Background Thromboses of the hepatic artery (HAT) and portal vein (PVT) may complicate orthotopic liver transplantation (OLT) and result in graft loss and mortality. Revision and retransplantation are treatment options, but their longterm outcomes remain undefined. This study was undertaken to evaluate the incidence of major vascular complications after OLT, determine efficacy of therapies, and identify factors influencing longterm outcomes. Study Design All patients undergoing OLT from 1984 to 2007 were evaluated. Kaplan-Meier analysis was performed to define the effects of vascular complications on posttransplant survival. Anastomotic revision and arterial thrombolysis were compared with retransplantation as treatment for HAT. After 2002, porta hepatis dissection was initiated with early occlusion of common hepatic artery (CHA) inflow; its impact on HAT incidence was determined. Results From 1984 to 2007, 4,234 OLTs were performed. HAT occurred in 203 patients (5%) and PVT in 84 (2%). Graft survival was significantly reduced by HAT or PVT; patient survival was reduced only by PVT. Retransplantation for HAT improved patient survival over revision or thrombolysis in the first year but did not provide longterm survival advantage (56% versus 56% at 5 years; p=0.53). Patients with HAT had only 10% graft salvage with anastomotic revision or thrombolysis. HAT was significantly reduced with early CHA inflow occlusion (1.1% versus 3.7%; p=0.002). Factors increasing risk of HAT included pediatric recipients, liver cancer, and aberrant arterial anatomy requiring complex reconstruction. Conclusions Both HAT and PVT significantly reduce graft survival after OLT; PVT more adversely affects patient survival. Revision and thrombolysis rarely salvage grafts after HAT; retransplantation provides superior short-term, but not longterm, survival. Avoidance of vascular complications in OLT is critical, especially with today's scarcity of donor livers. Early atraumatic CHA occlusion significantly reduces the incidence of HAT.

Vascular complications of orthotopic liver transplantation: experience in more than 4,200 patients.

Biliary reconstruction remains common in postoperative complications after liver transplantation. A systematic search was conducted on the PubMed database and 61 studies of retrospective or prospective institutional data were eligible for this review. The study comprised a total of 14,359 liver transplantations. The overall incidence of biliary stricture was 13%; 12% among deceased donor liver transplantation (DDLT) patients and 19% among living donor liver transplantation (LDLT) recipients. The overall incidence of biliary leakage was 8.2%, 7.8% among DDLT patients and 9.5% among LDLT recipients. An endoscopic strategy is the first choice for biliary complications; 83% of patients with biliary stricture were treated by endoscopic modalities with a success rate of 57% and 38% of patients with leakage were indicated for endoscopic biliary drainage. T-tube placement was not performed in 82% of duct-to-duct reconstruction. The incidence of biliary stricture was 10% with a T-tube and 13% without a T-tube and the incidence of leakage was 5% with a T-tube and 6% without a T-tube. A preceding bile leak and LDLT procedure are accepted risk factors for anastomotic stricture. Biliary complications remain common, which requires further investigation and the refinement of reconstruction techniques and management strategies.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2010.01202.x

Biliary reconstruction, its complications and management of biliary complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome.

Liver transplantation using fatty livers: Always feasible?

https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.12034

Biliary Complications After Liver Transplantation: Old Problems and New Challenges

Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.

Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury

Baccarani U, Isola M, Adani GL, Avellini C, Lorenzin D, Rossetto A, Curro G, Comuzzi C, Toniutto P, Risaliti A, Soldano F, Bresadola V, De Anna D, Bresadola F. Steatosis of the hepatic graft as a risk factor for post-transplant biliary complications. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01128.x. © 2009 John Wiley & Sons A/S.



Abstract: Background:  Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles’ heel of liver transplantation. The aim of this study is to retrospectively analyze the incidence of biliary complications and identify risk factors that might predispose to the development of biliary problems.



Methods:  From January 2004 to December 2007, 117 consecutive liver transplantations were retrospectively analyzed for the development of biliary complications by the review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74).



Results:  The overall biliary complication rate was 36.8% (leakage 6% and stricture 30.8%). Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (p = 0.037) and macrovacuolar steatosis of the graft > 25% (p = 0.004). Stepwise logistic regression model demonstrated that a macrosteatosis of the graft > 25% (OR = 5.21 CI 95% [1.79–15.15], p = 0.002) was the only independent risk factor predicting biliary complications after liver transplantation. No differences in patient’s and graft’s survival were noted between the two groups.



Conclusion:  According to our experience, transplanting a liver with > 25% of steatosis is a risk factor for the development of biliary complication.

Steatosis of the hepatic graft as a risk factor for post-transplant biliary complications

Background Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles' heel of liver transplantation. The aim of this study was to retrospectively analyze the incidence of biliary complications and identify predisposing risk factors. Methods From January 2004 to December 2007, 117 consecutive deceased donor liver transplantations were retrospectively analyzed for the development of biliary complications by review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74). Results The overall biliary complication rate was 36.8%; leakage 6% and stricture 30.8%. Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (P = .037) and macrovacuolar steatosis of the graft >25% (P = .004). A stepwise logistic regression model demonstrated that >25% macrosteatosis of the graft was the only independent risk factor predicting biliary complications after liver transplantation (odds ratio [OR] = 5.21; CI 95% [1.79–15.15]; P = .002). No differences were noted in patient or graft survival between the 2 groups. Conclusion Transplantation of a liver with >25% steatosis was a risk factor for the development of a biliary complication.

Steatosis of the graft is a risk factor for posttransplantation biliary complications.

Nonadherence to immunosuppressive regimens among solid organ transplantation to range has been estimated from 15% to 55%. This problem has been identified as a leading cause of preventable graft loss. Tacrolimus once daily Advagraf has been developed to provide a more convenient dosing regimen to improve adherence. The aim of this study was to analyze the safety of a 1:1 dose conversion from twice-daily tacrolimus (Prograf) to Advagraf in 36 stable liver transplant recipients. The tacrolimus whole blood trough level at T0 was 6.7 ± 2.9 ng/mL with a daily dose of 3.7 ± 1.8 mg. The mean tacrolimus blood trough levels at T1 (7 days) and T2 (14 days) were 5.8 ± 2.5 and 5.8 ± 1.8 ng/mL with mean daily doses of 3.9 ± 1.9 and 4.1 ± 1.8 mg, respectively. There was no significant difference between T0, T1, and T2, either for tacrolimus blood trough levels or for tacrolimus daily dosages. Liver and renal function tests remained stable; no episodes of acute rejection were encountered after the conversion. A switching policy using a dose ratio of 1:1 from twice-daily tacrolimus to once-daily prolonged-release tacrolimus was safely applied to stable liver transplant recipients.

Safety of Conversion From Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Human immunodeficiency virus (HIV) positivity is no longer a contraindication for orthotopic liver transplantation (OLT) due to the efficacy of antiretroviral therapy. The aim of this study was to compare OLT among HIV-positive and HIV-negative cohorts; the results were also stratified for hepatitis C virus (HCV) coinfection. Between 2004 and 2009, all HIV-infected patients undergoing OLT from heart-beating deceased donors (n = 27) were compared with an HIV-negative cohort (n = 27). The pure HCV infection rate was similar between HIV-positive and HIV-negative subjects (63% each). HIV-positive recipients were younger ( P = .013). The CD4 count for HIV-positive subjects was 376 ± 156 at transplantation. The mean model for end-stage liver disease (MELD) score at transplantation was 15 ± 7 in both groups ( P = .92). No differences were observed for donor age ( P = .72) or time on the waiting list ( P = .56). The median follow-up was 26 (range, 1–64) and 27 months (range, 1–48) for HIV and non-HIV recipients, respectively ( P = .85). The estimated 1-, 3-, and 5-year patient and graft survival rates were 88%, 83%, and 83% versus 100%, 73%, and 73% ( P = .95), and 92%, 87%, and 87% versus 95%, 88%, and 88% ( P = .59) for HIV and non-HIV cases, respectively. HIV/HCV–coinfected patients were younger, namely 47 (range, 40–53) versus 52 years (range, 37–68; P = .003), and displayed lower MELD scores at transplantation compared with HCV–mono-infected patients 10 (range, 7–19) versus 17 (range, 8–30) ( P = .008). For HIV/HCV–coinfected and HCV–mono-infected cases the estimated 1-, 3-, and 5-year patients and graft survival rates were respectively 93%, 76%, and 76% versus 100%, 70%, and 60% ( P = .99) and 93%, 84%, and 84% versus 100%, 70%, and 60% ( P = .64), respectively. No difference was observed in the histological severity of HCV recurrence. In conclusion, under specific, well-determined conditions, OLT can be a safe, efficacious procedure in HIV patients.

Long-term outcomes of orthotopic liver transplantation in human immunodeficiency virus-infected patients and comparison with human immunodeficiency virus-negative cases.

Early cholestatic graft dysfunction is a frequent cause of morbidity after orthotopic liver transplantation (OLT). We analyze the role of selective bilirubin plasma absorption (PAP) using Plasorba BR-350 in 4 OLT patients who had experienced early severe cholestatic graft dysfunction within 15 days after transplantation. Patients were treated with 3 consecutive cycles of PAP with Plasorba BR-350. The median amount of plasma treated was 7500 mL. Median treatment duration was 231 minutes. The average plasma bilirubin level was 37 ± 1 mg/dL before PAP and decreased to 15 ± 0.2 mg/dL at the end of the third cycle of PAP; 3 of 4 cases had progressive bilirubin normalization after PAP. The average amount of bilirubin removed from the plasma of the patients during each PAP treatment was 143 ± 24 mg. At the beginning of each cycle of PAP, the Plasorba BR-350 was able to remove >90% of the total plasma bilirubin, a percentage that decreased to 60%, 50%, and 40% after 2 L, 4 L, and 7 L of plasma were treated, respectively. Liver biopsies performed after the third treatment showed reduced cholestasis when compared with the pretreatment biopsy specimen. The preliminary data suggested that PAP selective for bilirubin removal may not only reduce the bilirubin level, but may also improve the histological pattern of the graft in terms of reduced cholestatic signs.

C. Comuzzi

Papers

Steatosis of the hepatic graft as a risk factor for post-transplant biliary complications

Steatosis of the graft is a risk factor for posttransplantation biliary complications.

Safety of Conversion From Twice-Daily Tacrolimus (Prograf) to Once-Daily Prolonged-Release Tacrolimus (Advagraf) in Stable Liver Transplant Recipients

Long-term outcomes of orthotopic liver transplantation in human immunodeficiency virus-infected patients and comparison with human immunodeficiency virus-negative cases.

Selective bilirubin removal by plasma treatment with Plasorba BR-350 for early cholestatic graft dysfunction.