Vincents J. Dindzans

Prevalence of endoscopic findings in 510 consecutive individuals with cirrhosis evaluated prospectively.

Upper gastrointestinal hemorrhage is one of the more important complications of cirrhosis and a major cause of death in such patients. The main sites of bleeding are esophageal varices, gastritis, and peptic ulcers. In order to determine the prevalence of either potential bleeding lesions or of other endoscopic findings in hemodynamically stable individuals with various etiologies of cirrhosis, 510 consecutive cirrhotic patients, evaluated for possible orthotopic liver transplantation (OLTx) underwent an upper gastrointestinal endoscopy for combined diagnostic and therapeutic purposes. The patients were divided into two main groups: 319 patients with parenchymal liver disease and 191 patients with cholestatic liver disease. Gastritis was found significantly more often in patients with parenchymal liver disease than in those with cholestatic liver disease (49.8% vs 30.9%; P <0.001). In contrast, the prevalence of esophagitis, esophageal and gastric varices, gastric ulcer, duodenal ulcer, and duodenitis was similar in both groups. Normal endoscopic findings were present in 5.0% of the parenchymal group and 11.5% of the cholestatic group (P <0.02). Ascites and encephalopathy were found significantly more often in subjects with parenchymal liver disease as compared to those with cholestatic liver disease. Portal hypertension and its degree, as assessed by the presence and size of esophageal varices, was similar in both groups, and in both groups there was a statistically significant qualitative trend of increasing prevalence of esophageal varices with increasing severity of disease as estimated using Pugh-Childs criteria.

Colonic disease in cirrhosis

Colonic disease is relatively uncommon in cirrhosis. To determine the prevalence of colonic lesions in cirrhosis of all types, cirrhotics evaluated for possible liver transplantation underwent combined pan upper endoscopy and colonoscopy. The patients were divided into two main groups, 248 with parenchymal liver disease (nonviral and viral) and 164 with cholestatic liver disease. The prevalence of the various colonic lesions identified was: polyps, 8.4%; nonspecific edema, 19.9%; inflammatory changes, 11.6%; hemorrhoids, 25.2%; and rectal varices, 3.6%. Normal findings were present in 42.4%. Except for an increased prevalence (P less than 0.05) of edema and a reduced prevalence (P less than 0.001) of inflammatory changes in the parenchymal liver disease group, the prevalence for all other lesions was similar in the two groups. Esophageal varices were present in most patients with hemorrhoids and in all with rectal varices. The degree of portal hypertension and/or disease severity was associated with hemorrhoids but not with rectal varices. The higher prevalence of inflammatory changes in the cholestatic group was because one fourth of this group had an inflammatory bowel disease.

Prevalence of Duodenal Ulcer in Cirrhotic Males Referred for Liver Transplantation Does the Etiology of Cirrhosis Make a Difference

The prevalence of symptomatic duodenal ulcer (DU) assessed primarily in alcoholic males with cirrhosis is estimated to be approximately fivefold increased compared to the normal population. Little information is available, however, as to the prevalence of DU in nonbleeding, nonalcoholic subjects with cirrhosis. In order to estimate the prevalence of DU in males with various types of cirrhosis and its relation to the degree of portal hypertension, 216 male cirrhotic patients (165 with parenchymal liver disease and 51 with cholestatic liver disease) being evaluated for liver transplantation at the University of Pittsburgh between January 1985 and June 1987 underwent pan-upper gastrointestinal endoscopy. The prevalence of DU in each group was 7.8%. However, among the various subgroups it was as follows: chronic active hepatitis due to HBV: 9.4%, alcoholic: 12.2%, cryptogenic: 3.5%, autoimmune chronic active hepatitis: 6.6%, primary sclerosing cholangitis (PSC): 9.5%. The reference data for this study consist of data reported in the literature obtained in 355 healthy asymptomatic male volunteers. The prevalence of DU in this group is significantly less than in the study group (2.2% vs 7.8%; P<0.005). While the estimated risk for a DU is increased 3.71-fold (95% CI: 8.74, 1.57; P<0.005) in cirrhotic males in general as compared to normal males, only the subgroups with CAH due to HBV, alcoholism, and PSC were found to have an increased estimated risk of DU (all at least P<0.01). No association between the prevalence of DU and degree of portal hypertension could be demonstrated in either group.

Cyclosporine Augments Hepatic Regenerative Response in Rats

A number of mechanisms participate in the hepatic injury that occurs during and following liver transplantation. A normal allograft regenerative response is probably essential for a successful transplant outcome. In this study, the effect of cyclosporine, a potent immunosuppressant used routinely after liver transplantation, on the regenerative response of the liver after partial hepatectomy was investigated. Male Wistar rats were pretreated for one week with either cyclosporine or the olive oil vehicle and were subjected to either a two-thirds partial hepatectomy or a sham operation. Animals were sacrificed at various times postoperatively and the remnant livers were weighed to determine the liver weight to body weight ratio, two biochemical measures of a regenerative response (cytosolic ornithine decarboxylase activity and thymidine kinase activity), and the hepatic content of estrogen and androgen receptors, as the content of these receptors has been shown to modulate, at least in part, the subsequent hepatic regenerative response. The preoperative hepatic cytosol content of ornithine decarboxylase, thymidine kinase, and estrogen receptor was significantly greater (P<0.05) in rats pretreated with cyclosporine than in those treated with the vehicle alone. A significant increase in ornithine decarboxylase and thymidine kinase activities occurred after partial hepatectomy in both the cyclosporine-pretreated and vehicle-pretreated animals. The absolute levels for each parameter were also greater in the cyclosporine-treated animals than in the vehicle-treated controls at 24 hr after partial hepatectomy (P<0.05). The pattern of change in the hepatic cytosolic content of estrogen and androgen receptors in both groups of animals was comparable with those described previously for regenerating liver. These data suggest that cyclosporine may predispose the liver to respond to either a regenerative signal or perceived need and thereby fortuitously enhance liver graft performance after successful surgical implantation.

Serum-ascites albumin gradients in nonalcoholic liver disease.

Several studies performed in alcoholics with advanced liver disease have demonstrated a positive correlation between the serum-ascites albumin gradient (SAAG) and measured portal venous pressure. A single study performed in 15 patients with exudative malignant ascites and 29 patients with alcoholic liver disease demonstrated that a SAAG of <1.1 was essentially diagnostic of a malignant origin of the ascites. In an effort to confirm and extend these observations to individuals with nonalcoholic liver disease, 24 patients with nonalcoholic liver disease and 11 with alcoholic liver disease undergoing orthotopic liver transplantation (OTLx) were studied. At the time of liver transplantation, each had their serum and ascitic fluid albumin levels determined, the gradient calculated, and their portal venous pressure (PVP) as well as the corrected portal venous pressure (PPc) measured directly. A significant correlation (r=0.624) between the PPc and the SAAG was found in the 11 alcoholics (P<0.05). No such correlation existed for those with nonalcoholic liver disease (r=0.398). Moreover, a SAAG <1.1 was found in three of nonalcoholics with cirrhosis in the absence of an abdominal malignancy. We conclude that (1) the SAAG and PPc are statistically related to each other in individuals with alcoholic liver disease but not in those with a nonalcoholic cause for cirrhosis, and (2) SAAG <1.1 is not diagnostic of abdominal malignancy but can occur in those with advanced nonmalignant hepatic disease.

Endoscopic findings in alcoholic liver disease: Does gender make a difference?

Alcohol abuse and alcoholic liver disease are major health problems in many parts of the world. The prevalence of alcoholic liver disease is directly related to both rate and duration of alcohol intake. It is a widely held belief that women are more susceptible to the hepatotoxic effects of ethanol, and develop alcohol-related liver disease more readily than do men. A lower volume of distribution for alcohol, greater immune reactivity and higher activity of alcohol metabolizing enzymes in women are considered, at least in part, to be responsible for the greater susceptibility of women to alcoholic liver disease. Little data exist as to the extent of gastrointestinal involvement in advanced alcoholic liver disease, and even less, as to the relationship of these potential gastrointestinal lesions with gender, and whether or not female patients develop gastrointestinal complications at an earlier time in their liver disease natural history and whether when it occurs it is more severe than that seen in males. To answer these questions, 75 subjects (49 men and 26 women) with alcoholic liver disease underwent elective upper and lower gastrointestinal endoscopy while they were clinically stable. The prevalence of the various gastrointestinal lesions did not differ significantly between male and female alcoholics except for gastric ulcer (GU) and nonspecific inflammatory changes of the colon which were more common in females than in males (23.1% vs. 6.1% and 11.1% vs. 0%, respectively; both p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of isolated portal hypertension on kupffer cell function

The increased incidence of infection in cirrhotics may in part be attributable to dysfunction of the reticuloendothelial system (RES) in removing pathogens from the circulation. The portosystemic shunting (PSS) that results from portal hypertension in cirrhotics may compromise RES function by allowing enteric pathogens to be shunted away from the Kupffer cells. A well-characterized model of portal hypertension induced by partial portal vein ligation (PVL), in which there is no hepatic parenchymal cell damage, was used. Kupffer cell function is unaltered and the effect of PSS alone on overall RES function can be evaluated. In addition to the usual immunologically inert [99mTc]sulfur colloid, an actual pathogen was also evaluated. PVL and sham-ligated rats were given either [99mTc]sulfur colloid orE. coli via the ileocolic vein. The right femurs, lungs, livers and spleens of the animals receiving99mTc were excised and the radioactivity counted. The lungs, livers, and spleens of the animals receivingE. coli were liquefied and the bacteria were quantified. For both groups the ratios of99mTc orE. coli in the lung, spleen, and femur to liver were calculated. PVL rats had significantly more99mTc in the lung, spleen, and femur than the sham rats. There were also significantly moreE. coli in the lungs for PVL rats but no significant difference in the spleen counts. These results imply that even in the absence of Kupffer cell dysfunction, PSS alters reticuloendothelial system function by causing a greater distribution of pathogens to the periphery. This altered distribution may contribute to an increased susceptibility to infection in cirrhotics.

Prophylactic versus emergency sclerotherapy of large esophageal varices prior to liver transplantation.

From January 1985 through July 1987, adult patients accepted for liver transplantation with large esophageal varices were enrolled in a study evaluating the use of prophylactic vs emergency sclerotherapy. Six hundred forty-eight subjects received prophylactic sclerotherapy, and 172 received emergent sclerotherapy. Esophageal stricture formation was increased 12.9-fold (P<0.001), esophageal perforation 6.4-fold (P<0.005), and postsclerotherapy bleeding esophageal ulcers 3.7-fold (P<0.001) in those receiving emergency sclerotherapy as opposed to prophylactic sclerotherapy. These differences were even greater if the number of sclerotherapy sessions rather than the number of patients was used as the denominator for the comparisons. In total, 19.6% of emergency sclerotherapy cases were associated with an untoward outcome of sclerotherapy; only 1.9% of cases receiving prophylactic sclerotherapy experienced an untoward outcome (P <0.001). These data demonstrate that emergency sclerotherapy is associated with a greater prevalence of complications and support earlier studies that show that sclerotherapy prevents variceal bleeding over the short term. The data also suggest that when applied to patients with large varices awaiting orthotopic liver transplantation, it enhances the chance of a patient surviving to be transplanted by preventing a variceal bleed and the spiral of liver failure and death that frequently follows an episode of acute variceal bleeding.

T-lymphocyte subsets in gut and blood of liver transplant recipients with and without cytomegalovirus gastroenteritis

The effects of orthotopic liver transplantation (OLTx) and cytomegalovirus (CMV) gastroenteritis on the type of mononuclear cells within the upper gastrointestinal tract were determined. Nineteen liver transplant recipients were studied both before and after transplantation. Each underwent a pan-upper gastrointestinal endoscopy with biopsy of the antrum and duodenum before and four weeks following liver transplantation. A panel of monoclonal antibodies prepared against HLA-DR, NK, IL-2R, T11, T4, T8, and B1 cell surface antigens was used to examine the tissues. Before OLTx, none of the 19 subjects studied had clinical or histologic evidence for CMV gastroenteritis. Following OLTx, five of the 19 subjects had CMV gastroenteritis. The number of HLA-DR positive staining lymphocytes present in biopsies obtained post-OLTx was significantly greater (P<0.005) than those present in biopsies obtained pre-OLTx regardless of the presence or absence of CMV gastroenteritis. No difference in the intensity of HLA-DR antigen expression between pre- and post-OLTx biopsies and those with and without CMV gatroenteritis was evident. No difference in the number of natural killer (NK) cells and the number of cells expressing the interleukin-2 receptor (IL-2R) was evident between biopsies obtained pre- and post-OLTx. In contrast, the number of T lymphocytes bearing the T11, T4, and T8 markers and the calculated T4/T8 ratio differed between biopsies obtained pre- and post-OLTx and between those positive for CMV gastroenteritis post-OLTx and those without evidence for CMV gastroenteritis either before or after OLTx, although these changes were not consistent throughout the gastrointestinal tract. In summary, these findings demonstrate that the process of OLTx and the presence of CMV infection alter the number and types of T cells present within the stomach and duodenum and the number of T lymphocytes that are activated as determined by the presence of HLA-DR antigen expression.