Mr Tom Gallagher, Division of Liver and Pancreas Transplantation, St. Vincent's University Hospital Transplant Centre, Dublin
Methodological Appraisers:
Katriona O'Donoghue, Centre for Evidence in Transplantation,The Royal College of Surgeons of England
Anam Ayaz-Shah, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Overall Guideline Assessment:
★★★★☆☆☆ (4 of 7)
Appraiser 1
Appraiser 2
Appraiser 3
5
3
4
Recommendation for future use
Appraiser 1
Appraiser 2
Appraiser 3
Yes with modifications
Yes with modifications
Yes
Domain 1 - Scope and Purpose
76%
Appraiser 1
Appraiser 2
Appraiser 3
1.
The overall objective(s) of the guideline is (are) specifically described
6
6
5
2.
The health question(s) covered by the guideline is (are) specifically described
4
5
6
3.
The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described
5
6
7
Domain 2 - Stakeholder Involvement
54%
Appraiser 1
Appraiser 2
Appraiser 3
4.
The guideline development group includes individuals from all the relevant professional groups
5
3
4
5.
The views and preferences of the target population (patients, public, etc.) have been sought
3
4
2
6.
The target users of the guideline are clearly defined
6
6
5
Domain 3 - Rigour of Development
54%
Appraiser 1
Appraiser 2
Appraiser 3
7.
Systematic methods were used to search for evidence
4
3
6
8.
The criteria for selecting the evidence are clearly described
4
2
3
9.
The strengths and limitations of the body of evidence are clearly described
7
6
2
10.
The methods for formulating the recommendations are clearly described
5
2
3
11.
The health benefits, side effects, and risks have been considered in formulating the recommendations
6
2
4
12.
There is an explicit link between the recommendations and the supporting evidence
6
4
5
13.
The guideline has been externally reviewed by experts prior to its publication
5
6
6
14.
A procedure for updating the guideline is provided
4
1
6
Domain 4 - Clarity of Presentation
78%
Appraiser 1
Appraiser 2
Appraiser 3
15.
The recommendations are specific and unambiguous
6
6
6
16.
The different options for management of the condition or health issue are clearly presented
5
4
5
17.
Key recommendations are easily identifiable
7
6
6
Domain 5 - Applicability
26%
Appraiser 1
Appraiser 2
Appraiser 3
18.
The guideline describes facilitators and barriers to its application
3
3
5
19.
The guideline provides advice and/or tools on how the recommendations can be put into practice
2
1
2
20.
The potential resource implications of applying the recommendations have been considered
4
2
2
21.
The guideline presents monitoring and/ or auditing
3
1
3
Domain 6 - Editorial Independence
61%
Appraiser 1
Appraiser 2
Appraiser 3
22.
The views of the funding body have not influenced the content of the guideline
5
5
6
23.
Competing interests of guideline development group members have been recorded and addressed
5
4
3
Living donor liver transplantation (LDLT) has been increasingly embraced around the world as an important strategy to address the shortage of deceased donor livers. The aim of this guideline, approved by the International Liver Transplantation Society (ILTS), is to provide a collection of expert opinions, consensus, and best practices surrounding LDLT. Recommendations were developed from an analysis of the National Library of Medicine living donor transplantation indexed literature using the Grading of Recommendations Assessment, Development and Evaluation methodology. Writing was guided by the ILTS Policy on the Development and Use of Practice Guidelines (www.ilts.org). Intended for use by physicians, these recommendations support specific approaches to the diagnostic, therapeutic, and preventive aspects of care of living donor liver transplant recipients.
Dr Kevin Lu, Institute of Urology, Asia University Hospital, Taiwan
Methodological Appraisers:
Anam Ayaz-Shah, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Katriona O'Donoghue, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Overall Guideline Assessment:
★★★★★☆☆ (5 of 7)
Appraiser 1
Appraiser 2
Appraiser 3
6
6
4
Recommendation for future use
Appraiser 1
Appraiser 2
Appraiser 3
Yes with modifications
Yes
Yes with modifications
Domain 1 - Scope and Purpose
81%
Appraiser 1
Appraiser 2
Appraiser 3
1.
The overall objective(s) of the guideline is (are) specifically described
7
7
6
2.
The health question(s) covered by the guideline is (are) specifically described
7
5
7
3.
The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described
5
5
4
Domain 2 - Stakeholder Involvement
56%
Appraiser 1
Appraiser 2
Appraiser 3
4.
The guideline development group includes individuals from all the relevant professional groups
6
7
4
5.
The views and preferences of the target population (patients, public, etc.) have been sought
2
6
2
6.
The target users of the guideline are clearly defined
5
4
3
Domain 3 - Rigour of Development
54%
Appraiser 1
Appraiser 2
Appraiser 3
7.
Systematic methods were used to search for evidence
2
4
3
8.
The criteria for selecting the evidence are clearly described
3
1
4
9.
The strengths and limitations of the body of evidence are clearly described
7
7
4
10.
The methods for formulating the recommendations are clearly described
5
3
3
11.
The health benefits, side effects, and risks have been considered in formulating the recommendations
7
6
4
12.
There is an explicit link between the recommendations and the supporting evidence
5
7
5
13.
The guideline has been externally reviewed by experts prior to its publication
2
2
1
14.
A procedure for updating the guideline is provided
5
6
6
Domain 4 - Clarity of Presentation
74%
Appraiser 1
Appraiser 2
Appraiser 3
15.
The recommendations are specific and unambiguous
7
3
5
16.
The different options for management of the condition or health issue are clearly presented
6
6
5
17.
Key recommendations are easily identifiable
7
6
4
Domain 5 - Applicability
39%
Appraiser 1
Appraiser 2
Appraiser 3
18.
The guideline describes facilitators and barriers to its application
2
5
3
19.
The guideline provides advice and/or tools on how the recommendations can be put into practice
2
6
4
20.
The potential resource implications of applying the recommendations have been considered
3
5
1
21.
The guideline presents monitoring and/ or auditing
4
4
1
Domain 6 - Editorial Independence
72%
Appraiser 1
Appraiser 2
Appraiser 3
22.
The views of the funding body have not influenced the content of the guideline
4
7
4
23.
Competing interests of guideline development group members have been recorded and addressed
6
7
4
With current treatment regimens, a relatively high proportion of transplant recipients experience underimmunosuppression or overimmunosuppression. Recently, several promising biomarkers have been identified for determining patient alloreactivity, which help in assessing the risk of rejection and personal response to the drug; others correlate with graft dysfunction and clinical outcome, offering a realistic opportunity for personalized immunosuppression. This consensus document aims to help tailor immunosuppression to the needs of the individual patient. It examines current knowledge on biomarkers associated with patient risk stratification and immunosuppression requirements that have been generally accepted as promising. It is based on a comprehensive review of the literature and the expert opinion of the Biomarker Working Group of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology. The quality of evidence was systematically weighted, and the strength of recommendations was rated according to the GRADE system. Three types of biomarkers are discussed: (1) those associated with the risk of rejection (alloreactivity/tolerance), (2) those reflecting individual response to immunosuppressants, and (3) those associated with graft dysfunction. Analytical aspects of biomarker measurement and novel pharmacokinetic-pharmacodynamic models accessible to the transplant community are also addressed. Conventional pharmacokinetic biomarkers may be used in combination with those discussed in this article to achieve better outcomes and improve long-term graft survival. Our group of experts has made recommendations for the most appropriate analysis of a proposed panel of preliminary biomarkers, most of which are currently under clinical evaluation in ongoing multicentre clinical trials. A section of Next Steps was also included, in which the Expert Committee is committed to sharing this knowledge with the Transplant Community in the form of triennial updates.
Dr Annemarie Weissenbacher, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
Methodological Appraisers:
Rhiannon Deierhoi Reed, University of Alabama at Birmingham, Comprehensive Transplant Institute, USA
Katriona O'Donoghue, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Overall Guideline Assessment:
★★★★☆☆☆ (4 of 7)
Appraiser 1
Appraiser 2
Appraiser 3
4
3
6
Recommendation for future use
Appraiser 1
Appraiser 2
Appraiser 3
Yes with modifications
No
Yes
Domain 1 - Scope and Purpose
76%
Appraiser 1
Appraiser 2
Appraiser 3
1.
The overall objective(s) of the guideline is (are) specifically described
6
5
7
2.
The health question(s) covered by the guideline is (are) specifically described
5
5
6
3.
The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described
5
4
7
Domain 2 - Stakeholder Involvement
39%
Appraiser 1
Appraiser 2
Appraiser 3
4.
The guideline development group includes individuals from all the relevant professional groups
5
1
6
5.
The views and preferences of the target population (patients, public, etc.) have been sought
1
1
1
6.
The target users of the guideline are clearly defined
2
7
6
Domain 3 - Rigour of Development
56%
Appraiser 1
Appraiser 2
Appraiser 3
7.
Systematic methods were used to search for evidence
5
7
7
8.
The criteria for selecting the evidence are clearly described
2
4
3
9.
The strengths and limitations of the body of evidence are clearly described
6
7
7
10.
The methods for formulating the recommendations are clearly described
5
1
5
11.
The health benefits, side effects, and risks have been considered in formulating the recommendations
6
4
7
12.
There is an explicit link between the recommendations and the supporting evidence
6
6
7
13.
The guideline has been externally reviewed by experts prior to its publication
1
1
4
14.
A procedure for updating the guideline is provided
1
1
2
Domain 4 - Clarity of Presentation
80%
Appraiser 1
Appraiser 2
Appraiser 3
15.
The recommendations are specific and unambiguous
6
6
6
16.
The different options for management of the condition or health issue are clearly presented
5
7
7
17.
Key recommendations are easily identifiable
6
2
7
Domain 5 - Applicability
33%
Appraiser 1
Appraiser 2
Appraiser 3
18.
The guideline describes facilitators and barriers to its application
2
4
2
19.
The guideline provides advice and/or tools on how the recommendations can be put into practice
1
4
5
20.
The potential resource implications of applying the recommendations have been considered
4
4
1
21.
The guideline presents monitoring and/ or auditing
5
1
3
Domain 6 - Editorial Independence
28%
Appraiser 1
Appraiser 2
Appraiser 3
22.
The views of the funding body have not influenced the content of the guideline
1
1
1
23.
Competing interests of guideline development group members have been recorded and addressed
5
1
7
Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended.
Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Methodological Appraisers:
Rhiannon Deierhoi Reed, University of Alabama at Birmingham, Comprehensive Transplant Institute, USA
Katriona O'Donoghue, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Overall Guideline Assessment:
★★★★★★☆ (6 of 7)
Appraiser 1
Appraiser 2
Appraiser 3
6
6
6
Recommendation for future use
Appraiser 1
Appraiser 2
Appraiser 3
Yes
Yes
Yes
Domain 1 - Scope and Purpose
96%
Appraiser 1
Appraiser 2
Appraiser 3
1.
The overall objective(s) of the guideline is (are) specifically described
6
7
7
2.
The health question(s) covered by the guideline is (are) specifically described
6
7
7
3.
The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described
7
7
7
Domain 2 - Stakeholder Involvement
48%
Appraiser 1
Appraiser 2
Appraiser 3
4.
The guideline development group includes individuals from all the relevant professional groups
4
7
7
5.
The views and preferences of the target population (patients, public, etc.) have been sought
1
1
1
6.
The target users of the guideline are clearly defined
2
7
5
Domain 3 - Rigour of Development
85%
Appraiser 1
Appraiser 2
Appraiser 3
7.
Systematic methods were used to search for evidence
5
7
5
8.
The criteria for selecting the evidence are clearly described
4
5
4
9.
The strengths and limitations of the body of evidence are clearly described
6
7
7
10.
The methods for formulating the recommendations are clearly described
6
5
7
11.
The health benefits, side effects, and risks have been considered in formulating the recommendations
5
7
7
12.
There is an explicit link between the recommendations and the supporting evidence
7
7
7
13.
The guideline has been externally reviewed by experts prior to its publication
5
7
7
14.
A procedure for updating the guideline is provided
7
7
6
Domain 4 - Clarity of Presentation
94%
Appraiser 1
Appraiser 2
Appraiser 3
15.
The recommendations are specific and unambiguous
6
7
7
16.
The different options for management of the condition or health issue are clearly presented
5
7
7
17.
Key recommendations are easily identifiable
7
7
7
Domain 5 - Applicability
19%
Appraiser 1
Appraiser 2
Appraiser 3
18.
The guideline describes facilitators and barriers to its application
2
2
1
19.
The guideline provides advice and/or tools on how the recommendations can be put into practice
2
2
1
20.
The potential resource implications of applying the recommendations have been considered
2
2
1
21.
The guideline presents monitoring and/ or auditing
4
6
1
Domain 6 - Editorial Independence
89%
Appraiser 1
Appraiser 2
Appraiser 3
22.
The views of the funding body have not influenced the content of the guideline
4
7
7
23.
Competing interests of guideline development group members have been recorded and addressed
6
7
7
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Mr Simon Knight, Centre for Evidence in Transplantation, The Royal College of Surgeons of England.
Methodological Appraisers:
Anam Ayaz-Shah, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Katriona O'Donoghue, Centre for Evidence in Transplantation, The Royal College of Surgeons of England
Overall Guideline Assessment:
★★★☆☆☆☆ (3 of 7)
Appraiser 1
Appraiser 2
Appraiser 3
4
4
2
Recommendation for future use
Appraiser 1
Appraiser 2
Appraiser 3
Yes with modifications
Yes with modifications
No
Domain 1 - Scope and Purpose
37%
Appraiser 1
Appraiser 2
Appraiser 3
1.
The overall objective(s) of the guideline is (are) specifically described
2
2
2
2.
The health question(s) covered by the guideline is (are) specifically described
3
6
3
3.
The population (patients, public, etc.) to whom the guideline is meant to apply is specifically described
4
4
3
Domain 2 - Stakeholder Involvement
15%
Appraiser 1
Appraiser 2
Appraiser 3
4.
The guideline development group includes individuals from all the relevant professional groups
5
3
1
5.
The views and preferences of the target population (patients, public, etc.) have been sought
1
1
1
6.
The target users of the guideline are clearly defined
2
2
1
Domain 3 - Rigour of Development
27%
Appraiser 1
Appraiser 2
Appraiser 3
7.
Systematic methods were used to search for evidence
2
1
1
8.
The criteria for selecting the evidence are clearly described
2
1
1
9.
The strengths and limitations of the body of evidence are clearly described
5
7
3
10.
The methods for formulating the recommendations are clearly described
2
1
1
11.
The health benefits, side effects, and risks have been considered in formulating the recommendations
6
6
2
12.
There is an explicit link between the recommendations and the supporting evidence
6
7
3
13.
The guideline has been externally reviewed by experts prior to its publication
1
1
1
14.
A procedure for updating the guideline is provided
1
1
1
Domain 4 - Clarity of Presentation
76%
Appraiser 1
Appraiser 2
Appraiser 3
15.
The recommendations are specific and unambiguous
6
7
4
16.
The different options for management of the condition or health issue are clearly presented
5
6
5
17.
Key recommendations are easily identifiable
6
7
4
Domain 5 - Applicability
8%
Appraiser 1
Appraiser 2
Appraiser 3
18.
The guideline describes facilitators and barriers to its application
2
1
1
19.
The guideline provides advice and/or tools on how the recommendations can be put into practice
2
1
1
20.
The potential resource implications of applying the recommendations have been considered
3
1
1
21.
The guideline presents monitoring and/ or auditing
3
1
1
Domain 6 - Editorial Independence
39%
Appraiser 1
Appraiser 2
Appraiser 3
22.
The views of the funding body have not influenced the content of the guideline
1
2
1
23.
Competing interests of guideline development group members have been recorded and addressed
6
6
4
The human BK polyomavirus (BKV) is the major cause of polyomavirus-associated nephropathy (PyVAN) putting 1-15% of kidney transplant patients at risk of premature allograft failure, but is less common in other solid organ transplants. Because effective antiviral therapies are lacking, screening kidney transplant patients for BKV replication in urine and blood has become the key recommendation to guide the reduction of immunosuppression in patients with BKV viremia. This intervention allows for expanding BKV-specific cellular immune responses, curtailing of BKV replication in the graft, and clearance of BKV viremia in 70-90% patients. Postintervention rejection episodes occur in 8-12%, most of which are corticosteroid responsive. Late diagnosis is faced with irreversible functional decline, poor treatment response, and graft loss. Adjunct therapies such as cidofovir, leflunomide and intravenous immunoglobulins have been used, but the benefit is not documented in trials. Retransplantation after PyVAN is largely successful, but requires close monitoring for recurrent BKV viremia.
