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Abnormalities in measures of liver function and injury in thyroid disorders.

Thyroid hormones exert their effect on all tissue and modulate the rate of metabolic activity appropriate for each situation. As a result of their actions, alterations in thyroid function can affect the liver and perturb measures of hepatic function and injury in the absence of liver disease. These alterations in the measure of hepatic function and injury may be difficult to recognize as being caused by thyroid dysfunction rather than hepatic disease. As a result, they may be quite troublesome for patients and physicians if their cause is not properly identified. Importantly, abnormalities in liver function tests return to normal once the primary thyroid pathology is recognized and treated.

Animals↗

Interference in an automated radial partition fluorescent immunoassay of thyrotropin associated with liver-function abnormalities.

In a previous evaluation of a "sensitive" radial partition fluorescent immunoassay on the Stratus system, thyrotropin (TSH) values exhibited a positive bias in icteric samples when compared with results of a nonsensitive radioimmunoassay. In the present study, we evaluated 366 patients samples to assess whether any biochemical markers of liver function could identify samples for which TSH values would be falsely increased. gamma-Glutamyltransferase and total bilirubin concentrations were unrelated to discrepant TSH values. In contrast, alkaline phosphatase (ALP) was significantly positively correlated with differences in Stratus and RIA TSH concentrations (P less than 0.001). However, this correlation explained only 34% of the observed residual variability around the estimated regression line. On average, the higher ALP values were associated with larger discrepancies between Stratus and RIA TSH values, although several samples with increased ALP did not have falsely increased Stratus TSH values. TSH measurements performed with a Stratus should be interpreted with caution in patients with abnormal biochemical markers of liver function.

Autoanalysis↗

Chronic hepatitis in patients with hemophilia A: histologic studies in patients with intermittently abnormal liver function tests.

Recent studies in multiply transfused patients with hemophilia A and persistent liver function abnormalities have shown a high incidence of chronic active hepatitis. The purpose of the present study was to determine the severity of liver disease in multiply transfused patients with intermittent liver enzyme abnormalities. Fifteen patients with elevated enzymes on two or three out of four determinations at 6-mo intervals were studied. None had signs or symptoms of chronic liver disease. Thirteen had serologic evidence of prior exposure to the hepatitis B virus. Liver biopsy performed on these patients after replacement therapy with factor VIII showed chronic persistent hepatitis or other mild forms of liver disease in 14 of the 15 patients. Patients with chronic persistent hepatitis had significantly higher mean liver enzymes at time of biopsy than patients with milder forms of hepatic inflammation, but there was no relationship between liver histology and hepatitis B serology or the amount of factor VIII used in the 6 mo preceding biopsy. These findings support the continued use of factor VIII concentrates in patients with hemophilia.

Adolescent↗

Multicentre controlled trial of tienilic acid in hyperuricaemic, hypertensive subjects, with intensive monitoring of liver function.

1 Tienilic acid, a diuretic with potent uricosuric properties, has been compared with conventional diuretic therapy, mainly thiazide, in a parallel group (random allocation) multicentre study in hyperuricaemic hypertensives (n = 96). 2 The study was designed to last 1 year but tienilic acid was withdrawn for suspected hepatotoxicity before the study was complete. Mean follow-up was 8.5 (range 1-12) months and the mean daily dose of tienilic acid was 278 (range 125-500 mg). 3 Blood pressure levels on tienilic acid and on conventional diuretics were similar. 4 Serum potassium and sodium levels were also similar in the two groups, but serum urea and creatinine rose somewhat more in the tienilic acid group. 5 Serum uric acid fell dramatically in the patients on tienilic acid from 0.56 to 0.32 mmol/l, but did not alter significantly in the control group. 6 There were no problems with renal failure or urate deposition probably because patients were instructed to drink plenty of fluid when tienilic acid was started, because initial dose was low and because all previous diuretics were stopped for 3 days before tienilic acid was started. 7 Mean liver function indices did not rise in either group. Mild elevation in liver enzymes occurred in one control patient and one patient on tienilic acid; the latter drug was stopped and the values returned to normal. 8 The general incidence of side-effects was low. 9 Our impression was that tienilic acid was a useful drug. Whether it could have been used safely with monitoring of liver function will not now be known.

Adult↗

[The positive rate of auto antibodies and autoimmune liver diseases in patients with abnormal liver function].

OBJECTIVE: To investigate the positive rate of auto antibodies and autoimmune liver diseases in patients with abnormal liver function and it's clinical significance. METHODS: 511 sera with abnormal ALT (>40 U/L) were continuously collected, all the sera were examined for antibodies and clinical information of 469 cases were studied. RESULTS: Among the 511 sera, 14.09% of them showed of ANA positive, 0.59% of SMA positive, 2.94% of AMA positive, 0.98% of AMA-M2 positive, 0.59% of SS-A positive, 0.19% of SS-B positive, 0.19% of JO-1 and 0.78% of dsDNA positive and all SLA/LP, LC-1 and LKM-1 and ANA profile were negative. Clinical information was analyzed on 469 cases which have complete data from the 511 patients. Of these 469 cases, 5 cases (1.06%) were found to be PBC, 2 case (0.43%) were AIH, no PSC was found, 77.78% patients among those with positive auto antibodies were diagnosed as viral hepatitis and there were 18.29% patients with viral hepatitis showed different auto antibodies. CONCLUSION: The high titer auto antibodies were important criterion for diagnosis of autoimmune liver diseases. The positive rate of autoantibodies of autoimmune liver diseases was similar to hepatitis C and E

Adolescent↗

Liver function reserve in surgical treatment of patients with portal hypertension: report of 146 cases.

OBJECTIVE: To evaluate the significance of intraoperative reassessment of liver function reserve in the selection of surgical procedures to optimize therapeutic results in the treatment of portal hypertension. METHODS: The data of 146 patients with portal hypertension treated in the past 10 years were retrospectively reviewed. Posthepatitis cirrhosis was found in 118 patients, schistosomial cirrhosis in 6, alcoholic cirrhosis in 1, mixed cirrhosis in 5, and other diseases in 16. According to Child's criteria, 45 patients were classified into class A, 92 class B, and 9 class C. At operation, 33 patients were reclassified into class A, 78 class B, and 35 class C. Disconnection procedure was performed in 89 patients (61.0%) and shunt procedure in 57 (39.0%). These operations included prophylactic operations in 27 patients (18.5%) and emergency disconnection operations in 2 (1.4%). RESULTS: One patient (0.7%) died of upper gastrointestinal bleeding during operation. Early rebleeding following operation occurred in 9 patients (6.1%) (disconnection in 5 patients and shunt in 4). Early encephalopathy after operation occurred in 2 patients (1.4%) (disconnection in 1 patient and shunt in 1). A total of 98 patients (67.6%) (disconnection in 61 patients and shunt in 37) were followed up (6 months to 9 years). Bleeding occurred again in 12 patients (12.2%) (disconnection in 9 patients and shunt in 3) 17 months after operation (4 to 41 months). Late encephalopathy occurred in 6 shunt patients at 19 months (3-40 months). The late rebleeding rates of shunt patients and disconnection patients were 8.1% (3/37 patients) and 14.9% (9/61) (P>0.05) respectively. The late encephalopathy rates of shunt patients and disconnection patients were 16.2% (6/37) and 0% (0/61) respectively (P<0.01). Eight patients (5.5%) died of upper gastrointestinal bleeding (2), hepatic failure (3), liver cancer (2), and rectal cancer (1) in the period of follow-up. CONCLUSIONS: The success and effectiveness of surgical procedures for portal hypertension are closely related to the status of patient's liver function reserve. Intra-operative reassessment of hepatic function reserve is crucial. Selection of procedures based on patient's hepatic function reserve, local anatomical conditions and surgeon's experience would optimize therapeutic results.

Adolescent↗

A comparison of liver function after hepatectomy in cirrhotic patients between sevoflurane and isoflurane in anesthesia with nitrous oxide and epidural block.

UNLABELLED: In this study, we compared postoperative liver function in patients with liver cirrhosis between isoflurane and sevoflurane anesthesia with nitrous oxide (N(2)O) and epidural block. Forty cirrhotic patients with Child-Pugh Grade A, aged 40 to 70 yr, scheduled for liver segmentectomy, had anesthesia induced with midazolam 0.1 mg/kg and fentanyl 4 micro g/kg. For maintenance, intermittent epidural administration of 1.5% lidocaine 4 to 6 mL and sevoflurane (sevoflurane group) or isoflurane (isoflurane group) with N(2)O 3 L/min in oxygen 3 L/min was used. Aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, choline esterase, albumin, prothrombin time, and platelet count were measured before and 1, 3, and 7 days after surgery. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase increased significantly, with the peaks at 3 days after surgery in both groups. The increases in these variables were significantly larger in the isoflurane group than those in the sevoflurane group. No patient developed hepatic failure. All increases in liver enzymes were small and of questionable clinical relevance. Whether sevoflurane might be a better anesthetic when combined with N(2)O and epidural block for cirrhotic patients than isoflurane with respect to liver damage remains to be determined. IMPLICATIONS: In cirrhotic patients with Child-Pugh Grade A, isoflurane induced more of an increase in serum concentrations of liver enzymes after surgery than sevoflurane when combined with nitrous oxide and epidural block. However, the increases were small, and there was no clinical liver damage.

Adult↗

The role of CEA and liver function tests in the detection of hepatic metastases from colo-rectal cancer.

Carcinoembryonic antigen and some liver function tests (alkaline phosphatase, gamma-glutamyltranspeptidase, lactic dehydrogenase and cholinesterase) were evaluated in patients with primary colorectal cancer in order to define their role in the pre-operative detection of liver metastases. The records of 278 consecutive patients admitted to the Istituto Nazionale Tumori of Milan between January 1982 and December 1983 who were suffering from primary invasive colo-rectal cancer and who underwent laparotomy were retrospectively analyzed. At laparotomy, liver metastases were found in 38 pts (13.7%). Considering single tests, CEA was the most sensitive (71%); no single test was found to be reliably predictive, when the result was abnormal. On the contrary, the normal value of each test was associated with a good prediction. When we considered all the five tests together in the single patient their predictive value, when abnormal, proved to be quite good only if four or five results were abnormal. On the other hand, liver metastases in the presence of all normal tests were found only in two patients, so giving a negative predictive value of about 97%. So we conclude that, in the lack of an infallible imaging technique for liver evaluation, in the presence of all normal tests any other investigation on the liver could be avoided. However, when liver tests are pathologic, some other imaging technique should be performed in order to supply the surgeon with information about the extent and the spread of the metastases.

Carcinoembryonic Antigen↗

[Liver function in newborn infants with conjugation hyperbilirubinemia after exchange transfusion and hemosorption].

Overall 40 neonates with conjugation jaundice were examined. A study was made over time (after 1 and 5 days) of the content of bilirubin, cholesterol, total protein, cholyl glycine, cholinesterase, and alanine aminotransferase before and after surgical treatment (substitution transfusion and hemoperfusion). It has been established that substitution transfusion inhibits protein synthesizing liver function and raises the content of cholyl glycine. In the authors, opinion, this reduces the bilirubin-binding capacity of albumin and increases hepatocyte membrane permeability. Extracorporeal detoxication makes protein synthesizing liver function return to normal, minimizes the content of cholyl glycine, promoting the growth of the bilirubin-binding capacity of albumin.

Bilirubin↗

Does cyclosporin A worsen liver function in patients with inflammatory bowel disease and total parenteral nutrition?

OBJECTIVE: inflammatory bowel disease (IBD), total parenteral nutrition (TPN) and immunosuppressive treatment with cyclosporin A (CsA) are well known factors in hepatobiliary disorders. Their association, however, has been little studied. METHOD: we retrospectively analyzed the results of liver function tests (transaminases, AST. ALT), total bilirubin, alkaline phosphatase, and gamma-glutamyltransferase (GGT) in a consecutive series of 50 patients (29 men, 21 women, mean age 32 years, range 16-78 years) hospitalized for a severe attack of IBD between January 1992 and July 1997. Basal laboratory values in all patients were normal. Thirty-eight patients had ulcerative colitis (UC) and 12 had Crohn's disease (CD), which debuted in 28% of the patients. All patients were treated with methylprednisolone (MP) (0.75-1.0 mg/kg daily i.v., and received TPN. 42% (21/50) required additional treatment with CsA (5 mg/kg daily i.v.) at the beginning or during the first week of TPN and during 7-24 days, because on nonresponse to steroid treatment. Two study groups were defined according to treatment: Group I consisted of 29 patients given MP + TPN, and group II comprised 21 patients who received MP + TPN + CsA. The groups were otherwise similar in all other variables analyzed. Liver function tests were done weekly until the end of the study period. RESULTS: 62% of the patients (31/50) showed hepatobiliary dysfunction, defined previously as a 2-fold or greater elevation of two or more parameters. There was no statistically significant difference between the two groups in the incidence of dysfunction (15/29 vs 16/21, n.s.). The parameters that showed the greatest alterations were GGT and ALT; the greatest elevation appeared during the third week of immunosuppressive treatment, and did not exceed 6-fold the normal value. The alterations disappeared once TPN and immunosuppressive treatment were discontinued. CONCLUSIONS: the hepatobiliary dysfunction in patients treated with both TPN and CsA was no more severe than associated with TPN alone.

Adult↗

[Atypical process of acute disturbance of liver function with severe thrombocytopenia in the third trimester].

The authors diagnosed disturbance of liver-function associated with severe thrombopenia in a pregnant woman in the third trimester. Principally, acute fatty liver of pregnancy can be characterized by existing symptoms, e.g. nausea, vomiting, epigastric pain, jaundice, hyperbilirubinemia, moderately elevated SGOT and SGPT levels, thrombopenia, leukocytosis, low fibrinogen level and disseminated intravascular coagulopathy, but hepatomegaly, purpura and petechia on lower and upper extremities, and high ALP and GGT levels during postpartum period do not confirm suspicion of this diagnosis. The present report draws attention to the difficulties of differential diagnosis of pregnancy-induced elevated liver enzymes diseases associated with low platelets, as there are several identical pathophysiological processes. Although causes and exact pathophysiology of disorders are unknown, similar symptoms during the process of diseases leave the question open whether they are different diseases or whether they are different manifestations of the same disease, and what kind of relationship exists between these diseases and preeclampsia. This case suggests careful evaluation of the whole clinical picture, moreover it is emphasized that prompt, aggressive treatment of hemostatic disturbance and the expeditious delivery can save maternal life.

Acute Disease↗

Liver function and halothane-diethyl-ether azeotrope anaesthesia. Re-evaluation of an obsolete drug with special reference to early postoperative effects.

A general anaesthetic drug that fulfils requirements for use under difficult circumstances is the inhalation agent halothane-diethyl-ether (HE) azeotrope. Although both halothane and diethyl ether have been described in detail, their effect on the liver when given together as an azeotrope has not been systematically characterised. The effect on liver function was evaluated and compared with the effects of halothane anaesthesia (H) and spinal anaesthesia with tetracaine (S), the last named serving as controls. The series consisted of 33 healthy men (ASA 1-2) receiving no medication and scheduled for inguinal hernia repair. The patients were randomly allocated to receive HE, H or S. The following parameters were estimated the day before surgery and on the first postoperative day: liver cell metabolism (bile acids, unconjugated bilirubin), cell integrity (aminotransferases), synthesizing capacity (Prothrombin complex), cholestasis (conjugated bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase), and global liver function (chenodeoxycholic load test). No major differences emerged between the groups. Unconjugated bilirubin was increased in all groups. Prothrombin complex activity was reduced in all groups. Conjugated bilirubin was increased in the H group. The oral bile acid load test and the fasting bile acid were unaltered by anaesthesia in all groups. No major impact on liver cell function was seen in the early post-operative period after HE azeotrope anaesthesia. The findings support our view that HE azeotrope could be considered as an alternative anaesthetic agent under field conditions.

Adult↗

Intrasplenic transplantation of encapsulated hepatocytes decreases mortality and improves liver functions in fulminant hepatic failure from 90% partial hepatectomy in rats.

BACKGROUND: Encapsulated cell therapy might be a promising approach to enable cell transplantation without immunosuppression. This study investigates the viability and hepatic function of hepatocytes encapsulated with alginate/poly-L-lysine in vitro and the effect of the intrasplenic transplantation of cultured encapsulated hepatocytes on survival in 90% hepatectomized rats as a preliminary step toward allogeneic hepatocyte transplantation without immunosuppression. MATERIALS AND METHODS: Rat hepatocytes were isolated and encapsulated using alginate/poly-L-lysine. Encapsulated hepatocytes were cultured for 28 days to measure cell viability, liver function, and morphology. Rats were treated with a 90% partial hepatectomy and then immediately underwent the intrasplenic transplantation of the cultured encapsulated hepatocytes, the capsule alone, or the allogeneic hepatocytes without the capsule. The survival rate, liver function, and cell morphology were assessed after transplantation. RESULTS: The cultured encapsulated hepatocytes maintained their viability and showed better metabolic activity than day 0 cultured encapsulated hepatocytes. The encapsulated cells strongly expressed albumin and were positive for periodic acid-Schiff staining. Electron microscopy demonstrated that the microencapsulated hepatocytes retained the structural elements of hepatic cytoplasm and nuclei. Intrasplenic transplantation of the encapsulated hepatocytes increased the survival rate and improved the hepatic function. Encapsulated hepatocytes transplanted into rat spleen survived well and retained their hepatic function. Moreover, dramatic liver regeneration was observed 48 hr after transplantation in the group that received intrasplenic transplantations of encapsulated hepatocytes. CONCLUSIONS: The intrasplenic transplantation of cultured encapsulated hepatocytes improved the survival rate of an acute liver failure rat model induced by a 90% partial hepatectomy.

Animals↗

Conventional and quantitative liver function tests after hepatic transplantation: a prospective long-term follow-up.

In long-term survivors of liver transplantation, hepatic function is obviously of vital importance. Therefore, we prospectively performed conventional and quantitative liver function tests in patients who had survived a first transplantation for at least 4 years. Compared to 6 months after transplantation, serum bilirubin concentration and gamma GT activity were significantly lower after 3, 4, and 5 years (bilirubin 1.2 +/- 0.2 mg/dl at 6 months vs 1.0 +/- 0.1, 1.0 +/- 0.2, and 0.8 +/- 0.1 mg/dl respectively; gamma GT 106 +/- 0 33 U/l at 6 months vs 56 +/- 17, 67 +/- 35, 39 +/- 10 U/l respectively). At these points in time, blood levels of cyclosporin A were also significantly lower. Other parameters of liver cell function and liver cell integrity (AP, AST, ALT, GLDH, total protein, thromboplastin time, partial thromboplastin time) were unchanged over time. Serial quantitative liver function tests (indocyanine green half-life, galactose elimination capacity, lidocaine half-life, and MEGX formation) also remained stable. Thus, we conclude that hepatic function remains stable in long-term survivors of liver transplantation for at least several years.

Adult↗

Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas.

The present study was carried out to assess the endocrine status and liver function in adult cows reared in polluted environment around different industrial units in India. The effect on endocrine system was examined by determination of plasma level of thyroid hormones, thyroxin (T4) (n=269) and triidothyronin (T3) (n=269), stress hormone cortisol (n=266), and reproductive hormones such as estradiol (n=84) and progesterone (n=84) in cows (>3 years) reared around different polluted industrial and non-polluted areas. The respective blood lead and cadmium concentration was also determined in all the cows. The mean plasma levels of both T3 and T4 were significantly (P<0.05) higher around lead zinc smelter (2.43+/-0.26 and 41.1+/-2.9nmol/L) and closed lead cum operational zinc smelter (1.81+/-0.16 and 42.4+/-6.2nmol/L), where the mean blood lead level (0.86+/-0.06 and 0.51+/-0.09mug/ml) was also significantly higher than that of cows (0.07+/-0.01mug/ml) from unpolluted areas. Regression analysis of data from 269 cows revealed a significant (P<0.01) positive correlation between the blood lead and plasma T3 (r=0.287) and T4 (r=0.173). The correlation between thyroidal hormones and the blood cadmium concentration (r=-0.079 and -0.48; P>0.05) was not significant. Plasma cortisol level had also a non-significant (P>0.05) correlation (r=-0.092) with blood lead level.However, the mean cortisol level (4.02+/-1.96nmol/L) of cows in phosphate rock mining areas was significantly (P<0.05) higher than that of controls (1.98+/-0.70nmol/L). The mean plasma estradiol level was significantly (P<0.05) higher in cows around closed lead cum operational zinc smelter (47.1+/-19.5pg/ml) than that of the control animals (21.8+/-3.9pg/ml) and in rest of the areas, the difference did not reach the statistical significance (P>0.05). The serum biochemical analysis in 36 cows around lead-zinc smelter with the highest mean blood lead level (0.86+/-0.06mug/ml) amongst all the industrial/urban areas surveyed, and in 15 animals from non-polluted areas revealed a significant positive correlation between blood lead and serum ALT (alanine transaminase) (r=0.688, P<0.01) and AST (aspartate transaminase) (r=0.390, P<0.01) and a negative correlation with serum total lipids (r=-0.337, P<0.05), total protein (r=-0.449, P<0.01) and albumin(r=-0.662, P<0.01). It is concluded from the study that the natural exposure to lead in polluted environments disturbs the endocrine profile and the higher blood lead level alters serum biochemical parameters indicative of liver functions.

Animals↗

Relation between liver function and hepatocyte ultrastructure in a case of paracetamol intoxication.

In a case of reversible paracetamol intoxication ultrastructural changes were correlated to changes in tests of microsomal and cytosolic liver function: the prothrombin index (PP) and the galactose elimination capacity (GEC), respectively. The decrease in the PP was at maximum after 2 days and in the GEC after 5 days, when the PP was normalized. Liver biopsies were taken after 1 and 5 days. Electron microscopy of the early biopsy revealed midzonal increased vacuolization of the endoplasmic reticulum (ER), detachment of ribosomes, and centrilobular mitochondrial injury. The late biopsy exhibited midzonal organelle-depleted areas with pale glycogen rosettes, perinuclear proliferating granulated ER, and centrilobular frank necrosis. These observations are in accordance with the concept that paracetamol-induced hepatocellular injury is due to damage to the membranes of the ER and indicate that the chronological dissociation of the liver function tests reflects the time sequence of the structural changes.

Acetaminophen↗

Liver function tests in patients with computed tomography demonstrated hepatic metastases.

One hundred patients with computed tomographic (CT) evidence of liver metastases (and confirmation by biopsy or progression of disease) had serum levels of alkaline phosphatase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase measured within two weeks of scanning. All three enzymes were within the normal range in 33% of patients. Even with advanced involvement (defined as three or more metastatic lesions over 3 cm in diameter), 20% of patients had normal levels of all three liver enzymes. Although liver function tests (LFTs) (enzyme levels) are inexpensive and simple to perform, they failed to detect a significant number of patients with liver metastases.

Adult↗