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Article first published online: 27 AUG 2012
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 18, Issue 9, pages 1069–1077, September 2012
How to Cite
Yamashiki, N., Sugawara, Y., Tamura, S., Nakayama, N., Oketani, M., Umeshita, K., Uemoto, S., Mochida, S., Tsubouchi, H. and Kokudo, N. (2012), Outcomes after living donor liver transplantation for acute liver failure in Japan: Results of a nationwide survey . Liver Transpl, 18: 1069–1077. doi: 10.1002/lt.23469
This study was supported in part by grants-in-aid from the Japanese Ministry of Health, Labor, and Welfare to the Study Group of Intractable Hepatobiliary Diseases. Noriyo Yamashiki, Yasuhiko Sugawara, Sumihito Tamura, and Norihiro Kokudo were supported by a grant-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science, and Technology and by grants-in-aid for research on human immunodeficiency virus/acquired immune deficiency syndrome and on measures for intractable diseases from the Japanese Ministry of Health, Labor, and Welfare.
See Editorial on Page 1005
- Issue published online: 27 AUG 2012
- Article first published online: 27 AUG 2012
- Accepted manuscript online: 11 MAY 2012 04:39AM EST
- Manuscript Accepted: 4 MAY 2012
- Manuscript Received: 15 FEB 2012
Nationwide surveys of acute liver failure (ALF) are conducted annually in Japan, and 20% of patients with ALF undergo liver transplantation (LT). We extracted data for 212 patients who underwent LT for ALF from the nationwide survey database of the Intractable Liver Diseases Study Group of Japan. After the exclusion of 3 patients who underwent deceased donor LT, 209 recipients of living donor liver transplantation (LDLT) were analyzed. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the disease's onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late-onset hepatic failure (LOHF). Long-term follow-up data were obtained from the registry of the Japanese Liver Transplantation Society. The 2 data sets were merged, and descriptive and survival data were analyzed. A Cox regression analysis was performed to define factors predicting overall mortality, short-term mortality (≤90 days after LT), and long-term mortality (>90 days after LT). One hundred ninety of the analyzed patients (91%) were adults (age ≥ 18 years); 70 patients (34%) were diagnosed with acute ALF, 124 (59%) were diagnosed with subacute ALF, and 15 (7%) were diagnosed with LOHF. Hepatitis B virus was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy–induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The cumulative patient survival rates 1, 5, and 10 years after LT were 79%, 74%, and 73%, respectively. Patient age was associated with short- and long-term mortality after LT, whereas ABO incompatibility affected short-term mortality, and donor age affected long-term mortality. In conclusion, the long-term outcomes of LDLT for ALF in this study were excellent, regardless of the etiology or classification. The majority of the donors were living donors. Increasing the deceased donor pool might be an urgent necessity. Liver Transpl, 2012. © 2012 AASLD.
Acute liver failure (ALF) is a severe clinical condition in which the rapid deterioration of liver function results in cognitive disturbances and coagulopathy in patients with previously normal liver function. ALF, which was formerly called fulminant hepatitis or acute hepatic necrosis, is defined as an international normalized ratio of at least 1.5 and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of more than 26 weeks' duration.1 ALF is a potentially fatal condition if emergency liver transplantation (LT) is not performed. Spontaneous recovery is expected in only 10% to 40% of patients with ALF, whereas the short-term survival rate after LT has been 68% to 84%2-5; more recently, short-term survival rates greater than 80% have been achieved.6, 7 In the United States and Europe, patients with ALF who are at higher risk of death are considered for LT, and applicable candidates are listed for deceased donor liver transplantation (DDLT). Although these patients with ALF are assigned to the highest priority category, the mortality rate while patients are waiting for a graft ranges from 10% to 70%.3, 7 In Asia, where deceased donors are scarce, living donor liver transplantation (LDLT) accounts for more than 90% of LT procedures.8 With survival rates of 70% to 87%, LDLT is almost the only option for such high-urgency patients.9-13 Even in Asian countries, however, the etiologies of ALF and the availability of deceased donor organs differ between centers, so the long-term outcomes after LT may also be different.14
A nationwide survey of ALF is conducted annually in Japan, and in 2011, the characteristics of 934 patients were reported in detail.15 An analysis of these data indicated that the survival rate of non-LT patients was 54% for acute ALF, 24% for subacute ALF, and 15% for late-onset hepatic failure (LOHF), whereas the survival rate was greater than 70% for patients who underwent LT.4 Because there were no long-term follow-up data for this nationwide survey, we obtained follow-up data from separate databases from the Japanese Liver Transplantation Society, and we analyzed the factors associated with short- and long-term survival.
PATIENTS AND METHODS
Between January 1998 and December 2008, 1090 patients with ALF were enrolled in the nationwide survey conducted by the Intractable Liver Diseases Study Group of Japan under the aegis of the Japanese Ministry of Health, Welfare, and Labor. Two hundred twenty-two of the 1090 patients (20%) underwent LT. Information on recipients, donors, and outcomes were obtained from a national database managed by the Japanese Liver Transplantation Society. After the exclusion of 10 cases due to insufficient data, 212 cases remained. Because there were only 3 DDLT cases, the data for the 209 LDLT cases were used for the analysis. This study was conducted with the approval of the ethics committees of Saitama Medical University and the Kagoshima University Graduate School of Medical and Dental Sciences (the sites of the data collection), and the use of the annual LT registry data was approved by the committee of the Japanese Liver Transplantation Society.
Definition of ALF
ALF was diagnosed according to Japanese diagnostic criteria.4, 16 In brief, the disease was diagnosed when grade II or deeper encephalopathy developed within 24 weeks of the first symptoms of acute hepatitis and the prothrombin time was less than 40% of the standardized value. ALF patients were placed into 3 subgroups according to the time from the onset of the disease to the occurrence of encephalopathy: patients who presented with encephalopathy within 10 days of the disease's onset were classified as having acute ALF, patients who presented within 11 to 56 days were classified as having subacute ALF, and patients who presented within 9 to 24 weeks were classified as having late-onset hepatic failure (LOHF). The etiologies of ALF included viral hepatitis, autoimmune hepatitis, drug allergy–induced liver injury, and acute hepatitis of indeterminate or unknown causes.4, 15 The diagnostic criteria for the etiologies of ALF were previously described.4 ALF cases caused by drug/chemical intoxication, microcirculatory disturbances, Wilson's disease, acute fatty liver of pregnancy, or Reye's syndrome were not included in this study: ALF cases due to these causes were excluded from the nationwide survey because of the previous Japanese definition of fulminant hepatitis.4
Indications for LT
The early determination of the indications for LT was based on the guidelines proposed by the Acute Liver Failure Study Group of Japan in 1996.16 At the time of the onset of grade II or higher severe hepatic encephalopathy, the following 5 variables were evaluated: age (≥45 years), time between the initial symptoms and encephalopathy (>11 days), standardized prothrombin time (<10%), serum bilirubin level (≥18 mg/dL), and direct bilirubin/total bilirubin ratio (<0.67).17 If 2 or more of these criteria were fulfilled, LT was suggested.
The following variables were obtained from the nationwide survey: disease etiology, laboratory data at the presentation of grade II or higher severe encephalopathy, therapies for treating the disease, methods of artificial liver support, and frequency of artificial liver support. The dates for the following events were also obtained: disease onset, jaundice, grade II or higher severe encephalopathy, and LT. From the Japanese Liver Transplantation Society database, the following recipient factors were obtained: outcome at the last follow-up (survival or death), time from LT to the outcome, height and body weight, ALF etiology, and blood type. The following donor factors were also obtained from the Japanese Liver Transplantation Society database: age, sex, height, and body weight; blood type; relationship with the recipient; and graft type (left liver, lateral lobe, right liver, or posterior lobe).
Continuous variables are reported as medians and interquartile ranges, and categorical variables are reported as proportions. Cumulative survival is shown with Kaplan-Meier curves, and differences in survival between groups were analyzed with a log-rank test. Factors associated with patient death were analyzed with a Cox regression analysis. Outcome variables were also analyzed for short-term mortality (≤90 days after LT) and long-term mortality (>90 days after LT). Variables with P < 0.1 in the univariate analysis were included in the multivariate analysis. All recipients were followed until death or September 2010, whichever came first. The median follow-up period was 5.6 years (range = 0.1-12.2 years). All statistical tests were 2-sided, and P < 0.05 was considered significant. These statistical analyses were performed with Stata 12 (Stata, College Station, TX).
Seventy of the 209 patients (34%) had acute ALF, 124 (59%) had subacute ALF, and 15 (7%) had LOHF. The patient characteristics by the disease subtype (acute ALF versus subacute ALF and LOHF) are shown in Table 1. The median age was 40 years (range = 2-70 years), and 19 patients were less than 18 years old. Hepatitis B virus (HBV) was the most common cause of acute ALF (61%), whereas autoimmune hepatitis (14%) and drug allergy–induced hepatitis (14%) were more frequent in patients with subacute ALF or LOHF. The etiology was not identified in 103 patients (49%).
|Characteristic||Total (n = 209)||Acute ALF (n = 70)||Subacute ALF and LOHF (n = 139)|
|Age (years)*||40 (2-70)||40 (2-66)||40 (7-70)|
|Adult: age ≥ 18 years [n (%)]||190 (91)||62 (89)||128 (92)|
|Male sex [n (%)]||79 (38)||27 (39)||52 (37)|
|Etiology [n (%)]|
|—HBV||58 (28)||43 (61)||15 (11)|
|—Viral (non-HBV)||9 (4)||7 (10)||2 (1)|
|—Autoimmune hepatitis||19 (9)||0||19 (14)|
|—Drug allergy–induced hepatitis||20 (10)||1 (1)||19 (14)|
|—Unknown/indeterminate||103 (49)||19 (27)||84 (60)|
|Total bilirubin (mg/dL)†||16.7 (9.1-23.6)||8.5 (6.0-12.3)||19.8 (15.2-26.6)|
|Prothrombin time (%)†||21 (14-29)||15 (9-27)||21 (16-30)|
|International normalized ratio†‡||3.2 (2.2-4.1)||3.3 (2.2-4.0)||3.2 (2.5-4.1)|
|Creatinine (mg/dL)†||0.6 (0.4-0.8)||0.6 (0.4-1.6)||0.6 (0.4-0.7)|
|Model for End-Stage Liver Disease score†‡||25 (18-30)||23 (17-29)||25 (22-30)|
|Naiki score†§||6 (4-7)||4 (3-5)||6 (5-7)|
|Symptoms (days)†∥||17 (8-29)||6 (4-8)||24 (17-36)|
|Jaundice (days)†∥||9 (3-19)||1 (1-3)||14 (9-23)|
|Transplantation (days)†¶||4 (3-9)||3 (2-5)||5 (3-11)|
LT was performed at a median of 4 days (interquartile range = 3-9 days) after the onset of encephalopathy.
The characteristics of the 209 living donors are summarized in Table 2. The median age of the living donors was 37 years (range = 19-64 years). The graft types of the living donors were as follows: left liver (n = 99), lateral lobe (n = 1), right liver (n = 105), and posterior lobe of the right liver (n = 4). One hundred ninety-six of the 209 patients (94%) received an ABO-identical or ABO-compatible graft, and 13 (6%) received an ABO-incompatible graft.
|Age (years)*||37 (19-64)|
|Male sex [n (%)]||123 (59)|
|Blood type [n (%)]|
|Relationship with recipient [n (%)]|
|Body mass index (kg/m2)†||22 (17.2-29.7)|
|Type of graft [n (%)]|
|Right liver||105 (50)|
|Posterior lobe of right liver||4 (2)|
|Left liver||99 (47)|
|Lateral lobe of left liver||1 (<1)|
Therapeutic Modalities Before LT
Plasma exchange was performed for 202 patients (97%). Hemodiafiltration was applied to 154 patients (74%). Lamivudine or entecavir was administered to 45 of the 58 patients (78%) with HBV-related acute hepatic failure. Other therapies included corticosteroids in 131 patients (63%), glucagon-insulin therapy in 61 patients (29%), prostaglandin E1 in 44 patients (21%), anticoagulants in 106 patients (51%), and cyclosporine A in 11 patients (5%).
The 1-, 5-, and 10-year cumulative patient survival rates after LT were 79%, 74%, and 73%. Kaplan-Meier survival curves for ALF subtypes and etiologies, recipient ages, donor ages, graft types, and blood type compatibility are shown in Fig. 1. The patient survival rates of the ALF subgroups were not significantly different: the 5-year patient survival rates were 73% for acute ALF, 73% for subacute ALF, and 86% for LOHF (P = 0.48). Similarly, patient survival was not affected by the graft type (right liver versus left liver; P = 0.21). Survival was poorer for older recipients and for recipients of grafts from ABO-incompatible donors.
Prognostic Factors Associated With Patient Survival After LT
Recipient and donor factors were analyzed for overall mortality, short-term mortality (≤90 days after LT), and long-term mortality (>90 days after LT). The results of univariate and multivariate analyses are shown in Table 3. According to the univariate analysis, recipient age and blood-type incompatibility were significant predictors of poorer short-term mortality, whereas none of the factors were significant for long-term mortality. Other factors, including laboratory data at the day of the disease's onset, treatment modalities, and graft types, were not significant. Factors with P < 0.1 were included in the multivariate analysis. According to the multivariate analysis, recipient age, donor age, and blood-type incompatibility were significant predictors for overall survival. Recipient age was associated with both short- and long-term mortality, whereas donor age was associated with long-term mortality and blood-type incompatibility was associated with short-term mortality.
|Short-Term Survival (≤90 Days)||Long-Term Survival (>90 Days)||Overall Survival|
|Hazard Ratio (95% Confidence Interval)||P Value||Hazard Ratio (95% Confidence Interval)||P Value||Hazard Ratio (95% Confidence Interval)||P Value|
|Recipient age (years)||1.034 (1.008-1.060)||0.008||1.027 (0.999-1.057)||0.06||1.031 (1.012-1.050)||0.001|
|Recipient age: pediatric versus adult||0.311 (0.042-2.284)||0.25||0.386 (0.052-2.869)||0.35||0.345 (0.084-1.416)||0.14|
|Recipient age: ≥40 years versus <40 years||2.441 (1.123-5.302)||0.02||2.139 (0.906-5.048)||0.08||2.302 (1.296-4.090)||0.004|
|Recipient sex: male versus female||0.785 (0.369-1.667)||0.53||0.669 (0.275-1.628)||0.38||0.733 (0.413-1.303)||0.29|
|ALF type: acute versus other||1.484 (0.727-3.029)||0.28||0.603 (0.224-1.626)||0.32||1.052 (0.597-1.852)||0.86|
|Etiology: HBV versus other||1.007 (0.463-2.187)||0.99||0.883 (0.348-2.241)||0.79||0.953 (0.525-1.730)||0.88|
|Coma to LT (days)||0.992 (0.959-1.027)||0.68||1.012 (0.993-1.033)||0.20||1.000 (0.987-1.023)||0.57|
|Donor age (years)||1.013 (0.984-1.042)||0.37||1.032 (0.998-1.067)||0.06||1.021 (0.999-1.043)||0.06|
|Donor age: ≥40 years versus <40 years||1.272 (0.629-2.574)||0.50||1.970 (0.852-4.552)||0.11||1.529 (0.893-2.617)||0.12|
|Donor sex: male versus female||0.757 (0.374-1.533)||0.44||1.071 (0.463-2.474)||0.87||0.876 (0.512-1.499)||0.63|
|Donor body mass index (kg/m2)||1.049 (0.936-1.174)||0.41||0.985 (0.853-1.138)||0.84||1.023 (0.936-1.119)||0.51|
|Donor ABO status: incompatible versus identical or compatible||3.267 (1.254-8.512)||0.02||0.989 (0.133-7.340)||0.99||2.346 (1.003-5.486)||0.049|
|Graft type: right liver versus left liver||0.811 (0.395-1.662)||0.57||0.591 (0.256-1.368)||0.22||0.708 (0.411-1.220)||0.21|
|Recipient age (years)||1.040 (1.014-1.066)||0.002||1.036 (1.006-1.066)||0.02||1.038 (1.019-1.058)||<0.001|
|Donor age (years)||1.027 (0.997-1.057)||0.07||1.043 (1.008-1.078)||0.02||1.034 (1.012-1.057)||0.002|
|Donor ABO status: incompatible versus identical or compatible||4.169 (1.567-11.090)||0.004||1.543 (0.201-11.083)||0.67||3.223 (1.351-7.691)||0.008|
This study reports the long-term outcomes of LDLT for patients with ALF in Japan. The 5-year survival rate was greater than 70%. Most of the patients who were included in the nationwide survey underwent LDLT, and only 3 patients received organs from deceased donors. ABO incompatibility affected short-term mortality, whereas donor age affected long-term mortality. Recipient age was significantly associated with both short- and long-term mortality. No other pretransplant factors significantly affected the prognosis after LDLT.
LT has a major impact on the outcomes of patients with ALF. In comparison with survival rates before the availability of LT (15%-20%), posttransplant survival is remarkably better today (>65%).5, 6, 18-20 This study also shows that LDLT is an effective treatment for patients with ALF in Japan; the reported transplantation-free survival rate is 40%.4 To evaluate the impact of LT on the outcomes of all patients with ALF, however, all eligible candidates should be followed. LT is not applicable to all patients because some patients may spontaneously recover without lifelong immunosuppressive therapy. In contrast, if patients are referred too late to the transplant center, some will either die or develop contraindications while they are undergoing the evaluation and awaiting LT.
Matsui et al.11 reviewed 96 patients with ALF who were evaluated at the University of Tokyo, and 69 were eligible for LT. Thirty-six of these 69 patients with a potential living donor eventually underwent LDLT. Only 1 of the remaining 33 patients underwent DDLT. Without a living donor, the chance of transplant survival was extremely low. Table 4 summarizes outcomes after the evaluation for LT. Although the probability of patients undergoing DDLT in the United States and Europe is high (21%-71%), less than 10% of listed patients with ALF in Asia eventually receive a deceased donor organ. Wait-list mortality is as high as 60%. Liu et al.13 analyzed the effect of having a potential living donor during the evaluation for LT, and they found that the wait-list mortality rate for patients with potential living donors was lower than the rate for patients without potential living donors. Thus, the LDLT assessment for patients with ALF has a major impact on patient outcomes. The use of a living donor in an emergency setting, however, is often hampered by insufficient time for the donor to ponder his or her spontaneous willingness or risk or for the doctors to evaluate the medical and ethical issues. Extra caution must be taken in such high-urgency situations because of the possibility of donor coercion. The risks and benefits of both LDLT and DDLT should be communicated to all patients and family members at the beginning of the evaluation for LT. If there are potential donors, their spontaneous willingness should be confirmed by nonsurgical specialists such as transplantation coordinators or psychiatrists.9, 24
|Study/Location||ALF (n)||Criteria Met for LT (n)||Potential Living Donors (n)||DDLT [n (%)]||LDLT [n (%)]||Survival After LT [n/N (%)]||Death on Waiting List [n/N (%)]||Survival on Waiting List [n/N (%)]|
|Castells et al.21 (1993)/Spain||62||49||NA||28 (57)||0||22/28 (79)||4/49 (8)||1/49 (2)|
|Shakil et al.19 (1997)/Pittsburgh, PA||NA||164||NA||80 (49)||0||53/80 (66)||60/164 (37)||19/164 (12)|
|Ostapowicz et al.2 (2002)/United States||308||135||NA||89 (66)||0||NA||30/135 (22)||NA|
|Liu et al.13 (2002)/Hong Kong||116*||50||34||4 (8)||16 (32)||18/20 (90)||30/50 (60)||0|
|Escorsell et al.22 (2007)/Spain||267||161||NA||150 (93)||0||104/150 (69)||11/161 (7)||0|
|Matsui et al.11 (2008)/Tokyo, Japan||96||69||36||1 (2)||36 (52)||94†||21/69 (30)||NA|
|Campsen et al.23 (2008)/United States||NA||NA||14||3 (21)||10 (71)||9/13 (69)||0||1/14 (7)|
|Ikegami et al.12 (2008)/Japan||NA||NA||42||NA||42 (100)||80†||NA||NA|
|Park et al.9 (2010)/Seoul, Korea||110||99||48||4 (4)||40 (40)||37/44 (84)||45/99 (45)||10/99 (10)|
Because of the rapid progression of the disease's severity, ALF should be treated intensively, and if necessary, LT should be performed promptly. In countries in which DDLT is actively performed, the median time from listing to transplantation ranges from 1 to 3 days. Reports from Asia, however, have noted that deceased donor organs become available several days to weeks after listing.13 If donor organs do not become available, death without LT occurs at a median of 7 days after the diagnosis.9, 13 In this study, 3 DDLT cases were removed from the analysis; DDLT was performed 2 to 10 weeks after the diagnosis. We speculate that all the other LT candidates died without transplantation before an organ became available. On the other hand, LDLT in this study was performed at a median of 4 days after the onset of encephalopathy. This time interval is similar to those reported for Western countries.
Therefore, indications and eligibility should be assessed as early as possible. Prognostic scoring systems have been suggested (eg, the Clichy criteria,25 the King's College Hospital criteria,26 decreased factor V levels,27 the grade of encephalopathy on admission,28 the severity of systemic inflammatory response syndrome, and serial computed tomography volumetry of the liver29, 30). A longer interval between jaundice and the onset of encephalopathy is a reported indicator for poorer survival.26, 28 In this study, the guidelines proposed by the Acute Liver Failure Study Group of Japan were assumed to be used in most of the cases. The criteria included the patient's age, the interval from the initial symptoms to the onset of encephalopathy, the prothrombin time, the serum bilirubin level, and the direct bilirubin/total bilirubin concentration ratio. More accurate criteria were recently proposed by Naiki et al.,31 who included 4 variables from previous guidelines and 2 additional variables (the interval from the initial symptoms to the onset of encephalopathy, the prothrombin time, the serum bilirubin level, the direct bilirubin/total bilirubin concentration ratio, the platelet count, and liver atrophy). This new prognostic scoring system was derived from data for nontransplant patients enrolled in the nationwide survey, and the sensitivity and specificity for predicting mortality were 0.75 and 0.80, respectively. Eighty-four percent of the patients with a score equal to or greater than 5 died without LT. In this study, the score was calculated for 177 cases, and the median score was 6 (interquartile range = 4-7). Although a direct comparison was not made between nontransplant and transplant patients, the summary of this score indicates that our studied population was at higher risk of death without LT.
As for the etiologies of ALF, HBV was most common, and nearly half of the patients had ALF of an unidentified etiology in this study. The etiologies of ALF, however, have been reported to differ significantly according to the location. Acetaminophen is the leading cause of ALF in the United States and United Kingdom,5, 6 whereas viral hepatitis is the leading cause in Spain,22 Korea,9 Hong Kong,10 and Japan.15 Patients with ALF induced by acetaminophen toxicity have better transplantation-free survival, and their outcomes should be assessed separately. Acetaminophen-induced ALF patients and shock liver patients were not enrolled in this study because these diseases and metabolic liver diseases were excluded from the diagnostic criteria for the nationwide survey in Japan. In this study, we found no ALF-specific pretransplant factors associated with posttransplant survival. ABO incompatibility, donor age, and recipient age significantly affected short- and/or long-term survival after LT. These factors, however, are also known to affect the outcomes after LT for any disease. Roberts et al.20 analyzed 17,044 samples from the United Network for Organ Sharing database to find factors affecting the posttransplant prognosis, and advanced recipient or donor age, liver disease severity, and impaired renal function were associated with poorer outcomes after LT in the entire sample. In their analysis, the effect of disease-specific mortality was stronger than the effects of the other prognosticators. ALF patients, for example, had the highest risk of death in the short term after LT, and patients with other chronic diseases had a higher risk of death over the long term. Among ALF patients, Devlin et al.32 failed to find pretransplant factors predictive of posttransplant mortality. Bernal et al. found that outcomes after transplantation were associated with the era of LT, a recipient age > 45 years, vasopressor requirements, and the use of high-risk grafts.7
In conclusion, this report describes long-term survival after LT for ALF. The 5-year survival rate was greater than 70%. The outcome was not affected by the etiology of ALF or other factors related to the disease or treatment, but it was affected by the ages of the patient and the donor. To assess the overall impact on survival for all patients with ALF, prospective follow-up studies are necessary. The proportion of DDLT cases was only 1%. Increasing the deceased donor pool might be an urgent necessity.
- 9Emergency adult-to-adult living-donor liver transplantation for acute liver failure in a hepatitis B virus endemic area. Hepatology 2010; 51: 903-911., , , , , , et al.
- 14Etiologies of acute liver failure: location, location, location! Liver Transpl 2007; 13: 1362-1363., .
- 16Re-evaluation of the guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. Hepatol Res 2008; 38: 970-979., , , , .
- 23for Adult-to-Adult Living Donor Liver Transplantation Cohort Study Group. Outcomes of living donor liver transplantation for acute liver failure: the adult-to-adult living donor liver transplantation cohort study. Liver Transpl 2008; 14: 1273-1280., , , , , , et al.;
- 31for Intractable Hepato-Biliary Disease Study Group supported by the Ministry of Health, Labor, and Welfare of Japan. Novel scoring system as a useful model to predict the outcome of patients with acute liver failure: application to indication criteria for liver transplantation. Hepatol Res 2012; 42: 68-75., , , , , , et al.;