Robert R. Schade

Nonalcoholic Cirrhosis Associated With Neuropsychological Dysfunction in the Absence of Overt Evidence of Hepatic Encephalopathy

Although much is known about the neuropsychological functioning of cirrhotic individuals with Laennecs (alcohol associated) cirrhosis, little is known about the neuropsychological functioning of individuals with nonalcoholic cirrhosis. In the present investigation, we have determined that individuals suffering from chronic nonalcoholic cirrhosis, despite the absence of clinical signs of hepatic encephalopathy, are impaired on neuropsychological tests that measure visuopractic capacity, visual scanning, and perceptual-motor speed. In contrast, intellectual, language, memory, attentional, motor, and learning abilities are intact. In comparison with a chronically ill control group of patients suffering from Crohns disease, individuals with advanced nonalcoholic cirrhosis exhibit less emotional disturbance, but are more impaired in their daily activities. These findings indicate that individuals with nonalcoholic cirrhosis, even in the absence of overt clinical signs of encephalopathy, manifest neuropsychological impairments and experience significant disruption in the routines of everyday living.

Effects of renal impairment on liver transplantation

To determine the incidence, prevalence, and prognostic value of preoperative and postoperative renal dysfunction occurring in adults undergoing orthotopic liver transplantation, the records of 102 consecutive adults who underwent orthotopic liver transplantation using cyclosporin A were reviewed. Renal dysfunction was defined arbitrarily as an increase in creatinine or blood urea nitrogen, or both, to 1.5 and 50 mg/dl, respectively, in patients previously having normal renal function or a 50% increase in either creatinine or blood urea nitrogen in patients with preexisting renal dysfunction. Twenty-six of the 102 patients had renal dysfunction before orthotopic liver transplantation. Sixty-eight of the 102 patients studied experienced an episode of renal impairment after orthotopic liver transplantation. Forty-nine of these episodes developed early, having occurred within the first 6 days. Late renal impairment occurred in 36 cases at 32 +/- 6 days after orthotopic liver transplantation. Using multivariate analysis, cirrhosis of a noncholestatic nature was found to be an independent predictor of early renal impairment. Trough blood cyclosporin A levels measured by radioimmunoassay were higher in those who experienced early renal impairment or late renal impairment than in those who did not (p less than 0.05). Several factors capable of adversely influencing renal function (nephrotoxic drugs, shock, and graft failure) other than cyclosporin A were present also in half of the patients who developed late renal impairment. Overall, 25 patients died. Multivariate analyses identified serious postoperative infection, graft failure, and preoperative renal dysfunction to be independent predictors of mortality.

Effect of metoclopramide on gastric liquid emptying in patients with diabetic gastroparesis

Metoclopramide tablets have been approved for use in the acute and chronic management of diabetic gastroparesis. Its efficacy as an antiemetic has been well documented. We measured the acute and chronic effects of oral metoclopramide on gastric liquid emptying in 12 diabetic patients with symptoms of stasis using scintiscanning techniques. We found that liquid emptying in these subjects was abnormal, as determined by residue area determination when compared to normal volunteers (P<0.01). Metoclopramide 10 mg orally acutely enhanced emptying, restoring it to control values (P<0.01). In contrast, when gastric emptying was evaluated following one month of chronic liquid metoclopramide use, 10 mg before each meal, the acute effect of the drug on emptying could no longer be demonstrated and residue areas returned to baseline values, suggesting that chronic oral administration of metoclopramide may result in a loss of the gastrokinetic properties of this drug.

Rapid growth of an intact human liver transplanted into a recipient larger than the donor

Two individuals undergoing orthotopic hepatic transplantation received livers from donors who were on average 10 kg smaller than themselves based on recipient ideal body weight. As a result, the donor livers in these 2 cases were 29%-59% smaller than would be expected had the donor liver and recipient been matched ideally. The liver grafts in the recipients steadily increased in size, as determined by serial computed tomography scanning, to achieve new volumes consistent with those that would have been expected in a normal individual of the recipients size, sex, and age. Fasting plasma levels of amino acids, glucagon, insulin, and standard liver injury tests were monitored to determine which measure best reflected the changes observed in the size of the grafts over time. No relationship between the changes observed in any of these parameters and hepatic growth was apparent. In both cases, the liver increased in volume at a rate of approximately 70 ml/day. These data demonstrate that a small-for-size liver transplanted into a larger recipient increases in size at a rate of approximately 70 ml/day until it achieves a liver volume consistent with that expected given the recipients size, age, and sex.

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.

Esophageal function after injection sclerotherapy: Pathogenesis of esophageal stricture☆

Injection sclerotherapy effectively controls hemorrhage from esophageal varices. Treatment must be repeated at intervals to obliterate varices. Long-term sequelae of such treatment are unknown but may include stricture formation. To assess the impact of repeated sclerotherapy on esophageal function, this prospective study measured lower esophageal sphincter pressure, reflux, and motility in patients before and after treatment. Injection sclerotherapy had no effect on lower esophageal sphincter pressure. Reflux was common before treatment and became even more prevalent after treatment, with reflux occurring in 60 percent of postsclerotherapy patients. Striking disturbances in esophageal motility were observed after treatment. Injection sclerotherapy induces a chemical esophagitis that impairs esophageal motility. Delayed acid clearance in the presence of reflux results in superimposed acid esophagitis. Esophageal strictures may thus be produced. We advise a standard antireflux medical regimen in our sclerotherapy patients.

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.

Does previous abdominal surgery alter the outcome of pediatric patients subjected to orthotopic liver transplantation

The medical, anesthesia, and surgical records of 89 consecutive pediatric patients who underwent an orthotopic hepatic transplantation procedure at the University of Pittsburgh from February 1981 to May 1984 were reviewed to evaluate the effect of prior abdominal surgery upon the morbidity and mortality of orthotopic liver transplantation in children. Fifty-seven children (group 1) had had prior abdominal surgery, whereas 32 (group 2) had not. The group 1 subjects were younger (p less than 0.001), had better prothrombin times (p less than 0.01), and better platelet counts (p less than 0.02) than did those in group 2. No difference in the duration of anesthesia or intraoperative use of fresh frozen plasma or platelets was evident between the two groups. However, group 1 patients were given more red blood cells intraoperatively than were the group 2 patients (p less than 0.01). The group 1 patients had more total postoperative infections (p less than 0.05), which was due solely to a greater number of abdominal infections (p less than 0.05), but similar total hospital and intensive care unit stays as did the group 2 patients. When those in group 1 were divided into those having a previous Kasai procedure versus those who did not, no differences between the two groups were apparent except for age. Based upon these data, we conclude that prior abdominal surgery does not affect mortality, the duration of hospital or intensive care unit stay, plasma or platelet requirements, and total anesthesia time required for orthotopic liver transplantation, but does enhance the number of red blood cell transfusions and infections, particularly abdominal infections, in children undergoing this procedure.

T-Lymphocyte Subsets in Liver Tissues of Patients with Primary Biliary Cirrhosis (PBC), Patients with Primary Sclerosing Cholangitis (PSC), and Normal Controls

T lymphocytes infiltrating hepatic tissues were typed and enumerated in liver biopsies of patients with primary biliary cirrhosis (PBC), patients with primary sclerosing cholangitis (PSC), and normal controls using monoclonal antibodies and the avidin-biotin-immunoperoxidase technique. The peripheral blood mononuclear cells were studied also by flow cytometry. In PBC, T lymphocytes were decreased (P<0.001) in the blood [absolute number was 426±200 (SE) vs 1351±416 in 15 controls], as was the helper/suppressor (T4/T8) ratio (1.0±0.1 vs normal 2.3±0.3). T lymphocytes were the most numerous mononuclear cells infiltrating portal areas of PBC livers: 749±93/5 high-power fields (HPF) in PBC vs 98±15/5 HPF (P<0.01) in controls. The T4/T8 ratios varied from 0.9 to 2.3 (mean, 1.8±0.1) in the portal triads (normal mean, 1.6±0.1), with the T4+ cells accounting for more than 75% of infiltrating T cells. In contrast, the mean T4/T8 ratio in portal triads of PSC was reduced (1.0±0.3) due to a significant increase (P<0.001) in the number of T8+ cells. The T cells around and in the walls of bile ducts in PBC were mostly T8+, and the T4/T8 ratio was 0.8±0.2. No T8+ cells were seen in this location in PSC and normal livers. Few mononuclear cells were present in hepatic lobules. Subtyping of T lymphocytes in liver tissues of patients with PBC and PSC may be helpful in the differential pathologic diagnosis. In patients with advanced PBC, a decrease in T4+ cells in the blood appeared to be accompanied by their accumulation in the portal triads. In contrast, T8+ cells accumulated preferentially around bile ducts.

Neurobehavioral correlates of cholestatic and hepatocellular disease: differentiation according to disease specific characteristics and severity of the identified cerebral dysfunction.

Subjects with three different types of hepatic cirrhosis were compared on a battery of neuropsychological tests to determine if cerebral dysfunction varied according to the type of liver disease. It was found that the manifest cognitive impairments varied according to the type and etiology of the liver disease. These findings underscore the sensitivity of neuropsychological tests in the detection of hepatic encephalopathy, particularly in cases where there are no overt clinical signs or symptoms of neurologic disturbance. They also suggest that the nature and severity of the measurable neuropsychological abnormalities may vary within patient populations depending upon the etiology of the individuals liver disease and the specific pathophysiological mechanisms involved in its progression.