Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion

Johns Hopkins University, Baltimore, Maryland, United States
Blood (Impact Factor: 10.45). 01/2003; 100(12):3903-7. DOI: 10.1182/blood-2002-03-0857
Source: PubMed


Graft-versus-host disease (GVHD) of the liver is characterized by bile duct damage and portal lymphocytic infiltrate. We report acute hepatitislike presentation of GVHD after donor lymphocyte infusion (DLI). Between April 1998 and September 2001, 73 patients received 94 DLI treatments. Liver GVHD developed after DLI in 22 (30%) patients whose median age was 43 years (range, 21 to 61 years). Onset of liver dysfunction was at 35 days (range, 11 to 406 days) after DLI. Fifteen patients underwent liver biopsy, and the diagnosis of liver GVHD was confirmed in 13 (87%) patients. After viral hepatitis and recent drug exposure were excluded, 11 (50%) patients were given a diagnosis of a hepatitic variant of GVHD based on histologic evidence of lobular hepatitis (n = 5), elevation of maximum serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level more than 10 times the upper normal limit (n = 9), or both. There was a significant difference in maximum ALT (P =.002) and AST (P =.01) level between the hepatitic-variant and classical GVHD groups. GVHD progressed in 14 (64%) patients, and 10 patients died after a median follow-up of 221 days (range, 31-1284 days). These observations suggest that GVHD that occurs after DLI may have distinct clinical features. Hepatitic-variant GVHD should be considered in the differential diagnosis in DLI recipients with unexplained hepatitis.

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    • "Isolated hepatic chronic GVHD is being seen with increased frequency with the use of donor-lymphocyte infusions (Arai et al, 2002). Furthermore, while cholestasis is the normal finding, the concept of hepatitic chronic GVHD is now being identified more often, with some patients presenting mostly with elevations of serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (Strasser et al, 2000; Akpek et al, 2002). Hepatitic GVHD can also be seen in children (Melin- Aldana et al, 2007). "
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    ABSTRACT: Chronic graft-versus-host disease (GVHD) is a major complication after allogeneic haematopoietic stem cell transplantation (HSCT). Not only is it the major cause of late mortality in HSCT patients, but it also accounts for significant morbidity. Much of the literature on chronic GVHD has focused on adults. Chronic GVHD is of major importance in children, especially since they have years to live following the complications of chronic GVHD and its therapy. The goal is to review incidence, manifestations, and therapies, especially when applicable to the paediatric population.
    Preview · Article · Aug 2010 · British Journal of Haematology
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    • "After three months, the occurrence of late hepatitis is possible, which coincides with a decrease in or discontinuation of immunosuppressive therapy and a return of cellular immunity [12] [13] [26] [30] [31]. The most difficult situation at this time is the unusual presentation of liver GVHD (hepatic Variant), resembling viral hepatitis [32] [33], also described after donor lymphocyte infusion [34], in which liver biopsy is essential to confirm GVHD. "
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    ABSTRACT: Hepatitis C virus (HCV) is a major cause of liver disease worldwide. After allogeneic Hematopoietic Cell Transplant (HCT), HCV is known to be associated with transient hepatitis in the immediate post-transplant period, and a potential risk factor of veno-occlusive disease (SOS). Very recently, HCV-infected HCT recipients have been shown to be at higher risk of earlier cirrhosis, leading to greater morbidity and mortality. Long-term survivors after HCT are thus at a high risk for HCV-related complications and, as a consequence, the treatment of HCV infection becomes critical. We describe here the potential clinical complications in HCV-infected recipients, in the short, but also the long-term follow-up after HCT. The pathophysiology of liver fibrosis is discussed as well as the present recommended therapy in this particular population.
    Preview · Article · Jul 2008 · Journal of Hepatology
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    • "The gastrointestinal manifestations include diarrhea which may become bloody, cramping, nausea, vomiting and failure to thrive [2]. Furthermore, jaundice from hyperbilirubinemia is the hallmark of liver GVHD [3], although a hepatitic variant of GVHD with a rise in liver enzymes like an acute viral hepatitis, has been recognized [4,5]. While acute GVHD is a clinical diagnosis, there are other conditions that can mimic or coexist with GVHD, such as drug toxicity (especially common in patients post transplant on multiple antimicrobial agents, immunosuppressive drugs, hyperalimentation, receiving methotrexate, etc.) and infection. "
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    ABSTRACT: Acute graft-versus-host disease (GVHD) occurs after allogeneic hematopoietic stem cell transplant and is a reaction of donor immune cells against host tissues. Activated donor T cells damage host epithelial cells after an inflammatory cascade that begins with the preparative regimen. About 35%-50% of hematopoietic stem cell transplant (HSCT) recipients will develop acute GVHD. The exact risk is dependent on the stem cell source, age of the patient, conditioning, and GVHD prophylaxis used. Given the number of transplants performed, we can expect about 5500 patients/year to develop acute GVHD. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea). One or more organs may be involved. GVHD is a clinical diagnosis that may be supported with appropriate biopsies. The reason to pursue a tissue biopsy is to help differentiate from other diagnoses which may mimic GVHD, such as viral infection (hepatitis, colitis) or drug reaction (causing skin rash). Acute GVHD is staged and graded (grade 0-IV) by the number and extent of organ involvement. Patients with grade III/IV acute GVHD tend to have a poor outcome. Generally the patient is treated by optimizing their immunosuppression and adding methylprednisolone. About 50% of patients will have a solid response to methylprednisolone. If patients progress after 3 days or are not improved after 7 days, they will get salvage (second-line) immunosuppressive therapy for which there is currently no standard-of-care. Well-organized clinical trials are imperative to better define second-line therapies for this disease. Additional management issues are attention to wound infections in skin GVHD and fluid/nutrition management in gastrointestinal GVHD. About 50% of patients with acute GVHD will eventually have manifestations of chronic GVHD.
    Full-text · Article · Feb 2007 · Orphanet Journal of Rare Diseases
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