William R. Hutson

Fulminant hepatic failure associated with the use of black cohosh: A case report

With data from the Womens Health Initiative indicating that estrogen plus progesterone are associated with an increased risk of cardiovascular events, many patients and practitioners are looking for alternative therapies to manage menopausal symptoms. One alternative is black cohosh, an herbal product used primarily to treat these symptoms. In recent years there have been several case reports associating this substance with hepatitis and fulminant hepatic failure. We present a case of a woman who developed hepatic failure requiring liver transplantation from the use of this herb. Liver Transpl 12:989–992, 2006.

Gastric Emptying Response to Variable Oral Erythromycin Dosing in Diabetic Gastroparesis

Intravenous erythromycin has been shown to improve gastric emptying in diabetic gastroparesis. Oral erythromycin also accelerates gastric emptying, but to a lesser degree. To determine if this is a dose-dependent phenomenon, gastric emptying was measured in 10 insulin-requiring diabetic patients with gastroparesis after administration of either 250 mg or 1000 mg of erythromycin or placebo. The drugs were orally administered in a randomized, double-blind fashion 30 min prior to ingestion of a meal containing [99mTc]-sulfur colloid-labeled beef stew and [111In]DTPA-labeled orange juice. Anterior and posterior gastric images were recorded for 3 hr at 15-min intervals using an externally positioned gamma camera. The results demonstrated that both doses of oral erythromycin significantly improved solid-phase gastric emptying. The mean half-emptying time of solids was decreased from 151±40 min with placebo to 58±10 min and 40±9 min with 250 mg and 1000 mg of erythromycin, respectively. However, a dose-dependent relationship was not demonstrated with the two doses of erythromycin employed. These results suggest that for most patients with diabetic gastroparesis, a single 250-mg dose of erythromycin will significantly improve gastric emptying. It is possible that a dose-dependent relationship will be demonstrated with doses of erythromycin less than 250 mg.

Liver transplantation in septuagenarians receiving model for end-stage liver disease exception points for hepatocellular carcinoma: the national experience.

Current liver allocation policy in the United States grants liver transplant candidates with stage T2 hepatocellular carcinoma (HCC) a priority Model for End‐Stage Liver Disease (MELD) score of 22, regardless of age. Because advanced age may portend an increase in all‐cause mortality after transplantation for any diagnosis, the aim of this study was to examine overall posttransplant survival in elderly patients with HCC versus younger cohorts. Based on Organ Procurement and Transplantation Network data, Kaplan‐Meier 5‐year survival rates were compared. Recipients undergoing primary liver transplantation were stratified into cohorts based on age (<70 or ≥70 years) and the receipt of MELD exception points for HCC. Log‐rank and Wilcoxon tests were used for statistical comparisons. In 2009, 143 transplants were performed for patients who were 70 years old or older. Forty‐two percent of these patients received a MELD exception for HCC. Regardless of the diagnosis, the overall survival rate was significantly attenuated for the septuagenarians versus the younger cohort. After 5 years of follow‐up, this disparity exceeded 10% to 15% depending on the populations being compared. The 1‐, 2‐, 3‐, 4‐, and 5‐year actuarial survival rates were 88.4%, 83.2%, 79.6%, 76.1%, and 72.7%, respectively, for the patients who were younger than 70 years and 81.1%, 73.8%, 67.1%, 61.9%, and 55.2%, respectively, for the patients who were 70 years old or older. Five‐year survival was negatively affected for patients with HCC who were younger than 70 years; this disparity was not observed for patients with HCC who were 70 years old or older. In conclusion, although patients who are 70 years old or older compose a small fraction of transplant recipients in the United States, patients in this group undergoing transplantation for HCC form an even smaller subset. Overall, transplantation in this age group yields outcomes inferior to those for younger cohorts. However, unlike patients who are less than 70 years old and receive MELD exception points, overall liver transplant survival is not affected by HCC at an advanced age. Liver Transpl 18:423–433, 2012.

Liver transplantation for cholangiocarcinoma.

Liver transplantation for cholangiocarcinoma (CCA) remains a controversial subject. More than 15 years after, a novel protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation was first used in patients with unresectable hilar CCAs, these methods have yet to reach broad application. Results have confirmed that this approach leads to significantly lower recurrence rates and higher long-term survival rates than other existing treatment modalities. Despite this, protocols to treat patients with CCA are not widespread, and are available at only a handful of transplant programs. At these centers, treatment success may ultimately hinge on regional model for end-stage liver disease scores and waiting time for transplant. While acknowledging these factors as well as a severe organ shortage, it is important that the transplant community not overlook a potentially effective form of therapy for a previously untreatable disease.

Safety of belatacept bridging immunosuppression in hepatitis C-positive liver transplant recipients with renal dysfunction.

Background Perioperative renal dysfunction in liver transplant recipients complicates maintenance immunosuppressive therapy, particularly in patients with hepatitis C. Calcineurin inhibitors exacerbate renal dysfunction and mammalian target-of-rapamycin inhibitors are generally avoided because of perceived perioperative risks. The authors’ experience with seven liver transplant patients who received belatacept and mycophenolic acid maintenance immunosuppression is reported. Methods A retrospective review of adult liver transplant recipients with hepatitis C receiving belatacept was conducted under Institutional Review Board approval. All patients were Epstein-Barr virus IgG seropositive. The primary endpoint was patient and graft survival, with secondary endpoints including the incidence of acute rejection, degree of renal function recovery, and occurrence of major side effects. Results Between December 19, 2011 and January 25, 2013, seven liver transplant recipients with hepatitis C received belatacept immunosuppression in the perioperative period. The primary indication for belatacept was perioperative renal dysfunction. Belatacept was initiated between 2 and 90 days posttransplant and the duration of belatacept therapy ranged from 19 to 89 days. Patients were transitioned onto calcineurin inhibitor therapy when they reached chronic kidney disease stage 2 or better. Six-month patient and graft survival was 86%. There was one episode of graft rejection on belatacept therapy in a patient who had also had early rejection before initiation of belatacept. Conclusions The results in this initial group of patients suggest that belatacept with mycophenolic acid may be a safe maintenance immunosuppression regimen in hepatitis C–positive liver transplant recipients with renal dysfunction, and that this regimen can serve as an effective bridge to calcineurin inhibitor therapy.

A Pilot Study to Evaluate Renal Hemodynamics in Cirrhosis by Simultaneous Glomerular Filtration Rate, Renal Plasma Flow, Renal Resistive Indices and Biomarkers Measurements

Background: Renal hemodynamic measurements are complicated to perform in patients with cirrhosis, yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics. Methods: In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic-sensitive and 2 diuretic-refractory ascites). Results: Patients with diuretic-refractory ascites had the lowest mean GFR (36.5 ml/min/1.73 m2) and RPF (133.6 ml/min/1.73 m2) when compared to those without ascites (GFR 82.9 ml/min/1.73 m2, RPF 229.9 ml/min/1.73 m2) and with diuretic-sensitive ascites (GFR 82.3 ml/min/1.73 m2, RPF 344.1 ml/min/1.73 m2). A higher mean filtration fraction (FF) (GFR/RPF 0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF ∼0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and β2-microglobulin performed better compared to Cr in estimating RPF, β-trace protein, β2-microglobulin, and SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index. Conclusion: The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention and reduce mortality from kidney failure in cirrhosis.

Cholangiocarcinoma in a 17-year-old boy with primary sclerosing cholangitis and inflammatory bowel disease.

JPGN Volume 52, N C holangiocarcinoma (CCA) is a known complication of primary sclerosing cholangitis (PSC) in adults. We describe a young patient who developed CCA 3 years after diagnosis of inflammatory bowel disease (IBD) and PSC. We describe the use of molecular marker techniques for diagnosis, and neoadjuvant cytoreductive therapy and orthotopic liver transplantation for therapy. The patient first presented at age 14 with 2 days of jaundice, fever, dyspnea, and chest and abdominal pain. He also complained of several months of nonbloody, watery diarrhea up to 9 times per day and fecal urgency both day and night, often waking him from sleep. This was unrelieved by daily loperamide and a prescribed course of empiric metronidazole. Medical and family histories were unremarkable. He was febrile, tachycardic, tachypneic, and mildly hypoxemic. Physical examination demonstrated jaundice with scleral icterus. He had a soft but tender abdomen with prominent splenomegaly. Breathing was labored with retractions, but the lungs were clear to auscultation. Initial laboratory studies revealed cholestasis, elevated transaminases, low albumin, leukocytosis, and a normal coagulation profile (Table 1). C-reactive protein and erythrocyte sedimentation rate were elevated and stool was positive for occult blood. Magnetic resonance cholangiopancreatography demonstrated an irregular and narrowed common hepatic duct, without biliary dilatation, cystic lesions, and intrahepatic mass. Liver biopsy revealed bile duct proliferation and periductular fibrosis consistent with PSC and without findings of overlap (Fig. 1). Anti-nuclear antibody and smooth muscle antibody were negative. Anti-nuclear cytoplasmic antibody was present in a 1:512 titer with peripheral staining pattern. Endoscopic retrograde cholangiopancreatography (ERCP) was not obtained at this time because clinical, radiographic, and histological findings were consistent with PSC and there was no biliary ductal dilatation on magnetic resonance imaging. Stool culture and Clostridium difficile cytotoxins were negative. Colonoscopy revealed regionally distributed inflammation and friable mucosa throughout the colon, with rectal sparing. A biopsy showed transmucosal chronic inflammatory cells, moderate crypt

Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver Transplant Patients With Acute Renal Failure

INTRODUCTION We have aggressively used continuous veno-venous hemofiltration (CVVH) on high model for end-stage liver disease (MELD) score liver transplant patients with acute kidney injury and hypothesized that the addition of intraoperative CVVH therapy would improve overall outcomes. METHODS We performed a retrospective review of all adult, single organ, liver transplant recipients requiring preoperative renal replacement therapy between January 1, 2011 and June 1, 2013. Intraoperative and perioperative records and laboratory values were collected and used to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplantation. RESULTS Twenty-one patients with new-onset renal failure requiring preoperative renal replacement therapy received a liver transplant alone. Fourteen received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for intraoperative CVVH vs 35; P = .8). Preoperative sodium and potassium were higher for the group receiving intraoperative CVVH, but still fell within normal ranges. Preoperative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs 2.0 mmol/L; P = .01). Intraoperative CVVH did not decrease intraoperative transfusion requirements or intensive care unit (ICU) and hospital lengths of stay. Differences in reoperative rates did not reach statistical significance. All patients were weaned off renal replacement therapy. One-year patient survival rate was 86% for intraoperative CVVH versus 71% without. CONCLUSION The judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable with less ill patients.

Physicians' attitude toward organ donation and transplantation in the USA.

The public views organ donation favorably, with 60–90% of survey responders expressing a willingness to be an organ donor (1, 2). However, this positive attitude translates to nationwide donation rate of less than 40% (3). There is a paucity of literature addressing organ donation from a provider viewpoint. We conducted a survey to find out the percentage of physicians who were registered organ donors and the attitude of physicians in the USA toward a one possible non-monetary incentivized system to increase organ donation pool. A multidisciplinary panel of gastroenterology fellows and transplant hepatologists developed a 19-question electronic survey. Content validation and survey methodology were completed utilizing literature review, item generation, and small and large group discussions. The survey questions were piloted with a focus group of 15 physicians at three different institutions for face and content validity, feasibility and to ensure that all content domains were covered. This included evaluation on relevance and readability of each item, revision of existing items, and additions to the survey as needed. An electronic invitation to participate in the electronic survey was sent to 4000 residency and fellowship program directors in the USA. The anonymous survey was run through Google Documents© and included questions characterizing demographics, awareness of organ shortage, respondent organ donation status, and attitude toward assigning a higher priority to organ donors should they require liver transplantation in the future and reasons for opting against organ donation. The survey (Supplement 1) can be accessed through the following website https://docs.google. com/spreadsheet/viewform?formkey=dC1PMGtq Vk00d0JuWWhlWENMTmszZkE6MA. A total of 724 physicians in different specialties and subspecialties representing a broad sample of trainees and attending physicians at institutions across the nation participated. Eighteen physicians were excluded due to missing donor status. Around 86% of responders were aware about organ shortage problem and its consequences. The estimated number of participating physicians in the USA is around 878,194 physicians (4). Thus, the calculated confidence interval is 3.65% (95% confidence level). Chi-square and Student’s t-test were used to examine differences between those respondents registered as donors (n = 539 physicians, 76.3%) and those who were registered as non-donors (n = 167 physicians, 23.7%). Table 1 summarizes the demographics and characteristics of the participants as well as attitude toward assigning a higher priority to organ donors should they require liver transplantation in the future. There were no differences between the two groups with regard to age, gender, specialty, level of training, location of practice, and involvement in the care of liver transplant recipients having liver disease or having a close relative or friend with liver disease. Respondents who were identified as donors were more significantly aware about issues related to organ shortage and its consequences (87.8% vs. 80.1%, p < 0.03). The most common reasons for declining to register as organ donor included the following: religious purposes, followed by concerns about resultant poor medical care should a donor require medical care, rejecting the idea of surgical intervention following death as well as beliefs that the current organ allocation system is unfair. Among industrial countries, Israel’s organ donation has been one of the lowest. This led to introduce a new measurements including The Organ Transplantation Law in 2008. One component of the law included granting prioritization in organ allocation to those who registered as organ donors. As a consequence, the number of new registered donor has increased. Furthermore, there was a significant increase in the number of deceased organ donors. The organ donation rate

Minimally invasive aortic valve replacement with orthotopic liver transplantation: report of a case

Cardiac surgery and liver transplantation (LT) are rarely performed at the same time, because of the potential risks of coupling two such complex surgical procedures [1–3]. This combined surgery is typically reserved for patients with structural heart disease, including multivessel obstructive coronary artery disease and severe valvular disease with heart failure and end-stage liver disease, in whom the untreated organ may decompensate if only one organ is addressed [4]. Combined aortic valve replacement (AVR) and LT is the rarest of such combined surgery, with only ten cases published previously. We present the first reported case of combined minimally invasive AVR and LT and review the literature on similar combined surgery.