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Validity of the 13C-caffeine breath test as a noninvasive, quantitative test of liver function.

The properties of caffeine render it an ideal substrate for a quantitative test of liver function. The aim of this study was to determine whether the caffeine breath test (CBT) using orally administered 13C-caffeine correlates reliably with plasma caffeine clearance and reflects varying degrees of liver dysfunction. The CBT was performed in 25 healthy controls; 20 subjects with noncirrhotic, chronic hepatitis B or C; and 20 subjects with cirrhosis. Plasma caffeine clearance was assayed simultaneously with the CBT in a cohort of these subjects. Over a broad range of caffeine clearances, the CBT exhibited a highly significant correlation with plasma clearance (r = 0.85, P <.001). Cirrhotic patients were characterized by significantly reduced CBT values (1.15 +/- 0.75 delta per thousand mg(-1)) compared with controls (2.23 +/- 0.76; P =.001) and hepatitic patients (1.83 +/- 1.05; P =.04). There was a significant inverse relationship between the CBT and Child-Pugh score (r = -.74, P =.002). The intraclass correlation coefficient between repeated CBTs in 20 subjects with normal and cirrhotic livers was 0.89. Although smoking was associated with an 86% to 141% increase in CBT in all groups, the CBT was able to distinguish control, hepatitic, and cirrhotic smokers (5.36 +/- 0.82, 3.63 +/- 1.21, and 2.14 +/- 1.14, respectively, P =.001). Multivariate analysis revealed that only smoking (P <.001) and disease state (P =.001) were significant predictors of the CBT. In conclusion, the 13C-CBT represents a valid indicator of plasma caffeine clearance and correlates reproducibly with hepatic dysfunction.

Adult↗

Liver function studies in children with acute lymphocytic leukemia after cessation of therapy.

We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood.

Adolescent↗

Do abnormal liver function tests predict inpatient imaging yield? An evaluation of clinical decision making.

RATIONALE, AIMS AND OBJECTIVES: Diagnostic abdominal imaging is frequently performed in hospitalized patients to assess the cause of abnormal liver function tests (LFTs). We undertook this study to assess whether the extent and severity of LFTs abnormalities predicted the yield of inpatient imaging. METHODS: We retrospectively reviewed inpatients' abdominal imaging studies performed for abnormal LFTs during a 27 month period. Imaging results were matched to LFTs performed during a 5 day collection window surrounding the image request date. Five LFTs were categorized by severity of abnormality and were then collapsed into three classes based on pathophysiology. RESULTS: Among 759 imaging studies completed for the indication of abnormal LFTs, 196 (26%) were positive (abnormal and explained the abnormal LFTs). Among the LFT classes, severity of laboratory test abnormality correlated with positive imaging examinations yield only for the transaminases: 18% for the normal-mildly abnormal transaminases compared with 31% for moderately-severely abnormal transaminases. The number of abnormal LFT classes per study correlated only slightly better: 21% of patients with none or one abnormal LFT class had a positive imaging study compared with 35% of patients with all three abnormal LFT classes. CONCLUSIONS: The yield of inpatient abdominal imaging for abnormal LFTs correlates only weakly with both the severity and the extent of different abnormal LFTs. Further research is needed to define the optimal imaging strategies for evaluating inpatients with suspected hepatobiliary disease.

Biliary Tract Diseases↗

Liver function tests in nonparenteral cocaine users.

Cocaine-induced hepatotoxicity is well known in animal models, and many cases of it have been reported in human beings. We reviewed the results of liver function tests performed on admission in 71 randomly selected hospitalized nonparenteral cocaine abusers. We found 11 patients to have elevated levels of aspartate aminotransferase that were less than 28 U above the upper limit of normal. Five of them also had elevated levels of alanine aminotransferase that were less that 12 U above the upper limit of normal. Two patients had isolated elevations in alanine aminotransferase (less than 9 U above the upper limit of normal), and two patients had elevations in alkaline phosphatase (less than 50 U above the upper limit of normal). There was not correlation with regard to age, sex, duration of drug use, last dose, amount of use, or timing of blood tests. This minimal elevation of liver enzyme levels is common, but severe hepatotoxicity is uncommon.

Adult↗

Quantitative evaluation of liver function with MRI Using Gd-EOB-DTPA.

OBJECTIVE: Gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a newly developed MR contrast agent. After intravenous injection, Gd-EOB-DTPA is gradually taken up by the hepatocytes and eventually excreted via the biliary pathway without any change to its chemical structure. Because of these characteristics, it can be used as a tracer for quantitative liver function testing. The purpose of this study is to develop a noninvasive method of quantitation of the hepatic function using Gd-EOB-DTPA through the deconvolution analysis. MATERIALS AND METHODS: Adult New Zealand white rabbits (n = 10, average body weight = 3.5 kg) were used in the present study. Hepatic injury was induced to by the intragastric administration of carbon tetrachloride (CCl4) three times a week for three weeks. Liver enzyme (aspartate aminotransferase, AST; alanine aminotransferase, ALT) levels and the plasma indocyanine green (ICG) retention rate 15 minutes after an intravenous injection of ICG (ICG R15), was checked before and after the three-week administration of CCl4. At the end of experimental period, an observer "blinded" to the treatment given the rabbits performed the histological examination. MRI studies were performed before and after the three-week administration of CCl4 on a 1.5 T scanner using a human extremity coil. After intravenous bolus injection of Gd-EOB-DTPA (0.3 mL of Gd-EOB-DTPA freshly prepared in 2.7 mL of normal saline) through the ear vein, the 250 axial single level dynamic MR images were obtained using a fast low angle shot (FLASH, T /TE = 11/4.2 msec, flip angle = 15, acquisition time 1 second, slice thickness = 5 mm, matrix = 128x128, field of view = 120 mm) sequence with 1.5 sec time intervals. The time-intensity curves were obtained at the abdominal aorta and the liver parenchyma that was devoid of blood vessels. Deconvolution analysis of the aortic (input function) and hepatic parenchymal (output function) time-intensity curves was performed with a modified Fourier transform technique to calculate the hepatic extraction fraction (HEF). The presence and type of hepatic injury were determined by the histopathologic examination and statistical analysis of the changes of the hepatic enzyme levels, the ICG R15 and Gd-EOBDTPA HEF values between the time before and after CCl4 administration with Wicoxon signed rank test. Correlation between the Gd-EOB-DTPA HEF and the change of the ICG R15 were analyzed with Pearson's correlation coefficient. RESULTS: Histopathologic examination showed findings that were compatible with hepatic fibrosis caused by chronic liver injury. The initial blood biochemical studies before the administration of carbon tetrachloride showed that the mean AST and ALT levels were 39.8+/-5.2 IU/L and 59.1+/-11.7 IU/L, respectively. The AST and ALT levels increased to 138.4+/-50.5 IU and 172.0+/-71.6 IU/L, respectively, after the three week administration of CCl4. The ALT and AST levels were significantly increased after the three weeks of CCl4 administration (p = 0.018). The ICG R15 values were 4.47+/-2.08% and 19.43+/-3.98% before and after three-week administration of CCl4, respectively. The ICG R15 values were significantly increased after hepatic injury (p = 0.018). After normalizing the HEF as 100% in each rabbit before CCl4 administration, the deconvoluted curve after CCl4 administration revealed less hepatocyte extraction efficiency with a mean value of 77.7+/-3.6. There was a significant correlation between the HEF and changes of the ICG R15 by the Pearson correlation coefficient assessment (correlation coefficient = -0.965, p = 0.000). CONCLUSION: The Gd-EOB-DTPA HEF could be calculated from deconvolution analysis of aortic and hepatic parenchymal time-intensity curves obtained by dynamic MRI. The Gd-EOB-DTPA HEF was well correlated with changes of the ICG R15, which is the most common parameter used in the quantitative estimation of the hepatic function. The Gd-EOB-DTPA HEF is a direct, noninvasive technique for the quantitative evaluation of liver function. It could be a promising alternative for the determination of noninvasive hepatic function in those patients with liver disease.

Alanine Transaminase↗

Liver function tests in adults with Plasmodium falciparum infection.

This study examines the levels of serum bilirubin, aspartate transaminase and alkaline phosphatase in adults with Plasmodium falciparum malaria. One hundred and six sets of liver function tests were obtained, and 63 (59.4%) patients had one of the above indices elevated outside the local reference range. Serum bilirubin and aspartate transaminase were relatively higher than alkaline phosphatase. Neither duration of illness nor severity of infection showed any significant correlation with any of the indices measured.

Adolescent↗

Liver function in a group of hospitalised alcoholics and non-hospitalised problem drinking probationers.

Twenty non-hospitalised problem male drinkers and 20 hospitalised problem drinkers were investigated by the Michigan alcohol screening test (MAST) and by liver function tests (AST, ALT). The MAST scores of the non-hospitalised group were above normal and indicative of alcohol addiction, AST and ALT tended to be higher in the hospitalised but not indicative of severe liver damage.

Adolescent↗

Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.

The serum level of the aminoterminal peptide of type III procollagen (P3NP) was measured in 51 psoriatic patients on long-term, once weekly, low-dose methotrexate and in a control group of patients with extensive psoriasis who had never had systemic treatment. Serum P3NP levels were normal in all control patients, but were elevated in the majority of methotrexate-treated patients, even those with normal or non-specific liver histology. Although the highest P3NP values were found in the groups of patients with fibrosis and cirrhosis, isolated P3NP measurements did not discriminate between individuals with and without significant liver pathology. Neither standard nor dynamic liver function tests were able to identify patients with significant liver damage and in most cases results were in the normal range.

Adult↗

Effect of uniplant on liver function in Egyptian women with asymptomatic hepatitis B virus infection.

Uniplant is a single 35mm contraceptive implant releasing nomegestrol acetate with an effective life span of one year. This study was undertaken to evaluate the possible effects of three-year use of uniplant on some liver enzymes (SGPT, SGOT and GGT) in Egyptian women and to evaluate whether the past asymptomatic hepatitis B virus infection would predispose to any changes in these enzymes. This is an uncontrolled prospective study including 187 women of reproductive age who desired contraception for three years (three segments each year). They were apparently healthy on clinical assessment with no history of jaundice or liver diseases. They also had normal levels of liver function enzymes (SGPT, SGOT & GGT). Fasting blood samples were drawn at admission for assessing the levels of these liver enzymes and to detect anti-HBS antibodies as a marker of past asymptomatic hepatitis B virus infection (HBV) and HBS antigen to diagnose the chronic carrier state. The liver enzymes were measured at 6th. 12th, 18th, 24th, 30th and 36th month of use, and 3-6 months after implant removal. Out of 187 subjects enrolled 159, 83 and 33 women completed one, two and three years of Uniplant use respectively. The mean levels of SGPT, SGOT and GGT showed slight but significant elevations at the end of the first and second years of use compared to the pre-insertion levels. By the end of the third year, the elevated mean values of all enzymes gradually decreased to approach the pre-insertion levels without any significant differences. The percentage of anti-HBS antibodies positive titre due to past asymptomatic infection was 23.3% (n = 41) while HBsAg positive antigenaemia (i.e., carrier state) was 3.4%, (n = 5). In both groups of women--anti-HBS antibodies positive (n = 41) without antigenaemia and anti-HBS antibodies negative (n = 129)--the changes in the mean levels of all enzymes during uniplant use were closely similar without any statistical significance. These results demonstrated that: (1) uniplant induced slight but significant elevations in the mean levels of SGPT, SGOT and GGT these elevations were within the normal ranges, completely reversible and of doubtful clinical significance. (2) The non-carrier women who had been exposed to past asymptomatic HBV infection showed no significant effects on the studied liver enzymes compared to the normal women during long-term use of Uniplant.

Adolescent↗

Effects of scutellarin on liver function after brain ischemia/reperfusion in rats.

AIM: To investigate the effects of scutellarin (Scu) on liver function after brain ischemia/reperfusion in Wistar rats. METHODS: Rats were pretreated with Scu for 7 d and then subjected to a brain ischemia/reperfusion injury induced by a middle cerebral artery occlusion. The levels of nitric oxide (NO), xanthine oxidase (XOD), alanine transaminase (ALT), and aspartate aminotransferase (AST) in serum or liver tissues and the activities of antioxidant enzymes and cytochrome P450-dependent monooxygenases (CYPs) in liver tissues after brain ischemia/reperfusion were determined. RESULTS: In vehicle-treated rats, XOD, ALT, and AST activities (P<0.01) in serum and the MDA level (P<0.05) in liver tissues were all elevated but were significantly reduced (P<0.05) by Scu pretreatment. The NO levels in serum and liver tissues were decreased (P<0.01) dramatically in vehicle-treated rats and returned to the levels in the sham-operated animals when pretreated with Scu. SOD (P<0.05) and GSH-PX (P<0.01) activities in cytosol fraction were increased significantly by Scu pretreatment. Furthermore, a loss of CYP3A activity (P<0.01), but no changes of CYP1A1, CYP1A2, and CYP2E1 activities in liver were observed after brain ischemia/reperfusion in rats. Scu had no effect on them. CONCLUSION: These results demonstrated that pretreatment with Scu could attenuate hepatocellular damage elicited by brain ischemia/reperfusion in rats and this protection is in major part by its antioxidant activity.

Alanine Transaminase↗

Contrasting liver function test patterns in obstructive jaundice due to biliary strictures [corrected] and stones.

BACKGROUND: Obstructive jaundice is believed to be characterized by abnormalities of alkaline phosphatase (ALP), rather than aspartate transaminase (AST). AIM: To compare liver function tests (LFTs) in obstructive jaundice due to malignant strictures with those of jaundice due to gallstones. METHODS: LFTs were measured immediately before endoscopic retrograde cholangio-pancreatography (ERCP) in 207 jaundiced patients. Group 1 (n = 69) had malignant strictures, group 2 (n = 97) had common bile duct stone(s), and group 3 (n = 41) appeared to have recently passed a stone. LFTs in groups 2 and 3 were also analysed at maximal liver enzyme derangement, maximum hyperbilirubinaemia and during acute pain episodes. RESULTS: Group 1 had higher median bilirubin, AST and ALP levels than groups 2 or 3 (p < 0.001). In group 1, median rise in ALP exceeded that in AST (4.3 x normal upper limit (NUL) vs. 2.6 x NUL, p < 0.01), but in groups 2 and 3, AST and ALP were similarly elevated (both approximately 2 x NUL). At the time of maximum enzyme derangement in groups 2 and 3, median AST elevation (4.4 x NUL, 185 IU/l) exceeded that for ALP (2.4 x NUL, 276 U/l), (p < 0.001), and this was also true at peak hyperbilirubinaemia in these groups (AST 3.6 x NUL, ALP 2.4 x NUL, p < 0.01. Similarly, severe pain episodes in groups 2 and 3 were accompanied by greater elevations in bilirubin and AST, but not ALP, compared with levels at ERCP. DISCUSSION: The conventional wisdom that ALP rises more than AST in obstructive jaundice holds true where the jaundice is due to strictures, but in obstructive stone disease, the rise in AST may equal that in ALP, or even exceed it during maximum jaundice and during painful episodes. Clinicians should consider the possibility of extrahepatic biliary obstruction, even when AST is the predominantly elevated enzyme.

Aged↗