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Liver function tests: what is the risk?

Five laboratory assays are commonly called liver function tests (LFTs), although these tests are neither specific to the liver nor true measures of liver function. As a result, alanine aminotransferase (ALT or SGPT), aspartate aminotransferase (AST or SGOT), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) and bilirubin have proven problematic for clinicians and risk selection professionals alike. Further, underwriters and insurance medical directors find these tests difficult to assess because of the lack of data directly relating LFT elevations to mortality outcome. Nonetheless, the tests are frequently encountered, so a strategy for evaluating abnormal results is critical to ensure accurate and fair pricing. This paper reviews basic information on LFTs, available mortality data and the application of this knowledge to the underwriting process.

Actuarial Analysis↗

Utility of liver function tests after laparoscopic cholecystectomy.

Many surgeons routinely obtain liver function tests (LFTs) after all laparoscopic cholecystectomies. Others argue that LFTs provide no useful information and add time and expense to the patient's hospitalization. This purpose of this study was to determine if routine postoperative LFTs predict complications. One hundred ninety-nine consecutive patients undergoing laparoscopic cholecystectomy were included in the analysis. Nine (4.5%) patients had postoperative complications: eight with retained common bile duct stones and one with a cystic duct stump leak. All were diagnosed with postoperative endoscopic retrograde cholangiopancreatography. Only four of the nine patients had hyperbilirubinemia. Overall, 39 patients had postcholecystectomy hyperbilirubinemia, with four (10%) patients having complications (three retained stones and one had a bile leak). For the entire study population, there was no difference between pre- and postoperative total bilirubin and aspartate aminotransferase levels (0.6 vs 0.6 mg/dL; P = 0.623 and 25 vs 41 U/L; P = 0.111, respectively). There was a statistically significant difference in pre- and postoperative alanine aminotransferase and alkaline phosphatase (31 vs 50 U/L; P = 0.003 and 95 vs 90 U/L; P = 0.001, respectively). Postoperative elevations in liver function tests are frequently seen after laparoscopic cholecystectomy. These elevations do not predict postoperative complications. LFTs should be obtained only when clinically indicated.

Adult↗

Nuclear medicine liver function tests for pregnant women and children. 1. Breath tests with 14C-methacetin and 13C-methacetin.

Stable isotopes, such as 13C, should be substituted for the long-lived radionuclide 14C in the 14C breath test when doing liver function tests in children and pregnant women. For comparison 13C, 15N-methacetin and 14C-methacetin were synthesized as suitable diagnostic agents. Methods are described for the measurement of 14C and 13C in the breath. After oral administration of labelled methacetin to healthy subjects and patients with liver diseases a good correspondence between 13C- and 14C-measurements in the same subject on the one hand, and a good discrimination between controls and patients on the other hand were shown. Findings with regard to 14C measurements in urine are discussed supporting the supposed advantage of 13C-methacetin over 14C-methacetin application.

Acetamides↗

Evidence for a substantial genetic influence on biochemical liver function tests: results from a population-based Danish twin study.

BACKGROUND: Biochemical liver function tests are widely used in the clinic and are some of the most frequently used tests in screening for diseases in older age groups. The aim of the present study was to estimate the relative importance of genetic and environmental factors to variations in these tests among the elderly. METHODS: We conducted a survey among Danish twins, 73-102 years of age, identified in the population-based Danish Twin Registry. Among the 2749 individuals in the study population, an interview was conducted with 79%. From these, a blood sample was collected from 290 same-sex twin pairs, total of 580 subjects, within a 6-month period and analyzed for alanine aminotransferase (ALT), lactate dehydrogenase (LDH), gamma-glutamyltransferase (GGT), bilirubin, and albumin. The interview included questions about alcohol consumption and body mass index (BMI; self-calculated height and weight). Heritability (proportion of the population variance attributable to genetic variation) was estimated using structural-equation analyses before and after correction for alcohol consumption and BMI. RESULTS: Structural-equation analyses revealed a substantial heritability (35-61%) for the four biochemical liver function tests: ALT, GGT, LDH, and bilirubin. The remaining variation could be attributed to individuals' nonfamilial environments. Adjustment for alcohol consumption and BMI had no influence on the heritability for ALT, GGT, LDH, and bilirubin. For albumin, two models fit equally well before adjustment for alcohol and BMI: a model including additive genetic and nonshared environmental factors (AE), and a model including shared and nonshared environmental factors (CE). After adjustment, the model including shared and nonshared environment was clearly the best fitting model. CONCLUSIONS: For both males and females, the effect of genetic factors on the biochemical liver function tests ALT, GGT, LDH, and bilirubin is substantial and accounts for one-third to two-thirds of the variation among individuals 73-102 years of age. The heritability is equal for males and females and does not change notably after controlling for alcohol consumption and BMI. For albumin, no major impact of genetic factors was found independent of BMI and alcohol consumption. An understanding of the genetic mechanisms underlying biochemical liver function tests among the very old may be of value in the interpretation of these tests in this age group.

Aged↗

Tumor markers, liver function tests and symptoms in 115 patients with isolated colorectal liver metastases.

Development of the hybridoma technique has made the identification of several new tumor antigens possible. Although it was hoped that they would be more tumor-specific, none of these markers are found exclusively in tumor or in serum of tumor patients. Compared with carcinoembryionic antigen (CEA) and liver function tests, the roles of these markers (CA 19-9, CA 125, CA 15-3) were prospectively evaluated in 115 patients with colorectal liver metastases. Patients were classified according to tumor volume (T1 less than 25%, T2 25-75%, T3 greater than 75%), and the extension of infiltration (solitary/multiple/diffuse; unilateral, bilateral). Patients with benign liver or biliary disease served as a control group (n = 63). Overall sensitivity was 87% for *1, 50% for *2 and 38% for *3, with a significant correlation with tumor size. CEA serum levels were elevated in 88% of all patients. CA 19-9 was less sensitive: positive in 59%. Because of some complementary elevations, the combined use of CEA, CA 19-9 and CA 125 raised sensitivity to 94%. CA 19-9 and LDH could be useful for confirmation because of their higher specificity; however, the specificity of CEA rose to 93% on using a cut-off of 10 ng/ml instead of 3 ng/ml. The results indicate that CEA and CA 19-9 as well as liver function tests are helpful for preoperative staging in conjunction with imaging procedures before liver resection or regional chemotherapy.

Antigens, Neoplasm↗

Liver function tests during antithyroid therapy in hyperthyroidism.

AIMS: To investigate the liver function tests during antithyroid treatment in the patients with hyperthyroidism. METHODOLOGY: Four hundred sixty five patients with hyperthyroidism (285 Graves' disease and 180 toxic nodular/multinodular goiter) and fifty healthy subjects were included in the study. The patients who had abnormal liver function tests were excluded from the study. Blood levels of thyrotropin (TSH), free thyroxine (FT4), alanine transaminase (ALT) and aspartate transaminase (AST) were detected at the beginning of the treatment (basal levels), and at the third and sixth months of the treatment. The patients were treated with propylthiouracil (PTU). RESULTS: Average of age was 40.1 +/- 5.8 years in the patient group and was 37.3 +/- 4.5 years in the control group. TSH, FT4, ALT and AST levels measured in the patient and control group are shown in Table 1. Basal levels of TSH were lower in the study group than in the control group (p<0.001), and basal levels of FT4 were higher in the study group than in the control group (p<0.001). Basal levels of ALT and AST, and the levels of TSH, FT4, ALT and AST measured at the third and sixth months were similar in both groups. CONCLUSIONS: We did not find abnormal liver function tests during the antithyroid treatment in the patients with hyperthyroidism.

Adult↗

Diagnostic value of liver function tests and Entamoeba histolytica antibody studies in East Africans.

Liver function tests and Entamoeba histolytica (E.H.) antibody titres have been studied in a variety of tropical and liver diseases. Patients with hepatic amoebiasis had a raised E.H. antibody titre and tended to have a low pseudocholinesterase activity. In two cases of amoebic liver abscess, which were treated by aspiration and emetine, there was a remarkable drop in the E.H. antibody titre. In a number of other hepatic and tropical conditions the E.H. antibody titre was not significantly raised and the liver function tests were typical of the various conditions studied.

Adolescent↗

[Determination of galactose eliminating capacity after intravenous administration--a liver function test].

The authors discuss a simple method for assessment of the galactose elimination capacity after intravenous administration of a 20% solution, total dose 0.5 g galactose/kg body weight. In six blood venous samples after termination of an infusion (after 25, 30, 35, 40, 45 and 50 minutes) from an inserted venous catheter after assessment of the enzymatic estimation of the galactose concentration in individual samples the elimination line of galactose is assessed as well as its point of intersection (t) with the time axis. By means of these data along with the data on the amount of injected galactose and the amount of galactose excreted in the urine the galactose elimination capacity is calculated. The method is suitable for evaluation and monitoring of the functional state of the liver. It reflects the functional mass of liver parenchyma and is therefore a quantitative test of liver function.

Galactose↗

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on quantitative liver function tests.

BACKGROUND/AIMS: The transjugular intrahepatic portosystemic stent-shunt (TIPS) has been established as a new effective treatment for portal hypertension in advanced liver disease. Impairment of liver function due to reduced portal venous perfusion is considered to be a major risk of TIPS, and the shunt leads to an increase in the incidence of hepatic encephalopathy (HE). Known complications, like the increase in the incidence of HE or TIPS stenosis, are diagnosed either clinically or by doppler ultrasound. It is not practicable to use quantitative liver function tests in the diagnostic work-up of HE, and medical or interventional therapy can be established after clinical diagnosis. Still, information is limited about the influence of TIPS on quantitative liver function tests in patients with liver cirrhosis. Therefore, the aim of this prospective study was to assess the effects of TIPS on various liver function tests. METHODOLOGY: Fifteen patients with liver cirrhosis, a hepatopetal portal flow before TIPS, and an uncomplicated course without stenosis after elective TIPS were analysed. Liver function was quantitatively measured using the [14C]aminopyrine breath test (ABT), considered to be independent of hepatic blood flow, the monoethylglycinexylidide test (MEGX), believed to be largely dependent on hepatic blood flow, serum bilirubin, serum albumin, and prothrombin time. Measurements were performed before, 1, 3 and 6 months after TIPS. RESULTS: TIPS decreased the portal venous pressure gradient from 31.0+/-2.0 cm (SEM) H2O to 16.9+/-1.8 cm H2O (p<0.01). One, 3 and 6 months after TIPS there was no significant deterioration of liver function as assessed by ABT, MEGX or serum bilirubin, serum albumin, and prothrombin time compared to baseline values before TIPS. ABT and MEGX were significantly correlated before TIPS (r=0.72; p<0.01) and after TIPS (r=0.76; p<0.05). CONCLUSIONS: These data show no significant deterioration of microsomal liver function as measured by the quantitative liver function tests ABT and MEGX over a period of 6 months after elective TIPS. In particular, there was no significant reduction of the MEGX-test considered to depend predominantly on hepatic blood flow. Thus, there is no need for the quantitative liver function tests ABT and MEGX in the routine management of patients following the TIPS procedure.

Adult↗

Prognosis of hepatitis B virus surface antigen carriers in relation to routine liver function tests: a prospective study.

The employees of the Japan National Railways Co. working in the Tokyo area, comprising 98% men over the age of 40 yr, were examined for hepatitis B virus seromarkers and routine liver function tests (serum glutamic oxaloacetic transaminase, alkaline phosphatase, and zinc turbidity test) and were followed for 5 yr. The examinees included 202 hepatitis B surface antigen carriers, 502 positive for hepatitis B surface antibody, and 2426 negative for both. We found that the frequency of continuously abnormal liver function test was higher in hepatitis B surface antigen carriers compared with noncarriers. Of the 202 carriers, 4 (1.98%) died from hepatocellular carcinoma with or without cirrhosis, whereas in 2928 noncarriers only 2 (0.07%) died from liver diseases unrelated to hepatitis B virus, the difference being 28.3-fold. Three of the 4 who died from hepatocellular carcinoma initially had normal liver function tests. Mortality in carriers with initially normal liver function tests was 44.5 times higher than that in noncarriers with normal tests. Thus, asymptomatic carriers carry a high risk of dying from chronic liver disease. Routine liver function tests appear of limited value in predicting prognosis.

Adult↗

Studies on changes of thyroid hormones in various liver diseases: usefulness of free thyroid hormones as liver function test.

Various thyroid parameters in liver disease which were morphologically diagnosed were measured, and their relationship to liver function was mainly studied. Serum T4 levels were elevated in acute hepatitis (AH), chronic persistent hepatitis (CPH) and chronic aggressive hepatitis (CAH) compared with in normal controls (C). Serum T3 levels were elevated in CAH and reduced in liver cirrhosis (LC). Serum reverse T3 (rT3) levels were elevated in AH and chronic liver diseases (CLD). T3/T4 ratios decreased in AH, CPH and CAH. RT3/T3 ratios increased in AH and CLD. Serum Free T3 (FT3) levels reduced in CLD in order of CPH, CAH and LC, and were low levels in AH with the same degree as LC. Moreover, serum FT3 levels revealed negative correlation with ICG-R15 and positive correlation with prothrombin time (PT) and serum albumin levels (Alb). Therefore serum FT3 level was considered to become a sensitive index of liver damage. Serum free T4 (FT4) levels did not change significantly in AH with high levels of transaminases and reduced in only LC. Therefore serum FT4 may become an index of severity of liver dysfunction. On the other hand, T3/T4 ratios and rT3/T3 ratios showed less correlation with liver function tests compared with free thyroid hormones.

Adult↗

[Deterioration of liver function following endoscopic injection sclerotherapy of esophageal varices--significance of the new liver function test "intravariceal injection (I.I.) index"].

Changes of liver functions associated with endoscopic injection sclerotherapy (EIS) were investigated in 143 patients with remarkable esophageal varices. The index used for evaluating hepatic reserve was the ratio between the increase of total bilirubin and the increase of LDH after EIS [I.I. index = (delta T.Bil./delta LDH) x 100] in cases treated by intravariceal injection of 5% ethanolamine oleate. I.I. index value caused by hemolysis was stable and always below 0.2, while the elevation of I.I. index above 0.2 was regarded as the reflection of the deterioration of liver function. After the entire sessions of EIS, the changes of liver function tests before and after EIS were estimated in 104 cases using 3 factors as follows; (1) delta T.Bil.; increase of total bilirubin more than 0.5 mg/dl (2) delta PT; decrease of prothrombin time more than 5% (3) delta ICG R15; increase of ICG R15 more than 5%. I.I. index of group I (without any changes of 3 factors mentioned above; n = 66) was 0.22 +/- 0.16, approximately within normal range. However, in group II (with 1 factor; n = 29), group III (with 2 factors; n = 5), group IV (with all factors; n = 4), I.I. index was elevated according to the severity of their liver dysfunction. The cases whose I.I. index value increased gradually during the course of EIS, were apt to deteriorate the liver functions and therefore, should be carefully observed. Also, I.I. index seems to reflect the prognosis of the patients treated by EIS for some extent, since the survival period of the cases treated by EIS were correlative with the value of I.I. index (r = -0.542, p < 0.01), and I.I. index of 32 cases who survived for longer than 5 years after EIS was almost normal (0.22 +/- 0.15).

Adult↗