Acute graft-versus-host-disease after liver transplantation: Two case reports and literature review

Graft versus host disease (GVHD) is an uncommon complication following liver transplantation. In the present case report, a 53-year-old male hepatitis B virus carrier was diagnosed with primary liver cancer with post-hepatitis cirrhosis. Preoperative cytomegalovirus (CMV), Epstein-Barr virus, coxsackievirus, herpes simplex virus and autoimmune antibody series were negative. Preoperative human leukocyte antigen type was also negative. Following classic orthotropic liver transplantation, postoperative treatment included immunosuppression therapy, infection protection, anti-human immunodeficiency virus therapy and CMV infection protection therapy. Chemotherapy was initiated at day 16 following surgery. At day 26 following the transplantation, the patient developed a fever of unknown cause, and a scattered red rash was observed behind the left ear and on the neck. The patient presented with a fever of unknown cause, rash, symptoms of the digestive tract, leukocytopenia and pancytopenia. A diagnosis of GVHD was confirmed following a skin biopsy. Symptomatic therapies, including antivirals, anti-anaphylaxis drugs and steroids were administered. However, the patient succumbed to infection, acute respiratory distress syndrome and multiple organ failure at day 46 following surgery. Therefore, an effective therapeutic strategy for the treatment of GVHD following liver transplantation is yet to be established, and further research is required prior to such a regimen being developed.

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Update on graft versus host disease.

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Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide and the third most common cause of cancer-related deaths; the number of new cases per year is approaching 750,000. The magnitude of the incidence of HCC has discouraged any attempts to apply liver transplantation (LT) as the prevailing curative therapy for HCC worldwide because of the limited sources of donated organs (deceased and living donors) and the poor access to sophisticated health care systems in some geographical areas. If these limitations continue to prevail throughout the world, any attempt to significantly reduce HCC-related mortality rates through the application of LT will be delusional. International experiences have confirmed, however, the potential of LT to definitively cure HCC because it presents a unique opportunity to remove both the tumor (HCC is associated with 695,000 deaths per year) and the underlying cirrhosis. Despite its limited access, LT has become the standard of care for patients with small HCCs and the main driving force for alternative strategies offered to patients with intermediate HCCs. In 1996, a prospective cohort study defined restrictive selection criteria that led to superior survival for transplant patients in comparison with any other previous experience with transplantation or other options for HCC. Since then, these selection criteria have become universally known as the Milan criteria (MC) in recognition of their origin. Ever since their adoption in clinical practice, the MC have helped doctors to single out early-stage HCC as a prognostic category of cancer presentation that is amenable to curative treatments. After their implementation, the favorable posttransplant outcomes that were observed in cohort series were so convincing that the MC immediately became the standard of care for early HCC, and further validation by randomized controlled trials (RCTs) was prevented. After the passage of approximately a decade, researchers began to challenge the MC with other proposals designed to capture those patients not meeting the MC who could achieve similar posttransplant survival rates through the expansion of the accepted tumor limits for transplant eligibility. None of these expanded criteria have become the new reference standard for selecting LT candidates with HCC; any broadening of the selection criteria for transplantation is inevitably hampered by severe

Retrospective-prospective study of safety and efficacy of sofosbuvir-based direct-acting antivirals in HIV/HCV-coinfected participants with decompensated liver disease pre- or post-liver transplant.

INTRODUCTION: The Acute Graft-versus-Host Disease (GVHD) is one of the rare complications after liver transplant (LT) with prevalence up to 2%. Among solid organ transplant, intestinal transplant has the highest incidence followed by LT. Unfortunately, no universal treatment guidelines are available for this disease with poor outcomes and mortality up to 85%. CASE DESCRIPTION/METHODS: 67-year-old male underwent orthotopic LT for end-stage liver failure due to Nonalcoholic steatohepatitis. CMV- patient received ABO identical cadaveric donor liver with CMV + serology. He had no peri-operative complications and was started on immunosuppression and antimicrobial therapies. Within 40 days of LT, he developed leukopenia and early transplant rejection, which was treated with medications. Within 100 days, patient developed rash on extremities and trunk that later spread to face, palms and soles. His course was further complicated by CMV seroconversion around 130 days post-LT. On day 168, patient presented with pancytopenia and continuing skin rash. The initial skin biopsy indicated drug induced reaction, but subsequent biopsy was consistent with GVHD. His treatment regime included steroid, tacrolimus, and rabbit Anti-thymocyte globulin (ATG) with broad-spectrum antimicrobials. Chimerism was initially 19% donor cells in the blood and it was 55% after 4 doses of ATG. He became septic and on day 209 succumbed to massive brain hemorrhage. DISCUSSION: GVHD after LT is in of the lethal complication that usually develops within 3-5 weeks. The key is to have a high index of suspicion with recognition of clinical signs; characteristic itchy palmar skin rash, diarrhea, fever, pancytopenia with normal LFTs. The symptoms are not specific and often diagnosed as infection or drug allergies. GVHD diagnosis can be established with skin lesion or GI tract biopsy and further confirmed with chimerism >30% in the blood of recipient. There is no consensus on treatment. Various strategies are adopted to suppress activated donor lymphocytes, including but not limited to, reduction or even withdrawal of immunosuppression, change in regimen with or without adding steroid boluses, IL-2 antagonist, antithymocyte/lymphocyte globulin, or use of OKT3. Broad-spectrum antimicrobial coverage is pivotal to prevent superimposed infection which is the main cause of death. Further studies are needed to raise the awareness among clinicians and to improve outcomes in patients who develop GVHD following LT.

Lack of Correlation of Endospcopy Findings and Pathological Results In GI-GvHD

Optimizing care for GI disorders in children after hematopoietic stem cell transplantation

To document the clinical experience in the diagnosis and treatment of graft-versus-host disease(GVHD) after liver transplantation. Clinical course was followed up and laboratory examinations were done in 3 patients with orthotopic liver transplantation (OLT) who developed acute GVHE. The diagnosis depended on clinical manifestations, skin biopsy, HLA typing and PCR short tandem repeat (PCR-STR). Immunosuppressive drugs were transferred and adjusted. Fever, shin rash, diarrhea and pancytopenia were found within 3 to 8 weeks after liver transplantation. The liver function was normal. CMV antigen (pp65) and EBV antibody (IgM) were negative. The donor's HLA was detected in the host's peripheral blood cells. One female recipient had the donor's Y chromosome microchimerism detected by PCR-STR. All 3 patients died from infection, alimentary tract bleeding, or multiple organ failure in the end. GVHD is not a rare complication easily misdiagnosed with pessimism out come after liver transplantation.

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Covering the Cover

The diagnosis of graft-versus-host disease (GvHD) after liver transplantation can be difficult because early symptoms are often nonspecific. In this study, the presence of donor lymphocyte macrochimerism in recipient peripheral blood was examined as a diagnostic aid for GvHD after cadaveric donor liver transplantation. Between 1996 and 2002, 33 liver transplant recipients with a clinical suspicion of GvHD (skin rash, diarrhea, pyrexia, pancytopenia, or anemia, without an obvious alternative cause) were investigated for peripheral blood donor lymphocyte macrochimerism. Donor macrochimerism was determined at the time of first clinical presentation by a low-sensitivity polymerase chain reaction (PCR) to detect donor human leukocyte antigen (HLA) alleles using genomic DNA extracted from recipient peripheral blood. Where donor HLA alleles were detected, the percentage of donor T cells was quantified by two-color flow cytometric analysis using antibodies specific for mismatched donor and recipient HLA alleles. The relationship between the presence or absence of donor lymphocyte macrochimerism and final diagnoses based on clinical and histological criteria was examined. Seven of the 33 patients were PCR positive for donor HLA alleles. All had macrochimerism, with donor T lymphocyte levels ranging from 4% to 50% of circulating lymphocytes. All seven patients had normal liver function tests, skin rash, and diagnosis of GvHD histologically confirmed by skin or gut biopsies. Twenty-six patients were PCR negative, and, in 23, an alternative diagnosis was eventually established. The remaining three patients made a rapid and spontaneous recovery with no further symptoms suggestive of GvHD. Donor lymphocyte macrochimerism was present in all patients in whom the diagnosis of GvHD was confirmed. In patients with symptoms consistent with GvHD and a negative PCR for donor HLA, an alternative diagnosis was eventually established or the patients recovered spontaneously. Detection of donor HLA alleles in recipient peripheral blood by PCR is a useful diagnostic tool for GvHD after liver transplantation.