Liver transplantation acute rejection: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}}; {{AE}} {{MAD}}
{{CMG}}; {{AE}} {{MAD}}
{{Liver transplantation}}
{{Liver transplantation}}


==Overview==
==Overview==
Early acute cellular rejection mostly occurs within 90 days. Risk factors for acute rejection include elevated transplant recipient [[prothrombin time]] or [[bilirubin]], donors older than 50 years, donor pre-surgical [[acidosis]], [[cytomegalovirus]] infection especially [[genotype]] gB1, fewer [[human leukocyte antigen]] (HLA)-DR matches, and cold [[ischemia]] time greater than 15 hours. Clinical picture include [[fever]], [[malaise]], [[abdominal pain]], and [[hepatosplenomegaly]]. elevated [[Aminotransferase|serum aminotransferases]], [[alkaline phosphatase]], [[gamma-glutamyl transpeptidase]], and [[bilirubin]] level.


==Liver transplantation acute rejection==
==Liver transplantation acute rejection==
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'''Risk factors for acute rejection''':<ref name="pmid9731552">{{cite journal| author=Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK et al.| title=Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. | journal=Hepatology | year= 1998 | volume= 28 | issue= 3 | pages= 638-45 | pmid=9731552 | doi=10.1002/hep.510280306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9731552  }}</ref><ref name="pmid12360439">{{cite journal| author=Ramji A, Yoshida EM, Bain VG, Kneteman NM, Scudamore CH, Ma MM et al.| title=Late acute rejection after liver transplantation: the Western Canada experience. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 10 | pages= 945-51 | pmid=12360439 | doi=10.1053/jlts.2002.34969 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12360439  }}</ref>
'''Risk factors for acute rejection''':<ref name="pmid9731552">{{cite journal| author=Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK et al.| title=Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome. | journal=Hepatology | year= 1998 | volume= 28 | issue= 3 | pages= 638-45 | pmid=9731552 | doi=10.1002/hep.510280306 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9731552  }}</ref><ref name="pmid12360439">{{cite journal| author=Ramji A, Yoshida EM, Bain VG, Kneteman NM, Scudamore CH, Ma MM et al.| title=Late acute rejection after liver transplantation: the Western Canada experience. | journal=Liver Transpl | year= 2002 | volume= 8 | issue= 10 | pages= 945-51 | pmid=12360439 | doi=10.1053/jlts.2002.34969 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12360439  }}</ref>
 
* Elevated transplant recipient [[prothrombin time]] or [[bilirubin]]
Recipient prothrombin time or bilirubin that remains steadily elevated
* Donors older than 50 years
 
* Donor pre-surgical [[acidosis]]
Donors older than 50 years
* [[Cytomegalovirus]] infection especially [[genotype]] gB1
 
* Fewer [[human leukocyte antigen]] (HLA)-DR matches
Donor pre-procurement acidosis
* Cold [[ischemia]] time greater than 15 hours
 
* For risk of late rejection, low blood concentration of [[cyclosporine]] or [[tacrolimus]]
Cytomegalovirus genotype gB1 infection
 
Fewer human leukocyte antigen (HLA)-DR matches
 
Cold ischemia time greater than 15 hours
 
For risk of late rejection, low blood concentration of cyclosporine or tacrolimus.
 
'''Clinical presentation'''
'''Clinical presentation'''
* Fever, malaise, abdominal pain, and hepatosplenomegaly.
* [[Fever]], [[malaise]], [[abdominal pain]], and [[hepatosplenomegaly]]
* None of these is specific for rejection.
* None of these is specific for rejection.
* Acute cellular rejection is generally suspected based upon the development of hepatic biochemical test abnormalities:<ref name="pmid1505912">{{cite journal| author=Henley KS, Lucey MR, Appelman HD, Baliga P, Brown KA, Burtch GD et al.| title=Biochemical and histopathological correlation in liver transplant: the first 180 days. | journal=Hepatology | year= 1992 | volume= 16 | issue= 3 | pages= 688-93 | pmid=1505912 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1505912  }}</ref>
* Acute cellular rejection is generally suspected based upon the development of hepatic biochemical test abnormalities:<ref name="pmid1505912">{{cite journal| author=Henley KS, Lucey MR, Appelman HD, Baliga P, Brown KA, Burtch GD et al.| title=Biochemical and histopathological correlation in liver transplant: the first 180 days. | journal=Hepatology | year= 1992 | volume= 16 | issue= 3 | pages= 688-93 | pmid=1505912 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1505912  }}</ref>
Serum aminotransferases
* [[Aminotransferase|Serum aminotransferases]]
 
* [[Alkaline phosphatase]]
Alkaline phosphatase
* [[Gamma-glutamyl transpeptidase]]
 
* [[Bilirubin]] level
Gamma-glutamyl transpeptidase
* Hepatocyte derived [[microRNAs]] (HDmiRs, mir-122, miR-148a) have been evaluated as markers of acute cellular rejection.<ref name="pmid27533743">{{cite journal| author=Shaked A, Chang BL, Barnes MR, Sayre P, Li YR, Asare S et al.| title=An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection. | journal=Hepatology | year= 2017 | volume= 65 | issue= 1 | pages= 269-280 | pmid=27533743 | doi=10.1002/hep.28786 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27533743  }}</ref>
 
Bilirubin level  
 
Hepatocyte derived microRNAs (HDmiRs, mir-122, miR-148a) have been evaluated as markers of acute cellular rejection.<ref name="pmid27533743">{{cite journal| author=Shaked A, Chang BL, Barnes MR, Sayre P, Li YR, Asare S et al.| title=An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection. | journal=Hepatology | year= 2017 | volume= 65 | issue= 1 | pages= 269-280 | pmid=27533743 | doi=10.1002/hep.28786 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27533743  }}</ref>  
 
'''Liver biopsy'''
'''Liver biopsy'''
* Liver histology is the gold standard for the diagnosis of acute cellular rejection.<ref name="pmid1959854">{{cite journal| author=Bubak ME, Porayko MK, Krom RA, Wiesner RH| title=Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy. | journal=Hepatology | year= 1991 | volume= 14 | issue= 6 | pages= 1063-5 | pmid=1959854 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1959854  }}</ref>
* Liver histology is the gold standard for the diagnosis of acute cellular rejection.<ref name="pmid1959854">{{cite journal| author=Bubak ME, Porayko MK, Krom RA, Wiesner RH| title=Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy. | journal=Hepatology | year= 1991 | volume= 14 | issue= 6 | pages= 1063-5 | pmid=1959854 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1959854  }}</ref>
* Presence of biliary strictures and biliary anastomosis with mixed inflammatory infiltrate in the portal triad is sign of rejection.<ref name="pmid9397978">{{cite journal| author=Larson AM, Chan GC, Wartelle CF, McVicar JP, Carithers RL, Hamill GM et al.| title=Infection complicating percutaneous liver biopsy in liver transplant recipients. | journal=Hepatology | year= 1997 | volume= 26 | issue= 6 | pages= 1406-9 | pmid=9397978 | doi=10.1002/hep.510260605 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9397978  }}</ref>
* Presence of [[biliary]] strictures and biliary anastomosis with mixed inflammatory infiltrate in the portal triad is sign of rejection.<ref name="pmid9397978">{{cite journal| author=Larson AM, Chan GC, Wartelle CF, McVicar JP, Carithers RL, Hamill GM et al.| title=Infection complicating percutaneous liver biopsy in liver transplant recipients. | journal=Hepatology | year= 1997 | volume= 26 | issue= 6 | pages= 1406-9 | pmid=9397978 | doi=10.1002/hep.510260605 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9397978  }}</ref>
* Nonsuppurative cholangitis is important for the prognosis of rejection. The affected ducts are surrounded by immunocytes, which may also be found between epithelial cells, inside the basement membrane, or even in the lumen.  
* Nonsuppurative [[cholangitis]] is important for the prognosis of rejection.
'''Histologic rejection activity index for liver transplants'''
* The affected ducts are surrounded by [[lymphocytes]], which may also be found between [[epithelial cells]], inside the [[basement membrane]], or even in the lumen.  
'''Histologic rejection activity index for liver transplants'''<ref name="pmid16799959">{{cite journal| author=Höroldt BS, Burattin M, Gunson BK, Bramhall SR, Nightingale P, Hübscher SG et al.| title=Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation? | journal=Liver Transpl | year= 2006 | volume= 12 | issue= 7 | pages= 1144-51 | pmid=16799959 | doi=10.1002/lt.20779 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16799959  }}</ref>
{| class="wikitable"
{| class="wikitable"
|'''Category'''
|'''Category'''

Latest revision as of 18:40, 28 December 2017


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]

Liver trasnsplantation Microchapters

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Complications

Acute rejection

Immune therapy

Post-surgical infection

Prognosis

Overview

Early acute cellular rejection mostly occurs within 90 days. Risk factors for acute rejection include elevated transplant recipient prothrombin time or bilirubin, donors older than 50 years, donor pre-surgical acidosis, cytomegalovirus infection especially genotype gB1, fewer human leukocyte antigen (HLA)-DR matches, and cold ischemia time greater than 15 hours. Clinical picture include fever, malaise, abdominal pain, and hepatosplenomegaly. elevated serum aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin level.

Liver transplantation acute rejection

Early acute cellular rejection mostly occurs within 90 days.[1]

Risk factors for acute rejection:[2][3]

Clinical presentation

Liver biopsy

  • Liver histology is the gold standard for the diagnosis of acute cellular rejection.[6]
  • Presence of biliary strictures and biliary anastomosis with mixed inflammatory infiltrate in the portal triad is sign of rejection.[7]
  • Nonsuppurative cholangitis is important for the prognosis of rejection.
  • The affected ducts are surrounded by lymphocytes, which may also be found between epithelial cells, inside the basement membrane, or even in the lumen.

Histologic rejection activity index for liver transplants[8]

Category Criteria Score
Portal inflammation –– 1
Expansion of most of all of the triads, by a mixed infiltrate containing lymphocytes with occasional blasts, neutrophils and eosinophils 2
Marked expansion of most or all of the triads by a mixed infiltrate containing numerous blasts and eosinophils with inflammatory spillover into the periportal parenchyma 3
Bile duct inflammation damage A minority of the ducts are cuffed and infiltrated by inflammatory cells and show only mild reactive changes such as increased nuclear:cytoplasmic ratio of the epithelial cells 1
Most or all of the ducts infiltrated by inflammatory cells. More than an occasional duct shows degenerative changes such as nuclear pleomorphism, disordered polarity and cytoplasmic vacuolization of the epithelium 2
As above for 2, with most or all of the ducts showing degenerative changes or focal lumenal disruption 3
Venous endothelial inflammation Subendothelial lymphocytic infiltration involving some, but not a majority of the portal and/or hepatic venules 1
Subendothelial lymphocytic infiltration involving some, but not a majority of the portal and/or hepatic venules 2
As above for 2, with moderate or severe perivenular inflammation that extends into the perivenular parenchyma and is associated with perivenular hepatocyte necrosis 3

References

  1. Levitsky J, Goldberg D, Smith AR, Mansfield SA, Gillespie BW, Merion RM; et al. (2017). "Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients". Clin Gastroenterol Hepatol. 15 (4): 584–593.e2. doi:10.1016/j.cgh.2016.07.035. PMC 5326609. PMID 27567694.
  2. Wiesner RH, Demetris AJ, Belle SH, Seaberg EC, Lake JR, Zetterman RK; et al. (1998). "Acute hepatic allograft rejection: incidence, risk factors, and impact on outcome". Hepatology. 28 (3): 638–45. doi:10.1002/hep.510280306. PMID 9731552.
  3. Ramji A, Yoshida EM, Bain VG, Kneteman NM, Scudamore CH, Ma MM; et al. (2002). "Late acute rejection after liver transplantation: the Western Canada experience". Liver Transpl. 8 (10): 945–51. doi:10.1053/jlts.2002.34969. PMID 12360439.
  4. Henley KS, Lucey MR, Appelman HD, Baliga P, Brown KA, Burtch GD; et al. (1992). "Biochemical and histopathological correlation in liver transplant: the first 180 days". Hepatology. 16 (3): 688–93. PMID 1505912.
  5. Shaked A, Chang BL, Barnes MR, Sayre P, Li YR, Asare S; et al. (2017). "An ectopically expressed serum miRNA signature is prognostic, diagnostic, and biologically related to liver allograft rejection". Hepatology. 65 (1): 269–280. doi:10.1002/hep.28786. PMID 27533743.
  6. Bubak ME, Porayko MK, Krom RA, Wiesner RH (1991). "Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy". Hepatology. 14 (6): 1063–5. PMID 1959854.
  7. Larson AM, Chan GC, Wartelle CF, McVicar JP, Carithers RL, Hamill GM; et al. (1997). "Infection complicating percutaneous liver biopsy in liver transplant recipients". Hepatology. 26 (6): 1406–9. doi:10.1002/hep.510260605. PMID 9397978.
  8. Höroldt BS, Burattin M, Gunson BK, Bramhall SR, Nightingale P, Hübscher SG; et al. (2006). "Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?". Liver Transpl. 12 (7): 1144–51. doi:10.1002/lt.20779. PMID 16799959.