Objectives: Since Japan began doing living-donor liver transplants, the demographics of living donors, including their age, have changed. We sought to assess the impact of aging on the feasibility and safety of doing a hepatectomy in living donors.

Materials and Methods: We analyzed data from 110 consecutive liver donors who had undergone a hepatectomy at our institution. To extract the graft, 34 patients had a lateral segmentectomy, 38 had a left lobectomy, and 38 had a right lobectomy. 

Results: Mean intraoperative blood loss was significantly greater in older donors (age > 40 years) than it was in younger donors (age ≤ 40 years). In addition, the mean number of days required for the serum albumin level to return to normal after surgery was significantly longer in older donors (34.3 ± 11.9 days vs 17.1 ± 9.7 days). A multivariate analysis showed donor age to be a significant risk factor for prolonged serum albumin recovery.

Conclusions: Donor age is a significant factor affecting postoperative liver functioning in the donor. 

Key words : Hepatectomy, Postoperative liver function, Serum albumin

In Japan, living-donor liver transplant has proved to be one of the most effective therapies for liver dysfunction (1). At the beginning of 2004, the Japanese government recognized the need for liver transplants in adult patients with liver cirrhosis, and the national insurance began to cover the costs of living-donor liver transplant. After this change, the number of living-donor liver transplant adult recipients increased rapidly (2). As the number of transplants rose, the backgrounds of the donors changed. Relationships with the recipient, donor age, operative methods, and perioperative medical conditions evolved (3). Recent years have shown an increase in the age of persons donating organs. These changes toward older donors could increase operative risks and thus, the status of the recipients involves crucial decisions regarding donor selection (4). 

The Japanese Liver Transplantation Society has reported that the average donor age for adult living-donor liver transplants is higher than is the donor age for children (5). However, the safe age range for donors and the age-related organ disadvantages (such as cardiovascular, respiratory, and renal functions) are still relatively unclear regarding living donors. In this study, we examine the outcomes related to surgical stress of a hepatectomy in older donors, and we assess the safety of older donors during surgery at our hospital.

Patients and Methods

Between August 2000 and February 2006, we did 110 living-donor liver transplants (without a domino transplant) according to the guidelines of the Japanese Liver Transplantation Society. The age range of the recipients (including 64 adults) was 16 to 56 years. Donors were family members who gave informed consent. Donors were subsequently evaluated by physical and radiologic examinations (6). 

Donor criteria, according to the Japanese Liver Transplantation Society, are a willingness to donate, age between 20 and 65 years (this is the recommended, although not required, age range), relation to the recipient within the fourth degree of consanguinity, healthy liver function, blood type compatibility, absence of relevant infections and serious morbidity, and absence of unsuitable liver abnormalities. 

After donor evaluations, 110 donors underwent a hepatectomy. The type of hepatectomy was based on the estimated liver volume and body weight ratio. In our institute, the minimum required body weight ratio is 0.7 or more (7). The standard liver volume (which has been reported as the optimal liver volume for the body) was estimated by the height and weight of donors using the formula: standard liver volume (mL) = 706.2 × body surface area (BSA) (m²) ± 2.4 (8). The standard surgical techniques for living-donor liver transplant have been described (9, 10). Postoperative care also has been described (9, 10). Postoperative complications were diagnosed clinically and radiologically. We surveyed the medical records of living donors at our institution. Data are expressed as means ± SD or as a range. The statistical software package StatView (version 4.5 for Macintosh; SAS Institute Inc, Cary, NC, USA) was used for the statistical analyses.

Results

Between August 2000 and February 2006, 110 patients underwent a hepatectomy to donate a liver graft. Grafts included 38 full left lobe grafts (including the middle hepatic vein), 38 left lateral segment grafts with a part of segment IV, 38 right lobe grafts without the middle hepatic vein, and 2 right lobe grafts with the middle hepatic vein. The data regarding the operative methods in each age bracket are shown in Table 1.

The 110 donors had a mean age of 38.1 ± 11.1 years (age range, 19-68 years). The mean donor age was 40.4 ± 11.6 years in adults and 34.5 ± 9.3 years in children; this difference was statistically significant (P = .0064).

Twenty-seven donors had underlying diseases or minor preoperative problems. Nine donors had mild steatosis, 4 donors had hypertension, and 1 donor had asthma. Three donors had a history of abdominal surgery. The presence of hepatitis B core antibodies revealed a previous hepatitis B viral infection in 6 patients. Three patients had a history of gastric ulcers and 2 had a history of psychological depression. There were 50 cases (86%) of identical healthy donors under 40 years of age. Nineteen donors (40%) aged older than 40 years had a preoperative problem: 9 donors had steatosis, 4 donors had hypertension, and 1 donor had asthma. Three donors had a past history of an abdominal operation. Presence of hepatitis B core antibodies revealed a previous hepatitis B viral infection in 6 patients. Three donors had a history of gastric ulcer and 2 had a history of psychological depression. 

The average sizes of the grafts in each age group are shown in Table 2. The standard liver volume (SLV) for the body was estimated by the height and weight of donors using the following formula (8): SLV (mL) = 706.2 × BSA (m²) ± 2.4. Based on the SLV, we calculated the estimated residual liver ratio of the donors in each age group: (SLV-graft)/SLV. The largest grafts (mean, 507 ± 167 g) were obtained from donors aged 40 to 60 years, because most of the older donors had a hemilobectomy (right lobectomy, 43.1%; left lobectomy, 43.1%). Consequently, their residual liver volume ratio was significantly less than that of the younger donors. 

We also analyzed the operative records according to donor age. Intraoperative blood loss and operation time in the donor groups are shown in Figure 1. The mean amount of intraoperative blood loss was significantly greater in the older donors (870 ± 478 mL) compared with the younger ones (534 ± 414 mL). The surgical procedures for the donors older than 40 years had significantly more blood loss and tended to require a longer time than did the procedures used in the younger donors. 

We analyzed postoperative laboratory examinations, including changes in levels of the complete blood count, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, total bilirubin, and serum albumin. There were no significant differences in these values between donors aged younger than 40 years and donors aged 40 years and older. Despite more-invasive surgical procedures for older donors, the laboratory data concerning liver functions did not show any significant differences between the 2 groups. Similarly, we found no significant differences regarding the time required to return to preoperative values for aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, platelets, and prothrombin time between younger and older donors. However, there was a significant correlation regarding serum albumin levels and their return to preoperative levels and older donors (Figure 2). The serum albumin recovery period was significantly longer in donors over 40 years old than it was for donors under 40 years old (34.3 days vs 17.1 days, P < .0001). A multivariate analysis (Table 3) showed that the factors involved in the prolongation of serum albumin recovery were donor age (P < .0001) and residual liver volume (P = .0004). However, no significant associations with operative blood loss and the operative time were detected. Donor age older than 40 years prolonged the serum albumin recovery period independent of the residual liver volume rate.

The incidence and the type of postoperative complications in each age group were examined. Biliary leakage was the most frequent complication (8.1%) after the donor operation (11), and the incidence of biliary leakage, infection, and others were not significantly different. All donors recovered well and returned to normal social activities within 3 months.

Discussion

Our study addressed the safety of older donors for living-donor liver transplants in Japan. Several plausible arguments have been offered for the effect of age on living-donor liver transplant (12). In our country, an upper age limit of 65 years has been deemed acceptable for donors. However, that indication was established during the initial period of living-donor liver transplants. The procedures and the backgrounds of donors have changed in Japan during recent years. The size of the graft is one of the most-critical factors taken into consideration for adult living-donor liver transplant, and more-invasive surgical procedures such as right lobectomies tend to be required (5). As a result, the operations in donors older than 40 years of age have been more invasive, with an increase in the volume of blood loss and operation times.

On the other hand, the degree of postoperative damage, as indicated by laboratory data in the short term, is not significantly different between the donor groups. This result is consistent with the results of previous studies of liver resections (13-15). Only serum albumin recovery time showed a significant difference between the donor age groups at our institute. In this study, not only a univariate analysis but also a multivariate analysis showed that the independent factors involved in prolonging serum albumin recovery were the donor age. Moreover, we compared the recovery period for serum albumin level in 46 cases of major hepatectomies (right and left lobectomy) and found statistically significant differences (P = .0001) between younger and older group. The mean number of days required for the serum albumin level to return to normal after a major hepatectomy was significantly longer in older donors (34.7 ± 11.9 days vs 19.8 ± 11.2 days). 

Although the incidence and severity of complications were not different between younger and older donors in this study, the influence of aging may have a long-term effect on normalizing liver functioning in older donors and these long-term effects on donors should be elucidated in the future.

In conclusion, recent innovations in living-donor liver transplants in Japan have changed donor demographics and have resulted in more-invasive operations for older donors. Donor safety has been maintained despite the increased number of older donors. However, we found that the recovery period for the serum albumin level was significantly longer in older donors. Our results indicate that expansion of the age criterion must be thoroughly investigated in view of donor recovery (16). More long-term follow-up studies are needed to better evaluate the effect of aging in living donors.

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