Candidates For Orthotopic Liver Transplantation Research Articles

Liver Stereotactic Body Radiation Therapy (SBRT) to Downstage Patients with Hepatocellular Carcinoma prior to Liver Transplant

Orthotopic liver transplantation (OLT) marks the most successful treatment for hepatocellular carcinoma (HCC) patients meeting Milan criteria. The process of reducing the disease burden of HCC patients not currently meeting criteria for OLT with local therapy is referred to as "downstaging" and has proven to be a feasible approach. RTOG 1112 recently demonstrated the efficacy and acceptable toxicity of liver SBRT for treating HCC. However, limited data currently exists describing the efficacy of SBRT for downstaging HCC patients and facilitating OLT. A single institution IRB approved prospective liver SBRT registry was surveyed for all patients outside of Milan criteria (1 lesion >5 cm; 2-3 lesions >3 cm) without vascular invasion or extrahepatic disease. Patients felt least likely to become OLT candidates with downstaging (age >80, >4 lesions, lesion >12 cm) were excluded. The primary endpoints were downstaging and OLT. Secondary endpoints were time to transplant, local control (LC), recurrence free survival (RFS) and overall survival (OS). A total of 38 HCC patients with a median age of 65 years (range 28 - 80) met inclusion criteria. Median follow up was 14 months (IQR 3 - 35). At baseline, median KPS was 80 (range 60 - 100) with 16 Child-Pugh (CP) A (42%), 13 CP B (34%), and 9 CP C patients (24%). All patients were outside of Milan criteria and 25 patients (66%) were outside of UCSF criteria at time of SBRT. No patients had extrahepatic disease or vascular invasion. Median number of lesions, largest tumor size, and total sum of lesions were 2 (range 1 - 4), 5.0 cm (IQR, 4.0 - 6.5), and 6.6 cm (IQR 5.9 - 9.2), respectively. Prior to SBRT, 22 patients (58%) had received non-SBRT local therapy. At time of SBRT a variety of dose fractionation schedules were selected with a median BED10 of 78 (IQR 62 - 100). Concurrent sorafenib was used in 2 patients (8%). Following completion of SBRT, 21 patients (55%) were successfully downstaged at a median 3.0 months (IQR 1.9 - 6.1) after treatment, most frequently secondary to decrease in size of the largest lesion (86%). Twelve patients (32%) proceeded to undergo OLT at a median 7 months (IQR 3 - 14) after SBRT and 105 days (IQR 18 - 344) following successful downstaging. Of the 25 patients initially exceeding UCSF criteria, 7 (28%) underwent OLT. Among those receiving OLT, 5 patients (42%) remain alive without evidence of disease, 3 patients (25%) have recurred, 3 patients (33%) died within 2 years from transplant complications, and 1 patient (8%) died from an unrelated cause. LC at 2 years was 83%. Median RFS and OS for the overall cohort were 7 months (95% CI 0 - 21) and 24 months (95% CI 11 - 36), respectively. Among the transplant recipients, the median OS was 37 months (95% CI 30 - 44) compared to 15 months (95% CI 6 - 23) among those not receiving transplant. With careful patient selection, liver SBRT serves as a feasible downstaging method to facilitate OLT in HCC patients.

Portopulmonary Hypertension: An Updated Review.

Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.

Cardiology Assessment of Patients Undergoing Evaluation for Orthotopic Liver Transplantation

<h2>Abstract</h2> Orthotopic liver transplantation (OLT) is a viable treatment option for end-stage liver disease. Significant perioperative stress is placed on the cardiovascular system because of hemodynamic changes and the length of the operation. Diagnosis and treatment of cardiovascular disease before OLT are imperative to ensure favorable outcomes. Considerable variability exists among practitioners caring for these patients. Institutions tailor their protocols on the basis of local and historical practices, the preferences of the cardiologists, and the OLT team, and algorithms are not often revised or updated on the basis of the available evidence. In collaboration with cardiology and hepatology experts from leading OLT centers, we sought to examine the diagnostic cardiovascular workup of OLT candidates, including a review of the available literature on the diagnostic modalities used to screen cardiovascular disease before OLT. We advocate an emphasis on noninvasive methods to assess cardiovascular risk with reserved use of invasive risk stratification in select patients.

Physical Effects, Safety and Feasibility of Prehabilitation in Patients Awaiting Orthotopic Liver Transplantation, a Systematic Review.

Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically "frail" and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51-61years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%-90% in unsupervised-to >94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population.

QuantiFERON-TB gold plus in liver transplant candidates: single-center experience

Background/Objectives: Latent tuberculosis infection (LTBI) screening prior to orthotopic liver transplant (OLT) is essential. The data on QuantiFERON-TB -Gold Plus (QFT-Plus) in OLT candidates is scarce. Methods: QFT-Plus results performed prior to transplant among OLT recipients transplanted between 4/2019 and 8/2020 were evaluated. Previous QFT-Gold In-Tube (QFT-GIT) results were obtained, if available, to evaluate for discordant results. The infectious diseases (ID) team plan for those with positive or indeterminate QFT-Plus was obtained. Results: We assessed 170 OLT recipients. QFT-Plus was performed in 124(73%) patients [8(6%) were positive, 20(16%) indeterminate and 96(77%) negative]. Nine (45%) of the QFT-Plus-indeterminate patients converted to negative. Twenty-one (17%) of the patients that were tested with QFT-Plus were previously tested with QFT-GIT [4(21%) of them had discordant results]. There were no differences in the survival and biopsy-proven rejection at 6 months post-transplant between QFT-Plus-positive and QFT-Plus-negative patients. ID team recommended isoniazid 300mg daily for 9 months for 7(88%) and 9(45%) patients with positive and indeterminate QFT-Plus, respectively. Conclusions: QFT-Plus appears to be appropriate for LTBI diagnosis in OLT candidates. In our cohort, indeterminate QFT-Plus is common and QFT-Plus conversion from indeterminate to negative is frequent. In the presence of risk factors, it might be wise to treat patients with indeterminate QFT-Plus.

Comparison of Coronary Artery Calcium Scoring with Dobutamine Stress Echo for Detection of Coronary Artery Disease Before Liver Transplantation.

BackgroundDobutamine stress echocardiography (DSE) is commonly used for cardiovascular assessment before orthotopic liver transplantation (OLT). The coronary artery calcium score (CACS) is a useful screening tool for coronary artery disease (CAD). We aimed to compare the sensitivity and specificity of DSE and CACS for CAD in OLT candidates.Material/MethodsA total of 265 of the 1589 patients who underwent OLT at our center between 2008 and 2019 had preoperative coronary angiography (CAG). Of these, 173 had DSE and 133 had a CT scan suitable for CACS calculation within 1 year of OLT. Patients with a nondiagnostic DSE were excluded (n=100). Two reviewers evaluated CACS on CT scans. The sensitivity/specificity of DSE and CACS for detection of angiographically significant CAD were calculated for patients with both tests (n=36).A separate analysis compared the sensitivity/specificity of a diagnostic DSE (n=73) and CACS (n=133) against CAG for all patients with either test.ResultsSensitivity and specificity were 57.1% and 89.7%, respectively, for DSE, compared with 71.4% and 62.1% for CACS at ≥100 Agatston score. For the analysis of all patients with either test, the sensitivity/specificity of DSE for detection of CAD and CACS were 30.8% and 85.0% and 80.0% and 62.8%, respectively. On ROC analysis, CACS was a satisfactory predictor of obstructive CAD (AUC, 0.76±0.06, 95% CI, 0.66–0.87; P<0.001).ConclusionsCACS may be an important tool for cardiovascular assessment in patients undergoing OLT. DSE was nondiagnostic in a large percentage of OLT candidates, limiting its use in this population.

Diagnostic Yield of Coronary Angiography in Asymptomatic Orthotopic Liver Transplantation Candidates

BackgroundThe ideal cardiac risk stratification strategy for orthotopic liver transplantation (OLT) is unknown. Our institution performed coronary angiography for asymptomatic OLT candidates at high risk for CAD: ≥65 years of age, diabetic and ≥55 years of age or diagnosed ≥5 years, abnormal stress test, or at the discretion of the OLT committee. MethodsThe analysis included 301 consecutive, asymptomatic OLT candidates who underwent coronary angiography. The primary outcome was the prevalence of obstructive CAD. ResultsAt 2-year follow-up, OLT was performed in 44.9%, and 42.2% died. The prevalence of obstructive CAD, involvement of the proximal or mid LAD, and 3-vessel CAD were 10.3%, 6.6%, and 0.7%, respectively. Percutaneous and surgical revascularization were performed in 7.0% and 1.3%, respectively. Stress test was performed in 54.8%. The sensitivity and specificity of stress testing were 0% and 87.1%, respectively. The negative and positive predictive values of stress testing were 91.4% and 0%, respectively. Chest computed tomography (CT) was performed in 83.1%. Moderate or severe coronary artery calcification (CAC) was present in 47.8%. The sensitivity and specificity of moderate or severe CAC were 88.9% and 57.3%, respectively. The negative and positive predictive values of moderate or severe CAC were 97.7% and 20.2%, respectively. Multivariate analysis demonstrated that CAC was an independent predictor of obstructive CAD (HR 10.7; 95% CI 3.2–37.9; p < 0.001). ConclusionsThe prevalence of obstructive CAD in asymptomatic OLT candidates at high risk was uncommon. Alternative diagnostic strategies may be preferred to coronary angiography.

Coronary Computed Tomography Angiography Demonstrates a High Burden of Coronary Artery Disease Despite Low-Risk Nuclear Studies in Pre-Liver Transplant Evaluation.

We investigated the presence and severity of coronary artery disease (CAD) in orthotopic liver transplantation (OLT) candidates using coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA) as compared with the prevalence of normal and abnormal single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). A total of 140 prospective OLT candidates without known CAD underwent coronary artery calcium (CAC) scans with (n=77) or without CCTA and coronary computed tomography angiography-derived fractional flow reserve (FFRCT ; n=57) using a dual-source computed tomography (CT) and were followed for 2.6±1.4years. Coronary plaque was quantified using the segment-involvement score (SIS) and segment stenosis score (SSS). The mean age was 59±6years, and 65.0% of patients were male. Mean Agatston CACS was 367±653, and 15.0% of patients had CACSs of 0; 83.6% received a SPECT MPI, of which 95.7% were interpreted as normal/probably normal. By CCTA, 9.1% had obstructive CAD (≥70% stenosis), 67.5% had nonobstructive CAD, and 23.4% had no CAD. Nonobstructive CAD was diffuse with mean SIS 3.0±2.9 and SSS 4.5±5.4. Only 14 patients had high risk-findings (severe 3v CAD, n=4, CACS >1000 n=10) that prompted X-ray angiography in 3 patients who had undergone CCTA, resulting in revascularization of a high-risk obstruction in 1 patient who had a normal SPECT study. Patients with end-stage liver disease have a high prevalence of nonobstructive CAD by CCTA, which is undiagnosed by SPECT MPI, potentially underestimating cardiovascular risk. Deferring X-ray angiography unless high-risk CCTA findings are present is a potential strategy for avoiding unnecessary X-ray angiography.

Cholecystitis in Patients Undergoing Liver Transplantation: A Five-Year Analysis of Incidence, Causes, and Impact.

There is a paucity of data on cholecystitis in liver transplant candidates (LTC), including the incidence of the cholecystitis and the associated outcomes in this patient population. As such, this study examines the incidence of and factors associated with cholecystitis in the high-acuity LTC population, as well as the association between cholecystitis and graft and patient survival. Liver transplant candidates undergoing orthotopic liver transplantation (OLT) at a large transplant center from January 1, 2012 to December 31, 2016 were included in the initial analysis. Surgical pathology reports were examined for the presence of cholecystitis. Univariate analyses were performed to determine the association between patient factors and cholecystitis. Kaplan-Meier analyses and multivariate Cox proportional hazard models were performed to examine the association between cholecystitis and graft and patient survival. Of the 405 patients in the final study population, 267 (65.9%) had no cholecystitis, 21 (5.2%) had acute cholecystitis, and 117 (28.9%) had chronic cholecystitis. The presence of cholecystitis was associated with preoperative WBC, sepsis within 10 days prior to transplant, location prior to transplant, and total length of stay. While this study revealed no association between cholecystitis and graft or patient survival, it also suggests that cholecystitis is under-recognized in high-model end-stage liver disease (MELD) OLT candidates. Therefore, a high index of suspicion for cholecystitis may be helpful in caring for this vulnerable patient population; however, further studies must be performed to determine the optimal management of cholecystitis in these patients.

Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension: Erratum.

Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension: Erratum.

P1552 Dobutamine stress echocardiography as a screening tool for coronary artery disease detection in patients with end-stage liver disease awaiting transplantation

Abstract Indroduction The prevalence of coronary artery disease (CAD) in patients with end-stage liver disease (ESLD) is unknown. However, patients with CAD and ESLD are at increased perioperative risk during liver transplantation. Currently there is no standard protocol for CAD screening in patients with ESLD awaiting orthotopic liver transplantation. We present preliminary data of our experience with dobutamine stress echocardiography in those patients. Methods Fifty patients (26 males, mean age of 59 years) with end-stage liver disease awaiting transplantation and no history of CAD underwent dobutamine stress echo. The etiology of their hepatic disease was hepatitis B (6 patients), hepatitis C (6 patients), primary billiary cirrhosis (10 patients), sclerosing cholangitis (8 patients), alcoholic hepatitis (10 patients) and polycystic disease (2 patients), while 8 patients had end-stage liver disease of unknown etiology. Twenty-six patients had risk factors for CAD. Eighteen patients had one risk factor and only 8 patients had 2 risk CAD factors. All patients received dobutamine infusion (at escalating doses of 5, 10, 20, 30 and 40 μgr/kg/min), targeting a 85% or more of their age-predicted maximum heart rate. Atropine was administered in 6 patients. Results All 50 patients had normal inotropic response of left ventricle, without evidence of ischemia (100% studies were negative for ischaemia). No patient had major intolerance to dobutamine. Eight patients experienced hypotension responded to infusion of normal saline. One patient developed paroxysmal supraventricular tachycardia, which was treated with intravenous bolus of adenosine. No patient had cardiovascular events during a follow-up ranging from 1 to 18 months. Twelve patients underwent liver transplantation without any periprocedural cardiovascular events. Conclusions Dobutamine stress echocardiography is a safe and reliable method for CAD screening in the labile patients with ESLD who are candidates for orthotopic liver transplantation. It seems that the prevalence of significant CAD in this high-risk population is low.

Neoadjuvant conformal radiotherapy before liver transplantation for hepatocellular carcinoma: a propensity score matched analysis of postoperative morbidity and oncological results.

Aim: To assess neoadjuvant conformal radiotherapy (CRT) before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) not suitable for standard locoregional treatments. Methods: Patients undergoing OLT for HCC with or without prior CRT were compared using 1:3 propensity score matching. Results: After propensity score matching, 23 patients with CRT were compared with 66 control subjects. Severe morbidity rate was 34.8 versus 24.2% in the CRT and non-CRT groups (p=0.289). Complete pathological response was observed in 47.8% of CRT-targeted nodules. The 1-/3-/5-year disease-free survivals were 77.3, 77.3 and 68.7% in the CRT group versus 85.4, 68.0 and 61.7% in the non-CRT group (p=0.829). Conclusion: Conformal radiotherapy represents a satisfactory neoadjuvant therapy for OLT candidates not suitable for standard HCC locoregional therapies.

Evaluation and treatment of acetaminophen toxicity.

A review of the typical clinical course, diagnosis and treatment of acetaminophen toxicity is provided. For an acute overdose, most adults must ingest about 12g or more acetaminophen (APAP) before risk of serious hepatotoxicity is of concern. A nomogram of serum APAP concentration vs hours post-ingestion can assist in determining risk of liver injury and need for treatment. However, histories concerning the time of ingestion and the amount of drug ingested are usually unreliable. Peak serum transaminase activities usually occur 48-96h after acute ingestion. It is possible for patients to present in liver failure days after ingestion with undetectable serum APAP concentrations. Patients who have chronically ingested excessive APAP doses and develop hepatotoxicity usually present with such, and renal failure is more common in this population. Current treatment centers on administration of N-acetylcysteine (NAC) to prevent hepatotoxicity, though NAC also improves outcomes in patients who present with acute liver failure. When given early after APAP ingestion, NAC's main mechanism of action is to maintain intracellular glutathione stores so to detoxify the electrophilic APAP metabolite, NAPQI. NAC is generally well-tolerated when given intravenously, with the main concern being anaphylactoid reactions. These reactions usually occur during loading doses and are easily treated with discontinuation of the NAC infusion, administration of antihistamines, and then restarting the loading dose at a slower infusion rate. There is concern that current NAC dosing is not large enough to adequately treat large APAP ingestions. Patients with acute liver failure may be candidates for orthotopic liver transplantation.

Hydrothorax in liver disease: pathogenesis, diagnosis, treatment.

The review discusses the current understanding of the pathogenesis, diagnostic methods and principles of treatment of hepatic hydrothorax. To search for scientific articles, we used PubMed database, Google Scholar search system, Cochrane systematic reviews, and reference lists. The corresponding objectives of the review of the publication were selectedfor the periodfrom 1994 to 2016 by the terms: «cirrhosis of the liver», «portal hypertension», «hepatic hydrothorax», «pathogenesis», «diagnosis», «treatment». Inclusion criteria were limited to uncomplicated hydrothorax in patients with liver cirrhosis. Analysis of the literature data showed that, despite the success of modern Hepatology, the presence of hepatic hydrothorax is associated with poor prognosis and high mortality. The majority ofpatients suffering from it are candidates for orthotopic liver transplantation. In normal clinical practice, the key to successful management of such patients may be stratification of the risk of adverse outcome and the definition of individual treatment tactics. Pathogenetically sound approach to the choice of pharmacotherapy, as well as the optimization of minimally invasive treatments will improve the quality of life and increase the survival of this category ofpatients.

Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension.

Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable. Any significant right ventricular dysfunction or dilatation along with an elevation in estimated pulmonary pressures usually triggers further investigation with right heart catheterization. The mainstays of therapy of POPH are vasodilators that are used in pulmonary arterial hypertension. They include monotherapy or combination therapy with prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors/guanylate cyclase stimulator. Limited evidence from smaller studies and case series suggests that a timely diagnosis of POPH and the early initiation of treatment improve patient outcomes, whether or not OLT is ultimately undertaken. Given the historically high perioperative mortality rate of more than 35%, POPH remains a contraindication to OLT unless it is treated and responsive to vasodilator therapy. We review the current literature and International Liver Transplant Society practice guidelines (2016) for the latest in understanding POPH, its pathogenesis, diagnosis, modern pharmacological treatment, indications, and contraindications for OLT, as well as perioperative management.

Cardio-hepatic risk assessment by CMR imaging in liver transplant candidates.

The preoperative workup of orthotopic liver transplantation (OLT) patients is practically complex given the need for multiple imaging modalities. We recently demonstrated in our proof-of-concept study the value of a one-stop-shop approach using cardiovascular MRI (CMR) to address this complex problem. However, this approach requires further validation in a larger cohort, as detection of hepatocellular carcinoma (HCC) as well as cardiovascular risk assessment is critically important in these patients. We hypothesized that coronary risk assessment and HCC detectability is acceptable using the one-stop-shop CMR approach. In this observational study, patients underwent CMRI evaluation including cardiac function, stress CMR, thoracoabdominal MRA, and abdominal MRI on a standard MRI scanner in one examination. Over 8years, 252 OLT candidates underwent evaluation in the cardiac MRI suit. The completion rates for each segment of the CMR examination were 99% for function, 95% completed stress CMR, 93% completed LGE for viability, 85% for liver MRI, and 87% for MRA. A negative CMR stress examination had 100% CAD event-free survival at 12months. A total of 63 (29%) patients proceeded to OLT. Explant pathology confirmed detection/exclusion of HCC. This study further defines the population suitable for the one-stop-shop CMR concept for preop evaluation of OLT candidates providing a road map for integrated testing in this complex patient population for evaluation of cardiac risk and detection of HCC lesions.

Hepatic hydrothorax: An update and review of the literature.

This review considers the modern concepts of pathogenesis, diagnostic methods, and treatment principles of hepatic hydrothorax (HH). HH is the excessive (> 500 mL) accumulation of transudate in the pleural cavity in patients with decompensated liver cirrhosis but without cardiopulmonary and pleural diseases. It causes respiratory failure which aggravates the clinical course of liver cirrhosis, and the emergence of spontaneous bacterial pleural empyema may be the cause of death. The information was collected from the PubMed database, the Google Scholar retrieval system, the Cochrane reviews, and the reference lists from relevant publications for 1994-2016 using the keywords: “liver cirrhosis”, “portal hypertension”, “hepatic hydrothorax”, “pathogenesis”, “diagnostics”, and “treatment”. To limit the scope of this review, only articles dealing with uncomplicated hydrothorax in patients with liver cirrhosis were included. The analysis of the data showed that despite the progress of modern hepatology, the presence of HH is associated with poor prognosis and high mortality. Most patients suffering from it are candidates for orthotopic liver transplantation. In routine clinical practice, stratification of the risk for an adverse outcome and the subsequent determination of individual therapeutic strategies may be the keys to the successful management of the patient’s condition. The development of pathogenetic pharmacotherapy and optimization of minimally invasive treatment will improve the quality of life and increase the survival rate among patients with HH.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria

Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N=214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein <400ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for transplantation.

Utility of Dobutamine Stress Echocardiography in Cardiac Risk Stratification of Patients Undergoing Orthotopic Liver Transplantation.

Cardiovascular diseases are a major cause of morbidity and mortality in patients after orthotopic liver transplantation (OLT). This review includes major original articles published in the English-language literature of patients who underwent dobutamine stress echocardiography (DSE) before OLT for cardiac risk stratification. Of a total of 10 original articles (total 1699 patients undergoing DSE), 6 studies used DSE to predict major adverse cardiac events (MACE) in patients undergoing OLT and 4 reported the role of DSE in coronary artery disease (CAD) prediction in patients with end-stage liver disease. The composite incidence of MACE was 11.4%. In predicting postoperative MACE, DSE had a composite sensitivity of 0.12 (95% CI, 0.07-0.19), a specificity of 0.96 (95% CI, 0.94-0.97), a positive predictive value (PPV) of 0.26 (95% CI, 0.16-0.38), and a negative predictive value (NPV) of 0.89 (95% CI, 0.88-0.91). The presence of known CAD in a patient was shown to increase the risk of cardiac events after OLT significantly in three of six studies. The average prevalence of CAD was 14.4%. In predicting CAD, DSE had a composite sensitivity of 0.47 (95% CI, 0.32-0.62), specificity of 0.74 (95% CI, 0.68- 0.79), PPV of 0.23 (95% CI, 0.15-0.33), and NPV of 0.89 (95% CI, 0.84-0.93). This review emphasizes the need for standardizing cardiac risk stratification protocol to screen and prevent cardiac morbidity after OLT, standardizing MACE definition to allow more uniform reporting, and the need for safer and efficacious alternatives to DSE in the evaluation of OLT candidates.

Portopulmonary hypertension: Updated review

Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain.