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CASE REPORT
Year : 2017  |  Volume : 11  |  Issue : 3  |  Page : 149-152

A case of acute graft-versus-host disease in postliver transplantation


Smt. G. R. Doshi and Smt. K. M. Mehta Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India

Date of Web Publication20-Dec-2017

Correspondence Address:
Dr. Pranjal Ramanlal Modi
Smt. G. R. Doshi and Smt. K. M. Mehta Institute of Kidney Diseases and Research Centre, Dr. HL Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_44_17

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  Abstract 


Graft-versus-host disease (GVHD) after liver transplantation, although rare, is well documented in liver transplant recipients. In this syndrome, donor T lymphocytes transferred with the graft are activated by alloantigens expressed by host antigen-presenting cells and initiate an immune response against recipient tissues, especially skin, gastrointestinal tract, and hemopoietic tissue. A descriptive study of clinical case and the management includes investigations, diagnosis, and treatment of GVHD. Diagnosis of the GVHD was based on combination of clinical features and histological features on skin biopsy. Possible differential diagnosis was ruled out on the basis of laboratory investigations. Empirical treatment with continuous immunosuppressant and antibiotics were continued. There was a transient response to the treatment with resurgence of the features culminating in multiple organ dysfunction leading to death. This first case of this rare complication in the experience of our institute of nearly one hundred and twenty liver transplantation amounts to the incidence of approximately 0.8%. This is in alignment with the worldwide incidence. The rarity of this complication coupled with fair incidence of infective complications of liver transplantation mimicking it clinically makes the diagnosis of GVHD more difficult until sought after proactively. Moreover, the balance between the immunosuppression and superadded infection thereof with ill-defined and ill-studied treatment options makes the treatment of the complication more difficult thus justifying its high mortality across the world. Although GVHD is a rare complication of LT and the mortality rate remains very high, clinical features represent an important tool for early diagnosis. The prognosis remains poor, and further research is needed to clarify the pathogenesis of GVHD and to provide new therapy.

Keywords: Graft-versus-host disease, immunological, liver transplant


How to cite this article:
Patel VD, Modi PR, Sutariya VK. A case of acute graft-versus-host disease in postliver transplantation. Indian J Transplant 2017;11:149-52

How to cite this URL:
Patel VD, Modi PR, Sutariya VK. A case of acute graft-versus-host disease in postliver transplantation. Indian J Transplant [serial online] 2017 [cited 2020 Jul 8];11:149-52. Available from: http://www.ijtonline.in/text.asp?2017/11/3/149/221191




  Introduction Top


Solid organ transplantation and in particular liver transplantation involves transfer of immunologically potent cells from donor to recipient. Out of the interaction between these cells and host cells arise a potential of devastation outcome called graft versus host disease (GVHD). It is classically described in bone marrow transplant, but is an uncommon occurrence post liver transplantation. Its incidence is 0.1%-2%.[1]

Aim

This study aims to discuss a rare case of GVHD in liver transplantation.


  Case Report Top


A 47-year-old male, a known alcoholic, blood group B-positive had signs of decompensated cirrhosis in the form of intractable ascites and bilateral lower limb edema hematemesis due to esophageal varices. The patient underwent deceased donor liver transplantation on May 6, 2015, after a waiting period of 2 months. Donor was 70-year-old male B-positive who was brain dead due to the right middle cerebral artery infarct. Intraoperative 10 fresh frozen plasma, 10 packed red cell units, and 30 platelet units were used. Cold ischemic time was 9 h. Rewarming time was 60 min. He was discharged on the 13th postoperative day with normalized bilirubin and liver function tests. Maintenance immunosuppressant given were tacrolimus 1.5 mg twice daily, prednisolone 20 mg once daily, and mycophenolate mofetil 500 mg thrice daily.

He was readmitted on the 30th postoperative day with profuse watery diarrhea, fever, cough, dysphagia, burning pain in eyes, maculopapular eruptions all over the body, burning pain with rashes involving palms, forearms, and soles [Figure 1] and [Figure 2].
Figure 1: Maculopapular rashes over forearm

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Figure 2: Maculopapular rash over trunk

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Differential diagnosis was GVHD, mycophenolate mofetil toxicity, cytomegalovirus (CMV) colitis, drug reaction, viral exanthema, and toxic epidermal necrolysis.

Blood parameters on readmission including hematology: Hb – 9.7 gm%, total leukocytes count – 7150/cumm, platelets – 171000/cumm, PT – 10 sec, APTT – 24 sec and Biochemistry: Bilirubin – 1.5 mg%, Albumin−3 gm%, SGPT – 20 U/L, serum glutamic oxaloacetic transaminase – 21 U/L, alkaline phosphatase – 89 U/L, Creatinine – 0.6 mg%, Na-130 meq/l, K – 3.5 meq/l [Figure 3], [Figure 4], [Figure 5], [Figure 6].
Figure 3: Time trend: Liver enzymes

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Figure 4: Time trend: Bilirubin and albumin

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Figure 5: Time trend: Total leukocyte count

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Figure 6: Time trend: Platelet count

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Blood culture and urine culture were negative. Sputum microscopy showed fungal buds with Gram-negative cocci in chains; CMV DNA qualitative assay was positive.

Skin biopsy revealed basal vacuolization; superficial dermis shows perivascular lymphohistiocytic inflammatory infiltration suggestive of GRADE-2 GVHD [2] (Horn modification of Lerner's grading of skin lesions in GVHD) [Figure 7], [Figure 8], [Figure 9].
Figure 7: Skin biopsy, low power; black arrow indicating basal vacuolization, H and E

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Figure 8: Skin biopsy; black full arrow indicating infiltrates in dermis, (H and E, ×20)

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Figure 9: Perivenular infiltration; black full arrow indicating perivenular infiltrates, (H and E, ×400)

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Initial treatment was given with triple immunosuppressant, antibiotic (ofloxacin) and symptomatic treatment along with intravenous fluid, nebulization, skin steroid cream, and antibiotic eye drops. Frequency of passing stool was reduced but did not get cured. Skin lesions improved and eye lesions disappeared. After initial recovery, there was increased frequency of diarrhea.

Mycophenolate mofetil was stopped and Azathioprine (100 mg) was added. Antiviral treatment in the form of ganciclovir started for CMV. A trial with pulse methyl prednisolone (500 mg) was given for 3 days. Further clinical course deteriorated causing respiratory failure requiring ventilator, renal failure requiring hemodialysis, and gastrointestinal failure requiring total parenteral nutrition. Severe hemorrhagic diarrhea along with multisystem failure ended in death in a course of 8 days of Intensive Care Unit admission.


  Discussion Top


The occurrence of GVHD is well characterized with the bone marrow transplant. Its incidence in solid organ transplant recipients is very low, in proportion to the number of T-lymphocytes which it contains at the time of transplant. Among the solid organ transplants, small intestine carries significant number of T-lymphocytes; hence, it carries maximum potential for GVHD. Liver graft carries about 109–1010 lymphocytes to the recipient.[3] The recipient age was 47 years and the donor was 70 years; this is inconsistent with the usual scenario of GVHD (young donors with more immunocompetent lymphocytes incite cytotoxicity in already diseased recipient with a superadded immunosuppression). Recipient age more than 65 years and donor–recipient age difference more than 40 years is significantly associated with the occurrence of GVHD.[4] The positive risk factor, etiology of alcoholic cirrhosis is often seen associated with GVHD.[4] The presence of early occurrence of fever and rash, diarrhea, and pancytopenia strongly points toward the severity of the disease. The liver function remained normal till the end suggesting the donor origin of the offending cells. The diagnosis was based on clinical features strongly suggestive of GVHD and supported by skin biopsy. Although the classical epithelial dyskeratosis along with the epithelial cell necrosis was not seen, changes such as basal vacuolization and inflammatory infiltrates up to superficial dermis were in accordance with the grade 2 GVHD according to the Lerner grading.

The human leukocyte antigen (HLA) typing of the donor and recipient was not possible, so any positive HLA match could not be identified. Diagnosis would have been supported on the basis of peripheral blood chimerism [5] (more than 20% CD3+ donor lymphocytes in peripheral blood); the nonresponse to reduced immunosuppression or additional immunosuppressive suggests multifaceted and complex etiopathogenesis. Routine HLA typing is useful or not is a matter of research given very low incidence and multidimensional etiology of this complication.


  Conclusion Top


Although GVHD is a rare complication of liver transplantation and the mortality rates remain very high, clinical features represent an important tool for early diagnosis. The prognosis remains poor, and further research is needed to clarify the pathogenesis of GVHD and to provide new therapeutic agents for treating this condition effectively.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Xu X, Ling Q, Wei Q, Wang K, Zhou B, Zhuang L, et al. Korean red ginseng: A new approach for the treatment of graft-versus-host disease after liver transplantation. Transplant Proc 2011;43:2651-5.  Back to cited text no. 1
[PUBMED]    
2.
Horn TD. Acute cutaneous eruptions after marrow ablation: Roses by other names? J Cutan Pathol 1994;21:385-92.  Back to cited text no. 2
[PUBMED]    
3.
Ferrara JL. Pathogenesis of acute graft-versus-host disease: Cytokines and cellular effectors. J Hematother Stem Cell Res 2000;9:299-306.  Back to cited text no. 3
[PUBMED]    
4.
Chan EY, Larson AM, Gernsheimer TB, Kowdley KV, Carithers RL Jr., Reyes JD, et al. Recipient and donor factors influence the incidence of graft-vs-Host disease in liver transplant patients. Liver Transpl 2007;13:516-22.  Back to cited text no. 4
    
5.
Chinnakotla S, Smith DM, Domiati-Saad R, Agura ED, Watkins DL, Netto G, et al. Acute graft-versus-host disease after liver transplantation: Role of withdrawal of immunosuppression in therapeutic management. Liver Transpl 2007;13:157-61.  Back to cited text no. 5
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9]



 

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