| As is known to all, liver transplantation is usually the only and the best therapy for end-stage liver disease patients. However, donor liver insufficiency always hampers the development of liver transplantatoin. As the progression in surgical techniques, newly invented organ reservation fluid, and especially the application of new immunosuppressants, clinical liver transplantation had made great progress. Unfortunately, insufficient donor liver supply remained the obstacle in promoting this method. In Western countries, as the development of (donation after cardiac death, DCD) and (donation after brain death, DBD), the shortage had some relief, as to China, DCD set out only for a short period of time, not to mention DBD, which is still under the recognition of the population and the society. In such a background, to make the best use of marginal donor is of great importance. As a major part of marginal donor, fatty liver gradually comes to our focus. As the development economic, people takes more calories, resulting in the higher prevalence of fatty liver. Internationally, the prevalence of fatty liver is3.23%～14%. The incidence seems to be high in obese child and adults,1.8%～68.6%, and higher in man than woman. In China, the general survey shows that the prevalence is3.9%～11.2%, highest in45-49years old people,11.2%, and also higher in man,11.4%, than woman,6.8%. These figures imply that it is more likely for a potential liver donor to be fatty liver. However,25%donor livers are rejected due to liver steatosis, in America. Ultrasound and CT scan has limited ability in evaluating steatosis, and the major effective method is biopsy. Clinical practitioners worry that fatty liver being a donor liver will lead to complications such as (primary non-function, PNF), and (early allograft dysfunction, EAD).Fatty liver is clinically classified as mild, moderate and severe. Temporally, most liver transplantation center adopt ANLTU fatty liver grading (The fatty liver here refers to macrovesicular steatosis):S0,(no steatosis), S1(mild, less than30%focal macrovesicular steatosis), S2(moderate,30-60%band macrovesicular steatosis) and S3(severe, over60%hepatic lobule macrovesicular steatosis).Till now, no any standard criteria in the evaluation of fatty liver as donors in liver transplantation has been advanced. Based on the insufficiency of donor liver, the criteria in evaluation fatty liver donors seem to be wider and wider. In early years, liver transplantation center of Pittsburgh illustrates that mild fatty liver (macrovesicular steatosis less than30%) can be considered as potential donors, while moderate fatty liver (macrovesicular steatosis over30%, but less than60%) is controversial, and severe fatty liver (macrovesicular steatosis over60%) shouldn’t be used as donors. Researches of Adam showed that more than30%of390transplatation cases that fatty liver were adopted as donors were stroked by PNF, in contrast, the prevalence of PNF in normal liver donor transplantations was only2.5%. Kwon evaluated245mild fatty liver transplantation cases, with macrovesicular steatosis less than30%. He made a comparasion between the subgroups of0-9%macrovesicular steatosis,10-19%macrovesicular steatosis and19-29%macrovesicular steatosis, and came up with the conclusion that no significant difference of total operation time, blood loss volume was found. As for moderate and severe fatty liver, Ploey found that80%severe fatty liver as donors developed PNF, and30%moderate fatty liver as donors occurred EAD. Hayash found no difference between mild and moderate donors about the transplantated liver function in the early post-operation stage, while severe fatty liver made a significant bad impact on the transplanted liver function and the survival of the patient. However, at the same time, some of research also suggests that moderate to severe fatty liver could be used as donors. Cho adopted alcholic hepatopathy liver with50%macrovesicular steatosis and30%micro vesicular steatosis as donor liver in auxiliary partial in-situ liver transplantation. They found that most indexes of both the recipent and the donor remained in the normal range. Deborah Verran studied that no significant difference was found in EAD occurance in moderate to severe fatty liver donors. Jan P. Deroosel research showed that when combined with long-term cold ischemic time, severe fatty liver donor made a significant effect on the transplanted liver, but if no more risk factor was added, severe fatty liver still could be chosed as donors.Fishbein studied40cases of severe microvesicular steatosis as donors and turned up that the PNF and IPF occurance was5%and10%, respectively, suggesting that no difference was found verses normal donor liver. As a result, they claimed that severe microvesicular steatosis shouldn’t be excluede as potential donor. Besides, Salizzoni’s study also supported that microvesicular steatosis, even severe microvesicular steatosis, can be clinically safe because hepatic lipid was soon mobilized and degenerated. Conclusively, in the evaulation of fatty liver as potential donors, there’s no essential in taking microvesicular steatosis into consideration. Summarily, microvesicular steatosis are generally accepted as potential donors, as well as mild macrovesicular steatosis, while moderate to severe type fatty liver is still controversial. Most studies believe severe fatty liver are not suitable, and the disagreement mainly remains in moderate fatty liver. In the background that the donor liver is in great demand, to make the best use of marginal liver donor is a great topic. Our retrospective study focused on the moderate to severe fatty liver donor transplatation cases during2010.4to2014.12of The1st Affilated Hospital of Zhejiang University, summaring the experience in fatty liver transplantation, to make a better use of marginal liver donor and broader the source of liver donors.Methods:Cases of The1st Affilated Hospital of Zhejiang University during2010.04to2014.12were collected. Data of patients’ age, sex, MELD scores, Child-Pugh scores, warm-ischemic time, cold-ischemic time, total operation time, blood loss volume during operation, whether maligant tumor, blood type compatibility, whether massive haemorrhage during operation, hospitalized time, rejection reaction, peri-operation infection, biliary complications, primary non-function and peri-operation death were collected.ANLTU clinical fatty liver grade was adopted, according to different extent of lipid degeneration, donor liver cases were classified as M0group (no steatosis detected), M1group (mild, less than30%macrovesicular steatosis), M2group (moderate, macrovesicular steatosis over30%but less than60%), and M3group (severe, macrovesicular steatosis over60%). Then M2group were further divided into M21group (macrovesicular steatosis30%-40%), M22group (macrovesicular steatosis40%-50%), and M23group (macrovesicular steatosis50%-60%). M0group was defined as control group. Demographic characteristics were analyzed by single factor analysis based on patients’ age, sex, MELD scores, Child-Pugh scores, warm-ischemic time, cold-ischemic time, total operation time, blood loss volume during operation and whether massive haemorrhage during operation. If no inter-group demographic characteristics differences were analyzed, then hospitalized time, rejection reaction, peri-operation infection, biliary complications, primary non-function and peri-operation death were analyzed for the difference of prognosis.Data of total bilirubin, ALT, AST, CHE of30days after operation were collected. LSD were used to compare the inter-group differences of total bilirubin, ALT, AST, CHE curves of30days after operation and7days after operation, evaluating the liver function recovery.Single factor analysis were adopted in evaluating the effects of patients’ age, sex, MELD scores, Child-Pugh scores, warm-ischemic time, cold-ischemic time, total operation time, blood loss volume during operation, whether maligant tumor, blood type compatibility, whether massive haemorrhage during operation, hospitalized time, rejection reaction, peri-operation infection, biliary complications, primary non-function and peri-operation death. Then, the factors with P<0.1in single factor analysis were further included in multi factor analysis.All statistical analysis were performed by SPSS. The statistical methods used include single factor ANOVA, LSD method, Pearson Chi-Square, multiple factor ANOVA, multiple factor logistic regression analysis and multiple factor COX regression model.ResultsAll the568cases of donor after death between2010.4and2014.12were collected. 399of568donors were found no steatosis,(MO group,70.2%),120were detected as mild macro vesicular steatosis (Ml group,21.1%),39were classified as moderate macro vesicular steatosis (M2group,6.9%), and only10were defined as severe macrovesicular steatosis donors (M3group,1.8%). Note that32of the568patients were second time liver transplantation recipients. In greater detail,18donors had the extent of macrovesicular steatosis between30%-40%(M21group,3.2%),14had the extent between40-50%,(M22group,2.5%) and7lay in the50-60%%level,(M23group,1.2%). For all the group of M0, M1, M21, M22, M23, and M3, the average (±SD) of age were47.60±11.94,47.19±9.74,46.44±7.83,48.93±9.65,45.00±11.50and48.50±7.96, respectively. The average (±SD) MELD score were19.93±11.27,17.90±9.74,21.00±11.00,22.36±11.02,27.29±9.05and22.30±11.72, respectively. The average (±SD) Child-Pugh score were8.87±2.64,8.60±2.50,10.11±3.27,9.57±2.28,10.14±1.35and9.00±3.06, respectively. Average (±SD) heat ischemic time (minutes) were8.46±6.74,7.00±5.37,8.06±9.62,7.93±4.70,7.14±5.67and6.70±2.79, respectively. Average (±SD) cold ischemic time (minutes) were634.73±313.87,627.52±160.50,670.56±171.08,666.86±235.59,645.29±132.37and620.80±122.73respectively. Average (±SD) operation time (minutes) were302.29±81.01,318.89±84.30,311.78±77.07,326.21±133.15,282.43±45.84and314.00±78.53respectively. Average (±SD) blood loss volume (ml) were2276.42±2307.97,2593.33±2401.04,3500.00±2948.38,3021.43±2423.34,3214.29±1576.31and3320.00±3104.05, respectively.The malignant tumor patients were165cases (41.4%),61cases (50.8%),7cases (38.9%),5cases (35.7%),2cases (28.6%) and4cases (40.0%), respectively. Blood type incompatible cases were108cases (27.1%),29cases (24.2%),6cases (33.3%),4cases (21.4%),3cases (42.9%) and5cases (50.0%), respectively. Great hemorrhage (blood loss over1500ml) during operation accounts for217(54.4%),57(47.5%),7(38.9%),5(35.7%),1(14.3%) and4(40.0%), respectively. Second time transplantation accounts for23(5.8%),6(5.0%),0,1(7.1%),0and2(20%), respectively. Compared with MO group, all comparison had a P value over0.05, except Child-Pugh score of M21group, warm-ischemic time of M1group, blood loss volume of M21group,(P=0.050,0.030and0.032, respectively). Arrange as M0, M1, M21, M22, M23and M3, mean (±SD) post-operational hospitalized time were28.21±14.04,30.71±17.49,20.70±21.20,26.28±13.94,21.14±16.98and19.86±13.89. The incidence of rejection reaction were5.5%(22),1.7%(2),11.1%(2),7.1%(1),0.0%(0) and0.0%(0). Peri-operational infection rate were14.5%(58),9.2%(11),5.6%(1),14.3%(2),28.6%(2) and20.0%(2). Biliary complication prevalences were7.5%(30),8.3%(10),5.6%(1),7.1%(1),14.3%(1) and0.0%(0). Primary non-function occurred in5.8%(23),7.5%(9),16.7%(3),28.6%(4),28.6%(2) and20.0%(2) patients. Peri-operational mortality were3.0%(12),4.2%(5),11.1%(2),21.4%(3),28.6%(2) and30.0%(3). And single factor analysis shows that more patients suffered from primary non-function in M22group than M0group (p=0.009). Peri-operational mortality was significantly higher in M22, M23and M3group verses M0group (P=0.011,0.021and0.004). M0as control group, we made a comparison about the curves of total bilirubin, ALT, AST, CHE in30days after operation, and came up with the result that ALT and CHE was significantly elevated in M3group (P=0.008, P=0.019, respectively), AST was significantly elevated in M2group (P=0.009), while TB had no obvious difference among all the group. As to the curves of total bilirubin, ALT, AST, CHE in7days after operation, we found that M22and M3group showed a higher ALT than M0(P=0.001and0.025), AST in M22group was significantly different from that of M0(P<0.001), and total bilirubin in M22and M23were higher than in M0(P=0.024and0.015), while no difference was found in CHE. Single factor logistic analysis showed that for malignant tumor recipients, the peri-operational infection and mortality were both lower than non-malignant tumor recipients (OR=0.23and0.357, P=0.001,0.002). Blood type incompatible recipients had higher peri-operational infection rate, peri-operational mortality and primary non-function rate than that of blood type compatible recipients (OR=1.812,2.451and2.103, P=0.021,0.002and0.037, respectively). There were higher risk for peri-operational infection and mortality in high MELD score patients than low MELD score patients (OR=1.044and1.056, P=0.001and0.001, respectively). Patients with higher Child-Pugh score also had higher risk for peri-operational infection and mortality (OR=1.241and1.330, P=0.001and0.001, respectively). Longer operational time increased peri-operational mortality and primary non-function rate (OR=1.005and1.004, P=0.004and0.017, respectively). If the patient suffered from great blood loss during operation, the peri-operational mortality, biliary complication rate and primary non-function rate also increased (OR=2.653,2.154and3.202, P=0.002,0.008and0.003, respectively). Peri-operational infection contributed to peri-operational mortality (OR=2.941, P=0.001). Second time transplantation recipients had a higher peri-operational infection rate (OR=2.739, P=0.015). Compared to M0, M22, M23and M3group had a higher peri-operational mortality (OR=5.128,6.923and6.154, P=0.005,0.013and0.006), as well as more risk for primary non-function in M21and M23group (OR=3.958and7.916, P=0.041and0.017). Multiple factor logistic analysis showed that operation time, incompatible blood type, moderate fatty liver donor (M22, M23) and severe fatty liver donor (M3) were the risk factors for peri-operational mortality. Great blood loss during operation was the independent risk factor for biliary complication (OR=2.154, P=0.008). Age of recipient and cold ischemic time were the risk factors for rejection reaction (OR=0.935and1.001, P <0.001and=0.032). Cold ischemic time, great blood loss, incompatible blood type and moderate fatty liver (M22) were the risk factors for primary non-function. Kaplan-Meier survival analysis showed that survival time were significantly reduced in M22, M23and M3group compared to M0group (p=0.002,0.001,0.004, respectively). Multiple factor COX regression analysis showed that great blood loss, operation time, incompatible blood type, malignant tumor recipient, age, moderate fatty liver donor (M22and M23) and severe fatty liver donor (M3) were the risk factors for survival time (OR=1.532, 1.003,1.530,2.313,1.026,4.077,4.167and3.432, P值0.035,0.002,0.029,<0.001,0.007,0.001,0.003and0.009, respectively), especially for moderate fatty liver, which made greater impact on the survival time.Conclusion1. Mild fatty liver and moderate fatty liver with extent of steatosis less than40%can be considered as safe donor.2. The steatosis extent of donor liver have a strong impact on primary non-function, peri-operational mortality and long-time survival. If the steatosis of donor liver reach or is more than40%, the primary non-function, peri-operational mortality would significantly increase, as well as reducing long-time survival.3. Incompatible blood type is the high risk factor of the primary non-function, peri-operational mortality, and reduces long-time survival.4. Great blood loss during operation is the independent risk factor of biliary complication and the high risk factor of primary non-function rate. Great blood loss is a negtive risk factor of long-time survival time also decreased.5. Extent of steatosis have no significant relationship with biliary complication, blood loss volume, post-operational hospitalized time and peri-operational infection rate. |
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