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PubMed1997

Quantitative evaluation of the hepatic functional reserve using technetium-99m DTPA-galactosyl human serum albumin before and after transjugular intrahepatic portosystemic shunt.

Transjugular intrahepatic portosystemic shunt (TIPS), a new therapeutic method, has been performed widely for the treatment of portal hypertension. TIPS produces a decrease in the portal blood flow to the hepatic parenchyma, which is considered to cause a reduction in hepatic functional reserve. To evaluate the changes in hepatic functional reserve after TIPS, we performed technetium-99m DTPA-galactosyl human serum algumin (99mTc-GSA) hepatic scintigraphy before and after TIPS in eight male patients, ranging in age from 54 to 72 years (mean 62.2 years). Two quantitative indices - blood clearance index (uptake ratio of the heart at 15 min to that at 3 min, HH15) and hepatic accumulation index (uptake ratio of the liver to the liver plus heart at 15 min, LHL15) - were calculated from the time-activity curves of the heart and liver. Early and late uptake constant indices (early and late KU) were also calculated from the time-activity curves of the heart and liver by means of Patlak plot. The values of HH15, LHL15 and late KU deteriorated after TIPS in all patients. Early KU (1-3 min) decreased by more than 55% in two patients who showed a poor prognosis and corresponded well with the status of the portosystemic shunt. It is concluded that 99mTc-GSA hepatic scintigraphy is a useful means of evaluating the degree to which hepatic function is compromised following TIPS. The post-TIPS alterations in HH15, LHL15 and late KU (5-10 min) reflect the changes in hepatic functional reserve, and early KU is a useful index for evaluating the degree of portosystemic shunt.

Humans↗
PubMed1993

Measuring lidocaine metabolite--monoethylglycinexylidide as a quantitative index of hepatic function in adults with chronic hepatitis and cirrhosis.

Lidocaine is metabolized to form monoethylglycinexylidide (MEGX) via oxidative N-deethylation in the liver. To assess the clinical value of this lidocaine metabolite as a quantitative liver function test, we measured the serum MEGX concentration 15 min after intravenous administration of a single dose of lidocaine (1 mg/kg) in 24 adults with chronic hepatitis, 47 patients with cirrhosis and 26 normal controls. A fluorescence polarization immunoassay was used to obtain the MEGX value. The MEGX concentration in controls was 67 (54-95) ng/ml (median with 16th-84th percentile in parentheses), which was higher than 43 (23-61) ng/ml in patients with chronic hepatitis and 24 (7-52) ng/ml in those with cirrhosis (P < 0.05). In addition, the serum MEGX levels are proportional to the galactose elimination capacity, and inversely proportional to Pugh's score, the prothrombin time and indocyanine green retention ratio. If a MEGX concentration of below 54 ng/ml is taken as an indicator of hepatic dysfunction, its diagnostic sensitivity for hepatic disorder is 84.5%, specificity 88.5% and accuracy 85.6%. Furthermore, after a 10-month follow-up, patients with MEGX formation above 30 ng/ml had a higher survival rate than those with a MEGX concentration below this level (P = 0.004). In conclusion, the MEGX formation test reflects the severity of hepatic dysfunction quite well, making it valuable both in the quantitative evaluation of liver function and in the prognostic prediction of adults with liver diseases.

Adult↗
PubMed2001

Gasless laparoscopy could avoid alterations in hepatic function.

BACKGROUND: In a previous clinical study, we showed that the duration and level of pneumoperitoneum are responsible for changes in hepatic function during laparoscopic procedures. These findings encouraged us to evaluate hepatic function during laparoscopy with and without carbon dioxide (CO(2)) pneumoperitoneum in a clinical setting. METHODS: We performed 63 laparoscopic cholecystectomies and 30 non-hepatobiliary laparoscopic procedures in 93 consecutive patients with normal preoperative liver function tests. The anesthesiologic protocol was uniform, using drugs at low hepatic metabolism. We performed laparoscopic cholecystectomies in 43 patients with a pneumoperitoneum; in the remaining 20, we used a gasless technique. We randomized the 43 laparoscopic cholecystectomies into 23 performed with pneumoperitoneum at 14 mmHg and 20 performed at 10 mmHg. All non-hepatobiliary laparoscopic procedures were performed with a pneumoperitoneum of 14 mmHg. The postoperative serologic levels of AST, ALT, and bilirubin, and the prothrombin time were measured at 6, 24, 48, and 72 h. The alterations in the serologic hepatic tests were then related to the type of procedure, its duration, and the level of pneumoperitoneum. RESULTS: The study group was comprised of 93 patients, 39 male and 54 female, with a mean age of 50.5 years (range, 15-74). There were no deaths. There was no morbidity in the pneumoperitoneum group, but there was one case of accidental omental injury during the placement of the abdominal, wall retractor in the gasless group. All patients had postoperative changes in serologic hepatic tests. Slow return to normality occurred 48 or 72 h after the operation. The increase in AST and ALT was statistically significant and correlated to the level and duration of pneumoperitoneum. The serologic change in the gasless group were significantly lower than in the laparoscopic cholecystectomy group with pneumoperitoneum at 14 mmHg. There was no statistically significant difference between the gasless group and the laparoscopic cholecystectomy group with pneumoperitoneum at 10 mmHg. There was a statistically the significant increase in the non-hepatobiliary laparoscopy group over the gasless group, despite the absence of hepatobiliary injuries in the first group. No symptoms were related to these serologic hepatic changes. CONCLUSIONS: The gasless technique causes smaller alterations in serological hepatic parameters than pneumoperitoneum at 14 mmHg. By contrast, the gasless technique and low-pressure pneumoperitoneum have the same effect on hepatic function. Therefore, the use of a subcutaneous abdominal wall retractor combined with a low-pressure pneumoperitoneum is recommended for patients with severe hepatic failure. Transaminases

Adolescent↗
PubMed1997

Liver-enriched transcription factors uncoupled from expression of hepatic functions in hepatoma cell lines.

Among the liver-enriched transcription factors identified to date, only expression of hepatocyte nuclear factor 4 (HNF4) and hepatocyte nuclear factor 1 (HNF1) is in strict correlation with hepatic differentiation in cultured rat hepatoma cells. Indeed, differentiated hepatoma cells that stably express an extensive set of adult hepatic functions express liver-enriched transcription factors, while dedifferentiated cells that have lost expression of all these hepatic functions no longer express HNF4 and HNF1. We describe a new heritable phenotype, designated as uncoupled, in which there is a spontaneous dissociation between the expression of these transcription factors and that of the hepatic functions. Cells presenting this phenotype, isolated from differentiated hepatoma cells, cease to accumulate all transcripts coding for hepatic functions but nevertheless maintain expression of HNF4 and HNF1. Transitory transfection experiments indicate that these two factors present in these cells have transcriptional activity similar to that of differentiated hepatoma cells. Characterization of the appropriate intertypic cell hybrids demonstrates that this new phenotype is recessive to the dedifferentiated state and fails to be complemented by differentiated cells. These results indicate the existence of mechanisms that inhibit transcription of genes coding for hepatocyte functions in spite of the presence of functional HNF4 and HNF1. Cells of the uncoupled phenotype present certain properties of oval cells described for pathological states of the liver.

Animals↗
PubMed2001

Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide.

We have demonstrated that the hepatic function may have an important role in the development of tolerance to the pyrogenic effect induced by endotoxin. To further investigate if the role of the hepatic function in the development of tolerance also extends to that induced by other pyrogenic stimuli, we investigated the effect of galactosamine, a specific inhibitor of the hepatic protein synthesis, on the development of tolerance to the pyrogenic effect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was observed after the second intravenous or intraperitoneal injection of MDP (500 microgram/kg), 24 h after the first injection, similar to what was observed with endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/kg ip) was injected simultaneously with MDP (500 microgram/kg iv) on the first day. When uridine (600 mg/kg ip) was administered simultaneously with galactosamine (300 mg/kg ip) and the first injection of MDP (500 microgram/kg ip), pyrogenic tolerance was again observed after the second injection of the peptidoglycan. In conclusion, the hepatic function may not be important only for the development of tolerance to endotoxin, but also to a totally different pyrogenic stimulus such as MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1991

Actinomycin D blocks the hepatic functional albumin mRNA increase in aminonucleoside-nephrotic rats.

Hepatic functional albumin-mRNA was measured in the following groups of rats: (a) puromycin aminonucleoside (PAN)-nephrotic rats, (b) PAN-nephrotic rats treated with actinomycin D prior to sacrifice, (c) control rats, and (d) control rats treated with actinomycin D. Albumin mRNA was translated in an mRNA-dependent cell-free system from rabbit reticulocyte lysate. Albumin-mRNA increased about 2-fold in PAN-nephrotic rats. This increase was abolished in vivo in PAN-nephrotic rats treated with actinomycin D. Albumin mRNA was not significantly modified in control rats treated with actinomycin D. These data suggest that the increased level of hepatic functional albumin mRNA observed in PAN-nephrotic rats in vivo was due mainly to the increased rate of albumin gene transcription.

Albumins↗
PubMed1999

Evaluation of hepatic function in liver cirrhosis: clinical utility of galactose elimination capacity, hepatic clearance of D-sorbitol, and laboratory investigations.

Assessment of hepatic function is based on both liver blood tests and functional tests, the extensive application of which is still controversial. The aim of this study was to evaluate the clinical utility of a few selected tests as discriminatory and prognostic indexes: serum albumin, pseudocholinesterase, prothrombin time, as well as galactose elimination capacity and hepatic sorbitol clearance. Two separate studies were performed: Study I to investigate how well these tests assessed severity, and Study II to evaluate their prognostic value. A total of 128 consecutive cirrhotic patients classified according to the Child-Pugh score were included in Study I; Study II was carried out on 47 of these 128 during a two-year follow-up period. Pairwise correlations between all tests and Child-Pugh score yielded higher significant values for liver blood tests than for the functional ones. In Study I functional tests such as galactose elimination capacity and hepatic sorbitol clearance did not appear to be better than conventional biochemical tests in discriminating clinical severity of cirrhotic patients, as defined by Child-Pugh classification. Results of Study II confirmed that in severe liver cirrhosis Child-Pugh score remains the best method for medium- and long-term prognosis and for planning liver transplantation. Functional tests should be reserved for defining the residual functioning liver mass or for studies about functional liver plasma flow.

Adolescent↗
PubMed2001

Functional hepatic volume measured by technetium-99m-galactosyl-human serum albumin liver scintigraphy: comparison between hepatocyte volume and liver volume by computed tomography.

OBJECTIVES: We investigated the usefulness of measuring the functional hepatic volume by single-photon emission CT with 99m-technetium galactosyl-human serum albumin scintigraphy (GSA-LV). We then compared this value to the total hepatocyte volume and the hepatic volume determined from CT (CT-LV) in the patients with hepatobiliary tumors. METHODS: Forty-seven patients were divided into two groups, the SM group (subsegmentectomy and monosegmentectomy) and the DT group (disegmentectomy and trisegmentectomy). These groups were further divided into subgroups with or without chronic hepatitis or cirrhosis. The GSA-LV, CT-LV, and the total hepatocyte volume were then calculated. The GSA-LV and CT-LV measurements were performed preoperatively, at 2 and 4 wk, and at 3 and 6 months after surgery. RESULTS: The preoperative GSA-LV values were significantly correlated with the hepatocyte volume and the 15-min retention rate of indocyanine green (ICGR15). Similarly, the hepatocyte volume correlated well with the CT-LV and ICGR15. However, the CT-LV was correlated only with the ICGR15. Recovery of the GSA-LV in the DT group was delayed, and about 90% of the volumetric and functional regeneration was observed within 6 months after the hepatectomy. In contrast, the CT-LV of DT group patients with normal liver remnants returned to approximately 90% of their initial volume within 1 month after the hepatectomy, whereas patients with injured livers regenerated gradually and regained approximately 80% of their preoperative value by 6 months after the hepatectomy. CONCLUSIONS: We conclude that the measurement of functional hepatic volume using the GSA-LV is useful in fully evaluating hepatic function based on hepatocyte volume.

Bile Duct Neoplasms↗
PubMed1998

Inorganic fluoride kinetics and renal and hepatic function after repeated sevoflurane anesthesia.

UNLABELLED: After repeated exposure to inhaled anesthetics, the hepatic function and metabolism of anesthetics may change. The purpose of this study was to investigate inorganic fluoride (F-) kinetics and renal and hepatic function after repeated exposure to sevoflurane. Ten patients (aged 40-70 yr) who had received sevoflurane anesthesia with a gas flow of 6 L/min for neurosurgery twice in 30-90 days were studied. Serum and urine F- concentrations were measured up to 24 h after anesthesia. Blood urea nitrogen, serum creatinine, serum and urine beta2-microglobulin, urine N-acetyl-beta-D-glucosaminidase, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin concentrations were measured up to 7 days after anesthesia. The area under the curve (AUC) of serum and urine F- concentration and half-life of serum F concentration were calculated. Urine beta2-microglobulin, AST, and ALT increased to abnormal levels after both anesthesias, with no difference between anesthesias. No measured variables, AUC of serum and urine F- concentration, or half-life of serum F- concentration showed any differences between the first and second anesthesias. In conclusion, the second exposure to sevoflurane with a high gas flow of 6 L/min in 30-90 days did not change the hepatic and renal function or affect the metabolism of sevoflurane. IMPLICATIONS: We studied the changes of metabolism of sevoflurane and hepatic and renal function after repeated sevoflurane anesthesia in 30-90 days. There were changes indicative of mild liver and kidney injury after sevoflurane anesthesia, but repeated exposure to sevoflurane did not enhance these changes.

Adult↗
PubMed1990

[Hepatic functional reserve and tumor size as prognostic factors in patients with primary liver cancer undergoing non-surgical therapy].

A prognostic study on 119 patients with primary liver cancer undergoing nonsurgical therapy was carried out to evaluate the relevance of hepatic functional reserve and tumor size to their cumulative survival rates. All patients were classified into the three groups of Child's classification (A, B and C) according to their hepatic functional reserve and were also divided into the five groups according to their tumor size. The cumulative survival rates of all patients at 1, 2, 3, 4 and 5 years after the diagnosis were 50.9, 28.3, 18.8, 13.5 and 6.7%, respectively. The cumulative survival rates of group V whose tumor occupied more than 40% of the liver area were significantly lower than those of the other tumor-size-groups. The survival rates of Child's group A were significantly higher than those of group B and C. But in those patients who were classified into group V according to their tumor size, there was no significant difference in their survival rates among the three groups of Child's classification. These results suggest that hepatic functional reserve as well as tumor size is an important prognostic factor in patients with primary liver cancer. But if the cancer once develops greater than 40% of the liver area, hepatic functional reserve diminishes in value as a prognostic factor.

Antineoplastic Agents↗
PubMed1985

Effect of combined ethinyl estradiol and norgestrel oral contraceptives on hepatic functions of albino rats.

The effect of two different doses of ethinyl estradiol and norgestrel combined oral contraceptives (OCs) on hepatic functions of albino rats was studied for a period of six months. Combined OCs treatment caused an increase in glycogen, RNA, total lipids, triglycerides, cholesterol and free fatty acids contents of liver and liver microsomes and decreased the liver weight/body weight ratio and phospholipid contents. Liver aminotransferase activities were elevated in the OCs treated animals whereas alkaline phosphatase activity remained unchanged. The biochemical changes were found to be dose dependent. Thus the present study has shown that the combined OCs treatment for six months is associated with altered hepatic functions. The possible mechanism of such an alteration of hepatic functions on OCs treatment is discussed.

Animals↗
PubMed1994

Impaired hepatic function in segmental biliary obstruction demonstrated with a receptor-binding radiotracer.

A patient with cholangiocarcinoma underwent left-sided cholangiojejunostomy, and hepatic functional imaging with a receptor-binding radiotracer and SPECT was performed to evaluate the distribution of functional reserve. It revealed decreased accumulation in the regions with residual dilatation of the intrahepatic bile ducts, indicating several kinds of focal damage in hepatic function caused by segmental biliary obstruction. The radioligand may be useful in assessing regional hepatic function, and the high spatial resolution provided by SPECT appears to play an important role for this purpose.

Aged↗
PubMed1997

Evaluation of preoperative hepatic function in patients with hepatocellular carcinoma undergoing hepatectomy.

BACKGROUND: Postoperative hepatic failure is the leading cause of hospital mortality following hepatectomy for hepatocellular carcinoma (HCC). This prospective study was performed to identify the best test for assessment of the adequacy of hepatic functional reserve in patients with HCC before hepatectomy. METHODS: Between April 1989 and June 1993, 127 patients with HCC underwent hepatectomy. Each patient was evaluated before operation with the indocyanine green (ICG) clearance test, the aminopyrine breath test and the amino acid clearance test. RESULTS: Fourteen patients (11 per cent) died after hepatectomy. ICG retention at 15 min showed significant differences between patients who survived or died. By discriminant analysis, the safety limit of ICG retention at 15 min for major hepatectomy was 14 per cent and the relative risk of hospital mortality was 3. CONCLUSION: The ICG clearance test, expressed as the percentage of ICG retained at 15 min, is the best discriminating preoperative test for evaluating hepatic functional reserve in patients with HCC before hepatectomy.

Adult↗
PubMed2004

Pharmacokinetics and safety of ebastine in patients with impaired hepatic function compared with healthy volunteers: a phase I open-label study.

OBJECTIVE: To assess the differences between patients with hepatic insufficiency and healthy subjects with regard to the pharmacokinetics, cardiac safety and overall safety of ebastine and its active metabolite carebastine. DESIGN: Open-label parallel-group study. PARTICIPANTS: 24 patients with varying degrees of hepatic insufficiency, as categorised by the Child-Pugh classification, and 12 healthy volunteers. METHODS: Healthy subjects and patients with Child-Pugh class A (n = 8) or B (n = 8) received ebastine 20 mg once daily for 7 days. Patients with Child-Pugh class C (n = 8) [single or repeated dose] received ebastine 10 mg. Plasma concentrations of ebastine and carebastine were determined for 23.5 hours following the initial dose on day 1 and for 96 hours following the dose on day 7 by using a sensitive liquid chromatography-tandem mass spectrometry assay with a minimum quantifiable limit of 0.05 microg/L for ebastine and 1.00 microg/L for carebastine. Hepatic function was assessed by blood clearance of indocyanine green 0.5 mg/kg administered intravenously on day 2. Cardiac and overall safety parameters were monitored. RESULTS: Overall, the pharmacokinetics of ebastine were not modified by hepatic impairment. No correlation between ebastine pharmacokinetics and hepatic function, as expressed by indocyanine green clearance, was observed. Comparison of the effective half-life of ebastine and carebastine between groups did not show relevant differences. Therefore, no apparent accumulation of ebastine occurred, and steady-state concentrations of ebastine and carebastine were predictable from single-dose pharmacokinetics both in healthy subjects and in hepatically impaired patients. Finally, no apparent difference was noted in the safety of ebastine between patients with hepatic insufficiency and healthy subjects as assessed by evaluation of adverse events, vital signs and laboratory parameters. CONCLUSION: Ebastine can be safely administered to patients with impaired hepatic function, as no clinically important differences can be anticipated from the pharmacokinetics and safety profile of ebastine/carebastine as compared with healthy subjects. Nevertheless, the dosage used in severely impaired patients (10mg daily) was half that used in patients with mild to moderate impairment, and any comedication did not include drugs affecting liver function; in clinical practice, both these factors should be taken into account.

Adult↗
PubMed2003

Association between dioxins/furans exposures and incinerator workers' hepatic function and blood lipids.

This study examined the effects of dioxins/furans on blood lipids and hepatic function and assessed potential interaction between hepatitis B virus (HBV) infection and dioxins on hepatic function for 133 male workers of municipal waste incinerators. We found that total cholesterol levels in workers with blood dioxins/furans levels of 15.4-59.0 pg TEQ/g lipid (high-exposure workers) averaged 13.5 mg/dL higher than workers with 5.5-15.3 pg TEQ/g lipid (low-exposure workers). The adjusted odds ratio for total cholesterol abnormality (>220 mg/dL) was 2.8 (95% confidence interval = 1.0-7.9) between high and low-exposure workers. High-exposure workers showed consistently, although not statistically significantly, higher abnormality in gamma-glutamyltransferase (>52 U/L), alanine aminotransferase (>41 U/L), and aspartate aminotransferase (>37 U/L) than did low-exposure workers. However, there was no statistically significant interaction between dioxins/furans and HBV on these hepatic enzymes among incinerator workers.

Adult↗