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Abstract

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Cystic lesions in the liver are often found through the evaluation of liver donors. Multiple cysts are worrisome, and donor candidates with multiple cysts may be unacceptable as liver donors, especially when their recipients have fibrocystic disease (FCD), which is an inherited disorder. This study reviewed 183 cases of living donor liver transplantation. We collected clinical and radiological data associated with donors with cystic lesions and with donors without cystic lesions, and we evaluated the outcomes of these donors and their recipients. As part of the preoperative radiological assessment of grafts, magnetic resonance cholangiography (MRC) was performed to evaluate the biliary anatomy of donor candidates with multiple cysts. Thirty-four donors (18.6%) had 1 or more cystic lesions in the liver, and 6 of these donors had multiple cysts (ie, >10). Donors with multiple cysts were older and heavier, and there was a significant relationship between these donors and recipients whose original disease was FCD. During the follow-up (median = 3.1 years), all donors with cystic lesions were found to be doing well without any major postoperative complications. Fifteen recipients who received grafts with cystic lesions (12 left-sided lobes and 3 right-sided lobes) had no complications related to the cystic lesions. In conclusion, donors with cystic lesions may be acceptable as liver donors, although our data are limited mostly to left-sided lobe donation with a short follow-up period. MRC should be preoperatively performed to rule out any biliary anomalies, especially in donor candidates whose recipients have FCD. Liver Transpl, 2012. © 2012 AASLD.

Because of the scarcity of deceased donors in Asian countries and especially in Japan, living donor liver transplantation (LDLT) has become a mainstream therapeutic option for patients with end-stage liver disease.1 Donor safety is the greatest priority, and donor selection should be carefully conducted through a precise medical evaluation; however, the number of acceptable donor candidates available from the family of a recipient is typically limited in the setting of LDLT.2

Cystic lesions in the liver are often found during the evaluation of liver donors. A solitary hepatic cyst is of no consequence, although multiple hepatic cysts are worrisome, especially when the recipient has fibropolycystic disease, which is an inherited disorder.3

Here we retrospectively review the characteristics of donors with cystic lesions in the liver and evaluate the outcomes of these donors and their recipients.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Recipients

We performed a retrospective study of donors with cystic lesions in the liver and recipients receiving grafts with cystic lesions among consecutive 183 cases undergoing LDLT at our institute. The study protocol received a priori approval by our institutional review committee. LDLT was performed 183 times (77 males and 106 females) at our institution between November 2005 and February 2012. The recipients' ages at the time of LDLT ranged from 1 month to 34 years (median = 14 months). The recipients' original diseases included cholestatic liver diseases (n = 86), metabolic liver diseases (n = 38), acute liver failure (n = 32), fibrocystic disease (FCD; n = 9), liver cirrhosis (n = 7), vascular disease (n = 6), liver tumors (n = 4), and graft failure after deceased donor liver transplantation (n = 1). LDLT was performed in a piggyback fashion without a venovenous bypass, as described elsewhere.1 The immunosuppression therapy consisted of tacrolimus and low-dose steroids.

Donors

In each case, after the family's consent to proceed with the operation was obtained, a thorough medical evaluation was performed to determine the suitability of the donor. Donors were selected on the basis of the results of this medical evaluation, which included liver function tests, ABO blood group typing, and graft/recipient size matching, as previously described.4 The preoperative radiological assessment of the grafts consisted of ultrasonography (USG) and computed tomography. If these 2 modalities detected considerable numbers of cystic lesions or cystic lesions with any radiological features requiring further evaluation, other potential donor candidates were selected for evaluation. If there were no other potential donor candidates, magnetic resonance imaging, including an evaluation of the donor's biliary anatomy, was performed for further examination. If the cystic lesions showed any radiological features that led to a suspicion of malignancy (eg, septation or mural nodularity), then the candidate was rejected as a donor. Tumor markers such as alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were confirmed to be within the normal ranges during the donor evaluation. The donors included 77 males and 106 females, who ranged in age from 20 to 62 years (median age = 35 years). With respect to the recipients, the donors included 103 mothers, 71 fathers, 3 grandfathers, 3 aunts, 2 brothers, and 1 husband. The donors voluntarily donated 117 left lateral segments (LLSs), 38 reduced LLSs, 22 left lobes, and 6 right lobes. The donor operations were performed via hepatic parenchymal transection without any blood inflow occlusion at the hepatic hilum, as described elsewhere.1 Intraoperative cholangiography (IOC) was performed in each case to visualize the donor's biliary anatomy precisely in order to prevent injury to the bile ducts. Wedge liver biopsy was also performed to evaluate the degree of steatosis, fibrosis, and so on at the time of the operation.

Liver function tests and radiological examinations were periodically performed for both the recipients and the donors after the operations. All data are presented as medians or as means and standard deviations. The statistical analyses were performed with nonparametric χ2 analysis or Kaplan-Meier analysis. Statistical significance was defined as a P value < 0.05.

RESULTS

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Donors With Cystic Lesions in the Liver

Thirty-four donors (18.6%) had 1 or more cystic lesions in the liver. Single cysts were found in 18 donors (52.9%), several cysts (<10) were found in 10 donors (29.4%), and multiple cysts (≥10) were found in 6 donors (17.6%). A comparison of the donors with cystic lesions and the donors without cystic lesions showed the median age of the donors with cystic lesions to be 39.5 years, which was significantly greater than the median age of the donors without cystic lesions (median age = 34 years). The donors with cystic lesions in the liver also significantly demonstrated the presence of concomitant cystic lesions in the kidneys. According to an analysis of the characteristics of the donors with cystic lesions in the liver (Table 1), the donors with multiple cysts were older and heavier, and they had higher body mass indices, although the differences were not statistically significant. There was a significant relationship between donors with multiple cysts and recipients whose original disease was FCD. Four of the 6 donors with multiple cysts had recipients with FCD [congenital hepatic fibrosis (CHF) in 3 cases and Caroli disease in 1 case]; all of these patients were diagnosed with causative gene mutations related to autosomal recessive polycystic kidney disease (ARPKD). The cystic lesions tended to be located in the right lobe. In addition, the diameter of the cystic lesions in the donors with multiple cysts tended to be larger than the others.

Table 1. Characteristics of Donors With Cystic Lesions in the Liver
CharacteristicSingle Cyst (n = 18)Several Cysts (n = 10)Multiple Cysts (n = 6)P Value
  • *

    The data are presented as medians and ranges.

Age (years)*37.0 (31-48)39.5 (30-51)44.5 (31-62)NS
Body weight (kg)*62.1 (47-74)55.5 (44-69)65.9 (51-72)NS
Body mass index (kg/m2)*22.0 (18.3-24.1)20.9 (18.2-23.7)22.5 (20.7-24.1)NS
Sex: male/female (n/n)10/83/75/1NS
Recipient's original disease [n (%)]    
 Cholestatic liver diseases6 (33.3)7 (70.0)2 (33.3) 
 FCD0 (0.0)0 (0.0)4 (66.7)<0.05
 Other12 (66.7)3 (30.0)0 (0.0) 
Cystic lesions    
 Location [n (%)]    
  Whole liver0 (0.0)5 (50.0)6 (100.0) 
  Right lobe only13 (72.2)5 (50.0)0 (0.0)<0.05
  Left lobe only5 (27.8)0 (0.0)0 (0.0) 
 Size (mm)    
  Mean diameter6.95.011.2NS
  Largest diameter201035NA
Concomitant cystic lesions in kidneys [n (%)]2 (11.1)3 (30.0)3 (50.0)NS
Type of operation [n (%)]    
 RL0 (0.0)3 (30.0)0 (0.0) 
 LL4 (22.2)0 (0.0)1 (16.7) 
 Left lateral sectionectomy12 (66.7)3 (30.0)4 (66.7)<0.05
 Left lateral sectionectomy with in situ reduction2 (11.1)4 (40.0)1 (16.7) 

Magnetic resonance cholangiography (MRC) was performed for all donors with multiple cysts, and no abnormal findings were observed for the biliary anatomy, aside from the findings of multiple cysts (Fig. 1A). IOC was performed for all donors with cystic lesions, and no communication between the cystic lesions and the intrahepatic biliary tracts was observed (Fig. 1B). Wedge liver biopsy at the time of the operation was performed for all donors with cystic lesions, and the biopsy samples did not reveal any abnormalities in the biliary structures.

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Figure 1. (A) MRC showed the presence of multiple cysts without any abnormal findings for the biliary anatomy. (B) IOC did not show any communication between the cystic lesions and the intrahepatic biliary tracts in the same donor.

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The donors with cystic lesions in the liver underwent left lateral sectionectomy (n = 19), left lateral sectionectomy with in situ reduction (n = 7), left lobectomy (LL; n = 5), or right lobectomy (RL; n = 3 cases). None of the donors with multiple cysts underwent RL. In each case, the donor's postoperative liver function, which was followed for 12 months after surgery, was analyzed with respect to the type of surgery (Fig. 2). There were no significant differences in postoperative liver function with respect to the type of surgery, although the serum total bilirubin levels in the donors undergoing RL tended to be higher in the early postoperative period than those of the donors undergoing other types of surgery.

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Figure 2. Comparison of the postoperative liver function with respect to the type of surgery: (A) AST, (B) ALT, and (C) total bilirubin.

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All donors with cystic lesions in the liver were found to be doing well without any major postoperative complications during a median follow-up period of 3.1 years (range = 1.5 months to 5.9 years). The size and number of cystic lesions in the remnant liver remained unchanged according to the findings of annual follow-up USG examinations.

Recipients Receiving Grafts With Cystic Lesions

Fifteen recipients received grafts with cystic lesions; 6 of their donors had multiple cysts, 5 had several cysts, and 4 had a single cyst (Table 2). As for the graft types, 8 recipients received an LLS, 3 received a reduced LLS, 1 received a left lobe, and 3 received a right lobe. Biliary complications, including leakage in 2 cases and a stricture in 1 case, occurred 3 times. The 2 recipients with biliary leakage received right lobe grafts from donors with several cysts, whereas the recipient with a biliary stricture received an LLS graft from a donor with a single cyst. All recipients with biliary complications were successfully managed with surgical or interventional radiological treatments. None of the recipients who received grafts with cystic lesions experienced any complications related to the cystic lesions. The size and number of cystic lesions in the grafts remained unchanged according to follow-up USG, which was performed at every outpatient visit. Although 1 patient in a critically ill state before LDLT died because of sepsis in the early postoperative period, the others were found to be alive during a median follow-up period of 3.2 years (range = 1.5 months to 5.6 years).

Table 2. Characteristics of Recipients Receiving Grafts With Cystic Lesions
Case NumberAge at LDLT/SexBody Weight at LDLT (kg)Original DiseaseGraft TypeCysts (n)Largest Cyst Diameter (mm)Biliary Complications (Onset)Outcome (Follow-Up)
Grafts from donors with multiple cysts        
 17 months/female5.8Alagille syndromeReduced LLS≥106NoAlive (1.5 months)
 24 years/male15.4CHFLLS≥105NoAlive (5.6 years)
 36 years/female21.3BALLS≥1035NoAlive (4.7 years)
 46 years/male18.0CHFLLS≥103NoAlive (1.7 years)
 59 years/female20.4CHFLLS≥1013NoAlive (1.4 years)
 610 years/male31.9Caroli diseaseLeft lobe≥105NoAlive (2 months)
Grafts from donors with several cysts        
 76 months/female5.5BAReduced LLS34NoAlive (2.4 years)
 87 months/male4.1Liver cirrhosisReduced LLS25NoDied (10 days)
 914 years/male51.5BARight lobe510NoAlive (3.9 years)
 1016 years/female63.8BARight lobe26Leakage (2 months)Alive (3.0 years)
 1121 years/female60.2BARight lobe34Leakage (1 month)Alive (3.3 years)
Grafts from donors with single cysts        
 126 months/male8.0Acute liver failureLLS110Stricture (4 months)Alive (4.8 years)
 131 year 1 month/male8.1Acute liver failureLLS117NoAlive (3.6 years)
 141 year 11 months/male11.0BALLS16NoAlive (3.2 years)
 153 years/female16.9Glycogen storage diseaseLLS110NoAlive (3.7 years)

DISCUSSION

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

A finding of cystic lesions in the liver can produce a wide spectrum of differential diagnoses. A simple hepatic cyst, which is frequently noted as an incidental finding on radiological modalities, is a benign collection of fluid. Simple hepatic cysts typically occur beneath the surface of the liver and have a size smaller than 10 mm.5 In the setting of LDLT, livers with a single cyst showing radiological findings compatible with simple hepatic cysts can be used as liver donor grafts without worry; however, the use of livers with multiple cysts (>10) as liver donor grafts is questionable. Because the literature had not previously reported on this issue, the aim of the current study was to determine the suitability of donors with multiple cysts.

Multiple cystic lesions are probably associated with FCD of the liver. FCD is a heterogeneous group of conditions in which there is increased hepatic fibrosis in association with cysts lined by biliary epithelium.6 These conditions include biliary microhamartomas (von Meyenburg complexes), autosomal dominant polycystic kidney disease, ARPKD, CHF, Caroli disease, and Caroli syndrome.7 The clinicopathological abnormality observed depends on the level of the biliary tree that is affected during embryogenesis. Ductal plate malformation (DPM) describes a lack of remodeling or wrong remodeling of embryonic ductal plates: Caroli disease and Caroli syndrome with DPM of larger hilar ducts; CHF and ARPKD characterized by DPM at the level of interlobular ducts; and autosomal dominant polycystic kidney disease as well as von Meyenburg complexes revealing DPM in finer, more peripheral ducts.8 The current study indeed showed a significant relationship between donors with multiple cysts and recipients whose original disease was FCD. Four of the 6 donors with multiple cysts had recipients with FCD, all of whom were diagnosed with causative gene mutations related to ARPKD. Such donors are likely to be diagnosed with biliary microhamartomas, one of the conditions related to FCD.

Biliary microhamartomas, which are also called von Meyenburg complexes, typically appear as incidental multiple lesions of a relatively uniform size (<15 mm) and are uniformly distributed throughout the liver.9 As for imaging studies, MRC has been suggested to be more sensitive than computed tomography at revealing irregularly delineated hyperintense nodules that demonstrate no communication with the biliary tree.9 These nodules are easily confused with metastatic tumors, although biliary microhamartomas are usually uniform in size and distribution in comparison with metastases.10 Communicating ductal cysts have more clinical significance because they tend to present in association with medical complications such as cholangitis and biliary calculi.6 During liver donor selection, MRC should be performed to confirm that no communication between the cystic lesions and the biliary tree exists. In the current study, IOC, which was performed for all donors with multiple cysts, did not show any communication between the cystic lesions and the intrahepatic biliary tracts, and this supported the preoperative findings of MRC.

The occurrence of cholangiocarcinoma in association with biliary microhamartomas, which has been reported in several cases, remains a considerable concern.11-13 Guarrera et al.14 reported the use of a graft with diffuse biliary microhamartomas in the setting of deceased donor liver transplantation and proposed oncological surveillance, including the regular checking of carbohydrate antigen 19-9. Despite the low risk of cholangiocarcinoma developing in association with biliary microhamartomas, it has been speculated that immunosuppressants administered after liver transplantation could account for the increased risk of carcinogenesis. In addition, there may be a risk for the future development of symptomatic FCD.14 Although the follow-up radiological examinations completed after LDLT did not show any remarkable abnormal changes in the cystic lesions in the grafts, long-term radiological follow-up to assess cystic lesions in donors and recipients is necessary.

The current study primarily involved left-sided lobe donations; in other words, there were only 3 right-sided lobe donations. Moreover, the cystic lesions tended to be located in the right lobes. Anatomical variations in the biliary tree are more frequently observed in right lobe donations, and this potentially increases the risk of biliary complications.15 In addition, the diameters of the cystic lesions in the donors with multiple cysts tended to be relatively large in this study. When right lobe donations are selected in the setting of LDLT for adults or older children, small-for-size grafts for recipients and insufficient remnant liver volumes after donation for donors are considerable concerns.16 As the presented figures show, multiple cysts of relatively small size (especially biliary microhamartomas) are uniformly distributed throughout the liver. The negative impact of the volume of cystic lesions on the graft or the remnant liver volume might be negligible, although this should be taken into account for living donations involving donors with considerable numbers of cystic lesions or large cystic lesions. Therefore, the current study cannot be used to determine the suitability of donors with multiple cysts for right lobe donation.

In conclusion, donors with multiple cystic lesions might be acceptable as liver donors for left-sided lobe donation, although our data are limited to a short follow-up period. MRC should be preoperatively performed to rule out any biliary anomalies, especially in donor candidates whose recipients have FCD. Further follow-up is required to determine the long-term suitability of these donors.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
  • 1
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    Yamamoto K, Takada Y, Fujimoto Y, Haga H, Oike F, Kobayashi N, Tanaka K. Nonalcoholic steatohepatitis in donors for living donor liver transplantation. Transplantation 2007; 83: 257-262.
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    Gunay-Aygun M. Liver and kidney disease in ciliopathies. Am J Med Genet C Semin Med Genet 2009; 151C: 296-306.
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    Ozawa K, Uemoto S, Tanaka K, Kumada K, Yamaoka Y, Kobayashi N, et al. An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors. Ann Surg 1992; 216: 547-553.
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    Federle MP. Hepatic cyst. In: Federle MP, Jeffrey RB, Woodward PJ, Borhani A, eds. Diagnostic Imaging: Abdomen. 2nd ed. Altona, NY: Lippincott Williams & Wilkins; 2009: III-1-122-125.
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    Desmet VJ. Congenital diseases of intrahepatic bile ducts: variations on the theme “ductal plate malformation”. Hepatology 1992; 16: 1069-1083.
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    Venkatanarasimha N, Thomas R, Armstrong EM, Shirley JF, Fox BM, Jackson SA. Imaging features of ductal plate malformations in adults. Clin Radiol 2011; 66: 1086-1093.
  • 10
    Mortelé B, Mortelé K, Seynaeve P, Vandevelde D, Kunnen M, Ros PR. Hepatic bile duct hamartomas (von Meyenburg complexes): MR and MR cholangiography findings. J Comput Assist Tomogr 2002; 26: 438-443.
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    Dekker A, Ten Kate FJ, Terpstra OT. Cholangiocarcinoma associated with multiple bile-duct hamartomas of the liver. Dig Dis Sci 1989; 34: 952-958.
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    Burns CD, Kuhns JG, Wieman TJ. Cholangiocarcinoma in association with multiple biliary microhamartomas. Arch Pathol Lab Med 1990; 114: 1287-1289.
  • 13
    Jain D, Sarode VR, Abdul-Karim FW, Homer R, Robert ME. Evidence for the neoplastic transformation of von-Meyenburg complexes. Am J Surg Pathol 2000; 24: 1131-1139.
  • 14
    Guarrera JV, Alkofer BJ, Feirt N, Sandoval R, Samstein B, Smith ET Jr, et al. Discovery of diffuse biliary microhamartomas during liver procurement. Liver Transpl 2007; 13: 1470-1471.
  • 15
    Nakamura T, Tanaka K, Kiuchi T, Kasahara M, Oike F, Ueda M, et al. Anatomical variations and surgical strategies in right lobe living donor liver transplantation: lessons from 120 cases. Transplantation 2002; 73: 1896-1903.
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    Liu CL, Fan ST. Adult-to-adult live-donor liver transplantation: the current status. J Hepatobiliary Pancreat Surg 2006; 13: 110-116.