Liver Transplantation in the MELD Era: A Single-Center Experience

Model for Endstage Liver Disease (MELD) score has been used to allocate organs since February 2002. This policy allocates organs to candidates with regard to severity of their underlying liver disease except in the case of hepatocellular carcinoma (HCC) patients. The purpose of this study was to determine the impact of MELD on waiting times, dropout rates, and transplantation rates in all patients awaiting liver transplantation at our center. The records of all patients listed for liver transplantation between May 28, 1999, and February 27, 2004, at the Mayo Clinic, Scottsdale, Arizona, were reviewed. Candidates were grouped by two time periods as pre-MELD or post-MELD based on date of MELD implementation (February 27, 2002). The incidence of deceased donor liver transplantation (DDLT), waiting time to DDLT, dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting for or after DDLT were determined for each group. Three hundred fifty-one patients were listed for liver transplantation (195 pre-MELD, 156 post-MELD) during the study period. HCC patients had an improved rate of transplantation after MELD (pre-MELD, 1.39 persons per year; post-MELD, 3.48 persons per year). In all groups, with the exception of hepatitis C virus, the transplantation rates were the same for both categories. The hepatitis C virus group also had improved transplantation rates in the post-MELD period. HCC candidates under the new allocation policy have an increased incidence of DDLT in our institution. However, this has not disadvantaged patients with non-HCC diagnoses. Thus, the new MELD-based allocation policy has benefited all candidates by allowing more timely transplants.     

Liver Transplantation Services During the Time of COVID-19

The coronavirus disease 2019 (COVID-19) is associated with high morbidity and mortality, prompting overwhelmed hospital systems to reallocate resources to those stricken with the disease. In response, many liver transplantation programs unexpectedly came to an abrupt halt, significantly affecting the lives of living donors and recipients around the world. As the risk-benefit scale of liver transplantation has changed in the era of COVID-19, it is prudent to understand the impact of COVID-19 on those with underlying liver disease and those in need of a liver transplant. In this review, we discuss recommendations put forth by hepatology and transplant societies, summarize results from emerging studies, and propose strategies to appropriately risk stratify patients prior to transplantation.     

Liver transplantation in Japan: Registry by the Japanese Liver Transplantation Society

As of 31 December 2017, a total of 9242 liver transplants have been carried out in 67 institutions in Japan. There were 447 deceased donor transplants (444 from heart‐beating donors and 3 from non‐heart‐beating donors) and 8795 living‐donor transplants. The annual total of liver transplants in 2017 was 416 (69 deceased donor transplants and 347 living‐donor transplants). The most frequent indication was cholestatic disease, followed by neoplastic disease and hepatocellular disease. In terms of hepatocellular disease in 2017, cirrhosis due to hepatitis C and B decreased (13 and 8, respectively), whereas alcoholic cirrhosis markedly increased (32). Patient survival following transplantation from heart‐beating donor (444 transplants: 1 year, 89.1%; 3 years, 85.2%; 5 years, 82.9%; 10 years, 75.4%; 15 years, 70.7%) was similar to that from living‐donor (8794 transplants: 1 year, 85.0%; 3 years, 80.9%; 5 years, 78.5%; 10 years, 73.2%; 15 years, 68.5%; 20 years, 65.7%; 25 years, 64.6%). Graft survival was very much the same as patient survival (heart‐beating donor: 1 year, 88.4%; 3 years, 84.5%; 5 years, 82.2%; 10 years, 74.7%; 15 years, 70.1%; living donor: 1 year, 84.3%; 3 years, 79.9%; 5 years, 77.3%; 10 years, 71.4%; 15 years, 66.3%; 20 years, 63.3%; 25 years, 61.9%). Survival data are reported according to age and sex of recipient, indication, age and sex of donor, ABO compatibility, and other factors.     

Hepatocellular Carcinoma: Downstaging to Liver Transplantation as Curative Therapy

Hepatocellular carcinoma (HCC) ranks among the leading cancer-related causes of morbidity and mortality worldwide. Downstaging of HCC has prevailed as a key method to curative therapy for patients who present with unresectable HCC outside of the listing criteria for liver transplantation (LT). Even though LT paves the way to lifesaving curative therapy for HCC, perpetually severe organ shortage limits its broader application. Debate over the optimal protocol and assessment of response to downstaging treatment has fueled immense research activity and is pushing the boundaries of LT candidate selection criteria. The implicit obligation of refining downstaging protocol is to ensure the maximization of the transplant survival benefit by taking into account the waitlist life expectancy. In the following review, we critically discuss strategies to best optimize downstaging HCC to LT on the basis of existing literature.     

Management of Hepatitis C Before and After Liver Transplantation in the Era of Rapidly Evolving Therapeutic Advances

Management of hepatitis C (HCV) in liver transplantation (LT) population presents unique challenges. Suboptimal graft survival in HCV+ LT recipients is attributable to universal HCV recurrence following LT. Although eradication of HCV prior to LT is ideal for the prevention of HCV recurrence it is often limited by adverse events, particularly in patients with advanced cirrhosis. Antiviral therapy in LT candidates needs careful monitoring, and prophylaxis with HCV antibodies is ineffective. Early antiviral therapy after LT has been investigated, but no clear benefit has been demonstrated. Protocol liver biopsy is generally recommended in HCV+ LT recipients, and antiviral therapy can be considered in those with severe/progressive HCV recurrence. Sustained virological response (SVR) can be achieved in approximately 30% of LT recipients with pegylated interferon/ribavirin (PEG-IFN/RBV) with survival benefit, but adverse effects are common. Favorable patient characteristics for response to therapy include non-1 genotype, previously untreated, low baseline HCV-RNA, and donor IL28B genotype CC. Direct acting antiviral (DAA)-based triple therapy is associated with higher rates of SVR, but with similar or slightly higher rates of side effects, and immunosuppressive regimens need to be closely monitored and adjusted during the treatment period. Notably, the safety and efficacy of HCV treatment are very likely to improve with newer generation DAA. The benefit of immunosuppressive strategy on the natural history HCV recurrence has not been well elucidated. Based upon available evidence, cyclosporine A (CSA), mycophenolate mofetil (MMF), and sirolimus appear to have a neutral or small beneficial impact on HCV recurrence. Donor interleukin 28 B (IL28B) polymorphisms appear to impact the course and treatment outcomes in recurrent HCV. Retransplantation should be considered for patients with reasonable survival probability.     

Prioritization for liver transplantation using the MELD score in Chile: Inequities generated by MELD exceptions.: A collaboration between the Chilean Liver Transplant Programs,the Public Health Institute and the National Transplant Coordinator

Introduction and aimThe MELD score has been established as an efficient and rigorous prioritization system for liver transplant (LT). Our study aimed to evaluate the effectiveness of the MELD score as a system for prioritization for LT, in terms of decreasing the dropout rate in the waiting list and maintaining an adequate survival post-LT in Chile.Materials and methodsWe analyzed the Chilean Public Health Institute liver transplant registry of candidates listed from October 15th 2011 to December 31st 2014. We included adult candidates (>15 years old) listed for elective cadaveric LT with a MELD score of 15 or higher. Statistical analysis included survival curves (Kaplan–Meier), log-rank statistics and multivariate logistic regression.Results420 candidates were analyzed. Mean age was 53.6 ± 11.8 years, and 244 were men (58%). Causes of LT included: Liver cirrhosis without exceptions (HC) 177 (66.4%); hepatocellular carcinoma (HCC) 111 (26.4%); cirrhosis with non-HCC exceptions 102 (24.3%) and non-cirrhotic candidates 30 (7.2%). LT rate was 43.2%. The dropout rate was 37.6% at 1-year. Even though the LT rate was higher, the annual dropout rate was significantly higher in cirrhotic candidates (without exceptions) compared with cirrhotics with HCC, and non-HCC exceptions plus non-cirrhotic candidates (47.9%; 37.2% and 24.2%, respectively, with p = 0.004). Post-LT survival was 84% per year, with no significant differences between the three groups (p = 0.95).ConclusionPrioritization for LT using the MELD score system has not decreased the dropout rate in Chile (persistent low donor's rate). Exceptions generate inequities in dropout rate, disadvantaging patients without exceptions.     

Neuropsychiatric Complications of Liver Transplantation

Liver transplantation (LT) is the best treatment for end-stage liver diseases but it entails a high incidence of neuropsychiatric complications. These may be related to the operation or occur postoperatively, usually within the first month. The occurrence of neurological problems after LT increases the risk of mortality. The etiology of such complications is various, often multifactorial, immunosuppression being one of the most important causes. Immunosuppressive drugs may cause a wide spectrum of neuropsychiatric complications—mainly affecting the CNS—ranging from mild to severe disorders. A survey of the most frequent disorders is presented. In the management of liver-transplanted patients, the awareness of potential neurological and psychiatric problems is crucial for patients' survival, since it assists clinicians in prevention, prompt diagnosis, and treatment.     

体外静脉－静脉转流在肝移植手术中的应用

使用离心泵行体外静脉－静脉（Ｖ－Ｖ）转流的技术，成功地应用于２例同种异体原位肝移植手术。结果表明：（１）肝移植手术使用Ｖ－Ｖ转流，腹腔内脏及下肢血液循环得到保证，避免了无肝期酸硷平衡失调和开放循环后电解质的紊乱；（２）使用离心泵能较好地控制转流期间体内外血流量的平衡，维持血流动力学的稳定；（３）血液变温器的使用可防止转流中及术后低温；（４）部分肝素化使激活凝血时间（ＡＣＴ）控制在２００秒左右，既可预防转流中循环管道系统凝血，又可避免因全身肝素化使手术出血增加。     

Hepatopulmonary Syndrome and Liver Transplantation: A Recent Review of the Literature

A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal hypertension, intrapulmonary vascular dilatations, and increased alveolar-arterial oxygen gradient. Prevalence varies according to various study groups from 4%–47%. While the most common presenting symptom of HPS is dyspnea, it is usually asymptomatic, and thus all liver transplant candidates should be screened for its presence. Pulse oximetry is a useful screening method, but arterial blood gas examination is the gold standard. If there is an abnormal P (A-a)O₂ gradient, microbubble transthoracic echocardiography should be done for diagnosis. Outcome is unpredictable, and there is currently no effective medical therapy. The only effective therapy is considered to be liver transplantation. Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.     

体外静脉－静脉转流在肝移植手术中的应用

使用离心泵行体外静脉－静脉（Ｖ－Ｖ）转流的技术，成功地应用于２例同种异体原位肝移植手术。结果表明：（１）肝移植手术使用Ｖ－Ｖ转流，腹腔内脏及下肢血液循环得到保证，避免了无肝期酸硷平衡失调和开放循环后电解质的紊乱；（２）使用离心泵能较好地控制转流期间体内外血流量的平衡，维持血流动力学的稳定；（３）血液变温器的使用可防止转流中及术后低温；（４）部分肝素化使激活凝血时间（ＡＣＴ）控制在２００秒左右，既可预防转流中循环管道系统凝血，又可避免因全身肝素化使手术出血增加。     

Hepatocellular Carcinoma and Liver Transplantation: State of the Art

Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in chronic liver disease and cirrhosis. The incidence of HCC is growing worldwide.With respect to any other available treatment for liver cancer, liver transplantation (LT) has the highest potential to cure. LT allows for removal at once of both the tumor (“seed”) and the damaged-hepatic tissue (“soil”) where cancerogenesis and chronic liver disorders have progressed together. The Milan criteria (MC) have been applied worldwide to select patients with HCC for LT, yielding a 4-year survival rate of 75%. These criteria represent the benchmark for patient selection and are the basis for comparison with any other suggested criteria.However, MC are often considered to be too restrictive, and recent data show that between 25% and 50% of patients with HCC are currently transplanted beyond conventional indications. Consequently, any unrestricted expansion of selection criteria will increase the need for donor organs, lengthen waiting periods, increase drop-out rates, and impair outcomes on intention-to-treat analysis. Management of HCC recurrence after LT is challenging. There are a few reports available regarding the safety and efficacy of sorafenib for HCC recurrence after LT, but the data are heterogeneous. A multi-center prospective randomized controlled trial comparing placebo with sorafenib is advised. Alternatively, a meta-analysis of patient survival with sorafenib for HCC recurrence after LT could be helpful to characterize the therapeutic benefit and safety of sorafenib.Here, we review the use of LT for HCC, with particular emphasis on the selection criteria for transplantation in patients with HCC and management of HCC recurrence after LT.     

Ethnic Differences in Hepatocellular Carcinoma: Implications for Liver Transplantation

Liver transplantation (LT) as a treatment for Hepatocellular Carcinoma (HCC) provides excellent outcomes if restricted to patients who meet the Milan criteria (MC). The aim of this study was to evaluate the influence of ethnicity on eligibility for LT based on the MC. This is a retrospective cohort study of patients diagnosed with HCC at our institution between January 2000 and September 2005. We identified 169 patients, of whom 135 were male (80%), 108 were Caucasian (64%), 29% were African American (AA) and 7% were of other ethnicity. Eighty two patients (49%) met the MC at diagnosis. Age, gender, severity of liver disease or insurance status was not predictive of meeting MC at diagnosis. Ethnicity was the only significant predictor for failure to meet MC. Significantly fewer Caucasians exceeded the MC compared to AA (44 vs. 71%; P = 0.0015). Conclusion AA are more likely to present with HCC that exceeds the MC.     

Neuropsychiatric Complications After Liver Transplantation: Role of Immunosuppression and Hepatitis C

Neuropsychiatric complications are an important source of morbidity following orthotopic liver transplantation. Etiology of liver disease and type of immunosuppression are possible related factors. The aim of this study was to describe the prevalence of neuropsychiatric complications after liver transplantation, the role of immunosuppression, and the association between these and specific liver diseases such as hepatitis C. One hundred twenty-eight patients with liver transplants were studied. Tacrolimus was the primary immunosuppressant in 101 patients and cyclosporine in 27 patients. Seventy-five complications in 49 patients (38.2%) were reported. In 43 patients, the etiology was associated with immunosuppression: 36 on tacrolimus and 7 on cyclosporine (P = 0.34). Seventeen and four-tenths percent of patients with hepatitis C and 4.6% of patients without hepatitis C developed depression (P = 0.02). There is no difference between types of primary immunosuppression and neuropsychiatric complications. There is a significantly greater incidence of depression in patients transplanted for hepatitis C.