Role Of Liver Transplantation Research Articles

Failure to rescue in living donor liver transplantation: Patterns and predictors

BackgroundAs a quality assessment tool, failure to rescue (FTR) has been employed in various surgical specialties. However, its role in liver transplantation has only recently been explored. To the best of our knowledge, role of FTR in living donor liver transplant (LDLT) has not been assessed previously. The objective of the current study was to determine failure to rescue (FTR) rate and it's predictors in an LDLT center. Materials and methodsWe reviewed a prospectively maintained database of patients who underwent LDLT at our center between 2012 and 2016. Patients who experienced grade 3B or above complications on Clavien-Dindo grading were included in this study. Primary outcome of interest was FTR rate in these patients. FTR was defined as a preventable major complication followed by death within one year after transplantation. We also looked at independent predictors of FTR in our patients and a multivariate analysis was performed. ResultsMedian age was 48.4(18–73) years. Male to female ratio was 3.3:1. Median MELD score was 17(6–42). The FTR rate in the current study was 52/131 (39.6%). Infectious complications were more common in the FTR group i.e. 22/32(68.8%) versus 10/32 (31.2%) (P < 0.0001). Biliary complications were more common in the non-FTR group i.e. 49/62 (79.1%) versus 13/62 (20.9%) (P < 0.0001). On multivariate analysis, there was a 60% increase in mortality following a major complication in the presence of early allograft dysfunction (Hazard ratio: 1.6, Confidence interval; 1.2–2.2, P = 0.002). A 40% reduction in FTR was seen in patients with a biliary complication versus other complications (Hazard ratio: 0.6, Confidence interval = 0.4–0.8, P = 0.009). ConclusionEarly allograft dysfunction and biliary complications are independent predictors of FTR in LDLT.

Transplantation for acute alcoholic hepatitis.

Transplantation for acute alcoholic hepatitis.

Liver transplantation for hepatocellular carcinoma: current update on treatment and allocation.

This review discusses the current imaging modalities and criteria used to diagnose, and the role of liver transplantation as well as nonsurgical hepatic-directed therapies to treat hepatocellular carcinoma in the setting of chronic liver disease. There has been continual evolution of guidelines, policies, and algorithms for the imaging diagnosis of hepatocellular carcinoma, particularly the Liver Imaging Reporting and Data System. The use of liver-directed therapy as a bridge to transplant is now common practice. Recently, patients have waited 6 months from listing before being granted a Model for End-Stage Liver Disease exception score of 28, with an increase every 3 months to a maximum score of 34. This policy change was developed to reduce disparities in outcomes for patients undergoing liver transplantation. The use of liver transplantation to treat hepatocellular carcinoma within the Milan criteria has good outcomes with a 5-year disease-free survival rate comparable to patients transplanted without malignancy. The development of guidelines both for the radiologic diagnosis and staging of the primary tumor and guidelines for assessing response to treatment allows for a more unified approach to the management of patients. With the partnership of oncologists, hepatologists, radiologists, pathologists, and surgeons, the outcomes of liver transplantation as treatment for hepatocellular continue to improve.

Acute Portal Vein Thrombosis (PVT) Causing Acute on Chronic Liver Failure: Is There a Role for Liver Transplantation?

Acute Portal Vein Thrombosis (PVT) Causing Acute on Chronic Liver Failure: Is There a Role for Liver Transplantation?

Acute and chronic hepatobiliary manifestations of sickle cell disease: A review.

Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process.

Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation

IntroductionAccumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. MethodsSerum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. ResultsThe concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. ConclusionsOur preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost.

Diagnosis and Treatment of Alcoholic Hepatitis: A Systematic Review.

Alcoholic hepatitis (AH) occurs in about one-third of individuals reporting long-term heavy alcohol use. It is associated with high short-term mortality, economic burden, and hospital resources utilization. We performed this systematic review to (i) describe clinical characteristics and genomics associated with the risk of AH; (ii) discuss role and limitations of liver biopsy and prognostic scoring systems; (iii) summarize evidence regarding the currently available therapies including liver transplantation; and (iv) outline emerging therapies with areas of unmet need. Literature search was performed for studies published in English language (January 1971 through March 2016). The following search engines were used: PubMed, Elsevier Embase, PsycINFO, and Cochrane Library. For the treatment section, only randomized controlled studies were included for this review. A total of 138 studies (59 randomized, 22 systematic reviews or meta-analyses, 7 surveys or guidelines, 7 population-based, and 43 prospective cohorts) were cited. There are over 325,000 annual admissions with AH contributing to about 0.8% of all hospitalizations in the United States. Liver biopsy may be required in about 25 to 30% cases for uncertain clinical diagnosis. Corticosteroids with or without N-acetylcysteine remains the only available therapy for severe episodes. Data are emerging on the role of liver transplantation as salvage therapy for select patients. Abstinence remains the most important factor impacting long-term prognosis. Results from the ongoing clinical trials within the National Institute on Alcohol Abuse and Alcoholism-funded consortia are awaited for more effective and safer therapies. AH is a potentially lethal condition with a significant short-term mortality. A high index of suspicion is required. There remains an unmet need for noninvasive biomarkers for the diagnosis, and predicting prognosis and response to therapy.

Biphenotypic liver malignancy: A role for liver transplantation?

Biphenotypic liver malignancy: A role for liver transplantation?

Role of liver transplantation in the treatment of metastases from neuroendocrine primaries: Patient selection and prediction of outcome

Aims: Neuroendocrine metastatic disease is the only secondary malignancy for which orthotopic liver transplantation is considered a viable treatment option. However, lack of agreed-upon criteria for patient selection and perioperative management precludes its widespread use. Methods: Review of published literature. Results: OLT is considered as a treatment option for patients with metastases from a neuroendocrine primary that are extensive, unresectable, or cause symptoms not otherwise controlled. It can also be an option for treatment of disease with unknown primary, as more and more of these cases are now recognised as primary hepatic neuroendocrine tumors. It takes place 6 months after resection of the primary focus in the abscence of recurrence or extrahepatic disease. Hepatomegaly and tumor bulk occupying > 50% of the liver, major simultaneous extrahepatic operation for removal of primary disease, poor tumor differentiation, Ki-67 and E-cadherin overexpression, age >45yrs and inability to perform a R0 resection are the most important factors that herald poor prognosis. In patients with well-differentiated primaries and 0 or 1 adverse factor, 5-yr survival rate has reached 60%–80% and the operation is considered curative in some cases. Disease-free survival can also extend beyond 5yrs, despite immunosuppression. It is suggested that pre-op treatment such as transarterial chemoembolization can minimize tumor load and improve post-op outcomes. OLT is still used as the last available treatment method, with a median time of 34 months from diagnosis to transplantation. The lack of commonly established criteria for patient selection makes benefit assessment difficult, as most series are small and include retrospectively collected data. Conclusions: OLT is emerging as a potent therapeutic modality for patients with neuroendocrine metastases. Establishment of widely accepted patient selection criteria and close follow-up will aid in its establishment as a potentially life-saving intervention.

Liver transplantation for adenomatosis: European experience.

The aim of this study was to collect data from patients who underwent liver transplantation (LT) for adenomatosis; to analyze the symptoms, the characteristics of the disease, and the recipient outcomes; and to better define the role of LT in this rare indication. This retrospective multicenter study, based on data from the European Liver Transplant Registry, encompassed patients who underwent LT for adenomatosis between January 1, 1986, and July 15, 2013, in Europe. Patients with glycogen storage disease (GSD) type IA were not excluded. This study included 49 patients. Sixteen patients had GSD, and 7 had liver vascular abnormalities. The main indications for transplantation were either a suspicion of hepatocellular carcinoma (HCC; 15 patients) or a histologically proven HCC (16 patients), but only 17 had actual malignant transformation (MT) of adenomas. GSD status was similar for the 2 groups, except for age and the presence of HCC on explants (P = 0.030). Three patients with HCC on explant developed recurrence after transplantation. We obtained and studied the pathomolecular characteristics for 23 patients. In conclusion, LT should remain an extremely rare treatment for adenomatosis. Indications for transplantation primarily concern the MT of adenomas. The decision should rely on morphological data and histological evidence of MT. Additional indications should be discussed on a case-by-case basis. In this report, we propose a simplified approach to this decision-making process.

Role Development of Nurse Practitioners and Physician Assistants in Liver Transplantation.

Nurse practitioners (NPs) and physician assistants (PAs) are increasingly utilized in health care. However, their roles in liver transplantation (LT) have not been investigated. In this study, we reviewed the employment and development of NPs and PAs and their impact on our deceased-donor LT (DDLT) program. We found a safe and efficient way to utilize NPs and PAs in a DDLT program. Since the beginning of our program, Model of End-Stage Liver Disease (MELD) scores have increased significantly, suggesting patients are sicker at the time of transplant, and wait times of patients have become longer. With the incorporation of NPs and PAs, we found that length of stay (LOS) was not affected. The overall median warm ischemic time did not increase. Outcomes of LT for both patient and graft survival actually improved and remain at or above the expected values. These results collectively support the usefulness and validity of NPs and PAs in a DDLT program. We have determined that surgical and medical NPs and PAs are essential for optimal patient outcomes. They facilitate a better learning experience for residents and fellows on their transplant rotations. Further investigations to assess the roles of these providers and their impact on the education of residents and fellows in transplantation are warranted. Further transplant hepatology education programs and/or fellowships are recommended to assist in the education and professional development of transplant NPs and PAs.

Role of Liver Transplantation in Bilio-Vascular Liver Injury After Cholecystectomy

BackgroundThe aim of this study was to report 2 cases of liver transplantation (LT) for iatrogenic bile-vascular injury (BVI) sustained during cholecystectomy and to review the literature for LT after cholecystectomy. MethodsBetween March 2001 and July 2013, within our institution, 12 patients were treated after cholecystectomy, 3 of 12 received LT, 1 for acute de-compensation in a cirrhotic patient and 2 after iatrogenic lesions. ResultsThe majority of iatrogenic injury occurred during video-laparocholecystectomy (63,6%; 7/11). Three patients of 12 (25%) received LT: the first patient developed acute de-compensation in chronic and after liver failure. The second patient developed recurrent cholangitis and secondary biliary cirrhosis. The third patient had undergone emergency hepatectomy because of bleeding and subsequent total hepatectomy with porto-caval shunt. Five of 12 (42%) patients were treated with bilio-digestive anastomosis: 1 patient with direct repair on T-tube; 2 patients (17%) with arterial vascular lesion requiring surgical treatment; and 1 patient treated with medical therapy. No deaths occurred. The post-operative morbidity included 1 re-intervention, 3 recurrent cholangitis, 1 anastomotic biliary stricture, 1 anastomotic bile leak, and cholestasis in 3 patients. The overall hospital stays were higher after LT. Median follow-up was 8.25 years (range, 2–14). ConclusionsThe management of iatrogenic injury during cholecystectomy depends on the time of recognition, extent of injury, experience of the surgeon, and the patient's general condition. If safe repair is possible, BVI should be treated promptly, otherwise all patients should be treated in an experienced center.

Controversies in criteria for liver transplantation in hepatocellular carcinoma

For patients with hepatic decompensation and hepatocellular carcinoma (HCC) within Milan criteria, liver transplantation provides the best long-term recurrence-free survival. However, there is controversy about the role of liver transplantation in other subgroups, including those with compensated cirrhosis, United Network for Organ Sharing (UNOS) T1 lesions, or HCC exceeding Milan criteria. For patients with compensated cirrhosis, surgical resection provides similar recurrence-free survival as liver transplantation and is the most cost-effective approach. Although a 'Wait and not Ablate' approach can facilitate priority listing in most patients with UNOS T1 lesions, nearly 10% will have rapid tumor growth beyond transplant criteria, thereby missing an opportunity for curative therapy. Patients exceeding Milan criteria have higher posttransplant recurrence rates and worse survival than those within Milan criteria, and any potential benefit of liver transplantation to these patients must be weighed against harms to others on the waiting list, particularly in areas with limited donor availability. Although downstaging may help select a subgroup of patients beyond Milan with good tumor biology and better prognosis, limitations of the current literature preclude rigorous evaluation. Until higher quality data become available that demonstrate transplant benefit in expanded criteria patients, liver transplantation should be reserved for patients within Milan criteria.

Incidental Intra-Hepatic Cholangiocarcinoma and Hepatocholangiocarcinoma in Liver Transplantation: A Single-Center Experience

BackgroundCholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). MethodsFrom 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55–42.04) and mean overall survival (OS) was 24.76 months (3.91–75.49). All patients died of recurrent tumor progression. ResultsiCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. ConclusionsFurther investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

Variable Use of Model for End-Stage Liver Disease Exception Points in Patients With Neuroendocrine Tumors Metastatic to the Liver and Its Impact on Patient Outcomes.

The role of liver transplantation in management of patients with metastatic neuroendocrine tumors (NETs) is controversial. Because many such patients have low waitlist priority, centers may apply for model for end-stage liver disease (MELD) exception points to increase likelihood of receiving a liver transplant. No formal criteria exist for application or receipt of exception points for this indication. Few studies have assessed waitlist and posttransplantation outcomes in patients with metastatic NETs, and none examined the impact of exception points. We analyzed all adult patients waitlisted for liver transplantation for metastatic NETs between February 27, 2002, and June 4, 2014, and fit a multivariable model to evaluate the association between exception point status and posttransplantation outcomes. There was variable use of MELD exception points across the United Network for Organ Sharing regions. Patients with an approved MELD exception were nearly twice as likely to be transplanted as those without exceptions (70.8% vs 39.1%, P < 0.001), and half as likely to be removed for death or clinical deterioration (9.2% vs 18.2%, P = 0.046). In multivariable models, posttransplantation survival was not associated with receipt of exception points, whereas risk of posttransplant mortality increased significantly with elevated serum total bilirubin level at transplantation. The 3-year posttransplant patient survival was 78% in transplant recipients with metastatic NETs whose total bilirubin level at transplantation was 1.3 mg/dL or less, compared to 36% in those with total bilirubin greater than 1.3 mg/dL. Serum total bilirubin may serve as a predictor of poor posttransplant survival in patients with metastatic NETs and could help risk-stratify patients applying for MELD exception points.

The role of liver transplantation or resection for patients with early hepatocellular carcinoma.

Liver resection (LR) and liver transplantation (LT) are curative treatments for early hepatocellular carcinoma (HCC), although their performance remains debated. We compared the survival of patients with HCC conforming to the Milan criteria (MC) after LT and LR and analyzed factors affecting clinical outcomes. Between January 2006 and January 2013, 65 and 184 patients received LT and LR for HCCs fulfilling the MC, respectively. Overall survival (OS) and disease-free survival (DFS) rates were compared between the two groups. To investigate effects of liver function and living donor liver transplantation (LDLT) on survival, two subgroup analyses were performed and associations with OS and DFS were examined. We found that OS rates were higher after LT than after LR since 3years postoperatively. DFS rates were significantly better after LT than after LR. Performance of LR, vascular invasion, and tumor multiplicity were associated with poor DFS, and factors affecting OS included the presence of vascular invasions, liver cirrhosis, and tumor multiplicity. In conclusion, despite of the effects of tumor characteristics on clinical outcomes, LT, including LDLT, should be considered the treatment of choice for patients with HCCs who met the MC. The role of LR is to identify poor prognostic factors through pathological examination.

Proposal for an algorithm for liver transplantation in Caroli's disease and syndrome: putting an uncommon effort into a common task.

Liver transplantation (LT) represents an uncommon indication for Caroli's disease (CD) or syndrome (CS). Excellent results of LT have been reported as shown by recent multicentric European and American registry reports. Clear therapeutic flowcharts to adopt in these diseases are still lacking. This review aims at analyzing highlighting recent transplant experiences in this field and also at focusing on the role of LT in case-specific comorbidities such as development of cholangiocellular cancer or renal failure are present.

Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management

Intrahepatic cholangiocarcinoma (ICC), the least common form of cholangiocarcinomas, is a rare hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts. The incidence of ICC has been rising in the global scale over the last twenty years, which may reflect both a true increase and the trend of earlier detection of the disease. Other than some well recognized causative risk factors, the association between viral and metabolic factors and ICC pathogenesis has been increasingly identified recently. Surgical resection is currently the only feasible modality with a curative ability, but the resectability and curability remain low. The high invasiveness of ICC predisposes the tumors to multifocality, node metastasis and vascular invasions, leading to poor long-term survival after resection. The role of liver transplantation is controversial, while locoregional treatments and systematic therapies may provide survival benefits, especially in patients with unresectable and advanced tumors. The present review discussed the epidemiology, risk factors, surgical and multimodal management of ICCs, which mainly focused on the outcomes and factors associated with surgical treatment.

The Roles of T Helper Type 17/Regulatory T Cells in Acute Rejection After Liver Transplantation in Rats

Liver transplantation is a widely accepted treatment for end-stage liver disease. The aim of our study was to investigate the imbalance between T helper type 17 (Th17) and CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells during hepatic allograft rejection in a rodent grafts model because their roles in liver transplantation is not fully understood. We compared median survival time (MST) survivals, Th17/Treg cells and related cytokines levels (interleukin [IL]-17, IL-6, IL-10, and transforming growth factor-β1), as well as serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T-Bili) after liver transplantation. In addition, the allograft groups were injected with IL-17 neutralizing antibody to evaluate the role of IL-17 in acute rejection. Th17 cells and related cytokines (IL-17 and IL-6) were obviously increased in the allograft group (all P < 0.01), whereas Treg cells and related cytokines (IL-10 and transforming growth factor-β1) were markedly lower than those of isograft and control groups (all P < 0.01). In addition, liver grafts in allograft groups rejected acutely (MST, 8.0 ± 1.2 days) accompanied by impaired liver function (AST, ALT, and T-Bili), while isograft groups survived long term (MST, 50.0 ± 3.8 days, all P < 0.01 vs. allograft group). Finally, neutralization of IL-17 in allograft groups significantly prolonged the survival (MST, 32.0 ± 4.8 days, P < 0.01), improved the liver function (AST, ALT, and T-Bili), and increased Treg cells in the liver (all P < 0.01). Th17 cells and secreted IL-17 play critical roles in acute rejection after liver grafts. The reduction of IL-17 may be 1 mechanism of immune tolerance after liver transplantation.

Galectin-1 in Stable Liver Transplant Recipients

IntroductionThe achievement of a state of tolerance and minimization of the immunosuppressive load form part of the “Holy Grail” in solid organ transplantation. Galectin-1 recently has been described to be involved in the maintenance of a tolerant environment, but there is no evidence of its role in human liver transplantation. The aim of our study was to measure the serum levels of galectin-1 in stable liver transplant recipients. MethodsSerum levels of galectin-1 were determined in 30 stable liver transplant recipients who had been free of rejection episodes for at least 8 years. Fifteen patients with an acute rejection episode and 34 healthy subjects were used as the control group. ResultsThe concentrations of galectin-1 were significantly higher in stable liver transplant recipients compared with healthy subjects and with the acute rejection group. ConclusionsThese preliminary results indicate that galectin-1 is upregulated in stable liver transplant recipients. Thus, our results extend the recent findings that galectin-1 may play an immune-suppressive role in liver transplantation. It remains to be established whether it might help to induce tolerance in liver transplantation.