Liver Function In Group Research Articles

Perioperative safety and prognosis in hepatocellular carcinoma patients with impaired liver function1

The benefits of liver resection for hepatocellular carcinoma (HCC) patients with concomitant impaired liver function were often considered questionable because of poor postoperative prognosis. This study will clarify whether an acceptable operative risk exists and whether limited resection will compromise the outcomes of these patients. Between July 1991 and December 1996, a total of 168 patients with HCC who underwent hepatectomies were enrolled and divided into normal (group A) and impaired (group B) liver function groups according to the value of indocyanine green retention rate at 15 minutes. Clinical features, surgical related features, pathologic features, and disease-free and overall survivals were compared between the groups. Operative morbidity and mortality in group A were 27.3% and 1.6%, and in group B were 40.0% and 2.5%, respectively (p = 0.129 and 0.506). Disease-free survival and overall survival at 5 years in group A were 43.2% and 59.6%, respectively, and in group B they were 30.6% and 56.8%, respectively (p = 0.607 and 0.378). Limited liver resection is safe and provides favorable prognosis in HCC patients with concomitant impaired liver function.

Risk Factors for Liver Dysfunction in Middle Aged Men based on Four Year Health Examination Data

Risk Factors for Liver Dysfunction in Middle Aged Men based on Four Year Health Examination Data: Kumiko Tajima, et al. Department of Public Health, Gunma University School of Medicine—In order to develop a better lifestyle improvement program, the relationship between lifestyle and changes in liver function were compared through data‐linkage of a self‐administered questionnaire to the results of annual health examinations over 4 years. In this study, 2,511 male subjects aged 40‐69 yr were asked to fill in the questionnaire. Of these, 824 subjects had a health examination in 1993. Two hundred and twenty‐eight of these remained within the normal range in liver function tests (LFT) in each of annual health examinations between 1994 and 1996, whereas 63 had worsened LFT results after the initial examination and were therefore called the decreased liver function (DLF) group. Controls age‐matched to the DLF group were chosen from the normal liver function group. Discriminant function analysis was carried out to identify the differences between the DLF group and the control group. The independent variables were selected from the variables which showed significant differences in the univariate analysis, considering multicollinearity. The independent variables used for the discriminant analysis were therefore alcohol consumption, diastolic blood pressure (DBP), BMI and “aggression” by THI. The Wilks' Lambda value was 0.787 (p value=0.0001). The overall correct identification rate in the discriminant analysis was 75.0%. The results of the present study suggest that men who are heavy drinkers, hypertensive, obese and aggressive had a high risk of developing liver dysfunction within a few years, even if their LFT values were within normal limits in any single year.

Indications for hepatectomy for hepatocellular carcinoma - what stage of the disease is the best indication for surgery?

To determine the clinical and tumor stage of hepatocellular carcinoma (HCC) that is the best indication for surgery, the postoperative long-term outcomes of patients who underwent hepatic resection were examined retrospectively. Of 975 patients with HCC who underwent regional therapy, 384 patients (39%) received hepatic resection (HR), 534 (55%) had transcatheter arterial chemoembolization (TACE), and the remaining 57 (6%) received percutaneous ethanol injection (PEI) into the tumor. The criteria defined by liver Cancer Study Group of Japan was used for staging and liver functional reserve (i.e., clinical staging). In the 133 patients with stage I HCC, there were no significant differences among the survivals of the HR, TACE, and PEI groups. In the 314 patients with stage II HCC, the 5- and 7-year survival rates were 51% and 46% in the HR group, 23% and 10% in the TACE group, and 0% and 0% in the PEI group. The survival of the HR group was significantly better than the survivals of the TACE and PEI groups (P < 0.001). The 5- and 10-year survivals of the stage II HCC patients who had HR were 64% and 47% in the clinical stage I (i.e., good liver function) group, significantly better than the 5; and 10-year survivals (32% and 23%) in the clinical stage II (i.e., bad liver function) group (P < 0.0001). Patients with good liver function in stage II are expected to have better survival and are considered to be the most suitable for HR.

Blood Propofol Levels in Patients with Normal and Impaired and Liver and Kidney-Function

In this study propofol, which has been shown to possess many suitable characteristics for an intravenous anesthetic agent, was used in order to evaluate its clinical effects and pharmacokinetic in patients with normal and impaired liver and kidney functtion in a single induction dose. Thirty patients in three groups each, comprising ten patients with impaired liver function (group 1), ten patients with impaired kidney function (group 2) and ten normal patients (group 3) all undergoing various surgical interventions, were included in the study. Heart rates, arterial systolic and diastolic pressures were recorded preoperatively, and 2, 5, 10 and 30 minutes after induction of anesthesia. Blood samples were collected after induction of anesthesia with 2.5 mg/kg bolus propofol at 2, 10, 30 minutes and 2, 6, 12 hours. Propofol concentrations were measured following extraction with a spectrofluorometric method. There were similar degrees of systolic hypotension following induction at two minutes in air three groups when compared to preoperative values, and significant differences were found only between groups, one and two with goups one and three at 30 minutes and 2 hours. Similar values of propofol were found at 2 and 10 minute and 6 and 12 hour samples in the there groups. These interim data show that the heart rate, systolic and diastolic pressure and the pharmacokinetics of profopol are generally similar in patients with impaired liver function and kidney function to those in normal patients.

Pharmacokinetics of temocapril, an ACE inhibitor with preferential biliary excretion, in patients with impaired liver function.

Six subjects with normal liver function (Group 1) and 7 patients with liver dysfunction (Group 2; mean ICGR15 value 30.5 (5.2)%; range 16 to 56) received a single oral dose of 1 mg temocapril, a prodrug-type ACE inhibitor, with preferentially excreted by the biliary route. The plasma temocapril concentrations in Group 2 at 30 min and 1 h postdose were significantly higher than in Group 1, but the difference had disappeared 2 h postdosing. Although the half life of temocapril diacid in Group 2 was significantly longer than in Group 1, there was no significant difference between the two groups in AUC, Cmax or tmax. In Group 2, urinary recovery of temocapril was significantly increased, suggesting a possible delay in the bioactivation of temocapril into the diacid, but recovery of the diacid itself was not abnormal. ACE inhibitory action in Group 2 remained unchanged. Temocapril is regarded as an ACE inhibitor the disposition and efficacy of which are little affected in patients with impaired liver function.

Contribution of cyclosporin metabolites to immunosuppression in liver-transplanted patients with severe graft dysfunction

The aim of this study was to analyse the immunosuppressive contribution of cyclosporin metabolites in liver-grafted patients. Therefore the immunosuppressive potency of 17 metabolites, alone and in combination, was tested in human mixed lymphocyte cultures, and the results were correlated with metabolite blood levels in liver-grafted patients. Of the 17 metabolites tested only six highly lipophilic metabolites showed a detectable immunosuppressive activity of up to 10% of the activity of cyclosporin; the effect of combining metabolites was additive. For calculation of the in vivo activity, blood levels of seven major cyclosporin metabolites were determined in liver-grafted patients with normal liver function (group A, 43 episodes) and with severe hyperbilirubinaemia (group B, 66 episodes). Both patient groups had comparable levels of parent drug (122.9 +/- 17.4 vs. 111.1 +/- 23.5 ng/ml by HPLC) and similar blood levels of the highly lipophilic metabolites 17, 1 and 18. By contrast, blood levels of the less lipophilic metabolites 8, 9, 26 and 203-218 were substantially increased in group B (P less than 0.05). High overall metabolite blood levels in group B were also indicated by a non-specific monoclonal RIA (520 +/- 199 ng/ml for group A vs. 1318 +/- 407 ng/ml for group B). Despite the very high levels in group B, however, the overall contribution of the metabolites to immunosuppression was similar in both groups (12.6 +/- 5.0% for group A vs. 13.8 +/- 5.6% for group B). These findings indicate that, despite a marked accumulation of cyclosporin metabolites in patients with severe cholestatic liver dysfunction, their immunosuppressive contribution remains low.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of enzyme induction, renal and cardiac function on ketamine plasma kinetics in patients with ketamine long-term analgosedation

Steady-state plasma levels of ketamine and its metabolites norketamine and dehydronorketamine were determined in 4 different groups of a total of 27 patients with ketamine long-term analgosedation (1.1 - 1.3 mg/kg/h). In 9 of the patients who had normal liver and kidney function (group 1), steady-state levels after 3 days of continuous infusion were 1.2 +/- 0.3 micrograms/ml ketamine, 1.0 +/- 0.6 micrograms/ml norketamine, and 2.6 +/- 1.0 micrograms/ml dehydronorketamine. The measured ketamine levels in group 1 were in agreement with the expected value, which may be calculated from published pharmacokinetic data after bolus injection. In 8 patients with acute renal failure (group 2), a tendency to about 20% higher ketamine steady-state plasma levels compared to group 1 was observed, but this difference was not significant. However, dehydronorketamine plasma levels were significantly higher in this group. Only a minor fraction of the ketamine dose (10% and 4%) was eliminated during hemodialysis or hemofiltration treatment, respectively. Steady-state plasma levels in 5 patients with cardiogenic shock (group 3) did not differ significantly from those of group 1. In 5 patients with long-term use of barbiturates (group 4), steady-state plasma levels of ketamine were significantly lower compared to groups 1 and 3, most likely due to barbiturate-induced enzyme induction. Hyperdynamic circulatory reactions were not observed in any of the patients. Psychomimetic effects could be excluded in 16 of the patients and were unlikely in 6 patients. In 5 further patients, psychomimetic effects could not definitely be excluded due to difficulties in non-verbal communication.

Portal venous velocity in biliary atresia

From December 1986 to April 1989, 38 patients with biliary atresia (eight newly diagnosed) were evaluated with doppler ultrasound of the portal venous system. Peak and mean velocities were computer derived from the spectral waveform. Good velocity was greater than 15 cm/s, intermediate velocity was 8 to 14 cm/s, abnormal velocity was less than 7 cm/s or hepatofugal. Patients were grouped according to clinical status: group 1 (n = 14), normal liver function; group 2 (n = 15), recurrent cholangitis; group 3 (n = 2), established bile drainage but complicated cirrhosis; group 4 (n = 7), failed portoenterostomy. All patients with normal liver function (group 1) had good or intermediate velocities. Thirteen of 15 patients with recurrent cholangitis (group 2) had good or intermediate velocities. Both patients in this group with abnormal velocities required transplantation. In group 3 the patient with abnormal velocity is on the transplant waiting list. In group 4, abnormal velocities preceded or coincided with deterioration of liver function in five of seven patients. Doppler ultrasound provides useful anatomic information, determines direction of flow, quantitates velocity of flow, and, when performed serially, provides adjunctive information on liver status in children with biliary atresia. These preliminary results suggest that patients with abnormal or significantly decreasing velocity are destined for transplantation. Patients with good portal venous velocity warrant ongoing, aggressive surgical management.

Pharmacokinetics and antiarrhythmic efficacy of intravenous ajmaline in ventricular arrhythmia of acute onset

21 patients with acute myocardial infarction and ventricular arrhythmia of Lown class II-IIIB of acute onset received a short infusion of (50 mg/5 min) ajmaline (Gilurytmal). 6 of the patients had normal kidney and liver function (Group 1), 4 patients had acute renal failure and hemodialysis treatment (Group 2), 4 patients had impaired hepatic function (Group 3), 3 patients had cardiogenic shock (Group 4), and 4 patients had been pretreated with phenobarbital for seizures for at least 5 days (Group 5). A distribution half-life of 6 +/- 1 min and an elimination half-life of 95 +/- 6 min was determined in Group 1. The total plasma clearance was significantly lower in patients with impaired liver or cardiac function and significantly higher in Group 5, whereas impaired renal function did not affect total plasma clearance. After short infusion, ventricular arrhythmia of Lown II-IIIB completely disappeared for at least 16 to 36 min (mean: 19 min), which was associated with an ajmaline plasma level of 0.1-0.45 micrograms/ml. Additionally, steady-state plasma levels of ajmaline were determined after continuous infusion of 10-50 mg/h to 16 patients (Group 6) with ventricular arrhythmia of acute onset (Lown class IVA-V). Ventricular arrhythmia completely disappeared or at least changed to lower Lown classes at ajmaline plasma levels of 0.4-2.0 micrograms/ml. The ajmaline plasma protein binding was 76 +/- 9%. Ajmaline had a special affinity to alpha 1-acid glycoprotein.

Plasma Manganese Concentrations in Infants and Children Receiving Parenteral Nutrition

Manganese is excreted primarily via the bile. The objective of this study was to determine if plasma Mn concentrations were elevated in infants and children fed intravenously who developed cholestatic liver disease. An additional aim was to determine the Mn content of intravenous solutions. The study included nine subjects with normal liver function (group A) and five subjects who developed cholestatic liver disease while fed intravenously (group B). Serum total bilirubin in group B had been elevated for 1 wk to 5 months prior to entry into this study. Mean plasma Mn for group A was 0.79 +/- 0.18 ng/ml, which was similar to that for adult controls. The mean for group B was 3.06 +/- 2.07 ng Mn/ml which was significantly higher (p less than 0.005). Plasma Mn was correlated positively with serum total bilirubin (r = 0.874, p less than 0.001). In four group B subjects studied longitudinally, plasma Mn declined. This decline was associated with a decline in serum total bilirubin in one subject and both a decline in serum total bilirubin and a reduction in, or a cessation of, supplemental intravenous Mn in two subjects. In the fourth subject, hepatic dysfunction remained severe, but plasma Mn declined to a near normal value after discontinuing supplemental intravenous Mn. The mean Mn contamination in the final intravenous infusate was 5.1 +/- 2.1 micrograms Mn/1. In conclusion, it is recommended that plasma Mn concentrations be monitored in patients fed intravenously who have evidence of cholestatic liver disease. If monitoring is not feasible, Mn supplements should be withheld.

Hepatitis B virus multiplication in the absence of usual serological markers: A study of 146 chronic alcoholics

The possible role of HBV infection in the progression of alcoholic liver disease remains debated. However, serum HBV markers in alcoholics, although present with a high frequency, mainly consist of anti-HBs and/or anti-HBc antibodies. In order to detect an HBV multiplication that could be missed by the usual markers, we looked for HBV-DNA in the serum of 146 chronic alcoholics; the results were compared with those of the usual serological HBV markers. Sixty-eight of the 146 patients could be studied for HBV-DNA both in the liver and the serum. The 146 alcoholics were divided in 48 with normal liver function (group I); 67 with non-cirrhotic alcoholic liver disease (group II); 31 with alcoholic cirrhosis (group III). Among the 146 patients, 17 had a viral multiplication reflected by serum positive HBV-DNA, as against none of 100 healthy controls (P less than 0.01). Six of the 17 had a normal liver function (6/48 = 12.5%), 7 were of group II (7/67 = 10.4%) and 4 had cirrhosis (4/31 = 12.9%). Serum HBV-DNA was associated with HBsAg in 3 occasions; in addition serum HBV-DNA was also present in 5 HBsAg-negative patients with anti-HBc and/or anti-HBs and even in 9 without any usual HBV marker. The overall prevalence of HBV markers in the 146 patients went from 30.8% to 37.0% when serum HBV-DNA was taken into account; it was similar in the 3 groups studied. Eight patients, of the 68 studied, were liver HBV-DNA-positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-base Status in Liver Cirrhosis. Disturbances in Stable, Terminal and Porta-caval Shunted Patients

Acid-base status was determined in 86 patients with cirrhosis of the liver. Group I comprised 55 patients living more than 3 months after examination (stable). Another 18 stable patients with a surgical porta-caval shunt (p.c.a.) formed group II. Group III consisted of 12 terminal patients without p.c.a. examined within the last week of life. With respect to liver function group II was intermediate between I and III. The most common acid-base disturbance in group I was compensated respiratory alkalosis (20%) followed by compensated metabolic alkalosis (15%). 50% of group II presented compensated respiratory alkalosis. 85% of group III showed metabolic acidosis, which was compensated in only half of the patients. Respiratory alkalosis seemed more related to impairment of liver function than to portasystemic shunting. The genesis of the terminal metabolic acidosis was complex. Renal function was reduced in 92% of group III, and lactic acidosis was found in 36%. In this group hepatic function was most severely impaired, and 60% were hypotensive. These disturbances were not related to aetiology or treatment of the liver disease.

Survival after portacaval shunt: who and how?

In a series of 74 portacaval-shunted patients no statistically significant differences in long-term survival or in incidence of postoperative encephalopathy have been observed between electively and emergency operated patients, between patients with slight and moderate impairment of liver function (groups A and B according to Child) or between patients with alcoholic and non-alcoholic cirrhosis. Patients older than 60 years had a higher risk of postoperative encephalopathy and a border-line significantly lower survival rate six months after the operation. Among the patients with more than six months' survival, about 50% returned to work.

Role of the mesentericocaval shunt in the management of portal hypertension

A series of sixteen mesentericocaval shunts is presented. These mesentericocaval shunts were carried out only in occasional complicated cases in which standard shunts had previously become thrombosed or were no longer possible for other reasons. Eleven of the mesentericocaval shunts were performed as emergency procedures and four of the patients belonged to liver function group C. The operative mortality was 14 per cent. Two of the sixteen mesentericocaval shunts have become thrombosed (12 per cent). Both required reoperation, and the patients have well functioning shunts at follow-up examination. Eleven of the fourteen patients are still alive and none has had any bleeding episodes after the mesentericocaval shunt. On the basis of the results, it is suggested that the range of indications for the mesentericocaval shunt could be widened considerably.