Arterial blood pressure waveform in liver transplant surgery possesses variability of morphology reflecting recipients' acuity and predicting short term outcomes.

We investigated clinical information underneath the beat-to-beat fluctuation of the arterial blood pressure (ABP) waveform morphology. We proposed the Dynamical Diffusion Map algorithm (DDMap) to quantify the variability of morphology.  The underlying physiology could be the compensatory mechanisms involving complex interactions between various physiological mechanisms to regulate the cardiovascular system. As a liver transplant surgery contains distinct periods, we investigated its clinical behavior in different surgical steps. Our study used DDmap algorithm, based on unsupervised manifold learning, to obtain a quantitative index for the beat-to-beat variability of morphology. We examined the correlation between the variability of ABP morphology and disease acuity as indicated by Model for End-Stage Liver Disease (MELD) scores, the postoperative laboratory data, and 4 early allograft failure (EAF) scores. Among the 85 enrolled patients, the variability of morphology obtained during the presurgical phase was best correlated with MELD-Na scores. The neohepatic phase variability of morphology was associated with EAF scores as well as postoperative bilirubin levels, international normalized ratio, aspartate aminotransferase levels, and platelet count. Furthermore, variability of morphology presents more associations with the above clinical conditions than the common BP measures and their BP variability indices. The variability of morphology obtained during the presurgical phase is indicative of patient acuity, whereas those during the neohepatic phase are indicative of short-term surgical outcomes.

Drug-Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir-Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis.

BACKGROUND: The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated. METHODS: Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD. RESULTS: The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration-time curve from time 0-12 hours (AUC0-12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed. CONCLUSIONS: Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.

Safety and long-term outcomes of early liver transplantation for pediatric methylmalonic acidemia patients.

BACKGROUND: LT is a treatment option for MMA patients, but renal function impairment is one of the long-term concerns. The aim of this study was to evaluate the outcomes of early LT in these patients. METHODS: A total of 11 MMA mut-type patients (including 10 mut0 cases and 1 mut-case) who received LT in our institute were reviewed. Their metabolic profiles were compared between the pre/post-transplant periods. Their immunosuppressant and renal function changes after transplantation were assessed. RESULTS: After a mean follow-up of 97.5 ± 38.4 months, there were two deaths, and the actual survival rate was 81.8%. Their metabolic profiles had improved (mean blood ammonia level 366.8 ± 105.5 vs. 53.1 ± 17.4 µg/dl, p < .001; C3/C2 ratio 2.68 ± 0.87 vs. 0.73 ± 0.22, p = .003; mean urine MMA level 920.5 ± 376.6 vs. 196.2 ± 85.4, p = .067), and hospital stays were decreased (78.8 ± 74.5 vs. 7.4 ± 7.0 days/year, p = .009) after transplantation. The mean age at transplant was 1.81 ± 2.02 years old, and nine of these patients received LT before the age of 1.5 years old (early LT). Under prospective immunosuppressant dose reduction, three of these early LT patients discontinued the drug and were sustained for more than 5 years. Most of the patients had a preserved renal function, and no patient is currently on dialysis. CONCLUSIONS: In addition to the improvement in the metabolic parameters, early LT in MMA patients may allow for a dose reduction of the immunosuppressant, and the patient's renal function could be preserved in the long term.

Safe Strategy to Initiate Total Laparoscopic Donor Right Hepatectomy: A Stepwise Approach From a Laparoscopy-Assisted Method.

BACKGROUND: Total laparoscopic donor right hepatectomy (TLDRH) for adult living liver donors has been reported by a few experienced centers, but with limited cases, its safety and feasibility remain controversial. We report our experience initiating TLDRH using a stepwise approach to gradually convert laparoscopy-assisted donor right hepatectomy (LADRH) to TLDRH. METHODS: We retrospectively analyzed the data of 61 LADRHs, 56 conventional open donor right hepatectomies (CODRHs), and 3 TLDRHs performed between March 2014 and June 2018. RESULTS: There were no significant differences in perioperative outcomes between donors undergoing LADRH and CODRH, except for a slight elevations in the operative time (436.5 vs 392.9 min, p < 0.001) and the graft warm ischemic time (5.4 vs 4.0 min, p < 0.001) in the LADRH group. The recipients' posttransplant one-year survival rates in the LADRH and CODRH groups were also similar (93.2% and 94.6%, p = 0.384). For three donors in whom TLDRH was converted from LADRH in a stepwise manner, the average operative time and blood loss were 570 min and 316.7 ml, respectively. Donors were discharged on postoperative day 10 without any surgical complications. CONCLUSIONS: LADRH can be performed routinely on liver living donors. A stepwise approach could be adopted to "covert" suitable donors from LADRH to a total laparoscopic procedure to maximize donor safety. This strategy is reliable and could be reproduced in most LDLT centers.

Trends in the use of maintenance immunosuppressive drugs among liver transplant recipients in Taiwan: a nationwide population-based study.

PURPOSE: During the past two decades, many novel immunosuppressive drugs have been approved for transplant recipients. Trends in the use of maintenance immunosuppressants after liver transplantation in Asia are unclear. Thus, we aimed to analyze the prescription trends in maintenance immunosuppressive drugs among liver transplant recipients in Taiwan and compare the results with the trends reported from western countries. METHODS: We conducted a retrospective nationwide population-based study utilizing the National Health Insurance Research Database (NHIRD) to analyze the prescribing patterns of immunosuppressants used in Taiwanese liver transplant recipients from 2000 to 2009. RESULTS: A total of 1686 liver transplant patients and their prescriptions of immunosuppressants were analyzed. The 5-year survival rate of liver transplant recipients was 79.6%. In 2009, the major immunosuppressive therapy among liver transplant recipients was a dual-drug regimen with tacrolimus and mycophenolic acid (57.3%). Among the calcineurin inhibitors (CNI), the use of cyclosporine decreased from 58.9% to 12.5%, while the use of tacrolimus notably increased from 23.3% to 77.5%. The use of azathioprine decreased from 21.3% to 0.4%, while the use of mycophenolic acid increased from 56.1% to 76.5%. Among the mammalian target of rapamycin (mTOR) inhibitors, sirolimus was approved in 2002, and its use increased to 8.7% in 2009. In the first 3 months after liver transplantation, a total of 17 different regimens were used in 2009, compared with seven regimens in 2000. CONCLUSIONS: Although the CNI-based combination obviously remains the major regimen, our results reveal a trend toward individualized immunosuppressive regimens among Taiwanese liver transplant recipients. Copyright © 2016 John Wiley & Sons, Ltd.

Entecavir and hepatitis B immune globulin in patients undergoing liver transplantation for chronic hepatitis B.

For patients undergoing liver transplantation (LT) for hepatitis B virus (HBV)-related liver disease, the current standard of care for preventing reinfection of the allograft is nucleoside analogue therapy combined with hepatitis B immune globulin (HBIG). Entecavir has demonstrated high efficacy and a favorable safety profile for chronic hepatitis B (CHB) treatment, but data for patients undergoing HBV-related LT are limited. This study assessed the safety and efficacy of entecavir combined with various HBIG regimens after CHB-related LT. In this phase 3b, single-arm, open-label study, 65 patients undergoing LT for CHB-related liver disease with an HBV DNA load <172 IU/mL at LT received entecavir (1.0 mg daily) for 72 weeks after LT. The primary endpoint was the proportion of evaluable patients (treated for ≥4 weeks) with virological recurrence (HBV DNA level ≥50 IU/mL) through week 72. Concomitant HBIG therapy was received by 64 of the 65 enrolled patients, and 44% of these patients received high-dose HBIG (any HBIG dose in the specified interval ≥10,000 IU). Through week 72, all 61 patients evaluable for the efficacy analysis had undetectable HBV DNA. The Kaplan-Meier estimate of patients without hepatitis B surface antigen (HBsAg) recurrence at week 72 was 0.9655. Two patients experienced a reappearance of HBsAg, but both remained HBV DNA(-) until the last follow-up. The frequency and nature of adverse events were consistent with those expected for this patient population. Serum creatinine increments ≥0.3 mg/dL and ≥0.5 mg/dL occurred in 62% and 39% of the patients, respectively, and all of these patients received calcineurin inhibitor therapy. In conclusion, in this population of patients treated with entecavir after CHB-related LT, entecavir was well tolerated and effective in maintaining viral suppression, even in individuals who experienced a reappearance of HBsAg.

A bidirectional approach for portal vein stent placement in a child with complete portal vein occlusion after living donor liver transplantation.

Delayed PV complications are not rare in pediatric liver transplantation. Although PTPV offers a treatment and minimizes surgical revision, in case of complete PV thrombosis (PVT), the failure rate of PTPV is high. Herein, we report a successful technique of PTPV in a case of complete PVT with a stent placement using a bidirectional approach in a child with living donor liver transplantation.

Correlation of histopathologic and dynamic tissue perfusion measurement findings in transplanted kidneys.

BACKGROUND: Cortical perfusion of the renal transplant can be non-invasively assessed by color Doppler ultrasonography. We performed the Dynamic Tissue Perfusion Measurement (DTPM) of the transplant's renal cortex using color Doppler ultrasonography (PixelFlux technique), and compared the results with the histopathological findings of transplant biopsies. METHODS: Ninety-six DTPM studies of the renal transplant's cortex followed by transplant biopsies were performed in 78 patients. The cortical perfusion data were compared with the parameter of peritubular inflammatory cell accumulation (PTC 0 to 3) based on Banff-classification system. RESULTS: A significant decrease of cortical perfusion could be demonstrated as the inflammatory cells accumulation in peritubular capillaries increased. Increasing peritubulitis caused a perfusion loss from central to distal layers of 79% in PTC 0, of 85% in PTC 1, of 94% in PTC 2, and of 94% in PTC 3. Furthermore, the perfusion loss due to peritubular inflammation was more prominent in the distal cortical layer. The extent of perfusion decline with increasing peritubulitis (from PTC 0 to PTC 3) was 64% in proximal 20% cortical layer (p20), 63% in proximal 50% cortical layer (p50), increased to 76% in distal 50% cortical layer (d50), and peaked at 90% in the distal 20% cortical layer (d20). For those without peritubulitis (PTC 0), the increase in the the Interstitial Fibrosis/Tubular Atrophy (IF/TA) score was accompanied by a significantly increased cortical perfusion. A Polyomavirus infection was associated with an increased cortical perfusion. CONCLUSIONS: Our study demonstrated that the perfusion of the renal transplant is associated with certain pathological changes within the graft. DTPM showed a significant reduction of cortical perfusion in the transplant renal cortex related to peritubular capillary inflammation.

Single-Center Experience in Managing Right Liver Grafts From Trifurcation or Independent Right Posterior Portal Vein in Adult Living Donor Liver Transplantation.

BACKGROUND: The right liver graft has sometimes been from the trifurcation portal vein (TPV) or independent right posterior portal vein (IRPPV). Managing these PV anatomies to increase the recipient's survival rate remains challenging. Many published techniques could overcome this problem, such as simple unification venoplasty (SUV), autologous portal Y-graft interposition, conjoined unification venoplasty (CUV) with a baseball-like conduit, and SUV plus circumferential fence-like vein extension. This study reviewed our strategy for managing the right liver grafts from TPV or IRPPV in adult living donor liver transplantation (aLDLT). METHODS: We enrolled the study population who underwent aLDLT using the grafts with TPV or IRPPV at our institute from October 2004 to October 2022. We analyzed the reconstruction methods for these grafts and postoperative PV complications in donors and recipients. RESULTS: During the study period, of 528 aLDLT recipients, we identified 26 donors with TPV (n = 10) or IRPPV (n = 16). Eight grafts from TPV had a single PV orifice. The other 18 grafts had dual right PVs that underwent initial PV management, including SUV (n = 13), recipient's right and left portal veins to graft's dual PVs (n = 2), Y-graft interposition (n = 1), CUV (n = 1) and SUV with fence-like vein extension (n = 1). One SUV graft changed to fence venoplasty due to significant tension for PV anastomosis. The acute right posterior PV thrombus and anterior PV stenosis happened in 2 cases with Y-graft interposition and native PVs direct anastomosis. One donor with TPV had portal vein thrombosis and needed thrombectomy with vein patch repair. CONCLUSIONS: The graft from TPV should be carefully planned. A single PV orifice may be feasible but not always possible. An SUV could cover most IRPPVs, but if the distance between the right anterior and posterior PVs is a problem, CUV would be an alternative method. In addition, SUVs with fence venoplasty could relieve PV anastomosis tension.

The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation.

BACKGROUND: The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. METHODS: Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. RESULTS: Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. CONCLUSION: OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.

Optimizing the Safe Washout Period for Liver Transplantation Following Immune Checkpoint Inhibitors with Atezolizumab, Nivolumab, or Pembrolizumab.

BACKGROUND: Using immune checkpoint inhibitors (ICIs) as a downstaging therapy for liver transplantation (LT) has improved outcomes for patients with advanced hepatocellular carcinoma (HCC). However, this therapy carries a risk of post-transplant graft rejection. The washout (WO) period between the last ICI dose and LT seems critical in preventing postoperative rejection. This study aimed to optimize the WO period by balancing tumor burden suppression and rejection prevention using ICIs before LT. METHODS: We reviewed published case reports or series from March 2020 to December 2022 regarding LT for HCC after downstaging or bridge therapy with ICIs and included 4 of our cases. Most patients received atezolizumab, nivolumab, or pembrolizumab; these ICIs shared a half-life of around 28 days. Therefore, we excluded cases without definite WO period data and those using non-atezolizumab/nivolumab/pembrolizumab ICIs and ultimately enrolled 22 patients for analysis. We compared their clinical outcomes and estimated the rejection-free survival for every 0.5 half-life interval. RESULTS: Most study subjects received nivolumab (n = 25). Six patients had severe rejections (nivolumab group, n = 5) and needed rescue management. Of the 6 cases, 1 patient died after rejection, and 2 underwent re-transplantation. The median WO period in these 6 patients was 22 days (IQR: 9-35 days). In addition, we found that a 1.5 half-life (42 days) was the shortest safe WO period associated with significant rejection-free survival (P = .005). CONCLUSIONS: Our results showed that 42 days was the safest WO period before LT for HCC after ICI with atezolizumab, nivolumab, or pembrolizumab.

Long-term outcomes of liver transplantation for alcohol-related liver disease.

BACKGROUND: Liver transplantation (LT) is being increasingly performed for alcohol-related liver disease (ALD). It is unclear whether the increasing frequency of LTs in ALD patients has a negative impact on deceased-donor (DDLT) allocation and whether the current policy of 6 months of abstinence before transplantation effectively prevents recidivism after transplantation or improves long-term outcomes. METHODS: A total of 506 adult LT recipients, including 97 ALD patients, were enrolled. The outcomes of ALD patients were compared with those of non-ALD patients. The 97 ALD patients were further divided into group A (6-month abstinence) and group N (nonabstinence) based on the pretransplant alcohol withdrawal period. The incidence of relapsed drinking and the long-term outcomes were compared between the two groups. RESULTS: The prevalence of LT for ALD significantly increased after 2016 (27.0% vs 14.0%; p < 0.01), but the frequency of DDLT for ALD remained unchanged (22.6% vs 34.1%, p = 0.210). After a median follow-up of 56.9 months, patient survival was comparable between the ALD and non-ALD patients (1, 3, and 5 years posttransplant: 87.6%, 84.3%, and 79.5% vs 82.8%, 76.6%, and 72.2%, respectively; p = 0.396). The results were consistent irrespective of the transplant type and disease severity. In ALD patients, 22 of the 70 (31.4%) patients reported relapsed drinking after transplantation, and the prevalence in group A had a higher tendency than that in group N (38.3% vs 17.4%, p = 0.077). Six months of abstinence or nonabstinence did not result in a survival difference, and de novo malignancies were the leading cause of late patient death in ALD patients. CONCLUSION: LT achieves favorable outcomes for ALD patients. Six months of abstinence pretransplant did not predict the risk of recidivism after transplantation. The high incidence of de novo malignancies in these patients warrants a more comprehensive physical evaluation and better lifestyle modifications to improve long-term outcomes.

Use of higher thromboelastogram transfusion values is not associated with greater blood loss in liver transplant surgery.

Plasma-containing products are given during the pre-anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty-eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 ± 6.49 versus 11.53 ± 6.66 U) and pheresis platelets (1.84 ± 1.33 versus 3.55 ± 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma-containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors.

Comparison of surgical resection and transarterial chemoembolization for hepatocellular carcinoma beyond the Milan criteria: a propensity score analysis.

BACKGROUND: Treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) is controversial. This study compared the long-term survival of patients beyond the Milan criteria who received surgical resection (SR) or transarterial chemoembolization (TACE). METHODS: A total of 268 and 455 HCC patients beyond the Milan criteria undergoing SR and TACE, respectively, were retrospectively evaluated. After propensity score analysis to adjust for baseline differences, 146 pairs of matched patients were selected from each treatment arm. Long-term survival was compared by the Kaplan-Meier method. Independent prognostic predictors were determined by the Cox proportional hazards model. RESULTS: Long-term survival was significantly better for the SR group by univariate survival analysis (P < .001). In the Cox model, SR was identified as an independent predictor of better prognosis (hazard ratio = 0.3, 95% confidence interval [95% CI]: 0.23-0.4; P < .001). Despite similar baseline characteristics in the propensity score model, patients who underwent SR had significantly better survival than patients who underwent TACE (P < .001). Patients receiving TACE had 2.56-fold increased risk of long-term mortality in the propensity model (95% CI: 1.73-3.78). The SR and TACE groups had comparable 30- and 90-day posttreatment mortality. The Cox model consistently disclosed the significant superiority of SR in terms of long-term survival in the propensity score model (P < .001). CONCLUSIONS: For HCC patients beyond the Milan criteria, SR is considered equally safe as TACE and provides better long-term survival. SR may be regarded as the priority treatment for these patients.

Retrograde arterial flush of the liver graft in living donor liver transplantation may ameliorate post-transplantational cholestasis--prospective randomized study.

Retrograde arterial flush (RGAF) of liver grafts, which prevents arterial intima injuries in living donor liver transplantation (LDLT), seemed to reduce post-transplantational cholestasis by our preliminary study. The aim of this study was to further confirm this effect of RGAF of grafts in LDLT by a prospective randomized study. The enrolled cases were randomly divided into two groups, RGAF (portal flush plus RGAF) and non-RGAF (portal flush only). The outcome measures included intra-operative hemodynamic changes, one-month post-transplantational liver function tests and acute cellular rejection, vascular and biliary complications, the length of postoperative hospital stay, and graft and patient survivals. The significant findings of results were lower postoperative serum bilirubin in the RGAF group until three wk after transplantation (days 1, 3, 7, 14, and 21 serum total bilirubin, mg/dL: 5.82±5.46, 3.95±4.28, 4.87±5.01, 3.62±5.32, and 3.63±6.91 vs. 8.41±5.49, 7.47±5.61, 10.0±10.1, 9.06±11.6, and 6.02±9.84, respectively, in RGAF and non-RGAF, p=0.017, 0.002, 0.014, 0.011, 0.109) and shorter postoperative hospital stay in the RGAF group (31.1±17.6 vs. 44.8±32.3 d, respectively, in RGAF and non-RGAF, p=0.035). In conclusion, the RGAF of liver grafts on a back table may ameliorate postoperative functional cholestasis in LDLT, which possibly reduces postoperative hospital stay.

Living donor liver transplantation using a graft from a donor with Dubin-Johnson syndrome.

DJS is an autosomal recessive disorder that causes an increase in conjugated bilirubin without elevation of liver enzymes. Most patients are asymptomatic and have normal life spans, but to the best of our knowledge, their livers have never been reported to be grafts in liver transplantation. Herein, we report an infant patient with MMA that received a partial liver graft from his mother, who had DJS. A biliary anastomosis stricture was noted five months after transplantation and was successfully treated with radiological interventions. Otherwise, the patient's liver functions were normal, and a liver biopsy showed a pathognomonic picture of DJS nine months after the transplantation. The patient was followed for one yr, and the results were satisfactory for an increase in oral intake and protein uptake, no recurrence of metabolic stroke and there was a gradual catch-up with regard to physical development despite having a persistently abnormal profile of amino acid analysis. From the experience of our case, we suggest that a liver from a donor with DJS can be used as a graft for liver transplantation, although long-term follow-up is mandatory to examine the grafted liver under the use of immunosuppressive medications.

Liver transplantation for a patient with homocystinuria.

A 24-yr-old man was diagnosed with HCU during neonatal screening and remained on a pyridoxine, vitamin B12, folic acid, and betaine regimen with dietary methionine restriction for more than 10 yr. He had normal mental development, marfanoid appearance, myopia because of lens dislocation, and recurrent ankle subluxation during adolescence. Thereafter, he was a poor adherent to the conventional diet-restrictive therapy, and LT was considered when he developed hypertension and multiple infarctions over the right cerebellum early in the second decade of his life despite taking aspirin as a prophylaxis from 17 yr of age. In November 2009, he received a deceased whole LT from a blood group compatible donor. Along with the success of the transplantation, he was completely disease free without dietary or nutritional control. To the best of our knowledge, this is the first case of LT intended to cure HCU, and with promising results. This case provides an insight into the role of LT for this congenital metabolic disease, for which the decision should be made by judging between the severity of the disease and the risk of the operation, as well as the life quality of the patient.

Repeated loco-regional therapies for hepatocellular carcinoma is associated with inferior outcome after living donor liver transplantation in cirrhotic patients.

BACKGROUND: Liver transplantation is the definitive treatment for defined stage hepatocellular carcinoma (HCC) in cirrhotic patients. Loco-regional therapy (LRT) may be considered before transplantation to prevent the disease progression and the patient from dropping out of the waiting list. This study aims to evaluate the impact of repeated pretransplant LRTs on the long-term outcomes in HCC liver transplant recipients. METHODS: Between 2004 and 2019, living donor liver transplantation (LDLT) recipients with viable HCC on the explant livers were enrolled. Uni- and multivariate analysis was performed with the Cox regression model to stratify the risk factors associated with HCC recurrence and patent survival after LDLT. RESULTS: A total of 124 patients were enrolled, in which 65.3% (n = 81) were Barcelona Clinic Liver Cancer classification stage B or D and 89% (n = 110) had advanced fibrosis or cirrhosis on the explanted livers. After a median follow-up of 41 months (IQR: 24-86.5), there were 18 cases (13.7%) of HCC recurrence. Univariate analysis showed that the model of end-stage liver disease and Child-Turcotte-Pugh score, pretransplant alpha-fetoprotein value (>500 ng/ml), repeated pretransplant LRTs (N > 4), increased tumor numbers and maximal size, presence of microvascular invasion, and the histological grading of the tumors are risk factors of inferior outcomes. In multivariate analysis, only repeated pretransplant LRTs (N > 4) had a significant impact on both the overall- and recurrence-free survival. The impact of pretransplant LRT was consistently significant among subgroups based on their LRT episodes (N = 0, 1-4, >4 respectively). CONCLUSION: Repeated LRT for HCC can be associated with the risk of tumor recurrence and inferior patient survival after LDLT in cirrhotic patients. Early referral of those eligible for transplantation may improve the treatment outcomes in these patients.

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus.

BACKGROUND: Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged. METHODS: In total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups. RESULTS: Majority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups. CONCLUSIONS: T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.

First-Pass Arrival Interval of Ultrasound Contrast Medium in the Hepatic Artery and Portal Vein as a Marker for Assessment of Liver Transplant Recipients.

BACKGROUND: This study measures the first-pass arrival times in the hepatic artery and portal vein of the transplanted liver using contrast-enhanced ultrasound (CEUS) and assess its correlation with graft performance in the early posttransplant period. METHODS: This study evaluated 35 liver transplant recipients who underwent CEUS examination within 1 month of transplant surgery. CEUS under contrast-specific harmonic imaging mode were recorded for 60 seconds immediately after intravenous administration of microbubble ultrasound contrast medium (Sonazoid, GE Healthcare, Oslo, Norway). The recorded video clips were reviewed by 2 readers to determine the first-pass arrival times in the hepatic artery and portal vein, and the difference between the 2 was defined as the arterial-portal arrival interval (APAI). Laboratory data on the same date of CEUS examination were collected as indicators to correlate with APAI. RESULTS: The intra- and inter-rater reliability for APAI measurement were excellent, with intraclass correlation coefficients > .95. The mean APAI was 4.5 ± 1.8 seconds (range, 2.0-10.5 seconds). The APAI was positively correlated with the serum total bilirubin level (r = 0.357, P = .035) and negatively correlated with the platelet count (r = -0.354, P = .037). At the 5 second cutoff point, a total serum bilirubin of >8 mg/dL was reported in 5 of 11 patients (45.4%) with APAI of >5 seconds and in only 3 of 24 patients (12.5%) with APAI of <5 seconds (P < .05). CONCLUSIONS: The APAI is a quantitative marker that links the hemodynamics and the clinical status of the liver graft.