Liver transplant mortality and morbidity following preoperative radiotherapy for hepatocellular carcinoma.

BACKGROUND: Radiotherapy (RT) can be used for tumor downstaging and as a bridge to transplantation in hepatocellular carcinoma (HCC), but its effect on surgical complications is unknown. Therefore, we investigated post-transplant mortality and acute readmission rates in HCC with and without preoperative RT using the National Cancer Database (NCDB). METHODS: After exclusion, 11,091 transplant patients were analyzed, 165 of whom received RT prior to transplant. Multivariable binomial logistic regression analysis identified characteristics associated with use of RT, and factors associated with increased 30/90-day mortality and 30-day readmission, following propensity matching. RESULTS: Although RT (median 40 Gy in 5 fractions) was more often delivered to larger tumors and advanced stages, it resulted in 59% downstaging rate, 39% pathologic complete response rate, and a median of 4 additional months to transplantation. Crude 30/90-day mortality rates were both 1.2% with preoperative RT, compared to 2.7% and 4.4% without. The 30-day readmission rate was 5.5% with RT and 10.7% without it. Propensity matched analysis demonstrated no statistical differences in 30/90-day mortality and a lower 30-day readmission rate with preoperative RT. Age >58, stage III disease, lack of transarterial chemoembolization, and shorter time to transplant independently predicted higher 90-day mortality. CONCLUSION: Preoperative RT for HCC did not increase postoperative mortality or length of stay following liver transplant.

Stereotactic Body Radiation Therapy: A New Strategy for Loco-Regional Treatment for Hepatocellular Carcinoma While Awaiting Liver Transplantation.

BACKGROUND: Trans-arterial chemoembolization and radiofrequency ablation are commonly used for control of hepatocellular carcinoma (HCC) on liver transplant (LTx) waiting list. Stereotactic body radiation therapy (SBRT) was introduced to our institution for HCC as a bridging or downsizing therapy to LTx. PATIENTS AND METHODS: Twenty-five HCC lesions in 22 patients were treated with SBRT while waiting for LTx from January 2010 to December 2015. Nineteen of these patients received deceased donor LTx. SBRT was defined as 40-50 Gy delivered in 4-6 fractions. Pre- and post-liver transplant outcome were analyzed in addition to the dropout rate and tumor response to SBRT. RESULTS: Median size of original tumors was 3.2 cm (2.0-8.9), and median size of tumor after SBRT was significantly smaller at 0.9 cm (0-3.2) in the explanted livers (p < 0.01). The dropout rate was 9%, and they were only downsized patients outside of Milan criteria. Liver disease did not progress between pre- and post-SBRT except one patient. Twenty-eight percent of treated HCCs showed complete pathologic response, and 22% had extensive partial response with some residual tumor. No HCC recurrence was experienced after LTx. CONCLUSION: SBRT is indicated to be safe, effective treatment for HCC on LTx waiting list, and it leads to satisfactory post-liver transplant outcomes.

Younger Age is an Independent Factor for Graft Weight Overestimation: Analysis of the Clinical Impact on Recipient Outcomes in 340 Japanese Living Liver Donors.

BACKGROUND: Accurate preoperative estimation of graft weight is essential for improving outcomes in living donor liver transplantation. METHODS: This retrospective study sought to identify factors associated with graft weight overestimation. From April 2006 to August 2015, 340 living donors were assigned to no-overestimate (n = 284) or overestimate (n = 56) groups. We defined graft weight overestimation as a discrepancy ≥15% between estimated graft volume and actual graft weight. Donor data were compared, and associated factors for graft weight overestimation were analyzed. Recipient outcomes were compared between the groups according to identified factors. RESULTS: Donors were significantly younger in the overestimate group than in the no-overestimate group (35.0 vs. 46.0 years; p < 0.001). Multivariate analysis identified donor age <45 years as an independent risk factor for graft weight overestimation (odds ratio 2.068; 95% confidence interval 1.114-3.839; p = 0.021). Among recipients with donors <45 years (n = 168), incidence of small-for-size dysfunction (SFSD) was significantly higher in the overestimate group than in the no-overestimate group (7/37 patients vs. 7/131 patients; p = 0.016); no significant difference was observed among recipients with donors ≥45 years (n = 172). First-year mortality was lower in SFSD recipients with donors <45 years (14.3 vs. 60.9%, p = 0.007). Among recipients with younger donors, graft survival was not significantly different between overestimate and no-overestimate groups. CONCLUSIONS: Younger donor age was an independent risk factor for graft weight overestimation leading to SFSD in recipients, but did not impair graft survival.

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

Oral administration of polyamines ameliorates liver ischemia/reperfusion injury and promotes liver regeneration in rats.

Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD.

Liver transplantation for advanced hepatocellular carcinoma in patients with Child-Pugh A and B.

PURPOSE: To investigate the outcomes of living donor liver transplantation for advanced hepatocellular carcinoma in Child-Pugh A/B patients and the usefulness of our expanded selection criteria, the Kyoto criteria. METHODS: A total of 82 recipients with a Child-Pugh class A (n = 27) or B (n = 55) status having either multiple hepatic nodules or solitary tumors ≥5 cm in size treated between February 1999 and August 2012 were enrolled in this study. RESULTS: The overall recurrence rate was significantly less for the Child-Pugh B patients than for the Child-Pugh A patients (P = 0.042), while the survival rates did not differ. In the Child-Pugh A and B patients, the survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P = 0.006, P = 0.001, P = 0.032 and P < 0.001, respectively). In the Child-Pugh B patients, the overall survival and recurrence rates did not differ between the patients treated with and without pretreatment for hepatocellular carcinoma. In the Child-Pugh B patients treated with pretreatment, the overall survival rate was significantly greater, while the recurrence rate was lower among the patients meeting the Kyoto criteria than those exceeding these criteria (P < 0.001, P < 0.001, respectively). CONCLUSIONS: Living donor liver transplantation performed within the Kyoto criteria achieves excellent overall survival and recurrence rates, especially for Child-Pugh B patients, even those with advanced hepatocellular carcinoma.

Impact of elderly donors for liver transplantation: A single-center experience.

Elderly donor grafts for liver transplantation (LT) are recognized to be marginal grafts. The present study investigated the impact of using elderly donors for LT. Between June 1990 and August 2012, 1631 patients received LT at Kyoto University Hospital. Out of 1631 patients, 1597 patients received living donor liver transplantation (LDLT), whereas the other 34 patients underwent deceased donor liver transplantation (DDLT). Seventy-five grafts that were used came from individuals who were ≥60 years old. We retrospectively analyzed the recipients' survival rates according to donor age. The overall survival rates of the recipients of all LDLT (P < 0.001), adult-to-adult LDLT (P = 0.007), all DDLT (P = 0.026), and adult-to-adult DDLT (P = 0.011) were significantly lower for the elderly donor group versus the younger group and especially for those who were hepatitis C-positive. A multivariate analysis revealed that donor age, ABO incompatibility, and preoperative intensive care unit stay were independent risk factors for poor patient survival in adult-to-adult LDLT. However, no significant differences existed between the 2 groups among those who received adult-to-adult LDLT in and after April 2006. No significant association was found between donor age and incidence of acute cellular rejection. In conclusion, donor age was closely related to the survival rate for LDLT and DDLT, although the impact of donor age was not shown in the recent cases.

Perioperative changes in nutritional parameters and impact of graft size in patients undergoing adult living donor liver transplantation.

Derangements of various serum biochemical nutritional/metabolic parameters are common in patients with end-stage liver disease who undergo liver transplantation (LT). The aim of this study was to explain the benefit of LT with respect to parameter changes and to examine the impact of the graft-to-recipient weight ratio (GRWR) on such changes. We investigated each parameter's course in 208 adult recipients for 1 year after living donor LT and analyzed changes in the parameters with a GRWR of 0.8% as the cutoff point. Bonferroni corrections were applied to account for multiple testing. Liver disease-induced high pretransplant ammonia and tyrosine levels and low branched-chain amino acids to tyrosine ratio (BTR) and zinc levels normalized within 2 weeks after transplantation, and the total lymphocyte count (TLC) normalized within 2 months, whereas low pretransplant prealbumin levels took 1 year to normalize. Branched-chain amino acids (BCAA), zinc, and TLC levels transiently dropped shortly after transplantation and then were corrected later. An accelerated recovery of ammonia and tyrosine levels and the BTR were found with larger grafts, especially early after transplantation, whereas zinc, prealbumin, BCAA, and TLC levels recovered regardless of the graft size. In conclusion, graft size had little effect on the recovery of nutritional/metabolic parameters except for ammonia and tyrosine levels.

Effect of cold perfusion and perfluorocarbons on liver graft ischemia in a donation after cardiac death model.

BACKGROUND: Effects of two perfluorocarbon (PFC) formulations (perfluorodecalin emulsion and perfluorodecalin liquid) on the quality of liver graft preservation, in a donation after cardiac death (DCD) rat model, were investigated. The significance of continuous graft perfusion during cold preservation was also explored. MATERIALS AND METHODS: DCD model: 30 min after cardiopulmonary arrest was initiated, livers were excised and flushed with cold University of Wisconsin (UW) solution (± PFC) and preserved in the same solution for 8 h. The study groups were preserved as follows: group 1: no perfusion; group 2: perfusion with UW; group 3: PFC was administered before cardiac arrest and the liver was perfused with UW alone; and groups 4 and 5: perfused with UW + 1 of two PFCs. In a baseline group used only for comparison of gene expression, livers were quick-frozen after cardiac arrest. Microarrays were used to analyze liver messenger RNA transcripts. Histopathologic, immunohistochemical, and ADP/ATP ratio evaluations were performed to assess the quality of graft preservation. RESULTS: Significant decreases in downregulation and increases in upregulation of hepatic genes (relative to baseline) were demonstrated in all perfusion groups. This trend was most pronounced in the PFC groups. Lower fat content and ADP/ATP ratio and a reduction in Caspase 3 activation were found in all perfusion groups. CONCLUSION: Hypothermic perfusion of rat DCD liver grafts with oxygenated UW solution (± PFC) produced superior preservation compared with nonperfusion storage. The observed changes in expression of hepatic genes may represent a protective effect in the DCD model.

Donor morbidity in right and left hemiliver living donor liver transplantation: the impact of graft selection and surgical innovation on donor safety.

This study investigated adequate liver graft selection for donor safety by comparing postoperative donor liver function and morbidity between the right and left hemilivers (RL and LL, respectively) of living donors. Between April 2006 and March 2012, RL (n = 168) and LL (n = 140) donor operations were performed for liver transplantation at Kyoto University Hospital. Postoperative hyperbilirubinemia and coagulopathy persisted in RL donors, whereas the liver function of LL donors normalized more rapidly. The overall complication rate of the RL donors was significantly higher than that of the LL donors (59.5% vs. 30.7%; P < 0.001). There were no significant differences in severe complications worse than Clavien grade IIIa or in biliary complication rates between the two donor groups. In April 2006, we introduced an innovative surgical procedure: hilar dissection preserving the blood supply to the bile duct during donor hepatectomy. Compared with our previous outcomes (1990-2006), the biliary complication rate of the RL donors decreased from 12.2% to 7.2%, and the severity of these complications was significantly lower. In conclusion, LL donors demonstrated good recovery in postoperative liver function and lower morbidity, and our surgical innovations reduced the severity of biliary complications in living donors.

Successful living donor kidney transplantation in a patient with prothrombin gene mutation: Case report and literature review.

We present a patient with known prothrombin gene mutation and a history of prior vascular events, who underwent living donor kidney transplantation. Given the presumed elevated risk of complication from known prothrombin mutation, clinical management was directed towards optimizing living donor allograft function.

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis.

Purpose: We report on the feasibility and outcomes of liver stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single-photon emission computed tomography (SPECT) functional treatment planning in patients with Child-Pugh (CP) B/C cirrhosis. Methods and Materials: Liver SPECT with 99mTc-sulfur colloid was coregistered to treatment planning computed tomography (CT) for the guided avoidance of functional hepatic parenchyma during SBRT. Functional liver volumes (FLVs) obtained from SPECT were compared with anatomic liver volumes defined on the planning CT. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were reported with at least 6 months of radiographic follow-up. Pre- and posttransplant outcomes were analyzed in a subset of patients who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease was used to score hepatic function before and after SBRT completion. Results: With a median follow-up of 32 months, 45 patients (58 lesions) with HCC and CP-B/C cirrhosis received SBRT to a median dose of 45 Gy (3-5 fractions). FLV loss (34%, P < .001) was observed in all patients, and the functional and anatomic liver volumes matched well in a control group of noncirrhotic/non-HCC patients. Despite marked functional parenchyma retraction, the amount of FLV on SPECT exposed to the threshold irradiation was significantly less than the CT liver volumes (P < .001) because of the optimized beam placement during dosimetry planning. Twenty-three patients (51%) successfully completed orthotopic liver transplant, with a median time to transplant of 9.2 months. With 91% in-field local control, the overall 2-year survival was 65% (90% after the orthotopic liver transplant), with no incidence of radiation-induced liver disease observed within 3 to 4 months or accelerated CP class migration from B to C within the first 6 months post-SBRT. Mean Model of End-Stage Liver Disease-Na score was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: Functional treatment planning with 99mTc sulfur colloid SPECT/CT allows identification and avoidance of functional hepatic parenchyma in patients with CP-B/C cirrhosis, leading to low toxicity and satisfactory transplant outcomes.

Endogenous signal transducer and activator of transcription 3 is required for the protection of hepatocytes against warm ischemia/reperfusion injury.

Warm ischemia/reperfusion (I/R) is a common clinical problem during liver transplantation and liver resection. Warm ischemia also occurs during trauma and shock. However, there is still no safe and promising strategy for protecting the liver from I/R injury. Signal transducer and activator of transcription 3 (STAT3) is a major immediate response molecule for protecting cell survival. In this study, we first confirmed that a pharmacological STAT3 inhibitor, (E)-2-cyano-3-(3,4-dihydrophenyl)-N-(phenylmethyl)-2-propenamide (AG490), significantly reduced the survival of HepG2 cells, regardless of the serum condition. Furthermore, we created hepatocyte-specific STAT3-deficient mice with the cyclization recombination-locus of X-over P1 (Cre-LoxP) system to study the mechanisms of STAT3 in liver I/R injury. We found that the alanine aminotransferase level was significantly higher in hepatocyte-specific STAT3-deficient mice versus wild-type (WT) mice in a 70% liver I/R injury model. A histopathological examination showed that hepatocyte-specific STAT3-deficient mice suffered more severe damage than WT mice despite similar numbers of polymorphonuclear neutrophils in the 2 groups. These results indicate that endogenous STAT3 signaling in hepatocytes is required for protection of the liver in vitro and in vivo against warm I/R injury. In conclusion, endogenous STAT3 plays an important role in protecting the liver against I/R injury, and STAT3-targeting therapy could be a therapeutic approach to combating liver I/R injury.

Association between plasma cyclic guanosine monophosphate levels and hemodynamic instability during liver transplantation.

The activation of cyclic guanosine monophosphate (cGMP) production in patients with end-stage liver disease (ESLD) has been associated with hemodynamic instability during orthotopic liver transplantation (OLT). The aim of this prospective, observational study was to investigate the involvement of cGMP in the mediation of profound hypotension during liver graft reperfusion. An additional objective was to determine whether preoperative cGMP levels are associated with intraoperative hemodynamic instability. Forty-four consecutive patients undergoing OLT were included in the study. Blood samples for cGMP analysis were obtained from (1) the radial artery before the surgical incision; (2) the radial artery, portal vein, and flush blood during the anhepatic phase; and (3) the radial artery 20 minutes after liver graft reperfusion. On the basis of a statistical analysis, the patients were divided into 2 groups: group 1 (preoperative cGMP level ≥ 0.05 µmol/L) and group 2 (preoperative cGMP level < 0.05 µmol/L). We demonstrated a significant correlation between the preoperative levels of cGMP and the amount of catecholamine required to maintain hemodynamic stability during reperfusion (r = 0.52, P < 0.001), the length of the hospital stay (r = 0.38, P = 0.01), and the length of the intensive care unit (ICU) stay (r = 0.44, P = 0.004). We also demonstrated a significantly higher intraoperative catecholamine requirement (P < 0.001) and a prolonged postoperative ICU stay (P = 0.02) in group 1 patients versus group 2 patients. In conclusion, this study demonstrates increased baseline cGMP production in patients with ESLD, which is significantly associated with severe hypotension during OLT. We suggest that preoperative levels of cGMP correlate with hemodynamic instability during liver graft reperfusion.

Liver transplantation with a strongly positive crossmatch: case study and literature review.

A positive crossmatch has been associated with increased risk in liver transplantation. To study the clinical significance of preformed donor-specific human leukocyte antigen antibodies (DSAs) in liver transplantation, we reviewed patients who underwent liver transplantation with a strongly positive flow cytometry crossmatch. DSAs were evaluated with a Luminex solid phase assay. The complement-fixing ability of DSAs was tested with a complement component 1q (C1q) assay. Using an assay correlation between complement-dependent cytotoxicity crossmatch, flow cytometry crossmatch, and DSA results, we reviewed the effects of DSAs on the outcomes of our patients as well as reported cases in the literature. Five of 69 liver recipients had a strongly positive crossmatch: 4 had a positive T cell crossmatch [median channel shift (MCS) = 383.5 ± 38.9], and 5 had a positive B cell crossmatch (MCS = 408.8 ± 52.3). The DSAs were class I only in 1 patient, class I and II in 3 patients, and class II only in 1 patient. Cholestasis, acute rejection, or both were observed in 3 of the 4 patients with a positive T cell crossmatch with an MCS approximately greater than 300. The C1q assay was positive for 3 patients. Two had either persistent cholestasis or early acute rejection. One patient who was treated with preemptive intravenous immunoglobulin had an unremarkable outcome despite a positive C1q result. One of the 2 patients with a negative C1q assay experienced persistent cholestasis and early and recurrent acute rejection; the other had an unremarkable outcome. None of the patients died or lost a graft within the first year of transplantation. Our study suggests that human leukocyte antigen antibody screening, flow cytometry crossmatch MCS levels, DSA mean fluorescent intensity levels, and C1q assays may be useful in assessing the risk of antibody-mediated rejection and timely interventions in liver transplantation.

Impact of geographic disparity on liver allocation for hepatocellular cancer in the United States.

BACKGROUND & AIMS: Liver allocation for hepatocellular cancer (HCC) is undergoing constant re-evaluation in the United States, but the impact of geographic differences in organ access has not been examined. METHODS: From February 28th, 2002 until November 20th, 2009, 9730 adult patients with T2 HCC and 326 Beyond Milan HCC patients were studied using the UNOS database. Kaplan-Meier survival curves were generated and log-rank tests were used to test for differences in survival curves. RESULTS: Length of waiting time and presence/absence of loco-regional therapy in T2 HCC patients did not significantly impact transplant recipient (p=0.65) and graft survival (p=0.74) (Fig. 1B). Regions with median waiting times >6 months performed more loco-regional therapy (Fig. 1D) and had significantly higher waiting list dropout rates (Regions 1: p=0.01; 5: p<0.001, and 9: p<0.001). T2 HCC post-transplant outcomes were not significantly different between UNOS regions (Fig. 2) or between T2 and Beyond Milan HCC patients (transplant recipient p=0.37, and graft p=0.72 survival) (Fig. 1C). The Beyond Milan cohort had significantly greater dropout/death (p=0.007) and a worse overall survival trend (p=0.11) (Fig. 1C). CONCLUSIONS: Analysis of the UNOS database shows inhomogeneous access to liver transplantation in the United States. Regions with longer waiting times had significantly higher T2 HCC dropout rates (Table 2), and used more loco-regional therapy (Fig. 1D). Conversely, T2 HCC patients had uniform liver transplant outcomes despite geographic differences (Fig. 2). Beyond Milan HCC patients showed significantly greater dropout/death (p=0.007) and a worse overall survival trend in an intent-to-treat analysis (p=0.11) (Fig. 1C).

How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score.

Autologous Islet Transplantation After Total Pancreatectomy in a Patient Recovered from SARS-CoV-2: A Case Report.

BACKGROUND SARS-CoV-2 infection or COVID-19 disease has been linked to the onset of diabetes and metabolic dysregulation because it has been suggested that viral entry proteins, specifically ACE2 and TMPRSS2, are expressed in the exocrine cells and ductal epithelium of the pancreas. Because of the unknown effect this can have on islet function, there can be doubt that patients with previous SARS-CoV-2 infections are good candidates for autologous islet transplantation after total pancreatectomy (TPAIT). CASE REPORT A patient with a history of chronic pancreatitis and previous non-surgical interventions was presented as a viable candidate for TPAIT at our institution. Approximately 1 month later, the patient contracted a SARS-CoV-2 infection, resulting in a mild case of COVID-19. The infection resolved without the need for hospitalization. At the time of this occurrence, COVID-19 was primarily considered a respiratory ailment, and little was known of the potential association between metabolic dysfunction and SARS-CoV-2. Islet isolation and surgery proceeded in a textbook manner with no surgical complications. The patient was weaned off exogenous insulin within 3 months after transplantation. CONCLUSIONS Favorable outcomes after surgery included pain reduction, islet function, and improved quality of life for the patient in the first 6 months after the procedure. These successful results demonstrate that SARS-CoV-2 infection did not prevent the patient from achieving good glucose regulation after auto-islet transplantation. This outcome suggests that, at least in this instance of mild infection, there were no long-lasting negative COVID-19-associated effects on the transplanted islets that might impact islet function.