation, and finally died after transplantation in Japan. It was the only reported case of living donor mortality in Asia to date and was presented at the 2003 Asia Liver Transplantation Symposium (Kyoto, Japan). When reviewing the wedge biopsy that was taken during donor operation, there was a considerable amount of macrovesicular steatosis with scanty microvesicular steatosis. Such pathologic findings must be unusual for ordinary fatty livers. Precedent reduction of body weight explicated the unusual pattern and dominant distribution of macrovesicular steatosis. We presumed that there might have been much more microvesicular steatosis in the donor liver before body weight reduction. This donor case implies that any arbitrary reduction of the body weight can give erroneous information, leading to underestimation of hepatic steatosis. Reversely, dominant macrovesicular fatty change with scanty microvesicular steatosis should be suspected for additional concealed steatosis or precedent weight reduction. Other pathological findings such as fibrosis, ballooning, or lobular inflammation should also be sought, on the suspicion of nonalcoholic steatohepatitis in donors with somewhat larger fatty changes.10, 11

Before trying reduction of donor weight, alcohol-related fatty liver should be excluded because its pathogenesis is quite different from that of simple fatty liver. Some beneficial effect can be expected from weight control and abstinence of alcohol, but it may be much less effective than in donors with simple steatosis. Potential donors with a history of excessive alcohol intake require special attention during the preoperative interview, as well as the interpretation of the PCNB specimen.

We think that short-term weight reduction of living donors will help alleviate excessive hepatic steatosis, especially in the microvesicular type, and will contribute to expanding the pool of marginal living donors. Baseline assessment of hepatic steatosis should be mandatory before reduction of body weight to prevent its erroneous underestimation.

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