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During liver transplantation, graft reperfusion triggers cerebral hyperemia, increases intracranial pressure, and disrupts the blood-brain barrier, thereby increasing the risk for immunosuppression neurotoxicity. Therefore, we tested the intraoperative optic nerve sheath diameter (ONSD) for predicting tacrolimus neurotoxicity after liver transplantation.We prospectively included 100 adult patients who underwent living donor liver transplantation. The ultrasonographic ONSD 5 min after reperfusion was used as the index test, whereas the occurrence of early tacrolimus neurotoxicity was used as the reference. The area under the receiver operating characteristic curve (AUROC) was used to estimate the ONSD prediction accuracy. We reported the specificity and sensitivity of ONSD 5 and 30 min after reperfusion. Cutoffs were derived from the ROC curves. In addition, we used regression to control for confounders while testing the association between the ONSD and tacrolimus neurotoxicity.The AUROC at T3 was 0.74 (95% confidence interval (CI), 0.63-0.85, P 0.001). An ONSD of ≥6.4 mm at T3 had an 86% sensitivity (95% CI, 68%-96%) and 53% specificity (95% CI, 41%-65%). An ONSD of ≥6.4 mm at T3 had an adjusted odds ratio for tacrolimus neurotoxicity of 6.3 (95% CI, 1.9-21, P = 0.003).This data indicates that intraoperative ultrasonic ONSD after reperfusion can predict tacrolimus neurotoxicity after liver transplantation.NCT03799770; registered on January 1st, 2019.

Background De novo malignancies are a major reason of long-term mortalities after liver transplantation. However, they usually receive minimal attention from most health care specialists. The current study aims to evaluate our experience of de novo malignancies after living-donor liver transplantation (LDLT). Methods We reviewed the data of patients who underwent LDLT at our center during the period between May 2004 and December 2018. Results During the study period, 640 patients underwent LDLT. After a mean follow-up period of 41.2 ± 25.8 months, 15 patients (2.3%) with de novo malignancies were diagnosed. The most common de novo malignancies were cutaneous cancers (40%), post-transplantation lymphoproliferative disorders (13.3%), colon cancers (13.3%), and breast cancers (13.3%). Acute cellular rejection (ACR) episodes occurred in 10 patients (66.7%). Mild ACR occurred in 8 patients (53.3%), and moderate ACR occurred in 2 patients (13.3%). All patients were managed with aggressive cancer treatment. The mean survival after therapy was 40.8 ± 26.4 months. The mean overall survival after LDLT was 83.9 ± 52.9 months. Twelve patients (80%) were still alive, and 3 mortalities (20%) occurred. The 1-, 5-, and 10-year overall survival rates after LDLT were 91.7%, 91.7%, and 61.1%, respectively. On multivariate regression analysis, smoking history, operation time, and development of ACR episodes were significant predictors of de novo malignancy development. Conclusions Liver transplant recipients are at high risk for the development of de novo malignancies. Early detection and aggressive management strategies are essential to improving the recipients’ survival.

Background: Post-reperfusion syndrome (PRS) is a serious hemodynamic event during liver transplantation, which increases early graft dysfunction and mortality. Many vasoactive drugs have been used, but norepinephrine boluses are new during PRS. Our study aimed to test the efficacy and safety of Norepinephrine boluses to prevent PRS during orthotopic liver transplantation. Methods: This feasibility phase II trial included 40 patients undergoing living donor liver transplantation. The intervention was an escalated protocol of higher than usual Norepinephrine boluses. The primary outcome was the incidence of PRS. The main secondary outcomes were arrhythmia, ECG ischemic changes, mean pulmonary pressure, 3-month survival, and one-year survival. Results: PRS occurred in 28 (70%) cases, (95% CI 54% to 83%, P-value < 0.001), with a relative risk reduction of 0.22 when compared to our previous results (90%). Twelve cases (30%) developed transient ECG ischemic changes (95% CI, 17% to 47%). All ECG ischemic changes returned to the baseline after correction of hypotension. There was no significant arrhythmia or bradycardia (95% CI 0 to 9%). The mean pulmonary artery pressure was not significantly higher than the normal limit, 20 mmHg. The 3-month survival was 95% (95% CI 83% to 99%), and the one-year survival was 93% (95% CI 80% to 98%). Conclusions: Our results suggest that escalating Norepinephrine boluses starting at 20 mcg is feasible and effective in reducing the risk of PRS during living donor liver transplantation. Additionally, Norepinephrine boluses were not associated with significant myocardial ischemic events, arrhythmia, or a rise in pulmonary pressure.

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types., Graphical abstract, D’Antonio et al. characterize associations between GWAS signals for COVID-19 disease and eQTLs in 69 human tissues to identify causal variants and their underlying molecular mechanisms. They show that diverse symptoms and disease severity of COVID-19 are associated with variants affecting gene expression in a wide variety of tissues.

BackgroundManagement of COVID-19 in transplant patients is a big challenge. Data on immunosuppression management, clinical picture, and outcomes are lacking.ObjectivesTo summarize the current literature on COVID-19 in transplant patients especially the data regarding the immunosuppression protocols, clinical presentation, and outcomes.Search strategyA systematic search of MEDLINE, EBSCO, CENTRAL, CINAHL, LitCovid, Web of Science, and Scopus electronic databases. The references of the relevant studies were also searched. The search was last updated on June 3, 2020.Selection CriteriaPrimary reports of solid organ transplant patients who developed COVID-19. An overlap of cases in different reports was checked.Data collection and analysisA descriptive summary of immunosuppression therapy (before and after COVID-19), clinical presentation (symptoms, imaging, laboratory, and disease severity), management (oxygen therapy, antiviral, and antibacterial), major outcomes (Intensive care admission, invasive mechanical ventilation, acute kidney injury), and mortality.Main resultsWe identified 74 studies reporting 823 cases of solid organ transplantation with COVID-19. Among 372 patients, 114 (30.6%) were mild COVID-19, 101 (27.2%) moderate, and 157 (42.2%) severe or critical.Major outcomes included intensive care unit admission, invasive ventilation, and acute kidney injury, which occurred in 121 (14.7%), 97 (11.8%), and 63 (7.7%) of patients, respectively. Mortality was reported in 160 (19.4%) patients. Missing individual data hindered making clinical correlations.ConclusionCOVID-19 in solid organ transplant patients probably has a more disease severity, worse major outcomes (Intensive care admission, invasive ventilation, acute kidney injury), and higher mortality than in non-transplant patients.

Highlights • Solitary adrenal recurrence of HCC after LDLT is extremely rare. • Strict follow up protocol is necessary to allow early detection of tumor recurrence. • Curative surgical resection of solitary recurrent HCC is a safe option. • It is associated with low morbidity and expected to have a good long-term survival., Introduction The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. Presentation 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son. The actual graft weight was 1208 g and GRWR was 1.5. The patient started oral direct acting antiviral drugs for recurrent HCV 2 years after LDLT. A left adrenal mass was detected on follow up radiology. No other metastatic lesions were detected on metastatic workup. Left adrenalectomy was done by an anterior approach. The postoperative course was uneventful and was discharged a week after operation. Postoperative pathological and immune-histochemical examinations confirmed the metastatic HCC nature of the mass. The patient is under regular follow up with no recurrences 6 month after resection. Discussion There is no consensus regarding the management of HCC recurrence after LDLT. Most patients had multi-organ recurrences and usually offered palliative or supportive care. Solitary HCC recurrence offers a better chance for more aggressive therapy, offering better prognosis. Conclusion Solitary adrenal recurrence of HCC after LDLT is extremely rare. Strict follow up protocol is necessary to allow early detection of tumor recurrence. Curative surgical resection is a safe option associated with low morbidity and expected to have a good long-term survival.

Introduction: Living donor liver transplantation (LDLT) is a complex surgery with high risk for massive bleeding and blood component transfusion. This retrospective study investigated the effect of adopting ROTEM based transfusion algorithm on blood products transfusion practice among LDLT recipients and the effect of this change on patient outcome. Material and methods: Data of 216 patients with predicted intraoperative massive bleeding (blood loss ≥70 ml blood/kg, or blood loss >150 ml/min with hemodynamic affection with continuing need for transfusion) were collected from our database. Patients were divided into two groups according to transfusion protocol applied; Pre-ROTEM group (n = 95), ROTEM group (n = 121). Basal characteristics, blood component transfusion, graft outcome and patient outcome (28-day mortality and one-year mortality) were compared between the two groups. Results: Transfused packed red blood cells (PRBCs) units, fresh frozen plasma (FFP) units, and application of massive transfusion protocol (MTP) were significantly lower in the ROTEM group compared to pre-ROTEM group [8(7) vs 4.5(5), p

Background and study aims Hepatitis C virus (HCV)-related cirrhosis is the leading cause of liver transplantation (LT). All patients who undergo LT with detectable serum HCV-RNA experience graft reinfection, which is the most frequent cause of graft loss and death in these patients. We estimated the rate of HCV recurrence and evaluated the current therapeutic regimens. Patients and methods The records of consecutive 325 living donor LT (LDLT) surgeries performed between May 2004 and August 2014 were retrospectively analysed; 207 of them were followed-up throughout the study. Clinical, laboratory, radiological and histopathological examinations were performed thoroughly. Patients received treatment in the form of either pegylated interferon (PEG-IFN) or sofosbuvir , both in combination with ribavirin . Results In total, 90.3% of recipients who were transplanted because of HCV-related end-stage liver disease experienced recurrence due to the virus. The donor age was older in the HCV recurrent group versus the non-recurrence group (28.7 ± 7.1 versus 22.6 ± 2.6 years: p ≤ 0.001 ), warm ischaemia time was prolonged (46.1 ± 18.1 versus 28.6 ± 4.1 min: p ≤ 0.001), median cold ischaemia time was 40.0 (10–175) versus 22.5 (15–38) min (p ≤ 0.001) and basal PCR was 414000 (546-116000000) versus 10766 (1230-40000) (p ≤ 0.001). Sustained virological response was achieved in 95.4% of patients treated with a combination of a fixed daily dose of 400 mg sofosbuvir with ribavirin and in 65.1% of those who were treated with PEG-IFN with ribavirin. Conclusions Older donor age and prolonged warm ischaemia time are independent predictors of HCV recurrence after LDLT, and early treatment with the direct-acting sofosbuvir is helpful in resolving the problem of post-LT HCV recurrence.

Background Reduction of anesthesia cost has become a necessity, especially in developing countries. Recently, automated control of end-tidal sevoflurane concentration (EtSev) has been proposed as a new technique with both cost-effectiveness and safety profiles. In this study, sevoflurane consumption (primary outcome variable) was evaluated during living donor hepatectomy using automated control of EtSev (EtC) at fresh gas flow (FGF) of 0.5 and 2 L/min compared to manual control (MC) technique at FGF of 2 L/min. Materials and methods Prospective, randomized, controlled trial including 60 Potential donors scheduled for living donor right hepatectomy. patients were randomized into 3 equal groups (according to target control of sevoflurane), MC group, EtC-2L group, and EtC-0.5L group. In MC group: FGF was set to 2 L/min, inspired concentration of Sevoflurane (FiSev) was set to 1.5–2% in 0.4 fractional inspired oxygen concentration (FiO2), while in EtC-2L group: FGF was set to 2 L/min, EtSev was set to 1–1.5% with end tidal oxygen concentration (EtO2) target of 0.35. In EtC-0.5L group, FGF was set to minimal flow and EtSev target to 1–1.5% and EtO2 target of 0.35. Anesthetic gases consumption (sevoflurane ml, Oxygen L, and air consumption L) per anesthesia hour were recorded at the end of surgery. Other recorded data included intraoperative hemodynamics, the number of user adjustments, and extubation time. Results Significant reduction in sevoflurane consumption when EtC-0.5L is used (4.2 ± 1.3 ml/h, 12.6 ± 2.6 ml/h, and 15 ± 2.9 ml/h respectively, p . 0.001). Also, a significant decrease in overall numbers of user adjustments between the three groups (8 times for EtC-0.5L group, 7 times in EtC-2L group, 22 times for MC group, p . 0.008) was observed. Conclusion automated control of EtSev during anesthesia of living donor hepatectomy significantly lowers sevoflurane consumption and decreases required user interventions without deleterious effect on patient safety.

Living donor liver transplantation (LDLT) is a valuable option for expanding the donor pool, especially in localities where deceased organ harvesting is not allowed. In addition, rejection rates were found to be lower in LDLT, which is attributed to the fact that LDLT is usually performed between relatives. However, the impact of genetic relation on the outcome of LDLT has not been studied. In this study, we examined the difference in rejection rates between LDLT from genetically related (GR) donors and genetically unrelated (GUR) donors. All cases that underwent LDLT during the period from May 2004 until May 2014 were included in the study. The study group was divided into 2 groups: LDLT from GR donors and LDLT from GUR donors. A total of 308 patients were included in the study: 212 from GR donors and 96 from GUR donors. Human leukocyte antigen (HLA) typing was not included in the workup for matching donors and recipients. GUR donors were wives (36; 11.7%), sons-in-law (7; 2.3%), brothers-in-law (12; 3.9%), sisters-in-law (1; 0.3%), and unrelated (38; 12.3%). The incidence of acute rejection in the GR group was 17.4% and 26.3% in the GUR group (P value = 0.07). However, there was a significant difference in the incidence of chronic rejection (CR) between the 2 groups: 7% in GR group and 14.7% in the GUR group (P value = 0.03). In terms of overall survival, there was no significant difference between both groups. LDLT from the GUR donors is not associated with a higher incidence of acute cellular rejection. However, CR was significantly lower when grafts were procured from GR donors. HLA matching may be recommended before LDLT from GUR donors. Liver Transplantation 23:43-49 2017 AASLD.

Highlights • Biliary reconstruction is a cornerstone of LDLT. • The use of trans-anastomotic biliary catheters is controversial. • We describe a rare case of intestinal obstruction due to internal herniation around biliary catheter. • Awareness of this complication plus early surgical intervention can prevent postoperative morbidity and mortality., Introduction Biliary reconstruction is a cornerstone of living-donor liver transplantation (LDLT). The routine uses of trans-anastomotic biliary catheters in biliary reconstruction had been a controversial issue. We describe a rare complication related to the use of trans-anastomotic biliary catheter after LDLT. In this case, intestinal obstruction occurred early after LDLT due to internal herniation of the small bowel around trans-anastomotic biliary catheter. Presentation A 42 years male patient with end stage liver disease underwent LDLT utilizing a right hemi-liver graft. Biliary reconstruction was done by single duct-to-duct anastomosis over trans-anastomotic biliary catheter. The patient was doing well apart from early postoperative ascites that was managed medically. Three weeks after surgery, the patient developed severe agonizing central abdominal pain not responding to anti-spasmodics and analgesics. The decision was to proceed for surgical exploration. Exploration revealed internal herniation of the small bowel loops around the trans-anastomotic biliary catheter without strangulation. Reduction of the internal hernia was done by releasing the fixation of the biliary catheter from the anterior abdominal wall. Small bowel resection was not required. The patient had smooth postoperative course and was discharged 10 days after surgery. Discussion Awareness regarding this rare complication plus early surgical intervention can prevent the development of postoperative morbidity and mortality. To the best of our knowledge this is the first report to describe such are complication after LDLT. Conclusion We report the first case of internal herniation of small bowel around biliary catheter early after LDLT.

Introduction.The possible risk factors for chronic kidney disease in transplant recipients have not been thoroughly investigated after living-donor liver transplantation.Material and Methods.A retrospective cohort study of consecutive adults who underwent living-donor liver transplantation between May 2004 and October 2016, in a single center, was conducted. Kidney function was investigated successively for all the patients throughout the study period, with 12 months being the shortest follow-up. Postoperative renal dysfunction was defined in accordance with the Chronic Kidney Disease Epidemiology Collaboration criteria. The patients’ demographic data, preoperative and intraoperative parameters, and outcomes were recorded. A calcineurin inhibitor-based immunosuppressive regimen, either tacrolimus or cyclosporine, was used in all the patients.Results.Of the 413 patients included in the study, 33 (8%) who survived for ≥1 year experienced chronic kidney disease 1 year after living-donor liver transplantation. Twenty-seven variables were studied to compare between the patients with normal kidney functions and those who developed chronic kidney disease 1 year after living-donor liver transplantation. Univariate regression analysis for predicting the likelihood of chronic kidney disease at 1 year revealed that the following 4 variables were significant: operative time,P< 0.0005; intraoperative blood loss,P< 0.0005; preoperative renal impairment,P= 0.001; and graft-to-recipient weight ratio (as a negative predictor),P< 0.0005. In the multivariate regression analysis, only 2 variables remained as independent predictors of chronic kidney disease at 1 year, namely, operative time with a cutoff value of ≥714 minutes and graft-to-recipient weight ratio as a negative predictor with a cutoff value of Conclusion.In this study, prolonged operative time and small graft-to-recipient weight ratio were independent predictors of chronic kidney disease at 1 year after living-donor liver transplantation.

Background Living donor liver transplantation (LDLT) is considered a safe alternative to deceased donor liver transplantation (DDLT). In Egypt, DDLT program is still awaited, making LDLT the only hope for patients with end-stage liver disease, mainly due to chronic hepatitis C virus (HCV) infection. The current study is conducted to evaluate our experience of LDLT and discuss the lessons learned from 500 consecutive cases in HCV area. Methods We reviewed the data of patients who underwent LDLT at Gastrointestinal Surgery Center, Mansoura University during the period between May 2004 and March 2017. Results During the study period, 500 cases underwent LDLT at our unit. The median age was 51 years, and most of our cases were males (446, 89.2%) and had HCV infection (453, 90.6%). The median MELD score was 15. Median ICU stay was 5 days, and hospital stay was 22 days. Postoperative morbidities occurred in 220 cases (44%). Early mortality occurred in 69 patients (13.8%), and late mortality occurred in 45 patients (9%). The 1-, 3-, 5-, and 7-year overall survival rates of all cases were 80.9%, 78.2%, 75.7%, and 75%, respectively. Preoperative creatinine, worm ischemia, blood transfusion, ICU stay, postoperative morbidities, and small for size syndrome were independent predictors for overall survival. Conclusions In countries lacking DDLT, LDLT is the only effective alternative. LDLT requires a teamwork to achieve successful outcomes. LDLT should only be performed in centers with the adequate experience to avoid and decrease the hazards related to this procedure.

Background Living liver donors represent a special group of patients. They are healthy individuals who are exposed to a major surgery, in which the dominant liver proportion is extracted as a graft. Of all potential donor-related morbidities, posthepatectomy liver dysfunction (PHLD) is the most significant as it may be directly related to donor mortality. We aimed to review our data of adult living donor liver transplantation (LDLT) utilizing the right hemiliver grafts to determine the incidence and potential predictors for the development of PHLD, defined according to the International Study Group of Liver Surgery. Methods We reviewed the data of all adult living donors who underwent right hemihepatectomy during the period between May 2004 and 2016. Results During the study period, 434 cases underwent right hemihepatectomy for adult LDLT. We divided our cases into 2 groups according to the occurrence of PHLD. A significant lower residual liver volume and percentage were noted in PHLD group. Longer intensive care unit stay and hospital stay, and more postoperative morbidities, were observed in PHLD group. PHLD occurred in 50 cases (11.5%), and most of them were grade A (47 cases [10.8%]). Two cases (0.5%) had grade B requiring diuretic therapy, and 1 case (0.2%) had grade C requiring ultrasound guided tube drainage and surgical exploration finally. Conclusions We should not underestimate the risks of liver donation surgery, especially when utilizing the right hemiliver graft. Donor safety should be ensured by accurate preoperative volumetric assessment of the remnant liver and remnant liver volume limitations must be strictly followed.

Living donor liver transplantation has shorter cold ischemia time, less preservative volume, and lower metabolic load compared to transplantation from deceased donors. We investigated the impact of rinsing the graft contents into the systemic circulation on operative course and postoperative outcomes. Donors had right hepatectomy, and grafts were preserved with cold histidine-tryptophan-ketoglutarate solution. On ending portal vein anastomosis, grafts were flushed by patient's portal blood either through incompletely anastomosed hepatic vein (extracorporeal rinse group, EcRg, n = 40) or into systemic circulation (circulatory rinse group, CRg, n = 40). The primary outcome objective was the lowest mean arterial blood pressure within 5 min after portal unclamping as a marker for postreperfusion syndrome (PRS). Secondary objectives included hemodynamics and early graft's and patient's outcomes. Within 5 min postreperfusion, mean arterial blood pressure was significantly lower in the CRg compared to the EcRg, yet this was clinically insignificant. Postoperative graft functions, early biliary and vascular complications, and three-month survival were comparable in both groups. Rinsing the graft into the circulation increased the incidence of PRS without significant impact on early graft or patient outcome in relatively healthy recipients.

Background: Transversus abdominis plane (TAP) block is a promising technique for analgesia after abdominal surgery. This prospective, randomized controlled trial assessed the effect of adding dexmedetomidine to bupivacaine in TAP block for donor hepatectomy. We hypothesized that this would improve postoperative morphine consumption and reduce analgesia related complication and inflammation. Methods: A total of 50 donor hepatectomy were enrolled in this study. Patients divided into two equal groups according to drugs used for TAP block. Group (B) received 20 ml of bupivacaine hydrochloride 0.25%, Group (BD) received 20 ml of bupivacaine hydrochloride 0.25% and 0.3 μg/kg dexmedetomidine, on both sides at the end of surgery and every 8 h for 48 h at right side only through inserted catheter. Primary outcome objective was morphine consumption at first 72 h. Secondary outcome objectives were morphine requirement, numbers of intake, time to first intake, pain score numerical analog scale (NAS), postoperative analgesia related complications, recovery of intestinal motility, and inflammatory markers. Results: Data were analyzed, rescue morphine analgesia was significantly lower in (BD) group compared with (B) groups as considering total morphine consumption (B 4 ± 1.9, BD 1.5 ± 0.5, P = 0.03), numbers of morphine intake (P = 0.04), morphine requirement (P = 0.03), and first time of analgesia intake (P = 0.04). NAS was significantly lower in group (BD) compared with group (B) group in the first 12 h (NAS 0 - P = 0.001, NAS 1 - P = 0.03). Adding dexmedetomidine improved gut motility, first oral intake without detectable anti-inflammatory effect. Conclusion: Adding dexmedetomidine to bupivacine in a surgically inserted catheter for TAP block in donor hepatectomy reduced morphine consumption without detectable anti-inflammatory effect.