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Portal flow modulation in living donor liver transplantation: review with a focus on splenectomy.
Yoshizumi, T, Mori, M
Surgery today. 2020;(1):21-29
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Abstract
Small-for-size graft (SFSG) syndrome after living donor liver transplantation (LDLT) is the dysfunction of a small graft, characterized by coagulopathy, cholestasis, ascites, and encephalopathy. It is a serious complication of LDLT and usually triggered by excessive portal flow transmitted to the allograft in the postperfusion setting, resulting in sinusoidal congestion and hemorrhage. Portal overflow injures the liver directly through nutrient excess, endothelial activation, and sinusoidal shear stress, and indirectly through arterial vasoconstriction. These conditions may be attenuated with portal flow modulation. Attempts have been made to control excessive portal flow to the SFSG, including simultaneous splenectomy, splenic artery ligation, hemi-portocaval shunt, and pharmacological manipulation, with positive outcomes. Currently, a donor liver is considered a SFSG when the graft-to-recipient weight ratio is less than 0.8 or the ratio of the graft volume to the standard liver volume is less than 40%. A strategy for transplanting SFSG safely into recipients and avoiding extensive surgery in the living donor could effectively address the donor shortage. We review the literature and assess our current knowledge of and strategies for portal flow modulation in LDLT.
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OPTN/SRTR 2018 Annual Data Report: Liver.
Kwong, A, Kim, WR, Lake, JR, Smith, JM, Schladt, DP, Skeans, MA, Noreen, SM, Foutz, J, Miller, E, Snyder, JJ, et al
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020;:193-299
Abstract
Data on adult liver transplants performed in the US in 2018 are notable for (1) continued growth in numbers of new waitlist registrants (11,844) and transplants performed (8250); (2) continued increase in the transplant rate (54.5 per 100 waitlist-years); (3) a precipitous decline in waitlist registrations and transplants for hepatitis-C-related indications; (4) increases in waitlist registrants and recipients with alcoholic liver disease and with clinical profiles consistent with non-alcoholic fatty liver disease; (5) increased use of hepatitis C virus antibody-positive donor livers; and (6) continued improvement in graft survival despite changing recipient characteristics such as older age and higher rates of obesity and diabetes. Variability in transplant rates remained by candidate race, hepatocellular carcinoma status, urgency status, and geography. The volume of pediatric liver transplants was relatively unchanged. The highest rate of pre-transplant mortality persisted for children aged younger than 1 year. Children underwent transplant at higher acuity than in the past, as evidenced by higher model for end-stage liver disease/pediatric end-stage liver disease scores and listings at status 1A and 1B at transplant. Despite higher illness severity scores at transplant, pediatric graft and patient survival posttransplant have improved over time.
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Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management.
Cigrovski Berkovic, M, Virovic-Jukic, L, Bilic-Curcic, I, Mrzljak, A
World journal of gastroenterology. 2020;(21):2740-2757
Abstract
Liver cirrhosis and diabetes mellitus (DM) are both common conditions with significant socioeconomic burden and impact on morbidity and mortality. A bidirectional relationship exists between DM and liver cirrhosis regarding both etiology and disease-related complications. Type 2 DM (T2DM) is a well-recognized risk factor for chronic liver disease and vice-versa, DM may develop as a complication of cirrhosis, irrespective of its etiology. Liver transplantation (LT) represents an important treatment option for patients with end-stage liver disease due to non-alcoholic fatty liver disease (NAFLD), which represents a hepatic manifestation of metabolic syndrome and a common complication of T2DM. The metabolic risk factors including immunosuppressive drugs, can contribute to persistent or de novo development of DM and NAFLD after LT. T2DM, obesity, cardiovascular morbidities and renal impairment, frequently associated with metabolic syndrome and NAFLD, may have negative impact on short and long-term outcomes following LT. The treatment of DM in the context of chronic liver disease and post-transplant is challenging, but new emerging therapies such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) targeting multiple mechanisms in the shared pathophysiology of disorders such as oxidative stress and chronic inflammation are a promising tool in future patient management.
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4.
Management of Recurrent HCC After Liver Transplantation.
Sarici, B, Isik, B, Yilmaz, S
Journal of gastrointestinal cancer. 2020;(4):1197-1199
Abstract
BACKGROUND Liver transplantation is the best treatment option for hepatocellular carcinoma (HCC). Although centers use strict selection criteria, there is a risk of recurrence, reaching up to 20% which are mostly observed within two years following the procedure. The survival after the recurrence is poor and it has been reported to be between 7-16 months. This poor prognosis is due to the systemic course of the recurrence even its presentation is local initially. RESULTS The clinical management and treatment algorithm of recurrence is challenging and there is no guideline regarding the situation. Staging of the disease and multi-disciplinary approach are important. The decision for choice of treatment is given depending on the localization and spread of the recurrence. Adjusting and switching the immunosuppressive therapy should be the first attempt. When the recurrence is limited or confined to resectable regions, surgery should be the choice of treatment. Multiple recurrence sites such as adrenal glands, lung, lymph nodes are not contraindication for curative surgery. Resection of the graft for intrahepatic recurrence is the most beneficial procedure for survival. If resection is not possible due to advanced hepatic disease, loco-regional therapies such as TACE, RF, microwave ablation should be considered. SBRT may be an alternative both for hepatic and extra-hepatic recurrence. In case of systemic disease, sorafenib should be the drug choice.
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Acute kidney injury: A critical care perspective for orthotopic liver transplantation.
MacDonald, AJ, Karvellas, CJ
Best practice & research. Clinical anaesthesiology. 2020;(1):69-78
Abstract
Acute kidney injury (AKI) is associated with high perioperative mortality in patients undergoing liver transplantation (LT). In the era of Model of End-stage Liver Disease score-based allocation, more patients with impaired renal function are receiving LT. The majority of preoperative AKI is secondary to azotemia, including hepatorenal syndrome - a progressive form of renal impairment unique to liver failure. Prompt recognition and initiation of cause-directed therapies are central to improving post-transplant survival. Given that, the healthcare providers must develop an expertise in liver failure-related renal complications, specifically their management and perioperative implications. Notably, AKI may complicate intraoperative course, exacerbating hemodynamic instability, metabolic acidosis, and electrolyte and coagulation abnormalities. Adjunctive intraoperative continuous renal replacement therapy has been employed; however, prospective studies remain necessary to validate potential benefits.
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Pharyngeal metastasis following living-donor liver transplantation for hepatocellular carcinoma: a case report and literature review.
Tohyama, T, Sakamoto, K, Tamura, K, Nakamura, T, Watanabe, J, Wakisaka, H, Takada, Y
World journal of surgical oncology. 2020;(1):109
Abstract
BACKGROUND The most common sites of recurrence after liver transplantation for hepatocellular carcinoma (HCC) have been reported to be the liver, lung, bone, and adrenal glands, but there have also been many reports of cases of multiple recurrence. The prognosis after recurrence is poor, with reported median survival after recurrence of HCC ranging from 9 to 19 months. Here, we report a case of long-term survival after recurrence of pharyngeal metastasis following living-donor liver transplantation (LDLT) for HCC within the Milan criteria, by resection of the metastatic region and cervical lymph node dissection. CASE PRESENTATION A 47-year-old man with a Model End-stage Liver Disease (MELD) score of 11 underwent LDLT for HCC within the Milan criteria for liver cirrhosis associated with hepatitis B virus infection, with his 48-year-old elder brother as the living donor. One year and 10 months after liver transplantation, he visited a nearby hospital with a chief complaint of discomfort on swallowing. A pedunculated polyp was found in the hypopharynx, and biopsy revealed HCC metastasis. We performed pharyngeal polypectomy. Two years later, cervical lymph node metastasis appeared, and neck lymph node dissection was performed. Although recurrence subsequently occurred three times in the grafted liver, the patient is still alive 12 years and 10 months after recurrence of pharyngeal metastasis. He is now a tumor-free outpatient taking sorafenib. CONCLUSION It is necessary to recognize that the nasopharyngeal region is a potential site of HCC metastasis. Prognostic improvement can be expected with close follow-up, early detection, and multidisciplinary treatment, including radical resection.
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Is Macroscopic Portal Vein Tumor Thrombosis of HCC Really an Exclusion for Liver Transplantation?
Aydin, C, Yilmaz, S
Journal of gastrointestinal cancer. 2020;(4):1137-1140
Abstract
PURPOSE Hepatocellular carcinoma is a heterogenous group of disease with a spectrum of disease presentations that developed on the setting of liver cirrhosis, although the achievements made in the imaging techniques have enabled the early diagnosis in nearly 60% of the cases in cirrhotic patients. However, hepatobiliary centers and tertiary liver transplant centers have to treat patients with advanced hepatocellular carcinoma with portal venous tumor thrombosis. METHODS In this review, liver transplantation results in hepatocellular carcinoma patients with portal vein tumor thrombosis is reviewed. RESULTS Although historically portal venous tumor thrombosis is considered a contraindication for radical surgical procedures such as liver transplantation, current data suggests that patients with hepatocellular carcinoma and macrovascular invasion can achieve favorable outcomes with liver transplantation provided that strict selection criteria is applied. One of the cornerstones of treatment of these patients is development of locoregional therapy such as transarterial chemo and radioembolizations. Transarterial radioembolization is effective in patients if the pretreatment liver failure is mild and the tumor burden including extension to the portal vein is low. Although data is lacking especially radioembolization could even help physicians to differentiate tumors with favorable biologic characteristics. CONCLUSIONS Therefore, these patients should be subject of multimodality treatment, and liver transplantation should be offered whenever objective and significant response is obtained by locoregional therapies.
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Post-transplantation Outcomes in Patients with PA or MMA: A Review of the Literature.
Yap, S, Vara, R, Morais, A
Advances in therapy. 2020;(5):1866-1896
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Abstract
INTRODUCTION Liver transplantation is recognised as a treatment option for patients with propionic acidemia (PA) and those with methylmalonic acidemia (MMA) without renal impairment. In patients with MMA and moderate-to-severe renal impairment, combined liver-kidney transplantation is indicated. However, clinical experience of these transplantation options in patients with PA and MMA remains limited and fragmented. We undertook an overview of post-transplantation outcomes in patients with PA and MMA using the current available evidence. METHODS A literature search identified publications on the use of transplantation in patients with PA and MMA. Publications were considered if they presented adequate demographic and outcome data from patients with PA or MMA. Publications that did not report any specific outcomes for patients or provided insufficient data were excluded. RESULTS Seventy publications were identified of which 38 were full papers. A total of 373 patients underwent liver/kidney/combined liver-kidney transplantation for PA or MMA. The most typical reason for transplantation was recurrent metabolic decompensation. A total of 27 post-transplant deaths were reported in patients with PA [14.0% (27/194)]. For patients with MMA, 18 post-transplant deaths were reported [11% (18/167)]. A total of 62 complications were reported in 115 patients with PA (54%) with cardiomyopathy (n = 12), hepatic arterial thrombosis (HAT; n = 14) and viral infections (n = 12) being the most commonly reported. A total of 52 complications were reported in 106 patients with MMA (49%) with viral infections (n = 14) and renal failure/impairment (n = 10) being the most commonly reported. CONCLUSIONS Liver transplantation and combined liver-kidney transplantation appears to benefit some patients with PA or MMA, respectively, but this approach does not provide complete correction of the metabolic defect and some patients remain at risk from disease-related and transplantation-related complications, including death. Thus, all treatment avenues should be exhausted before consideration of organ transplantation and the benefits of this approach must be weighed against the risk of perioperative complications on an individual basis.
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Economic Implications of Hepatocellular Carcinoma Surveillance and Treatment: A Guide for Clinicians.
Likhitsup, A, Parikh, ND
PharmacoEconomics. 2020;(1):5-24
Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide, with significant morbidity and associated costs. Treatment allocation depends on the stage of diagnosis; however, resource utilization can be significant across all stages. We aimed to summarize the available data on the cost effectiveness of surveillance of and treatments for HCC in the context of current treatment guidelines. We performed a focused review of studies investigating the economic burden and cost effectiveness of HCC surveillance treatment modalities published between January 2000 and January 2019. The overall economic burden of HCC is increasing in the USA and in several countries worldwide due to its rising incidence and the proliferation of therapies. Liver transplantation is a cost-effective strategy for early-stage HCC treatment in selected patients. In settings where liver transplantation is not available or in patients awaiting transplant, ablative or locoregional therapies are cost effective with increases in quality-adjusted life-years. First-line therapy with sorafenib for advanced stage HCC is cost effective in the treatment of compensated cirrhosis. The cost effectiveness of recently approved systemic therapies for advanced HCC require further investigation. Existing studies have shown that guideline-recommended surveillance techniques and several available therapies for the treatment of HCC are cost effective; however, there are limitations in the literature, including reliance on suboptimal modeling with incomplete/simplified model structure or inadequate inputs. With increasing therapeutic options in patients with HCC, understanding their relative value is critical in designing HCC treatment algorithms.
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It takes a village: primary care of the pediatric liver transplant recipient.
Hassan, S, Ng, VL, Aqul, A
Current opinion in pediatrics. 2019;(5):636-644
Abstract
PURPOSE OF REVIEW Long-term survival is now the rule rather than the exception for infants and children who undergo liver transplantation for end-stage liver disease, metabolic liver conditions and a variety of other indications. Pediatricians and primary care providers play vital roles in the care and management of this patient population. The purpose of this review is to highlight key aspects important to the care of the pediatric liver transplant recipient. RECENT FINDINGS Significant advances in immunosuppressive therapies and surgical techniques have contributed to improved graft and patient survival rates, shifting the focus beyond immediate survival to strategies to minimize comorbidities related to long-term immunosuppression during growing years, attend to patient and parent-reported outcomes and enhance quality of life. A multidisciplinary approach allows for monitoring and surveillance of both routine (growth, nutritional rehabilitation, cognitive development, mental and psychosocial health, contraception and daily activities) and transplant-related (adverse effects of immunosuppression, susceptible infections, extra-hepatic systems, transition from childhood to adolescence to adulthood) themes. SUMMARY Effective communication between the primary care physician and the transplant team is imperative for optimizing best outcomes. The primary care provider should be aware of the multifacet nature of posttransplant management, which includes medication regimens, common complications and infections.