Clinical outcomes of patients with hepatorenal syndrome after living donor liver transplantation

Authors


  • This study was supported by grant A102065 from the Korea Healthcare Technology R&D Project (Korean Ministry for Health and Welfare).

Abstract

Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). However, the clinical benefits of living donor liver transplantation (LDLT) are not yet well established. We, therefore, investigated the outcomes of patients with HRS who underwent LDLT and patients with HRS who received transplants from deceased donors. This study focused on 71 patients with HRS out of a total of 726 consecutive adult Korean patients who underwent LT at a single Asian center. We compared 48 patients who underwent LDLT with 23 patients who underwent deceased donor liver transplantation (DDLT). Patients with HRS showed poorer survival than patients without HRS (P = 0.01). Poorer survival was associated with higher in-hospital mortality for patients with HRS (18.3% versus 5.2%, P < 0.001). In comparison with DDLT, LDLT was associated with younger donors and shorter ischemic times. The survival rate with LDLT was significantly higher than the survival rate with DDLT (P = 0.02). Among patients with high Model for End-Stage Liver Disease scores (≥30) or type 1 HRS, the survival rates for the LDLT group were not inferior to those for the DDLT group. LDLT significantly improved recipient survival after adjustments for several risk factors (hazard ratio = 0.20, 95% confidence interval = 0.05-0.85, P = 0.03). Kidney function was significantly improved after LT, and there was no difference between LDLT and DDLT. No patients in the HRS cohort required maintenance renal replacement therapy. In conclusion, LDLT may be a beneficial option for patients with HRS. Liver Transpl 18:1237–1244, 2012. © 2012 AASLD.

Hepatorenal syndrome (HRS) is characterized by the rapid progression of functional renal failure, and patients with HRS have an extremely poor prognosis.1 Renal dysfunction associated with HRS not only affects overall survival but also influences outcomes and survival after liver transplantation (LT).2-4 LT is an effective cure for both liver disease and associated renal failure and is, therefore, the treatment of choice for patients with end-stage liver disease and HRS.5-7

Long-term survival after LT for patients with HRS is excellent, with the 3-year survival rate approaching 60% to 65%.2, 3 Living donor liver transplantation (LDLT) is an alternative therapeutic option for patients with HRS, although it is not currently the option of choice. However, the risk-benefit balance of LDLT for recipients with severe liver disease remains unknown, and LDLT is thus usually practiced for patients with less severe disease at most centers. A partial liver graft is an additional risk factor for poor posttransplant outcomes in critically ill patients because the small graft volume may result in liver dysfunction.

Since the LDLT program began in 1996, the number of LDLT procedures in Korea has been increasing,8-10 and LDLT can now constitute up to 80.0% of LT procedures according to data from the Korean Network for Organ Sharing registry.11 The frequency of LDLT may help to explain the favorable prognosis for both donors and recipients in Korea. If comparable outcomes for LDLT and deceased donor liver transplantation (DDLT) can be confirmed, LDLT might represent a favorable alternative when we consider the currently dismal prognosis of HRS and the shortage of deceased donors. However, there have been no reports about the outcomes of LDLT for patients with HRS.

In this study, we investigated the effects of living donation on posttransplant outcomes for patients with HRS, and we compared these outcomes to the outcomes associated with deceased donation in a cohort at a single Asian center.

Abbreviations:

ATN, acute tubular necrosis; CNI, calcineurin inhibitor; DDLT, deceased donor liver transplantation; DMN, diabetic nephropathy; eGFR, estimated glomerular filtration rate; HBGN, hepatitis B–associated glomerulonephritis; HRS, hepatorenal syndrome; LDLT, living donor liver transplantation; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; PT-INR, prothrombin time/international normalized ratio; RRT, renal replacement therapy.

PATIENTS AND METHODS

Study Population

In this study, we reviewed the data for 726 consecutive adult Korean patients (age > 18 years) who underwent LT at Seoul National University Hospital between 2000 and 2010, and we focused on those patients with HRS. The diagnostic criteria for HRS were based on the International Ascites Club guidelines12 and included the following: a creatinine level > 1.5 mg/dL; no shock, ongoing bacterial infections, fluid loss, or current treatment with nephrotoxic drugs; no sustained improvement in renal function after diuretic withdrawal and an expansion of the plasma volume with 1.5 L of a plasma expander; proteinuria (<500 mg/day); and no ultrasonographic evidence of an obstructive uropathy or parenchymal renal disease. Type 1 HRS is characterized by rapidly progressive impairment of renal function (a doubling of the initial serum creatinine level to >2.5 mg/dL in <2 weeks). Type 2 HRS is characterized by moderate renal failure (serum creatinine level = 1.5-2.5 mg/dL) with a steady or slowly progressive course.

Patients with acute hepatitis A and renal failure were also excluded because the high urinary sodium concentrations, microscopic hematuria, and proteinuria in patients with acute renal failure associated with a hepatitis A virus infection did not support a diagnosis of HRS.13 Except for those who died within 6 months of transplantation, all recipients were followed up for 6 months or more. This study was approved by the institutional review board of Seoul National University Hospital. All clinical investigations were conducted in accordance with the guidelines of the Declaration of Helsinki of 2000. Informed consent was obtained from all donors and recipients before transplantation.

Data Collection

The following were recorded: donor type, recipient sex and age, comorbidities, pretransplant renal replacement therapy (RRT), body mass index, underlying liver disease, presence of hepatocellular carcinoma, Child-Pugh score, Model for End-Stage Liver Disease (MELD) score, HRS type and duration, ischemic times, immunosuppressant regimens, adefovir use, terlipressin use, donor age and sex, and pretransplant laboratory findings [including the serum creatinine levels, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and bilirubin levels, and prothrombin time/international normalized ratio (PT-INR)]. In the case of LDLT, information was also collected on the time interval between the donor evaluation and transplantation, the proportion of donors evaluated after the development of HRS, the graft weight, the graft-versus-recipient weight ratio, and the graft type (right or left).

Hypertension was defined as a systolic blood pressure > 140 mm Hg, a diastolic pressure > 90 mm Hg, or the use of antihypertensive medications. Diabetes mellitus was diagnosed if a patient had a random blood glucose concentration ≥ 200 mg/dL or a fasting plasma glucose concentration ≥ 126 mg/dL on at least 2 separate measurements or was using antidiabetic medications. The MELD score was calculated for each patient with the following equation:

equation image

where serum creatinine is measured in milligrams per deciliter and serum bilirubin is measured in milligrams per deciliter.

Measurement of Kidney Function and Outcomes

Serum creatinine was measured with a commercially available assay based on the modified Jaffe method reported by Larsen.14 eGFR was calculated with the abbreviated Modification of Diet in Renal Disease formula:

equation image

where serum creatinine is measured in milligrams per deciliter and age is measured in years. The primary outcome was the recipient survival rate. Secondary outcomes were the hepatic allograft survival rate, the posttransplant hemodialysis rate, the change in eGFR after LT, and the trough levels of calcineurin inhibitors (CNIs).

Immunosuppressive Treatment Protocols

A standardized immunosuppression protocol involving a combination of CNIs and steroids was initiated within 24 hours of surgery with intraoperative immunosuppressive induction (anti–interleukin-2 receptor antibodies). The choice of CNI (cyclosporine or tacrolimus) was determined by the transplantation team. In the tacrolimus-based protocol, the trough level was 8 to 13 ng/mL for the first 3 months, and it was decreased to 5 to 10 ng/mL thereafter. In the cyclosporine-based treatment, the trough level was maintained between 200 and 300 ng/mL for the first 3 months, and it was reduced to 100 to 200 ng/mL thereafter. Prednisolone was started at 20 mg/day and was gradually tapered. Purine synthesis inhibitors such as mycophenolate mofetil were used as an initial immunosuppressive treatment according to clinical decisions. Recipients with HRS at the time of the operation received CNIs 24 hours after LT, and these were maintained at a relatively low trough level.

Statistical Methods

The statistical analysis was performed with SPSS 12.0K (SPSS, Inc., Chicago, IL). Quantitative variables were expressed as means and standard deviations. Categorical variables were presented as numbers and percentages. Continuous and categorical data were compared with the independent t test and Fisher's exact test, respectively. The Kaplan-Meier method with the log-rank test was used to compare cumulative patient survival rates. A Cox regression analysis was used to calculate adjusted hazard ratios and 95% confidence intervals for the multivariate analysis. We included factors in the multivariate model that were significant or showed a trend toward statistical significance (P < 0.1) in the univariate analysis. P values less than 0.05 were considered significant.

RESULTS

Baseline Characteristics

Seventy-one of the 726 LT recipients in the cohort undergoing transplantation between 2000 and 2010 satisfied the International Ascites Club criteria for HRS (Fig. 1). Patients were excluded from the analysis if they had other causes of renal failure, which included prerenal failure (11 patients), parenchymal kidney disease (17 patients), nephrotoxic renal failure (3 patients), and hepatitis A with renal failure (8 patients). Forty-eight patients with HRS underwent LDLT, and 23 patients underwent DDLT. The mean duration of follow-up was 3.9 ± 3.1 years (range = 0.0-10.5 years).

Figure 1.

Flow diagram of the study protocol.

The clinical and laboratory characteristics of the patients with HRS are listed in Table 1. The mean age at LT was 49.4 ± 9.7 years, and 74.6% of the recipients were male. The most common etiology of liver disease was hepatitis B virus (76.1%), and this was followed by alcoholic liver disease (8.5%) and hepatitis C virus (5.6%). The mean Child-Pugh and MELD scores were 12.5 ± 1.5 and 38.0 ± 8.0, respectively; 46.5% of the patients had type 1 HRS. The pretransplant serum creatinine level was 3.04 ± 1.71 mg/dL, and the eGFR was 28.8 ± 13.4 mL/minute/1.73 m2. The donor age was younger for LDLT versus DDLT (29.5 ± 10.0 versus 40.1 ± 10.4 years, P < 0.001). The proportion of DDLT patients was higher in the more recent era (2006-2010) versus the earlier era (2000-2005; 48.6% versus 16.7%, P = 0.01). There was no difference between the LDLT and DDLT groups in the proportions of patients receiving pretransplant RRT. The duration of HRS was not significantly shorter in the LDLT group versus the DDLT group (19.8 ± 18.5 versus 14.6 ± 18.7 days), but the ischemic time was significantly shorter in the group LDLT (P < 0.001). No DDLT recipients received cyclosporine, and 2 received no CNIs because of acute infective conditions during the immediate postoperative period. The mean time interval between the donor evaluation and transplantation for the LDLT group was 19.1 ± 16.2 days, and approximately 50% of the living donors started their evaluation after the development of HRS. Most living donors donated right lobes (95.8%), the graft weight was 691 ± 114 g, and the graft-versus-recipient weight ratio was 1.1% ± 0.2%.

Table 1. Clinical and Laboratory Characteristics of Patients With HRS
CharacteristicHRS PatientsP ValueHRS Patients With a MELD Score ≥ 30P ValuePatients With Type 1 HRSP Value
All (n = 71)LDLT (n = 48)DDLT (n = 23)LDLT (n = 39)DDLT (n = 21)LDLT (n = 23)DDLT (n = 10)
  • NOTE: The data are presented as means and standard deviations unless otherwise noted.

  • *

    Ranges are shown in parentheses.

Recipient sex: male [n (%)]53 (74.6)40 (83.3)13 (56.5)0.0232 (82.1)11 (52.4)0.0618 (78.3)6 (60.0)0.40
Recipient age (years)49.4 ± 9.750.0 ± 7.848.0 ± 12.90.4249.3 ± 8.047.2 ± 13.10.4650.4 ± 7.946.7 ± 17.70.40
Era [n (%)]   0.01  0.03  0.26
 2000-200536 (50.7)30 (62.5)6 (26.1) 24 (61.5)6 (28.6) 13 (56.5)3 (30.0) 
 2006-201035 (49.3)18 (37.5)17 (73.9) 15 (38.5)15 (71.4) 10 (43.5)7 (70.0) 
Pretransplant diabetes   mellitus [n (%)]13 (18.3)11 (22.9)2 (8.7)0.209 (23.1)1 (4.8)0.084 (17.4)1 (10.0)>0.99
Pretransplant hypertension [n (%)]6 (8.5)5 (10.4)1 (4.3)0.665 (12.8)0 (0.0)0.151 (4.3)0 (0.0)>0.99
Pretransplant RRT [n (%)]17 (23.9)10 (20.8)7 (30.4)0.3910 (25.6)7 (33.3)0.5610 (43.5)5 (50.0)>0.99
Body mass index (kg/m2)24.0 ± 4.124.5 ± 4.423.0 ± 3.00.1524.6 ± 4.522.9 ± 3.10.1324.1 ± 4.223.1 ± 2.90.48
Underlying disease [n (%)]   0.14  0.32  0.31
 Hepatitis B virus54 (76.1)39 (81.2)15 (65.2) 33 (84.6)14 (66.7) 18 (78.3)7 (70.0) 
 Hepatitis C virus4 (5.6)3 (6.2)1 (4.3) 1 (2.6)1 (4.8) 1 (4.3)1 (10.0) 
 Alcoholic liver disease6 (8.5)4 (8.3)2 (8.7) 3 (7.7)2 (9.5) 3 (13.0)0 (0.0) 
 Other7 (9.9)2 (4.2)5 (21.7) 2 (5.1)4 (19.0) 1 (4.3)2 (20.0) 
Fulminant cases [n (%)]18 (25.4)12 (25.0)6 (26.1)>0.9912 (30.8)6 (28.6)>0.998 (34.8)2 (20.0)0.68
Hepatocellular carcinoma [n (%)]18 (25.4)12 (25.0)6 (26.1)>0.997 (17.9)4 (19.0)>0.993 (13.0)2 (20.0)0.63
Child-Pugh score12.5 ± 1.512.4 ± 1.612.6 ± 1.10.6912.8 ± 1.512.6 ± 1.20.6412.7 ± 1.312.8 ± 1.50.78
MELD score38.0 ± 8.037.1 ± 8.24.0 ± 7.30.1540.0 ± 5.641.2 ± 6.40.4641.3 ± 6.543.6 ± 5.90.35
HRS type [n (%)]   0.73  0.59   
 133 (46.5)23 (47.9)10 (43.5) 22 (56.4)10 (47.6)    
 238 (53.5)25 (52.1)13 (56.5) 17 (43.6)11 (52.4)    
Duration of HRS (days)18.1 ± 18.619.8 ± 18.514.6 ± 18.70.2816.6 ± 14.015.6 ± 19.30.8219.1 ± 13.819.1 ± 23.8>0.99
Ischemia (hours)          
 Total ischemia time197 ± 124130 ± 48338 ± 116<0.001131 ± 48340 ± 119<0.001131 ± 57374 ± 88<0.001
 Cold ischemia time154 ± 12088 ± 49.0290 ± 111<0.00188 ± 47292 ± 115<0.00190 ± 56333 ± 78<0.001
 Warm ischemia time43 ± 1841 ± 1348 ± 260.1542 ± 1248 ± 270.2341 ± 1141 ± 140.91
CNI type [n (%)]   0.01  0.04  0.29
 Tacrolimus57 (80.3)36 (75.0)21 (91.3) 31 (79.5)19 (90.5) 19 (82.6)10 (100.0) 
 Cyclosporine A12 (16.9)12 (25.0)0 (0.0) 8 (20.5)0 (0.0) 4 (17.4)0 (0.0) 
 No CNI2 (2.8)0 (0.0)2 (8.7) 0 (0.0)2 (9.5) 0 (0.0)0 (0.0) 
Mycophenolate mofetil [n (%)]39 (54.9)32 (66.7)7 (30.4)0.0226 (66.7)7 (33.3)0.04815 (65.2)5 (50.0)0.46
Adefovir [n (%)]6 (8.5)5 (10.4)1 (4.3) 5 (12.8)1 (4.8)0.423 (13.0)1 (10.0)>0.99
Terlipressin [n (%)]46 (64.8)34 (70.8)11 (47.8)0.1029 (74.4)9 (42.9)0.0217 (73.9)5 (50.0)0.24
Pretransplant laboratory values          
 Serum creatinine (mg/dL)3.04 ± 1.712.90 ± 1.563.35 ± 2.00.313.16 ± 1.613.49 ± 2.020.494.00 ± 1.634.66 ± 2.010.33
 eGFR (mL/minute/1.73 m2)28.8 ± 13.430.3 ± 13.725.7 ±12.40.1727.4 ± 13.524.5 ± 12.20.4119.5 ± 10.216.9 ± 9.50.49
 Hemoglobin (g/dL)8.9 ± 2.18.9 ± 2.08.7 ± 2.40.958.8 ± 1.88.9 ± 2.50.938.8 ± 1.79.7 ± 3.10.31
 Albumin (g/dL)2.9 ± 0.43.0 ± 0.502.9 ± 0.30.393.0 ± 0.52.9 ± 0.30.523.1 ± 0.42.9 ± 0.40.31
 Total bilirubin (mg/dL)22.9 ± 13.822.7 ± 14.523.4 ± 12.30.8526.2 ± 13.625.0 ± 11.70.7224.1 ± 12.519.8 ± 12.30.36
 PT-INR2.8 ± 1.02.8 ±1.02.9 ± 1.10.673.0 ± 0.93.0 ± 1.10.822.9 ± 1.03.4 ± 1.50.22
Donor and graft factors          
 Donor sex: male [n (%)]53 (74.6)38 (79.2)15 (65.2)0.2532 (82.1)14 (66.7)0.2117 (73.9)7 (70.0)>0.99
 Donor age (years)32.9 ± 11.229.5 ± 10.040.1 ± 10.4<0.00129.4 ± 10.339.4 ± 10.60.00129.3 ± 10.640.1 ± 10.30.01
 Time from donor evaluation   to transplantation (days)* 19.1 ± 16.2 (1-68)  15.6 ± 12.8 (3-68)  14.5 ± 12.2 (1-43)  
 Donor evaluation after development   of HRS [n (%)] 23 (47.9)  21 (53.8)  15 (65.2)  
 Graft weight (g) 691 ± 114  690 ± 116  699 ± 91  
 Graft-versus-recipient   weight ratio (%) 1.1 ± 0.2  1.1 ± 0.2  1.1 ± 0.2  
 Graft type: right/left (n/n) 46/2  38/1  23/0  

Improved Survival in LDLT Recipients With HRS

The recipient survival rates and hepatic allograft survival rates for patients without HRS were significantly better than the rates for recipients with HRS (Fig. 2A,B). Nineteen recipients with HRS died during follow-up, and most (68.4%) died before discharge. In-hospital mortality was significantly higher for recipients with HRS versus recipients without HRS (18.3% versus 5.2%, P < 0.001; Table 2). The 1- and 3-year survival rates were 80.3% and 76.6%, respectively, for recipients with HRS and 90.7%, and 85.3%, respectively, for recipients without HRS.

Figure 2.

Survival among LDLT recipients with HRS: (A,B) recipient and graft survival rates for patients with or without HRS, (C,D) recipient and graft survival rates for LDLT and DDLT recipients with HRS, (E) survival rates for LDLT and DDLT recipients with high MELD scores (≥30), and (F) survival rates for LT recipients with type 1 HRS.

Table 2. In-Hospital Mortality and Hemodialysis for Recipients With HRS
PatientsIn-Hospital Mortality [n (%)]P ValuePosttransplant Renal Failure Needing Replacement Therapy [n (%)]P Value
HRS (n = 655)34 (5.2)< 0.001  
HRS+ (n = 71)13 (18.3)  
All HRS    
 LDLT (n = 48)6 (12.5)0.1012 (25.0)0.06
 DDLT (n = 23)7 (30.4)11 (47.8) 
MELD score ≥ 30    
 LDLT (n = 39)5 (12.8)0.1712 (30.8)0.26
 DDLT (n = 21)6 (28.6)10 (47.6) 
Type 1 HRS    
 LDLT (n = 23)3 (13.0)0.639 (39.1)0.45
 DDLT (n = 10)2 (20.0)6 (60.0) 

Among patients with HRS, survival was higher for LDLT recipients versus DDLT recipients (log-rank P = 0.02; Fig. 2C). The 1- and 3-year survival rates were 87.5% and 85.3%, respectively, for the LDLT group and 60.9% and 60.9%, respectively, for the DDLT group. The most common cause of death was uncontrolled infection in both groups. There were no differences in the causes of death between the LDLT and DDLT groups (Supporting Table 1). There were no hepatic graft failures among the LDLT recipients with HRS, but 1 DDLT recipient suffered from graft failure.

To exclude biases caused by differences in disease severity, we performed a subgroup analysis for the recipients with high MELD scores (≥30) and the recipients with type 1 HRS, and we found that the survival rate with LDLT was not inferior to the survival rate with DDLT among these patients with more severe disease (Fig. 2E,F). DDLT demonstrated no survival benefit over LDLT in a subgroup of patients with nonfulminant disease (Supporting Fig. 1).

A multivariate Cox regression analysis revealed that LDLT was associated with significantly improved recipient survival after adjustments for various risk factors, which included the ischemic time, donor sex and age, HRS type and duration, MELD score, CNI types, and posttransplant RRT (hazard ratio = 0.20, 95% confidence interval = 0.05-0.85, P = 0.03; Table 3).

Table 3. Multivariate Risk Factor Analysis of Death in LT Recipients With HRS
CharacteristicHazard Ratio95% Confidence IntervalP Value
LDLT versus DDLT0.200.05-0.850.03
Total ischemia time (minutes)1.010.99-1.010.11
Donor age (years)1.010.96-1.080.59
Duration of HRS1.010.99-1.030.40
MELD score1.040.97-1.110.23
Posttransplant RRT versus no RRT5.481.55-19.420.01

Posttransplant RRT and Kidney Function in Recipients With HRS

Twenty-three recipients (32.4%) required temporary RRT after LT surgery (Table 2). Twenty-five percent of the LDLT patients and 47.8% of the DDLT patients received posttransplant hemodialysis (P = 0.06). Among patients with type 1 HRS, 39.1% in the LDLT group and 60.0% in the DDLT group needed posttransplant hemodialysis (P = 0.45). No patient in either group required long-term RRT.

Kidney function was significantly improved after LDLT and remained unchanged after 1 month (eGFR at 1 month, 52.8 ± 27.1 mg/dL; eGFR at 6 months, 46.5 ± 15.5 mg/dL; and eGFR at 12 months, 49.6 ± 17.2 mg/dL). Kidney function 1 month after transplantation was better in the DDLT group, but there was no significant difference between the LDLT and DDLT groups after 1 month (Fig. 3). Tacrolimus trough levels were 8.4 ± 3.0 ng/mL 1 month after transplantation, 6.1 ± 2.4 ng/mL at 6 months, and 4.8 ± 1.7 ng/mL at 12 months (Supporting Table 2). Trough levels were unaffected by the donor source.

Figure 3.

Posttransplant kidney function in recipients with HRS. *,P<0.05.

Effects of the HRS Duration and the Duration of the Donor Evaluation on Posttransplant Outcomes

Thirty-five patients underwent LT within 10 days of the development of HRS (Table 4). A shorter duration of HRS (≤10 days) did not affect posttransplant survival for either LDLT or DDLT patients. However, the duration of HRS did influence posttransplant RRT: only 2 LDLT recipients (10.0%) with a short HRS duration required posttransplant RRT, whereas 32.1% of LDLT recipients with a long HRS duration (P = 0.09) and 46.7% of DDLT recipients with a short HRS duration (P = 0.02) did.

Table 4. Impact of the Pretransplant Duration of HRS on Posttransplant Survival and Renal Failure
PatientsHRS Duration (Days)Posttransplant Survival [n (%)]P ValuePosttransplant Renal Failure Needing Replacement Therapy [n (%)]P Value
All≤10 (n = 35)27 (77.1)>0.999 (25.7)0.44
>10 (n = 36)27 (75.0)13 (36.1) 
LDLT≤10 (n = 20)17 (85.0)>0.992 (10.0)0.09
>10 (n = 28)23 (82.1)9 (32.1) 
DDLT≤10 (n = 15)10 (66.7)0.669 (46.7)>0.99
>10 (n = 8)4 (50.0)4 (50.0) 

The duration of the donor evaluation for LDLT recipients whose evaluation began after HRS was significantly shorter than the duration for LDLT recipients whose evaluation started before HRS (8.7 ± 5.3 versus 27.8 ± 17.3 days, P < 0.001). However, the duration of the donor evaluation did not affect posttransplant outcomes (P = 0.82; Supporting Fig. 2).

DISCUSSION

HRS is a serious complication of end-stage liver disease, and its presence affects patient survival after LT. DDLT is the treatment of choice for HRS, but the shortage of organ donors represents a major hurdle to this lifesaving treatment. LDLT may offer an alternative, but it also may be associated with additional risks of poor outcomes for critically ill patients because the small graft volume may result in insufficient recovery of liver and kidney function. Limited information is currently available about the outcomes of LDLT for recipients with HRS. This study has demonstrated for the first time that LDLT is a viable therapeutic option for patients with HRS.

The general advantages of LDLT versus DDLT include shorter waiting and ischemic times, the possibility of scheduled surgery, and a mean donor age of approximately 30 years (usually <50 years in adult LDLT). Our institute recommends LDLT when patients have candidate donors; however, DDLT should be considered for patients without appropriate donor candidates. The ischemic time with LDLT was significantly shorter than the ischemic time with DDLT for recipients with HRS, although there was no difference in the pretransplant duration of HRS.

The survival rate of untreated patients with type 1 or 2 HRS and high MELD scores (>20) is less than 20%,15 but this can be improved up to 60% after LT.2, 3 However, patients with HRS who receive transplants experience more complications and have a higher in-hospital mortality rate than patients without HRS16, 17; the mortality of patients with HRS has been shown to be as high as 25% within the first month after transplantation.18 The 3-year patient survival rate for recipients with HRS in the present study was 76.6%. Only 1 previous case series concerning the outcomes of LDLT for recipients with HRS has been reported: Testa et al.19 reported 7 LDLT patients, 4 of whom experienced renal failure before transplantation and 3 of whom died within the first week after transplantation. Kam20 concluded that patients with severe liver disease (eg, United Network for Organ Sharing status 2A) were not appropriate candidates for LDLT. The present study, however, found better outcomes with LDLT versus DDLT. The probability of early-phase survival, in particular, was superior. These results suggest that recent advances in surgical techniques and perioperative care may be associated with improved outcomes of LDLT, even in recipients with HRS.

HRS was associated with a higher incidence of end-stage renal disease after LT3; however, no patients in the current cohort required long-term RRT. Most patients with HRS experienced improved kidney function after LT,2, 3, 21, 22 but moderate kidney dysfunction persisted during follow-up.1 An enhanced nephrotoxic effect of CNIs in patients with preoperative renal impairment may have been the main cause of dysfunction. The present findings are consistent with those of our previous study,23 which indicated that kidney function could not increase above 60 mL/minute/1.73 m2 in most cases with pretransplant kidney impairment (eGFR ≤ 29 mL/minute/1.73 m2).

The results of the current study are valuable because there are currently few reports of LDLT for serious cases with HRS or high MELD scores. In addition, randomized controlled trials are unfeasible because of ethical issues. However, the study has several limitations. First, it is a retrospective study; a prospective design would be necessary for a precise diagnosis of HRS to be made. Second, it is a single-center study with a relatively small sample size. Although the long-term outcomes of LDLT for the serious cases were not inferior to the outcomes of DDLT, a large, prospective study is required to validate these results.

In conclusion, this is the first study to investigate the outcomes of LDLT for the treatment of HRS. LDLT was associated with favorable outcomes for both patients with HRS and donors. LDLT, therefore, represents a viable option for the treatment of patients with end-stage liver disease and HRS.

Ancillary