liver_referencesWarm HTK donor pretreatment reduces liver injury during static cold storage in experimental rat liver transplantation W. Schoening, et al, Hepatobiliary Pancreat Dis Int,2015

Organ shortage has led to an increased number of transplantations from extended criteria donors. These organs are more vulnerable to ischemia-reperfusion injury. Thus, improvement of organ preservation is needed. HTK is a widely used preservation solution for static cold storage in liver transplantation. The present study was to investigate the beneficial effect of warm HTK donor pretreatment on liver preservation.

Comparison of Histidine-Tryptophan-Ketoglutarate (HTK) Solution versus University of Wisconsin (UW) Solution for Organ Preservation in Human Liver Transplantation J. Erhard, et al, Transp Int (1994) 7: 177-181

One of the original studies used in the approval of Custodiol® in the United States for liver transplantation. This study is a prospective randomized study with 60 patients (30 in each group). Criteria studied were need for fresh-frozen plasma, length of ICU stay, SGOT, SGPT, GLDH, fibrinogen, TPZ, lactate, rejection episodes, complications (biliary) and survival time. The author found no significant differences in the two groups regarding the evaluation criteria, even when cold ischemia time exceeded 15 hours. A slight, yet not significant, increase in late complications of the biliary anastomoses could be seen in the UW group (as also reported by Pittsburgh in 2003).

Comparison of Histidine-Tryptophan-Ketoglutarate Solution (HTK) and University of Wisconsin Solution (UW) in Adult Liver Transplantation Richard S. Mangus et al, Liver Transplantation 12:226-230, 2006

This study compared the perioperative and first year outcomes of liver transplantation using UW or Custodiol®. The study retrospectively matched UW patients to Custodiol® HTK patients, with a total study population of 378 patients. Outcomes included 1-, 6-, and 12-month graft survival and patient survival and 1-, 7-, 14-, and 30-day liver function and serum creatinine. Custodiol® group had higher day 1 median AST, ALT, and total bilirubin, but the two groups were similar thereafter. There were no differences in graft or patient survival. Cost savings with Custodiol® were realized.

Preservation Solutions in Liver Transplantation: What are the Options? Bijan Eghtesad, Federico Aucejo, John J. Fung Liver Transplantation 12:196-198, 2006

This paper reviews historical outcomes with Custodiol®, including the University of Pittsburgh’s groundbreaking work with Custodiol® in the United States. Pittsburgh first reported results in 253 liver transplants comparing Custodiol® to UW at the ATC meeting in 2003. Similar results were obtained between the two solutions in terms of primary nonfunction and graft function, and contrary to expectations there was no difference as ischemic times went beyond 14 hours. The paper notes reports or higher biliary complications with UW compared to HTK and why this may occur. Also reviewed is usage in DCD donors.

Experience with Histidine Tryptophan Ketoglutarate versus University of Wisconsin Preservation Solutions in Transplantation Ruben Canelo et al, Int. Surg 2003;88 145-151

This is a study comparing 63 liver transplants versus 71 UW transplants. The UW cohort is a retrospective analysis. This paper also provides a brief literature review of pancreas and kidney transplantation. Biochemical parameters, complications and survival were used to compare results. There were no differences in these findings, however, bilirubin was higher in the UW group. The rate of biliary complications was higher in the UW group. The author found that, with the exception of biliary complications, the two solutions are considered comparable. The same conclusions were made based on an analysis of the literature for kidneys and in smaller groups of pancreas transplants.

Safety and Efficacy of Living Donor Liver Preservation with HTK Solution B. Ringe et al, Transplantation Proceedings Vol. 37 No. 1 Jan/Feb 2005

This paper reviews 24 patients with living donor liver transplantation. There was no primary nonfunction and all partial livers showed good recovery. The results of this paper confirm that HTK solution is safe and effective when used in LDLTx. Potential advantages identified include low potassium concentration, low viscosity, no particles, no need to flush before reperfusion, improved biliary protection, better recovery of microcirculatory changes, ready to use, and lower costs.

Applicability of Histidine-Tryptophan-Ketoglutarate Solution in Right Lobe Adult-to Adult Liver Donor Liver Transplantation See Ching Chan et al, Liver Transplantation, Vol 10 No 11, 2004: pp1415-1421

Dr. Chan conducted a prospective study in a consecutive series of 60 right lobe adult-to-adult LDLTx comparing safety and efficacy of UW and HTK solutions. Main outcomes were post-transplant liver biochemistry, prothrombin time, recipient morbidity and graft and patient survival. There were no significant differences of the outcomes measures of the two groups. The low potassium content of the HTK offered logistical advantages.

New Preservation Solutions for use in Liver Transplantation David C. Mulligan et al Current Opinion in Organ Transplantation 2004, 9:159-162

This paper is a comprehensive review of several new preservation solutions, comparing them to each other and to UW solution. Dr. Mulligan reviews publications by Eghtesad et al, Canelo et al, Testa et al as well as the local results obtained at the Mayo Clinic in Scottsdale. Such studies showed at least comparability between Custodiol® and UW, with several logistical and practical advantages being noted. The Mayo Clinic’s own results in living donor livers showed better 30 day graft survival with HTK.

AMINALAI, A., et al, Morphological Investigation of the Porcine Liver Directly Following Preservation with EuroCollins, University of Wisconsin and Bretschneider’s HTK Solution, Langenbecks Arch. Chir. 376 (1992)

CANELO, R.. et al HTK vs. UW Preservation Solutions: Clinical Experience at a Single Center, Abstract

CHOK, K.S.H. et al, Bile Duct Anastomotic Stricture After Adult-to-Adult Right Lobe Living Donor Liver Transplantation, Liver Transplantation, 17:47-52, 2011

This study of prospectively collected data from 265 patients was collected between 1994 and 2008.  The study aimed to establish the rates of biliary anastomotic stricture (BAS) and associated factors looking at adult-to-adult right lobe living donor liver transplantation (ARLDLT). BAS rates were 21.4% for recipients undergoing duct-to-duct anastomosis (DDA) during transplantation, 18.9% for recipients undergoing hepaticojejunostomy (HJ) and 18.2% for recipients who underwent both procedures.  Prior to August 2002, UW solution was used but for the remainder of the study, HTK was instead used.  The authors concluded that “BAS remains common after ARLDLT regardless of DDA or HJ.  Operative findings found UW solution to be a risk factor for BAS, but this was not shown to be significant in the multi-variate analysis.  The graft cold ischemia time and postoperative acute cellular rejection are significantly associated with postoperative BAS.”

CLAIR CORPS, et al, The Influence of Preservation Solution on Ischemic Changes in the Liver 2006 July WTC Abstracts Abstract 2591

CYWINSKI, J. B. et al, Association Between Donor-Recipient Serum Sodium Differences and Orthotopic Liver Transplant Graft Function, Liver Transplantation 14:59-65, 2008

DALGIC, A. et al, Duct-to Duct Biliary Anastomosis with a “Corner-Saving-Suture” Technique in Living Related Liver Transplantation Transplantation Proceedings, 37, 3137-3140 2005

DE VERA, M.E. et al, Liver Transplantation Using Donation After Cardiac Death Donors: Long-Term Follow-Up from a Single Center, American Journal of Transplantation 2009, 9: 773-781

EHTESAD, B. et al, Technical Considerations in Liver Transplantation: What a Hepatologist Needs to Know (and Every Surgeon Should Practice) Liver Transplantation, Vol. 11 No. 8 August (2005) 261-271

EGHTESAD, B. et al, Comparison of HTK Solution vs. UW Solution for Organ Preservation in Liver Transplantation Abstract #1172

EGHTESAD, B. et al, Comparison of Histidine-Tryptophan-Ketoglutarate Solution vs. University of Wisconsin Solution For Organ Preservation in Liver Transplantation ATC 3-3-03 Abstract #1172

ERHARD, J. et al, Comparison of Histidine Tryptophan Ketoglutarate Solution vs. University of Wisconsin Solution for Organ Preservation in Human Liver Transplantation Abstract 198,

ERHARD, J., et al, Transplantation of the Liver after Preservation with the Cardioplegic Solution of Bretschneider, Lancet 2 (1990)

FENG, Li et al, Histidine Tryptophan Ketoglutarate Solution vs. University of Wisconsin Solution for Liver Transplantation: A Systematic Review Liver Transplantation 13:1125-1136, 2007

FENG, Li, et al Characteristics Associated with Liver Graft Failure: The Concept of a Donor Risk Index, American Journal of Transplantation 2006, 6: 783-789

FENG, X.-N. et al, Current status and perspective of liver preservation solutions, Hepatobility Pancreat Dis Int, Vol. 5, No. 4, November 15, 2006

FRIDELL, J. et al, A Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solutions in Extended Criteria Liver Allografts 2006 WTC 7-06 Abstract #64

GOKHAN, M. et al, Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solution in Living Donor Liver Transplantation 2006 WTC 7-06 Abstract #64

GONDALESI, G. et al, Biliary Complications in 96 Consecutive Right Lobe Living Donor Transplant Recipients Transplantation Vol. 77, 1842-1848 No. 12 June 2004

GUBERNATIS, G et al, Extended Cold Preservation Time (20 hours 20 minutes) of a Human Liver Graft by Using Cardioplegic HTK Solution Transplantation Proceedings Vol. 23 No.5(October), 1991 pp. 2408=409

GUBERNATIS, G., et al, Uniform Standardized Technique of Donor Liver Removal Irrespective of Arterial Anomalies, Transplantation Proceedings 25 (1993), 3160-3161

GUBERNATIS, G., et al, HTK-Solution (Bretschneider) for Human Liver Transplantation First Clinical Experiences, Langenbacks Arch. Chir. 375 (1990), 66-70

HATANO, E et al, Superiority of HTK Solution to UW Solution for Tissue Oxygenation in Living Related Liver Transplantation Transplantation Proceedings Vol 28, No 3 (June), 1996: pp. 1880-1881

HATANO, E et al, Hepatic Preservation with Histidine Tryptophan Ketoglutarate Solution in Living-Related and Cadaveric Liver Transplantation Clinical Science (1997) 93, 81-88

HELLINGER, A, et al, Preservation of Pig Liver Allografts after Warm Ischemia: normothermic perfusion vs. cold Storage Langenbacks Arch Chir (1997) 382: 175-184

HESSE, U.J., et al, Organ Preservation with HTK and UW Solution, Pabst Science Publishers, D-49525 Lengerich, 1999

JAIN, A. et al, Use of UW vs. HTK Perfusion and Preservation in Live Donor Liver Transplantation Abstract AT5SL , 2005 ATC

KEHRER, G., et al, Influence of Tissue Acidification and Halothane Anesthesia on Hepatic Electrical and Biochemical Properties during Ischemia, Z. Gastroenterol., 29 (1991), 22-30

LORF, T. et al, Is HTK Preservation Solution Suitable in Clinical Liver Transplantation? XVII World Congress of the Transplantation Society 1998 Book of Abstracts, Abstract 1604

MANGUS R. et al, Comparison of Histidine Tryptophan Ketoglutarate Solution and University of Wisconsin Solution in Adult Liver Transplantation Liver Transplantation 12:226-230, 2006

MANGUS, R. S. et al, Comparison of Histidine-Tryptophan-Ketoglutarate Solution and University of Wisconsin Solution in Extended Criteria Liver Donors, Liver Transplantation, 14: 365-373, 2008

MARTINEZ, J. et al, Histidine Tryptophan Ketoglutarate Solution is Clinically Equivalent but less Expensive than the University of Wisconsin Solution for Cadaveric Liver Transplantation. A Prospective Study 2006 WTC 7-06 Abstract #405

MARZI, I. et al, Microcirculatory Disturbances and Leukocyte Adherence in Transplant Livers after Cold Storage in Euro-Collins, UW and HTK Solutions Transplant Int. 1991 (4) 45-50

MEINE, M. et al, Graft Preservation with UW or HTK in Liver Transplantation Liver Transplant, Vol. 11 No.7 July 2005

MEINE, M. et al, Randomized Clinical Assay for Hepatic Grafts Preservation with UW or HTK Solutions in Orthotopic Liver Transplantation Abstract 104, WTC Congress 6-20-2007

MEYER-VENTER, R. et al, Is HTK Preservation Solution Suitable in Clinical Liver Transplantation, 8th Congress of the European Society for Organ Transplantation, 1997, Abstract 29

MOENCH, C. et al, Prevention of Ischemic Type Biliary Legions by Arterial Back Table Flush Pressure Perfusion, Liver Transplantation, Vol. 9 No. 3, March (2003) pp 285-289

MONBALIU, D. et al, Primary Graft Nonfunction and Kupffer Cell Activation After Liver Transplantation From Non-Heart-Beating Donors in Pigs Liver Transplantation 13:239-247, 2007

MONBALIU, D. et al, Liver from Non-Heart-Beating Donors Tolerate Short Periods of Warm Ischemia Transplantation 2005;79:1-5

MORAY, G. et al, Comparison of Histidine Tryptophan Ketoglutarate and University of Wisconsin Solution in Living-Donor Liver Transplantation Transplantation Proceedings, 38, 3572-3575 (2006)

MULLIGAN, D., et al, New Preservation Solutions for Use in Liver Transplantation Current Opinion in Organ Transplantation 2004, 9:159-162

PICHLMAYR, R., et al, Technique and Preliminary Results of Extracorporeal Liver Surgery (Bench Procedure) and of Surgery on the In-Situ Perfused Liver, Br. J. Surg., 77 (1990), 21-26

POKORNY, H. et al, Liver Transplantation with HTK Infused Organs: A Multicenter Study XIX International Congress of The Transplantation Society, August 2002 Abstract 56

POKORNY, H., et al, Histidine Tryptophan Ketoglutarate Solution for Organ Preservation in Liver Transplantation – A Prospective Study Transplant, (2004), 256-260

POKORNY, H. et al Preservation of the Liver – Is it Possible to Extend the Time of Storage? Transplantation Proceedings, 31, 2074-2076 (1999)

RAMOS, R et al, Doppler Ultrasound Hepatic Arterial Resistive Indices are Similar after Histidine Tryptophan Ketoglutarate and University of Wisconsin Preservation in Liver Transplantation, Poster Session ATC Meeting, 5-7-07 Abstract #1285

RINGE, B. et al, Liver Preservation with HTK Solution in Live Donor Liver Presentation, Transplantation Volume 10 Number 6 – June 2004

SOTIL EVA URTASUN et al, Comparison of HTK to UW in Living Donor Liver Transplantation, Abstract 104, WTC Congress 6-20-2007

SPIEGEL, H.U., et al, Organ Preservation with EC, HTK and UW Solution in Orthotopic Rat Liver Transplantation Part II. A Morphological Study Journal of Investigative Surgery, 12:195-203, 1999

TELLIOGLU, G. et al,  Histidine-Tryptophan-Ketoglutarate Solution VS University of Wisconsin Solution for Deceased Donor Liver Transplantation: Analysis of UNOS Database,  P-281, ILTS Conference, New York, NY, (July 9, 2009)

This study evaluated the impact of organ preservation solutions (OPS) on outcomes in adult deceased donor liver transplant using a database analysis of the UNOS database which, reviews the cases of 20,908 patients who underwent transplants with organs preserved in an OPS, 17,559 (84%) of which used UW and 3349 (16%) used HTK.  The data was further refined using the SRTR database to remove patients with missing data points.  The study found that “HTK produces similar graft and patient survival outcomes compared to UW.”

TESTA, G. et al, Histidine Tryptophan Ketoglutarate vs. University of Wisconsin Solution in Living Related Liver Transplantation: Results of a Prospective Study Liver Transplantation, Vol. 9 No. 8, 2003 (August) pp. 822-826

TROISI, R. et al, HTK and UW Solutions for Flush and Preservation of Right Lobe Living Donor Grafts: Evaluation of Early Graft Function and Hemodynamics XIX Intl Congress of The Transplantation Society, Aug. 2002 Abstract 3217

WELLING, T. H. et al, Biliary Complications Following Liver Transplantation in the Model for End-Stage Liver Disease Era: Effect of Donor, Recipient, and Technical Factors, Liver Transplantation 14:73-80, 2008

This study conducted at the University of Michigan Medical Center, looked at 256 consecutive deceased donor liver transplants to evaluate variables associated with anastomotic biliary complications. Bile leak and stricture rates were analyzed.  Over the course of the study, Welling et al came to observe that HTK had a protective effect.  They ultimately concluded that “donor, recipient, and technical factors appear to differentially affect the incidence of anastomotic biliary complications, with warm ischemia, use of HTK, and use of a stent emerging as the most important variables.”  Use of HTK was found to significantly reduce biliary complications in the multivariate analysis.

WELLING, T. et al Risk Factors for Biliary Strictures Following Liver Transplantation During the MELD Era: Effect of Donor, Recipient, and Preservation Principles, American Journal of Transplantation, 6: Supp 2, 726 Aug. 2006