Intraoperative Optic Nerve Sheath Diameter as a Predictor of Early Tacrolimus Neurotoxicity after Living Donor Liver Transplantation.

BACKGROUND: 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. BASIC PROCEDURES: 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. MAIN FINDINGS: 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). CONCLUSIONS: This data indicates that intraoperative ultrasonic ONSD after reperfusion can predict tacrolimus neurotoxicity after liver transplantation. TRIAL REGISTRATION: NCT03799770; registered on January 1st, 2019.

Norepinephrine boluses for the prevention of post-reperfusion syndrome in living donor liver transplantation: A prospective, open-label, single-arm feasibility trial.

Background and Aims: Post-reperfusion syndrome (PRS) is a serious haemodynamic event during liver transplantation (LT), which increases early graft dysfunction and mortality. This study aimed to test the efficacy and safety of norepinephrine (NE) boluses to prevent PRS during orthotopic LT. Methods: This feasibility phase II trial prospectively recruited a single arm of 40 patients undergoing living donor LT. The intervention was an escalated protocol of NE boluses starting at 20 µg. The primary outcome was the incidence of PRS. The secondary outcomes were arrhythmia, electrocardiographic (EKG) ischaemic changes, mean pulmonary pressure after reperfusion, 3-month survival and 1-year survival. Results: PRS occurred in 28 (70%) cases [95% confidence interval (CI) 54% to 83%, P < 0.001], with a relative risk reduction of 0.22 when compared to our previous results (90%). Twelve cases developed transient EKG ischaemic changes. All EKG ischaemic changes returned to baseline after correction of hypotension. There was no significant arrhythmia or bradycardia (95% CI 0 to 0.9). After reperfusion, the mean pulmonary artery pressure was not significantly higher than the normal limit (20 mmHg) (P = 0.88). The 3-month survival was 0.95 (95% CI 0.83 to 0.99), and the 1-year survival was 0.93 (95% CI 0.8 to 0.98). Conclusion: Our findings suggest that NE boluses starting with 20 µg is feasible and effective in lowering the risk of PRS during living donor LT. Additionally, NE boluses were not associated with significant myocardial ischaemic events, arrhythmia or a rise in pulmonary pressure.

Adrenalectomy for solitary recurrent hepatocellular carcinoma five years after living donor liver transplantation: A case report.

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.

Internal hernia of the small intestine around biliary catheter after living-donor liver transplantation: A case report.

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.

Renal Dysfunction after Living-Donor Liver Transplantation: Experience with 500 Cases.

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 <0.91. 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.

Predictors of hepatitis C virus recurrence after living donor liver transplantation: Mansoura experience.

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±2.6years: p≤0.001), warm ischaemia time was prolonged (46.1±18.1 versus 28.6±4.1min: 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 400mg 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.

Short-term effects of extracorporeal graft rinse versus circulatory graft rinse in living donor liver transplantation. A prospective randomized controlled trial.

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.

Biliary complications in living donor right hepatectomy are affected by the method of bile duct division.

The bile duct division is a crucial step in the donor hepatectomy. Multiple small ducts will make the biliary reconstruction more difficult and may influence the outcome of the recipient. Biliary leakage, bilomas and biliary strictures are well recognized donor complications that may be directly linked to bile duct division. Biliary division still needs more standardization. This work aims to analyze our experience with two different methods of bile duct division in relation to the development of intraoperative and postoperative biliary complications. Between April 2004 and March 2013, 216 liver donors underwent right hepatectomy, in Gastro-Enterology Surgical Center, Mansoura University, Egypt. According to the method of bile duct division, the study population was divided into 2 groups; 1- extrahepatic dissection group (EDG) and 2- fluoroscopy guided transection group (FGG), each comprised 108 patients. Data were collected from a prospectively registered database, with special emphasis on the occurrence of biliary complications. Complications were classified according to the latest version of Clavien classification. Intraoperative biliary complications did not differ between both groups, p = 0.313. The commonest postoperative complication was biliary leak/biloma accounting for 32.5% of all donor complications, followed by non-biliary fluid collections. 24 (11.1%) donors developed 27 biliary complications. The FGG showed significantly less biliary complications (5.6%, 6 donors), when compared to EDG (15.7%, 18 donors), p = 0.015. Grade 3 complications were significantly higher in EDG, p = 0.024. On multivariate analysis, the only significant factor predicting the occurrence of biliary complications was the use of fluoroscopy guided bile duct division, p = 0.009. In conclusion, we believe that the proposed method of biliary division is safe, simple and reproducible.

Factors affecting recurrence and survival after living donor liver transplantation for hepatocellular carcinoma.

BACKGROUND/AIMS: HCC is a leading cause of cancer-related deaths worldwide. The main etiological factor in Egypt is HCV infection. Lack of cadaveric transplantation in Egypt makes LDLT the only available option for liver transplantation for HCC patients with advanced cirrhosis and/or non-resectable tumors. METHODOLOGY: Between January 2004 and April 2012, 170 patients underwent LDLT at the Liver Transplantation Unit, Mansoura University, and 52 (30.6%) were shown to have HCC by pathological examination. Patient demographics, preoperative interventions and pathological findings were evaluated for their influence on recurrence and survival. Patients were followed-up with abdominal sonography and AFP every 3 months and CT scans every 6 months. Median follow-up was 22.9 months. RESULTS: The main cause of underlying cirrhosis was HCV (96.2%). One or more different pre-transplant treatments of HCC were performed in 14 (27.4%) patients. The median total size was 4cm (0.8-15.5). Microvascular invasion was detected in 16 (31.4%) patients; 16 patients proved to have tumors beyond the Milan criteria. Pre-transplantation AFP more than 200ng/mL, total tumor size more than 8cm and microvascular invasion influenced recurrence rate on univariate analysis. Multivariate analysis identified AFP (p = 0.016) as independent factor for recurrence. Survival was significantly affected by AFP (p = 0.003) and microvascular invasion (p = 0.003). CONCLUSIONS: LDLT is a feasible option for patients with HCC on top of cirrhosis with good survival and recurrence-free survival rates.

The impact of portopulmonary hypertension on intraoperative right ventricular function of living donor liver transplant recipients.

BACKGROUND: Portopulmonary hypertension (PPH) burdens a right ventricle (RV) already exposed to physiologic stress during liver transplantation. The magnitude of the impact of PPH on RV function, especially early reperfusion, has not been evaluated adequately by prospective controlled trials. In this study, we prospectively quantified the impact of PPH on the RV function in living donor liver transplant recipients. METHODS: Twenty patients undergoing living donor liver transplant were stratified based on mean pulmonary artery pressure (mPAP) into a control group (mPAP <25 mm Hg) and a PPH group (mPAP ≥25 mm Hg). Standard anesthetic technique and monitoring were used. Fiberoptic pulmonary artery catheters enabled to measure RV ejection fraction (RVEF) were used. Hemodynamics were recorded after induction of anesthesia, the end of hepatectomy, before portal unclamping, 5 and 30 minutes after reperfusion, and at skin closure. RESULTS: The PPH group had significantly lower RVEF, stroke volume, and higher central venous pressure and RV end-diastolic volume index after portal unclamping versus the controls. Pulmonary vascular resistance index and mPAP were significantly higher throughout the operation in the PPH group, but RV stroke work index did not differ significantly between groups. RVEF was significantly reduced in the PPH group after reperfusion compared with baseline, but the control group did not experience such a reduction. CONCLUSIONS: Mild to moderate PPH was associated with reduced RVEF during liver transplantation, especially after reperfusion, likely because of a reduced RV contractile reserve in PPH patients. This reduction in RVEF was clinically well tolerated by patients with mild to moderate PPH.

Outcome of right hepatectomy for living liver donors: a single Egyptian center experience.

BACKGROUND: This study aims to evaluate living liver donor outcome after right hepatectomy in a single Egyptian center. PATIENTS AND METHODS: Between April 2004 and July 2010, 100 living donors underwent right hepatectomy. Their medical records and postoperative follow-up visits were retrospectively revised. Perioperative complications were reported. Postoperative complications were classified according to the five tier version of Clavien system. RESULTS: There were 71 males and 29 females. The mean age was 27.6 ± 7.4 years. The mean graft weight was 999 ± 167 g and the mean volume percent of the remaining liver was 36.8 ± 8%. The mean ICU and hospital stay were 2.6 ± 2.7 and 12.4 ± 9.1, respectively. A total of 57 complications developed in 38 donors (38%). The commonest complication type was biliary complications. There were 22 grade I, 6 grade II, 15 grade IIIa, 12 grade IIIb, 1 grade IVa, and 1 grade V complications. One donor died due to posttransfusion ARDS on the 30th postoperative day. On follow-up, no donor developed long lasting disability. A donor died in a road traffic accident 1 year after donation. DISCUSSION AND CONCLUSIONS: Donor right hepatectomy is not an entirely safe procedure. Biliary complications are the commonest early postoperative complications.