Aplastic Anemia Complicating Orthotopic Liver Transplantation for Non-A, Non-B Hepatitis

Aplastic anemia developed in 9 of 32 patients (28 percent) undergoing orthotopic liver transplantation for acute non-A, non-B hepatitis, at one to seven weeks after the procedure. No patient previously had evidence of hematologic dysfunction or conditions known to be associated with aplastic anemia. No other cases of aplastic anemia were identified among 1463 patients undergoing liver transplantation for all other indications at the four centers participating in the study (chi-square = 415, P<0.001; 95 percent confidence interval for the incidence of aplastic anemia after transplantation for non-A, non-B hepatitis, 13 to 44 percent, vs. 0.00 to 0.13 percent for all other indications). The operative and postoperative treatment of these patients was not otherwise different, indicating that the aplastic anemia was a complication of the hepatitis, not of the transplantation procedure. Four of the nine patients died of complications due to infections. Three of the surviving patients have been followed for less than six months, one for one year, and one for two years. The two patients followed the longest have recovered marrow function to an appreciable degree, and two of the others have evidence of early recovery. We conclude that patients undergoing orthotopic liver transplantation for non-A, non-B hepatitis are at a high risk for the development of aplastic anemia. (N Engl J Med 1988; 319:393–6.) © 1988, Massachusetts Medical Society. All rights reserved

Liver transplantation for patients with human immunodeficiency virus and hepatitis C virus coinfection with special reference to hemophiliac recipients in Japan.

Liver transplantation for patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) remains challenging. The advent of highly active antiretroviral therapy (HAART) for HIV has reduced mortality from opportunistic infection related to acquired immunodeficiency syndrome dramatically, while about 50% of patients die of end-stage liver cirrhosis resulting from HCV. In Japan, liver cirrhosis frequently develops after HCV-HIV coinfection resulting from previously transfused infected blood products for hemophilia. The problems of liver transplantation for those patients arise from the need to control calcineurin inhibitor with HAART drugs, the difficulty of using interferon after liver transplantation with HAART, and the need to control intraoperative coagulopathy associated with hemophilia. We review published reports of liver transplantation for these patients in the updated world literature

Viral interleukin-10 gene therapy to induce tolerance to solid organ transplants in mice

In this study, a novel gene therapy approach to prolong allograft survival was designed. Autologous (syngeneic) hematopoietic stem cell–enriched bone marrow cells (HSC; lin −) engineered with the vIL-10 gene (vIL-10-HSC) were injected (4 to 6 × 10 6 cells, iv) into lethally (9.5 Gy) or sublethally (4 Gy) irradiated CBA/J mice 6 weeks prior to allogeneic heart (C57BL/6) transplantation (Tx). Cardiac allograft survival was significantly ( P 100 days; recipient T lymphocytes demonstrated hyporeactivity to donor and third-party antigens in mixed lymphocyte cultures. These findings have important implications and potential therapeutic applications in transplantation and autoimmune diseases

Effect of Pretransplant Hepatitis C Virus RNA Status on Posttransplant Outcome

Undetectable hepatitis C virus (HCV) RNA [RNA(−)] before liver transplantation (OLT) has been shown to decrease the rates of disease recurrence. We sought to determine whether RNA(−) subjects differ in post-OLT recurrence (virological/VR, histological/HR), graft failure (GF), or patient survival from RNA(+) patients using a retrospective review. From 1995 to 2004, a total of 49 patients were RNA(−) at OLT as a result of interferon-based therapy: 22 SVR and 27 with end-of-treatment response (ETR) transplanted when RNA(−) within 6 months of ET. Forty-eight RNA(+) patients were analyzed as controls. Virological recurrence (VR) was seen in 55% of RNA(−) subjects with no difference in HR between RNA(−) vs (+) groups, namely 36.7% versus 56.3% ( P = .068), respectively. The RNA(+) subjects showed a lower time to HR (5.6 vs 11 months; P = .027). The SVR subjects displayed lower VR (36.4%) and histological recurrence (HR) (13.6%) compared to ETR (VR 70.4%, P = .023; HR 55.6%, P = .003) or RNA(+) (HR 56%, P = .0008). The SVR subjects, who were identified with a sensitive assay (SVR(S), lower limit <600 IU/mL) showed no VR, HR, or GF. The 1- and 5-year survivals were 87.8%/75.6% and 89.6%/77.8% for RNA(−) and (+) groups, respectively ( P = .77). In conclusion, RNA(−)-transplanted patients displayed lower VR and longer time to HR. The SVR patients showed lower VR and HR compared to ETR and RNA(+) patients

Abdominal Wall Transplantation: Surgical and Immunologic Aspects

Abdominal wall transplantation is a type of composite tissue allograft that can be utilized to reconstitute the abdominal domain of patients undergoing intestinal transplantation. We have presented herein combined experience and long-term follow-up results of a series of abdominal wall transplants performed at 2 institutions. A total of 15 abdominal wall transplants from cadaveric donors were performed in 14 patients at the end of intestinal transplant surgery or, in 2 cases, a few days after the primary intestinal transplant. The vascular supply was through the inferior epigastric vessels, from the iliac vessels in 12 cases and via a microsurgical technique in 3 cases. Immunosuppression consisted of induction with alemtuzumab and maintenance treatment with tacrolimus monotherapy. Two grafts lost to vascular thrombosis were removed. Five patients are still alive, although all deaths were unrelated to the abdominal wall transplant. There were 3 episodes of abdominal wall graft rejection, treated with steroids; the abdominal wall graft and the intestinal grafts experienced rejection independent from each other. In summary, abdominal wall transplantation is a feasible technique for recipients of intestinal or multivisceral transplants, when the closure of the abdominal cavity by primary intention is technically impossible

Impact of Steroids on Natural Killer Cells Against Cytotoxicity and Hepatitis C Virus Replication

Natural killer (NK) cells play important roles in killing tumor and virus-infected cells. Immunosuppression used after organ transplantation is thought to increase the risk of tumor recurrence and viral infections. However, the effect of immunosuppressive drugs on NK cells has not yet been clearly established. Therefore, we examined the effect of immunosuppression on NK cells. NK cells were cultured for 7 days in the presence of interleukin-2 (100 U/mL) with or without the following immunosuppressive drugs: tacrolimus, cyclosporine A, corticosteroid (methylprednisolone [MP]), mycophenolate mofetil, and rapamycin. The effect of the drugs on NK cell activation was tested on the basis of the following: NK cell phenotype, NK cell proliferation, cytotoxicity against K562 cells, cytokine production by NK cells, and anti-hepatitis C virus (HCV) activity with HCV genomic replicon cells. NK cells showed relatively robust functions in the presence of tacrolimus and cyclosporine A. Mycophenolate mofetil and rapamycin significantly prevented only NK cell proliferation (P < .05). In contrast, MP significantly inhibited the proliferation, cytotoxicity, and anti-HCV effect (10.9%, 18.5%, and 1.9%, respectively) of NK cells. Furthermore, MP specifically inhibited the expression of NK cell activation markers and the production of interferon-γ (P < .05). Corticosteroids have distinct effects on NK cells, which may have important implications for NK cell function in cytotoxicity and HCV effect after transplantation

Expanded use of transplantation techniques: abdominal wall transplantation and intestinal autotransplantation

Surgical principles and techniques derived from organ transplantation surgery can provide novel applications in general surgery. We present an update on our 5-year experience with intestinal autotransplantation and abdominal wall transplantation. Nine patients underwent intestinal or multivisceral transplantation with the addition of 10 abdominal wall grafts to cover the large open areas from previous surgeries. Seven patients underwent near-total abdominal evisceration, ex vivo resection of masses at the base of the mesentery, followed by intestinal autotransplantation; 44% of the abdominal wall graft recipients are alive, but none of the fatalities were related to the graft itself. In two cases the graft had to be removed due to venous thrombosis. Of patients with intestinal autotransplants, 71% are alive with two mortalities due to recurrent metastatic malignancy. In only one case, the intestinal autograft had to be removed because of venous thrombosis. All surviving patients but one are on a regular diet; two are on supplemental enteral feeds. These results show that anastomotic and resection techniques derived from the experience in solid organ transplant can be utilized in complex wound closure, as is the case of abdominal wall transplantation, or resection of large retroperitoneal tumors with intestinal autotransplantation

The Impact of Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome on Progression of Fibrosis in Patients With Recurrent HCV After Liver Transplantation

Nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MS) have been shown to play a role in disease progression and response to therapy in patients with chronic hepatitis C virus (HCV) infection. The primary objective of this study was to evaluate the impact of coexisting NAFLD and MS on the progression of fibrosis in patients with recurrent HCV treated with interferon (IFN)/ribavirin after orthotopic liver transplantation (OLT). From 1998 to 2004, a total of 418 patients underwent OLT in our center for HCV-related cirrhosis. Thirty-five patients with recurrent HCV on IFN/ribavirin treatment, who had at least 2 posttransplant liver biopsies at least 6 months apart, were included in the study. Patients who had MS at the time of their first posttransplant biopsy were identified. The first and last posttransplant biopsies were assessed for the presence and severity of NAFLD, grade of inflammation, and stage of fibrosis. The fibrosis progression rate (FPR) was calculated and expressed in fibrosis units per month (FU/mo). Among 35 patients, 34% were diagnosed with NAFLD in the first posttransplant biopsy. The mean FPR was 0.05 ± 0.16 FU/mo in the presence of NAFLD compared to 0.07 ± 0.10 FU/mo in its absence ( P = .68) and 0.03 ± 0.06 FU/mo in the presence of MS versus 0.10 ± 0.15 FU/mo in its absence ( P = .06). When FPR values were divided into two categories of <0.16 FU/mo or ≥0.16 FU/mo (below/above the 25% upper quartile) or <0.08 FU/mo or ≥0.08 FU/mo (below/above the 50% upper quartile), there was no correlation between FPR categories and the presence of NAFLD with or without MS, only MS, or the absence of both in the first liver transplant biopsy ( P = .13). Coexisting NAFLD or MS had no significant effect on the progression of fibrosis after OLT in patients with treated hepatitis C after OLT