N-acetylglucosaminyltransferase III in human serum, and liver and hepatoma tissues: increased activity in liver cirrhosis and hepatoma patients

An N-acetylglucosaminyltransferase III which catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage (bisecting N-acetylglucosamine) to the beta-linked mannose of the trimannosyl core structure of N-linked oligosaccharides of glycoproteins was measured in human serum, and liver and hepatoma tissues. The enzyme activity in serum was significantly elevated in patients with hepatomas and liver cirrhosis, and the activity markedly decreased on the transcatheter arterial embolization treatment. High activities were also found in the hepatoma and cirrhotic liver tissues, indicating that the serum activity reflected the activity in the tissues. The assaying of the enzyme activity in serum appears to be useful for the detection and monitoring of primary hepatomas.     

Diet-induced thermogenesis in patients with liver cirrhosis

Summary. Diet-induced thermogenesis after ingestion of a mixed meal was investigated in eight patients with documented liver cirrhosis and in eight age- and sex-matched healthy controls. Respiratory gas exchange was measured continuously for one hour in the basal state and for three hours after ingestion of a mixed liquid meal, consisting of 17% kJ protein, 28% kJ lipids and 55% kJ carbohydrates and dispensed to correspond to 60% of the individually computed energy expenditure. Arterial substrate and hormone concentrations were determined before and at timed intervals for three hours after the meal. Urine was collected for determination of nitrogen excretion. The patients' oxygen uptake, energy expenditure and respiratory quotient were similar to those of the controls in the basal state. After the meal, pulmonary oxygen uptake and energy expenditure rose markedly in both groups during the first hour and were subsequently stable. The average increase in oxygen uptake above basal during the whole study period was 21·2 ± 1·8% and 22·3 ± 1·2% (NS) in patients and controls, respectively. The corresponding increase in energy expenditure was 24·8 ± 2·0% in the patients and 24·9 ± 1·4% in the controls (NS). The respiratory quotient was elevated throughout the postprandial period in both groups but the quotient was significantly higher in the patients (P<0·05–0·001), suggesting a greater proportion of carbohydrate oxidation. The basal arterial concentrations of insulin and glucagon were significantly higher in the patients. After the meal the insulin level increased 10- to 20–fold in both groups. Glucose concentration rose significantly in both groups to a maximum of 8·82 ± 1·00 and 8·03 ± 0·95 mmol/l in patients and controls, respectively, at 60 min after the meal. This was accompanied by a fall in the levels of glycerol and ketone bodies in both groups, indicating decreased lipolysis. It is concluded that both the basal energy expenditure and the thermogenic response to a mixed meal are similar in patients with liver cirrhosis and in healthy controls. The patients' carbohydrate oxidation rose to a greater extent after the meal, probably as a consequence of excessive increases in insulin concentration, demonstrating that insulin resistance in these patients may be compensated for by postprandial hyperinsulinaemia.     

Pharmacokinetics of miocamycin in patients with liver cirrhosis

The pharmacokinetics of miocamycin, a new macrolide antibiotic, was studied in 6 healthy controls and 6 patients with compensated liver cirrhosis. The results indicate that in chronic liver disease the kinetics of the drug is altered. Therefore, a dosage adjustment of miocamycin is recommended when dealing with these patients.     

Pharmacokinetics of zidovudine in patients with liver cirrhosis

The pharmacokinetics of zidovudine (azidothymidine, AZT) was investigated after oral administration (200 mg) in 14 human immunodeficiency virus seronegative patients with liver cirrhosis. They were divided in three groups according to the severity of the liver disease quantitated by the Child-Pugh score. Plasma and urine concentrations of zidovudine and its glucuronidated metabolite (GAZT) were measured simultaneously by HPLC assay. Findings were compared with those previously measured in six healthy volunteers. As a consequence of a marked drop in oral clearance (10 +/- 4 versus 38 +/- 15 ml/min/kg), zidovudine concentrations, half-life, and mean residence time were increased in patients with cirrhosis. No difference could be established between the three groups. The reason for such a decrease in oral clearance of zidovudine was the reduction in the GAZT formation clearance (236 +/- 73 versus 1540 +/- 540 ml/min); this led to a decrease in the AUC ratio of GAZT and zidovudine (1.3 +/- 0.6 versus 4.6 +/- 0.7), which was directly related to the severity of the cirrhosis. In patients, as in volunteers, formation of GAZT rate limits its elimination. To avoid important cumulation of zidovudine after repeated dosing in patients with acquired immunodeficiency syndrome who have hepatic impairment, a dosage adjustment could be proposed.     

Platelet and plasma serotonin in patients with liver cirrhosis

To evaluate the role of serotonin in liver cirrhosis, serotonin was determined by high-performance liquid chromatography in plasma, platelets and ascitic fluids from 14 cirrhotic patients. Plasma-free serotonin was within the normal range, but intraplatelet serotonin was significantly low in cirrhosis (p less than 0.001) and this decrease paralleled the severity of the disease. The concentration of serotonin in ascitic fluids was 12% of the corresponding plasma concentrations. Our data indicate that serotonin levels are influenced by hepatic injury, but the reasons for these changes are still unclear.     

Portal hypertension and varices in patients with liver cirrhosis

Portal hypertension is a complication seen in patients with liver cirrhosis and is characterised by high pressure in the portal vein. As portal hypertension worsens, varices can form, leading to increased morbidity and mortality if these rupture. Bleeding can be prevented with pharmacological agents and endoscopic therapy; however, some patients will experience variceal haemorrhage. Medical and nursing management of acute variceal haemorrhage is key to a successful outcome, and after initial resuscitation, endoscopic therapy should be undertaken. Long-term management to prevent re-bleeding may involve surgery to implant shunts, which aim to reduce portal venous pressure. However, patients often require referral to specialist centres for transplant assessment.     

Management of patients with advanced liver cirrhosis

This article provides an overview of liver cirrhosis. The pathophysiology, common investigations and the nursing management of patients with advanced liver cirrhosis are examined.     

Symptom experience in Korean patients with liver cirrhosis

This study was done to examine the level of symptom experience, and symptom variation in relation to demographic and clinical variables, in Korean patients with liver cirrhosis (LC). Symptom experience was measured using a scale developed by the researchers through a literature review on LC. Participants were 129 patients whose mean age was 53.6 (standard deviation [SD] = 9.28) years. The results indicated that (1) overall symptom experience was relatively low (mean 41.67, SD 24.71); (2) the main symptoms needing a management were fatigue, abdominal distension and/or peripheral edema, and muscle cramps; and (3) among the study variables, the severity of LC (P < 0.001) and the number of hospitalizations (P = 0.014) showed a significant relationship with overall symptom experience. These results suggest that symptom assessment requires a multidimensional approach and that it is imperative to consider disease severity in developing tailored symptom management programs for Korean patients with LC.     

Fleroxacin pharmacokinetics in patients with liver cirrhosis.

In this open-label study, the disposition of fleroxacin in liver disease in 12 healthy male volunteers, 6 male cirrhotics without ascites (group A), and 6 male cirrhotics with ascites (group B) was evaluated. Fleroxacin (400 mg) was administered orally and intravenously to each subject in a random crossover fashion. Fleroxacin was completely absorbed and achieved similar peak concentrations in plasma in all three study groups (P greater than 0.05). The volume of distribution exceeded 1 liter/kg in healthy controls and was not affected by liver impairment (P greater than 0.05). Only group B demonstrated differences in the pharmacokinetic parameters evaluated: the systemic and renal clearances of fleroxacin and the renal clearances and clearances of the two major metabolites of fleroxacin formed, N-demethyl fleroxacin and fleroxacin N-oxide, were significantly lower and the half-lives of the parent drug and its metabolites were significantly longer in group B than in healthy controls and group A (P less than 0.05). The elimination of the two metabolites appeared to be formation rate limited in all three study groups. It was concluded from this study that a 50% reduction in the fleroxacin maintenance dose in patients with liver disease appears justified only in patients with ascites. However, no change in the fleroxacin loading dose is needed in patients with compromised liver function.     

Rational diuretic therapy in patients with liver cirrhosis

When ascites develops in a patient with liver cirrhosis his probability to survive the following two years amounts to 50%. It is determined essentially by the residual functional capacity of the liver. In 80 to 90% of patients ascites due to portal hypertension can be managed by salt restriction and diuretics. A daily reduction of body weight of 0.5 to 0.75 kg should not be exceeded because prerenal failure may become a threat. Aldosterone-antagonists are more efficient and have fewer side-effects than loop diuretics. The urinary ratio of Na/K may be used to adjust the therapy. They may lower portal hypertension by an additional direct effect on the vasculature. If diuretics are insufficient or when a rapid therapeutic success is needed, paracentesis of 4-6 l is a safe option if intravascular volume is substituted simultaneously with albumin. Only in the few patients whose ascites is intractable by the forementioned measures, alternatives such as peritoneo-, venous or porto-systemic shunts (nowadays mostly by interventional techniques via a transjugular catheter) should be evaluated. The only treatment which not only attacks ascites symptomatically but also corrects the underlying disease is liver transplantation.     

Kinetics and dynamics of enalapril in patients with liver cirrhosis

The pharmacokinetics and pharmacodynamics (blood pressure, heart rate, serum angiotensin-converting enzyme, and plasma renin activity) of enalapril and enalaprilat were studied after oral administration of enalapril maleate (10 mg) to seven biopsy-proven cirrhotic patients and to seven healthy subjects. The mean Cmax, AUC, and urinary excretion of enalapril and enalaprilat were greater and less (p less than 0.01), respectively, and mean oral clearance of enalapril was less (p less than 0.01) in the cirrhotic group than in the healthy group. However, there was no significant difference in the mean total drug (enalapril plus enalaprilat) excretion between the two groups. Blood pressure fell (p less than 0.05) only at 3 or 4 hours postdose, with no change in heart rate in the two groups. Serum angiotensin-convering enzyme (ACE) decreased (p less than 0.001) and plasma renin activity (PRA) increased (p less than 0.05) in the two groups. The magnitude of the percentage of inhibition of ACE activity was comparable between the two groups. Serum enalaprilat concentration correlated (p less than 0.001) with the percentage of inhibition of ACE activity. The results suggest that the bioactivation of enalapril to enalaprilat is considerably impaired in patients with cirrhosis but that the pharmacodynamic effects do not appear to be blunted in those patients. The mechanism and clinical implications remained unclear.     

Pharmacokinetics of ornidazole in patients with severe liver cirrhosis

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was studied after intravenous injection in 10 patients with severe alcoholic cirrhosis and 10 healthy volunteers. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 (alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol) and M4 (3-(2-methyl-5-nitroimidazole 1-yl) 1,2 propane diol), were measured by HPLC. The t1/2 of ornidazole was 14.1 +/- 0.5 hours for normal subjects and 21.9 +/- 2.9 hours for patients with cirrhosis. Mean plasma clearance was 50.6 +/- 2.1 ml/min in control subjects and 34.9 +/- 4.9 ml/min in patients, whereas apparent V SS was not modified in hepatic insufficiency. In healthy volunteers, M1 and M4 levels are well below levels of the parent drug; in cirrhosis both metabolites accumulate in plasma as a result of decreased elimination. Hepatic cirrhosis prolongs ornidazole elimination, and to avoid cumulation the interval between repeated doses could be doubled.     

肝硬化患者肝性脑病风险预测模型的构建及应用研究

目的探讨肝硬化患者发生肝性脑病的独立危险因素并建立预测模型。方法调查本院2018年7月—9月的276例肝硬化患者,将其是否发生肝性脑病分为无肝性脑病组(n=245)和肝性脑病组(n=31),比较两组危险因素并建立预测模型,采用ROC曲线验证预测模型的预测效能。结果经单因素及多因素分析发现,肝性脑病病史、总胆红素、经颈静脉肝内门体分流术和肝肾综合征是肝硬化患者发生肝性脑病的独立危险因素。预测模型为P=ex/(1+ex),X=-3.791+2.190×肝性脑病病史的赋值+0.685×总胆红素的赋值+2.490×经颈静脉肝内门体分流术的赋值+2.914×肝肾综合征的赋值,ROC曲线下面积为0.840(95%CI:0.757～0.924),敏感性为83.9%,特异性为77.6%。模型验证结果:灵敏度为90.5%、特异度为85.0%、正确率为85.5%,提示其预测效果较好。结论肝硬化患者肝性脑病风险预测模型能较好地预测肝性脑病的发生风险,可为医护人员及时采取预防性管理措施提供参考。