Secondary Logo

Journal Logo

Marked Decrease in Urgent Listing for Liver Transplantation Over Time

Evolution of Characteristics and Outcomes of Status-1 Liver Transplantation

Wong, Linda L. MD1,2; Truong, Hung P. MD1; Seto, Todd MD3; Lacar, Lea BS2; Naugler, Willscott E. MD4

doi: 10.1097/TP.0000000000001967
Original Clinical Science—Liver
Free
SDC
Social Media Collection

Background Approximately 5% of liver transplants annually are performed urgently with “status-1” designation. This study aims to determine if the demand, characteristics, and outcome for status-1 liver transplantation has changed over time.

Methods We used the Scientific Registry of Transplant Patients (2003-2015) to characterize 2352 adult patients who underwent 2408 status-1 liver transplants and compared them between Era1 (2003-6/2009) and Era2 (7/2009-2015).

Results Overall, there were fewer liver transplants performed with the status-1 designation in Era2 than Era1 (1099 vs 1309). Although the number of urgent liver transplants was relatively constant with successive years, the proportion transplanted with status-1 designation decreased markedly over time. Era2 patients were older (43.2 years vs 41.7 years, P = 0.01) and less likely be ABO-incompatible (1.1% vs 2.4%, P = 0.01) or retransplant (77 vs 124, P = 0.03). In terms of disease etiology, the largest group was “acute liver failure (ALF), nonspecified” (43.4%). There was no difference in proportion with drug-induced liver injury (DILI), but the subset of herbal/dietary supplements increased in Era2 (1.3% vs 0.46%, P = 0.04). Survival was increased in Era2 in the overall cohort and for patients with autoimmune disease (P < 0.05), despite longer waiting times for this etiology (186 days vs 149 days). DILI or nonspecified ALF had shorter waiting times, and 90% were transplanted within 7 days.

Conclusions Liver transplantation for the most urgent indications (status-1) is decreasing while survival remains excellent. Fewer incidences of ALF are classified as indeterminate, mostly as a result of increasing awareness of autoimmune hepatitis and DILI as causes of the syndrome.

Based on the Scientific Registry of Transplant Patients (2003-2015), the authors assess changes in demand, characteristics, and outcomes for status-1 liver transplantation over time showing a decrease in these cases as well as lower mean waiting time, fewer ABO-incompatible transplants, together with improved survival.

1 Department of Surgery, John A. Burns School of Medicine, University of Hawaii, Honolulu, HI.

2 Transplant Center, Queens Medical Center, Honolulu, HI.

3 Center for Outcomes Research and Evaluation, Queens Medical Center, Honolulu, HI.

4 Department of Medicine/Gastroenterology and Hepatology, Oregon Health and Science University, Portland, OR.

Received 27 May 2017. Revision received 2 September 2017.

Accepted 11 September 2017.

The authors declare no funding or conflicts of interest.

L.L.W. participated in research design and writing of the article. H.P.T. participated in data collection and analysis. T.S. participated in statistical analysis and writing of the article. L.L. participated in data collection and analysis. W.E.N. participated in critical review and writing of the article.

Correspondence: Linda L. Wong, MD, 550S, Suite 403, Beretania St, Honolulu, HI 96813. (hepatoma@aol.com).

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

The demand for liver transplantation (LT) continues to outpace the supply of donor livers and the transplant community struggles to find the optimal allocation of this limited resource. Current Model for End-Stage Liver Disease (MELD)-based allocation focuses on “sickest first” and “waitlist mortality,” whereas transplant center performance is based on patient and graft survivals. Individual centers must manage these metrics with cost and reimbursement and find some way to remain viable. Because of the limited liver supply, patients are transplanted with increasingly higher MELD scores and long-term survival in those with the highest MELD scores can be affected.1-5 Much is being done to address this, but while waiting for more definitive answers, the transplant community should also optimize use of LT for patients listed as status-1.

Patients who are transplanted in the status-1 category have the highest priority and the requirement as outlined in the United Network for Organ Sharing (UNOS) policy is that these patients have “a life expectancy without liver transplant of less than 7 days.” The UNOS policy delineates very specific requirements to qualify for this category, including acute liver failure (ALF) in the absence of preexisting liver disease, anhepatic, acutely decompensated Wilson disease, primary nonfunction or hepatic artery thrombosis within 7 days of a previous LT. Patients with failing previous LT allografts must meet certain laboratory criteria. Patient with ALF must have encephalopathy within 56 days of the first sign of liver disease and have at least 1 of the following: ventilator dependence, requirement for dialysis or a prothrombin time international normalized ratio (INR) more than 2.0.6 Status-1 may also be conferred on patients with acute decompensation of autoimmune hepatitis (AIH) or hepatitis B virus if the presentation is fulminant. Strict documentation is necessary and audits by UNOS and Centers for Medicare and Medicaid Services are performed to assure that transplant centers are compliant with this policy.

This study was performed to characterize patients in the United States who received LT under the status-1 category over 2 eras. Ultimately, we aimed to identify changes in demographics, disease etiology and outcome over time, and establish potential areas to improve transplantation for this category. Decreasing the demand for status-1 LT will ultimately increase liver availability for those requiring transplant under the MELD scheme.

Back to Top | Article Outline

MATERIALS AND METHODS

We accessed the Scientific Registry of Transplant Recipients (SRTR) database for all LT performed in the category of status-1 during the 13-year period between January 1, 2003, and December 31, 2015. This national database of transplant recipient statistics has been maintained by hospitals and organ procurement organizations across the United States since 1987. Institutional research board approval was obtained by our medical center to conduct this study. General information on all patients who underwent LT and patients who were listed with the status-1 designation by year were obtained from the Organ Procurement and Transplantation Network (OPTN).7

The cohort of patients in this study was transplanted with the primary diagnosis of “acute hepatic necrosis.” The OPTN defines three subcategories in the primary diagnosis including “acute hepatic necrosis: drug induced,” “acute hepatic necrosis: etiology unknown,” and “acute hepatic necrosis: other.” In the last category of “other,” this included acute viral infection, fulminant AIH. The data also included a column in which a more detailed description of the diagnosis was allowed.

In the final cohort, we included only adults, 18 years or older who received either a living or deceased donor. Demographic information available included: recipient age, ethnicity, sex, and ABO blood type. Donor information included age, ethnicity, sex, ABO blood type, and type of donor (living vs deceased). Transplant date, waiting time, graft status, and patient status were also recorded. Between the categories of acute hepatic necrosis, we were able to reclassify the etiology of liver failure into the following: drug-induced liver injury (DILI), viral, AIH, retransplantation, chronic problems, metabolic disease (including Wilson disease), other, and nonspecified ALF. For unclear reasons, there were patients who underwent status-1 LT with a more detailed diagnosis of nonalcoholic steatosis, hepatitis C cirrhosis, alcoholic cirrhosis, and polycystic liver disease, and these were categorized as “chronic problems.” For the DILI etiology, we subcategorized the drugs into: acetaminophen, antibiotics, antituberculous medications, herbal/dietary supplements (HDS), and other. The “other” group included known etiologies, such as mushroom poisoning, heatstroke, postpartum, vascular and postsurgical catastrophes. “Nonspecified ALF” included all of the other cases in which a liver transplant was performed as a status-1, but there was no additional information provided that could categorize the etiology.

With this information, we were able to determine transplants that were done with ABO incompatibility and survival (1 and 3 years). Waiting time was expressed as mean, median, and the percentage of patients with waiting time 7 days or less. Detailed information on retransplants including time between transplants and etiology for primary nonfunction was also noted.

We divided the cohort into 2 groups of equal duration for comparison: Era1 (January 1, 2003 thru June 30, 2009) and Era2 (July 1, 2009 thru December 31, 2015). The main outcome measures included mean/median waiting time, percentage of those with waiting time 7 days or less, and survival at 1, 3, and 5 years. These data were compared between the 2 eras for the entire cohort and the subcategories of autoimmune, DILI, nonspecified ALF, retransplant, and all others.

Back to Top | Article Outline

Statistics

We used descriptive statistics to describe our study population, and unpaired t-tests, Fisher exact test and the Wilcoxon rank-sum test as appropriate to compare demographic and clinical characteristics between Era1 and Era2 patients. We performed separate analyses for the entire study cohort and for each subcategory of liver failure. We also graphed the survival of Era1 and Era2 patients using Kaplan-Meier estimates, and compared the 2 groups using the log-rank test. To account for baseline differences in demographics and clinical characteristics, we screened for potential confounders by performing univariate comparisons and included any variable associated with mortality at P value less than 0.25 into a proportional hazards model. From this, we calculated the hazard ratio (HR) and 95% confidence interval (95% CI) for the risk of death for the entire cohort. We performed additional estimates for the 5 largest subtypes of liver disease: autoimmune (n = 367), DILI (n = 626), nonspecified fulminant hepatic failure (n = 1046), retransplant (n = 201), and all others (n = 369). All analyses were performed using Stata 9.0 (College Station, TX) and SAS 9.4 (Carey, NC).

Back to Top | Article Outline

RESULTS

Overall Cohort

Between January 2003 and December 2015, a total of 3195 liver transplants were performed as UNOS status-1. Of these, 787 were pediatric cases and were excluded from this study. Fifty-six patients who were initially listed at status-1 underwent retransplant also at status-1; thus of the 2408 transplant procedures, there were 2352 unique patients. Male to female ratio was 791:1617 with mean age 42.4 (SD, 14.37) years. Ethnic distribution was as follows: white, 60.2%; black, 19.4%; Hispanic, 12.3%; Asian, 5.9%; American Indian/Native Alaska, 1.0%; and Native Hawaiian/Pacific Islander, 0.17% (Table 1).

TABLE 1

TABLE 1

In the entire cohort, the etiology for UNOS status-1 listing included: nonspecified ALF (43.4%), DILI (26%), autoimmune disease (15.2%), retransplant (8.3%), viral (2.9%), other (2.0%), chronic problem (1.6%), and metabolic (0.4%).

Overall, the mean waiting time was 49.7 (SD, 234.3) days with a range of 0 to 4032 days and median of 3.0 days. Most of the patients were transplanted within 7 days (75.9%), and only a small proportion (1.8%) received an ABO-incompatible donor. Mean donor age was 38 years (SD, 16.7 years) and 56.6% were men (Table 1). Graft failure occurred in 331 (13.8%) and 1946 (80.8%) had a functioning graft. Information on current graft status was not available in 131 (5.4%) patients. In terms of patient survival, 1567 (65.1%) were living, 551 (22.9%) had died, 161 (6.7%) underwent retransplantation, and 129 (5.4%) were lost to follow-up. Of the deaths in the cohort, 67.7% died with a functioning graft. Overall 1-, 3-, and 5-year survivals were 85.3%, 78.0%, and 71.9%, respectively.

There was a clear trend of decreasing numbers of patients listed with the status-1 designation with each successive year as indicated in Figure 1. There are also higher proportions of listed status-1 patients who undergo LT with each successive year and a trend to fewer retransplants in the more recent years. Figure 2 shows that the proportion of all liver transplants that are done with status-1 designation is relatively stable over time.

FIGURE 1

FIGURE 1

FIGURE 2

FIGURE 2

Back to Top | Article Outline

Comparison Between Era1 (2003-2009) and Era2 (2009-2015)

Recipients in Era2 were statistically older (43.2 years vs 41.7 years, P = 0.03), but there was no difference in the sex or ethnicity distribution compared with Era1. There were significant differences in the distribution of the disease etiology. In the latter era a greater proportion of patients received a liver transplant due to AIH, while a smaller proportion was transplanted for nonspecified ALF or retransplantation (Table 2).

TABLE 2

TABLE 2

The mean waiting time significantly decreased in Era2 compared with Era1 (41.4 days vs 56.7 days, P = 0.005) but there was no difference in the proportion who received a liver within 7 days. These data are confusing because 76% of patients in the entire cohort were transplanted within 7 days, and likely reflect differences in a relatively small group of patients with AIH who were listed with chronic disease but changed to a fulminant course at some point. Such patients would be noted as having long waitlist times, though the actual amount of time while in status-1 may have been short. Also, in the latter period, patients with AIH were more likely to be transplanted within 7 days compared with the previous era.

Donors were significantly younger and there were minor differences in ethnicity in the later era. Fewer patients in Era2 received an ABO-incompatible graft. Overall survival was significantly better for patients in Era2 compared with patients in Era1 (see Figure 3). After controlling for potential confounders, the risk of death for patients in Era1 was significantly higher than for patients in Era2 (HR, 1.28; 95% CI, 1.06-1.55). The lower 5-year survival rate from the latter period is likely skewed, as 5-year data was not available for most of that cohort. Indeed, all other measures of survival (1- and 3-year survivals, overall percentage alive, and retransplants) were significantly improved in the latter era (Supplemental material, SDC,http://links.lww.com/TP/B492).

FIGURE 3

FIGURE 3

Back to Top | Article Outline

Subgroups of Patients by Cause of Liver Failure

AIH

There were 367 cases of AIH (15.2% of total cases) and of the specific disease etiology groups, this was the only group that had an increase in the number of cases over time (219 vs 148 in Era2 vs Era1) and a higher proportion (19.9% vs 11.3% in Era2 vs Era1) Survival was significantly better for Era2 than for Era1 patients on univariate analysis, (P = 0.05), with a nonsignificant trend favoring Era2 patients after adjusting for potential confounders (HR, 1.72; 95% CI, 0.98-3.01) (Figure 3). Mean waiting times and transplant within 7 days did not differ between the eras. However, waiting times were long compared to other disease etiology groups (Table 3).

TABLE 3

TABLE 3

Back to Top | Article Outline

Drug-Induced Liver Disease

There were 626 cases of DILI which comprised 26% of the entire cohort. The drugs responsible included: acetaminophen (n = 300), antibiotics (n = 30), antituberculous medications (n = 30), HDS (n = 20), antiepileptic medications (n = 15), nonsteroidal anti-inflammatory drugs (n = 12), statins (n = 10), antivirals for HIV therapy (n = 4), antihypertensive medication (n = 4), disulfiram (n = 4), propylthiouracil (n = 4), methotrexate (n = 2), anesthetics (n = 2), amiodarone (n = 2), and narcotics (n = 2). Seventeen cases were due to multiple drugs, 14 due to “other drug,” and 154 cases did not list a specific drug. There was no difference in the proportion of cases that were DILI between eras (341 cases in Era1 vs 285 cases in Era2). Acetaminophen was the leading cause of non-HDS DILI in both Era1(n = 155, 11.8%) and Era2 (n = 145, 13.2%). HDS were the cause of DILI in 6 cases in Era1 and 14 cases in Era2. (P = 0.04). There was no significant difference in survival in DILI patients between Era2 and Era1 patients (adjusted HR, 1.37; 95% CI, 0.94-2.01) (Figure 3).

Back to Top | Article Outline

Nonspecified Fulminant Hepatic Failure

The nonspecified ALF group comprised the largest group at 1046 patients (43.4%) however, there were fewer cases and a smaller proportion of these patients in the later era. The mean waiting time improved significantly in Era2 (12.1 days vs 47.7 days, P = 0.001), and more patients were transplanted within 7 days (85.2% vs 75.7%, P < 0.001). Survival among Era2 and Era1 patients was not significant on univariate (P = 0.31) or adjusted analysis (HR, 1.13; 95% CI, 0.83-1.54) (Figure 3).

Back to Top | Article Outline

Retransplants

In the entire cohort, 201 retransplants occurred in 192 patients. Nine patients received 3 transplants each. Of the 201 retransplants, 145 patients were initially transplanted for chronic reasons with MELD allocation. Reasons for retransplantation included: 76 hepatic artery thrombosis, 52 primary nonfunction and 3 with severe acute rejection. The remaining 14 patients had other reasons including chronic issues, nonspecific ALF, and ischemic cholangiopathy. Forty-seven patients were initially transplanted as a status-1 and required retransplant, again at status-1. Patients who underwent retransplant had the worst 1- and 3-year survival compared with other etiologies for status-1 transplantation. There was no significant difference in survival between Era2 and Era1 patients (Figure 3).

Back to Top | Article Outline

Viral, Chronic Disease, Metabolic, Other

Status-1 liver transplant for viral etiologies comprised 2.9% of the cohort. Of these 70 patients, 44 patients had fulminant hepatitis B and 16 had an unknown viral etiology. Other viral illnesses included: 4 herpes virus, 3 hepatitis E, 2 hepatitis C/human immunodeficiency virus, 2 and 1 cytomegalovirus infection. In comparing eras, there was no difference in 1-, 3-, and 5-year survival, mean waiting times or proportion waiting less than 7 days.

Thirty-nine (1.6%) patients had chronic diseases listed as the etiology for liver transplant that received a status-1 liver transplant. Ten patients had hepatitis C cirrhosis and 10 had fat-related liver problem listed as either “fatty liver,” “nonalcoholic steatohepatitis,” or “steatosis.” Eight patients had “end-stage liver disease” without additional details. Two patients had an acute alcohol related liver failure. Other diagnosis included polycystic liver disease, family hypercholesterolemia, Eagle-Barrett syndrome, primary sclerosing cholangitis, and familial adenomatous polyposis. Waiting times were long in this group, and there was limited detail to determine the reason for status-1 LT.

Ten patients had metabolic problems as a reason for status-1 LT including 9 with Wilson disease and 1 with hyperhomocysteinuria. Finally, there were 49 patients who had various etiologies that could not be combined into a single large group. Sixteen patients required LT for an acute vascular problem including portal vein thrombosis (n = 13) and Budd-Chiari syndrome (n = 3). Thirteen patients had ALF related to pregnancy/postpartum (acute fatty liver [n = 6], hemolysis/elevated liver enzymes/low platelet syndrome [n = 5], and nonspecified ALF [n = 2]). Eight patients had liver failure as a result of a surgical catastrophe or traumatic injury, including 4 liver resections, 3 ruptured livers due to trauma/benign tumor, 1 cholecystectomy, and 1 iatrogenic arterial injury. The remaining cases included mushroom toxicity (n = 5), heatstroke (n = 3), and 1 case of epitheloid angiosarcoma. Survival rates for the category of “all others” were excellent and unchanged between the eras, although the heterogeneity of the cases may be too small to draw conclusions. Mean waiting time for transplant improved in the “other” group in Era2 (4.0 days vs 56.2 days for Era1, P = 0.05); however, the proportion who waited 7 days or less was similar.

Back to Top | Article Outline

DISCUSSION

Use of the status-1 designation for urgent LT comprises a small but important fraction of patients receiving LT annually. Status-1 patients have a high mortality on the waiting list and potentially poor outcome if transplantation is not done in a timely manner. Despite these challenges, this study demonstrated that outcome is excellent and overall survival from status-1 LT has improved over time. With time, there have been fewer cases of status-1 liver transplant, fewer retransplants, lower mean waiting time and fewer ABO-incompatible transplants. About 75% to 80% of these patients were able to receive an LT within 7 days.

Just which patients should be considered for urgent LT is becoming increasingly important as the demand for LT increases and patients get sicker while waiting for suitable donors.8 Indeed, recent studies show that patients with end-stage liver disease and MELD scores greater than 35 have higher waitlist mortality compared to patients qualifying for status-1 (ALF and urgent retransplants).9,10 Status-1 has been traditionally reserved for the sickest patients whose death is thought to be imminent without urgent LT. This study demonstrated a marked decrease in the number of patients listed with the status-1 designation over the last 12 years. The overall number of urgent LT was relatively constant with successive years, but has decreased as a proportion of the overall number of LT. What are the causes for these changes? Almost certainly, one of the major reasons is an overall improvement in the care of patients with ALF.11,12 Transplant-free survival for patients with ALF has increased significantly over the last decade, probably due to better clinical understanding of the syndrome and improved critical care management. These changes have occurred in the face of an unchanging incidence of ALF.12 Data from the 2015 annual OPTN/SRTR statistics on liver transplant noted that the pretransplant mortality rates for ALF have remained stable at 18% to 20% over the same period.13 One can conclude from this data in combination with ours that many patients were listed, not transplanted, and recovered without the need for transplant, especially in the earlier years. Similarly, the significant decline in status-1 listings over time in face of stable waitlist mortality rate suggests that the transplant community has become more proficient at identifying patients actually needing transplant for the most urgent indications. Although it is unclear from the data which etiologies of ALF have accounted for the decrease in listings, the likely etiology is acetaminophen overdose, given significant advances in identification, treatment, and intensive care unit care for these patients.

Our study also demonstrated a decrease in the need for urgent retransplant and better survival in recent years. Improved surgical techniques and vigilant ultrasound monitoring to detect early vascular problems may be contributing to early recognition and timely surgical rescue.14,15 More recently, nonoperative endovascular techniques may allow salvage of hepatic artery stenosis/thrombosis to avoid the need for retransplant.16-21 Use of donors after circulatory death may have more ischemic cholangiopathy, but the need for urgent retransplant in this group may not be different from a standard donor. Allen et al reviewed 950 cases of retransplantation in the SRTR and this showed only 0.7% of donors after circulatory death transplants compared to 3.8% of standard criteria donor required status-1 retransplant.22 Although the exact reasons for decreased urgent retransplant is beyond the scope of this study, appropriate donor selection and recipient management of vascular issues likely have contributed.

AIH is one of a few liver diseases that may initially present as a chronic condition but later transition to ALF. Nonfulminant AIH can progress to cirrhosis and about 10% of all patients with AIH will eventually need liver transplant.23 Because AIH may present as a chronic and relatively stable condition, these patients are frequently placed on the transplant list electively, only later to have an acute flare and be reclassified as ALF (and given the status-1 designation). Data from this study support this notion, with long mean waiting time likely reflecting time on the list while in a chronic phase of the disease. In the more recent period, more patients received urgent LT for AIH compared with the earlier period. This “increase” in urgent LT for AIH likely reflects improved recognition of AIH as the cause of ALF. Indeed, the most significant decrease in etiology of liver disease receiving urgent LT was “nonspecified ALF,” probably because many of these patients were more promptly diagnosed with AIH in more recent years. This is also supported by the changes in mean waiting time for nonspecified ALF (decrease) and AIH (increase) over time, likely because some of the patients in the nonspecified ALF in the earlier era were actually AIH (and correctly identified in the recent era) In our series, patients with AIH had longer waiting times compared to the overall cohort (49.7 days) and only 42-50% waited less than 7 days. These patients may have initially been listed with the MELD scheme but then changed to status-1 after rapid progression of disease but the available data could not determine this exactly. Regardless of these waiting times, 1-, 3-, and 5-year survival have remained excellent over time and similar to multiple reported series.24-26

Our study represents the largest series of DILI requiring status-1 liver transplant and an update of previous analyses of the SRTR in 2004 and 2009.27,28 The proportion of patients receiving urgent LT for DILI was unchanged over the periods we studied (about 25% of urgent LT), and the relative proportions of acetaminophen and nonacetaminophen as indications for urgent LT were also stable (approximately 50% each). These numbers are remarkable as the incidence of acetaminophen-related hepatotoxicity is increasing in the United States and Europe.29,30 That there are not increasing numbers of urgent LT for acetaminophen toxicity likely speaks to the higher transplant-free survival for these patients compared to nonacetaminophen etiologies as well as increasing numbers of patients with acetaminophen toxicity and psychiatric contraindications to LT.31 Patients undergoing urgent LT for acetaminophen continue to enjoy excellent 1-, 3-, and 5-year posttransplant survival rates, but there has been a striking decrease in 5-year survival for nonacetaminophen DILI patients for unclear reasons.

Other nonacetaminophen drugs such as HDS have become more culpable in recent years.32,33 Specifically there were 6 cases HDS in Era1 compared to 14 cases in Era2 (P = 0.04). HDS will likely continue to impact the demand for liver transplant as dietary supplements constitute a US $29 billion industry and more than half of the US population takes some type of supplement.34 The National Medicine Comprehensive Database has more than 54,000 dietary supplement products of which only a third have some level of safety and effectiveness, while 12% have known safety concerns.35 The Drug-Induced Liver Injury Network (DILIN), which prospectively studies hepatotoxicity, noted that 15.5% of the patients enrolled had injury from an HDS and this proportion increased from 7% to 20% during the 10 years studied.36 One-, 3-, and 5-year survival for DILI are excellent and unchanged over time and similar to that reported previously.28 Early survival in the nonacetaminophen DILI is good; however, the 5-year survival is significantly worse in the later era. Newer drugs including HDS may impact the need and survival for status-1 LT and will need to be monitored closely in the future.

Limitations of the study reflect limitations of the SRTR database. A significant number of status-1 cases (>40%) were classified as having a “nonspecified” etiology for ALF, which may skew the results. The data show that more recently the transplant community has been better at reporting specific diagnoses, but many cases remain without identified etiology. Although the number of nonspecified ALF is likely to further decrease in the future, there will always be a significant proportion of ALF with unrecognized cause. Increasing recognition of DILI and AIH will hopefully decrease some uncertainty in the future. Second, the large number of patients with prolonged waiting times as status-1 highlights the limitations of this retrospective database. More detailed data as to whether patients were waiting in a MELD-based status before conversion to status-1 would be necessary to truly make conclusions about waiting time. Finally, the SRTR includes only patients listed for transplant—not the entire population of ALF patients for whom liver transplant might be indicated. This limitation prevents true assessment for the marked decrease in status-1 listing over time. Future studies using ALF/acute liver injury databases in conjunction with SRTR data are clearly warranted.

Despite these limitations, our study showed that status-1 LT continues to yield good survival, but fewer transplants and retransplants were performed more recently likely due to improvements in management of patients with ALF. Mean waiting times are improved and 75% to 80% of those who underwent liver transplant were able to obtain a liver within a week. Transplant centers are improving in their assignment of a specific diagnosis but continued efforts should be made to identify etiologies for fulminant failure and report these, so we can educate the public and medical community on potential hepatotoxic agents and preventable etiologies. Minimizing the need for status-1 liver transplant will ultimately allow more donor livers to be available for chronic, nonpreventable illnesses.

Back to Top | Article Outline

ACKNOWLEDGMENTS

The authors would like to thank Guang Xiang Zhang for his statistical assistance and expertise.

Back to Top | Article Outline

REFERENCES

1. Nekrasov V, Matsuoka L, Rauf M, et al. National outcomes of liver transplantation for model for end-stage liver disease score ≥40: the impact of share 35. Am J Transplant. 2016;16:2912–2924.
2. Halazun KJ, Mathur AK, Rana AA, et al. One size does not fit all—regional variation in the impact of the share 35 liver allocation policy. Am J Transplant. 2016;16:137–142.
3. Taniguchi M. Liver transplantation in the MELD era—analysis of the OPTN/UNOS registry. Clin Transpl. 2012:41–65.
4. Ravaioli M, Grazi GL, Dazzi A, et al. Survival benefit after liver transplantation: a single European center experience. Transplantation. 2009;88:826–834.
5. Habib S, Berk B, Chang CC, et al. MELD and prediction of post-liver transplantation survival. Liver Transpl. 2006;12:440–447.
6. OPTN Policies—Organ Procurement and Transplantation, Policy 9: Allocations of Liver and Liver-Intestine. at www.optn.transplant.hrsa.gov/media/1200/optn_policies. Accessed October 29, 2016.
7. Organ Procurement and Transplantation Network, National Data. at https://optn.transplant.hrsa.gov/data/view-data-reports/national-data/#. Accessed January 4, 2017.
8. Northrup PG, Intagliata NM, Sha NL, et al. Excellent Mortality on the Liver Transplant Waiting list: unintended policy consequences and model for end-stage liver disease (MELD) inflation. Hepatology. 2015;61:285–291.
9. Ahn J, Bhuket T, Mosadeghi S, et al. End-stage liver disease patients with MELD >40 have higher waitlist mortality compared to status 1A patients. Hepatol Int. 2016;10:838–846.
10. Sharma P, Schaubel DE, Gong Q, et al. End-stage liver disease candidates at the highest model for end-stage liver disease scores have higher wait-list mortality than status-1A candidates. Hepatology. 2012;55:192–198.
11. Donnelly MC, Davidson JS, Martin K, et al. Acute liver failure in Scotland: changes in aetiology and outcomes over time (the Scottish Look-Back Study). Aliment Pharmacol Ther. 2017;45:833–843.
12. Reuben A, Tillman H, Fontana RJ, et al. Outcomes in adults with acute liver failure between 1998 and 2013: an observational cohort study. Ann Intern Med. 2016;164:724–732.
13. Kim WR, Lake JR, Smith JM, et al. OPTN/SRTR 2015 Annual Data Report: liver. Am J Transplant. 2017;17:174–251.
14. García-Criado A, Gilabert R, Nicolau C, et al. Early detection of hepatic artery thrombosis after LT by Doppler ultrasonography: prognostic implications. J Ultrasound Med. 2001;20:51–58.
15. Sheiner PA, Varma CV, Guarrera JV, et al. Selective revascularization of hepatic artery thromboses after liver transplantation improves patient and graft survival. Transplantation. 1997;64:1295–1299.
16. Rajakannu M, Awad S, Ciacio O, et al. Intention-to-treat analysis of percutaneous endovascular treatment of hepatic artery stenosis after orthotopic liver transplantation. Liver Transpl. 2016;22:923–933.
17. Le L, Terral W, Zea N, et al. Primary stent placement for hepatic artery stenosis after liver transplantation. J Vasc Surg. 2015;62:704–709.
18. Grodzicki M, Anysz-Grodzicka A, Remiszewski P, et al. Treatment of early hepatic artery thrombosis after liver transplantation. Transplant Proc. 2011;43:3039–3042.
19. Sabri SS, Saad WE, Schmitt TM, et al. Endovascular therapy for hepatic artery stenosis and thrombosis following liver transplantation. Vasc Endovascular Surg. 2011;45:447–452.
20. Pereira K, Salsamendi J, Dalal R, et al. Percutaneous endovascular therapeutic options in treating posttransplant hepatic artery thrombosis with the aim of salvaging liver allografts: our experience. Exp Clin Transplant. 2016;14:542–550.
21. Mourad MM, Liossis C, Gunson BK, et al. Etiology and management of hepatic artery thrombosis after adult liver transplantation. Liver Transpl. 2014;20:713–723.
22. Allen AM, Kim WR, Xiong H, et al. Survival of recipients of livers from donation after circulatory death who are relisted and undergo retransplant for graft failure. Am J Transplant. 2014;14:1120–1128.
23. Liberal R, Vergani D, Mieli-Vergani G. Update on autoimmune hepatitis. J Clin Transl Hepatol. 2015;3:42–52.
24. Vogel A, Heinrich E, Bahr MJ, et al. Long-term outcome of liver transplantation for autoimmune hepatitis. Clin Transplant. 2004;18:62–69.
25. Schramm C, Bubenheim M, Adam R, et al. Primary liver transplantation for autoimmune hepatitis: a comparative analysis of the European Liver Transplant Registry. Liver Transpl. 2010;16:461–469.
26. Campsen J, Zimmerman MA, Trotter JF, et al. Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal. Liver Transpl. 2008;14:1281–1286.
27. Reddy KR, Ellerbe C, Schilsky M, et al. Determinants of outcome among patients with acute liver failure listed for liver transplantation in the United States. Liver Transpl. 2016;22:505–515.
28. Russo MW, Galanko JA, Shrestha R, et al. Liver transplantation for acute liver failure from drug induced liver injury in the United States. Liver Transpl. 2004;10:1018–1023.
29. Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364–1372.
30. Gulmez SE, Larrey D, Pageaux GP, et al. Liver transplant associated with paracetamol overdose: results from the seven-country SALT study. Br J Clin Pharmacol. 2015;80:599–606.
31. Simpson KJ, Bates CM, Henderson NC, et al. The utilization of liver transplantation in the management of acute liver failure: comparison between acetaminophen and non-acetaminophen etiologies. Liver Transpl. 2009;15:600–609.
32. Mindikoglu AL, Magder LS, Regev A. Outcome of liver transplantation for drug-induced acute liver failure in the United States: analysis of the United Network for Organ Sharing database. Liver Transpl. 2009;15:719–729.
33. Fontana RJ. Acute liver failure due to drugs. Semin Liver Dis. 2008;28:175–187.
34. Gahche J, Bailey R, Burt V, et al. Dietary supplement use among U.S. adults has increased since NHANES III (1988-1994). NCHS Data Brief. 2011:1–8.
35. Dangerous supplements: what you don’t know about these 12 ingredients could hurt you. Consumer Reports. September 2010. At www.consumerreports.org/cro/2012/05/dangerous-supplements/index.html. Accessed August 6, 2014.
36. Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60:1399–1408.

Supplemental Digital Content

Back to Top | Article Outline
Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.