Susceptibility to SARS-CoV-2 Infection and Immune Responses to COVID-19 Vaccination Among Recipients of Solid Organ Transplants.

Solid organ transplant recipients (SOTRs) are at high risk for infections including SARS-CoV-2, primarily due to use of immunosuppressive therapies that prevent organ rejection. Furthermore, these immunosuppressants are typically associated with suboptimal responses to vaccination. While COVID-19 vaccines have reduced the risk of COVID-19-related morbidity and mortality in SOTRs, breakthrough infection rates and death remain higher in this population compared with immunocompetent individuals. Approaches to enhancing response in SOTRs, such as through administration of additional doses and heterologous vaccination, have resulted in increased seroresponse and antibody levels. In this article, safety and immunogenicity of mRNA COVID-19 vaccines in SOTRs are explored by dose. Key considerations for clinical practice and the current vaccine recommendations for SOTRs are discussed within the context of the dynamic COVID-19 vaccination guideline landscape. A thorough understanding of these topics is essential for determining public health and vaccination strategies to help protect immunocompromised populations, including SOTRs.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

COVID-19 and transplantation-Data censoring.

During the early wave of the COVID-19 pandemic, the Scientific Registry of Transplant Recipients (SRTR) designated a "black out" period between March 12, 2020, and June 12, 2020, for transplant outcomes reporting. We discuss the implications and potential bias it has introduced as it may selectively favor the outcomes for certain regions and harm other regions due to varied effects of different waves of COVID-19 infections across the United States.

Optimal Timing of Administration of Direct-acting Antivirals for Patients With Hepatitis C-associated Hepatocellular Carcinoma Undergoing Liver Transplantation.

OBJECTIVE: To investigate the optimal timing of direct acting antiviral (DAA) administration in patients with hepatitis C-associated hepatocellular carcinoma (HCC) undergoing liver transplantation (LT). SUMMARY OF BACKGROUND DATA: In patients with hepatitis C (HCV) associated HCC undergoing LT, the optimal timing of direct-acting antivirals (DAA) administration to achieve sustained virologic response (SVR) and improved oncologic outcomes remains a topic of much debate. METHODS: The United States HCC LT Consortium (2015-2019) was reviewed for patients with primary HCV-associated HCC who underwent LT and received DAA therapy at 20 institutions. Primary outcomes were SVR and HCC recurrence-free survival (RFS). RESULTS: Of 857 patients, 725 were within Milan criteria. SVR was associated with improved 5-year RFS (92% vs 77%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 92%, and 82%, and 5-year RFS of 93%, 94%, and 87%, respectively. Among 427 HCV treatment-naïve patients (no previous interferon therapy), patients who achieved SVR with DAAs had improved 5-year RFS (93% vs 76%, P < 0.01). Patients who received DAAs pre-LT, 0-3 months post-LT, and ≥3 months post-LT had SVR rates of 91%, 93%, and 78% (P < 0.01) and 5-year RFS of 93%, 100%, and 83% (P = 0.01). CONCLUSIONS: The optimal timing of DAA therapy appears to be 0 to 3 months after LT for HCV-associated HCC, given increased rates of SVR and improved RFS. Delayed administration after transplant should be avoided. A prospective randomized controlled trial is warranted to validate these results.

Lung Injury Combined with Loss of Regulatory T Cells Leads to De Novo Lung-Restricted Autoimmunity.

More than one third of patients with chronic lung disease undergoing lung transplantation have pre-existing Abs against lung-restricted self-Ags, collagen type V (ColV), and k-α1 tubulin (KAT). These Abs can also develop de novo after lung transplantation and mediate allograft rejection. However, the mechanisms leading to lung-restricted autoimmunity remain unknown. Because these self-Ags are normally sequestered, tissue injury is required to expose them to the immune system. We previously showed that respiratory viruses can induce apoptosis in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), the key mediators of self-tolerance. Therefore, we hypothesized that lung-tissue injury can lead to lung-restricted immunity if it occurs in a setting when Tregs are impaired. We found that human lung recipients who suffer respiratory viral infections experienced a decrease in peripheral Tregs. Pre-existing lung allograft injury from donor-directed Abs or gastroesophageal reflux led to new ColV and KAT Abs post respiratory viral infection. Similarly, murine parainfluenza (Sendai) respiratory viral infection caused a decrease in Tregs. Intratracheal instillation of anti-MHC class I Abs, but not isotype control, followed by murine Sendai virus infection led to development of Abs against ColV and KAT, but not collagen type II (ColII), a cartilaginous protein. This was associated with expansion of IFN-γ-producing CD4(+) T cells specific to ColV and KAT, but not ColII. Intratracheal anti-MHC class I Abs or hydrochloric acid in Foxp3-DTR mice induced ColV and KAT, but not ColII, immunity, only if Tregs were depleted using diphtheria toxin. We conclude that tissue injury combined with loss of Tregs can lead to lung-tissue-restricted immunity.

De novo development of antibodies to kidney-associated self-antigens angiotensin II receptor type I, collagen IV, and fibronectin occurs at early time points after kidney transplantation in children.

Chronic rejection is the leading cause of graft loss following pediatric kidney transplantation. Our group and others have demonstrated an association between the development of Abs to self-antigens and chronic rejection following adult lung and heart transplantation. The goal of this study was to determine whether Abs to kidney-associated self-antigens develop following pediatric renal transplantation. We investigated post-transplant development of Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, and collagen IV in a pediatric cohort. Using ELISA, we measured Abs to kidney-associated self-antigens in serum. Our cohort included 29 subjects with samples collected pretransplant and for 12 months post-transplant. No samples had Abs to kidney-associated self-antigen pretransplant. In contrast, 50% (10/20) of subjects developed Abs to one or more kidney-associated self-antigen post-transplantation. The median time to antibody appearance and duration of persistence were 103 and 61 days, respectively. Development of Abs did not correlate with graft function. Half of subjects developed Abs to kidney-associated self-antigens angiotensin II receptor type I, Fn, or collagen IV in the first year after kidney transplantation--a higher rate of early antibody development than expected. In this small study, Abs did not correlate with worse clinical outcomes.

Perioperative blood transfusion affects hepatitis C virus (HCV)-specific immune responses and outcome following liver transplantation in HCV-infected patients.

OBJECTIVES: Perioperative factors can affect outcomes of liver transplantation (LT) in recipients with hepatitis C virus (HCV) infection. This study was conducted to investigate whether the immunomodulatory effects of packed red blood cells (PRBC) and platelets administered in the perioperative period might affect immune responses to HCV and thus outcomes in LT recipients. METHODS: Data for a total of 257 HCV LT recipients were analysed. Data on clinical demographics including perioperative transfusion (during and within the first 24 h), serum cytokine concentration, HCV-specific interferon-γ (IFN-γ) and interleukin-17 (IL-17) producing cells, and outcomes including graft and patient survival were analysed. RESULTS: Patient survival was higher in HCV LT recipients who did not receive transfusions (Group 1, n = 65) than in those who did (Group 2, n = 192). One-year patient survival was 95% in Group 1 and 88% in Group 2 (P = 0.02); 5-year survival was 77% in Group 1 and 66% in Group 2 (P = 0.05). Group 2 had an increased post-transplant viral load (P = 0.032) and increased incidence of advanced fibrosis at 1 year (P = 0.04). After LT, Group 2 showed increased IL-10, IL-17, IL-1ß and IL-6, and decreased IFN-γ, and a significantly increased rate of IL-17 production against HCV antigen. Increasing donor age (P = 0.02), PRBC transfusion (P < 0.01) and platelets administration were associated with worse survival. CONCLUSIONS: Transfusion had a negative impact on LT recipients with HCV. The associated early increase in pro-HCV IL-17 and IL-6, with decreased IFN-γ, suggests that transfusion may be associated with the modulation of HCV-specific responses, increased fibrosis and poor transplant outcomes.

Expanding Indications for Liver Transplantation in the Treatment of Hepatocellular Carcinoma.

Improvements in downstaging therapies have expanded the indications for liver transplantation (LT) for hepatocellular carcinoma (HCC). Patients with more advanced disease are now considered candidates due to advancements in radiation therapy, combination therapies, and immunotherapy. Combination stereotactic body radiation therapy (SBRT) and trans-arterial chemoembolization (TACE) has been shown to be superior to the historic treatment, sorafenib, in patients with macrovascular invasion. These patients are now candidates for LT with stable disease after LRT. Patients with ruptured HCC and prolonged stability have also been shown to have acceptable outcomes. The role of neoadjuvant immunotherapy needs to be further defined and has the potential to further improve tumor control prior to transplant.

Size Matching Deceased Donor Livers: The Tampa General Measurement System.

BACKGROUND: No reliable or standardized system exists for measuring the size of deceased donor livers to determine whether they will fit appropriately into intended recipients. METHODS: This retrospective, single-center study evaluated the efficacy of Tampa General Hospital's size-matching protocol for consecutive, deceased donor liver transplantations between October 2021 and November 2022. Our protocol uses cross-sectional imaging at the time of organ offer to compare the donor's right hepatic lobe size with the recipient's right hepatic fossa. Outcomes were analyzed, including large-for-size syndrome, small-for-size syndrome, early allograft dysfunction, primary nonfunction, graft survival, and patient survival. RESULTS: We included 171 patients in the study. The donor liver physically fit in all the patients except one whose pretransplant imaging was outdated. One patient (0.6%) had large-for-size syndrome, none had small-for-size syndrome, 15 (10%) had early allograft dysfunction, and none had primary nonfunction. There were 11 (7%) patient deaths and 11 (7%) graft failures. CONCLUSION: Our measurement system is fast and effective. It reliably predicts whether the donor liver will fit in the intended recipient and is associated with low rates of early allograft dysfunction.

Immune response to extracellular matrix collagen in chronic hepatitis C-induced liver fibrosis.

Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h) 2) and T helper 17 (T(h) 17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly T(h) 2 and T(h) 17 cytokine profile.

Malnutrition in free-living elderly in rural south India: prevalence and risk factors.

OBJECTIVE: To estimate the prevalence of malnutrition among free-living elderly in a rural population of south India. DESIGN: Cross-sectional study. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire, which is an eighteen-item nutritional screening instrument used in the elderly. SETTING: Kaniyambadi block, a rural development block in the state of Tamil Nadu, south India. SUBJECTS: Community-dwelling elderly (aged 60 years and above). RESULTS: As evaluated by the MNA, 14 % of the 227 subjects were malnourished and 49 % were at risk of malnourishment. No significant difference was found between men and women. The majority of the elderly were living with their children, had no income and consumed three meals per day. Older age (P < 0.001), decreased food intake (P < 0.001) and consuming fewer meals (P < 0.001) were independently associated with lower MNA scores. CONCLUSIONS: More than 60 % of the subjects had low MNA scores (<23.5) indicating that deficient protein-energy intake is common among rural elderly of south India and requires more attention.

Multidisciplinary treatment for hilar and intrahepatic cholangiocarcinoma: A review of the general principles.

Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, and associated with a high mortality if untreated. CCA is locally aggressive and located in close proximity to vital structures i.e. the portal vein and hepatic artery. A complete extirpation of the tumor including microscopically detectable disease R0 resection offers the best possibility of long-term survival in patients with CCA. As such, the surgical approach to achieve a R0 resection is dictated by the location of the tumor and the presence of underlying liver disease. The present article focuses on the general principles of the multidisciplinary treatment of hilar and intrahepatic CCA.

On the impact of correlation between collaterally consanguineous cells on lymphocyte population dynamics.

During an adaptive immune response, lymphocytes proliferate for five to twenty-five cell divisions, then stop and die over a period of weeks. Based on extensive flow cytometry data, Hawkins et al. (Proc Natl Acad Sci USA 104:5032-5037, 2007) introduced a cell-level stochastic model of lymphocyte population dynamics, called the Cyton Model, that accurately captures mean lymphocyte population size as a function of time. In Subramanian et al. (J Math Biol 56(6):861-892, 2008), we performed a branching process analysis of the Cyton Model and deduced from parameterizations for in vitro and in vivo data that the immune response is predictable despite each cell's fate being highly variable. One drawback of flow cytometry data is that individual cells cannot be tracked, so that it is not possible to investigate dependencies in the fate of cells within family trees. In the absence of this information, while the Cyton Model abandons one of the usual assumptions of branching processes (the independence of lifetime and progeny number), it adopts another of the standard branching processes hypotheses: that the fates of progeny are stochastically independent. However, new experimental observations of lymphocytes show that the fates of cells in the same family tree are not stochastically independent. Hawkins et al. (2008, submitted) report on ciné lapse photography experiments where every founding cell's family tree is recorded for a system of proliferating lymphocytes responding to a mitogenic stimulus. Data from these experiments demonstrate that the death-or-division fates of collaterally consanguineous cells (those in the same generation within a founding cell's family tree) are strongly correlated, while there is little correlation between cells of distinct generations and between cells in distinct family trees. As this finding contrasts with one of the assumptions of the Cyton Model, in this paper we introduce three variants of the Cyton Model with increasing levels of collaterally consanguineous correlation structure to incorporate these new found dependencies. We investigate their impact on the predicted expected variability of cell population size. Mathematically we conclude that while the introduction of correlation structure leaves the mean population size unchanged from the Cyton Model, the variance of the population size distribution is typically larger. Biologically, through comparison of model predictions for Cyton Model parameterizations determined by in vitro and in vivo experiments, we deduce that if collaterally consanguineous correlation extends beyond cousins, then the immune response is less predictable than would be concluded from the original Cyton Model. That is, some of the variability seen in data that we previously attributed to experimental error could be due to intrinsic variability in the cell population size dynamics.

Liver Transplantation for Malignant Primary Pediatric Hepatic Tumors.

BACKGROUND: Malignant primary pediatric hepatic tumors (MPPHTs) are rare and account for approximately 1% of all childhood malignancies. In recent years, liver transplantation has emerged as a viable treatment options for select patients with MPPHTs. STUDY DESIGN: We performed a single-center retrospective study using a prospective database to compare outcomes of pediatric liver transplant recipients, with and without cancer, between January 2000 and December 2014. RESULTS: One hundred fifty-three children underwent 173 liver transplantations during the study period. Of these, 21 (12%) children received 23 (13.3%) transplants for unresectable MPPHTs: 16 hepatoblastomas (HBs), 3 embryonal cell sarcomas (ECS), and 2 hepatocellular carcinomas (HCCs). There was no significant difference in 1-, 3-, and 10-year patient and graft survival rates between MPPHT and non-MPPHT patients (95.2%, 81.2%, 81.2%, and 95.2%, 72,2%, 72.2% for MPPHT vs 92.7%, 89.8%, 87.6% and 85.4%, 81.1%, 75% for the non-MPPHT group, respectively) (p > 0.05). Rates of 1-, 5-, and 10-year disease-free survival for MPPHT patients were 76%, 76%, and 76%, respectively. Median age at transplantation for MPPHT patients was 3.1 years (range 58 days to 17 years), median listing time was 81 days, and median wait list time was 15 days. Eight (38%) children had 2 tumors or more and 4 of 16 (25%) HB patients had metastatic disease at presentation. All children received neoadjuvant treatment, with radiographic response in 19 of 21 patients. Presence of metastatic HB at presentation, International Society of Pediatric Oncology Epithelial Liver (SIOPEL) high risk status, and persistently elevated alpha fetoprotein levels after neoadjuvant chemotherapy might be risk factors for tumor recurrence and decreased survival. CONCLUSIONS: Liver transplantation is an excellent option for select patients with unresectable MPPHTs, with outcomes comparable to those after transplantation for nonmalignant causes.

Organ Donor Recovery Performed at an Organ Procurement Organization-Based Facility Is an Effective Way to Minimize Organ Recovery Costs and Increase Organ Yield.

BACKGROUND: A new era in organ donation with national redistricting is being proposed. With these proposals, costs of organ acquisition are estimated to more than double. Traditionally, organ recoveries occur in the donor hospital setting, incurring premium hospital expenses. The aim of the study was to determine organ recovery costs and organ yield for donor recoveries performed at an organ procurement organization (OPO) facility. STUDY DESIGN: In 2001, we established an OPO facility and in 2008 began transferring the donor expeditiously when brain death was declared. The OPO donor and hospital costs on a per donor basis were calculated. Donation after cardiac death donors cannot be transferred and were included in the hospital cost analysis. RESULTS: From January 2009 to December 2014, nine hundred and sixty-three donors originating in our OPO had organs recovered and transplanted. Seven hundred and sixty-six (79.5%) donors were transferred to the OPO facility 8.6 hours (range 0.6 to 23.6 hours) after declaration of brain death. Donor recovery cost was 51% less when donors were transferred to the OPO facility ($16,153 OPO recovery vs $33,161 hospital recovery; p < 0.0001). Organ yield was 27.5% better (3.43 organs) from OPO-recovered donors vs an organ yield of 2.69 from hospital-recovered donors (p < 0.0001). Standard criteria donor organ yield from our OPO was 6% higher than the national average (3.92 vs 3.7 nationally; p = 0.012) and expanded criteria donor organ yield was 18% higher (2.2 vs 1.87 nationally; p = 0.03). CONCLUSIONS: An OPO facility for donor organ recovery increases efficiency and organ yield, reduces costs, and minimizes organ acquisition charge. As we face new considerations with broader sharing, increased efficiencies, cost. and organ use should be considered.

Results of Simultaneous Liver and Kidney Transplantation: A Single-Center Review.

BACKGROUND: The decision for a simultaneous liver and kidney transplantation (SLKT) is fraught with controversy. The aim of this study was to compare SLKT with liver transplantation alone (LTA) in patients with pretransplantation renal failure. STUDY DESIGN: A retrospective review comparing patients undergoing SLKT and LTA (with renal failure) between January 2000 and December 2014 was performed. RESULTS: Of 1,129 liver transplantations, 132 had renal failure pretransplantation; 52 had SLKT and 80 recipients had LTA. Model for End-Stage Liver Disease score and BMI were lower in the SLKT group (p = 0.001). Simultaneous liver and kidney transplantation patients had better overall survival rates at 1 and 5 years compared with LTA (92.3% and 81.6% vs 73.3% and 64.3% respectively; p < 0.01). Graft survival was also superior in patients undergoing SLKT vs LTA. Six of 52 (11.5%) SLKT patients had final positive cross match, but only 1 of 52 (1.9%) kidney grafts was lost to rejection. In the SLKT group, 9 of 52 (17.3%) patients required dialysis post transplantation, but only 2 remained on dialysis beyond 30 days. All patients in the LTA group were on dialysis pretransplantation and significantly more patients (52 of 80 [65%]) required dialysis post LTA (p ≤ 0.0001); 31 of 80 (38.8%) were dialysis dependent for more than 30 days or died on dialysis within 30 days. Two LTA recipients were subsequently listed for kidney transplant. CONCLUSIONS: Patients with end-stage liver disease on dialysis who undergo liver transplantation have significantly better survival when SLKT is performed. In selected patients, SLKT is an appropriate use of a scarce resource, but better prognostic indicators for selection of patients are still needed.

ABO incompatible renal transplants and decreased likelihood for developing immune responses to HLA and kidney self-antigens.

Immune responses to HLA and tissue-restricted self-antigens (SAgs) have been proposed to play a role in the pathogenesis of renal allograft (KTx) rejection. However, ABO incompatible (ABOi) KTx recipients (KTxR) following depletion of antibodies (Abs) to blood group antigens had fewer rejections. To determine the mechanisms, pre- and post-transplant sera from ABOi (n=18) and ABO-compatible (ABOc) (n=45) KTxR were analyzed for Abs against HLA class I and II by LABScreen single antigen assay. The development of Abs to SAgs was measured by ELISA. Immunity to Collagen IV (Col-IV) and cytokines induced were measured by ELISPOT. While 8/45 (18%) ABOc KTxR developed new donor specific antibodies to HLA (DSA) following transplantation, 0/18 ABOi KTxR developed DSA. ABOi KTxR failed to develop Abs to kidney SAgs (Col-IV and fibronectin (FN)). In contrast, 7 ABOc KTxR developed Abs to both Col-IV and FN. Col-IV stimulation of lymphocytes from ABOc KTxR demonstrated increased IFNγ, IL-17 and decreased IL-10. In contrast ABOi recipients following stimulation with antigens resulted in more IL10 and reduced IFN-γ and IL17 production. At one year, the GFR in ABOi KTxR were significantly better (p<0.04) than ABOc KTxR. De novo DSA and immune responses to SAgs are reduced or absent in ABOi KTxR which we propose leads to less acute rejection and better long term function following ABOi KTx.

Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma.

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.