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PubMed1992

Evaluation of hepatic function using the pharmacokinetics of a therapeutically administered drug. Application to the immunosuppressant cyclosporin.

A method is presented for the simultaneous estimation of functional hepatic blood flow and intrinsic clearance. The method uses pharmacokinetic data of a therapeutically employed drug and one of its primary metabolites following intravenous and oral administration of the parent compound. When the disposition of the drug is linear, this method can cope with complicated dosage regimens commonly confronted in clinical data. The feasibility of the method was demonstrated in 10 patients who had undergone liver transplantation and were receiving cyclosporin in the immediate postoperative period. Mean hepatic blood flow was estimated to be 0.89 (95% CI: 0.62 to 1.23) L/h/kg and intrinsic cyclosporin clearance as 0.60 (95% CI: 0.49 to 0.72) L/h/kg. Apart from the hepatic parameters, bioavailability and the fraction of the dose absorbed, a detailed pharmacokinetic description of the parent drug and the elimination pharmacokinetics of a primary metabolite are provided. This information not only allows optimisation of individual therapy, but also may be used to compare absorption properties of different pharmaceutical formulations.

Administration, Oral↗
PubMed1976

Effects of experimental hepatic artery embolization on hepatic function.

The hepatic artery was embolized with Gelfoam in 12 dogs to evaluate the effect of embolization on hepatic function. Liver function studies, including SGPT, alkaline phosphatase, BSP test, and bilirubin, were done serially over a 6 week period following the embolization. Eleven of the 12 embolized dogs survived the 6 week experimental period. Hepatic artery embolization caused some liver damage; however, recovery occurred by 6 weeks. These results suggest a possible therapeutic role for hepatic artery embolization in patients with massive hepatic bleeding or hemobilia who are not surgical candidates and who would require hepatic lobectomy or dearterialization to control the bleeding.

Animals↗
PubMed1993

Effect of lidocaine on in vivo hepatic function.

Lidocaine is administered to assess donor or recipient liver function during hepatic transplantation. This study was performed to determine whether lidocaine administered at a constant concentration affected hepatic function or had demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were randomly allocated to receive either a two-stage infusion of lidocaine hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic portal venous and hepatic arterial blood flow readings made on animals anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for histological analysis and determination of adenine nucleotide status prior to and after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine concentration of 5.9 micrograms/ml was achieved during the second hour of infusion. There were no differences between the two groups in a large number of indices of hepatic function and plasma composition prior to and during the second hour of the respective infusions. Hepatic blood flow was also similar at these times. On histological examination there were no electron microscopic changes that could be specifically attributed to the administration of lidocaine. However, there were progressive changes with time. This study suggests that in anesthetized pigs a constant lidocaine concentration of about 6 micrograms/ml has no detrimental effect on hepatic function. Progressive hepatic ultrastructural changes occurred that could not be attributed to the administration of lidocaine. These may be the result of anesthetic administered or the surgery performed.

Animals↗
PubMed1995

The functional hepatic volume assessed by 99mTc-GSA hepatic scintigraphy.

The accuracy of measurement of the functional hepatic volume by single photon emission computed tomography (SPECT) with 99mTc-galactosyl serum albumin (99mTc-GAS) was evaluated. 99mTc-GSA planar scintigraphic images were obtained dynamically and the hepatic SPECT imaging was then performed in 25 patients with hepatobiliary tumors. The patients were divided into 4 groups with normal hepatic function, and mild, moderate and severe hepatic dysfunction. The functional hepatic volume determined by SPECT was compared with the morphological hepatic volume determined by compute tomography. The ratio of the hepatic volumes obtained by the two methods was calculated. The mean hepatic volume ratio was 96.6 +/- 2.3% in the normal hepatic function group and 95.9 +/- 2.2% in the mild dysfunction group (n.s.). In both the moderate and severe hepatic dysfunction groups, the hepatic volume ratio was smaller than that in the normal group (87.9 +/- 5.2%, p < 0.0001, and 71.9 +/- 7.6%, p < 0.0001, respectively). There was a linear correlation between the hepatic volume ration and various indices of reserve hepatic function, such as LHL15 (r = 0.83, p < 0.0001), HH15(r = 0.74, p < 0.0001), and ICG15 (r = 0.75, p < 0.0005). These results indicate that the hepatic volume ratio is proportional to the severity of hepatic dysfunction, and suggest that the functional hepatic volume measured with 99mTc-GSA faithfully reflects the functioning hepatocyte mass. 99mTc-GSA scintigraphy and hepatic SPECT therefore provide information regarding global and regional reserve hepatic function.

Adult↗
PubMed1995

Study of hepatic functions and prevalence of hepatitis-B surface antigenaemia in Omani children with sickle cell disease.

The prevalence of persistent hepatitis-B surface (HBS) antigenaemia and hepatic functions have been determined in 125 children with sickle cell disease (SCD) as well as in 100 age-matched healthy children. Hepatic functions and the presence of HBS antigenaemia have been followed for 1 year in six children with SCD and 10 normal children following acute hepatitis-B infection. The prevalence of chronic HBS antigenaemia (3 per cent) in children with SCD is not higher than in normal children (11 per cent). The significant elevation of serum alanine transferase (ALT) and bilirubin concentrations in sickle cell children denotes a process of mild hepatocellular dysfunction which is unrelated to hepatitis-B viral antigenaemia. The high incidence of chronic HBS antigenaemia accompanied by elevated serum ALT and bilirubin concentrations in sickle cell children following acute hepatitis-B infection, in addition to the significant impairment of hepatic functions in sicklers with chronic HBS antigenaemia compared to those without the antigenaemia, point out to the high risk of continual parenchymal hepatic damage in these children following acute hepatitis-B infection. Vaccination against hepatitis-B virus should eliminate this risk.

Anemia, Sickle Cell↗
PubMed2004

Functional hepatic flow in patients with liver cirrhosis.

AIM: To evaluate hepatic reserve function by investigating the change of functional hepatic flow and total hepatic flow in cirrhotic patients with portal hypertension. METHODS: HPLC method was employed for the determination of concentration of D-sorbitol in human plasma and urine. The functional hepatic flow (FHF) and total hepatic flow (THF) were determined by means of modified hepatic clearance of D-sorbitol combined with duplex doppler color sonography in 20 patients with cirrhosis and 10 healthy volunteers. RESULTS: FHF, evaluated by means of the D-sorbitol clearance, was significantly reduced in patients with cirrhosis in comparison to controls (764.74+/-167.91 vs 1195.04+/-242.97 mL/min, P<0.01). While THF was significantly increased in patients with cirrhosis in comparison to controls (1605.23+/-279.99 vs 1256.12+/-198.34 mL/min, P<0.01). Portal blood flow and hepatic artery flow all were increased in cirrhosis compared to controls (P<0.05 and P<0.01). D-sorbitol total clearance was significantly reduced in cirrhosis compared to control (P<0.01), while D-sorbitol renal clearance was significantly increased in cirrhosis (P<0.05). In controls FHF was similar to THF (1195.05+/-242.97 vs 1256.12+/-198.34 mL/min, P=0.636), while FHF was significantly reduced compared with THF in cirrhosis (764.74+/-167.91 vs 1605.23+/-279.99 mL/min, P<0.01). CONCLUSION: Our method that combined modified hepatic clearance of D-sorbitol with duplex doppler color sonography is effective in the measurement of FHF and THF. FHF can be used to estimate hepatic reserve function.

Adult↗
PubMed2003

How reversible is hepatic functional impairment in autoimmune hepatitis?

BACKGROUND AND AIMS: We quantifed the short-term effects of immunosuppressive therapy on hepatic metabolic function in autoimmune hepatitis to establish how long it takes to achieve maximum functional improvement. METHODS: We studied 14 newly diagnosed patients with autoimmune hepatitis (12 type 1, two type 2) by antipyrine clearance and conventional liver tests, then repeated studies at 3-6 month intervals during the first 18 months of immunosuppressive therapy. RESULTS: Low values for antipyrine clearance were found in 13 of 14 cases; serum albumin concentration was low in four, bilirubin raised in eight and prothrombin time prolonged in four. Following immunosuppressive treatment for 3 months, antipyrine clearance improved by 98% (standard error of the mean 24%), which was proportionally greater than for serum albumin, bilirubin or prothrombin time. Antipyrine clearance and serum albumin continued to improve after 6-12 months of immunosuppressive treatment in several cases, whereas there were no further improvements in alanine aminotransferase (ALT), bilirubin and prothrombin time. CONCLUSIONS: In the short term, immunosuppressive therapy for autoimmune hepatitis markedly improves hepatic metabolic function, which is particularly striking for the sensitive metabolic test antipyrine clearance, but may also be seen with serum albumin. However, it may take up to 12 months to achieve maximal functional recovery. Management guidelines on autoimmune hepatitis should be extended to emphasize that changes in hepatic metabolic function, as well as ALT and gamma-globulin levels, be taken into consideration in the definition of remission.

Adolescent↗
PubMed1990

Study on some hepatic functions and prevalence of hepatitis B surface antigenaemia in Egyptian children with schistosomal hepatic fibrosis.

Several different hepatic parenchymal lesions, including chronic hepatitis and cirrhosis, have been increasingly reported in children with schistosomal hepatic fibrosis (SHF) despite the known mesenchymal nature of the disease. The prevalence of persistent hepatitis (B) surface (HBs) antigenaemia and some hepatic functions have been determined in 52 children with SHF as well as in 100 age-matched healthy children. High prevalence of chronic HBs antigenaemia (58 per cent) has been demonstrated in children with SHF, but only in 2 per cent of the normal children. This denotes that children with SHF represent a dangerous reservoir for hepatitis B infection to the community. Serum alanine transferase (ALT) was higher than normal in 58 per cent of HBS seropositive patients and in none of the seronegative patients. This points to the risk of continual hepatic parenchymal injury to the HBs seropositive patients with schistosomiasis.

Adolescent↗
PubMed2005

[Effect of heptral and folic acid on the hepatic functions during toxic hepatitis].

The aim of study was to evaluate effectiveness of heptral (S-Adonosylmethionine-Adomet) and folic acid during the acute toxic damage of the liver induced by carbon tetrachloride. Experiments have been carried out on pubertal rats. The carbon tetrachloride intoxication was performed by subcutaneous injection of CCL(4) 1 ml/kg dissolved in 1 ml of olive oil. The activity of aspartat-and alaninaminotransferases, alkaline phosphatase, the content of free and total billirubine in the blood, as well as total oxidant and antioxidant activity of the blood, were measured by the spectrophotometric techniques. Oxidative stress, cytolyses of the hepatocytes and cholestasis were observed during CCL(4) intoxication. Heptral, and in less degree, folic acid improved liver function during the acute toxic damage, but complex therapy with heptral and folic acid revealed more expressive hepatoprotective effect. It is suggested that better positive effect of complex therapy with heptral and folic acid compared with monotherapy by each drug is probably associated with resynthesis of methionine from homocystein (toxic metabolite of adenosylmethionine) by folate. This combination allows reducing the side effects of heptral induced by homocysteine.

Animals↗
PubMedDate not supplied

[Impact of seasons on efficacy of physiotherapeutic correction of hepatic function in toxic hepatitis in experiment].

Experiments on 172 Wistar rats modeled CCl4-hepatitis in transitory phases of about-annual cycle. In the autumn phase the animals with toxic hepatitis demonstrated poor normalization of biochemical parameters while the efficacy of physiotherapy (sapropel combined with magnetic field) was very high. In spring, normalization of the biochemical parameters was very high while the above physiotherapeutic complex was low effective.

Animals↗
PubMedDate not supplied

Hepatic function in hypothermically stored porcine livers: comparison of hypothermic machine perfusion vs cold storage.

Hypothermic machine perfusion (HMP) has a potential to relieve the current donor liver crisis by providing an improved and extended preservation method. This study examined the effect of HMP on hepatocellular functions, using a prototype liver transporter capable of preserving livers for 24 hours. Livers obtained from adult farm pigs (28 to 32 kg body weight) were divided into three groups: fresh control, HMP, and simple cold storage (n = 4 each). A 4-hour normothermic reperfusion of livers was conducted to assess hepato-metabolic and cellular functions. The hepatic transport function, as indicated by canalicular excretion of indocyanine green, was improved in the HMP group than in the SCS group. The overall tissue viability, as indicated by oxygen consumption levels, was notably improved in HMP and control livers as compared to the SCS group. Higher bile production in both the preserved groups as compared to the fresh control livers could be a result of biliary edema and leakage of plasma into the canaliculus. The hepato-cellular injury, measured by ALT, release was significantly greater in the SCS group as compared to the HMP and control groups. These findings suggest that HMP could be a better method to preserve hepatic function and overall tissue viability as compared to SCS. Improved hepatic functions are indirect indicators of superior microcirculation and sinusoidal endothelial cell functions. Further studies in progress will evaluate these functions to confirm the significance of these observations.

Alanine Transaminase↗
PubMed2003

Clinical assessment of hepatic functional reserve using 99mTc DTPA galactosyl human serum albumin SPECT to prognosticate chronic hepatic diseases--validation of the use of SPECT and a new indicator.

RATIONALE: It is generally known that scintigraphy of 99mTc diethylenetriamine pentaacetic acid-galactosyl human serum albumin (99mTc-GSA) is useful for assessing hepatic functional reserve. For hepatic functional indicators, the index of the calculated planar image has been used in previous studies. However, there have been few reports that suggest that the indicators calculated from static SPECT data would be useful for the assessment of hepatic function. The aims of this study were to establish a simple method for assessing hepatic functional reserve using the liver SPECT of 99mTc-GSA and to apply this method for rich stratification in patients with chronic hepatic diseases. METHODS: A liver phantom (a 50% concentration of 99mTc solution) was used to compare the planar and SPECT methods. According to the definition of the new indicator, the liver SPECT of 99mTc-GSA was divided by a syringe SPECT of 99mTc-GSA and was called the liver uptake ratio (LUR). We correlated the LUR and the liver uptake ratio calculated according to the blood-sampling method. 99mTc-GSA SPECT was performed in 137 patients with hepatic diseases, including chronic hepatic diseases, and 20 healthy volunteers. The LUR was correlated between the formed subtypes for all subjects. RESULTS: The acquired phantom-count ratio calculated by the SPECT method was more accurate than that acquired by the planar method. A good correlation was obtained between the LUR and the blood-sampling method (r = 0.971). The LUR was significantly lower in subjects with severe cirrhosis than in healthy subjects or those with chronic hepatitis and mild cirrhosis, and it was significantly lower in subjects with chronic hepatitis and mild cirrhosis than in healthy subjects. The LUR was significantly correlated with other hepatic function tests. Based on LUR, the chronic hepatic diseases were divided into two groups: Group A, with LURs 30% and higher, and Group B, with LURs below 30%. An LUR of 30% marked the 25th percentile of the mild-cirrhosis group. The cumulative survival rates were lower in Group B than in Group A. CONCLUSION: The SPECT method was superior to the planar method for assessing LURs. LUR was a suitable indicator of 99mTc-GSA clearance from the blood pool and of binding to the asialo-glycoprotein receptor. LUR is a simple and clinically useful indicator for the assessment of hepatic functional reserve in chronic hepatic diseases.

Chronic Disease↗