Fatty liver in liver transplantation and surgery

Steatosis of the liver is common in Western countries, affecting about 25% of donors for liver transplantation and 20% of patients undergoing liver resection. Transplantation of livers with severe steatosis (> 60%) is associated with a high risk of primary nonfunction, and these livers should not be used for organ donation. In contrast, transplantation with livers containing mild steatosis (< 30%) yields results similar to those of transplantation performed with nonfatty livers. The outcome of livers with moderate steatosis (30 to 60%) are varying, and the use of these organs depends on the existence of additional risk factors. Similarly, liver resection in patients with steatosis is associated with a risk of postoperative mortality when compared with patients with nonfatty livers (14% versus 2%). Although hepatic steatosis is an important risk factor for surgery, little is known about the mechanisms of injury. In animal experiments, steatosis is associated with decreased ATP production and a disturbance of sinusoidal flow. Further contributing factors may include Kupffer cell dysfunction and leukocyte adhesion. Fatty hepatocytes have reduced tolerance against ischemic injury with a predominant necrotic form of cell death. In addition, the ability of hepatocytes to regenerate after major tissue loss is impaired in the steatotic liver. Very few protective strategies are known. Ischemic preconditioning and intermittent clamping protect the human liver against prolonged periods of ischemia. These techniques appear to be particularly protective in the steatotic liver. New insights into the mechanisms of liver failure in steatotic organs are needed to decrease the risk of surgery and increase the pool of organ donors.     

Cardiac surgery after liver transplantation

An aortic valve replacement and an aorto-coronary bypass were done in a woman of 57 years old after an orthotopic liver transplantation. The surgical risk was increased by the antecedent liver transplantation, the immunosuppression, chronic renal insufficiency and antiphospholipid syndrome. Surgery and the post-operative period were not complicated. Cardiac surgery is not a contraindication for patients with a prior organ transplant. These individuals have a higher cardiovascular risk and require a cardiovascular follow-up the modalities of which are yet to be defined.     

Relevance of ADAMTS13 to liver transplantation and surgery

A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) specifically cleaves unusually-large von Willebrand factor (VWF) multimers under high shear stress, and down-regulates VWF function to form platelet thrombi. Deficiency of plasma ADAMTS13 activity induces a life-threatening systemic disease, termed thrombotic microangiopathy (TMA) including thrombotic thrombocytopenic purpura (TTP). Children with advanced biliary cirrhosis due to congenital biliary atresia sometimes showed pathological features of TMA, with a concomitant decrease of plasma ADAMTS13 activity. Disappearance of their clinical findings of TTP after successful liver transplantation suggested that the liver is a major organ producing plasma ADAMTS13. In situ hybridization analysis showed that ADAMTS13 was produced by hepatic stellate cells. Subsequently, it was found that ADADTS13 was not merely responsible to development of TMA and TTP, but also related to some kinds of liver dysfunction after liver transplantation. Ischemia-reperfusion injury and acute rejection in liver transplant recipients were often associated with marked decrease of ADAMTS13 and concomitant formation of unusually large VWF multimers without findings of TMA/TTP. The similar phenomenon was observed also in patients who underwent hepatectomy for liver tumors. Imbalance between ADAMTS13 and VWF in the hepatic sinusoid might cause liver damage due to microcirculatory disturbance. It can be called as “local TTP like mechanism” which plays a crucial role in liver dysfunction after liver transplantation and surgery.     

Effects of multimodal fast-track surgery on liver transplantation outcomes

BACKGROUND: Fast-track surgery and enhanced recovery after surgery have been applied to many surgical procedures;however, data on fast-track surgery and enhanced recovery after surgery following liver transplantation is limited. This study aimed to conduct a prospective study to determine the effects of fast-track surgery on prognosis after liver transplan-tation. METHODS: This was a prospective, single-blinded, random-ized study. One hundred twenty-eight patients undergoing liver transplantation were selected for the fast-track (FT group, n=54) or conventional process (NFT group, n=74). The prima-ry endpoints were intensive care unit (ICU) stay and hospital stay. The secondary endpoints were as follows: operative time, anhepatic phase time, intraoperative blood loss, intraopera-tive blood transfusion volume, postoperative complications, readmission rate, and postoperative mortality. RESULTS: There was no significant difference in preoperative demographics between the two groups. The median ICU stay was 2 days (range 1-7 days) in the FT group and 5 days (range 3-12 days) in the NFT group (P<0.01). Furthermore, the hospital stay was also significantly reduced in the FT group (P<0.01). The operative time, anhepatic phase time, intraop-erative blood loss, and intraoperative blood transfusion vol-ume were decreased in the FT group compared with the NFT group (P<0.05). Based on Spearman correlation analysis, the ICU stay and hospital stay may be positively correlated with operative time, anhepatic phase time and intraoperative blood loss. There were no differences in the incidence of postopera-tive complications, readmissions, and postoperative mortality between the two groups. CONCLUSION: Fast-track procedures effectively reduce the ICU stay and hospital stay without adversely affecting progno-sis. This study demonstrated that fast-track protocols are safe and feasible in liver transplantation.     

Feasibility of hanging maneuvers in orthotopic liver transplantation with inferior vena cava preservation and in liver surgery

Background/Purpose

The aim of this work was to study the feasibility and complication rates of liver hanging maneuvers: the Belghiti liver hanging maneuver (BLHM) in liver resection and the modified liver hanging maneuver (MLHM) in orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation.

Methods

From January 2001 to August 2003, BLHM was planned in 26 consecutive right hepatectomies and MLHM in 28 consecutive OLTs with IVC preservation.

Results

BLHM was performed in 24/26 patients (92%). In the 2 remaining patients, chronic biliary infection (n = 1) and intraparenchymal hemorrhagic hepatocellular carcinoma (n = 1) did not allow BLHM to be achieved. Bleeding during the BLHM procedure occurred in 1 patient (4%), with no need for interruption. MLHM was performed in all 28 patients, and in none of them was bleeding observed during the maneuver.

Conclusions

BLHM and MLHM are important technical refinements with several advantages. Feasibility rates were 92% and 100%, respectively. Bleeding risk remained low (4%) for BLHM and was 0% for MLHM. The rate of BLHM failure suggests that the feasibility rate may be higher in normal liver parenchyma.

     

Combined cardiac surgery and liver transplantation: three decades of worldwide results

BACKGROUND: Patients with end-stage-liver-disease (ESLD) require orthotopic liver transplantation (OLT) as treatment. However, cirrhotic cardiomyopathy can be clinically revealed during OLT, with the possible development of a transient overt congestive heart failure. A number of patients require a combined procedure of liver transplantation and heart surgery, which includes heart transplantation, aortic valve replacement or coronary artery bypass grafting. Indications for combined liver-heart transplantation include heart failure with associated cardiac cirrhosis, familial amyloidosis, familial hypercholesterolemia and hemochromatosis, and homozygous β-thalassemia. METHODS/RESULTS. We performed a thorough research of Pubmed/ Medline, gathering and discussing data concerning this clinical condition and its treatment. CONCLUSION: In patients with end-stage liver disease, who are unable to tolerate an OLT post-operatively due to cardiac dysfunction, combined cardiac surgery and OLT appears to have certain advantages.     

Liver transplantation and liver cell transplantation

Liver transplantation is nowadays the recognized treatment of many liver diseases and liver-based metabolic disorders in childhood. The indications are congenital cholestatic diseases, mainly biliary atresia, metabolic disorders and fulminant hepatic failure. Potential candidates have to be evaluated early in a specialized center, as the survival rate is worse if the child is transplanted with end-stage liver failure. The graft is in most cases partial, either a split liver from a deceased donor (the other part going to an adult recipient), or the left lobe or left liver from a living donor. The patient's survival rate is about 80-90% at 1 year, 70-80% at 10 years, and the graft survival rate 60-70% at 10 years. Immuno-suppression depends on a calcineurin inhibitor (cyclosporin or tacrolimus), and either steroids or an induction with a monoclonal antibody against IL2-receptor. Early surgical complications are a non-function of the graft (rare), arterial or portal thrombosis, biliary problems (more frequent with partial grafts), bleeding. Infections with bacteria and fungi are frequent and often severe. CMV infection is prevented, or screened and preemptively treated. EBV infection is frequent and may induce a posttransplant lymphoproliferative disease, that can develop into a lymphoma. Early stages are treated with reduction of immuno-suppression and monoclonal antibodies against CD20. Acute rejection is frequent but usually easily controlled. Chronic rejection may be due to poor compliance. Late graft loss is due to chronic rejection or long-standing biliary complications. Long-term complications are progressive graft fibrosis, renal failure due to drug toxicity (mainly calcineurin inhibitors), and cancers (skin and lymphoma).     

Robotic liver surgery is the optimal approach as bridge to transplantation

The role of minimally invasive liver surgery as a bridge to transplantation is very promising but still underestimated. However, it should be noted that surgical approach for hepatocellular carcinomas(HCC) is not merely a technical or technological issue. Nowadays, the epidemiology of HCC is evolving due to the increasing role of non-alcoholic fatty-liver-disease, and the emerging concerns on direct-acting antivirals against hepatitis C virus in terms of HCC incidence. Therefore, a fully multidisciplinary study of the cirrhotic patient is currently more important than ever before, and the management of those patients should be reserved to tertiary referral hepatobiliary centers. In particular, minimally invasive approach to the liver showed several advantages compared to the classical open procedure, in terms of:(1) the small impact on abdominal wall;(2) the gentle manipulation on the liver;(3) the limited surgical trauma; and(4) the respect of venous shunts. Therefore, more direct indications should be outlined also in the Barcelona Clinic Liver Cancer model. We believe that treatment of HCC in cirrhotic patients should be reserved to tertiary referral hepatobiliary centers, that should offer patient-tailored approaches to the liver disease, in order to provide the best care for each case, according to the individual comorbidities, risk factors, and personal quality of life expectations.     

The results of liver transplantation with adjuvant chemotherapy for hepatobiliary surgery

This is an update of a pilot trial in which doxorubicin 10 mg/m² was used pre-, intra-, and postoperatively as adjuvant chemotherapy during liver transplant for unresectable hepatocellular carcinoma. The patients had advanced disease, with 17 of 20 having tumors that were multifocal, larger than 5 cm diameter unifocal, or tumors with vascular invasion. Individual followup is now 35–76 months, with a median observation time of 46 months. Eleven of the patients are alive (55%), 2 with recurrences (45% tumor free). Six patients have died from recurrent tumor and 3 from recurrent hepatitis B without evidence of malignancy. Of the eight patients with recurrent tumor, only 1 presented in the grafted liver.     

Enhanced recovery after surgery is feasible and safe in liver transplantation: a cohort study

BackgroundThe principles of enhanced recovery after surgery (ERAS) are being applied to still more advanced procedures. Liver transplantation offers a unique opportunity for a multimodal approach including donor care as well. Our objective was to determine if ERAS was applicable and safe in orthotopic liver transplantation (OLT).MethodsA national single centre retrospective study showing the implementation of ERAS from 2013 to 2019 with the proceeding 2 years serving as baseline. The primary endpoints were mortality, length of stay (LOS) in the ward and intensive care unit stay. Secondary endpoints were complications estimated by Dindo-Clavien classification, comprehensive complication index (CCI®) and re-admissions.ResultsA total of 334 patients were included. LOS was significantly reduced from a median of 22.5 days at introduction to 14 days at 2019. Cold ischaemia time was reduced from a mean of 10.7 to 6.0 h and the use of blood products (erythrocytes, plasma and thrombocytes) from a median of 28 to 6 units. Complications were reduced in severity. Mortality and readmission rates were not affected.ConclusionERAS principles are safe and recommended in patients undergoing OLT resulting in reduced severity of complications and LOS without affecting re-admissions or mortality.     

Successful treatment of complex cholangiolithiasis following orthotopic liver transplantation with interventional radiology

Bile duct stones are a serious and the third most common complication of the biliary system that can occur following liver transplantation.The incidence rate of bile duct stones after liver transplantation is1.8%-18%.The management of biliary stones is usually performed with endoscopic techniques;however,the technique may prove to be challenging in the treatment of the intrahepatic bile duct stones.We herein reporta case of a 40-year-old man with rare,complex bile duct stones that were successfully eliminated with percutaneous interventional techniques.The complex bile duct stones were defined as a large number of bile stones filling the intra-and extrahepatic bile tracts,resulting in a cast formation within the biliary tree.Common complications such as hemobilia and acute pancreatitis were not present during the perioperative period.The follow-up period was 20 mo long.During the postoperative period,the patient maintained normal temperature,and normal total bilirubin and direct bilirubin levels.The patient is now living a high quality life.This case report highlights the safety and efficacy of the percutaneous interventional approach in the removal of complex bile duct stones following liver transplantation.     

Artificial Intelligence in hepatology,liver surgery and transplantation: Emerging applications and frontiers of research

The integration of artificial intelligence (AI) and augmented realities into the medical field is being attempted by various researchers across the globe. As a matter of fact, most of the advanced technologies utilized by medical providers today have been borrowed and extrapolated from other industries. The introduction of AI into the field of hepatology and liver surgery is relatively a recent phenomenon. The purpose of this narrative review is to highlight the different AI concepts which are currently being tried to improve the care of patients with liver diseases. We end with summarizing emerging trends and major challenges in the future development of AI in hepatology and liver surgery.     

Ethics in liver transplantation

In little over 30 years, liver transplantation has become the preferred therapy for many forms of end-stage liver disease. Improvements in immunosuppression, management of comorbidities, and surgical techniques have contributed to the spectacular improvement in patient and graft survival. Unfortunately, global application of this lifesaving therapy is limited by the inadequate supply of livers available for transplantation. Therefore, in an effort to minimize the mortality among patients waiting for liver transplantation, allocation based on the model for end-stage liver disease (MELD) has been adopted. Unfortunately, the current allocation system, initially developed to distribute deceased-donor kidneys for transplantation, has many deficiencies when applied to the allocation of deceased-donor livers. One such deficiency is exemplified by the unequal distribution of deceased-donor livers across and within regions with respect to MELD. Consequently, the national directive to transplant the sickest first among those awaiting liver transplantation has yet to be realized among all patients listed irrespective of region.     

Immunosuppression in liver transplantation

Prevention of graft rejection while minimizing morbidity remains the single most important objective in liver transplantation. Advances in immunosuppression have provided excellent patient and graft survival with relatively low incidences of acute rejection. However, it is apparent that the toxicity of the present immunosuppressive drugs accounts for much of the morbidity after transplantation. Attention is now being focused on combination drug therapies to reduce morbidity while maintaining the excellent results achieved with present immunosuppressive agents.