Intraoperative terlipressin therapy reduces the incidence of postoperative acute kidney injury after living donor liver transplantation.

OBJECTIVE: To evaluate the effect of intraoperative infusion with terlipressin on the incidence of acute kidney injury (AKI) after living donor liver transplantation (LDLT). DESIGN: Retrospective case-controlled study. SETTING: Government hospital. PARTICIPANTS: The medical records of 303 patients who underwent LDLT were reviewed retrospectively. INTERVENTIONS: Patients were divided into 2 groups on the basis of intraoperative administration of terlipressin. The primary outcome was AKI, as defined by the Acute Kidney Injury Network criteria. Secondary outcomes included the requirement for postoperative dialysis and in-hospital mortality. MEASUREMENTS AND MAIN RESULTS: The incidence of AKI was 38% (n = 115); AKI occurred in 24 (24.2%) patients who received terlipressin versus 91 (44.6%) in the control group (p = 0.001). The incidence of postoperative dialysis was 9.2% (n = 28). Postoperative dialysis was needed by 8 patients (8.1%) in the terlipressin group versus 20 patients (9.8%) in the control group (p = 0.62). Multivariate logistic regression analysis indicated that terlipressin protected against AKI (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.2-0.8; p = 0.013) but not the need for dialysis (OR, 0.7; 95% CI, 0.2-2.2; p = 0.53) or the in-hospital mortality (OR, 1.1; 95% CI, 0.5-2.3; p = 0.7). Adjustment, using the propensity score, did not alter the association between the use of terlipressin and AKI reduction (OR, 0.46; 95% CI, 0.22-0.89; p = 0.03). CONCLUSION: These results suggested that intraoperative terlipressin therapy is associated with significant reductions in the risk of AKI in LDLT patients.

Outcome of living donor liver transplantation in patients with preoperative portal vein thrombosis.

BACKGROUND AND STUDY AIMS: Portal vein thrombosis (PVT) is no longer an absolute contraindication for living donor liver transplantation (LDLT). This study aimed to assess the short-term outcomes of LDLT and compare the 1-year survival rates between patients with and without preoperative PVT. PATIENTS AND METHODS: This combined prospective and retrospective cohort study was conducted on patients who underwent LDLT at Ain Shams Centre for Organ Transplantation (ASCOT) between 2008 and 2020. The study included 60 patients with PVT and 60 patients without PVT. The two groups were compared in terms of preoperative data, operative details, postoperative complications, and 1-year survival. RESULTS: Most patients with PVT were Child C (65%) and had higher model for end stage liver disease scores (16.23 ± 4.03) compared to the non-PVT group (13.9 ± 4.5). The PVT group showed longer cold ischemic time (CIT), hospital stay, and intensive care unit stay and significantly shorter 1-year survival rate (63.3%) compared to the non-PVT group (86.7%) (P = 0.003). Those with PVT grades I, II, and III had 1-year survival rates of 72.5%, 50%, and 40%, respectively. CONCLUSION: Preoperative PVT reduces the 1-year survival after transplantation, with patients with higher PVT grades exhibiting lower 1-year survival. LDLT for PVT still remains challenging and requires further studies.

The use of terlipressin during living donor liver transplantation: Effects on systemic and splanchnic hemodynamics and renal function.

OBJECTIVES: To assess the effect of the intraoperative use of terlipressin on splanchnic hemodynamics and postoperative renal function in patients undergoing liver transplantation. DESIGN: Open-label, prospective, randomized study. SETTING: Single-center study. PATIENTS: Thirty patients who underwent elective, living-donor liver transplantation with portal pressure >20 mm Hg. INTERVENTIONS: Patients were assigned randomly to one of two equal groups. The control group received saline, whereas the treatment group (TP group) received an initial bolus dose of terlipressin (1 mg over 30 mins) followed immediately by a continuous infusion of 2 µg·kg(-1)·h(-1) for 48 hrs. MEASUREMENTS AND MAIN RESULTS: Portal pressure and gas exchange (radial artery, portal vein, and hepatic vein, blood gas analyses, and lactate concentration) were assessed at baseline (after ligation of the hepatic artery) and 2 hrs after drug administration. Systemic hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Renal function was assessed by measurement of serum cystatin C after induction of anesthesia and on the first 2 days postoperatively. After the infusion of terlipressin, portal venous pressure decreased significantly from 26.3 ± 3.3 to 21.3 ± 3.6 mm Hg (p < .001). The mean arterial pressure and systemic vascular resistance were significantly higher in the TP group than in the control group, whereas heart rate and cardiac index were comparable between the groups. Portal and hepatic base excess, and the level of serum lactate, did not differ between the two groups. The serum levels of both cystatin C and creatinine were significantly higher in the control group than in the TP group on postoperative day 2. CONCLUSION: Perioperative use of terlipressin abrogates the early postoperative decline in renal function of patients who have chronic liver disease and undergo liver transplantation without any detrimental effect on hepatosplanchnic gas exchange and lactate metabolism.

Biliary complications in recipients of living donor liver transplantation: A single-centre study.

BACKGROUND: Biliary complications (BCs) after liver transplantation (LT) remain a considerable cause of morbidity, mortality, increased cost, and graft loss. AIM: To investigate the impact of BCs on chronic graft rejection, graft failure and mortality. METHODS: From 2011 to 2016, 215 adult recipients underwent right-lobe living-donor liver transplantation (RT-LDLT) at our centre. We excluded 46 recipients who met the exclusion criteria, and 169 recipients were included in the final analysis. Donors' and recipients' demographic data, clinical data, operative details and postoperative course information were collected. We also reviewed the management and outcomes of BCs. Recipients were followed for at least 12 mo post-LT until December 2017 or graft or patient loss. RESULTS: The overall incidence rate of BCs including biliary leakage, biliary infection and biliary stricture was 57.4%. Twenty-seven (16%) patients experienced chronic graft rejection. Graft failure developed in 20 (11.8%) patients. A total of 28 (16.6%) deaths occurred during follow-up. BCs were a risk factor for the occurrence of chronic graft rejection and failure; however, mortality was determined by recurrent hepatitis C virus infection. CONCLUSION: Biliary complications after RT-LDLT represent an independent risk factor for chronic graft rejection and graft failure; nonetheless, effective management of these complications can improve patient and graft survival.

Impact of biliary complications on quality of life in live-donor liver transplant recipients.

BACKGROUND: Despite significant advancements in liver transplantation (LT) surgical procedures and perioperative care, post-LT biliary complications (BCs) remain a significant source of morbidity, mortality, and graft failure. In addition, data are conflicting regarding the health-related quality of life (HRQoL) of LT recipients. Thus, the success of LT should be considered in terms of both the survival and recovery of HRQoL. AIM: To assess the impact of BCs on the HRQoL of live-donor LT recipients (LDLT-Rs). METHODS: We retrospectively analysed data for 25 LDLT-Rs who developed BCs post-LT between January 2011 and December 2016 at our institution. The Short Form 12 version 2 (SF 12v2) health survey was used to assess their HRQoL. We also included 25 LDLT-Rs without any post-LT complications as a control group. RESULTS: The scores for HRQoL of LDLT-Rs who developed BCs were significantly higher than the norm-based scores in the domains of physical functioning (P = 0.003), role-physical (P < 0.001), bodily pain (P = 0.003), general health (P = 0.004), social functioning (P = 0.005), role-emotional (P < 0.001), and mental health (P < 0.001). No significant difference between the two groups regarding vitality was detected (P = 1.000). The LDLT-Rs with BCs had significantly lower scores than LDLT-Rs without BCs in all HRQoL domains (P < 0.001) and the mental (P < 0.001) and physical (P = 0.0002) component summary scores. CONCLUSION: The development of BCs in LDLT-Rs causes a lower range of improvement in HRQoL.

Biliary complications including single-donor mortality: experience of 207 adult-to-adult living donor liver transplantations with right liver grafts.

BACKGROUND: After right lobe donation, biliary complication is the main cause of morbidity. Mortality after right lobe donation has been estimated to be less than 0.5%. PATIENTS AND METHODS: Between November 2001 and December 2008, 207 adult-to-adult living donor liver transplantations (ALDLT) were undertaken using right lobe grafts. Donors included 173 men and 34 women with a mean age of 28.4 +/- 5.2 years. RESULTS: Siblings comprised 144 (69.6%) cases whereas unrelated donors comprised 63 (30.4%) with a mean body mass index (BMI) of 25.2 +/- 2.4. Single and multiple right hepatic ducts (RHD) were present in 82 (39.6%) and 125 (60.3%) donors, respectively. Mean operative time was 360 +/- 50 min with an estimated blood loss of 950 +/- 450 ml and returned cell-saver amount of 450 +/- 334 ml. Mean donor remnant liver volume was 33.5 +/- 3.2%. Mean intensive care unit (ICU) stay was 3 +/- 0.7 days and mean hospital stay was 14 +/- 3.5 days. Modified Clavien classifications were used to stratify all donor biliary complications The overall biliary complications occurred in 27 cases (13.0%). After modified Clavien classification, biliary complications were graded as grade I (n= 10), grade II (n= 2), grade III (n= 14) and grade V (n= 1). Grade I and II (n= 12) biliary complications were successfully managed conservatively. Grade III cases were treated using ultrasound-guided aspiration (USGA), endoscopic retrograde cholangiography (ERCP) and surgery in 10, 2 and 2 donors, respectively. Single donor mortality (Grade V) (0.4%) occurred after uncontrolled biliary leakage with peritonitis that necessitated exploration followed by ERCP with stent insertion but the donor died on day 43 as a result of ongoing sepsis. CONCLUSION: Although the majority of biliary complications are minor and can be managed conservatively, uncontrolled biliary leakage is a serious morbidity that should be avoided as it could lead to mortality.

Effect of Ramadan fasting on Muslim recipients after living donor liver transplantation: A single center study.

BACKGROUND AND STUDY AIMS: Several factors affect the quality of life and personal well-being of transplant recipients, including Ramadan fasting for Muslims. This study aimed to assess the effect of Ramadan fasting on the renal and liver functions of liver transplantation recipients and to propose a protocol for adapting an Immunosuppression regimen and follow-up schedule for patients wishing to fast after liver transplantation. PATIENTS AND METHODS: This prospective study was conducted on 45 recipients who wished to fast Ramadan from 17th May to 14th June 2018, at Ain Shams Center for Organ Transplantation, Cairo, Egypt. RESULTS: The mean age of the patients was 55.5 ± 7.2 (37-68) years, and 84.4% were males; the mean time from liver transplantation was 51.6 ± 28 months (14-117). Thirty-seven patients (82.2%) completed Ramadan fasting, three patients (6.6%) had interrupted fasting, and five patients (11.1%) had to stop fasting because of an unacceptable rise in renal function. There was a statistically significant difference between the pre- and post-fasting states in terms of the serum creatinine level (p = 0.004).However, the serum creatinine did not exceed the upper normal value in the patients who completed fasting. CONCLUSION: Our data seem promising for Ramadan fasting with an adapted immunosuppression protocol and regular follow-up for recipients wishing to fast. Further multicentre studies on a larger number of patients are warranted.

The safety of modern hydroxyethyl starch in living donor liver transplantation: a comparison with human albumin.

BACKGROUND: Intravascular volume replacement therapy is an important issue in the perioperative management of liver transplantation. There is paucity of data on the safety of hydroxyethyl starch (HES) in patients undergoing liver transplantation. We evaluated the safety of a new HES 130/0.4 in the perioperative management of liver transplantation, with a special emphasis on renal function. METHODS: Forty patients undergoing living donor liver transplantation were prospectively randomized into two groups. Patients in the ALB group (n = 20) received 5% human albumin. Patients in the HES group (n = 20) received third generation HES (6% HES 130/0.4). Total colloid administration was limited to 50 mL x kg(-1) x d(-1). The volume was given to maintain pulmonary artery occlusion pressure or central venous pressure between 5 and 7 mm Hg. If additional fluids were required, balanced crystalloid solution was used. Anesthetic and surgical techniques were standardized. Serum creatinine and cystatin C plasma levels were measured from arterial blood samples after induction of anesthesia, at the end of surgery, and on the first 4 postoperative days. RESULTS: All 40 enrolled patients completed the study. Demographic and intraoperative variables were comparable in both groups. Postoperatively, the mean +/- sd volume was 6229 +/- 1140 mL and 4636 +/- 1153 mL in HES and ALB groups, respectively (P = 0.003). There was significantly greater [corrected] net cumulative fluid balance in the HES [corrected] group 3047 +/- 2000 [corrected] mL compared with the ALB group 1100 +/- 900 [corrected] mL, P = 0.029. Serum creatinine, creatinine clearance, and cystatin C plasma levels showed no significant differences between the two groups. One patient in each group developed acute renal failure requiring renal replacement therapy. CONCLUSION: The use of HES 130/0.4 as an alternative to human albumin resulted in equivalent renal outcome after liver transplantation.

Efficacy of loco-regional treatment for hepatocellular carcinoma prior to living donor liver transplantation: a report from a single center in Egypt.

BACKGROUND AND AIM: The number of loco-regional therapies (LRTs) for hepatocellular carcinoma (HCC) has increased dramatically during the past decade, bridging or downstaging patients on the waiting list for liver transplantation. This study aimed to analyze the outcomes of LRTs prior to living donor liver transplantation in patients with HCC. METHODS: Sixty-two HCC patients received living donor liver transplantation at Ain Shams Center for Organ Transplantation over a 2-year period. Data from 29 HCC patients were analyzed. Twenty patients (68.97%) met the Milan Criteria and 4 patients (13.8%) exceeded the Milan Criteria, but met the University of California, San Francisco Criteria. Five patients (17.2%) exceeded the University of California, San Francisco Criteria. All patients underwent preoperative LRTs. The protocol of bridging/downstaging, methods, duration of follow-up, the number of patients who were successfully downstaged before liver transplantation (LT), and their outcomes after LT were recorded. RESULTS: There was a decrease in the mean overall size of focal lesions (from mean 5.46 to 4.11 cm) in the last abdominal computed tomography (CT) scan after LRT (p=0.0018). Discrepancies between the radiological findings and histopathology were as follows: in 16 patients (55.17%) the CT findings were consistent with the histopathological examination of the explanted liver. Underestimated tumor stage was documented in 10 patients (34.48%), and was overestimated by CT scan findings in 3 patients (10.34%). The 1-year survival rate was 93%. No patient had HCC recurrence after median follow-up of 21 months (range 1-46 months). CONCLUSION: These results encouraged tumor bridging/downstaging as a potential treatment option among carefully selected patients with HCC beyond conventional criteria for LT. Further studies on a large number of patients are necessary.

Bacterial infections post-living-donor liver transplantation in Egyptian hepatitis C virus-cirrhotic patients: A single-center study.

AIM: To determine risk factors, causative organisms and antimicrobial resistance of bacterial infections following living-donor liver transplantation (LDLT) in cirrhotic patients. METHODS: This prospective study included 45 patients with hepatitis C virus-related end-stage liver disease who underwent LDLT at Ain Shams Center for Organ Transplant, Cairo, Egypt from January 2014 to November 2015. Patients were followed-up for the first 3 mo after LDLT for detection of bacterial infections. All patients were examined for the possible risk factors suggestive of acquiring infection pre-, intra- and post-operatively. Positive cultures based on clinical suspicion and patterns of antimicrobial resistance were identified. RESULTS: Thirty-three patients (73.3%) suffered from bacterial infections; 21 of them had a single infection episode, and 12 had repeated infection episodes. Bile was the most common site for both single and repeated episodes of infection (28.6% and 27.8%, respectively). The most common isolated organisms were gram-negative bacteria. Acinetobacter baumannii was the most common organism isolated from both single and repeated infection episodes (19% and 33.3%, respectively), followed by Escherichia coli for repeated infections (11.1%), and Pseudomonas aeruginosa for single infections (19%). Levofloxacin showed high sensitivity against repeated infection episodes (P = 0.03). Klebsiella, Acinetobacter and Pseudomonas were multi-drug resistant (MDR). Pre-transplant hepatocellular carcinoma (HCC) and duration of drain insertion (in days) were independent risk factors for the occurrence of repeated infection episodes (P = 0.024). CONCLUSION: MDR gram-negative bacterial infections are common post-LDLT. Pre-transplant HCC and duration of drain insertion were independent risk factors for the occurrence of repeated infection episodes.

Living donor liver transplantation for high model for end-stage liver disease score: What have we learned?

AIM: To assess the impact of model for end-stage liver disease (MELD) score on patient survival and morbidity post living donor liver transplantation (LDLT). METHODS: A retrospective study was performed on 80 adult patients who had LDLT from 2011-2013. Nine patients were excluded and 71 patients were divided into two groups; Group 1 included 38 patients with a MELD score < 20, and Group 2 included 33 patients with a MELD score > 20. Comparison between both groups was done regarding operative time, intra-operative blood requirement, intensive care unit (ICU) and hospital stay, infection, and patient survival. RESULTS: Eleven patients died (15.5%); 3/38 (7.9%) patients in Group 1 and 8/33 (24.2%) in Group 2 with significant difference (P = 0.02). Mean operative time, duration of hospital stay, and ICU stay were similar in both groups. Mean volume of blood transfusion and cell saver re-transfusion were 8 ± 4 units and 1668 ± 202 mL, respectively, in Group 1 in comparison to 10 ± 6 units and 1910 ± 679 mL, respectively, in Group 2 with no significant difference (P = 0.09 and 0.167, respectively). The rates of infection and systemic complications (renal, respiratory, cardiovascular and neurological complications) were similar in both groups. CONCLUSION: A MELD score > 20 may predict mortality after LDLT.

Integrated Management of Childhood Illness (IMCI) Approach in management of Children with High Grade Fever ≥ 39°.

BACKGROUND: Fever is one of the most frequently encountered pediatric problems, accounting for 25% of visits to pediatric emergency room. There is no specific standardized approach to reach to a final diagnosis in children with fever as this may be difficult and individualized for each child. The integrated management of childhood illness (IMCI) approach is an approach designed to reach a classification rather than a specific diagnosis. OBJECTIVE: Comparison between IMCI and Non-IMCI approaches in management of children with high grade fever≥ 39°. PATIENTS AND METHODS: This is a prospective study carried out on 50 children less than five years old presented with fever ≥ 39° attended the outpatient clinic of Minia university hospital from September 2012 to May 2014. These 50 children divided into 2 groups: group I (25 children) subjected to the (IMCI) approach and group II (25 children) subjected to the traditional approach. RESULTS: Most of children according to the IMCI approach (64%) were classified and diagnosed during the first day, while most of children in traditional approach were diagnosed by the fourth (34%) or fifth day (20%). Sixty percent of children treated according to IMCI approach were improved clinically compared to 12% in traditional approach. Forty percent of children treated according to traditional approach had worse outcomes compared to 16% treated according to the IMCI. CONCLUSION: The IMCI approach can be applied upon children under five years old with high grade fever to reach to a classification, early diagnosis, much better outcomes and less daily cost than the traditional approach.

Safety, Efficacy, and Tolerability of Sofosbuvir and Ribavirin in Management of Recurrent Hepatitis C Virus Genotype 4 After Living Donor Liver Transplant in Egypt: What Have We Learned so far?

BACKGROUND: Recurrence of HCV after living donor liver transplant (LDLT) is nearly universal, with almost one third of recipients developing cirrhosis and graft failure within 5 years after LDLT. Different studies have been published on the effect of sofosbuvir after liver transplantation on recurrent HCV with different genotypes. OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of sofosbuvir and ribavirin in LDLT recipients with recurrent HCV genotype 4. PATIENTS AND METHODS: Thirty-nine Egyptian LDLT recipients were treated for recurrent HCV after LDLT with nucleos(t)ide analog NS5B polymerase inhibitor, sofosbuvir, and ribavirin without pegylated interferon for 6 months (November 2014 to June 2015) in this intention-to-treat analysis. RESULTS: One recipient died 1 week after starting the treatment, but the remaining 38 patients completed 24 weeks of treatment and were then followed for 12 weeks after end of treatment (EOT). The sustained virological response (SVR) at week 12 after EOT was achieved in 76% (29/38) of recipients. SVR was significantly higher in treatment-naïve patients and in recipients with a low stage of fibrosis. Only 2 (5%) recipients developed severe pancytopenia and acute kidney injury. CONCLUSIONS: We recommend initiating treatment as soon as possible after liver transplantation with newer combinations, such as ledipasvir/sofosbuvir or sofosbuvir/simeprevir, rather than sofosbuvir with Ribavirin, to achieve higher rates of SVR.

Reversibility of minimal hepatic encephalopathy following liver transplantation in Egyptian cirrhotic patients.

AIM: To evaluate the reversibility of minimal hepatic encephalopathy (MHE) following liver transplantation (LT) in Egyptian cirrhotic patients. METHODS: This prospective study included twenty patients with biopsy-proven liver cirrhosis listed for LT and twenty age- and sex-matched healthy control subjects. All underwent neuro-psychiatric examination, laboratory investigations, radiological studies and psychometric tests including trail making test A (TMT A), TMT B, digit symbol test and serial dotting test. The psychometric hepatic encephalopathy score (PHES) was calculated for patients to diagnose MHE. Psychometric tests were repeated six months following LT in the cirrhotic patient group. RESULTS: Before LT, psychometric tests showed highly significant deficits in cirrhotic patients in comparison to controls (P < 0.001). There was a statistically significant improvement in test values in the patient group after LT; however, their values were still significantly worse than those of the controls (P < 0.001). The PHES detected MHE in 16 patients (80%) before LT with a median value of -7 ± 3.5. The median PHES value was significantly improved following LT, reaching -4.5 ± 5 (P < 0.001), and the number of patients with MHE decreased to 11 (55%). The pre-transplant model for end-stage liver disease (MELD) score ≥ 15 was significantly related to the presence of post-transplant MHE (P = 0.005). More patients in whom reversal of MHE was observed had a pre-transplant MELD score < 15. CONCLUSION: Reversal of MHE in cirrhotic patients could be achieved by LT, especially in those with a MELD score < 15.

Assessment of health-related quality of life in Egyptian HCV-infected recipients after living donor liver transplantation.

OBJECTIVE: Understanding issues pertaining to quality of life is essential for any disease, particularly in recipients of liver transplantation. The aim of this study was to evaluate the impact of liver transplantation on Egyptian recipients' health-related quality of life (HRQOL). METHODS: A prospective study carried out at the Ain Shams Center for Organ Transplantation (Cairo, Egypt), including 35 recipients for the evaluation of HRQOL using short form 36 score (Arabic version) and Beck Depression Inventory scores pre-transplantation and 1 and 6 months afterwards. RESULTS: The mean age of the recipients was 49.27 ± 8.16 years. Among them, 17 patients were highly educated. A statistically significant improvement in all dimensions of their HRQOL was observed after liver transplantation. Their physical functioning was 45.00 ± 34.34 before liver transplantation while after 1 and 6 months it was 57.50 ± 20.66 and 74.83 ± 19.27, respectively (P < 0.001). All 17 patients completed their first year after transplantation, showing a statistically significant improvement in all dimensions of their HRQOL one year after liver transplantation except that in mental health, role limitation due to emotional health emotional and social functioning domains. CONCLUSION: HRQOL is an important aspect of liver transplantation that should not be neglected.

Donor rejection before living donor liver transplantation: causes and cost effective analysis in an egyptian transplant center.

BACKGROUND: In the living donor liver transplant setting, the preoperative assessment of potential donors is important to ensure the donor safety. OBJECTIVES: The aim of this study was to identify causes and costs of living liver-donors rejection in the donation process. MATERIALS AND METHODS: From June 2010 to June 2012, all potential living liver donors for 66 liver transplant candidates were screened at the Ain Shams Center for Organ Transplantation. Potential donors were evaluated in 3 phases, and their data were reviewed to determine the causes and at which phase the donors were rejected. RESULTS: One hundred and ninety two potential living liver donors, including 157 (81.7%) males, were screened for 66 potential recipients. Of these, 126 (65.6%) were disqualified for the donation. The causes of rejection were classified as surgical (9.5 %) or medical (90.5 %). Five donors (3.9 %) were rejected due to multiple causes. Factor V Leiden mutation was detected in 29 (23 %) rejected donors (P = 0.001), 25 (19.8 %) donors had positive results for hepatitis serology (P = 0.005), and 16 (12.7 %) tested positive for drug abuse. Portal vein trifurcation (n = 9, 7.1%) and small size liver graft estimated by CT volumetric analysis (n = 6, 4.8 %) were the main surgical causes which precluded the donation. CONCLUSIONS: Among potential Egyptian living liver donors, Factor V Leiden mutation was a significant cause for live donor rejection. A stepwise approach to donor assessment was found to be cost-effective.