|Year : 2019 | Volume
| Issue : 2 | Page : 130-133
Graft-versus-host disease: Rare complication postliver transplant
Nivedita Pandey1, Bhavna Bansal2, Akash Jaiswal3, Subhash Gupta4
1 Department of Gastroenterology and Hepatology, Max Super Specialty Hospital, New Delhi, India
2 Department of Pathology, Max Super Specialty Hospital, New Delhi, India
3 Department of Hepatology, School of Digestive and Liver Disease, Institute of Postgraduate Medical Education and Research, SSKM Hospital, Kolkata, West Bengal, India
4 Center for Liver and Biliary Sciences, Max Super Specialty Hospital, New Delhi, India
|Date of Submission||29-Oct-2018|
|Date of Acceptance||02-Dec-2018|
|Date of Web Publication||28-Jun-2019|
Dr. Nivedita Pandey
Department of Gastroenterology and Hepatology, Max Super Specialty Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
Graft-versus-host disease (GVHD) following liver transplantation (LT) is an uncommon complication but has high mortality and represents a major diagnostic challenge. A 63-year-old male with nonalcoholic steatohepatitis-related decompensated cirrhosis underwent deceased donor LT. His postoperative course was complicated by fever, diarrhea, skin rashes, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the duodenum and skin were consistent with acute GVHD. This was confirmed by chimerism study performed on the bone marrow. The patient was treated with basiliximab, corticosteroids, tacrolimus, and mycophenolate; however, he had minimal response to intensive immunosuppressive therapy. The patient died due to multiorgan failure.
Keywords: Graft-versus-host disease, liver transplant, skin rash
|How to cite this article:|
Pandey N, Bansal B, Jaiswal A, Gupta S. Graft-versus-host disease: Rare complication postliver transplant. Indian J Transplant 2019;13:130-3
|How to cite this URL:|
Pandey N, Bansal B, Jaiswal A, Gupta S. Graft-versus-host disease: Rare complication postliver transplant. Indian J Transplant [serial online] 2019 [cited 2019 Jul 19];13:130-3. Available from: http://www.ijtonline.in/text.asp?2019/13/2/130/261847
| Introduction|| |
Acute graft-versus-host disease (GVHD), a reaction of donor immune cells against host tissues, is a frequent complication (35%–50%) after allogeneic hematopoietic stem cell transplantation (HSCT). In 1988, Burdick et al. first described acute GVHD after orthotopic liver transplantation (OLT). Acute GVHD after liver transplantation (LT) is rare, occurring in 0.1%–2% of patients; however, it is a severe complication with an 85% mortality rate in adult recipients.,,, Acute GVHD typically occurs 1–8 weeks after LT with symptoms of fever, diarrhea, and skin rashes in the early clinical course, followed by pancytopenia, sepsis, and even death. At present, the correct diagnosis and management of GVHD following LT remain a major challenge. Herein, we report a patient with acute GVHD after LT confirmed with chimerism study; the patient was treated aggressively but succumbed to his diagnosis.
| Case Report|| |
A 63-year-old male with a history of nonalcoholic steatohepatitis-related decompensated chronic liver disease underwent ABO-compatible deceased donor-related LT in September 2017. Induction immunosuppression was given with methylprednisolone followed by tacrolimus, mycophenolate mofetil, and prednisone. Early postoperative course was uneventful. Four weeks after transplant, the patient was admitted with fever, diarrhea, and an erythematous, targetoid, macular desquamating rash with oral ulcers. He was pancytopenic, white cell count was 300/uL, hemoglobin was 7.3 g/dL, and platelets were 40,000/uL. The rash progressed to involve the entire integument and was most pronounced on the palms and soles. An infectious workup was negative. Liver function tests were normal.
Skin biopsy findings were: epidermis was thinned out/atrophic with vacuolar degeneration of basal cell layer, mild spongiosis, and lymphocytic exocytosis. A large number of necrotic/apoptotic keratinocytes were seen in the basal layer and at all the levels of the epidermis. Lymphocyte satellitosis was seen around few necrotic keratinocytes. Focally melanin pigment was seen in the corneum. Focal mild epidermal clefting was seen. Superficial debris showed minimal perivascular lymphocytic infiltrate. Dermis showed loss of pilosebaceous structures and thickened collagen bundles in the papillary and reticular dermis [Figure 1], [Figure 2], [Figure 3], [Figure 4].
|Figure 3: Necrotic/Apoptotic keratinocytes involving all layers of epidermis|
Click here to view
Bone marrow aspiration smears were particulate and showed markedly hypocellular particles. Erythroid and myeloid precursors were markedly reduced in number and only scattered forms were seen exhibiting normal morphology. Megakaryocytes appeared to be adequate. Background population of lymphocytes and macrophages was seen [Figure 5] and [Figure 6].
Chimerism study on the bone marrow specimen showed that 49% cells show XX pattern (female donor) and 51% cells show XY pattern (patient).
Based on the clinical picture, histology, and bone marrow findings, a diagnosis of acute GVHD with dermal sclerodermoid features was made. The patient was treated with methylprednisolone and intravenous basiliximab. Immunosuppression was continued. Despite aggressive treatment, the patient continued to deteriorate and died within a week of presentation due to multiorgan failure.
| Discussion|| |
GVHD in OLT is rare but has a mortality rate of 85%.,, In OLT, immunocompetent donor-derived lymphocytes undergo activation following exposure to recipient-derived antigens. Activated donor T-lymphocytes mediate an immune response against recipient tissue. The target tissues in GVHD following OLT are the bone marrow, skin, and the gut, with notable sparing of the liver.
The pathogenesis of GVHD in OLT occurs in three continuous phases. In the first phase, surgery induces a pro-inflammatory state where host macrophages release tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1), resulting in increased host antigen-presenting cell activity. In the second phase, donor-derived T-lymphocytes residing in the donor's liver activate, stimulated by the HLA/peptide complex interactions, resulting in IL-2 receptor expression and clonal expansion, ultimately leading to the release of pro-inflammatory cytokines IL-2 and interferon gamma., In the third phase, anti-host T-cells release granzyme and perforin, leading to further inflammation and promotion of GVHD.,
In OLT, GVHD presents 1–8 weeks after transplant., In 15% of cases, the patient presents with only dermatologic symptoms of rash involving the palms and soles, with eventual bullous transformation and desquamation., GVHD resulting in multisystem organ failure has an 85% mortality rate. The natural history of post-OLT GVHD is a relapsing-remitting pattern of diarrhea, rash, fever, and neutropenia, culminating in sepsis and death. A diagnosis of GVHD after OLT is confirmed by biopsy of the affected tissues, which will demonstrate donor-derived lymphocytic infiltration in the appropriate clinicopathological setting.,
GVHD should be suspected in symptomatic patients if chimerism is demonstrated by polymerase chain reaction or HLA typing of lymphocytes in the peripheral blood.,, Early recognition requires thoughtful synthesis of the pathological, laboratory, and clinical data, and prompt treatment is essential. There are no guidelines for the treatment of post-OLT GVHD. Current therapy is borrowed from GVHD treatment following HSCT and consists of immunosuppression with high doses of corticosteroids or calcineurin inhibitors.,, However, this is frequently complicated by toxicity and infections.,,,, Salvage therapies in steroid-refractory GVHD after OLT are mostly ineffective. Administration of OKT3 or anti-thymocyte globulin (ATG) produces a profound immunosuppression but is not associated with remission and frequently results in fatal infections., Targeting T-lymphocytes with daclizumab and basiliximab are associated with remission of skin GVHD but are usually inadequate in suppressing gut GVHD., Anti-TNFα agents are also not effective in treating GVHD and are associated with fungal infections.,
Decreasing immunosuppression following LT allows host lymphocytes to regain activity against donor lymphocytes with the risk of graft rejection.,, Finally, T-lymphocyte elimination with ATG or irradiation has not proven to be worthwhile due to the unknown risk of impairing engraftment.,, Extracorporeal photopheresis has been effective in GVHD following HSCT and is regarded as a second-line treatment, resulting in response rates as high as 80% and up to 50% long-term survival, but its role in post-LT GVHD is not clear.,,
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]