End-stage Liver Disease Patients Research Articles

Factors Affecting Intraoperative Changes in Regional Cerebral Oxygen Saturation in Patients Undergoing Liver Transplantation

BackgroundRegional oxygen saturation (rSO2) is a sensitive marker of cerebral hypoperfusion during liver transplantation. However, bilirubin absorbs near-infrared light, resulting in falsely low rSO2 values. We sought to determine whether rSO2 values vary in response to bilirubin concentrations during liver transplantation and to assess whether rSO2 changes were associated with factors reflecting cerebral oxygen delivery in patients with hyperbilirubinemia. MethodsMeasurements of rSO2 values continuous cardiac output (CO), mean arterial pressure, central venous pressure, body temperature, arterial blood gas analysis, and laboratory parameters were simultaneously performed at 1 hour after the surgical incision (baseline) and at 3 predetermined times during the anhepatic and neohepatic phases in 95 end-stage liver disease patients including 67 males of Child A/B/C/29/29/37 categories respectively. Relationships between changes in parameters were evaluated by correlation and multivariate regression analyses. ResultsThe 273 measurements revealed changes in rSO2 (range, −18% to 40%) to correlate significantly with alterations in hemoglobin (Hb), serum glucose, lactate, prothrombin time, pH, partial arterial CO2 pressure (PaCO2), and CO, but not with serum total bilirubin (TB). Multivariate linear regression analysis revealed that changes in Hb, CO, PaCO2, and pH were independent of rSO2 changes during liver transplantation. ConclusionsOur findings showed that rSO2 changes were independently associated with factors reflecting cerebral oxygen delivery, such as Hb, CO, PaCO2, and pH, whereas rSO2 values did not correlate with changes in bilirubin concentrations, indicating that rSO2 changes reveal cerebral oxygen balance regardless of TB levels among patients undergoing liver transplantation.

Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients

Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, P<0.001). The frequency of CD4+IL-17+ cells in peripheral blood was positively correlated with the rejection activity index (r=0.79, P=0.0002). Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

Predicting in-hospital mortality among critically ill patients with end-stage liver disease

PurposeCritically-ill patients with end-stage liver disease (ESLD) are at high risk for death during intensive care unit hospitalization, and currently available prognostic models have limited accuracy in this population. We aimed to identify variables associated with in-hospital mortality among critically ill ESLD patients and to develop and validate a simple, parsimonious model for bedside use. Materials and methodsWe performed a retrospective chart review of 653 intensive care unit admissions for ESLD patients; modeled in-hospital mortality using multivariable logistic regression; and compared the predictive ability of several different models using the area under receiver operating characteristic (AU-ROC) curves. ResultsMultivariable predictors of in-hospital mortality included Model for End-stage Liver Disease (MELD) score, Acute Physiology and Chronic Health Evaluation (APACHE) II score, mechanical ventilation, and gender; there was also an interaction between MELD score and gender (P < .02). MELD alone had better discrimination (AU-ROC 0.83) than APACHE II alone (AU-ROC 0.76), and adding mechanical ventilation to MELD achieved the single largest increase in model discrimination (AU-ROC 0.85; P < .01). In a parsimonious, 2-predictor model, higher MELD scores (OR 1.14 per 1-point increase; 95% CI 1.11-1.16), and mechanical ventilation (OR 6.20; 95% CI 3.05–12.58) were associated with increased odds of death. Model discrimination was also excellent in the validation cohort (AU-ROC 0.90). ConclusionsIn critically ill ESLD patients, a parsimonious model including only MELD and mechanical ventilation is more accurate than APACHE II alone for predicting in-hospital mortality. This simple bedside model can provide clinicians and patients with valuable prognostic information for medical decision-making.

Polyomavirus BK Infection Before Liver Transplantation in Patients With Chronic Kidney Disease

End-stage liver disease (ESLD) and chronic kidney disease (CKD) patients are both immunocompromised populations but polyomavirus BK (BKV) replication before liver transplantation is rare. We evaluated BKV prevalence among liver transplant recipients with renal dysfunction and the possible role of CKD as a risk factor for BKV replication in ESLD. From 2010 to 2011 we selected 31 ESLD patients awaiting liver transplantation to identify, the presence of CKD: No CKD (n = 22; 18 males) and CKD group (n = 9; 5 males). BKV infection was defined on the basis of viremia evaluated using quantitative real-time polymerase chain reactions. The prevalence of viremia among the No CKD group was 14% versus 56% in the CKD group (Fisher test; P = .027).We hypothesized that the presence of CKD may represent an additional condition of immunologic dysfunction regarding antiviral surveillances other than the antibacterial one that characterizes ESLD immunodysfunction, which could have promoted BKV replication. The specific immunologic mechanisms involved in pretransplantation diseases may have a role in BKV reactivation that could become responsible for nephropathy after transplantation.

Stages of Early Acute Renal Dysfunction in Liver Transplantation: The Influence of Graft Function

The development of early acute renal dysfunction (eARD) occurring in the first week after orthotopic liver transplantation (OLT) is mainly influenced by more severe degrees of pre-OLT hepatic insufficiency and liver graft dysfunction. The aim of our study was to evaluate the incidence of eARD post-OLT as well as its association with pre- and post-OLT hepatic dysfunction. We selected 54 end-stage liver disease patients who underwent OLT from 2008 to 2011. The prevalence of eARD was 53.7% (29/54) classified according to AKIN criteria in ARD-Risk (55.2%), ARD-Injury (27.6%) and ARD-Failure (17.2%). The worst stage of post-OLT eARD (eARD-Failure) seems to be influenced by the poor pre-OLT hepatic function as well as by early suboptimal recovery of graft function.

Is it justifiable to transplant infected livers into haemophilia recipients?

Is it justifiable to transplant infected livers into haemophilia recipients?

In This Issue

In This Issue

Treatment of bone loss in patients with chronic liver disease awaiting liver transplantation

BackgroundMost of the patients awaiting liver transplantation already have osteopenia or even osteoporosis by end-stage liver disease.In a retrospective study, we investigated the effect of pre-treatment with oral monthly ibandronate (150 mg), vitamin D3 (800 IU/day) and calcium (1 g/day) for osteopenia and osteoporosis caused by end-stage liver disease in patients before and after liver transplantation (LT).MethodsThe bone mineral density (BMD) of the lumbar spine (LS) and the femoral neck was measured prospectively pre- and post-LT in 31 patients with existing pre-transplant osteopenia. Patients had osteopenia of the LS prior to LT (T-score −1.8 ± 1.5) so that the treatment medication was initiated immediately after the diagnosis.ResultsThe study group showed a permanently increased BMD with significant differences (g/cm²) from baseline up to 12 months post LT at the lumbar spine (LS: pre-LT 0.80 ± 0.11 g/cm², three months: 0.90 ± 0.08 (P <0.005); six months: 0.95 ± 0.11 (P < 0.008); 12 months: 1.00 ± 0.09 -0.85 (P <0.012).ConclusionThe combined pre- and post-operative treatment with oral ibandronate had significantly improved bone mineral density of the lumbar spine at 3, 6 and 12 months post LT. The immediate post-operative bone loss after LT can be significantly avoided by pre-treatment of liver transplant candidates affected by osteopenia.

The impact of intrapulmonary shunting after liver transplantation in pediatric patients

Intrapulmonary shunting (IPS) due to pulmonary vascular dilatation is frequently observed among patients with end-stage liver disease (ESLD). This study investigated the prevalence and impact of IPS after liver transplantation (LT) in children. A total of 77 pediatric patients who underwent primary LT were enrolled. All patients had trans-thoracic contrast echocardiography before LT and at least 1 year after transplantation. The patients with IPS and without IPS after LT were designated as group 1 and group 2, respectively. The prevalence of IPS after LT was 6.1%. The patients in group 1 (n=5) were younger (6.4 +/- 2.8 vs. 9.9 +/- 3.6, p=0.036) than in group 2 (n=72). There were no significant differences in gender, weight, hemoglobin level, O(2) saturation, or complications between the two groups. Fourteen patients had abnormal liver function tests, two patients in group 1 and 12 patients in group 2 (p=0.22).The overall follow-up period was 6.7 +/- 2.7 years (range, 1.6-13.0). At the latest follow-up, all 5 patients with mild IPS after LT remain asymptomatic with good liver graft function. Among pediatric ESLD patients with preoperative IPS, approximately 6% continue to have mild IPS after LT. Patients with mild IPS after LT remain asymptomatic and have good liver graft function.

Pediatric combined heart–liver transplantation performed en bloc: A single‐center experience

Pediatric CHLT is rarely performed in transplant centers and even fewer are performed en bloc. In the hands of an experienced surgeon with the appropriate patient selection, CHLT performed en bloc may have several operative and immunologic benefits, thereby resulting in improved outcomes for the transplant recipient. A single-institutional, retrospective review from 1/1/06 to 12/31/10 was conducted. Three pediatric patients with end-stage heart and liver disease who were considered low immunologic risk were included. All were managed by the same surgeon with a herein-described CHLT donor and recipient operation. Data were collected on patient and graft survival, rejection episodes, infectious complications, operative time, intraoperative transfusion requirements, and immunosuppression regimens. One-yr patient and graft survival rates were 100%. No patients experienced antibody-mediated or cell-mediated rejection. No patients had postoperative infections, and all patients were free of opportunistic infections at one-yr post-transplant. All patients were maintained safely on steroid-free immunosuppression. There were no intraoperative complications. In pediatric end-stage heart and liver disease patients with low immunologic risk, it is reasonable to proceed with en bloc CHLT so long as there is an experienced surgeon to perform the case. This offers operative and immunologic advantages to the recipient while maintaining equivalent, if not improved, recipient and graft outcomes.

A new era for hepatitis C-new diagnostics tools and new weapons.

A new era for hepatitis C-new diagnostics tools and new weapons.

Sa1020 A Study of Trends in Diagnosis, Outcomes and Costs of Hepatorenal Syndrome in End-Stage Liver Disease Patients - Results From Nationwide Inpatient Database 2000-2009

Sa1020 A Study of Trends in Diagnosis, Outcomes and Costs of Hepatorenal Syndrome in End-Stage Liver Disease Patients - Results From Nationwide Inpatient Database 2000-2009

How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score.

Effects of Liver Function on Ionized Hypocalcaemia following Rapid Blood Transfusion

Hypocalcaemia detrimentally affects the cardiovascular system and massive transfusion-related hypocalcaemia is particularly severe in end-stage liver disease patients undergoing liver transplantation (LT). This study, therefore, compared the severity and duration of ionized hypocalcaemia between patients with normal and impaired liver function. Patients (n = 26 per group) were transfused at a rate of 10 ml/kg within 10 min with packed red blood cells (PRBCs) during LT (group LP) or spinal surgery (group SP), or were infused with 0.9% normal saline during spinal surgery (group SN). Serum levels of ionized calcium were assessed before (T(0)), just after (T(1)), and at 20 (T(2)) and 60 min (T(3)) after transfusion. Transfusion with PRBCs caused more severe ionized hypocalcaemia than 0.9% normal saline at T(1). In contrast to the faster (20 min) normalization in group SP, ionized hypocalcaemia in group LP persisted at T(3). Serum ionized calcium levels at T(3) showed correlations with vital signs, blood glucose, serum potassium, base deficit and lactate. Rapid blood transfusion caused more severe and prolonged ionized hypo calcaemia in patients with liver dysfunction than in those with normal liver function.

New index for assessing the chronotropic response in patients with end-stage liver disease who are undergoing dobutamine stress echocardiography

The inability to achieve 85% of the maximum predicted heart rate (MPHR) on dobutamine stress echocardiography (DSE) is defined as chronotropic incompetence and is a predictor of major cardiac events after orthotopic liver transplantation (OLT). The majority of patients with end-stage liver disease (ESLD) receive beta-blockers for the prevention of variceal bleeding. In these patients, it is impossible to determine whether chronotropic incompetence is secondary to cirrhosis-related autonomic dysfunction or is merely a beta-blocker effect. We evaluated the usefulness of the maximum achieved heart rate (MAHR) and the heart rate reserve (HRR) in the detection of chronotropic incompetence in ESLD patients on beta-blocker therapy before DSE. We also evaluated the usefulness of a new index, the modified heart rate reserve (MHRR), in diagnosing chronotropic incompetence and predicting major cardiovascular adverse events after OLT. The study population consisted of 284 ESLD patients. The mean values of MAHR (expressed as a percentage of 85% of MPHR) and HRR were significantly lower for patients on beta-blockers versus patients off beta-blockers [97.1% versus 101.6% (t = 5.01, P < 0.001) and 71.7% versus 77.3% (t = 4.03, P < 0.001), respectively], whereas the values of MHRR were similar in patients on beta-blockers and patients off beta-blockers [102.3% versus 102.1% (t = 0.04, P = 0.97)]. A regression analysis showed a significant association of MAHR (P < 0.001) and HRR (P < 0.001) with beta-blockers, whereas MHRR was not associated with beta-blocker treatment (P = 0.92). MAHR and HRR were found to have no value for diagnosing chronotropic incompetence in ESLD patients. MHRR was not affected by beta-blocker therapy. Patients who developed heart failure (HF) and myocardial infarction (MI) after OLT had significantly lower MHRR values according to pretransplant DSE. MHRR was significantly associated with the subsequent development of HF (P = 0.01) and MI (P = 0.01) after OLT. MHRR may be useful for the determination of the target heart rate for stress testing, the diagnosis of chronotropic incompetence, and the prediction of adverse cardiac events after OLT.

Metronidazole-induced encephalopathy in a patient with end-stage liver disease.

Purpose. Metronidazole-induced encephalopathy (MIE) has been rarely reported. We report a case in a patient with end-stage liver disease (ESLD). Summary. A 63-year-old male with ESLD secondary to hepatitis C virus presented with progressively worsening fatigue, slurred speech, aphasia, vomiting, and left-sided facial droop after completing a 2-week course of metronidazole for recurrent Clostridium difficile-associated diarrhea. He completed a previous course of metronidazole 3 weeks prior to presentation. He is on the liver transplant waiting list and has known hepatic encephalopathy. MRI revealed hyperintense T2 signals involving the bilateral dentate nuclei, inferior colliculi and splenium of the corpus callosum, and increased diffusion restriction at the splenium of the corpus callosum. His neurological function improved over the next several days. He underwent liver transplantation 6 days after admission. A follow-up MRI 6 weeks after presentation revealed resolution of abnormalities; however, paresthesias persisted 6 months after MIE diagnosis. Conclusion. An ESLD patient with hepatic encephalopathy developed MIE after a relatively short course of metronidazole. Metronidazole has been shown to accumulate in patients with ESLD. Increased awareness for neurotoxicity when using metronidazole in ESLD patients is warranted, especially in those with potentially confounding hepatic encephalopathy.

Microbial Translocation and Infectious Diseases: What Is the Link?

Microbial Translocation and Infectious Diseases: What Is the Link?

Diagnostic accuracy of α‐fetoprotein and des‐γ‐carboxy prothrombin in screening for hepatocellular carcinoma in liver transplant candidates

Although hepatocellular carcinoma (HCC)-specific serum tumor markers, α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), are used in the screening for HCC, their utility in pre-transplantation evaluation is not well established. This study aimed to evaluate the accuracy of AFP and DCP measurement for the diagnosis of HCC in liver transplant candidates. A total of 315 consecutive adult patients (174 men and 141 women, mean age 52 years), who were to receive liver transplantation for end-stage liver diseases, were enrolled. The pre-transplant levels of AFP and DCP were compared with the histopathology of explanted liver. Hepatocellular carcinoma was present in the explanted liver of 106 recipients (median number of nodules 2, mean diameter 2.5 cm). The area under receiver operating characteristic curve for the diagnosis of HCC was 0.83 (95% confidence interval, 0.78-0.88) for AFP and 0.47 (0.41-0.54) for DCP. With the cut-off value of 100 mAU/mL, 20/106 (18.9%) patients with HCC and 54/194 (27.8%) patients without HCC were positive for DCP. DCP positivity was associated with vascular invasion, tumor differentiation and size among patients with HCC, which was associated with albumin level among patients without HCC. Vitamin K was administered prior to transplantation to 20 patients who were positive for DCP (two with and 18 without HCC), resulting in a decrease in DCP levels in 19 of them. Serum DCP levels may be raised in end-stage liver disease patients without HCC, and cannot be used as a reliable marker for HCC among liver transplant candidates.

Alleviating the Patient’S Price of Privacy Through a Partially Observable Waiting List

In the United States, end-stage liver disease patients join a waiting list and then make accept/reject decisions for transplantation as deceased-donor organs are offered to them over time. These decisions are largely influenced by the patient’s prospect for future offers, which can be ascertained most accurately by knowing the entire composition of the waiting list. Under the current transplantation system, however, UNOS (United Network for Organ Sharing), in an effort to strike a balance between privacy and transparency, only publishes an aggregated version of the waiting list. However, it is not clear whether the published information is good enough (compared to perfect information) to help patients make optimal decisions that maximize their individual life expectancies. We model and analyze this accept/reject problem from an individual patient’s perspective using a partially observed Markov decision process (POMDP) framework, which incorporates the imperfect waiting list information as currently published into patient’s decision-making. In addition to analyzing structural properties of this model, we compare, in a clinically driven numerical study, the results of this model to those of an existing MDP model that differs from our model in assuming the availability of perfect waiting list information. This comparison allows us to assess the quality of the published imperfect information as measured by a patient’s so-called price of privacy (i.e., the opportunity loss in expected life days due to a lack of perfect waiting list information). Previous work estimates a percent loss of about 5%, on average, when a patient has no waiting list information compared to full information. In this paper, we find that the currently published partial information is nearly sufficient to eliminate this loss, resulting in a negligible price of privacy and supporting current UNOS practice.

Alleviating the Patient's Price of Privacy Through a Partially Observable Waiting List

In the United States, end-stage liver disease patients join a waiting list and then make accept/reject decisions for transplantation as deceased-donor organs are offered to them over time. These decisions are largely influenced by the patient's prospect for future offers, which can be ascertained most accurately by knowing the entire composition of the waiting list. Under the current transplantation system, however, the United Network for Organ Sharing (UNOS), in an effort to strike a balance between privacy and transparency, only publishes an aggregated version of the waiting list. However, it is not clear whether the published information is good enough (compared with perfect information) to help patients make optimal decisions that maximize their individual life expectancies. We provide a novel model of this accept/reject problem from an individual patient's perspective using a partially observed Markov decision process (POMDP) framework, which incorporates the imperfect waiting list information as published currently into the patient's decision making. We analyze structural properties of this model. In particular, we establish conditions that guarantee a monotone value function and a threshold-type optimal policy with respect to the partially observable rank state that captures the imperfect waiting list information. Furthermore, we develop an improved solution methodology to solve a generic POMDP model. This solution method guarantees, for any fixed grid, the best possible approximation to the optimal value function by solving linear programs to compute the optimal weights used for the approximation. Finally, we compare, in a clinically driven numerical study, the results of this model with those of an existing Markov decision process model that differs from our model in assuming the availability of perfect waiting list information. This comparison allows us to assess the quality of the published imperfect information as measured by a patient's so-called price of privacy (i.e., the opportunity loss in expected life days due to a lack of perfect waiting list information). Previous work estimates a significant loss in a patient's life expectancy, on average, when the patient has no waiting list information compared with full information. In this paper, we find that the currently published partial information is nearly sufficient to eliminate this loss, resulting in a negligible price of privacy and supporting current UNOS practice. This paper was accepted by Assaf Zeevi, stochastic models and simulation.