Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation

Fukazawa K, Poliac LC, Pretto EA. Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation.
Clin Transplant 2010: 24: 515–519.
© 2009 John Wiley & Sons A/S. Abstract: The incidence of porto‐pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP] > 45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT.     

Maternal grafts protect daughter recipients from acute cellular rejection after pediatric living donor liver transplantation for biliary atresia

Some studies have found that gender mismatch between donors and recipients are related to poor graft prognosis after liver transplantation. However, few studies have investigated the impact of gender mismatch on acute cellular rejection (ACR) in pediatric living donor liver transplantation (LDLT). This retrospective study investigated the clinical significance of these factors in ACR after pediatric LDLT. Between November 2001 and February 2012, 114 LDLTs were performed for recipients with biliary atresia (BA) using parental grafts. We performed univariate and multivariate analyses to identify the factors associated with ACR. The donor–recipient classifications included mother donor to daughter recipient (MD; n = 43), mother to son (n = 18), father to daughter (FD; n = 33), and father to son (n = 20) groups. The overall incidence rate of ACR in the recipients was 36.8%. Multivariate analysis showed that gender mismatch alone was an independent risk factor for ACR (P = 0.012). The FD group had a higher incidence of ACR than the MD group (P = 0.002). In LDLT, paternal grafts with gender mismatch were associated with a higher increased incidence of ACR than maternal grafts with gender match. Our findings support the possibility that maternal antigens may have an important clinical impact on graft tolerance in LDLT for patients with BA.     

Successful treatment of pulmonary hypertension secondary to congenital extrahepatic portocaval shunts (Abernethy type 2) by living donor liver transplantation after surgical shunt ligation

In this report, we describe a living donor liver transplantation (LDLT) in a patient (7-year-old boy) with Abernethy type 2 congenital extrahepatic portocaval shunts (CEPS). This patient underwent a surgical shunt ligation as the first treatment for pulmonary hypertension; pulmonary hypertension was improved and controlled successfully 4 years after the first operation. However, pulmonary hypertension recurred gradually because of multiple intrahepatic portosystemic shunts; therefore, LDLT was performed as a radical treatment of intrahepatic portosystemic shunts. His pulmonary arterial pressure was also controlled 22 months after LDLT, the postoperative continuous intravenous prostaglandin I₂ (PGI₂) treatment could be withdrawn successfully. We suggest that clinicians carefully follow up the recurrent portosystemic shunt and cardiopulmonary disorders secondary to Abernethy type 2 CEPS.     

Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation

Kyoden Y, Tamura S, Sugawara Y, Matsui Y, Togashi J, Kaneko J, Kokudo N, Makuuchi M. Incidence and management of biliary complications after adult‐to‐adult living donor liver transplantation.
Clin Transplant 2010: 24: 535–542.
© 2009 John Wiley & Sons A/S. Abstract: Background: There are few detailed reports of biliary complications in a large adult living donor liver transplantation (LDLT) series. Patient and methods: Biliary complications, treatment modalities, and outcomes in these patients were retrospectively analyzed in 310 adult LDLT. Results: One patient underwent retransplantation. Duct‐to‐duct anastomosis was primarily performed in 223 patients (72%). During the observation period (median 43 months), biliary complications were observed in 111 patients (36%); 53 patients (17%) had bile leakage, 70 patients (23%) had bile duct stenosis, and 12 patients (4%) had bile leakage followed by stenosis. A biliary anastomotic stent tube was placed in 266 patients (86%) at the time of transplantation. Univariate analysis of various clinical factors revealed duct‐to‐duct anastomosis as the single significant risk factor (p = 0.009) for biliary complications. The three‐yr and five‐yr overall patient survival rates were 88% and 85% in those with biliary complications, and 85% and 83%, respectively, in those without biliary complications (p = 0.59). Conclusion: Biliary complications are a major cause of morbidity following LDLT. Duct‐to‐duct anastomosis carried a higher risk for bile duct stenosis. With appropriate management, however, there was little influence on overall survival.     

Long-term outcome of living donor liver transplantation for primary biliary cirrhosis

In living donor liver transplantation (LDLT) for primary biliary cirrhosis (PBC), the majority of donors are genetically related to their recipients, leading to concerns of an earlier recurrence of PBC and a poorer prognosis due to genetic susceptibility. Totally 81 patients who underwent LDLT for PBC were the subjects of the present study. Immunosuppressive agents consisted of tacrolimus and methylprednisolone. In the outpatient clinic, when the aspartate and alanine aminotransferase level exceeded the upper limit of the normal range, the dose of methylprednisolone was increased from 4 to 6 mg/day for several months. Blood was examined every 2 weeks for 3 months and a liver biopsy was performed when aminotransferase levels did not decrease to the upper limit of the normal range after more than 3 months. Five-year survival and recurrence rates were estimated and the prognostic factors were analyzed. The mean observation period was 6.2 years. Five years after LDLT for PBC, the biopsy-proven PBC recurrence rate was 1%. The 5-year patient survival rate was 80%. The nonrelated or blood-related donor factor and number of human leukocyte antigen matches did not correlate with prognosis. PBC recurrence rate after LDLT in our series was lower than that in previous studies.     

Long-term outcomes of endoscopic management for biliary strictures after living donor liver transplantation with duct-to-duct reconstruction

Biliary strictures after living donor liver transplantation (LDLT) with duct-to-duct (D-D) reconstruction are associated with postoperative morbidity and mortality. The aims of this study were to evaluate the long-term outcomes of endoscopic deployment of plastic stents, and to investigate factors associated with the stent deployment failure. Between April 2001 and May 2007, 96 patients received LDLT with D-D reconstruction at Okayama University Hospital. Among them, 41 patients (43%) had anastomotic biliary strictures, and all were referred first for endoscopic retrograde cholangiography (ERC). When deployment was unsuccessful, a percutaneous transhepatic procedure was employed. Successful stent deployment was achieved in 35 out of total 41 patients (85%) by both procedures. Among the 35 patients, 28 had their stents removed as a result of strictures resolution. Eight patients underwent ERC and repeated stent deployment as a result of recurrence of the strictures. Finally, 21 out of 41 (51%) patients with biliary stricture were completely treated by endoscopic therapy during the observation period (median 873 days: range 77–2060). By multivariate analysis, biliary leakage was associated with stent deployment failure. Endoscopic deployment of plastic stents is a first-line therapy for patients with biliary stricture after LDLT.     

Heart–lung vs. double‐lung transplantation for idiopathic pulmonary arterial hypertension

Patients with idiopathic pulmonary arterial hypertension (IPAH) have improved survival after heart–lung transplantation (HLT) and double‐lung transplantation (DLT). However, the optimal procedure for patients with IPAH undergoing transplantation remains unclear. We hypothesized that critically ill IPAH patients, defined by admission to the intensive care units (ICU), would demonstrate improved survival with HLT vs. DLT. All adult IPAH patients (>18 yr) in the Scientific Registry of Transplant Recipients (SRTR) database, who underwent either HLT or DLT between 1987 and 2012, were included. Baseline characteristics, survival, and adjusted survival were compared between the HLT and DLT groups. Similar analyses were performed for the subgroups as defined by the recipients' hospitalization status. A total of 928 IPAH patients (667 DLT, 261 HLT) were included in this analysis. The HLT recipients were younger, more likely to be admitted to the ICU, and have had their transplant in previous eras. Overall, the adjusted survivals after HLT or DLT were similar. For recipients who were hospitalized in the ICU, DLT was associated with worse outcomes (HR 1.827; 95% CI 1.018–3.279). In IPAH patients, the overall survival after HLT or DLT is comparable. HLT may provide improved outcomes in critically ill IPAH patients admitted to the ICU at time of transplantation.     

Living‐donor single‐lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins

This is a case report of a successful single‐lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6‐year‐old boy underwent living‐donor single‐lobe transplantation with the right lower lobe from his 31‐year‐old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO₂/FiO₂ in the intensive‐care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT‐guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.     

Decreased risk of graft failure with maternal liver transplantation in patients with biliary atresia

The presence of maternal cells in offspring may promote tolerance to noninherited maternal antigens (NIMAs). Children with biliary atresia (BA) have increased maternal cells in their livers, which may impact tolerance. We hypothesized that patients with BA would have improved outcomes when receiving a maternal liver. We reviewed all pediatric liver transplants recorded in the SRTR database from 1996 to 2010 and compared BA and non-BA recipients of maternal livers with recipients of paternal livers for the incidences of graft failure and retransplantation. Rejection episodes after parental liver transplantation were examined for patients transplanted at our institution. BA patients receiving a maternal graft had lower rates of graft failure compared to those receiving a paternal graft (3.7% vs. 10.5%, p = 0.02) and, consequently, fewer episodes of retransplantation (2.7% vs. 7.5%, p = 0.04). These differences were not seen among non-BA patients or among BA patients who received female deceased donor grafts. In patients transplanted at our institution, paternal liver transplantation was associated with an increased incidence of refractory rejection compared to maternal liver transplantation only in BA. Our data support the concept that maternal cells in BA recipients promote tolerance to NIMAs and may be important in counseling BA patients who require liver transplantation.     

Living‐donor liver transplantation for liver hemorrhaging due to peliosis hepatis in X‐linked myotubular myopathy: Two cases and a literature review

X‐linked myotubular myopathy (MTM) (OMIM 310400) is a severe neuromuscular disorder caused by mutations in the myotubularin (MTM1) gene. Liver hemorrhaging due to peliosis hepatis (PH) is a fatal complication. We herein report 2 successful cases of living‐donor liver transplantation (LDLT) for MTM patients due to liver hemorrhaging caused by PH and review previous reports. A boy who was 9 years and 4 months old initially underwent left lateral segmentectomy due to massive hepatic and intraperitoneal hemorrhaging. As bleeding from the remnant liver continued after hepatectomy, this patient emergently underwent LDLT using a left lateral segment graft from his father. Another boy who was 1 year and 7 months old underwent transcatheter arterial embolization due to hepatic hemorrhaging and was referred to our hospital for LDLT using a left lateral segment graft from his father. The pathological findings in both cases showed sinusoidal dilatation with degenerative changes in reticular fiber and hematoma in the explanted liver, which were consistent with PH associated with MTM. LT should be considered as a treatment option for patients with episodes of hepatic hemorrhaging due to MTM in order to protect against fatal bleeding.     

Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single‐center Asian experience

Sun C‐K, Chen C‐L, Concejero AM, Wang C‐C, Wang S‐H, Liu Y‐W, Yang C‐H, Yong C‐C. Liver transplantation for primary biliary cirrhosis in a hepatitis endemic region: a single‐center Asian experience.
Clin Transplant 2011: 25: 47–53. © 2010 John Wiley & Sons A/S. Abstract: From March 1984 to November 2008, we performed 539 primary liver transplantations (LTs). Nineteen (19, 3.5%) were transplanted for end‐stage liver disease secondary to primary biliary cirrhosis (PBC). There were 17 (89%) female and 2 (11%) male recipients. The overall mean age was 50.3 ± 6.3 yr. The mean model for end‐stage liver disease, and Child–Turcotte–Pugh scores were 20.7 ± 2.1, and 11.0 ± 0.5, respectively. There were 2 (11%) United Network for Organ Sharing status 3, 16 (84%) 2B, and 1 (5%) 2A patients. Fourteen patients (14, 73.7%) underwent living donor LT, and five patients (26.3%) received deceased donor LT. The primary immunosuppression consisted of cyclosporine (n = 5) and tacrolimus (n = 14). Liver function returned to normal one month after transplantation. The overall mean follow‐up was 5.8 ± 0.8 yr (range, four months to 15.7 yr). The overall one‐, three‐, and five‐yr survival rates were 94.7%, 89.2%, and 89.2%, respectively. Without hepatitis B virus (HBV) prophylaxis, one patient acquired de novo HBV infection after receiving a graft from an anti‐HBc(+) donor. Another patient developed recurrent hepatitis C infection and expired 25 months after transplantation. Our results showed that HBV prophylaxis was effective not only against de novo infection, but it also worked on pre‐transplant HBV carrier with PBC and helped in virus clearance.     

Technique of bile duct reconstruction and management of biliary complications in right lobe living donor liver transplantation

From December 1999 to January 2002, 50 right lobe living donor liver transplantations were performed. The donor operations included an intraoperative cholangiography to elicit variations in bile duct anatomy. The biliary reconstruction was done whenever possible as an end-to-end microanastomosis of the donor right hepatic duct with the recipient's bile duct. As a result of the early segmental branching of the donor biliary tree, two segment bile ducts had to be anastomosed in 20 patients and three segment bile ducts in three patients. In 12 patients, a Roux-en-Y hepaticojejunostomy was performed. All anastomoses were drained externally. We observed two leakages at the resection surface which could be treated successfully by an external drainage. Six leaks occurred at the site of end-to-end biliary anastomoses. Twice the problem could be conservatively solved placing a stent percutaneously. In two patients a hepaticojejunostomy was performed after a bile duct necrosis. In two patients with an anastomotic leak, occurring 3 d, respectively, 3 month after the original transplantation, the bile duct could be directly reconstructed over a T-tube. Two anastomotic stenoses were observed, one in combination with a leak treated by percutaneous stent implantation and the second, 3 month after transplantation which was treated surgically. Biliary reconstruction after living donor liver transplantation requires microsurgical techniques and can be performed as a direct end-to-end anastomosis in most cases. Biliary complications were treated by percutaneous drainage or surgical revision in all cases.     

Double‐lung versus heart‐lung transplantation for precapillary pulmonary arterial hypertension: a 24‐year single‐center retrospective study

Transplant type for end‐stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart‐lung (HLT) versus double‐lung (DLT) transplantation. Single‐center analysis (38 HLT–30 DLT; 1991–2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug‐induced (nine); hepato‐portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six). HLT decreased from 91.7% [1991–1995] to 21.4% [2010–2014]. Re‐intervention for bleeding was higher after HLT; (P = 0.06) while primary graft dysfunction grades 2 and 3 occurred more after DLT; (P < 0.0001). Graft survival at 90 days, 1, 5, 10, and 15 years was 93%, 83%, 70%, 47%, and 35% for DLT vs. 82%, 74%, 61%, 48%, and 30% for HLT, respectively (log‐rank P = 0.89). Graft survival improved over time: 100%, 93%, 87%, 72%, and 72% in [2010–2014] vs. 75%, 58%, 42%, 33%, and 33% in [1991–1995], respectively; P = 0.03. No difference in chronic lung allograft dysfunction (CLAD)‐free survival was observed: 80% & 28% for DLT vs. 75% & 28% for HLT after 5 and 10 years, respectively; P = 0.49. Primary graft dysfunction in PH patients was lower after HLT compared to DLT. Nonetheless, overall graft and CLAD‐free survival were comparable and improved over time with growing experience. DLT remains our preferred procedure for all forms of precapillary PH, except in patients with complex CHD.     

Living donor liver transplantation for primary biliary cirrhosis: retrospective analysis of 50 patients in a single center

Summary Although living donor liver transplantation (LDLT) is accepted as an alternative therapy for primary biliary cirrhosis (PBC), the postoperative results are not well known. Fifty patients with PBC underwent LDLT at Tokyo University Hospital. Their clinical records were retrospectively analyzed. Postoperative death occurred in four patients within 2 months (mortality, 8%), while later death occurred in three patients. In the median follow-up period of 35 months (range 4-84 months), the 1, 3, and 5-year overall survival rates were 90%, 88%, and 80%, respectively. The laboratory data indicated that graft function was sufficient. No recurrence of PBC was confirmed. Multivariate analysis indicated that an updated Mayo score of <10 was a significantly favorable factor for short hospitalization (hazard ratio, 9.52; 95% confidence interval, 1.14-79.5; P = 0.03). In conclusion, LDLT provides a satisfactory long-term survival with the PBC patients.     

The beneficial impact of temporary porto‐caval shunt in orthotopic liver transplantation: a single center analysis

The use of temporary porto‐caval shunt (TPCS) has been shown to improve hemodynamic stability and renal function in patients undergoing orthotopic liver transplantation (OLT). We evaluated the impact of TPCS in OLT and analyzed the differences according to model for end‐stage liver disease (MELD), donor risk index (DRI) and D‐MELD. This is a retrospective single‐center analysis of 148 consecutive OLT. Fifty‐eight OLT were performed using TPCS and 90 without TPCS. Donor and recipient data with pre‐OLT, intraoperative and postoperative variables were reviewed. Overall graft survival was 89.9% at 3 months and 81.7% at 1 year. Graft survival at 3 months and 1 year was 93.1% and 79.2%, respectively, in TPCS group versus 85.6% and 82.2%, respectively, in non‐TPCS group (P = NS). Intraoperative packed red blood cells requirement was lower in TPCS group (7.5 ± 5.8 vs. 12.2 ± 14.2, P = 0.006) and non‐TPCS group required higher intraoperative total dose of phenylephrine (16% vs. 28%, P = 0.04). TPCS group had lower 30‐day postoperative mortality (1.7% vs. 10%, P = 0.04), no difference was observed at 90 days. Graft survival was lower in patients with high DRI; in this group graft loss was higher at 1 month (25% vs. 4.3%, P = 0.005) and 3 months (25% vs. 4.3%, P = 0.005) when TPCS was not used. TPCS improves perioperative outcome, this being more evident when high‐risk grafts are placed into high‐risk patients.