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PubMed1992

[Characteristics of clinical pathology and changes of liver function in blood stasis syndrome in liver diseases].

The experimental study on 30 patients of the Blood Stasis Syndrome of liver diseases was discussed in this paper. Two characteristics were found. One was the pathological feature which manifested as follows: (1) DIAGNOSIS: the Blood Stasis Syndrome of liver disease was mainly diagnosed in the chronic active hepatitis and the early stage of cirrhosis of liver, while that of non-Blood Stasis was mainly observed in the chronic persistent hepatitis (P less than 0.01); (2) Pathological change: The histological changes such as piecemeal necrosis, bridging necrosis, the destruction of limiting plate, eosinophilic change, etc. It was more obvious in the Blood Stasis group than that with non-Blood Stasis Syndrome (P less than 0.01), (3) The manifestation of Blood Stasis Syndrome was not in parallel with the severity of the liver disease. The another characteristic was the changes of liver function, which expressed more markedly in the Blood Stasis group with higher level of SGPT, lower ratio of A/G and increased globulin, they were more obvious than that in non-Blood Stasis group (P less than 0.01).

Adolescent↗
PubMed2003

Effect of the CD14 promoter polymorphism on liver function tests and its association with alcohol and obesity.

OBJECTIVE: To investigate the effect of the functional CD14 promoter polymorphism on serum liver function tests and abnormally elevated liver function tests in a general population sample. METHODS: We recruited 310 subjects at random from general practitioner lists in Surrey. A previously validated medical questionnaire was completed and a serum sample provided for estimation of liver function test and genotyping of CD14 promoter polymorphism. RESULTS: The TT polymorphism was associated with significantly reduced serum levels of alanine aminotransferase 0.49 (95% confidence interval 0.26-0.93), gamma-glutamyl transferase 0.49 (95% confidence interval 0.38-0.89) and aspartate aminotransferase 0.48 (95% confidence interval 10.38-0.89). The TT polymorphism was associated with a reduced frequency of liver function test abnormalities, especially gamma-glutamyl transferase (odds ratio 0.113; 0.015-0.851). CONCLUSION: The TT promoter polymorphism was associated with reduced serum levels of alanine aminotransferase, gamma-glutamyl transferase and aspartate aminotransferase in healthy patients, and a low level of liver function test abnormalities. The relationship with gamma-glutamyl transferase stands after correction for age, gender, obesity and alcohol consumption. This raises the possibility that this genotype may offer protection from the development of fatty liver disease.

Aged↗
PubMed1996

Caffeine clearance test: a quantitative liver function assessment in patients with liver cirrhosis.

BACKGROUND: Quantitative assessment of live function is an important work-up for patients with liver cirrhosis. The aim of the present study was to clarify the role of caffeine clearance test in the quantitative measurement of metabolizing capacity of the liver. METHODS: Twenty-eight patients with liver cirrhosis and 28 normal healthy volunteers were enrolled in this study. After an overnight fast, the first blood sample was collected at 8 a.m., immediately followed by an oral administration of 150 mg caffeine. Subsequent samples of venous blood were obtained at 8.30 a.m., 9 a.m., 11 a.m., 2 p.m. and 5 p.m. The caffeine clearance was determined using two caffeine concentrations from blood samples taken at 2 p.m. and 5 p.m., which were then measured by an enzyme multiple immunoassay technique. RESULTS: The serum caffeine clearance was significantly higher in the control group than in the patient group (1.72 +/- 1.06 vs. 0.78 +/- 0.77 ml/min/kg, p < 0.0001). Elimination half-life was significantly prolonged in the patient group (3.74 +/- 1.05 vs. 2.69 +/- 0.75 hours, p < 0.0001). The influence of cigarette smoking was also evident: higher clearance and shorter half-life of caffeine were noted in the smoking subjects. In the non-smokers, caffeine clearance was 1.30 +/- 0.90 and 0.51 +/- 0.47 ml/min/kg and half-life of caffeine was 2.89 +/- 0.78 and 4.06 +/- 0.93 hours, respectively (control vs. patient, p < 0.05). In the smokers, caffeine clearance was 2.30 +/- 0.98 and 1.13 +/- 0.96 ml/min/kg and half-life of caffeine was 2.41 +/- 0.63 vs. 3.31 +/- 1.06 hours, respectively (control vs. patient, p < 0.05). During the mean six-month period of follow-up, the mortality rate was significantly higher in those patients with caffeine clearance less than 0.5 ml/min/kg than in those with clearance more than 0.5 ml/min/kg (46.1% vs. 6.7%, p < 0.05). A significantly negative correlation between the serum caffeine clearance and the Child-Pugh's score was also demonstrated (r = -0.851, p < 0.0001). CONCLUSIONS: Serum caffeine clearance determined at two points of blood concentration is a useful method to evaluate the severity of liver disease and predict short-term survival of cirrhotic patients. It offers another choice for the quantitative measurement of liver functional reservoir.

Adult↗
PubMed1993

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.

Adult↗
PubMed2000

Perioperative safety and prognosis in hepatocellular carcinoma patients with impaired liver function.

BACKGROUND: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: Limited liver resection is safe and provides favorable prognosis in HCC patients with concomitant impaired liver function.

Adult↗
PubMed1997

Pharmacokinetics of imidapril and its active metabolite imidaprilat following single dose and during steady state in patients with impaired liver function.

OBJECTIVE: The possible influence of impaired liver function on the pharmacokinetic disposition of imidapril, a novel prodrug type angiotensin-converting enzyme (ACE) inhibitor, and its active metabolite, imidaprilat, was investigated. METHODS: Eight subjects with normal liver function and eight patients with liver dysfunction received an oral dose of 10 mg imidapril once daily for 7 days. RESULTS: Plasma imidapril concentrations after single and, although less pronounced, after repeated dosing were higher in the liver disease patients, whereas imidaprilat concentrations were lower. This suggests that the conversion of imidapril into imidaprilat in the liver is delayed in patients with impaired liver function. However, the slower biotransformation did not result in statistically significant differences in Cmax and AUC for either imidapril or its active metabolite following repeated administration. Moreover, no relevant accumulation of either imidapril or imidaprilat occurred after repeated dosing. CONCLUSIONS: Imidapril is regarded as an ACE inhibitor of which the pharmacokinetic disposition is only slightly affected in patients with impaired liver function.

Adult↗
PubMed1993

Dynamics of normal and injured human liver regeneration after hepatectomy as assessed on the basis of computed tomography and liver function.

We compared liver volume and function kinetics after partial hepatectomy according to extent of resection and severity of coexisting liver disease in 57 adults with uneventful postoperative courses. Liver volume and massiveness of resection, or resection rate, were estimated on computed tomography. Patients were categorized into three groups on the basis of reaction rate: small (< 30%), medium (30%-50%) and large (> 50%). The regenerative patterns of normal livers in the medium and large groups consisted of three phases: a rapid increase during the first month, some decrease in the second month and a final, slower increase. This contrasted with the pattern of injured livers with chronic hepatitis or cirrhosis, which generally showed a phase of less rapid, gradual increase. The regeneration rate (volume gain, cm3/day) during the first month was found to be proportional to resection rate in the presence or absence of liver disease. Normal livers regenerated at least twice as rapidly as injured livers in patients with comparable resection rates. Normal livers reached plateau levels within 1 to 2 mo regardless of the massiveness of resection, whereas regeneration took 3 to 5 mo in injured livers. Liver function (albumin, bilirubin) recovered concomitantly with liver volume in the medium group, whereas in the large group they generally returned to their initial values behind volume restoration, particularly in cirrhotic patients. In conclusion, human liver regeneration is strongly influenced by the massiveness of the resection and presence of coexisting liver disease. However, we found that some cirrhotic livers can regenerate, albeit more slowly and less completely, as long as the extent of hepatectomy remains within safe functional limits.

Adult↗
PubMed1995

The liver-spleen scan as a quantitative liver function test: correlation with liver severity at peritoneoscopy.

Sulfur colloid distribution on liver-spleen scan is determined by the perfused Kupffer cell mass. The perfused Kupffer cell mass is proportional to the perfused hepatocyte mass, but is less affected by acute changes in hepatocyte function. Thus, sulfur colloid distribution parameters (precisely measured by quantitative liver-spleen scan [QLSS]) may be an excellent test of the perfused hepatic mass. Although no gold standard exists for confirmation, a close correlation should exist between liver disease severity assessed at peritoneoscopy and sulfur colloid distribution. Peritoneoscopy severity (scored as total peritoneoscopy score [PS]; range, 0-5) was assessed in 76 patients who also had QLSS. Multivariate equation were generated to estimate liver disease severity from the QLSS. These were then applied prospectively in 20 consecutive patients to validate these equations. In 76 patients, 62 were evaluated because of chronic liver disease (CLD) and included those with micronodular (20) and macronodular (20) cirrhosis with various degrees of severity (Child's A, 16; B, 29; C, 17). Multivariate analysis yielded a number of combinations of QLSS parameters that correlated with peritoneoscopic severity. These equations were used to estimate liver disease severity. Estimates of liver disease severity (estimated PS [EPS]) correlated well with the PS in these 76 patients (r = .9064; r2 = .8216; P < .0001). Adding histological fibrosis to the QLSS parameters yields an equation for estimating PS that was even more effective (r = .9462; r2 = .8953; P < .001). However, validation of multivariate equations requires confirmation of their value in a second population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Liver function tests in patients of pulmonary tuberculosis using four different drug regimens.

BACKGROUND: Chemotherapy is the basic approach to clinical tuberculosis control. Antituberculous therapy causes derangement of hepatic functions revealed by disturbed liver function tests. The incidence of side effects may vary depending upon a number of factors. The primary purpose of this study was to determine the relative and absolute hepatotoxicity of different antituberculous drug regimens in Pakistani population where majority of the tuberculous patients belong to poor socioeconomic status. METHODS: One hundred patients between 30 to 70 years of age with newly diagnosed pulmonary tuberculosis were selected and divided into four groups on the basis of different drug regimens. Blood and urine tests of these patients were made. Liver function tests were performed before therapy and then after one, two, three, six and nine months of treatment. RESULTS & CONCLUSIONS: Antituberculous therapy causes derangement of hepatic function to a variable extent in patients of four different antituberculous drug regimens under study. Drug combination of Streptomycin, Isoniazid and Myambutol seem to be best tolerated of all the four regimens. Monitoring of the liver function in patients on antituberculous therapy indicated that liver dysfunction most frequently occurs during first three months of therapy. There is a tendency for enzyme values to return to normal inspite of continuous treatment. The mechanism underlying this adaptation to injury to the liver is unknown. Biochemical tests in the patients presenting with jaundice yielded the pattern of acute hepatocellular necrosis with high transaminases and moderately elevated Alkaline Phosphatase. None of the patients had hepatitis associated antigen in their serum.

Adult↗
PubMed1996

Assessment of functional liver mass and plasma flow in acromegaly before and after long-term treatment with octreotide.

Functional liver mass and functional liver plasma flow (FLPF) were assessed in 11 patients with clinical features of acromegaly by determining galactose elimination capacity (GEC) and extrarenal clearance of sorbitol, before and 5 to 7 months after treatment with the long-acting somatostatin analog, octreotide (150 to 600 micrograms/d in three subcutaneous injections). Growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels, as well as liver size by ultrasound, were also recorded. Baseline GEC was increased in every patient but one, for a mean of 0.78 +/- 0.10 g/min (normal, 0.53 +/- 0.07; P < .01). At reevaluation after 5 to 7 months of octreotide treatment, a significant reduction of GEC was observed (0.62 +/- 0.08 g/min, P < .001). Changes of GEC paralleled those of GH (38.6 +/- 34.4 v 11.7 +/- 15.2 micrograms/L, P < .01) and IGF-I (5.0 +/- 1.7 v 2.7 +/- 2.2 U/ml, P < .001). Significant correlations were found between GEC and GH (r = .50, P < .05) and between GEC and IGF-I (r = .55, P < .01). FLPF, assessed by extrarenal clearance of sorbitol, was within the normal limit in all cases (0.98 +/- 0.19 v 0.97 +/- 0.12 L/min, NS) and remained normal after 5 to 7 months of octreotide treatment (0.99 +/- 0.11 L/min). Hepatic structure determined with ultrasonic scanning and conventional liver-function tests were basally normal in all patients, with a slight increase of liver volume in three cases. No change of biochemical and/or morphological features occurred during follow-up evaluation. The results support the hypothesis that GH and especially IGF-I enhance liver metabolic capacity; conversely, functional liver perfusion is largely independent of their actions. Our data also suggest that octreotide is unable to produce well-structured changes of liver circulation when administered long-term.

Acromegaly↗
PubMed1987

Monoethylglycinexylidide formation kinetics: a novel approach to assessment of liver function.

A novel quantitative liver function test is described which is based on monoethylglycinexylidide (MEGX) formation after lidocaine bolus injection. Following the administration of small single doses of lidocaine hydrochloride (1 mg/kg), monoethylglycinexylidide serum concentration-time curves were determined by a novel highly sensitive fluorescence polarisation immunoassay (FPIA) in healthy volunteers, liver donors and patients with liver cirrhosis. The FPIA allowed rapid and reliable monoethylglycinexylidide determinations in serum and urine (between-days coefficient of variation: less than 10.3%, recovery: 80-113%). Monoethylglycinexylidide concentrations measured by FPIA in 32 serum samples from patients correlated well those determined by HPLC. The monoethylglycinexylidide concentration in serum determined 15 min after a lidocaine bolus injection proved to be a highly sensitive and specific indicator of hepatic dysfunction. Average monoethylglycinexylidide concentrations in serum obtained 15 min after lidocaine injection were substantially lower in patients with liver cirrhosis than in healthy volunteers. The average monoethylglycinexylidide concentrations in serum were also substantially lower in liver donors with ballooning or fatty changes of hepatocytes than in donors without relevant alterations of liver histology. By means of monoethylglycinexylidide formation in the liver donors, primary function of the transplanted liver was correctly predicted in 32/37 cases and initial non-function in 4/6 cases.

Chromatography, High Pressure Liquid↗
PubMed1992

[Liver function tests in a clinical comparison].

Various liver function tests were evaluated in regard to a quantitative estimation of the impairment of liver function related to the Child-Pugh classification in 32 patients with cirrhosis. Only the ICG-test revealed significant differences between healthy subjects and cirrhotic patients in stadium Child A, B and C. When ICG-dye retention values were plotted as a function of the individual score units of the Child-Pugh classification, a linear relationship with a correlation coefficient of 0.7 was obtained. In contrast to the ICG-test, the MEGX- and galactose elimination capacity (GEC)-test as well as static parameters of liver function (cholinesterase activity, prealbumin concentration, coagulation factor V and VII) resulted in less significant differentiation of the various Child classes. The MEGX-test, GEC, concentration of prealbumin, coagulation factor V and VII were only weakly correlated to the score units of the Child-Pugh index. The results of this study indicate that of all evaluated parameters only the ICG-test is suitable for objective and graduated analysis of liver function in patients with cirrhosis.

Cholinesterases↗
PubMed1993

Protein C, factor VII and prothrombin time as early markers of liver function recovery or failure after liver transplantation.

Irreversible initial non-function of the graft liver is a life-threatening early complication of orthotopic liver transplantation (OLT), which needs immediate retransplantation if the patient is to survive. Since protein C (PC) is a vitamin K dependent protein synthesized in the liver and with the same half-life as factor VII (FVII), the behaviour of PC in patients undergoing OLT was studied in comparison with prothrombin time (PT) and FVII. Twelve OLT patients were divided into two groups on the basis of clinical outcome: group A (six cases) in which OLT was successful, and group B (six cases) who developed initial non-function of the graft liver. PT, FVII activity (FVII:act) and antigen (FVII:Ag) and PC activity (PC:act) and antigen (PC:Ag) were carried out on six blood samples collected during the operation. At baseline, coagulation disorders were in agreement with the underlying liver disease, but no differences were seen between the two groups when all tests were considered. Ten minutes, 1, 2 and 3 h after liver reperfusion, mean PT and FVII:act were always significantly increased in good responder patients compared to non-responders. FVII:Ag and PC:Ag were significantly higher in group A than in group B starting 2 h after the liver graft reperfusion; no difference was seen in PC:act levels between the two groups. In addition, PC:Ag mean levels were increased with respect to corresponding PC:act values in non-responder patients, suggesting a qualitative rather than quantitative defect of protein synthesis due to liver damage. In conclusion, PT and FVII:act were more sensitive than PC activity as early prognostic indices of clinical outcome in OLT.

Adult↗
PubMedDate not supplied

Hepatocellular carcinomas do not compromise quantitative tests of liver function.

BACKGROUND/AIMS: Hepatocellular carcinoma, which usually develops in cirrhotic livers, is one of the most frequent cancers worldwide. If and how far hepatoma growth influences liver function is unclear. Therefore, we compared a broad panel of quantitative tests of liver function in cirrhotic patients with and without hepatocellular carcinoma. METHODOLOGY: Patients with (n=40) and without (n=40) hepatocellular carcinoma were matched according to Child-Pugh grade and subjected to testing of aminopyrine demethylation capacity, galactose elimination capacity, sorbitol clearance and indocyanine green clearance. RESULTS: Compared to healthy controls, patients with cirrhosis Child-Pugh grade B and grade C revealed reduced metabolic (aminopyrine demethylation capacity, galactose elimination capacity) and perfusion-dependent QTLF (sorbitol clearance, indocyanine green clearance). Comparing values of quantitative tests of liver function in matched patients with and without hepatocellular carcinoma, no differences in liver function parameters were observed. CONCLUSIONS: Quantitative tests of liver function correlated inversely with the Child-Pugh grade. Since these parameters are not affected by the occurrence of hepatocellular carcinoma, the emergence of hepatic neoplasia in cirrhotics does not appear to be determined by the degree of hepatic functional deterioration.

Aged↗
PubMedDate not supplied

Prospective evaluation of abnormal liver function tests in pregnancy.

Abnormalities in liver function tests (LFT) during pregnancy are a commonly encountered problem often associated with serious consequences especially when it occurs in the third trimester. The spectrum of abnormal liver functions in pregnancy can be fairly wide and diagnostic work up often challenging. There is insufficient prospective data on the spectrum and outcome of liver disease in pregnant population from south India. This study was performed to assess the causes of deranged liver function in the pregnant population and also to prospectively determine the outcome of liver dysfunction in pregnancy. All abnormal LFT results observed in serum samples from pregnant patients attending the obstetric unit of our hospital from January 2003 to January 2005 were evaluated and prospectively followed throughout pregnancy. Laboratory investigations included coagulation profile, renal function tests, serology for viral markers (HBsAg, anti-HCV, IgM anti-HEV and IgM anti-HAV) and other relevant biochemical tests. In those with liver dysfunction in the third trimester the maternal and perinatal outcome was evaluated. A total of 125 patients were identified with abnormalities in LFT results during this period. The majority of causes were related to pregnancy specific conditions (57.6%). Most episodes of abnormal LFT occurred in the third trimester (59.2%). Hyperemesis gravidarum (55.8%) and viral hepatitis (47%) were the most common causes of abnormal LFT in the first and second trimesters respectively. HELLP (28.3%) and AFLP (14.8%) were the most common causes of abnormal LFT in the third trimester. There were no mAternal deaths due to liver dysfunction in the first or second trimester. Liver dysfunction in the third trimester (74 patients) was associated with serious consequences. DIC was the most common complication (20.2%). The overall and perinatal mortality was 20.2% and 24.6% respectively. AFLP and HELLP syndromes were associated with poor maternal and fetal outcome. We conclude that liver dysfunctions were directly related to pregnancy in the majority of patients especially in the third namely trimester. Incidence of the most serious conditions AFLP and HELLP syndromes is much greater than what has been reported and is often associated with a high maternal mortality and poor perinatal outcome.

Adult↗
PubMed1993

Assessment of lidocaine metabolite formation in comparison with other quantitative liver function tests.

In clinical practice, the seriousness of liver disease is assessed based on the combined information from clinical examination, routine biochemical tests, and liver histology. Recently, the assessment of hepatic lidocaine metabolism has been proposed as a quantitative liver function test offering valuable additional information. To evaluate whether this new liver function test reflects the combined clinical assessment, we prospectively measured lidocaine metabolism in 111 patients with well characterized liver disease. In addition, lidocaine test results were compared with the aminopyrine breath test and the galactose elimination capacity. Lidocaine (1 mg/kg) was injected i.v. and serum concentrations of its main metabolite monoethylglycinexylidide were determined after 15 min. The results varied widely and the means (+/- S.D.) were similar among patients with mild liver disease (46 +/- 23 ng/ml), but significantly (P < 0.05) lower among patients with Child class A cirrhosis (19 +/- 11 ng/ml) or Child class B or C cirrhosis (21 +/- 19 ng/ml). The [13C]aminopyrine breath test, however, gave a better discrimination among patients with increasing severity of liver disease than lidocaine metabolite formation. The galactose elimination capacity finally best separated patients with mild liver disease from those with cirrhosis. The correlations between any two of the different quantitative liver function tests were weak (R2 consistently < 0.2). We conclude that lidocaine metabolite formation, like other quantitative liver function tests that are based on the microsomal metabolism of model compounds, quantitates a very particular enzymatic reaction which may not be representative for the functional reserve of the entire organ.

Adolescent↗