What's new in Hepatology

Vanguard Reports: highlights of the Joint Congress of ILTS, ELITA & LICAGE, Lisbon 2018, edited by Prashant Bhangui (click above or below...)

 

ILTS/LICAGE/ELITA Prague 24-27 May 2017: Congress commentaries by Deniz Balci and Christian Toso

 

Presentations reviewed by Deniz Balci: 

 

State of the Art lecture: Liver inflammation and immunology: from basic science to liver transplantation  

Speaker: Frank Tacke 

  • Dr Tacke started with defining new concepts and roles of monocytes and macrophages which could be summarized as: impact homeostasis and inflammation, hepatocyte injury, hepatic stellate cell activation and angiogenesis.
  • In liver, macrophage heterogeneity results with difficult immunological functions in disease progression as well as regression. 
  • Targeting macrophages could be via different methods namely microbubble, liposome or polymer in decreasing order of size of their respective particules. 
  • A proof-of-concept paper was published by Bartnect et al, showed decreased liver fibrosis using dexamethasone loaded liposomes. (Bartneck M, Warzecha KT, Tacke F. Therapeutic targeting of liver inflammation and fibrosis by nanomedicine. Hepatobiliary Surgery and Nutrition. 2014;3(6):364-376. doi:10.3978/j.issn.2304-3881.2014.11.02.)
  • In another model of therapeutic targeting of monocytes in liver disease; LY6C high inflamatory macrophage becomes a fibrogenic macrophage that results with Hepatic stellate cell activation and extracellular matrix increase, while Ly6C low macrophage induces activated hepatic stellate cell apoptosis which may have a potential in reversal of fibrosis, showing potential benefit of therapeutic targeting of LY6C.
  • The other cell line with various functions are Kupffer cells. Kupffer cell-mediated immunological tolerance to particulate antigens is abrogated in liver injury and fibrosis. They may assist in restoring antimicrobial surveillance in the early period after LT and promote tolerogenic actions in the long term. 
  • In liver transplantation, donor Kupffer cells may block activation before I/R injury occurs. 
  • Macrophages also take part in resolution of ischemia reperfusion injury in mice and man. There are various clinical implications.  
  • Monocyte-derived macrophages of the recipient are helpful in blocking infiltration after I/R injury
  • After the transplantation, they could potentially be blocked to prevent graft fibrosis hence prevent disease recurrence. 
  • And, they may also counterbalance over-immunosuppression which may be helpful for HCC recurrence. 
  • Dr. Tacke concluded that, targeting monocyte/ macrophages can be therapeutic in liver diseases (e.g. CCR2/5 inhibitor in Nash fibrosis) which could be an interesting approach to novel interventions not only in chronic liver disease but also during and after liver transplantation.

 

Concurrent Oral Video Abstract Session: 

Moderators: O Martin, K S Suh

 

Living Donor Liver Transplantation Using a Right Anterior Section of the Liver

Kyung-Suk Suh, Seoul, Republic of Korea

Dr Suh described a novel donor hepatectomy technique using right anterior section for the graft in LDLT for a recipient of 49-year-old male with BMI of 25. Donor volumetry was 0.57 for both the right posterior section and left hemiliver which were insufficient. The right anterior section was 710 ml with GRWR 0.96, with favorable portal and arterial anatomy hence selected as the graft. The total operation time was 292 minutes without transfusion and intra-operative complications. The middle hepatic vein of the right anterior section graft was anastomosed to the recipient's right hepatic vein and the rest were in standard fashion.

 Dr. Suh concluded that despite being a complex donor operation with 2 parenchymal transection lines, this novel concept may expand the cadaveric donor pool and indication of LDLT.

 

A New Technique for Living Donor Liver Transplantation: Backtable Outflow Reconstruction and Bicaval Anastomosis with Veno-venous Bypass: Back to Basics

Deniz Balci, Ankara, Turkey

Dr Balci reported a new LDLT technique which simplifies outflow reconstruction and, at the same time aiming to increase safety for the recipient considered to be sensitive to hemodynamic instability due to systemic comorbidities.    

The operation was divided into 3 steps: Hepatectomy without caval preservation and simultaneous veno-venous bypass (VVB) was set up using percutaneous femoral,  internal jugular vein and portal vein cannulation. Back-table harvest of the recipient IVC from the diseased liver and new living donor graft outflow reconstruction. Finally, bi-caval anastomosis in the recipient before withdrawing VVB. 

Dr Balci concluded that the technique may enable to simplify complex hepatic vein and caval anastomoses in LDLT using the VVB system under safe and hemodynamically stable conditions.

 

Pure Laparoscopic Living Donor Right Hepatectomy for Adult Liver Transplantation (4K, UHD)

Ki-Hun Kim, Seoul, Republic of Korea 

Dr Kim presented a case of totally laparoscopic living donor right Hepatectomy. The donor was a 27 y.o woman with total liver volume of 1100 cm3 and right lobe was 630 cm3. Graft to recipient weight ratio was 0.82. The operation started with right hepatic artery and portal vein dissection. Parenchymal transection was completed using intermittent Pringle maneuver. The MHV was identified with intraoperative USG and tributaries from segments V and VIII were identified and divided. Finally, right bile duct was found and divided after performing intraoperative cholangiography with a mobile C-arm. The operation time was 300mins, and the estimated blood loss was less than 125ml. Graft weights were 610g Perioperative period was uneventful.

Dr. Kim suggested that the laparoscopic donor right hepatectomy is safe and feasible for liver transplantation, but should be performed in selected cases with a favorable anatomy in experienced centers .

 

Pure Right Lobe Donor Hepatectomy Using 3-D Laparoscopy for Adult-to-Adult Living Donor Liver Transplantation

Hye Ryeon Choi, Daegu, Republic of Korea 

Laparoscopic-assisted Living Donor Right Hepatectomy 

Adel Bozorgzadeh, Worcester, United States 

 

Two more presentations were also reporting on a case of Laparoscopic Right Hepatectomy, Dr Choi from S.Korea presented pure laparoscopic right graft harvest using a Three-dimensional(3-D) imaging which they claim to enhance depth perception and facilitate operation. In Another presentation from the US by Dr Bozorgzadeh’s group, Hand-assisted laparoscopic right graft harvest technique was shown using a hand gelport placed on the right subcostal incision and three laparoscopic ports. The estimated blood loss was 500ml. The early postoperative course was uneventful for both the donor and recipient and they were discharged after 7 and 12 days, respectively. The authors concluded that hand-assisted laparoscopic living donor right hepatectomy is reproducible and can be safely performed.

 

Introduction of extrahepatic Glissonean approach for living donor hepatectomy

Taizo Hibi, Tokyo, Japan

Dr Hibi presented their extrahepatic Glissonean approach for living donor hepatectomy. The rational was to decrease bile duct injuries after living donor hepatectomy by both  preserving blood supply of the hilar plate in the remnant liver by minimizing dissection and obtaining maximum margin of hilar structures for bile duct division. They defined 3 steps, Step 1. Isolation of the The right or the left  Glissonean pedicle with an umbilical tape Step 2. Identification of hilar structures using Intraoperative cholangiography to find the point of bile duct division. Step 3 was Parenchymal division with modified liver hanging maneuver followed by division of hilar structures and graft retrieval. Dr Hibi concluded that extrahepatic Glissonean approach for living donor hepatectomy is safe and rational.

 

Laparoscopic Approach for Living Donor to Paediatric Liver Transplant 

Javier Briceño, Cordoba, Spain 

Dr Briceno reported their experience with 5 consecutive purely laparoscopic left lateral sectionectomy for adult-to-paediatric living liver donation, concluding that in specialized units, minimally invasive approach to living donor can be safely performed.

 

 

Presentations reviewed by Christian Toso:

 

Patient Selection and Organ Recovery: Oral Abstracts

Moderators: John O’Grady and Jaroslav Chiupac

 

Increasing Liver Transplant Waitlist Dropout for Hepatocellular

Carcinoma with Widening Geographical Disparities: Implications for

Organ Allocation

Neil Mehta, San Francisco, United States

This study, based on UNOS data, suggests that the risk of drop-out for HCC patients has increased greatly in the US in the recent years, and especially so in long wait-time regions. This data promotes creating regions with more homogeneous waiting times throughout the country, or tailoring exception MELD points according to wait time.

Liver Transplantation for HCC Patients with High AFP Level – How to Select?

WC Dai, Pokfulam, Hong Kong

This retrospective study of 330 patients transplanted for HCC demonstrated that AFP (< vs. >400) can predict post-transplant overall and disease-free survival.

Outcome of Liver Transplant Recipients after the First Episode of Bacterial Infection

Alberto Ferrarese, Padua, Italy

Single-center retrospective cohort study of 114 patients experiencing a bacterial infection on the waiting list, and match to 762 patients without infection (using propensity). SBP was the most common infection. Infection is associated with an increased short-term risk of death. Once having recovered, patients with infection did not show an increased risk factor of death on multivariate analysis.

The Objective Liver Frailty Index Significantly Improves the Clinician “Eyeball Test” to Predict Mortality in Liver Transplant Candidates

Jennifer Lai, San Francisco, United States

The Liver Frailty Index (grip strength, chair standing strength, balance testing) helps predicting the risk of death on the waiting list independently of MELD. Compared to the subjective assessment by hepatologists (1 to 5), the risk of death on the waiting list was better predicted using the Frailty index in 529 patients (and even more so when combining both with a c-statistics of 0.74).

 

Association of Cardiac Structural Abnormalities to the Frail Phenotype in Liver Transplant Candidates: From the Functional Assessment in Liver

Transplantation (FrAILT) Study

Lorena Puchades, Valencia, Spain

Frailty index correlates with the cardiac structural and functional impairments on TTE (including left chamber measurement, ejection fraction) in a cohort of 374 patients.

Normothermic Regional Perfusion (NRP) Improves Outcomes after Liver Transplantation from cDCD Donors

Gabriel Oniscu, Edinburgh, United Kingdom

In Scotland, livers of DCD donors are not used as often as in other part of the country. In order to improve this issue, a team has been flying with a machine in 45 donors in order to perform regional perfusion (similar to ECMO). Comparing a subgroup of 14 patients with NRP and 45 standard DCD, NRP was associated with lower post-transplant ALT, no cholangiopathy (vs24% in the standard DCD group), no primary non-function (vs. 4 in the standard DCD group), and better graft survival (p<0.05). In the audience, a member from the Bilbao team confirms similarly good results at his institution.

Human Liver Transplantation after Normothermic Machine Perfusion (NMP), the First Report in the United States

Qiang Liu, Cleveland, United States

Phase 1 trial of liver graft NMP of 2 to 18 hours prior to transplantation, with perfusion of both the artery and the vein. After 10 transplantations, including 2 DCD, only one patient demonstrated early allograft dysfunction (one of the two transplants from DCD).

The Impact of Hypothermic Oxygenated Perfusion on Liver Viability Tested during Normothermic Machine Perfusion

Yuri Boteon, Birmingham, United Kingdom

Study of 10 discarded livers on HOPE (6 h) followed by NMP (2h, n=5) vs. on NMP (6h, n=5). HOPE effectively recharged cell energy, and increased the number of viable cells. The author suggests that both strategies could be combined in the future.

Repair on the Pump: Effective Delivery of Mesenchymal Stromal Cells (MSCs) to Liver Grafts during Isolated Machine Perfusion

Monique M.A. Verstegen, Rotterdam, Netherlands

The study infused GFP-expressing human MSCs into six pig livers on HOPE. The engraftment was similar with injection into the portal vein vs. the artery (yet a bit better through the artery). After one hour of HOPE, the engraftment appeared stable (as assessed by qPCR). Answering to a question, the author proposes to infuse donor MSCs into the liver graft prior to transplant.

 

 

Patient Selection and Organ Recovery: Oral Abstracts

Moderators: John O’Grady and Jaroslav Chiupac

 

Increasing Liver Transplant Waitlist Dropout for Hepatocellular

Carcinoma with Widening Geographical Disparities: Implications for

Organ Allocation

Neil Mehta, San Francisco, United States

This study, based on UNOS data, suggests that the risk of drop-out for HCC patients has increased greatly in the US in the recent years, and especially so in long wait-time regions. This data promotes creating regions with more homogeneous waiting times throughout the country, or tailoring exception MELD points according to wait time.

Liver Transplantation for HCC Patients with High AFP Level – How to Select?

WC Dai, Pokfulam, Hong Kong

This retrospective study of 330 patients transplanted for HCC demonstrated that AFP (< vs. >400) can predict post-transplant overall and disease-free survival.

Outcome of Liver Transplant Recipients after the First Episode of Bacterial Infection

Alberto Ferrarese, Padua, Italy

Single-center retrospective cohort study of 114 patients experiencing a bacterial infection on the waiting list, and match to 762 patients without infection (using propensity). SBP was the most common infection. Infection is associated with an increased short-term risk of death. Once having recovered, patients with infection did not show an increased risk factor of death on multivariate analysis.

The Objective Liver Frailty Index Significantly Improves the Clinician “Eyeball Test” to Predict Mortality in Liver Transplant Candidates

Jennifer Lai, San Francisco, United States

The Liver Frailty Index (grip strength, chair standing strength, balance testing) helps predicting the risk of death on the waiting list independently of MELD. Compared to the subjective assessment by hepatologists (1 to 5), the risk of death on the waiting list was better predicted using the Frailty index in 529 patients (and even more so when combining both with a c-statistics of 0.74).

 

Association of Cardiac Structural Abnormalities to the Frail Phenotype in Liver Transplant Candidates: From the Functional Assessment in Liver

Transplantation (FrAILT) Study

Lorena Puchades, Valencia, Spain

Frailty index correlates with the cardiac structural and functional impairments on TTE (including left chamber measurement, ejection fraction) in a cohort of 374 patients.

Normothermic Regional Perfusion (NRP) Improves Outcomes after Liver Transplantation from cDCD Donors

Gabriel Oniscu, Edinburgh, United Kingdom

In Scotland, livers of DCD donors are not used as often as in other part of the country. In order to improve this issue, a team has been flying with a machine in 45 donors in order to perform regional perfusion (similar to ECMO). Comparing a subgroup of 14 patients with NRP and 45 standard DCD, NRP was associated with lower post-transplant ALT, no cholangiopathy (vs24% in the standard DCD group), no primary non-function (vs. 4 in the standard DCD group), and better graft survival (p<0.05). In the audience, a member from the Bilbao team confirms similarly good results at his institution.

Human Liver Transplantation after Normothermic Machine Perfusion (NMP), the First Report in the United States

Qiang Liu, Cleveland, United States

Phase 1 trial of liver graft NMP of 2 to 18 hours prior to transplantation, with perfusion of both the artery and the vein. After 10 transplantations, including 2 DCD, only one patient demonstrated early allograft dysfunction (one of the two transplants from DCD).

The Impact of Hypothermic Oxygenated Perfusion on Liver Viability Tested during Normothermic Machine Perfusion

Yuri Boteon, Birmingham, United Kingdom

Study of 10 discarded livers on HOPE (6 h) followed by NMP (2h, n=5) vs. on NMP (6h, n=5). HOPE effectively recharged cell energy, and increased the number of viable cells. The author suggests that both strategies could be combined in the future.

Repair on the Pump: Effective Delivery of Mesenchymal Stromal Cells (MSCs) to Liver Grafts during Isolated Machine Perfusion

Monique M.A. Verstegen, Rotterdam, Netherlands

The study infused GFP-expressing human MSCs into six pig livers on HOPE. The engraftment was similar with injection into the portal vein vs. the artery (yet a bit better through the artery). After one hour of HOPE, the engraftment appeared stable (as assessed by qPCR). Answering to a question, the author proposes to infuse donor MSCs into the liver graft prior to transplant.

 

 

ILTS Consensus Conference on Immunosuppression in Liver Transplantation

 

Park City, Utah  February 7-8, 2017

A distinguished international faculty led by Michael Charlton and Josh Levitsky provided a state-of-the-art overview of current issues and progress in this field, soon to be summarized in an ILTS Consensus Statement and published in the official ILTS journal Transplantation.

 

Lectures and podcasts now available to ILTS members under Lectures...

 

The ILTS physician web administrator for the specialty sections is Dr John Klinck. To contact him with constructive comments and ideas on these sections use john.klinck@addenbrookes.nhs.uk

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