COMPASS: A Pilot Trial of an Early Palliative Care Intervention for Patients With End-Stage Liver Disease.

CONTEXT: Palliative care interventions have shown promise in improving quality of life and reducing health-care utilization among patients with chronic organ failure. OBJECTIVES: To evaluate the effect of a palliative care intervention for adults with end-stage liver disease. METHODS: A randomized controlled trial of patients with end-stage liver disease admitted to the hepatology service at a tertiary referral center whose attending hepatologist indicated they would not be surprised if the patient died in the following year on a standardized questionnaire was performed. Control group patients received usual care. Intervention group patients received inpatient specialist palliative care consultations and outpatient phone follow-up by a palliative care nurse. The primary outcome was time until first readmission. Secondary outcomes included days alive outside the hospital, referral to hospice care, death, readmissions, patient quality of life, depression, anxiety, and quality of end-of-life care over 6 months. RESULTS: The trial stopped early because of difficulties in accruing patients. Of 293 eligible patients, only 63 patients were enrolled, 31 in the intervention group and 32 in the control group. This pace of enrollment was only 25% of what the study had planned, and so it was deemed infeasible to complete. Despite stopping early, intervention group patients had a lower hazard of readmission (hazard ratio: 0.36, 95% confidence interval: 0.16-0.83, P = 0.017) and greater odds of having more days alive outside the hospital than control group patients (odds ratio: 3.97, 95% confidence interval: 1.14-13.84, P = 0.030). No other statistically significant differences were observed. CONCLUSION: Logistical obstacles hindered completion of the trial as originally designed. Nevertheless, a preemptive palliative care intervention resulted in increased time to first readmission and more days alive outside the hospital in the first six months after study entry.

Early outcomes using hepatitis C-positive donors for cardiac transplantation in the era of effective direct-acting anti-viral therapies.

BACKGROUND: Given the shortage of suitable donor hearts for cardiac transplantation, and the favorable safety and efficacy of current agents used to treat hepatitis C virus (HCV), our institution recently piloted transplantation of select patients using HCV-positive donors. METHODS: Between September 2016 and March 2017, 12 HCV-naive patients and 1 patient with a history of treated HCV underwent heart transplantation (HT) using hearts from HCV-positive donors after informed consent. Patients who acquired HCV were referred to hepatology and treated with direct-acting anti-viral therapies (DAAs). Data collection and analysis were performed with institutional review board approval. RESULTS: At the time of HT, mean age of recipients was 53 ± 10 years, and 8 patients (61.5%) were on left ventricular assist device support. After consent to consider an HCV-positive heart, mean time to HT was 11 ± 12 days. Nine of 13 patients (69%) developed HCV viremia after transplant, including 8 who completed DAA treatment and demonstrated cure, as defined by a sustained virologic response 12 weeks after treatment. One patient died during Week 7 of his treatment due to pulmonary embolism. DAAs were well tolerated in all treated patients. CONCLUSIONS: In the era of highly effective DAAs, the use of HCV-positive donors represents a potential approach to safely expand the donor pool. Additional follow-up is needed to elucidate long-term outcomes.

Acoustic liver biopsy in patients with hepatitis C and advanced liver fibrosis using endoscopic ultrasound.

BACKGROUND: Transabdominal ultrasound cannot be used to quantitate fibrosis in patients with advanced liver fibrosis due to variability in the abdominal wall thickness and composition. This variability can be eliminated by using endoscopic ultrasound. AIM: The purpose of this study was to determine the amount of fibrosis in the liver of hepatitis C patients with advanced fibrosis using endoscopic ultrasound. METHODS: Endoscopic ultrasound images of the liver were recorded by keeping the gain, contrast, frequency, magnification and acoustic power constant on the ultrasound processor. Videotaped images of the liver were digitized on Image-Pro Plus software. Using adobe Photoshop, a histogram was produced to quantitate the luminosity of the five areas of interest per image. Quantification of the ultrasound images were done by two independent investigators blinded to the Ishak liver fibrosis score. The mean luminosity of the ultrasound images were compared with the Ishak fibrosis score. The study was performed in seven patients (mean age 54 years; 3 male, 4 female) with hepatitis C and advanced liver fibrosis. RESULTS: The correlation between the two independent investigators for the ultrasound images was 0.93. The correlation between the mean luminosity on ultrasound images to the Ishak fibrosis score was r = 0.77, r = 0.72 and r = 0.73 for the most hyperechoic area of interest, total hyperechoic area and for the entire liver, respectively. CONCLUSION: A new technique was developed that uses endoscopic ultrasound to evaluate the degree of fibrosis in patients with advanced liver fibrosis. There is a good correlation between the luminosity on endoscopic ultrasound and the Ishak fibrosis score.

Minimally invasive measurement of esophageal variceal pressure and wall tension (with video).

BACKGROUND: There is no simple method to measure intravariceal pressure in patients with esophageal varices. OBJECTIVE: Our purpose was to develop a new noninvasive technique to measure resting intravariceal pressure and wall tension. DESIGN: A model was developed. A long balloon (varix) was fitted inside an airtight cylinder (esophagus). Fluid ran through the model varices to maintain 5 different constant pressures. An endoscope was placed in the model esophagus, and pressure was increased by air insufflation. The endoscopy and pressure readings from the esophagus and varix were recorded continuously until variceal collapse. SETTING: Patient studies were done in an endoscopy suite with the patient under fentanyl and midazolam sedation. PATIENTS: Esophageal pressure was measured during air insufflation in patients with varices until the varices collapsed. EUS was used to measure radius and wall thickness to calculate wall tension. RESULTS: In the varix model, the mean (SD) intraluminal esophageal pressures at variceal flattening for the model varices at 5, 10, 15, 20, and 25 mm Hg were 5.69 (0.34), 11 (0.32), 15.72 (0.51), 21.55 (0.63), and 25.8 (0.14) mm Hg. The correlation between actual and measured variceal pressure in the model at variceal flattening was r = 0.98. In the patients, a total of 10 varices in 3 patients were evaluated. The mean (SD) for the varices in each subject was 12.16 (2.4), 23.2 (1.3), and 6.5 (2.2) mm Hg for subjects 1, 2, and 3, respectively. CONCLUSION: Standard endoscopy with air insufflation and manometry can be used as an accurate, simple, and reproducible method to measure intravariceal pressure.

Muscle shortening along the normal esophagus during swallowing.

Longitudinal shortening of the esophagus during peristaltic contraction has been previously analyzed globally using spaced mucosal clips. This method gives a relatively crude measurement. In this study, local longitudinal shortening (LLS) was evaluated using simultaneous high-resolution endoluminal ultrasound (HREUS) and manometry based on basic principles of muscle mechanics. We sought to determine if there are regional differences in LLS of the esophageal muscle during swallow-induced peristaltic contraction and evaluate shortening of the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the esophagus. Twenty normal subjects underwent simultaneous HREUS/manometry at 4 levels (5, 10, 15, and 20 cm above the upper border of the lower esophageal sphincter [LES] high-pressure zone) in the esophagus with 5-mL swallows of water. Ultrasound images were recorded with synchronized manometric pressure data. The images were digitized and the cross-sectional surface area (CSA) of the LSM, CSM, and total muscle (TM) were measured at baseline (at rest) and at peak intraluminal pressure (implying peak CSM contraction) during swallowing. LLS was calculated for the CSM and LSM using the principle of mass conservation, whereby the change in CSA relative to the resting CSA is quantitatively equal to the relative change in length of a local longitudinal muscle segment.CSM, LSM, and TM all shortened longitudinally, with the circular muscle shortening more than the longitudinal muscle, LLS of the CSM and TM layers at 5 cm above the LES was significantly greater than at 20 cm (CSM: 30% difference, P < .001; TM: 18% difference, P < .05). The greater shortening of LSM at 5 versus 20 cm was found not to be statistically significant (11% difference, P > .05). Peak intraluminal pressure strongly correlated with peak muscle thickness of all layers at all levels (r = 0.96-0.98).LLS increases from the proximal to the distal esophagus during bolus transport. CSM and LSM both shorten longitudinally, with CSM shortening more than LSM. The increase in LLS increases the efficiency of peristaltic contraction and likely contributes to the axial displacement of the LES preceding hiatal opening and esophageal emptying.

Simplified method of hepatic fibrosis quantification: design of a new morphometric analysis application.

INTRODUCTION: Semiquantitative evaluation of liver specimens is considered the standard method for measuring fibrosis; however, these systems lack the precision of a quantitative technique. METHODS: We developed an image analysis application (FibroXact) that automates and simplifies color segmentation. Trichrome slides were scanned and the program was used to evaluate each pixel based upon hue, lightness, and saturation values. Percent fibrosis was automatically calculated after thresholding. RESULTS: Linear regression demonstrated a strong relationship between the FibroXact result and the semiquantitative result (P<0.001). CONCLUSION: We have developed an image analysis application to quantify liver fibrosis. Correlation between our results and a standard semiquantitative system was demonstrated.

A new ultrasound-guided esophageal variceal pressure-measuring device.

OBJECTIVE: To develop a noninvasive method and device to determine intravariceal pressure and variceal wall tension by measuring the variables of the Laplace equation and test this device in a model of esophageal varices. METHODS: Two variceal pressure measurement devices were constructed. The first device consists of an Olympus 20 MHz ultrasound transducer placed next to a latex balloon catheter attached to a pressure transducer. The second device was constructed by placing the same ultrasound transducer inside a latex condom balloon attached to a pressure transducer. These pressure measurement devices were tested blindly in varix models with different intravariceal pressures, by inflating the balloon to flatten the varix models. Each variceal pressure was measured 10 times by two separate investigators blinded to the actual pressures. The mean intravariceal pressures were calculated. The variceal models were made of a latex balloon filled with water and coffeemate. RESULTS: The correlation coefficient between the actual and measured varix pressures for both devices was 0.99. The percent error ranged from 0 to 10%. The correlation coefficient between the investigators making the blinded measurements for both devices was 0.98. CONCLUSION: Two pressure-measuring devices were developed to determine intravariceal pressure in a model varix system. These devices demonstrate a low percent error and a high correlation to the actual variceal pressures with low intra- and interobserver variability. These devices have the potential to measure all the variables of the Laplace equation for wall tension. We plan to test these devices in human subjects.