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[Protective actions of acupoint magnetic medicated plaster therapy on hepatic function in the patient of cirrhosis after hepatitis].

OBJECTIVE: To observe the therapeutic effect of acupoint magnetic medicated plaster therapy on cirrhosis after hepatitis. METHODS: One hundred and twenty patients with cirrhosis after hepatitis were randomly divided into 2 groups. The control group (n=60) were treated by the hepatic protective therapy (diammonium glyeyrrhiznate, Silymarin, compound Tanshin, vitamin E), and the treatment group were treated by the liver-protective therapy and acupoint magnetic medicated plaster therapy, for 2-6 therapeutic courses. Clinical symptoms, hepatic function, serum markers of hepatitis B virus and indexes of hepatic fibrosis were investigated. RESULTS: The markedly effective rate and the total effective rate were 65.0% and 95.0% in the treatment group, and 43.3% and 91.7% in the control group, and the serum indexes of hepatic fibrosis decreased signficantly, with significantly diferences (all P < 0.05). CONCLUSION: Acupoint magnetic medicated plaster therapy can improve clinical symptoms, rapidly restore hepatic function, decrease serum indexes of hepatic fibrosis in the patient of cirrhosis after hepatitis.

Acupuncture Points↗

Mephenytoin disposition and serum bile acids as indices of hepatic function in chronic viral hepatitis.

BACKGROUND AND OBJECTIVES: The effect of chronic viral hepatitis on liver function may vary from none to hepatic failure. Changes in function are usually the result of impaired hepatocyte function or altered vascular flow and architecture. Conventional liver function tests usually cannot distinguish contributions from these mechanisms or indicate degree of hepatic metabolic dysfunction. An alternative approach is to measure the hepatic metabolism of a highly extracted compound whose oral clearance and systemic bioavailability are dependent on both hepatocyte function and degree of portosystemic shunt. METHODS: The stereoselective metabolism of racemic mephenytoin (100 mg oral dose) was investigated in 35 patients with chronic viral hepatitis and compared with 153 healthy subjects. The mephenytoin R/S enantiomeric ratio and cumulative excretion of the 4'-hydroxymephenytoin metabolite in a 0- to 8-hour urine sample were used in addition to serum bile acid levels and pathologic examination of biopsy specimens to assess the severity of hepatic dysfunction and portosystemic shunting. RESULTS: The patients as a group excreted less 4'-hydroxymephenytoin and had a smaller R/S enantiomeric ratio of mephenytoin. The two measures were discriminatory between the patient groups classified by either serum cholylglycine level or pathologic examination of biopsy specimens. Combination of the two measures of mephenytoin metabolism allowed the patients to be classified into three groups: normal hepatocyte function without portosystemic shunt, normal hepatocyte function with portosystemic shunt, and low hepatocyte function with or without portosystemic shunt. CONCLUSION: This study has shown the potential usefulness of mephenytoin metabolism as a sensitive indicator of hepatic pathologic condition with an ability to discriminate between contributory alternative mechanisms.

Adult↗

The pharmacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbon-tetrachloride-intoxicated rats.

The relationships between the pharmacokinetic behaviour of glycyrrhizin and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl4-treated rats). In patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were 62.2 +/- 7.4 and 64.4 +/- 7.5%, respectively, after daily 80 mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63.1 +/- 19.1 and 68.7 +/- 15.2% after 120 mg doses. The present work suggests that the threshold plasma glycyrrhizin concentration for sufficient effect is near 5 micrograms mL-1. In rats, the total body clearance (Cltot) for glycrrhizin in the CCl4-treated rats after i.v. administration of glycyrrhizin (5 mg kg-1 dose) was three-tenths of that of the control, and the t1/2 for glycyrrhizin was 3.4-fold longer than that of the control. A good correlation was observed between Cltot and AST (r = -0.838) or ALT (r = -0.873) activity in both rats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl4-treated rats showed a greater improvement than for a 10 mg kg-1 dose. Furthermore, the finding on the threshold plasma concentration in patients as above was also supported from the results of the experiments in rats.

Alanine Transaminase↗

How I do it: assessment of hepatic functional reserve for indication of hepatic resection.

Liver resection of up to 75% of the total liver volume (TLV) has been regarded as safe in normal livers, but this concept was challenged by the results of living donor hepatectomies. In normal livers or livers with resolved jaundice, hepatectomy of 65% of TLV may be safe, except for patients with an indocyanine green retention rate at 15 min (ICG R15) of over 15%, excessive hepatic steatosis, and age of over 70 years. However, the permissible extent of hepatectomy has been much restricted in cirrhotic livers because most post-hepatectomy liver failure (PHLF) has occurred in cirrhotic livers. Our routine protocols for the assessment of functional hepatic reserve (FHR) include biochemical liver function tests, ICG R15, Doppler ultrasonography, and triphasic liver computed tomogram (CT) with volumetry. Blood cell count and gastroesophageal endoscopic findings are taken into consideration for cirrhotic livers, as well as age, diabetes, cardiopulmonary function, and general performance. Preoperative portal vein embolization has been used for safe hepatectomy even in cirrhotic livers. We think that any cirrhotic liver showing optimal FHR should have a remnant liver of 40% of TLV to prevent PHLF. ICG R15 and triphasic CT with volumetry have been the most useful methods for assessment of FHR and determination of hepatectomy extent in our institution.

Coloring Agents↗

Hepatic lobar differences in progression of chronic liver disease: correlation of asialoglycoprotein scintigraphy and hepatic functional reserve.

We studied the hepatic functional reserve in the lobes of the liver in 28 patients with chronic liver disease and 13 controls using single photon emission computed tomography (SPECT) imaging with a radiolabeled asialoglycoprotein analog, Technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin (Tc-99m GSA). Counts of Tc-99m GSA radioactivity in the liver on SPECT images significantly correlated (P < .0001) with the serum albumin level (r = .612), log (serum cholinesterase activity) (r = .618), serum bilirubin level (r = .628), prothrombin time (r = .715), hepaplastin test (r = .637), and indocyanine green retention rate at 15 minutes (r = .771), making it possible to estimate the distribution of functional reserve in the liver based on counts. Using the intact hepatocyte theory, we estimated the number of viable hepatocytes based on the counts. With progression of hepatic functional degeneration, counts per unit hepatic volume decreased (rho = .779, P < .0001), and left lobe to right lobe ratio of this parameter increased (rho = .491, P = .0019) significantly. These findings suggest that the reduction of hepatic functional reserve per unit hepatic volume and numerical density of the hepatocytes, and the proliferation of fibrosis in patients with chronic liver disease is slower in the left lobe than in the right. We discuss a possible biological basis for these apparent lobar differences and for hepatic morphological changes seen in cirrhosis.

Adult↗

The relationship between pharmacokinetic behaviour of glycyrrhizin and hepatic function in patients with acute hepatitis and liver cirrhosis.

The pharmacokinetic behavior of glycyrrhizin in four patients with acute hepatitis (hepatitis group) and six patients with liver cirrhosis (cirrhosis group) receiving chronically an IV administration of a 120 mg dose once a day or once every other day of glycyrrhizin was investigated. The plasma concentration of glycyrrhizin declined monoexponentially in both groups. The elimination half-life (t1/2) for glycyrrhizin in the hepatitis and cirrhosis groups varied significantly in the range of 2.7-7.6 h and 6.2-40.1 h, and the total body clearance (CLtot) in the range of 2.8-23.2 mL h-1 kg-1 and 1.4-12.9 mL h-1 kg-1, respectively. The t1/2 for glycyrrhizin in the hepatitis and the cirrhosis groups was about twice and eight times that in normal subjects, respectively, as reported previously, and CLtot values were about 0.7 and 0.23 times that in normal subjects, respectively. There was significant correlation between the CLtot and hepatic function (aspartate aminotransferase and alanine aminotransferase in serum) in both patient groups. With improvement of the liver function, the CLtot for glycyrrhizin increased from 2.8 ml h-1 kg-1 to 11.4 mL h-1 kg-1, and the t1/2 shortened from 7.6 h to 3.4 h. These findings indicated that the variation of pharmacokinetic behaviour of glycyrrhizin in both groups was closely related to the extent of the liver function.

Adult↗

Functional hepatic flow and Doppler-assessed total hepatic flow in control subjects and in patients with cirrhosis.

Functional hepatic flow and total hepatic flow were determined by non-invasive techniques in 32 patients with cirrhosis and in 32 paired control subjects. Functional hepatic flow was measured by the hepatic clearance of D-sorbitol, while total hepatic flow was determined by pulsed echo-Doppler, as the sum of portal and hepatic arterial blood flow. Functional hepatic flow was significantly reduced in patients with cirrhosis (927 +/- 314 vs. 1287 +/- 315; p < 0.0001), while total hepatic flow was slightly increased (1511 +/- 540 vs. 1261 +/- 321 in controls; p = 0.028). In control subjects functional hepatic flow significantly correlated with total hepatic flow (r = 0.823; p < 0.001), while no correlation was observed in cirrhosis. Functional hepatic flow and the difference between total hepatic flow and functional hepatic flow significantly correlated with the Child-Pugh score in patients with cirrhosis. The data obtained in control subjects support the measurement of functional hepatic flow and total hepatic flow by non-invasive techniques. The finding that in cirrhosis functional hepatic flow is significantly decreased, while Doppler-assessed total hepatic flow is preserved or even increased, confirms that a relevant part of blood flowing through the liver is diverted by intrahepatic shunts. The simultaneous assessment of these two parameters by non-invasive techniques may be proposed as a reliable tool for the study of functional shunting of cirrhosis.

Adult↗

Surgical hepatosplenic mansonic schistosomiasis in adolescents: repercussions of the post-treatment schistosomotic burden on the hepatic functional reserve.

Schistosomiasis mansoni affects the hepatic functional reserve. Clinical treatment with oxamniquine is not 100% effective and there has been found strain of this parasite resistant to this drug. The aims of this investigation were: (1) to examine the presence of residual parasite burden after medical and surgical treatment on adolescents with surgical schistosomiasis mansoni and (2) to assess the effect on the hepatic functional reserve in patients with and without residual infection. Twenty nine children with hepatosplenic schistosomiasis mansoni and bleeding esophageal varices were treated with oxamniquine. They underwent splenectomy, ligature of the left gastric vein and autologous implantation of spleen tissue into the greater omentum. After a mean post-operative follow up of five years they underwent rectal biopsy for schistosomotic egg search. They were divided in patients with and without infection. In 20 patients the submucosal egg search was negative, however, in 9 it was positive. The hepatic functional reserve in the patients without infection was as follows: 17 were Child-Pugh A and 3 Child-Pugh B. In the patients who were still infected 6 were Child-Pugh A and 3 Child-Pugh B. The chi2 analysis of the hepatic functional reserve showed chi2 = 3.19 - p= 0.07. From the results the following conclusion can be drawn: residual infection or reinfection in the follow up period had not interfered with the distribution of the hepatic functional reserve of the patients in this series. However, there was a trend for a decrease of this parameter in patients with residual infection.

Adolescent↗

Effects of fasting on hepatic function in ponies.

Hepatic function was measured, using sulfobromophthalein sodium (BSP) in fed and fasted ponies. In the 1st experiment, single injections of BSP were administered, and the rate of removal of BSP from plasma was determined. Fasting decreased the rate of BSP removal from plasma, as indicated by increased half-time (t 1/2). In the 2nd experiment, BSP was infused for 5 hours, and its clearance from plasma was determined. Fasting decreased BSP clearance. In the 3rd experiment, BSP was infused consecutively at 2 dose rates, and maximal excretion and hepatic storage were determined. Although fasting did not affect maximal excretion, it decreased hepatic storage. Thus, results in the 3 experiments indicated a decreased hepatic clearance of BSP during fasting.

Animals↗

Effects of quinestrol on hepatic function in the rat.

Hepatic function in female rats given 200 microgram of quinestrol every 15 days for up to 210 days was studied. Prolonged treatment with quinestrol affected liver weight, serum cholestrol levels, biliar flux, and bromosulphthalein test, but these parameters tended toward control levels after 30 days of treatment. Quinestrol failed to affect alkaline phosphatase, oxalacetic and pyruvic transaminases and the concentration of bilirubin in serum and bile. The effects of quinestrol on hepatic function are similar to the effects of other estrogen derivatives.

Alkaline Phosphatase↗

Copper and hepatic function.

When hepatic excretion of copper into bile is impaired, the amount of copper in the liver increases. This happens in extrahepatic cholestasis, primary biliary cirrhosis and in two inherited diseases of copper disease. By six months of age the homozygously affected Bedlington terrier has already begun to accumulate copper in its liver. The trend continues, peaking at the age of five to eight years, when hepatic copper may exceed 10 000 microgram/g dry weight (normal 90--400 microgram/g in livers from mongrels). Despite these concentrations, which are several times higher than those found in any human disease, there is remarkable little evidence of hepatic inflammation or fibrosis in younger Bedlington terriers. The copper is condensed in lysosomes and is identified by X-ray emission spectroscopy. Hepatic cirrhosis eventually develops and death is often associated with ascites and jaundice. Despite characteristic histological differences between the livers in Wilson's disease and in the Bedlington disease, there is a striking general resemblance between the two conditions.

Aging↗

Correlation of detectability of hepatitis C virus genome in saliva of elderly Japanese symptomatic HCV carriers with their hepatic function.

The hepatitis C virus (HCV) genome was sought in the saliva of 76 chronic HCV carriers (mean age nearly 60 years) in a rural Japanese town, who had high serum titers of c-100 and anti-core second generation antibodies. In 27 samples (27 cases, 36%), the HCV-RNA genome was detected by the reverse transcriptase - polymerase chain reaction with either of two sets of primers covering two regions of the HCV genome: the 5'noncoding region and the region encompassing the putative envelope (E1). Transaminase values at the time of sampling were higher in the patients with than in those without detectable HCV RNA in saliva (p = 0.04 for alanine aminotransferase, p = 0.04 for aspartate aminotransferase; Wilcoxon test). The prevalence of the positivity was higher by 5'noncoding primers (14/59 vs. 15/68). Our data show that the severity and duration of hepatic dysfunction influence the detectability of the HCV genome in the saliva. This has been a controversial point among investigators.

Adult↗

[99mTc-GSA dynamic SPECT for regional hepatic functional reserve estimation: assessment of quantification].

For the estimation of regional hepatic functional reserve, we produced a three-dimensional hepatic functional mapping method employing 99mTc-GSA dynamic SPECT. In this analyzing protocol, we applied Patlak plot for the estimation of the liver uptake parameter of GSA, which is named hepatic GSA clearance, because it is relatively simple and suitable for matrix by matrix analysis. In this study, we assessed the physiological implication of estimated parameters and the clinical value of this analyzing method for hepatic functional reserve estimation. After venous injection of 185 MBq of GSA (3 mg), fifteen sequential sets of SPECT data were acquired for 15 minutes. First 5 sets (minutes) SPECT images were analyzed by Patlak plot and hepatic GSA clearance (ml/min) was obtained in each matrix. The sum of hepatic GSA clearance in each matrix (total hepatic GSA clearance) was calculated as an index of whole liver functional reserve. Total hepatic GSA clearance was compared with receptor index or effective blood flow (EHBF) of whole liver which were analyzed by Direct Integral Linear Least Square Regression (DILS) method for the assessment of the physiological implications of hepatic GSA clearance. The clinical value of total hepatic GSA clearance was assessed in comparisons with the conventional hepatic function test. A very good correlations were observed between total hepatic GSA clearance and receptor index (r = 0.935, p < 0.0001, n = 49), whereas the correlations between total hepatic GSA clearance and EHBF were not significant. Significant correlations were also observed between total hepatic GSA clearance and the conventional hepatic function tests, such as choline esterase (r = 0.517, p = 0.0001, n = 47), albumin (r = 0.612, p < 0.0001, n = 49), hepaplastin test (r = 0.539, p < 0.0001, n = 47), ICG R15 (r = -0.616, p < 0.0001, n = 37). These results suggested that hepatic GSA clearance strongly reflects hepatic receptor function and this parameter seemed to be useful for the hepatic functional reserve estimation.

Chronic Disease↗

[Effects of prostaglandin E1 on hepatic function and hepatofibrosis in patients with chronic hepatitis B].

To search for an effective drug to cure patients with chronic hepatitis B. Twenty eight patients with chronic hepatitis B were treated with prostaglandin E1. The comprehensive indexes, including glutamic pyruric tranasaminase (GPT), serum total bilirubin (TBIL), total bile acid (TBA), hyaluronic acid (HA) and precollagen type III (PCIII), were examined before and after treatment. The levels of GPT, TBIL, TBA, HA, PCIII after 1 month of the treatment were significantly lower than those before the treatment (P < 0.05), there were significant differences between the treated and the controlled group patients with chronic hepatitis B (P < 0.05). The results suggest that the treatment with PGE1 might improve hepatic function, and resist the hepatic fibrosis in patients with chronic hepatitis B.

Adult↗

The pharmacokinetics of ziprasidone in subjects with normal and impaired hepatic function.

AIMS: To assess whether hepatic impairment influences the pharmacokinetics of ziprasidone. METHODS: Thirty subjects with normal hepatic function or a primary diagnosis of clinically significant cirrhosis (Child-Pugh A or B) were enrolled into an open-label, multicentre, multiple-dose study. The subjects with chronic, stable hepatic impairment and the matched control subjects received ziprasidone 40 mg day(-1), given orally with food, as two divided daily doses for 4 days and a single 20 mg dose on the morning of day 5. Pharmacokinetic variables were determined from multiple venous blood samples collected on days 1 and 5. Liver function was evaluated quantitatively using antipyrine. RESULTS: On day 1 there were no statistically significant differences in the pharmacokinetics (AUC(0,12 h), Cmax, tmax) of ziprasidone between the two groups. On day 5 there were no statistically significant differences in the Cmax or tmax for ziprasidone between the two groups. The mean AUC(0,12 h) for ziprasidone was statistically significantly greater in the hepatically impaired subjects compared with the normal subjects (590 ng ml(-1) h vs. 467 ng ml(-1) h, P = 0. 042). However, the AUC(0,12 h) increased by only 26% in the cirrhotic group compared with the matched control group. The ziprasidone lambda(z) in the subjects with normal hepatic function was statistically significantly greater than that in the hepatically impaired subjects (P<0.001). There was no correlation between antipyrine lambda(z) and ziprasidone lambda(z) in the subjects with normal hepatic function or in those with hepatic impairment. CONCLUSIONS: The findings of this study indicate that mild to moderate hepatic impairment does not result in clinically significant alteration of ziprasidone pharmacokinetics.

Adolescent↗

A rapid method for determination of hepatic amino nitrogen to urea nitrogen conversion ('the Functional Hepatic Nitrogen Clearance').

The Functional Hepatic Nitrogen Clearance (FHNC) is a measure of the functional liver mass as to conversion of amino-N to urea-N. FHNC is the slope of the linear regression of multiple samples (10-20) of urea-N synthesis rates (UNSR) on blood alpha-amino-N concentrations (alpha-AN) during infusion of amino acids. UNSR is measured as urinary urea-N excretion rate corrected for accumulation in total body water (TBW) and loss in gut. A simplified method which estimates FHNC from only two samples of UNSR and alpha-AN was developed. Urine was collected in two hourly intervals: before infusion of alanine, and from 2 to 3 h after start of alanine infusion. Blood-urea-N and alpha-amino-N was measured at the beginning and at the end of each urine sampling interval. TBW was estimated from a nomogram, and gut loss of urea was assigned a fixed value (14%). The two-sample FHNC was calculated as delta UNSR (mmol h-1)/delta mean alpha-AN (mmol l-1). Linear regression analysis of the two-sample estimates of FHNC on the 'true' multiple-sample values of FHNC in an independent population of control and cirrhotic subjects showed the two-sample estimates to be closely related with values of the multiple-sample method, the regression equation being: two-sample FHNC = -0.24 + 0.99 x multiple-sample FHNC, r2 = 0.98. A close relationship was also obtained when cirrhotic patients were considered alone: two-sample FHNC = 0.01 + 0.94 x multiple-sample FHNC, r2 = 0.98.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗

[Hepatic protein synthesis rate as an index of hepatic functional reserve in human liver].

Hepatic protein synthesis rate (HPS) in human livers were measured to evaluate hepatic functional reserve. HPS of 34 patients who underwent operations were studied and were divided into 4 groups. Normal liver (n = 7), obstructive jaundice (n = 9), liver cirrhosis (n = 8) and other hepatic dysfunction (n = 10). HPS in normal liver was 6.9 +/- 3.0 nmol/mg wet wt./10 min. HPS in obstructive jaundice liver was 17.1 +/- 10.3, and HPS in liver cirrhosis was 47.5 +/- 17.8. There were significant differences among these three groups. HPS correlated well with cholinesterase (r = -0.6533, P less than 0.01) and ICGR15 (r = 0.7315, P less than 0.01). In 15 patients who received hepatectomy, relations between HPS and postoperative complication were studied. There were no complications in patients whose HPS were less than 20 nmol/mg wet wt./10 min. in major hepatic resection and in patient whose HPS were less than 40 in a segmentectomy. Even if HPS were elevated, the operations were safe in subsegmentectomy and partial hepatectomy. So HPS would be one of the good indices to evaluate hepatic functional reserve.

Biopsy, Needle↗

Parenteral glutamine protects hepatic function during bone marrow transplantation.

Hepatic veno-occlusive disease (VOD) of the liver is a common complication following high-dose cytotoxic therapy for bone marrow transplantation (BMT). The major pathological changes are seen in centrilobular (zone 3) hepatocytes and adjacent endothelium. Glutathione (GSH) becomes depleted following chemotherapy and experimental evidence suggests reduced levels predispose to centrilobular hepatocyte and endothelial cell injury. Animal studies have shown that glutamine infusions can maintain GSH levels and protect against free radical injury. We have prospectively studied the effect of glutamine supplementation during BMT. Thirty-four patients undergoing BMT were randomised to receive either glycl-L-glutamine (n = 18) or an isonitrogenous mixture of non-essential amino acids (n = 16). Glutamine was shown to significantly preserve protein C (days +4 and +7, P < 0.05) and albumin levels (days 0 and +4, P < 0.02). Markers of thrombin and plasmin generation (thrombin-antithrombin, prothrombin fragment F1+2 and plasmin-antiplasmin levels) were not significantly changed between the two groups. These findings suggest that glutamine preserves hepatic function but does not alter thrombin or plasmin generation during BMT. Previous studies have shown reductions in protein C, albumin, factor X and factor VII levels post BMT. Falling protein C levels have been shown to be predictive of severe VOD. These data suggest a role for glutamine in the protection of hepatic function following BMT.

Adolescent↗