Rowen K. Zetterman

Donor age and outcome of liver transplantation.

To evaluate the effect of donor age on graft and patient outcome after liver transplantation an analysis of a large‐scale cohort study was performed at three tertiary referral liver transplant centers. Between April 1990 and June 1994, 772 adults underwent an initial single‐organ liver transplantation. The age of the donors averaged 35 years;193 (25%) were 50 or above, the age used to define “older” donors. Groups were compared for demographic, clinical, and biochemical features. Outcome was measured using results of biochemical tests after transplantation and by graft and patient survival. Compared with younger donors, older donors were more commonly women (59% vs. 33%:P ≤ .001) and died of central nervous system causes (79% vs. 28%) as opposed to trauma (13% vs. 63%:P ≤ .001). The recipients of the two groups of donor livers did not differ in important respects. However, intraoperatively, livers from older donors were more likely to be assessed as either “poor” or “fair” as opposed to “good” (17% vs. 4%:P ≤ .001) by the harvesting surgeon and to have initial “poor” or “fair” bile production (29% vs. 18%:P ≤ .001). During the first week postoperatively, the serum aminotransferase and bilirubin levels and prothrombin times were higher in recipients of older than those of younger donor livers. During follow‐up, graft survival was less for recipients of older donor livers at 3 months (81% vs.91%:P = .0001) and at 1 (76% vs. 85%:P = .007) and 2 years (71% vs. 80%:P = .005); patient survival showed similar though less marked differences. This association of donor age and poorer graft survival persisted after adjusting for many variables using bivariate and multivariate analyses. Importantly, however, the association with poor graft survival was largely among recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers assessed as good had a retransplant‐free survival similar to that of younger donor livers (87% vs. 91% at 3 months). Thus, use of older donor livers, the quality of which are judged to be good by the harvesting surgeon, is not associated with a decrease in patient or graft survival after liver transplantation. differences. This association of donor age and poorer graft survival persisted after adjusting for many variables using bivariate and multivariate analyses. Importantly, however, the association with poorer graft survival was largely among recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers, the quality of which was assessed as fair or poor by the harvesting surgeon; recipients of older donor livers assessed as good had a retransplant‐free survival similar to that of younger donor livers (87% vs. 91% at 3 months). Thus, use of older donor livers, the quality of which are judged to be good by the harvesting surgeon, is not associated with a decrease in patient or graft survival after liver transplantation.

Significance of megamitochondria in alcoholic liver disease

The significance of megamitochondria in the alcoholic liver injury of humans was investigated as part of a large Veterans Administration cooperative study of the natural history of alcoholic hepatitis. Two hundred twenty patients were clinically stratified into the following three groups according to disease severity using serum bilirubin and prothrombin time as indicators: Group 1 (mild disease), serum bilirubin levels less than 5 mg/dl and prothrombin time prolonged for less than 4 s; group 2 (moderate disease), serum bilirubin levels greater than 5 mg/dl but prothrombin time prolonged for less than 4 s; and group 3 (severe disease), serum bilirubin levels greater than 5 mg/dl and prothrombin time prolonged for greater than 4 s. Megamitochondria were observed in 20% of the patients (45 of 220). Of these, 43 patients were in groups 1 and 2 of severity and only 1 patient belonged in group 3. The association of megamitochondria with cirrhosis was infrequent (33%, 15 of 45 patients). The differences in severity correlated with the differences in mortality: in patients with megamitochondria, only 1 had died at 6 mo compared with 40 deaths in patients without megamitochondria. By 12 mo, there were two deaths in patients with megamitochondria versus 51 deaths in those patients without. No complications were present in 72% of patients with megamitochondria versus 39% for those without. Infection, gastrointestinal bleeding, pancreatitis, hyperglycemia, azotemia, delirium tremens, seizures, and hepatic encephalopathy were all more common in patients without megamitochondria. The patients with megamitochondria appear to represent a subcategory of alcoholic hepatitis with a milder degree of clinical severity, lower incidence of cirrhosis, fewer complications, and good long-term survival.

Suppressor cell activity in primary biliary cirrhosis

Recent evidence has suggested that peripheral blood suppressor cell populations can modulate immune responsiveness. Absence of suppressor cell activity has been noted in diseases of presumed autoimmune basis. We determined inducible suppressor cell activity in patients with primary biliary cirrhosis (PBC) as compared to age and sex-matched controls. There was a significant loss of suppressor cell activity for mitogen response in patients with PBC (−4.5±8.0%) versus controls (43.7±7.8%). No correlation of this loss to clinical parameters was observed. This study suggests PBC patients lack inducible suppressor cell activity. Such loss could allow continued reactivity to hepatic autoantigens and might provide partial explanation for the perpetuation of this disease.

Unconjugated bilirubin inhibits in vitro major histocompatibility complex-unrestricted cytotoxicity of human lymphocytes

Septic complications have been major problems in the management of patients with obstructive jaundice and neonatal jaundice. This study investigates effects of unconjugated bilirubin on lymphocyte-mediated cytotoxicity against human tumor target cells. In vitro exposure of human peripheral blood lymphocytes (PBL) with bilirubin IX alpha in bovine albumin solution resulted in a dose-dependent decrease of both natural killer activity and antibody dependent cellular cytotoxicity (ADCC) activity. Inhibition of both activities correlated with the amounts of intracellular bilirubin. Expression of cell surface CD16, CD56 antigen, and IL-2 receptor beta chain was unchanged in bilirubin-treated PBL as compared to bilirubin-untreated PBL. When bilirubin-treated PBL were cultured with interleukin-2 (IL-2), a dose-dependent decrease of lymphokine-activated killing activity, ADCC activity, and DNA synthesis was observed. Expression of CD56 antigen and IL-2 receptor alpha chain was unchanged in bilirubin-treated PBL following IL-2 stimulation as compared to bilirubin free control. These results suggest that bilirubin inhibits major histocompatibility complex-unrestricted cytotoxicity in both unstimulated and IL-2 stimulated lymphocytes. These observations may help explain the increased susceptibility to infection observed in hyperbilirubinemic patients.

Liver disease of the alcoholic.

Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.

Ascites progressing to an abdominal mass due to extramedullary hematopoiesis in a patient with agnogenic myeloid metaplasia (AMM)

SummaryWe report a patient with long-standing agnogenic myeloid metaplasia who developed ascites which progressed over 6 months to a massive solid peritoneal mass as a consequence of intraperitoneal extramedullary hematopoiesis The clinical and radiographic features of this unusual case are presented.

Malnutrition and Alcoholism–An Overview

Publisher Summary This chapter discusses the role of malnutrition in the pathogenesis of clinical and laboratory abnormalities in alcoholism. Alcoholics with identical patterns of food and alcohol intake exhibit different biochemical and morphologic lesions, suggesting genetic and constitutional factors are of key importance. Nutritional and metabolic alterations combine to produce a decrease in cerebral oxidative metabolism in uncomplicated delirium tremens. An increase in the spinal fluid lactate-pyruvate acid ratio, in the absence of change in blood lactate, is characteristic of this state that appears following withdrawal from alcohol or less commonly, despite maintained intake of large quantities of ethanol. Persons hospitalized because of complications of alcoholism regularly exhibit clinical and/or laboratory evidence of nutritional deficiency. The common clinical abnormalities are glossitis, nutritional anemia, and peripheral neuropathy; the most frequent laboratory evidence of a deficiency is decreased circulating levels of B complex vitamins. A good correlation exists between circulating and tissue levels of vitamins, so that the alcoholic with a reduction in total body vitamin content has a concomitant decrease in vitamins in biological fluids and tissues.

Esophageal ulceration following doxycycline ingestion.

Esophageal ulceration occasionally occurs in patients taking doxycycline capsules or tablets. In the case described here, examination of biopsy specimens obtained at endoscopy showed polarizable matrix material in the ulcer bed, thus confirming the diagnosis.

Where do we go from here|[quest]|

I chose to talk today about Where do we go from here? Ill give you a litany of the past year and end up with what I think are some of the important issues that affect the American College of Gastroenterology and its future.

Gastrointestinal Pathology. By Parakrama Chandrasoma, Appleton & Lange, 1999, ISBN 0-8385-3093.

This addition to our repertoire on gastrointestinal pathology serves two functions: a textbook and an atlas. It is written by a senior, experienced gastrointestinal pathologist with the active participation of his team of residents, fellows, and assistant professors. It then represents a “School” in which a standard approach to the task of surgical pathology diagnoses has been reached after considerable experience. This has the advantage of a unified style, contrasting with available books in which several authors, each an authority in a narrow field, contributes his/her chapter. It is, therefore, very useful as a companion in surgical pathology sign-out teams, especially when several senior, junior, and “in-training” pathologists participate. It is abundantly illustrated with mostly excellent gross and microscopic photographs. In most chapters, the state of the art in diagnostic pathology is well represented. In most cases, a choice has been made in discussing and recommending the author’s own interpretation of controversial issues. By the nature of its approach and authorship, this book can be of great help in dealing with the most common nosological entities and their most frequent histopathological manifestations. It may be less helpful in resolving uncommon entities or situations in which the pathologists need in-depth search for experts with more focused experiences. Similarly, it should not be expected to find in this book insights into the physiopathology or pathogenesis of the entities under study. For example: while discussing the role of the M cells overlying lymphoid follicles, the authors consider that their reported function may be of theoretical value but not of particular use “as yet.” In summary, this book can be highly recommended as a tool in surgical pathology diagnosis of gastrointestinal diseases, and especially for residents and junior pathologists. In the words of the author, they are going through an experience similar to that of the Jedi Knights in the movie Star Wars, and their leader, the senior surgical pathologist, is in charge of making sure they conquer “The Force.”