Robert E. Weesner

Protein-calorie malnutrition associated with alcoholic hepatitis. Veterans administration cooperative study group on alcoholic hepatitis

Three hundred sixty-three alcoholic patients with alcoholic hepatitis were studied in six Veterans Administration medical centers. By history, alcohol consumption was 227.9 g per day, with a mean duration of 23.8 years. Cirrhosis accompanied the alcoholic hepatitis in 58.7 percent of the patients who underwent biopsy or autopsy. Complete nutritional assessment was performed in 284 patients, and observed nutritional changes were classified into those associated with marasmus or those characterizing kwashiorkor. A smaller comparison group of 21 alcoholic patients matched for age and alcohol consumption but without clinically evident liver disease was also studied in an identical manner. None of the patients with liver disease was completely free from malnutrition, whereas 62 percent of the alcoholic patients without liver disease showed abnormalities. In patients with alcoholic hepatitis, some findings associated with marasmus were seen in 86 percent, and some features of kwashiorkor were observed in 100 percent. When present together, the complete picture of kwashiorkor and marasmus correlated closely with the clinical severity of the liver disease (p less than 0.005). The nearly constant association of either complete or partial kwashiorkor or marasmus suggests that the separation of these two entities is artificial in alcoholic patients with liver disease. Although, experimentally, malnutrition may not be essential for the development of alcoholic hepatitis, clinically, it appears to precede the development of the liver injury, which suggests an interaction. Recognition is important so that appropriate nutritional therapy can be provided.

Protein energy malnutrition in severe alcoholic hepatitis : diagnosis and response to treatment

Background: Active nutrition therapy and the anabolic steroid oxandrolone (OX), in selected patients with severe alcoholic hepatitis, significantly improved liver status and survival. We report here on the changes in their nutritional parameters. Methods: Protein energy malnutrition (PEM) was evaluated and expressed as percent of low normal in 271 patients initially, at 1 month and at 3 months. Active therapy consisted of OX plus a high caloric food supplement vs a matching placebo and a low calorie supplement. Results: PEM was present in every patient; mean PEM score 60% of low normal. Most of the parameters improved significantly from baseline on standard care; the largest improvement seen in visceral proteins, the smallest in fat stores (skinfold thickness). Total PEM score significantly correlated with 6 month mortality (p=.0012). Using logistic regression analysis, creatinine height index, hand grip strength and total peripheral blood lymphocytes were the best risk factors for survival. When CD lymph...

VA Cooperative Study on Alcoholic Hepatitis III: Changes in Protein-Calorie Malnutrition Associated with 30 Days of Hospitalization with and without Enteral Nutritional Therapy

Patients with moderate to severe alcoholic hepatitis and features of protein-calorie malnutrition were studied with respect to changes in their nutritional status during 30 days of hospitalization. Thirty-four patients served as controls, were given a 2500 kcal hospital diet and allowed to eat ad libitum. Twenty-three patients were given, in addition to the hospital diet, a nutrition supplement high in calories, protein, and branched-chain amino acids (Hepatic Aid). Because of anorexia, the controls consumed lesser amounts of both calories and protein while those given the nutritional therapy exceeded their estimated energy requirements (116.1%) and consumed a mean of 98.3 g of protein per day. This was well tolerated despite the fact that portal systemic encephalopathy was present in 72% of the patients. Mortality associated with the liver disease was comparable in both groups, 16.7% in the treated vs 20.6% in the controls. In those patients that survived the 30 days of hospitalization, clinical and biochemical tests of liver injury improved in both groups. With respect to their nutritional status, those given nutritional therapy showed significant improvement in six of the nine parameters (67%) used to assess nutrition. In the controls significant improvement was observed in only two nutritional parameters (22%) while three parameters (33%) deteriorated further. These three were all associated with calorie deprivation (marasmus). This study suggests that patients with acute alcoholic hepatitis require additional nutritional therapy to maintain and improve their nutrition parameters, especially those related to marasmus; and that Hepatic Aid is well tolerated for this purpose.

Cell-mediated hepatic injury in alcoholic liver disease

BACKGROUND The mechanism responsible for the initiation and perpetuation of alcoholic liver disease (ALD) remains poorly understood. This investigation attempted to elucidate the role of cell-mediated immune phenomena in the pathogenesis of ethanol-induced liver injury. METHODS Frozen liver biopsy specimens from 144 patients with moderate to severe ALD were examined by the avidin-biotin immunoperoxidase technique for the expression of antigenic markers of T and B lymphocytes, natural killer cells, and class I and II MHC molecules in the tissue. RESULTS Expression of CD3 by lymphocytes correlated significantly with regenerating nodules, intralobular inflammation, central sclerosis, and abnormalities of Kupffer cells. B cells were rarely present, and natural killer cells were absent. CD3+ lymphocytes expressed either CD4 or CD8 surface molecules. Enhanced class I MHC expression correlated significantly with portal inflammation, limiting plate erosion, vascular abnormalities, and hemosiderosis. Expression of class II MHC molecules correlated significantly with necrosis, bile stasis, and Mallory bodies. CONCLUSIONS The distribution and persistence of CD4+ and CD8+ cells in actively advancing ALD, the enhanced MHC expression on hepatocytes, and their relationship to alcoholic hyalin and necrosis lend support to the hypothesis that a cytotoxic T lymphocyte-hepatocyte interaction plays a role, perhaps via lymphokine production, in the genesis or perpetuation of ALD.

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.

Colonic abscess and focal peritonitis secondary to India ink tattooing of the colon

Colonoscopy is the method of choice for removing most colonic polyps. At times, however, small polyps or tumors are detected which cannot be safely or completely removed by this procedure and are therefore referred for surgical resection. Many of these lesions are not visible or palpable to the surgeon, and resection must be planned on the basis of the endoscopists estimation of the location of the lesion. Although colonoscopy is a highly sensitive means by which to detect lesions, it is less precise in anatomically localizing lesions to a specific area of the colon. Errors in endoscopic localization of lesions have led to blind removal of uninvolved segments of colon, leaving the lesion behind.2 In an attempt to improve the accuracy of anatomic localization, endoscopists have used metal clip placement,3 barium enemas,2 fluoroscopy,4 and intra-operative colonoscopy,5 with less than optimal results. Currently, some experts8 in the field of gastrointestinal endoscopy recommend endoscopic tattooing as an ideal way by which to mark the colon because it is simple, inexpensive, safe, and accurate. Endoscopic tattooing results in an easily visible serosal stain which allows the surgeon to accurately remove the involved segment of bowel. India ink has been the only agent used in this procedure because of the intensity and prolonged duration of the tattoo marks it produces. Although this localization method has been used since 1975, there is little information in the literature about it. To date, only 15 cases of India ink tattoos of the colon have been reported and no complications

Hepatitis B vaccination

Alcoholics are at risk to develop hepatitis B infections, chronic active hepatitis, and even hepatoma. Hence, immunization with hepatitis B vaccine is recommended. However, immune abnormalities may coexist which alter their responsiveness to vaccination. This study compares the immune response to this vaccine in controls (group I), alcoholics without overt liver disease (group II), and alcoholics with clinical liver disease (group III). By the seventh month after the initial vaccination, 89% in group I, 70% in group II, and 18% in group III had a response >36 RIA units. The magnitude of the response was significantly different in groups I, II, and III (19,456 vs 8,326 vs 153 RIA units, respectively; P <0.05, group I vs III). In those who did not respond, a significant (P < 0.02) lower helper/inducer (T4)class of lymphocytes was observed as compared to patients who exhibited an adequate response. These observations suggest: (1) that the response to hepatitis B vaccine is a T-cell-dependent event and (2) that in this population, using the existing vaccine, postvaccination evaluations of antibody concentrations are needed before protection against hepatitis B infection can be assumed.

High-fat diet in a short bowel syndrome. Intestinal absorption and gastroenteropancreatic hormone responses.

A patient with only 137 cm of jejunum suffereing from excessive jejunostomy losses was studied on three isocaloric liquid formula diets (3850 kcal/24 hr) differing only in carbohydrate and fat content. An increase in dietary fat from 64 g to 200 g per 24 hr and a reciprocal decrease in dietary carbohydrates resulted in a linear increase in the amount of fat absorbed, from 44 g to 133 g and in a 2.5-fold decrease in ostomy fluid bile acids. No undesirable side effects were noted on the 200-g fat diet: the ostomy fluid dry weight was lower than on 64 g of fat and the ostomy fluid output was lowest of all diets. Compared to healthy adults, the patient had higher fasting blood insulin and pancreatic glucagon. Meal-stimulated insulin, glucagon, gastrin, and GIP were also more than two standard errors above mean responses observed in healthy subjects. Smallest meal-stimulated increase in insulin, gastrin and GIP was noted on the 200-g fat diet. This diet induced the highest levels of glucagon. In a hormonally hyperactive individual after massive resection of the distal intestine favorable effects of a high-fat diet consist of increased absorption of dietary fat and bile acids and reduced release of gastroenteropancreatic hormones with the exception of glucagon.

Use of omeprazole in the management of giant duodenal ulcer: Results of a prospective study

BACKGROUND Giant duodenal ulcer (GDU) is generally thought to require surgical intervention. Proton pump inhibitors have beneficial effects in peptic ulcer disease, but their role in GDU disease is unknown. We examined the use of omeprazole in GDU management. METHODS Twenty-eight patients were diagnosed with GDU. One patient required immediate operative intervention. The remaining 27 were placed on omeprazole (40 mg daily). When ulcer healing was documented by endoscopy, the patients were placed on oral histamine-2 receptor antagonist therapy. RESULTS Of the 28 study patients, 20 (71.4%) did not require operative intervention, and 8 (28.6%) required operation for ulcer complications. Of the 15 patients with adherent clot or a visible vessel at initial endoscopy, 7 (46.7%) required operative intervention, as compared with 1 (7.7%) of the 13 patients without a visible vessel or adherent clot. This difference was statistically significant (P < .05). Twenty-three patients underwent antral biopsy and/or enzyme-linked immunosorbent assay for Helicobacter pylori, and 9 (39.1%) had a positive result. CONCLUSIONS Omeprazole is effective in the treatment of GDU disease. An adherent clot or a visible vessel at endoscopy indicates a higher likelihood of complications requiring operation. The relatively low H pylori infection rate, as compared with other peptic ulcer disease, may indicate a different pathophysiology in GDU.

Effect of chronic ethanol consumption on the pancreas of the hamster

The purpose of this study was to determine the effect of chronic ethanol consumption on pancreatic morphology and biochemistry in the hamster, with special attention to lipid changes. A control group of Syrian golden hamsters fed a synthetic liquid diet was compared to an ethanol group pair-fed the same diet with ethanol substituted for 35% of the carbohydrate calories. The animals were sacrificed at 7 weeks and 3, 6, 9, and 12 months. After 12 months of ethanol consumption, a significant decrease in pancreatic triglycerides and a significant increase in pancreatic RNA was seen. These changes were associated with a rise in pancreatic weight and protein content in the ethanol group, reversing a six-month decline in these values. This rise in RNA and protein in the ethanol-treated group corresponded with the appearance of large abnormal zymogen granules. Other ultrastructural features such as lipid droplets, mitochondria, and endoplasmic reticulum were not altered by ethanol. Ethanol did increase the water content of the pancreas. Although ethanol had no effect on the fasting levels of insulin or pancreatic polypeptide, the fasting serum gastrin immunoreactivity was significantly lower in the ethanol animals. This study shows that chronic ethanol consumption produces a metabolic change in the hamster by 12 months which is suggestive of increased protein synthesis with a decrease in pancreatic triglycerides and no lipid droplet formation.