Cirrhotic cardiomyopathy: Implications for the perioperative management of liver transplant patients

Cirrhotic cardiomyopathy is a disease that has only recently been recognised as a definitive clinical entity. In the setting of liver cirrhosis, it is characterized by a blunted inotropic and chronotropic response t o s t r e s s, i m p a i r e d d i a s t o l i c r e l a x a t i o n o f t h e myocardium and prolongation of the QT interval in the absence of other known cardiac disease. A key pathological feature is the persistent over-activation of the sympathetic nervous system in cirrhosis, which leads to down-regulation and dysfunction of theβ-adrenergic receptor. Diagnosis can be made using a combination of echocardiography(resting and stress), tissue Doppler imaging, cardiac magnetic resonance imaging, 12-lead electrocardiogram and measurement of biomarkers. There are significant implications of cirrhotic cardiomyopathy in a number of clinical situations in which there is an increased physiological demand, which can lead to acute cardiac decompensation and heart failure. Prior to transplantation there is an increased risk of hepatorenal syndrome, cardiac failure following transjugular intrahepatic portosystemic shunt insertion and increased risk of arrhythmias during acute gastrointestinal bleeding. Liver transplantation presents the greatest physiological challenge with a further risk of acute cardiac decompensation. Peri-operative management should involve appropriate choice of graft and minimization of large fluctuations in preload and afterload. The avoidance of cardiac failure during this period has important prognostic implications, as there is evidence to suggest a long-term resolution of the abnormalities in cirrhotic cardiomyopathy.     

Physiopathology of splanchnic vasodilation in portal hypertension

In liver cirrhosis, the circulatory hemodynamic alterations of portal hypertension significantly contribute to many of the clinical manifestations of the disease. In the physiopathology of this vascular alteration, mesenteric splanchnic vasodilation plays an essential role by initiating the hemodynamic process. Numerous studies performed in cirrhotic patients and animal models have shown that this splanchnic vasodilation is the result of an important increase in local and systemic vasodilators and the presence of a splanchnic vascular hyporesponsiveness to vasoconstrictors. Among the molecules and factors known to be potentially involved in this arterial vasodilation, nitric oxide seems to have a crucial role in the physiopathology of this vascular alteration. However, none of the wide variety of mediators can be described as solely responsible, since this phenomenon is multifactorial in origin. Moreover, angiogenesis and vascular remodeling processes also seem to play a role. Finally, the sympathetic nervous system is thought to be involved in the pathogenesis of the hyperdynamic circulation associated with portal hypertension, although the nature and extent of its role is not completely understood. In this review, we discuss the different mechanisms known to contribute to this complex phenomenon.     

From portal to splanchnic venous thrombosis:What surgeons should bear in mind

The present study aims to review the evolution of surgical management of portal(PVT) and splanch-nic venous thrombosis(SVT) in the context of liver transplantation over the last 5 decades. PVT is more commonly managed by endovenous thrombectomy, while SVT requires more complex technical expedients. Several surgical techniques have been proposed, such as extensive eversion thrombectomy, anastomosis to collateral veins, reno-portal anastomosis, cavo-portal hemi-transposition, portal arterialization and combined liver-intestinal transplantation. In order to achieve satisfactory outcomes, careful planning of the surgical strategy is mandatory. The excellent results that are ob-tained nowadays confirm that, even extended, splanch-nic thrombosis is no longer an absolute contraindication for liver transplantation. Patients with advanced portal thrombosis may preferentially be referred to specialized centres, in which complex vascular approaches and even multivisceral transplantation are performed.     

Acute portal vein thrombosis after liver transplant presenting with subtle ultrasound abnormalities:A case report and literature review

BACKGROUND Portal vein thrombosis(PVT) after liver transplantation(LT) is an uncommon complication with potential for significant morbidity and mortality that transplant providers should be cognizant of.Recognizing subtle changes in postoperative ultrasounds that could herald but do not definitively diagnose PVT is paramount.CASE SUMMARY A 30-year-old female with a history of alcohol-related cirrhosis presented with painless jaundice and received a deceased donor orthotopic liver transplant.On the first two days post-operatively,her liver Doppler ultrasounds showed a patent portal vein,increased hepatic arterial diastolic flows,and reduced hepatic arterial resistive indices.She was asymptomatic with improving labs.On postoperative day three,her resistive indices declined further,and computed tomography of the abdomen revealed a large extra-hepatic PVT.The patient then underwent emergent percutaneous venography with tissue plasminogen activator administration,angioplasty,and stent placement.Aspirin was started to prevent stent thrombosis.Follow-up ultrasounds showed a patent portal vein and improved hepatic arterial resistive indices.Her graft function improved to normal by discharge.Although decreased hepatic artery resistive indices and increased diastolic flows on ultrasound are often associated with hepatic arterial stenosis post-LT,PVT can also cause these findings.CONCLUSION Reduced hepatic arterial resistive indices on ultrasound can signify PVT post-LT,and thrombolysis,angioplasty,and stent placement are efficacious treatments.     

Effect of laparoscopic abdominal surgery on splanchnic circulation: Historical developments

With the developments in medical technology and increased surgical experience, advanced laparoscopic surgical procedures are performed successfully. Laparoscopic abdominal surgery is one of the best examples of advanced laparoscopic surgery (LS). Today, laparoscopic abdominal surgery in general surgery clinics is the basis of all abdominal surgical interventions. Laparoscopic abdominal surgery is associated with systemic and splanchnic hemodynamic alterations. Inadequate splanchnic perfusion in critically ill patients is associated with increased morbidity and mortality. The underlying pathophysiological mechanisms are still not well understood. With experience and with an increase in the number and diversity of the resulting data, the pathophysiology of laparoscopic abdominal surgery is now better understood. The normal physiology and pathophysiology of local and systemic effects of laparoscopic abdominal surgery is extremely important for safe and effective LS. Future research projects should focus on the interplay between the physiological regulatory mechanisms in the splanchnic circulation (SC), organs, and diseases. In this review, we discuss the effects of laparoscopic abdominal surgery on the SC.     

Stability of cirrhotic systemic hemodynamics ensures sufficient splanchnic blood flow after living-donor liver transplantation in adult recipients with liver cirrhosis

AIM： To investigate the correlation between systemic hemodynamics and splanchnic circulation in recipients with cirrhosis undergoing living-donor liver transplantation （LDLT）, and to clarify how systemic hemodynamics impact on local graft circulation after LDLT.
METHODS： Systemic hemodynamics, indocyanine green （ICG） elimination rate （K,cG） and splanchnic circulation were simultaneously and non-invasively investigated by pulse dye densitometry （PDD） and ultrasound. Accurate estimators of optimal systemic hyperdynamics after LDLT [i.e., balance of cardiac output （CO） to blood volume （BV） and mean transit time （MTT）, defined as the time required for half the administered ICG to pass through an attached PDD sensor in the first circulation] were also measured. Thirty recipients with cirrhosis were divided into two groups based on clinical outcomes corresponding to postoperative graft function.
RESULTS： Cirrhotic systemic hyperdynamics characterized by high CO, expanded BV and low total peripheral resistance （TPR） were observed before LDLT. TPR reflecting cirrhotic vascular alterations was slowly restored after LDLT in both groups. Although no significant temporal differences in TPR were detected between the two groups, CO/BV and M＇IT differed significantly. Recipients with good outcomes showed persistent cirrhotic systemic hyperdynamics after LDLT, whereas recipients with poor outcomes presented with unstable cirrhotic systemic hyperdynamics and severely decreased KICG. Systemic hyperdynamic disorders after LDLT impacted on portal venous flow but not hepatic arterial flow.
CONCLUSION： We conclude that subtle systemic hyperdynamics disorders impact on splanchnic circulation, and that an imbalance between CO and BV decreases portal venous flow, which results in critical outcomes.     

Interventional radiology in living donor liver transplant

The shortage of deceased donor liver grafts led to the use of living donor liver transplant (LDLT). Patients who undergo LDLT have a higher risk of complications than those who undergo deceased donor liver transplantation (LT). Interventional radiology has acquired a key role in every LT program by treating the majority of vascular and non-vascular post-transplant complications, improving graft and patient survival and avoiding, in the majority of cases, surgical revision and/or re-transplant. The aim of this paper is to review indications, diagnostic modalities, technical considerations, achievements and potential complications of interventional radiology procedures after LDLT.     

Role of vaptans in the management of hydroelectrolytic imbalance in liver cirrhosis

Ascites and hyponatremia are the most common complications in patients with liver cirrhosis and develop as a consequence of a severe impairment of liver function and portal hypertension. Increasing evidences support the central role of renal function alterations in the pathogenesis of hydroelectrolytic imbalances in cirrhotic patients, thus implying a dense cross-talk between liver and kidney in the systemic and splanchnic vascular homeostasis in such subjects. Since Arginin Vasopressin (AVP) hyperincretion occurs at late stage of cirrhosis and plays an important role in the development of refractory ascites, dilutional hyponatremia and finally hepato-renal syndrome, selective antagonists of AVP receptors V₂ (vaptans) have been recently introduced in the therapeutic algorithm of advanced cirrhotic patients. Despite the promising results of earlier phase-two studies, randomized controlled trials failed to find significant results in terms of efficacy of such drugs both in refractory ascites and hyponatremia. Moreover, concerns on their safety profile arise, due to the number of potentially severe side effects of vaptans in the clinical setting, such as hypernatremia, dehydration, renal impairment, and osmotic demyelination syndrome. More robust data from randomized controlled trials are needed in order to confirm the potential role of vaptans in the management of advanced cirrhotic patients.     

Intensive care management of liver transplanted patients

Advances in pre-transplant treatment of cirrhosis-related organ dysfunction,intraoperative patient management,and improvements in the treatment of rejection and infections have made human liver transplantation an effective and valuable option for patients with end stage liver disease.However,many important factors,related both to an increasing "marginality" of the implanted graft and unexpected perioperative complications still make immediate post-operative care challenging and the early outcome unpredictable.In recent years sicker patients with multiple comorbidities and organ dysfunction have been undergoing Liver transplantation;appropriate critical care management is required to support prompt graft recovery and prevent systemic complications.Early post-operative management is highly demanding as significant changes may occur in both the allograft and the "distant" organs.A functioning transplanted liver is almost always associated with organ system recovery,resulting in a new life for the patient.However,in the unfortunate event of graft dysfunction,the unavoidable development of multi-organ failure will require an enhanced level of critical care support and a prolonged ICU stay.Strict monitoring and sustainment of cardiorespiratory function,frequent assessment of graft performance,timely recognition of unexpected complications and the institution of prophylactic measures to prevent extrahepatic organ system dysfunction are mandatoryin the immediate post-operative period.A reduced rate of complications and satisfactory outcomes have been obtained from multidisciplinary,collaborative efforts,skillful vigilance,and a thorough knowledge of pathophysiologic characteristics of the transplanted liver.     

Systemic hemodynamics in advanced cirrhosis: Concerns during perioperative period of liver transplantation

Advanced liver cirrhosis is usually accompanied by portal hypertension. Long-term portal hypertension results in various vascular alterations. The systemic hemodynamic state in patients with cirrhosis is termed a hyperdynamic state. This peculiar hemodynamic state is characterized by an expanded blood volume, high cardiac output, and low total peripheral resistance. Vascular alterations do not disappear even long after liver transplantation(LT), and recipients with cirrhosis exhibit a persistent systemic hyperdynamic state even after LT. Stability of optimal systemic hemodynamics is indispensable for adequate portal venous flow(PVF) and successful LT, and reliable parameters for optimal systemic hemodynamics and adequate PVF are required. Even a subtle disorder in systemic hemodynamics is precisely indicated by the balance between cardiac output and blood volume. The indocyanine green(ICG) kinetics reflect the patient's functional hepatocytes and effective PVF, and PVF is a major determinant of the ICG elimination constant(kICG) in the well-preserved allograft. The kICG value is useful to set the optimal PVF during living-donor LT and to evaluate adequate PVF after LT. Perioperative management has a large influence on the postoperative course and outcome; therefore, key points and unexpected pitfalls for intensive management are herein summarized. Transplant physicians should fully understand the peculiar systemic hemodynamic behavior in LT recipients with cirrhosis and recognize the critical importance of PVF after LT.     

Perioperative thromboprophylaxis in liver transplant patients

Improvements in surgical and anesthetic procedures have increased patient survival after liver transplantation(LT). However, the perioperative period of LT can still be affected by several complications. Among these, thromboembolic complications(intracardiac thrombosis, pulmonary embolism, hepatic artery and portal vein thrombosis) are relatively common causes of increased morbidity and mortality. The benefit of thromboprophylaxis in general surgical patients has already been established, but it is not the standard of care in LT recipients. LT is associated with a high bleeding risk, as it is performed in a setting of already unstable hemostasis. For this reason, the role of routine perioperative prophylactic anticoagulation is usually restricted. However, recent data have shown that the bleeding tendency of cirrhotic patients is not an expression of an acquired bleeding disorder but rather of coexisting factors(portal hypertension, hypervolemia and infections). Furthermore, in cirrhotic patients, the new paradigm of ‘‘rebalanced hemostasis' ' can easily tip towards hypercoagulability because of the recently described enhanced thrombin generation, procoagulant changes in fibrin structure and platelet hyperreactivity. This new coagulation balance, along with improvements in surgical techniques and critical support, has led to a dramatic reduction in transfusion requirements, and the intraoperative thromboembolic-favoring factors(venous stasis, vessels clamping, surgical injury) have increased the awareness of thrombotic complications and led clinicians to reconsider the limited use of anticoagulants or antiplatelets in the postoperative period of LT.     

Different behaviour of BK-virus infection in liver transplant recipients

Polyomavirus BK(BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A Pub Med search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease(CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.     

Management of bacterial infection in the liver transplant candidate

Bacterial infection(BI) is a common cause of impairment of liver function in patients with cirrhosis, especially in the liver transplant candidates. These patients share an immunocompromised state and increased susceptibility to develop community and hospital-acquired infections. The changing epidemiology of BI, with an increase of multidrug resistant strains, especially in healthcareassociated settings, represents a critical issue both in the waiting list and in the post-operative management. This review focused on the role played by BI in patients awaiting liver transplantation, evaluating the risk of drop-out from the waiting list, the possibility to undergo liver transplantation after recovery from infection or during a controlled infection.     

多层螺旋CT门静脉成像评价肝硬化患者肝功能分级价值研究

目的 探讨采用多层螺旋CT门静脉成像（MSCTP）检查对肝硬化患者肝功能分级的评价价值。方法 2015年8月~2017年9月我院收治的肝硬化患者62例,选择同期健康人62例作为对照组,均行MSCTP检查,观察脾静脉（SPV）、肝内门静脉左支（IHLPV）、门静脉主干（MPV）和肝内门静脉右支（IHRPV）直径,并比较不同Child-Pugh分级患者的上述指标及胃左静脉（LGV）直径和食管下段静脉曲张断面数。结果 肝硬化患者SPV、IHLPV、MPV和IHRPV直径分别为（14.4±3.6） mm、（13.5±3.1） mm、（17.9±4.2） mm和（13.8±3.9） mm,均显著大于健康人[分别为（8.9±1.7） mm、（9.7±2.3） mm、（11.2±2.9） mm和（9.5±2.5） mm,P<0.05];随着肝功能Child-Pugh分级变差,SPV、IHLPV、MPV和IHRPV直径也逐渐增大[A级为（13.2±2.7） mm、（12.1±3.2） mm、（16.4±4.6） mm和（12.3±3.3） mm,B级为（15.1±3.5） mm、（14.3±3.7） mm、（18.5±4.8） mm和（14.7±3.6） mm,C级为（16.3±4.1） mm、（15.8±4.3） mm、（20.8±5.1） mm和（16.1±4.7） mm,P<0.05],差异显著,LGV直径和食管下段静脉曲张断面数亦逐渐增大或增多[Child-Pugh A级分别为（6.4±1.5） mm和（3.8±1.1）个,B级为（9.1±2.2） mm和（7.4±1.6）个,C级为（9.7±2.6） mm和（7.7±1.8）个],其中Child-Pugh B级或C级与A级比,差异有统计学意义（P<0.05）,而Child-Pugh B级与C级比较,差异无统计学意义（P>0.05）。结论 采用MSCTP检查门静脉系统并检测有关指标,能很好地评估肝硬化患者肝功能状态,具有重要的临床意义。     

Immunization of liver and renal transplant recipients: a seroepidemiological and sociodemographic survey

Abstract: Several life‐threatening infections, a major risk to adult solid organ transplant (SOT) recipients on immunosuppressive therapy, can be prevented by immunization. We analyzed sociodemographic parameters and the immunization status of adult liver transplant recipients (LTX‐R, n=267) and renal transplant recipients (RTX‐R, n=197) SOT recipients at the Transplantation Center, Berlin, Germany. Date, number, and provider of recommended vaccines were recorded and seroprotection rates determined. The social status in both groups was similar. Most patients (89%) were not adequately informed about immunizations; and if informed, main sources were physicians (47%) and the media (40%). Vaccinations were predominantly provided by family doctors (LTX‐R, 66%; RTX‐R, 31%) or hemodialysis centers (RTX‐R, 37%). Before transplantation, RTX‐R had significantly more often received booster vaccinations against tetanus and diphtheria (P<0.005), and a primary hepatitis B immunization (55%); whereas in LTX‐R, post‐transplant vaccinations against hepatitis A (16%) and pneumococcal disease (13%) were more frequent. Seroprotection rates against tetanus were fairly high in LTX‐R (85.3%) and RTX‐R (86.8%), and considerably lower for diphtheria, hepatitis A, and influenza. Immunization rates are too low in SOT recipients. Improvement will depend on a more active role of health care providers.     

Management of hypertension in liver transplant patients

Hypertension is a common co-morbidity and a frequent complication in liver transplant patients. The aim of this paper is to concisely review available clinical data and propose a hypertension treatment algorithm in liver transplant patients. Calcium channel blockers are mainstay of the treatment due to their potent vasodilatory effects. Dihydropyridine calcium channel blockers are preferable due to their least interaction with cytochrome P450 enzyme system and, therefore, minimal risk of potential disruption of immunosuppressive drug levels. Beta-blockers may be considered first line drugs in patients with resting tachycardia and in those with high cardiac outputs. Data support the use of beta-blockers for patients intolerant or unresponsive to calcium channel blockers. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers have little value when used early after liver transplant but may have a more pronounced role during the later periods. Diuretics may be of value in combination with other drugs, especially to counteract the potassium-retaining effects of calcineurin inhibitors. Treatment of post liver transplantation hypertension in patients with co-morbid conditions such as coronary artery disease, diabetes mellitus, congestive heart failure, and renal disease will likely require combination therapy.     

肝硬化门静脉血栓形成的临床分析

目的　探讨肝硬化 (LC)门静脉血栓 (PVT)形成对LC病程发展的影响。方法　检索我院自 1 995至 2 0 0 2年肝硬化PVT形成患者 ,血栓诊断依据彩色多普勒和 (或 )CT。 4 8例肝硬化PVT形成患者入选血栓组 ;同阶段LC门脉高压症的非血栓病例中选择 5 2例作为对照组。对两组患者的肝功能Child Pugh分级、凝血功能、门静脉、脾静脉宽度及脾脏面积、厚度进行比较。行t检验 ,χ2 检验 ,Logistic回归分析。结果　肝硬化PVT形成除继发于脾切除等手术后 ,75 .0 %隐匿发病 ,85 .4 %的血栓发生于门静脉主干 ,脾脏增大与门静脉增宽是PVT形成的危险因素 (P =0 .0 0 3、0 .0 1 0 )。血栓组门静脉及脾静脉宽度分别为 (1 .4 8± 0 .2 6 )cm ,(1 .2 3± 0 .38)cm ,与对照组比较差异有显著性 [(1 .37± 0 .2 2 )cm ,(1 .0 5± 0 .30 )cm ,P =0 .0 37,0 .0 31 ]。血栓组脾面积平均值为 (96 .6 4± 33.4 )cm2 ,脾厚径为 (6 .0 7± 1 .2 0 )cm ,分别大于对照组的 (80 .81± 2 8.9)cm2 ,(5 .2 3± 1 .0 8)cm(P =0 .0 36 ,0 .0 0 1 )。血栓组食管胃底静脉曲张程度重于非血栓组 ,大出血、大量腹水比例高 (P <0 .0 5 )。血栓形成后 1年内死亡率为1 6 .6 % ,较非血栓组增高 (P =0 .0 2 3)。两组肝功能Child Pugh分级、凝血功能、血小板计     

The effect of exercise on regional adipose tissue and splanchnic lipid metabolism in overweight Type 2 diabetic subjects

Aims/hypothesis To test the hypothesis that adipose tissue lipolysis is enhanced in patients with Type 2 diabetes mellitus, we examined the effect of exercise on regional adipose tissue lipolysis and fatty acid mobilisation and measured the acute effects of exercise on the co-ordination of adipose tissue and splanchnic lipid metabolism.Methods Abdominal, subcutaneous adipose tissue and splanchnic lipid metabolism were studied by conducting measurements of arterio-venous concentrations and regional blood flow in six overweight Type 2 diabetic subjects before, during and after exercise.Results Exercise induced an increase in adipose tissue lipolysis and fatty acid release. However, the increase in adipose tissue blood flow was small, limiting fatty acid mobilisation from this tissue. Some of the fatty acids were released in excess in the post-exercise phase. The splanchnic fatty acid uptake was unchanged during the experiment but splanchnic ketogenesis increased in the post-exercise phase. The arterial glucose concentration decreased during exercise and continued to decrease afterwards, indicating an imbalance between splanchnic glucose production and whole-body glucose utilisation.Conclusions/interpretation Regional subcutaneous, abdominal adipose tissue lipolysis is no higher in patients with Type 2 diabetes than in young, healthy subjects. Exercise stimulates adipose tissue lipolysis, but due to an insufficient increase in blood flow, a high fraction of the fatty acids liberated by lipolysis cannot be released to the blood. Splanchnic glucose release is smaller than whole-body glucose utilisation during exercise and post-exercise recovery.Abbreviations ICG indocyanine green - 3-OHB 3-hydroxybutyrate - TAG triacylglycerol - VO_2,max peak oxygen consumption     

Significance of progressive liver fibrosis in pediatric liver transplants: A review of current evidence

This article reviews the current evidence and knowledge of progressive liver fibrosis after pediatric liver transplantation. This often-silent histologic finding is common in long-term survivors and may lead to allograft dysfunction in advanced stages. Surveillance through protocolized liver allograft biopsy remains the gold standard for diagnosis, and recent evidence suggests that chronic inflammation precedes fibrosis.