David A. Sass

Terlipressin Plus Albumin Is More Effective Than Albumin Alone in Improving Renal Function in Patients With Cirrhosis and Hepatorenal Syndrome Type 1

BACKGROUND & AIMSnHepatorenal syndrome type 1 (HRS-1) in patients with cirrhosis and ascites is a functional, potentially reversible, form of acute kidney injury characterized by rapid (<2 wk) and progressive deterioration of renal function. Terlipressin is a synthetic vasopressin analogue that acts, via vascular vasopressin V1 receptors, as a systemic vasoconstrictor. We performed a phase 3 study to evaluate the efficacy and safety of intravenous terlipressin plus albumin vs placebo plus albumin in patients with HRS-1.nnnMETHODSnAdult patients with cirrhosis, ascites, and HRS-1 (based on the 2007 International Club of Ascites criteria of rapidly deteriorating renal function) were assigned randomly to groups given intravenous terlipressin (1 mg, nxa0= 97) or placebo (nxa0= 99) every 6 hours with concomitant albumin. Treatment continued through day 14 unless the following occurred: confirmed HRS reversal (CHRSR, defined as 2 serum creatinine [SCr] values ≤1.5 mg/dL, at least 40 hours apart, on treatment without renal replacement therapy or liver transplantation) or SCr at or above baseline on day 4. The primary end point was the percentage of patients with confirmed CHRSR. Secondary end points included the incidence of HRS reversal (defined as at least 1 SCr value ≤1.5 mg/dL while on treatment), transplant-free survival, and overall survival. The study was performed at 50 investigational sites in the United States and 2 in Canada, from October 2010 through Februaryxa02013.nnnRESULTSnBaseline demographic/clinical characteristics were similar between groups. CHRSR was observed in 19 of 97 patients (19.6%) receiving terlipressin vs 13 of 99 patients (13.1%) receiving placebo (Pxa0= .22). HRS reversal was achieved in 23 of 97 (23.7%) patients receiving terlipressin vs 15 of 99 (15.2%) receiving placebo (Pxa0= .13). SCr decreased by 1.1 mg/dL in patients receiving terlipressin and by only 0.6 mg/dL in patients receiving placebo (P < .001). Decreases in SCr and survival were correlated (r(2)xa0= .882; P < .001). Transplant-free and overall survival were similar between groups. A significantly greater proportion of patients with CHRSR who received terlipressin survived until day 90 than patients who did not have CHRSR after receiving terlipressin (P < .001); this difference was not observed in patients who did vs did not have CHRSR after receiving placebo (Pxa0= .28). There were similar numbers of adverse events in each group, but patients in the terlipressin group had more ischemic events.nnnCONCLUSIONSnTerlipressin plus albumin was associated with greater improvement in renal function vs albumin alone in patients with cirrhosis and HRS-1. Patients had similar rates of HRS reversal with terlipressin as they did with albumin. ClinicalTrials.gov no: NCT01143246.

Relationship of Visceral Adipose Tissue to Recurrence of Adenomatous Polyps

OBJECTIVES:Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer.METHODS:As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4–L5 interspace. The scan was performed around the time of the subjects year 4 colonoscopy that determined adenoma recurrence.RESULTS:Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma (p = 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4, p = 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat.CONCLUSION:In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required.

Portal Hypertension and Variceal Hemorrhage

Portal hypertension is a progressively debilitating complication of cirrhosis and a principal cause of mortality in patients who have hepatic decompensation. This article describes the classification system and pathophysiology of portal hypertension. It also discusses a practical approach to prevention of first variceal hemorrhage, general management of the acute bleeding episode, and secondary prophylaxis to prevent rebleeding. Pharmacologic, endoscopic, radiologic, and surgical modalities are all described in detail.

Liver transplantation in the 21st century: expanding the donor options.

Over the past decade, use of ECD organs for OLT has allowed many transplant programs to afford patients access to an otherwise scarce resource and to maintain center volume. Although overall posttransplant outcomes are inferior to results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD organs significantly lowers median wait-times for OLT, MELD score at OLT, and death while awaiting transplantation. It is incumbent on the transplant community to provide continued scrutiny of the many factors involved in ECD organ utilization, evaluate the degree of risk and benefit such allografts may impart on particular recipients, and thereby provide suitable “matching” to maximize favorable outcomes. Transplant caregivers need to provide patients with evidence-based care decisions, be good stewards of a scarce resource, and maintain threshold survival results for their programs. This requires balancing the urgency with which a transplant is needed and the utility of such a transplant. There is a clear necessity to pursue additional donor research to improve use of these marginal grafts and assess interventions that enhance the safety of ECD livers.

Rescue of a Living Donor with Liver Transplantation

Postoperative liver failure is a rare complication after living donor liver resection. This is a case report of a 22‐year‐old healthy donor who was rescued with liver transplantation 11 days after right hemihepatectomy. Nine months later the patient is alive, and has fully recovered from his multiple organ failure. According to a review of the literature, there are four additional living liver donors, who received a liver transplant. Our own patient is the only survivor, so far. This case demonstrates that even in supposedly healthy living donors postoperative complications cannot be completely prevented. Although liver failure is rare in these patients, timely transplantation may need to be considered as the only life‐saving treatment.

Jejunal gastrointestinal stromal tumor: a cause of obscure gastrointestinal bleeding.

In cases of obscure gastrointestinal bleeding, when a source for blood loss is not apparent from examination of the colon and upper gastrointestinal tract, the small bowel usually becomes the focus of investigation. A tumor with interesting pathologic features was found in a patient who presented with recurrent episodes of massive obscure gastrointestinal hemorrhage. This case highlights the importance of considering small intestinal tumors as the likely cause of obscure gastrointestinal hemorrhage in young patients and how a noninvasive test, eg, abdominal computed tomography scan, might obviate the need for more invasive testing.

The impact of biopsychosocial factors on quality of life: Women with primary biliary cirrhosis on waiting list and post liver transplantation

OBJECTIVESnPrimary biliary cirrhosis (PBC) is the second most common reason for liver transplants among women in the USA. While survival rates are high, there is evidence of persistent problems post-transplant. This study aimed to identify significant contributors to quality of life (QOL) for women with PBC on waiting list (WL) and post-transplant (PT) and compare QOL in each group with US population norms.nnnDESIGNnA cross-sectional, two-group study design was used.nnnMETHODSnWL and PT participants were recruited through medical centres and on-line. QOL was measured by the Short Form-36 and an indicator of Social QOL created for this study. A biopsychosocial model incorporating demographic, biomedical, psychological, and sociological factors guided choice of variables affecting QOL. Analyses examined (1) all factors for differences between WL and PT groups, (2) association between factors and QOL outcomes within each group, (3) multivariate regression of QOL on factors in the model for the sample as a whole, and (4) comparison of QOL outcomes with national norms.nnnRESULTSnOne hundred women with PBC participated in the study, 25 on WL and 75 PT. Group comparisons showed improvement for PT participants in most biomedical and psychological variables and in QOL outcomes. QOL was related to many, but not all, of the variables in the model. In multivariate analysis, Fatigue, Depression, Coping, and Education - but not Transplant Status - were identified as indicators of QOL. Physical QOL improved significantly after 5 years PT, when it was no longer worse than national norms. Mental QOL remained worse than national norms despite distance in time from transplant.nnnCONCLUSIONSnThe model proved useful in identifying a range of factors that contributed to QOL for women with PBC before and after transplant. Recommendations were made for clinical practice to improve QOL through a combination of treatment and self-management.

Uncertainty and Liver Transplantation: Women with Primary Biliary Cirrhosis Before and After Transplant

Uncertainty is a frequent feature of chronic illness and can have a particularly important impact in the case of organ transplantation. This study of 100 women with primary biliary cirrhosis who were either waiting for or had already had a liver transplant focused on both changes in uncertainty with transplant and the correlates of uncertainty both pre- and post-transplant. While those who were post-transplant had significantly lower uncertainty scores (measured by the Mishel Uncertainty in Illness Scale-Adult Version-MUIS-A) than those on the waiting list, uncertainty was still persistent and associated with a reduced quality of life. The most significant factors in relation to uncertainty were fatigue, depression, anxiety, and dissatisfaction with medical information received. It is important for both patients and transplant team members to recognize the impact of uncertainty on a patients well-being, both before and after a transplant, and to address the underlying factors that continue to compromise quality of life even after a life-saving procedure.

Liver and Kidney Transplantation: A Half-Century Historical Perspective

This article describes the evolution of solid organ kidney and liver transplantation and expounds on the challenges and successes that the early transplant researchers and clinicians encountered. The article highlights the surgical pioneers, delves into the milestones of enhanced immunosuppression protocols, discusses key federal legislative and policy changes, and expounds on the ongoing disparities of organ supply and demand and the need for extended criteria and live donor organs to combat these shortages. Finally, recent changes in organ allocation and distribution policies are discussed. The authors also spotlight novel interventions that will further revolutionize abdominal transplantation in the next 50 years.

Liver Disease in Pregnancy

This article briefly discusses gestational physiologic changes and thereafter reviews liver diseases during pregnancy, which are divided into 3 main categories. The first category includes conditions that are unique to pregnancy and generally resolve with the termination of pregnancy, the second category includes liver diseases that are not unique to the pregnant population but occur commonly or are severely affected by pregnancy, and the third category includes diseases that occur coincidentally with pregnancy and in patients with underlying chronic liver disease, with cirrhosis, or after liver transplant who become pregnant.