Hepatitic graft-versus-host disease after hematopoietic stem cell transplantation: Clinicopathologic features and prognostic implication

Department of Medicine, Queen Mary Hospital, Hong Kong, China.
Transplantation (Impact Factor: 3.83). 05/2004; 77(8):1252-9. DOI: 10.1097/01.TP.0000120383.30088.A4
Source: PubMed


Graft-versus-host disease (GVHD) of the liver after allogeneic hematopoietic stem cell transplantation classically presents with increased bilirubin and alkaline phosphatase (ALP) levels. A hepatitic variant was recently recognized, with more than a 10-fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. This study defines the clinicopathologic features and prognostic implications of hepatitic GVHD compared with classic liver GVHD.
A total of 38 cases of hepatitic GVHD, 68 cases of classic liver GVHD, and 13 cases of hepatitis B virus (HBV)-related hepatitis after hematopoietic stem cell transplantation were analyzed.
Hepatitic GVHD cases showed significantly higher ALT, AST, and ALP levels compared with classic liver GVHD cases (at onset, mean ALT: 154 vs. 58 U/L, P <0.001; AST: 167 vs. 77 U/L, P <0.001; at peak, ALT: 435 vs. 112 U/L, P <0.001; AST: 587 vs. 150 U/L, P <0.001; ALP: 416 vs. 238 U/L, P =0.001), persisted longer (74 vs. 32 days, P =0.006), and showed more lobular pathologic changes in biopsy (lobular changes: 16/26 vs. 4/19, P =0.007; hepatocyte necrosis: 16/26 vs. 6/19, P =0.008; acidophil bodies: 15/26 vs. 4/19, P =0.014) but less cholestasis (4/26 vs. 8/19, P =0.045). However, cumulative doses of immunosuppressants prescribed, response, and outcome were similar. Compared with hepatitic GVHD, HBV-related hepatitis occurred later (95 vs. 184 days, P =0.049), but clinical and biochemical profiles were similar, requiring liver biopsies for their distinction.
Hepatitic and classic liver GVHD differed biochemically and pathologically, but these differences showed no obvious impact on outcome. The distinction of hepatitic GVHD from other hepatitis is mandatory.

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    • "GVHD of the liver after allogeneic hematopoietic stem cell transplantation classically presents with increased bilirubin and alkaline phosphatase (ALP) levels. A hepatitic variant presenting more than a 10- fold increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels was recently recognized [41]. Finally, human mesenchymal stem cell transfusion has demonstrated to improve liver function in acute-on-chronic liver failure patients [42]. "
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    ABSTRACT: To evaluate the potential therapeutic effect of the infusion of hMSCs for the correction of liver injuries, we performed total body radiation exposure of NOD/SCID mice. After irradiation, mir-27b level decreases in liver, increasing the directional migration of hMSCs by upregulating SDF1 α . A significant increase in plasmatic transaminases levels, apoptosis process in the liver vascular system, and in oxidative stress were observed. hMSC injection induced a decrease in transaminases levels and oxidative stress, a disappearance of apoptotic cells, and an increase in Nrf2, SOD gene expression, which might reduce ROS production in the injured liver. Engrafted hMSCs expressed cytokeratin CK18 and CK19 and AFP genes indicating possible hepatocyte differentiation. The presence of hMSCs expressing VEGF and Ang-1 in the perivascular region, associated with an increased expression of VEGFr1, r2 in the liver, can confer a role of secreting cells to hMSCs in order to maintain the endothelial function. To explain the benefits to the liver of hMSC engraftment, we find that hMSCs secreted NGF, HGF, and anti-inflammatory molecules IL-10, IL1-RA contributing to prevention of apoptosis, increasing cell proliferation in the liver which might correct liver dysfunction. MSCs are potent candidates to repair and protect healthy tissues against radiation damages.
    Full-text · Article · Nov 2013
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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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    • "Tissue defects, including cellular loss and/or function, can be treated with stem cell regenerative therapy. Contending with the HBV epidemic made China a pioneer in the advancement of allogeneic hematopoietic stem cell transplantation for the prevention or deferral of hepatitis (Lau et al., 2002; Ma et al., 2004). As a result of high incidence of insulin resistance in China, researchers at the Third Military Medical University in Chongqing are investigating the plasticity and transdifferentiation potential of adult pancreatic ductal cells as potential stem cells into insulin producing islet cells with positive findings (Yao, Qin, Liu, Chen, & Zhou, 2004). "
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    ABSTRACT: Science and technology of Republican China (1912-1949) often replicated the West in all hierar- chies. However, in 1949 when the Chinese Communist Party (CCP) declared the nation the Peo- ple's Republic of China, it had assumed Soviet pseudo-science, namely neo-Lamarckian and anti- Mendelian Lysenkoism, which led to intense propaganda campaigns that victimized intellectuals and natural scientists. Not until the 1956 Double Hundred Campaign had China engaging in meaningful exploration into modern genetics with advancements of Morgan. The CCP encour- aged discussions on the impact of Lysenkoism which cultivated guidelines to move science for- ward. However, Mao ended the campaign by asserting the Anti-Rightist Movement (1957) that reinstated the persecution of intellectuals, for he believed they did not contribute to his socialist ethos of the working people. The Great Leap Forward (1958-1959), an idealist and unrealistic attempt to rapidly industrialize the nation, and the Cultural Revolution (1966-1976), a grand at- tempt to rid China of the "technological elite," extended China's lost years to a staggering two decades. Post-Mao China rapidly revived its science and technology frontier with specialized sci- ences: agricultural biotechnology, major genomic ventures, modernizing Traditional Chinese Medicine, and stem-cell research. Major revisions to the country's patent laws increased interna- tional interest in China's resources. However, bioethical and technical standards still need to be implemented and locally and nationally monitored if China's scientific advances are to be glob- ally accepted and commercialized.
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