Liver function and failure: the evolution of liver physiology.
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History, 18th Century↗
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Prevalence, outcome and associated factors of deranged liver function tests in patients on home parenteral nutrition.
INTRODUCTION: The prevalence of deranged liver function tests (LFT) in patients on long-term home parenteral nutrition (HPN) is poorly documented. The aim of our study was to document the prevalence of this complication and possible associated factors. METHOD: Retrospective analysis of case notes of 107 patients on HPN was performed. Deranged LFT was defined as any biochemical parameter of LFT that is 1.5 times above the reference range. RESULTS: There were 39 males and the median age was 51 (range 20-73) years old. Median duration of HPN was 40 (range 6-252) months. Underlying diagnoses were Crohn's disease (40%), ischaemic bowel disease in 28.1% (arterial or venous), post-surgical intestinal adhesion and fistula (16.9%) and others (21.7%). The mean energy intake from HPN was 1003+/-544(SD) kcal/day with 845+/-474 kcal/day from glucose, 157+/-127 kcal/day from fat and mean nitrogen intake was 6.2+/-3.6 g/day. Raised alkaline phosphatase (mean 197+/-143(SD)U/L) was the most common abnormality (40 patients). Two patients had hyperbilirubinaemia; one patient had hereditary spherocytosis and in the other patient, the cause could be attributed to HPN with bilirubin of 54 micromol/l. Fifty-one patients (47.7%) had deranged LFT as judged from raised parameters on LFT. Abnormality in LFT was transient in nine patients. For the other 42 patients (39%), abnormalities in LFT remained stable for median duration of follow-up of 18.5 (range 3-180) months. No patients developed decompensated liver disease. On univariate analysis, length of small bowel of less than 100 cm, a higher total caloric intake from HPN (mean 1117+/-486 kcal against 907+/-576 kcal, P<0.05), and higher daily caloric intake from HPN in relation to calculated daily energy requirement (70+/-32% against 57+/-36%) were noted to be significantly associated with deranged LFT. However, on multivariate analysis, length of small bowel of less than 100 cm was the only significant variable for deranged LFT. CONCLUSION: Our finding showed the prevalence of deranged LFT to be 39% and raised alkaline phosphatase was the most common abnormality. Length of small bowel of less than 100 cm was found to be a significant independent variable for deranged LFT and the reason for this observation could be due to higher parenteral caloric intake. In our experience, LFT abnormalities are associated with a good prognosis as none of the patients developed decompensated liver disease.
Adult↗
[Lidocaine elimination and MEGX formation after oral lidocaine administration--a practicable test for assessment of quantitative liver function].
Oral load with 200 mg Lidocain was performed in 370 patients with chronic liver disease. The 120- and 240-minute Lidocain plasma concentrations as well as the 30- and 60-minute MEGX plasma concentrations, main metabolite of Lidocain, were measured by means of gas chromatography and with the commercial TDX test from the firm Abbott. No side effects caused by the load were observed and all of the patients resorbed Lidocain. Peak concentrations were found both for Lidocain and for MEGX in the 60-minute tests. Patients with liver cirrhosis of different aetiology showed significantly higher Lidocain plasma concentrations and lower MEGX values than patients with chronic non-cirrhotic liver disease. The differentiation of these two groups of patients was most successful via the determination of the 240-minute Lidocain plasma concentration. Oral load with 200 mg Lidocain has turned out to be a practicable and meaningful test for the estimation of the Cytochrom P450-dependent liver function.
Administration, Oral↗
Etiologic diagnosis of hepatic lesions in cancer patients. Value of ultrasound and liver function tests.
The purpose of this study was to evaluate the value of a combination of ultrasound (US) and liver function tests (LFT) for determination of the benign or malignant nature of one or more hepatic lesions in cancer patients. A total of 1235 patients with hepatic metastases and 832 patients with benign liver lesions investigated by US-LFT over a 12-year period were analyzed retrospectively. Ultrasound patterns considered indicative of a benign process (cyst, calcification without mass, irregular hyperechoic area without mass effect, small hyperechoic focal lesion as less than 3 cm) or malignancy (peritumoral halo, hypoechoic focal lesion, multiple solid nodules) were associated with LFT results. A US pattern of a benign process associated with normal LFT led to a diagnosis of benign disease with a false negative rate for malignancy of 11.6%. The highest figure corresponded to small hyperechoic nodules, for which the positive predictive value of malignancy (PPVM) depended on the type of primary cancer: 2.1% for breast cancer versus 62.5% for colorectal cancer. A US criterion of malignancy associated with abnormal LFT led to a diagnosis of malignancy (PPV 96.2% to 100%). Overall, the combination of US and LFT had a sensitivity of 80.6% and a specificity of 99.4%. The US-LFT combination correctly determined the benign or malignant nature of 74.5% of all hepatic lesions; the PPV was never less than 96.2% (small and solitary hyperechoic focal lesions were excluded because their PPV for malignancy is too high).
Calcinosis↗
Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction.
OBJECTIVE: Troglitazone treatment has been associated with idiosyncratic hepatic reaction leading to hepatic failure and death in some patients. This raises questions regarding whether all thiazolidinediones or peroxisomal proliferator-activated receptor-gamma (PPAR-gamma) agonists are hepatotoxic and whether data from clinical trials are adequate to detect a signal of potentially serious drug-related hepatotoxicity. The purpose of this study was to assess whether the idiosyncratic liver toxicity reported with troglitazone is molecule-specific or a thiazolidinedione class effect, based on liver enzyme data collected prospectively during phase 2/3 clinical trials with rosiglitazone, a new, potent, and specific member of the thiazolidinedione class. RESEARCH DESIGN AND METHODS: This is an analysis of liver function in type 2 diabetic patients at baseline and serially in 13 double-blind, 2 open-label active-controlled, and 7 open-label extension studies of rosiglitazone treatment conducted in outpatient centers throughout North America and Europe. The study comprised > 6,000 patients aged 30-80 years with type 2 diabetes. Patients underwent baseline liver function studies and were excluded from clinical trials if they had an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase value 2.5 times greater than the upper limit of the reference range. The main outcome measures were liver enzyme levels, which were assessed at screening, at baseline, and every 4 weeks for the first 3 months of treatment and at 6- to 12-week intervals thereafter. Patients with at least one on-therapy ALT value >3 times the upper limit of the reference range were identified, and their case records examined in detail. RESULTS: At baseline, 5.6% of the patients with type 2 diabetes (mean HbA(1c) 8.5-9.0%) had serum ALT values between 1.0 and 2.5 times the upper limit of the reference range. On antidiabetic therapy, most of those patients ( approximately 83%) had a decrease in ALT values, many into the normal range. The percentages of all patients with an on-therapy ALT value >3 times the upper limit of the reference range during double-blind and open-label treatment were as follows: rosiglitazone-treated 0.32%, placebo-treated 0.17%, and sulfonylurea-, metformin-, or insulin-treated 0.40%. The respective rates of ALT values >3 times the upper limit of the reference range per 100 person-years of exposure were 0.29, 0.59, and 0.64. CONCLUSIONS: No evidence of hepatotoxic effects was observed in studies that involved 5,006 patients taking rosiglitazone as monotherapy or combination therapy for 5,508 person-years. This is in keeping with hepatic data from clinical trials of another member of the class, pioglitazone, and in contrast to the clear evidence of hepatotoxic effects observed during the troglitazone clinical trial program. These findings suggest that the idiosyncratic liver toxicity observed with troglitazone is unlikely to be a thiazolidinedione or a PPAR-gamma agonist class effect. Poorly controlled patients with type 2 diabetes may have moderate elevations of serum ALT that will decrease with improved glycemic control during treatment with rosiglitazone or other antihyperglycemic agents.
Adult↗
Rapid determination of functional liver plasma flow in ICU patients by a modified hepatic D-sorbitol plasma clearance method.
Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluating functional liver plasma flow, which is in reasonable agreement with the direct blood measurement. However, its determination requires D-sorbitol infusion for 3 h or administration of a D-sorbitol bolus and withdrawal of blood specimens every 3-5 min. Since both variants are impractical in the ICU setting, a bolus/infusion technique was tested. A combined technique applying a bolus (0.85 mg/kg) and steady-state infusion (0.0014 mg/kg/min) of D-sorbitol was tested in 10 ICU patients without hepatic disease (group 1) and in 10 ICU patients with liver disease (group 2). Steady-state plasma levels (+/- 9%, P < 0.05) could be achieved within 60 min in all patients. The modified D-sorbitol clearance method requires a bolus and an infusion of D-sorbitol and withdrawal of a single blood specimen after 60 min. The lowest values of functional liver plasma flow were determined in patients with decompensated liver cirrhosis, acute fatty degeneration of the liver or Budd-Chiari syndrome. The method for routine determination of functional hepatic plasma perfusion proved to be rapid, safe and non-invasive in ICU patients. Hepatic D-sorbitol clearance may be especially useful for assessing the functional aspect of liver perfusion.
Adult↗
Elimination of 16-acetyl-gitoxin in patients suffering from impaired liver function.
In ten patients suffering from moderate to severe disturbances of liver function (hepatic cirrhosis, carcinomatous metastases of the liver) the elimination of 16-acetyl-gitoxin from plasma was measured after a single oral dose of 1.2 mg pengitoxin. In 9 of 10 patients the mean half-life amounted to 67.3 h (SD 14.2 h). In one patient with carcinomatous infiltration of the liver and concomitant cirrhosis, the half-life was prolonged to 165.3 h. The results point to an unchanged elimination of 16-acetyl-gitoxin in patients suffering from liver cirrhosis.
Acetyldigoxins↗
Hypophosphatemia and renal tubular dysfunction in alcoholics. Are they related to liver function impairment?
The study was designed to evaluate (a) the role of reduced renal phosphate reabsorptive capacity assessed as the ratio of maximum capacity for renal phosphate reabsorption (TmPO4) to glomerular filtration rate (GFR) in the pathogenesis of hypophosphatemia in alcoholics, (b) possible mechanisms leading to reduced TmPO4/GFR, and (c) the effect of liver function impairment on TmPO4/GFR. The TmPO4/GFR, its major extrarenal determinants, ratios of urinary excretion gamma-glutamyl transpeptidase and of alpha-glucosidase to GFR (uGGT/GFR and uAGL/GFR), indices of structural damage of renal tubular cells, and fractional clearance of lysozyme, an index of proximal renal function, were evaluated in 31 alcoholics with alcohol-related liver disease, 24 alcoholics without alcohol-related liver disease, 14 patients with non-alcohol-related liver disease, and 25 control subjects. Hypophosphatemia was found in 35% of alcoholics with alcohol-related liver disease, 29% of alcoholics without alcohol-related liver disease, and no patients with non-alcohol-related liver disease. A reduced TmPO4/GFR was the major determinant of hypophosphatemia in both groups of alcoholics. No difference in extrarenal determinants of TmPO4/GFR was found between alcoholics with and without hypophosphatemia. Alcoholics with and without alcohol-related liver disease had increased uGGT/GFR and normal uAGL/GFR regardless of serum phosphate level. Fractional clearance of lysozyme, instead, was increased only in hypophosphatemic alcoholics with and without alcohol-related liver disease. The TmPO4/GFR correlated inversely with the fractional clearance of lysozyme in both groups of alcoholics (P less than 0.01). The TmPO4/GFR and urinary enzymes were normal in patients with non-alcohol-related liver disease. It was concluded that a reduced TmPO4/GFR is involved in the pathogenesis of hypophosphatemia in alcoholics. A proximal tubular dysfunction seems to be responsible for the reduced TmPO4/GFR. Liver function impairment is not required for the expression of this tubular dysfunction.
Adult↗
Abnormal liver function tests in the patient transplanted 3 years ago for alcoholic liver disease.
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Alcoholism↗
Effect of bilateral vasectomy on liver function in langur monkeys (Presbytis entellus entellus Dufresne).
Changes in serum biochemical measures associated with liver dysfunction and biochemical and histological structure of the liver after vasectomy have been studied in langur monkeys. No appreciable changes were observed in the serum SGOT, SGPT, LDH and alkaline phosphatase levels after vasectomy as compared with sham operated controls. Likewise glycogen and cholesterol contents of the liver were found to be unchanged after vasectomy. Histologic structure of liver remained normal. The present investigation has suggested that vasectomy does not cause any adverse effect on liver function in langur monkeys.
Animals↗
[Evaluation of liver function tests and protein instability reaction in long existing parenchymatous changes of the liver].
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Liver↗
[Effect of ursodeoxycholic acid (UDCA) therapy for compensatory liver cirrhosis on liver function tests and serum bile acid metabolism].
Effect of ursodeoxycholic acid (600 mg/day 12 weeks) on liver function tests and bile acid metabolism were investigated in 6 patients with compensatory liver cirrhosis (CLC) and 6 with chronic active hepatitis (CAH). Serial determination of serum GOT, GPT and gamma-GTP after the initiation of UDCA revealed significant reduction in mean levels of these enzymes after 4 weeks, and further improvement was observed at the end of the 12-weeks treatment regimen (CLC: 79.3%, 81.1%, 51.5% of initial values, respectively, CAH: 61.2%, 59.3%, 42.8%). On the other hand, after UDCA administration, serum total bile acid increased and UDCA became the predominant bile acid in CLC and CAH patients. Other endogenous bile acids decreased in both groups, but reduction rate of serum chenodeoxycholic acid level in CLC was smaller than that in CAH group (CLC: 86.1% of initial values, respectively, CAH: 54.2%). During UDCA treatment, apparent side effect was not observed. We suggest that UDCA administration might constitute effective treatment for compensatory liver cirrhosis as well as chronic hepatitis.
Adult↗
The importance of abnormalities of liver function tests in predicting mortality in chronic heart failure.
A number of simple clinical and laboratory variables were analysed in a group of patients with chronic heart failure to evaluate their prognostic significance. Five hundred and fifty-two patients were followed for a maximum of 13 years with a total exposure time to death or censored survival of 1148 years. Of the clinical variables, diuretic dose and NYHA class were related to mortality (P < 0.01), and ischaemic heart disease was associated with a worse prognosis than other aetiologies (P < 0.05). Of the laboratory variables, abnormalities of liver function tests including bilirubin (P < 0.01), aspartate transaminase (P < 0.005), gamma glutamyl transpeptidase (P < 0.005) and alkaline phosphatase (P < 0.01) were all related to mortality as was plasma urate (P < 0.01). Multivariate survival analysis of all variables showed aspartate transaminase (chi 2 17.36, P < 0.001) accounted for the greatest variance followed by serum bilirubin (chi 2 14.35, P < 0.005). Thus, abnormalities in liver function tests have prognostic importance in chronic heart failure.
Aged↗
Contraception with subdermal ST-1435 capsules: side-effects, endocrine profiles and liver function related to different lengths of capsules.
One Silastic capsule of 15 mm, 20 mm or 30 mm length was inserted subcutaneously into the ventral aspect of the left forearm or upper arm of 28 healthy women during menstrual bleeding or not later than on the seventh day of the menstrual cycle. A new capsule of the same length was inserted after six months and both capsules were removed twelve months after the first insertion. Side-effects, including changes in body weight, blood pressure, menstrual bleeding and liver function test results, were registered. Blood samples were taken from selected subjects twice a week during the 1st, 2nd, 3rd, 6th, 7th and 12th month of use. Plasma concentrations of ST-1435 were measured by radioimmunoassay and the effects of treatment on pituitary and ovarian function were determined by assaying plasma concentrations of LH, FSH, estradiol and progesterone. There were no differences in hormonal side-effects between subjects who had a 30 mm capsule or subjects who had 20 mm or 15 mm capsules, but subjects who had 20 or 15 mm capsules had significantly longer bleeding or spotting periods in comparison with subjects who had a 30 mm capsule. There were no changes in blood pressure, body weight or liver function test results in comparison with pre-insertion values. The plasma level of ST-1435 was not significantly higher during the use of 30 mm capsules than during the use of 20 or 15 mm capsules. During the use of the shorter ST-1435 capsules, plasma estradiol elevation and slightly suppressed FSH were seen, while the use of longer capsules resulted in a slight suppression of LH. Progesterone concentrations during monitored cycles indicated anovulation. No pregnancies occurred during the study period of one year. The continuation rate at one year was 71% in the 30 mm capsule group and 57% in the 20 and 15 mm capsule groups taken together.
Adult↗
Thrombocytopenia, leukopenia and abnormal liver function tests in the initial phase of tick-borne encephalitis.
One-hundred-seventy-five patients in whom bone marrow puncture had been performed at the Department of Infectious Diseases, University Medical Centre, Ljubljana, during the period from 1988 to 1992, were analysed in a retrospective study. In five out of these 175 patients, tick-borne encephalitis virus infection was confirmed by serological tests and in all of them bone marrow puncture was performed in the initial phase of the illness as part of diagnostic work-up in a patient with a febrile illness accompanied by leukopenia and thrombocytopenia. Bone marrow examination revealed minimal reactive changes or normal findings. In addition to leukopenia and thrombocytopenia, abnormal liver function tests were also found in four patients. All these patients later developed meningoencephalitis, i.e. they had clinically typical tick-borne encephalitis with biphasic course of the illness. In the initial phase of tick-borne encephalitis in addition to well-known leukopenia, thrombocytopenia and abnormal liver function tests may be found.
Adult↗
[Study on improvement of liver cirrhosis and liver function in hepatolenticular degeneration patients treated with integrated Traditional and Western medicine].
OBJECTIVE: To observe the effects of sodium dimercaptosulphonate (DMPS) plus Gandou tablet, DMPS and calcium disodium ethylene diaminotetraacetate (EDTA) on improving liver cirrhosis and liver function of hepatolenticular degeneration (HLD) patients. METHODS: One hundred and forty-six HLD patients were divided into A, B, C three groups, and treated with DMPS plus Gandou tablet, DMPS and EDTA respectively, the therapeutic course was 8 weeks for three groups. The ultrasonography of liver, electrophoresis of serum protein and excretion of urinary copper were observed. RESULTS: The ultrasonography of liver was improved in all groups, the rate of improvement of group A was 54.0%, B was 44.0% and C was 39.1%. The amounts of serum albumin in A and B groups increased (P < 0.01, P < 0.05), and gamma-globulin decreased in all groups (P < 0.05). The excretion of urinary copper increased obviously in all groups (P < 0.01), and A, B groups increased more than that of C group (P < 0.05). CONCLUSIONS: The de-copper therapy could improve liver cirrhosis and liver function. The effect of DMPS plus Gandou tablet was better than that of DMPS and EDTA.
Adolescent↗
Isocaloric feeding and medium chain triglycerides fail to improve liver function tests in a patient with Crohn's disease and a high output stoma.
A patient with Crohn's disease complicated by multiple fistulae to the skin and bladder and a high-output stoma following previous multiple short bowel resections developed liver dysfunction during total parenteral nutrition. Isocaloric feeding based on calorimetry and changing from a long chain triglyceride emulsion to a mixture of medium and long chain triglyceride emulsion failed to improve liver function. Surgical removal of the affected small bowel resulted in a rapid improvement of the liver function despite continuation of total parenteral nutrition.
Journal Article↗
Enhanced liver functions of hepatocytes cocultured with NIH 3T3 in the alginate/galactosylated chitosan scaffold.
Formation of primary hepatocyte spheroids in the hydrogel scaffold is a promising approach for enhancing liver-specific functions in liver tissue engineering as well as for developing bioartificial liver (BAL) devices. In the present study, a highly porous hydrogel scaffold composed of alginate (AL) and galactosylated chitosan (GC) as a synthetic extracellular matrix (ECM) for hepatocytes was fabricated with 150-200 microm pore size in diameter. Cell adhesion onto AL/GC and AL/chitosan film was 72.7 and 45% at 1 wt% of GC (or chitosan) to AL content whereas cell adhesion onto AL film was 28.5%. The optimal concentration of GC in AL/GC sponge was 1 wt% to AL content by the measurement of albumin secretion. Cell viabilities performed on AL and AL/GC sponges were 72.2+/-3.6 and 81.3+/-3.5% of control, respectively, after 10 days incubation. Hepatocytes were aggregated to form multicellular spheroids in AL/GC sponge with diameter enlarged up to about 100 microm, 36 h postseeding, whereas most of them in the AL sponge remained as single cells and only a few cells began to form aggregates. Intercellular molecules such as connexin32 and E-cadherin genes related with cell-cell contact were expressed in hepatocytes within AL/GC sponge at 36 h after incubation, but not in AL sponge. Treatment with a gap junctional intercellular communication (GJIC) inhibitor, 18beta-glycyrrhetinic acid, resulted in a 1.5-fold marked decrease in albumin secretion levels in AL/GC sponge. Specially, coculture of hepatocytes in AL and AL/GC sponges with NIH3T3 in a transwell insert resulted in enhanced increase of liver-specific functions, such as albumin secretion rates, ammonia elimination rates, and ethoxyresorufin-O-deethylase activity by cytochrome P4501A1, compared to those in hepatocyte monoculture. The results suggest that formation of hepatocyte spheroids in coculture system enhances liver-specific functions for the AL/GC sponge as a new synthetic ECM to design developed BAL devices.
Alginates↗