C.-F. Lee

Clinical perspective of acute humoral rejection after blood type-compatible liver transplantation.

Acute humoral rejection (AHR) is antibody-mediated rejection caused by complement activation and antibodies against the donor graft, and it usually occurs immediately (hyperacute) or during the first week (acute) after organ transplantation (1). The liver allograft has been considered relatively resistant to immunologic rejection, and most liver graft rejections are cellular rejections (2). Although AHR is well described in blood type-incompatible liver transplantation (LT) (3), its occurrence in blood type-compatible LT is an uncommon complication. Clinically, AHR diagnosis currently relies on histologic findings, presence of donor-specific antibodies, and graft dysfunction (1, 4). However, early detection and treatment of AHR after LT remains uncertain. Among 316 LTs, 6 patients (1.9%) had AHR within 2 weeks after LT (range 5–14 days). Table 1 summarizes the clinical features of AHR patients after LT. All patients first presented with rapid increase of liver enzymes, which increased by 2or 3-fold every 6 hr (see Figure 1A, Supplemental Digital Content 1, http://links.lww.com/TP/A348). However, increased liver enzymes levels were refractory to pulse therapy and recycling steroids. Main portal vein stenosis or thrombosis were not observed; however, Doppler sonography showed a markedly decreasing portal flow (see Figure 1B, Supplemental Digital Content 1, http://links.lww.com/TP/A348). Furthermore, examination of artery flow revealed no significant variation. Tissue biopsies of liver grafts for histologic examinations were obtained from three patients; all demonstrated massive coagulative necrosis of the liver parenchyma and occluded small branches of portal vessels. However, no inflammatory cell infiltration existed in the remaining portal tracts, and immunohistochemical examinations were all positive for C4d deposition in vessel walls. These finding indicate that the deterioration of liver function was not because of vascular complication but likely related to AHR. Five (83%) of six patients with AHR died because of inappropriate management, and only one patient was successfully rescued by early plasmapheresis combined with bortezomib therapy. At the start of AHR, this patient also exhibited extensive increase of liver enzymes, followed by decreased portal flow. There-

Impact of portal venous hemodynamics on indices of liver function and graft regeneration after right lobe living donor liver transplantation

The aim of this study was to evaluate the effects of portal hemodynamics on indices of liver function and graft regeneration in patients after adult right lobe living donor liver transplantation (R‐LDLT). Sixty‐four patients who underwent R‐LDLT and had an uneventful postoperative course were enrolled in this study. The contribution of portal flow was greater to the recipient grafts versus the donor livers (90.74% versus 69.12%, P < 0.0001). Portal flow variations decreased significantly during the first 10 days after R‐LDLT (P < 0.0001); variations in the hepatic arterial flow were more constant during this period (P = 0.812). The mean portal venous pressure (PVP) before recipient hepatectomy (the initial PVP) was 23.1 ± 4.0 mm Hg; the mean PVP after reperfusion (the final PVP) was 15.0 ± 4.3 mm Hg (P < 0.0001). Furthermore, the mean hepatic portal venous gradient (ie, PVP − central venous pressure) before recipient hepatectomy was 17.1 ± 4.3 mm Hg; it decreased to 10.6 ± 4.5 mm Hg after reperfusion (P < 0.0001). These findings suggest that after graft reperfusion, the vascular resistance of the hepatic parenchyma decreased, and there was an associated mild decrease in the portal hypertension. Multiple regression analysis indicated that PVPs correlated significantly with indices of liver function after living donor liver transplantation (P < 0.05). Patients were separated into 4 groups according to their PVP values: group A (initial PVP ≥ 23 mm Hg, final PVP ≥ 15 mm Hg), group B (initial PVP < 23 mm Hg, final PVP ≥ 15 mm Hg), group C (initial PVP ≥ 23 mm Hg, final PVP < 15 mm Hg), and group D (initial PVP < 23 mm Hg, final PVP < 15 mm Hg). Immediately after R‐LDLT, the peak values for aspartate aminotransferase, alanine aminotransferase, the international normalized ratio and the average ascites production varied appreciably in these groups. The regeneration rate of the liver graft 3 months after R‐LDLT was significantly greater in group A versus the other groups. In conclusion, PVP is a significant hemodynamic factor that influences the functional status of the liver and graft regeneration after R‐LDLT. Liver Transpl 17:1035–1045, 2011.

Inhibition of allogenic T-cell cytotoxicity by hepatic stellate cell via CD4⁺ CD25⁺ Foxp3⁺ regulatory T cells in vitro.

BACKGROUND The liver is considered to be an immune-privileged organ. Several types of liver cells have been implicated in the induction of immunologic tolerance. Hepatic stellate cells (HSCs) seem to participate in hepatic fibrosis and to display immunological properties. MATERIALS AND RESULTS In this study, HSCs isolated from C3H mice were highly positive for GFAP (98.4%) and α-SMA (95.4%). After stimulation by interferon-γ (IFN-γ), HSCs were more active in morphology with enhanced expression of H2-K(K), I-A(K), CD80, and CD54, similar to mature myelogenic dendritic cells (MDCs). Through allogeneic stimulation, C3H HSCs induced proliferation of both CD8(+) and CD4(+) T cells in B6 mice. However, the T cells activated by allogeneic HSCs produced less INF-γ, interleukin (IL)-4, IL-10, and IL-17, but large amount of transforming growth factor-β. These T cells expressed immunoregulatory rather than effector functions. Naïve T cells stimulated by allogeneic HSCs expressed Foxp3 compared with MDCs (8.67% vs 2.14%, P < .05). CD8(+) T cells activated by HSCs lost their allogeneic cytotoxicity, and CD4(+) T cells activated in this fashion suppressed the allogeneic cytotoxicity of CD8(+) T cells activated by MDCs. CONCLUSION HSCs seem to act as liver-resident antigen-presenting cells instructing the generation of Foxp3(+) regulatory T cells, a property suggestion of induction of immunologic tolerance.

Split-Liver Transplantation in 2 Adults: Significance of Caudate Lobe Outflow Reconstruction in Left Lobe Recipient: Case Report

Split-liver transplantation is a well-known procedure for increasing the donor pool. The procedure is commonly used in 1 adult and 1 child, but is less commonly performed in 2 adults because of technical difficulty and poor outcome in left-lobe recipients. Preservation of caudate lobe function is important in recipients with borderline graft-recipient weight ratio to achieve better results. Herein, we report a case in which caudate lobe outflow was reconstructed in a left lobe with a caudate lobe graft in split-liver transplantation in 2 adults.

Outcome of Living Donor Liver Transplantation for Patients With Preoperative Portal Vein Thromobosis.: Abstract# D2614

D2615 58 Consecutive Living Liver Donors. Implementation of an Educational Service Agreement Between Fundacion Programa Metropolitano De Trasplante De Hígado at Caracas, Venezuela and The Liver Transplant Center of Columbia University at New York, USA. M. De Guglielmo,1 D. Del Valle,1 E. Pestana,1 D. Marin,1 M. Vasallo,1 C. Rodriguez,1 T. Kato,2 P. Rivas.1 1Programa Metropolitano de Trasplante de Higado Fundahigado, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of; 2Department of Surgery, Center for Liver Disease and Transplantation, Columbia University, New York, NY. Background: Liver transplant (LT) is the only therapeutic option for patients with end stage liver disease. Living donor liver transplant (LDLT) program was initiated in our country in 2005 as part of an Educational Service Agreement between the Programa Metropolitano de Trasplante de Hígado-Fundahígado and the LT Program at Columbia University in New York. This is a report after 58 consecutive cases Patients and methods: 143 patients were initially evaluated, 43 potential donors were rejected, 16 are still in evaluation and 27 patients withdrew for personal reasons. The medical fi les of 58 donors that were used for actual liver transplantwere reviewed. Each donor underwent a pretransplant evaluation protocol that included standard cardiopulmonary and renal work up and complete blood evaluation, angioTAC, colangioMRI, psychiatric, social evaluation and hepatic biopsy if necessary. Results: we included 58 donors with ages raging between 18 and 52 years. 26 left lateral, 24 left and 8 right hepatectomies were performed. 13 donors developed complications: 8 grade I, 3 grade II, 1 grade IIIa and 1 IIIb, according to the Clavien classifi cation system for surgical complications (4 intraabdominal collections, 5 wound infections, 2 biliary fi stulae, 1 endocarditis, 1 enterocolitis, and 1 patient needed surgery for an intrabdominal collection). Mortality in this group was 0 %. All donors are in excellent physical conditions and returned to their daily activities within a period between 1 and 3 months after donation. Conclusion: Living Donor Liver transplantation is a safe procedure for donors. Surgery was performed with excellent results and cero mortality. The rate of complication was 22.4% however most of them where low grade complications. All donors returned to their daily activity within three weeks after surgery. Abstract# D2616 Living Donor Liver Transplantation. Outcome After 58 Transplants in Adult and Children in a Single Center. M. De Guglielmo,1 D. Del Valle,1 E. Pestana,1 D. Marin,1 L. Aguero,1 C. Lozada,1 A. Sala,1 M. Vasallo,1 C. Rodriguez,1 H. Malavé,1 T. Kato,2 P. Rivas.1 1Programa Metropolitano de Trasplante de Higado Fundahigado, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of; 2Department of Surgery, Center for Liver Disease and Transplantation, Columbia University, New York, NY. Background: Liver transplantation (LT) is the only therapeutic option for patients with end stage liver disease. Living donor liver transplant (LDLT) program was initiatedin our country in 2005 as part of an Educational Service Agreement between the Programa Metropolitano de Trasplante de Hígado-Fundahígado and the LT Program at Columbia University in New York. This is the fi rst report after 58 consecutive cases Patients and methods: The medical fi les of LDLT recipients from April 2005 to November 2013 were reviewed. Living LiverDonor (LLD) evaluation protocol included standard cardiopulmonary and renal work up and complete blood evaluation, angioTAC, colangioMRI, psychiatric, social evaluation and hepatic biopsy if necessary. Recipients underwent standard LT work up.Graft and patient survival was determined by Kaplan-Meier method. Results: 58 patients [40 (69%) pediatrics patients and 18 (31%) adults] received LDLTfrom LDL. 26 left laterals, 24 left and 8 right lobes grafts were transplanted. The most common indication for transplantation was biliary atresia in children (35%) and autoimmune hepatitis in adults (28%). 13 donors developed complications (8 grade I, 3 grade II, 1 grade IIIa and 1 IIIb, according to the Clavien classifi cation system for surgical complications). All donors are in excellent physical conditions and returned to their daily activities within a period between 1 and 3 months after donation. In the recipients theincidence of mayor vascular complications was 20% in pediatric and 22% in adult recipients. Biliary complications developed in 10% of pediatric and 11% of adult patients. Graft and patient survival were 89% and 80% respectively at 1 year and 82% and 74% at 5 years. Conclusion: Living donor liver transplantation constitutes an alternative for our patients with end stage liver disease. It is a safe procedure with a low complication rate for liver donors. Abstract# D2617 Volumetry Guided Right Hepatectomy in The Presence of Hypolastic Left Lateral Segment in the LivingDonor. S. Kapoor,1 S. Maheshwari,2 B. Nath,1 V. Varma,1 A. Shah,1 V. Kumaran.1 1Liver Transplantation & HPB Surgery, Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute, Mumbai, Maharashtra, India; 2Radiodiagnosis, Kokilaben Dhirubhai Ambani Hospital& Medical Research Institute, Mumbai, Maharashtra, India. D2617 Volumetry Guided Right Hepatectomy in The Presence of Hypolastic Left Lateral Segment in the LivingDonor. S. Kapoor,1 S. Maheshwari,2 B. Nath,1 V. Varma,1 A. Shah,1 V. Kumaran.1 1Liver Transplantation & HPB Surgery, Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute, Mumbai, Maharashtra, India; 2Radiodiagnosis, Kokilaben Dhirubhai Ambani Hospital& Medical Research Institute, Mumbai, Maharashtra, India. Background:Variant anatomy often leads to exclusion of potential living donors. However, in Asia andIndia, there is near total reliance on living donation. We report the case of a successful living donor righthepatectomy in the presence of hypoplastic segments 2 &3. Method:A 42 year old male suffering fromcirrhosis, MELD 16, hepato-hydrothorax & ascites with SBP. was evaluated for Liver transplant. His brother,aged 32 years, volunteered to donate. On evaluation, his LAI(liver attenuation index) was +1 and Liver biopsyhad 15% macro-vesicular steatosis. After psychological, cardiac and pulmonology evaluation he was acceptedfor donation. His triphasic C T scan of liver & volumetry showed a congenitally small left lateral segment (Wholeliver 1107 ml; Segment 2&3 81 ml). Routine transection plane through the Middle Hepatic Vein (MHV) yielded aright graft of 840 ml {GRWR(Graft to Recipient Weight Ratio) =1.1} and RLV(Remnant Liver Volume) 267ml(24%)precluding safe donor hepatectomy. Since the left liver was mainly constituted by Segment 4, thehepatectomy plane was modifi ed according to portal vein supply and leaving MHV in the donor to prevent anycongestion in Segment 4. The new plane yielded right graft volume of 750 ml and RLV 357 ml (32.2%). After extensive counseling and authorization committee approval, transplant was done. The recipient operation wasdelayed till the donor hilar dissection ensured that the transection plane matched the preoperative plan.Results:The donor hepatectomy was uneventful (blood loss 500 ml; no transfusion). The donor made anuneventful recovery and was discharged on POD 7. The retrieved graft was 720 grams (GRWR= 0.940).Therecipient had a smooth post -operative course. .Follow up donor C T at 3 months showed increase in Left livervolume to 902 ml (RLV 357) ;segment 4 from 276 to 633 ml and seg 2&3 from 81 to 269 ml.C onclusion: In theabsence of a viable deceased donor program, predominantly living donor centers will be forced to acceptdonors with variant anatomy. Preoperative planning and use of imaging and volumetry to guide hepatectomy can allow retrieval of grafts from these donors without increasing the risk.